Dr. Robert Lustig: How Sugar & Processed Foods Impact Your Health

00:00:00.000 | - Welcome to the Huberman Lab Podcast,

00:00:02.280 | where we discuss science and science-based tools

00:00:04.880 | for everyday life.

00:00:05.900 | I'm Andrew Huberman,

00:00:10.160 | and I'm a professor of neurobiology and ophthalmology

00:00:13.160 | at Stanford School of Medicine.

00:00:15.080 | My guest today is Dr. Robert Lustig.

00:00:17.680 | Dr. Robert Lustig is an endocrinologist.

00:00:20.080 | That is, he's a specialist in the function of hormones

00:00:22.460 | in the body and a professor of pediatric endocrinology

00:00:25.240 | at the University of California, San Francisco.

00:00:27.720 | He has authored more than 100 peer-reviewed studies

00:00:30.460 | exploring how different types of nutrients,

00:00:32.560 | that is food, impact our cellular functioning,

00:00:35.300 | our organ functioning, and thereby our health.

00:00:38.380 | During today's discussion, we discuss the idea

00:00:41.040 | of whether or not a calorie is indeed a calorie

00:00:43.980 | and whether or not our body weight and body composition

00:00:46.980 | only reflects the number of calories we eat

00:00:49.560 | versus the calories that we burn.

00:00:51.520 | We talk about how different food types,

00:00:53.680 | that is how the different macronutrients, protein, fat,

00:00:56.080 | and carbohydrates are processed in the body

00:00:58.480 | and the important role that fiber and the gut microbiome

00:01:01.460 | plays in that process.

00:01:02.720 | And we pay particular attention to the topic

00:01:05.280 | of how different types of sugars and fructose in particular

00:01:09.160 | can indeed be addictive to the brain

00:01:11.140 | and can modify the way that hormones in the body,

00:01:14.040 | in particular insulin, impact our liver health,

00:01:17.000 | kidney health, and indeed the health

00:01:18.620 | of all of our cells and organs.

00:01:20.920 | Indeed, Dr. Lustig is an expert in how sugar

00:01:24.640 | impacts the brain and body.

00:01:26.760 | We talk about how certain types of sugars

00:01:29.040 | can indeed be addictive in the same way

00:01:31.520 | that certain drugs of abuse and behaviors

00:01:33.600 | can become addictive.

00:01:34.680 | So in other words, how sugar actually changes the way

00:01:37.520 | that the brain works.

00:01:38.900 | And we discuss how the food industry,

00:01:41.200 | that is the commoditization and sale

00:01:43.080 | of particular types of food has altered the way that we eat

00:01:46.200 | and indeed the foods that we crave.

00:01:48.580 | Today's discussion covers all of that.

00:01:50.480 | And by the end of today's discussion,

00:01:52.340 | you'll have a thorough understanding

00:01:54.080 | of how foods are processed when they enter your body

00:01:56.820 | and how those different food choices

00:01:58.800 | are impacting your immediate and long-term health.

00:02:01.840 | Before we begin, I'd like to emphasize that this podcast

00:02:04.320 | is separate from my teaching and research roles at Stanford.

00:02:07.020 | It is however, part of my desire and effort

00:02:09.080 | to bring zero cost to consumer information about science

00:02:11.620 | and science related tools to the general public.

00:02:14.460 | In keeping with that theme,

00:02:15.560 | I'd like to thank the sponsors of today's podcast.

00:02:18.600 | Our first sponsor is Eight Sleep.

00:02:20.580 | Eight Sleep makes smart mattress covers

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00:02:25.160 | I've spoken many times before in this podcast

00:02:27.160 | about the fact that sleep is the foundation

00:02:29.240 | of mental health, physical health, and performance.

00:02:31.820 | Now, a key component of getting a great night's sleep

00:02:34.480 | is that in order to fall and stay deeply asleep,

00:02:37.080 | your body temperature actually has to drop

00:02:38.920 | by about one to three degrees.

00:02:40.520 | And in order to wake up feeling refreshed and energized,

00:02:43.520 | your body temperature actually has to increase

00:02:45.560 | by about one to three degrees.

00:02:47.320 | One of the best ways to make sure

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00:03:42.760 | Today's episode is also brought to us by Levels.

00:03:45.540 | Levels is a program that lets you see

00:03:47.120 | how different foods affect your health

00:03:49.000 | by giving you real-time feedback on your diet

00:03:51.000 | using a continuous glucose monitor.

00:03:53.540 | One of the most important factors

00:03:54.960 | in your immediate and long-term health

00:03:56.560 | is your blood sugar or blood glucose regulation.

00:03:59.480 | With Levels, you can see how different foods

00:04:01.800 | and food combinations, exercise, and sleep patterns

00:04:05.220 | impact your blood glucose levels.

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00:04:13.680 | and it downloads the data about your blood sugar levels

00:04:16.440 | in the preceding hours.

00:04:18.040 | Using Levels has allowed me to learn a tremendous amount

00:04:20.800 | about what works best for me

00:04:22.320 | in terms of nutrition, exercise, work schedules, and sleep.

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00:04:51.360 | AeroPress is similar to a French press for making coffee,

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00:04:57.440 | I first learned about AeroPress well over 10 years ago,

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00:05:02.160 | AeroPress was developed by Alan Adler,

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00:05:17.580 | And I used to see Alan, believe it or not,

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00:05:23.540 | So he was sort of famous in our community

00:05:26.400 | for developing these different feats of engineering

00:05:29.280 | that turned into commercial products.

00:05:31.120 | Now, I love coffee.

00:05:32.220 | I'm somebody that drinks coffee nearly every day,

00:05:34.360 | usually about 90 to 120 minutes

00:05:36.680 | after I wake up in the morning, although not always.

00:05:38.600 | Sometimes if I'm going to exercise,

00:05:40.160 | I'll drink coffee first thing in the morning.

00:05:42.520 | But I love, love, love coffee.

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00:06:38.240 | And now for my discussion with Dr. Robert Lustig.

00:06:41.940 | Dr. Robert Lustig, welcome.

00:06:43.940 | - Pleasure.

00:06:44.780 | Truly, just being here, being invited,

00:06:49.780 | high honor, really appreciate it.

00:06:52.040 | And it's not doctor, it's just Rob.

00:06:55.080 | - Okay, Rob, I've been looking forward

00:06:56.560 | to this conversation for a long time.

00:06:58.880 | I've seen your now famous, can we also say infamous,

00:07:02.320 | but famous YouTube video about sugar.

00:07:04.880 | We'll put a link to it in the show note captions.

00:07:07.060 | It's been viewed many, many millions of times.

00:07:09.860 | - Yeah, and I still can't figure out why that is, you know?

00:07:12.380 | - Well, I can.

00:07:13.220 | - I didn't think my mother would watch it and she didn't,

00:07:14.700 | but 24 and a half million people did.

00:07:17.400 | - Well, I think people are very interested

00:07:19.120 | in what to eat, what not to eat.

00:07:22.080 | And we'll start off simply talking about

00:07:26.360 | what most everyone believes and understands,

00:07:29.760 | which is that a calorie is a form of heat energy

00:07:33.060 | that's given off during the processing

00:07:36.340 | of some food bit or some thing.

00:07:39.980 | If that's mysterious to people,

00:07:41.160 | just understand that a calorie is a unit of energy.

00:07:43.780 | And I was taught and still many, many people

00:07:47.880 | worldwide believe that a calorie is a calorie,

00:07:50.400 | meaning if I consume more calories in whatever form,

00:07:54.580 | then I metabolize by thinking, feeling, moving,

00:07:59.480 | exercising, et cetera, then I will gain weight.

00:08:03.000 | And if I consume fewer calories than I burn,

00:08:07.120 | I will lose weight.

00:08:08.500 | And we could talk a lot about

00:08:11.420 | where that weight loss comes from.

00:08:12.920 | Does it come from adipose body fat stores

00:08:15.440 | or from muscle or from protein,

00:08:18.180 | or muscle, of course, is protein, et cetera.

00:08:20.880 | But let's start off with, is a calorie truly a calorie

00:08:25.280 | when it comes to the processing

00:08:27.240 | of different types of calories?

00:08:29.320 | Everyone thinks that obesity is about energy balance.

00:08:34.200 | That is calories in, calories out.

00:08:38.240 | Therefore, two behaviors, gluttony and sloth.

00:08:43.740 | Therefore, if you're fat, it's your fault.

00:08:47.060 | Therefore, diet and exercise.

00:08:50.240 | Therefore, any calorie can be part of a balanced diet.

00:08:53.680 | Therefore, don't pick on our calories,

00:08:57.080 | go pick on somebody else's calories.

00:08:58.940 | This is actually what the food industry uses

00:09:01.620 | to assuage their culpability

00:09:04.080 | for the change in the food supply

00:09:06.160 | and the rise in obesity and chronic disease like diabetes.

00:09:11.160 | Now, it is true that a calorie is that unit of energy

00:09:16.280 | that raises one gram of water one degree centigrade.

00:09:23.040 | And so therefore, a calorie burned is a calorie burned.

00:09:26.720 | I don't argue that, that's true.

00:09:28.100 | That's the first law of thermodynamics.

00:09:30.920 | But that doesn't mean a calorie eaten is a calorie eaten.

00:09:35.920 | That's not the same.

00:09:37.640 | And that's where people get it wrong.

00:09:40.040 | So let me give you some examples

00:09:42.360 | of how that calorie eaten is not a calorie eaten.

00:09:46.820 | You like almonds?

00:09:49.800 | - I do.

00:09:50.680 | - Me too, almonds are great.

00:09:52.880 | You eat 160 calories in almonds.

00:09:56.360 | How many of those do you absorb?

00:09:57.960 | 130.

00:10:00.420 | You eat 160, you absorb 130, where'd the other 30 go?

00:10:05.940 | - In the processing of that food energy?

00:10:08.520 | - No.

00:10:09.360 | Turned out, the fiber in those almonds,

00:10:13.880 | both soluble and insoluble fiber,

00:10:15.820 | and by the way, fiber's sort of the key

00:10:17.540 | to the kingdom in this story,

00:10:19.040 | forms a gel on the inside of your intestine.

00:10:23.960 | The insoluble fiber, the cellulose, forms a fishnet,

00:10:28.880 | if you will, a latticework on the inside of your duodenum.

00:10:32.240 | The soluble fiber, which are globular,

00:10:33.960 | plug the holes in that fishnet.

00:10:35.560 | Together, they form a secondary barrier.

00:10:38.440 | You can actually see it on electron microscopy,

00:10:40.400 | a whitish gel, and that prevents absorption

00:10:44.520 | of those 30 calories.

00:10:46.840 | So yes, 130 get absorbed, but many of them don't.

00:10:51.120 | They end up going further down the intestine

00:10:54.680 | to the next part, called the jejunum,

00:10:56.920 | and that's where the microbiome is.

00:10:58.980 | Now, everyone knows about the microbiome nowadays.

00:11:03.320 | It's all the bacteria.

00:11:04.640 | We always say, when women are pregnant,

00:11:06.840 | you're eating for two.

00:11:07.680 | Well, we're always eating for 100 trillion.

00:11:10.220 | Now, they have to eat.

00:11:13.080 | Well, what do they eat?

00:11:13.980 | They eat what you eat.

00:11:14.920 | The question is, how much did you get

00:11:16.360 | versus how much did they get?

00:11:17.680 | Well, if you ate almonds, they're getting those 30 calories.

00:11:21.520 | So even though you count the calories at your lips,

00:11:24.480 | that doesn't matter.

00:11:26.800 | What really matters is counting the calories

00:11:29.760 | at your intestinal brush border, okay?

00:11:32.640 | And they're not the same.

00:11:34.120 | So if you feed your gut, that's a good thing

00:11:38.000 | because then your gut will take those calories

00:11:40.560 | and turn it into things like short-chain fatty acids,

00:11:43.040 | which end up being protective

00:11:45.320 | against chronic metabolic disease,

00:11:48.520 | acetate, propionate, butyrate, valerate.

00:11:51.080 | Those are actually good.

00:11:52.400 | They're anti-inflammatory, anti-Alzheimer's

00:11:55.600 | because you fed your microbiome.

00:11:58.240 | So even though you ate 160, you absorbed 130.

00:12:02.560 | So a calorie eaten is not a calorie eaten

00:12:04.320 | because if you ate it with fiber, it wasn't for you.

00:12:08.320 | It was for your bacteria,

00:12:09.640 | but that's not the way you count them up.

00:12:12.680 | So that's problem number one.

00:12:15.220 | Problem number two, amino acids.

00:12:18.340 | So we all eat protein.

00:12:20.020 | Let's say you eat too much protein.

00:12:23.220 | You have, you know, the porterhouse steak, all right?

00:12:27.200 | Now, if you're a bodybuilder,

00:12:28.860 | those amino acids might go to muscle

00:12:33.880 | and you might increase your muscle mass

00:12:35.900 | because you're a bodybuilder,

00:12:36.880 | because you're putting excess force on those muscles

00:12:41.000 | and you're growing those muscles, okay?

00:12:43.000 | But let's say you're not a bodybuilder.

00:12:44.620 | Let's say you're a mere mortal like me.

00:12:46.280 | - Or let's say you're a kid going through puberty

00:12:48.480 | who's synthesizing a lot of muscle,

00:12:50.840 | not because they're lifting weights,

00:12:51.920 | because they're in growth. - But because testosterone's

00:12:53.880 | making it happen, yeah, absolutely.

00:12:56.140 | But let's say you're not.

00:12:56.980 | Let's say, you know, you're just, you know,

00:12:58.600 | just schlump off the street like, you know, Joe Schmo, okay?

00:13:02.200 | And you eat that porterhouse.

00:13:03.740 | You've taken on all these amino acids.

00:13:06.820 | There's no place to store it other than muscle.

00:13:09.580 | So your liver takes the excess

00:13:12.960 | and deamidates that amino acid,

00:13:15.940 | takes the amino group off

00:13:18.600 | to turn it from a amino acid into an organic acid.

00:13:21.880 | And then that organic acid can then enter the Krebs cycle,

00:13:25.000 | the tricarboxylic acid cycle,

00:13:26.720 | what goes on in the mitochondria in order to generate ATP,

00:13:30.120 | the chemical energy that your body needs

00:13:32.240 | in order to power itself.

00:13:33.760 | Okay, now that's a good thing.

00:13:36.600 | It takes double the amount of energy

00:13:40.160 | to prepare that amino acid for burning,

00:13:45.160 | as it does to prepare a carbohydrate for burning.

00:13:49.100 | - Or fat, 'cause when I asked about,

00:13:51.320 | when you asked about almonds, why the 160 versus 130,

00:13:55.000 | I thought it was the processing.

00:13:56.080 | It turned out it was fiber.

00:13:57.180 | You're saying for protein, let's make it realistic

00:14:00.080 | for a really nice big porterhouse steak,

00:14:02.580 | which I love, by the way.

00:14:04.120 | Let's say 800 calories. - Me too.

00:14:07.760 | - Well, it turns out-- - How much of that is,

00:14:10.720 | so that's what goes in your mouth, my mouth.

00:14:13.960 | How much of it is actually eaten,

00:14:18.960 | to stay with your calorie eaten is not a calorie eaten.

00:14:21.980 | In the processing of that,

00:14:23.640 | what percentage actually goes

00:14:25.360 | into your total caloric intake?

00:14:28.000 | - Right, so about 10% of everything you eat

00:14:32.400 | goes to just maintaining body temperature.

00:14:34.860 | It's called the thermic effect of food.

00:14:36.800 | But when you're eating protein,

00:14:38.440 | you actually generate more heat.

00:14:41.680 | And the reason is because it takes two ATP

00:14:45.400 | to phosphorylate that organic acid,

00:14:48.960 | as opposed to one ATP

00:14:51.120 | to phosphorylate that carbohydrate for consumption.

00:14:55.560 | So you actually have a net loss of energy

00:14:59.440 | because it was an amino acid versus a monosaccharide,

00:15:04.080 | a sugar.

00:15:05.400 | Now, you brought up fat.

00:15:07.040 | Fat doesn't need to be phosphorylated.

00:15:09.280 | So it actually doesn't have any thermic effect

00:15:13.160 | of food at that point.

00:15:14.420 | So it depends on what it is

00:15:16.240 | as to whether or not you have loss.

00:15:19.240 | - Okay, so in this, let's make it actually realistic.

00:15:22.840 | A 1,600 calorie porterhouse with a nice slab of--

00:15:27.840 | - Butter. [laughs]

00:15:28.680 | - Of grass-fed butter on there.

00:15:29.800 | I do this every once in a while, not often.

00:15:32.280 | - With some creamed spinach

00:15:33.480 | and maybe some mushrooms along the side.

00:15:35.040 | - Honestly, when I'm eating a porterhouse,

00:15:37.280 | I don't want to adulterate the taste with anything else

00:15:41.280 | except maybe some butter, maybe a salad afterwards.

00:15:44.880 | But let's say 1,600 calories of,

00:15:47.800 | it's got some fat in there for sure.

00:15:50.100 | Let's say 1,000 of those calories is protein.

00:15:54.880 | The other 600 are fat.

00:15:56.580 | - Something like that.

00:15:58.760 | - Something like that, depending on how marbled it is.

00:16:01.160 | Okay, so based on what you just said

00:16:03.400 | about the thermic effect of food and protein in particular,

00:16:06.560 | of that 1,000 calories, how much actually can we count?

00:16:10.820 | I'm not a calorie counter,

00:16:11.880 | but does one include as calories truly ingested?

00:16:15.900 | - Well, if you ingested 1,600--

00:16:18.200 | - Well, that's what went in the mouth,

00:16:19.320 | but what is going to go against your burn deficit?

00:16:24.320 | - Right.

00:16:25.280 | So I would have to actually do the math to figure that out.

00:16:28.740 | But as a guess--

00:16:30.760 | - Yeah, back of the envelope.

00:16:31.720 | - Back of the envelope calculation,

00:16:33.280 | you're going to lose about 25% of that.

00:16:35.680 | - Wow, so we're talking 750 calories.

00:16:39.480 | - Yeah.

00:16:40.320 | - And to translate this a bit,

00:16:41.900 | so what we're saying here is if you're somebody

00:16:43.400 | who is trying to lose weight or maintain weight,

00:16:46.920 | or perhaps even gain weight,

00:16:48.560 | you eat a 1,600 calorie porterhouse

00:16:51.040 | with a slab of butter on it,

00:16:53.020 | 600 of those calories we're saying in this is fat,

00:16:56.120 | with the remaining 1,000 calories,

00:16:57.880 | that all went in your mouth.

00:17:00.560 | - So you counted at your mouth.

00:17:02.440 | - Right.

00:17:03.280 | - But 700, but then when you compare it

00:17:04.400 | against your energy burn for that day,

00:17:06.920 | to maintain temperature, brain activity, physical activity,

00:17:10.960 | really it's only 750 calories.

00:17:13.040 | - That's right.

00:17:13.880 | - That's a huge difference.

00:17:15.160 | - Exactly, and another reason why a calorie's not a calorie.

00:17:18.820 | Now let's take the third, let's take fats.

00:17:21.240 | So over here we have Omega-3s,

00:17:23.440 | heart-healthy, anti-inflammatory, anti-Alzheimer's,

00:17:27.060 | save your life.

00:17:28.600 | And over here we have trans fats, the devil incarnate,

00:17:31.560 | consumable poison, because you can't break

00:17:35.880 | the trans double bond, you don't have the desaturase

00:17:39.040 | to break that trans double bond.

00:17:40.500 | So it basically accumulates, lines your arteries,

00:17:44.660 | lines your liver, causes chronic metabolic disease,

00:17:48.040 | causes insulin resistance.

00:17:49.940 | Omega-3s don't even get broken down for energy,

00:17:55.280 | because they're so important, they stay intact,

00:17:58.760 | because your brain needs them, your heart needs them,

00:18:01.600 | whereas trans fats can't be broken down

00:18:06.160 | because of that trans double bond.

00:18:08.300 | One, save your life, other one, kill you.

00:18:10.840 | They're both nine calories per gram,

00:18:12.400 | if you explode them in a bomb calorimeter,

00:18:15.120 | because a calorie burned is a calorie burned,

00:18:18.340 | but a calorie eaten is not a calorie eaten,

00:18:20.320 | because one will save your life, one will kill you.

00:18:23.320 | And finally, the big kahuna,

00:18:25.320 | the one that blows everything else out of the water,

00:18:28.280 | fructose and glucose.

00:18:30.120 | All right, now, glucose is the energy of life.

00:18:32.480 | - So here we're talking carbohydrates.

00:18:34.040 | I think most of our audience will be familiar

00:18:36.020 | with the so-called macronutrients.

00:18:37.480 | So we talked about fat, in this case, almonds.

00:18:39.680 | There's some fiber in there,

00:18:40.920 | probably a little bit of carbohydrate.

00:18:42.420 | - Little bit. - Little bit.

00:18:43.580 | Talked about the porterhouse with butter.

00:18:45.200 | - Right. - You can be hungry already.

00:18:47.060 | That's protein and fat, very little, if any, carbohydrate.

00:18:51.280 | It should be zero, essentially, maybe one.

00:18:53.280 | - Zero, zero. - Yeah, yeah.

00:18:56.840 | And then now we're talking about carbohydrates,

00:18:58.680 | and we're gonna subdivide that into glucose and fructose.

00:19:01.440 | - Right, galactose basically becomes glucose in the liver,

00:19:04.560 | so we can dispense with that,

00:19:06.720 | unless you have a disease called galactosemia,

00:19:09.060 | which is about 120,000, and causes neonatal meningitis,

00:19:14.060 | and it's a disease, as a pediatric endocrinologist,

00:19:17.300 | I would take care of,

00:19:18.140 | but we can dispense with that for the moment.

00:19:20.880 | All right, so glucose, fructose.

00:19:23.680 | Glucose is the energy of life.

00:19:25.840 | Every cell on the planet burns glucose for energy.

00:19:28.280 | Glucose is so damn important

00:19:30.680 | that if you don't consume it, your body makes it.

00:19:33.220 | So it will take an amino acid and turn it into glucose.

00:19:36.080 | - That's gluconeogenesis. - Gluconeogenesis, that's right.

00:19:38.760 | It will take a fatty acid and turn it into glucose,

00:19:42.280 | and specifically the glycerol portion of the triglyceride

00:19:45.640 | will turn into glucose.

00:19:47.720 | So the Inuit, they didn't have any place

00:19:52.040 | to grow carbohydrate.

00:19:53.520 | They had ice, they had whale blubber.

00:19:55.760 | They still have serum glucose level,

00:19:58.060 | and the reason is because you had to.

00:20:00.840 | You have to have a serum glucose level

00:20:02.720 | in order to power your brain, in order to power your heart.

00:20:06.680 | Yes, you can use ketones, of course you can,

00:20:10.180 | but only if you're in a ketogenic state

00:20:13.760 | will you use exclusively ketones,

00:20:15.840 | and you also need glucose for structural changes

00:20:20.480 | in specific proteins and particularly hormones.

00:20:24.180 | So glucose molecules will stud TSH, LH, FSH,

00:20:29.180 | different pituitary hormones

00:20:31.140 | in order to increase their potency.

00:20:33.720 | It's one of the reasons why aging

00:20:36.600 | leads to defective hormoneogenesis.

00:20:40.360 | For instance, hypogonadism, hypothyroidism

00:20:43.020 | is the loss of glycosylation

00:20:45.480 | on individual peptide hormones

00:20:50.320 | because of the inability to add glucose.

00:20:54.200 | - Because of insulin?

00:20:55.860 | - No, no, it's an aging phenomenon.

00:20:58.260 | - Okay, we'll come back to this

00:20:59.200 | 'cause I think it's really important.

00:21:00.860 | The idea that ingestion of carbohydrates

00:21:03.960 | and the, as you called it,

00:21:06.580 | the studying of carbohydrate molecules on hormones

00:21:09.680 | can augment the function of those hormones,

00:21:11.920 | and with aging that's a less efficient process.

00:21:14.580 | - It's a less efficient process,

00:21:15.640 | but it's not because of consumption.

00:21:18.480 | - Right, people are still, I see the plenty of folks

00:21:22.680 | who are 65 and older eating plenty of carbohydrates.

00:21:26.860 | You're saying a lot of them have deficient thyroid,

00:21:30.020 | testosterone, estrogen, prolactin, et cetera,

00:21:33.720 | because of the way those carbohydrates

00:21:36.860 | are not studying the hormones.

00:21:40.120 | - Exactly, so all of those are glycoprotein hormones.

00:21:43.640 | - Let's tee that up for later

00:21:44.640 | 'cause I think that's an interesting avenue to go down.

00:21:46.760 | - Okay, and there's a disease in children and babies

00:21:50.040 | called congenital disorders of glycosylation,

00:21:52.500 | where you can't put glucose molecules on specific proteins,

00:21:57.500 | and it causes severe mental retardation,

00:22:01.380 | all sorts of metabolic havoc,

00:22:03.200 | and a lot of those babies die for that matter.

00:22:06.240 | So that's an important thing.

00:22:07.980 | All right, but that's how important glucose is.

00:22:10.460 | Fructose, on the other hand, this sweet molecule,

00:22:15.440 | the molecule we seek, the reason why the food industry

00:22:19.020 | studs every food in the grocery store,

00:22:23.520 | and 73% of all items in the American grocery store

00:22:27.280 | have added sugar on purpose for the food industry's purposes,

00:22:31.620 | not for yours, because fructose is addictive,

00:22:35.200 | activates the nucleus accumbens,

00:22:37.040 | the reward center of the brain,

00:22:38.720 | in the same way that cocaine, heroin, nicotine, alcohol do,

00:22:43.440 | and drives dopamine receptors down,

00:22:46.440 | just like nicotine, alcohol, cocaine, heroin do.

00:22:50.840 | That molecule, fructose, is number one,

00:22:56.480 | completely vestigial to all vertebrate life.

00:23:01.520 | There is no biochemical reaction in any vertebrate

00:23:05.200 | that requires dietary fructose.

00:23:07.720 | That's number one.

00:23:08.600 | Number two--

00:23:09.420 | - Okay, sorry, I'm gonna just answer.

00:23:11.200 | So you're saying that even though we can process fructose--

00:23:15.000 | - We have a limited capacity to process it,

00:23:17.120 | in the same way we have a limited capacity

00:23:18.720 | to metabolize alcohol.

00:23:20.000 | Now, if you have one drink a day, you're okay.

00:23:25.920 | If you have two drinks a day, depends on how big you are.

00:23:29.240 | You know, you and I can probably--

00:23:30.200 | - I would argue two drinks a week is the maximum,

00:23:32.200 | but let's not go there.

00:23:34.120 | But in terms of, you're saying, when you say fructose,

00:23:39.540 | processing of fructose is vestigial,

00:23:41.400 | what you're saying is that we don't need to do it.

00:23:43.920 | It's like the appendix.

00:23:44.880 | It's an organ for which it has no function.

00:23:46.680 | - Exactly.

00:23:47.520 | And fructose has no function in the human body, period.

00:23:51.960 | - You don't need it.

00:23:52.800 | - You don't need it.

00:23:53.800 | Don't need it.

00:23:56.180 | But our diet is replete with it.

00:24:00.100 | In fact, our fructose consumption's gone up 25-fold

00:24:04.360 | since the beginning of the last century.

00:24:06.280 | - I have to ask this now.

00:24:08.060 | I love fruit, I eat berries galore,

00:24:11.720 | especially since the price of berries

00:24:13.040 | seems to have come down.

00:24:14.280 | It used to be the only get 'em certain times a year.

00:24:16.240 | I'm what you call a drive-by blueberry eater.

00:24:18.880 | So I'll just walk past and just take a fistful.

00:24:21.000 | You can't put them in front of me without me eating them.

00:24:23.560 | This is even difficult for me

00:24:24.720 | when other people I don't know are eating them.

00:24:26.360 | So I eat lots of blueberries, strawberries,

00:24:30.360 | blackberries if they're in season, I love them.

00:24:33.020 | - No problem.

00:24:33.860 | - Loaded with fructose?

00:24:34.800 | - No.

00:24:35.720 | - Plenty of fiber, low fructose?

00:24:37.640 | - Low fructose.

00:24:38.480 | And berries, berries are the lowest fructose

00:24:40.840 | of all the different fruits.

00:24:41.680 | - I was so worried about asking you this today.

00:24:43.220 | - Not a bit.

00:24:44.060 | - Okay.

00:24:45.020 | - And fruit is okay because of the fiber.

00:24:48.020 | So the molecule, the fructose molecule's the same

00:24:51.300 | whether it's in a berry or in a banana

00:24:56.300 | or for that matter in a Coca-Cola.

00:24:59.420 | The fructose molecule is the same molecule.

00:25:02.020 | The difference is that in the berry

00:25:03.800 | it comes with a whole lot of fiber.

00:25:05.720 | In the banana it comes with a whole lot less fiber.

00:25:08.280 | And in the Coca-Cola, it doesn't come with any fiber.

00:25:11.360 | And the fiber is what mitigates the absorption.

00:25:15.840 | So when you consume the fructose with fiber,

00:25:18.740 | so your blueberries, you're feeding your microbiome.

00:25:22.800 | That fructose wasn't for you.

00:25:25.360 | - Got it.

00:25:26.200 | Such a relief.

00:25:27.040 | And I must say recently I had a whole body MRI

00:25:31.080 | as a preemptive thing.

00:25:33.240 | - How was that?

00:25:34.480 | - It was great.

00:25:35.380 | I got to watch a Netflix in there

00:25:37.060 | and I never had a whole body MRI.

00:25:38.780 | I learned a few things that were useful to me.

00:25:40.940 | I've got a clean bill of health, so that's great.

00:25:43.100 | - Well, that's good.

00:25:43.940 | - But one of the pieces of feedback I got is

00:25:46.300 | that my gut was filled with this very high contrast stuff.

00:25:51.300 | And they asked, do you consume a lot of blueberries?

00:25:54.360 | And I said, indeed I do, why?

00:25:56.760 | And they said, because that high contrast of it

00:26:00.200 | shows up white on the scan is high concentrations

00:26:03.640 | of magnesium that we see in people

00:26:06.760 | that ingest large amounts of blueberries,

00:26:08.840 | which is pretty rare.

00:26:10.240 | And yours are comparable to a bear in blueberry season.

00:26:14.560 | - Wow.

00:26:15.520 | - And basically my entire gut was filled with blueberries.

00:26:17.780 | I suppose I need to cut back a little bit.

00:26:19.320 | But now I know that fruit is okay,

00:26:21.900 | especially if the fruit has a lot of fiber,

00:26:24.480 | but fructose itself,

00:26:25.860 | especially if it's not partnered with fiber,

00:26:28.000 | is first of all, not required for survival at all.

00:26:33.120 | But you're telling me is problematic.

00:26:35.800 | - Yeah, and let me tell you why it's problematic.

00:26:37.800 | We haven't gotten to that yet.

00:26:39.000 | We're just talking about whether

00:26:40.480 | it's vestigial versus needed.

00:26:42.960 | Now let's talk about what fructose does.

00:26:46.240 | Turns out fructose inhibits three, count 'em,

00:26:51.160 | three separate enzymes necessary

00:26:53.320 | for normal mitochondrial function.

00:26:55.320 | Now, your mitochondria make ATP.

00:26:59.480 | Your mitochondria have to work at peak efficiency.

00:27:02.200 | That's what metabolic health is.

00:27:05.200 | Is mitochondria working at peak efficiency?

00:27:07.700 | Well, there are three enzymes

00:27:09.540 | that are inhibited by fructose.

00:27:12.840 | Number one, AMP kinase, all right?

00:27:16.360 | Now, AMP kinase is the fuel gauge on the liver cell.

00:27:19.620 | It's the thing that tells the liver

00:27:21.440 | to make more mitochondria, fresher mitochondria,

00:27:24.240 | because if your AMP levels are high,

00:27:27.260 | that means you've dephosphorylated a bunch of ATPs

00:27:30.440 | and you have to regenerate 'em,

00:27:31.760 | so you need some more mitochondria,

00:27:33.200 | so it's a negative feedback pathway.

00:27:35.240 | Well, you need that AMP kinase

00:27:36.920 | to generate that mitochondrial biogenesis signal,

00:27:40.760 | except that fructose, a metabolite of fructose

00:27:44.560 | called methylglyoxal, MGO, sits in the active site

00:27:49.040 | of the gamma subunit of that AMP kinase

00:27:51.720 | and actually binds to arginines in that active site,

00:27:55.860 | rendering that enzyme now dead.

00:28:01.040 | It's an irreversible inhibition

00:28:03.400 | because of the covalent bonding of that methylglyoxal,

00:28:06.760 | that aldehyde, to the arginine,

00:28:09.720 | and now that enzyme is dead.

00:28:11.920 | Okay, so it basically acts like a key

00:28:13.940 | that doesn't turn the lock,

00:28:15.080 | but prevents the key that you want in that lock

00:28:18.560 | from entering the lock.

00:28:20.040 | It's like gluing a lock shut, yeah.

00:28:23.520 | Got it, so that's one of the enzymes.

00:28:25.400 | That's one.

00:28:26.440 | Second one, ACAD-L, acyl-CoA dehydrogenase long chain.

00:28:31.440 | So this is necessary to cleave two carbon fragments

00:28:34.080 | off fatty acids to prepare them for metabolism.

00:28:38.760 | So it inhibits that one.

00:28:41.520 | And then finally, it inhibits

00:28:43.920 | carnitine palmitoyl transferase one, now CPT-1.

00:28:48.680 | Now that's the enzyme that regenerates carnitine.

00:28:50.720 | Carnitine is the shuttle mechanism

00:28:52.360 | by which you get the fatty acids from the outer

00:28:56.360 | mitochondrial membrane through

00:28:58.720 | to the inner mitochondrial membrane

00:29:00.560 | so that they can be beta-oxidized for energy.

00:29:03.960 | So if you don't have that CPT-1,

00:29:08.240 | you're basically carnitine-less,

00:29:10.180 | and therefore you can't generate beta-oxidation.

00:29:14.380 | You said fructose inhibits all three

00:29:15.880 | of these enzymatic pathways.

00:29:17.640 | As a biologist, I have to ask you,

00:29:19.480 | how potently does it inhibit them?

00:29:21.140 | I mean, 'cause there are drugs that block receptors,

00:29:24.520 | and then there are drugs that block receptors

00:29:26.560 | with unbelievable affinity.

00:29:28.780 | So I mean, mechanistically in a dish, meaning in vitro,

00:29:32.360 | you can see all sorts of things.

00:29:34.080 | But how significant is this for obesity,

00:29:38.320 | for mitochondrial function in vivo in us?

00:29:41.120 | - All right, so the dose determines the poison, right?

00:29:45.740 | Paracelsus 1537.

00:29:49.140 | There are toxins that are parts per billion

00:29:53.280 | and will kill you, like sarin, ricin, cyanide.

00:29:56.960 | By the way, cyanide's a good analogy

00:29:58.780 | because it's working on mitochondria.

00:30:01.860 | It's basically causing mitochondria

00:30:04.560 | to be completely defective, all right?

00:30:07.920 | Then there are intermediate toxins,

00:30:10.760 | like arsenic and carbon tetrachloride.

00:30:13.420 | Parts per million, and they take a little longer to work.

00:30:16.580 | They're not gonna kill you on the spot.

00:30:18.240 | That's why I can eat an apple seed

00:30:20.080 | that has a little bit of arsenic in it,

00:30:21.740 | but I'm not gonna die.

00:30:22.640 | - Right, and then finally there,

00:30:24.640 | and by the tobacco smoke goes in there.

00:30:27.120 | And then finally, you have weak toxins, all right?

00:30:31.840 | And you know, where it's not one exposure

00:30:34.100 | that will kill you.

00:30:34.940 | It's, you know, 10,000 exposures that'll kill you,

00:30:37.160 | like alcohol.

00:30:38.120 | - Or toxic people.

00:30:39.480 | - Yeah, or toxic people.

00:30:40.780 | Well, it depends on how toxic. - Sometimes it only takes one.

00:30:43.680 | Couldn't resist, sorry.

00:30:44.520 | Sometimes it only, mildly toxic people.

00:30:46.520 | Anyway, the point is that fructose is in that last category.

00:30:51.080 | So it's not what you do one day that kills you.

00:30:55.760 | It's what you do every day that kills you.

00:30:59.240 | And if you basically eat ultra-processed food,

00:31:03.200 | high in sugar, for 10 years in a row,

00:31:06.720 | it's gonna show up in terms of your comorbidities.

00:31:10.040 | And ultimately, yeah, it will kill you.

00:31:12.360 | And we have the data to show how many years you will lose.

00:31:17.360 | So right now in America, we pay an eight-year longevity tax.

00:31:23.000 | If you look at Japan, they have a mean age of death of 88.

00:31:29.520 | We have a mean age of 80, okay?

00:31:34.080 | We're paying an eight-year longevity tax just by living here.

00:31:37.320 | And we're talking about the healthy people.

00:31:38.860 | Now, if you have metabolic syndrome,

00:31:41.180 | it's a 15-year longevity tax.

00:31:43.400 | And, sorry, if you have obesity,

00:31:45.360 | it's a 15-year longevity tax.

00:31:46.620 | And if you have metabolic syndrome,

00:31:47.720 | it's a 20-year longevity tax.

00:31:49.700 | That is primarily, not completely, but primarily sugar.

00:31:54.900 | It's also, you know, Omega-6s, it's also trans fats,

00:31:59.040 | you know, left over because now they're gone.

00:32:01.000 | But, you know, people are still suffering the ravages

00:32:04.580 | of the trans fats, you know, from the previous generation.

00:32:07.560 | - Are they gone?

00:32:08.400 | I mean, I do remember as a kid

00:32:09.580 | when we had margarine in our refrigerator.

00:32:11.800 | This is actually a big debate in my home.

00:32:13.720 | One parent, I won't identify which, was pro-margarine.

00:32:18.040 | The other was pro-butter, anti-margarine.

00:32:20.420 | The marriage didn't last, but there were other reasons.

00:32:23.520 | - That's probably why.

00:32:24.840 | - I went butter.

00:32:25.900 | - Butter is fine.

00:32:28.760 | In fact, time declared, you know, front cover,

00:32:32.880 | butter's back, you know.

00:32:35.160 | Margarine was the bad guy, without question.

00:32:38.840 | And we know now, but, you know,

00:32:40.460 | back when we thought it was a calorie, it was a calorie.

00:32:43.040 | We thought, oh, margarine, you know,

00:32:45.840 | it's the same, you know, nine calories per gram.

00:32:48.460 | And we said, it lowers your triglycerides.

00:32:52.600 | Bad idea.

00:32:55.540 | It was, because what it did was, it lined your liver.

00:33:00.260 | Because you couldn't break that trans double bond.

00:33:03.900 | And, you know, so they're now gone from our food supply.

00:33:08.100 | - They're illegal.

00:33:09.300 | - They're illegal, they're banned.

00:33:10.660 | But you can make trans fats in your own kitchen

00:33:14.020 | by taking olive oil and heating it

00:33:16.120 | to beyond the smoking point.

00:33:18.020 | So they're not completely gone.

00:33:20.100 | They're just gone from ultra-processed food.

00:33:22.860 | So now sugar's the big problem,

00:33:25.100 | because of these three enzymes that you are inhibiting.

00:33:28.460 | The point is, we started this with a calorie's a calorie.

00:33:31.700 | Well, if you are inhibiting mitochondrial function,

00:33:34.340 | then a calorie's not a calorie, is it?

00:33:36.260 | - You're reducing the intensity of the furnace.

00:33:39.380 | - Yeah, exactly.

00:33:40.960 | So this whole calorie's a calorie just makes no sense.

00:33:45.340 | And it hasn't worked at any level.

00:33:47.500 | And there is no study that actually shows

00:33:50.660 | that cutting calories makes a difference.

00:33:52.980 | And I can show you, you know, voluminous data

00:33:55.780 | that shows that virtually every weight loss study

00:33:58.580 | that led to caloric restriction basically didn't work.

00:34:03.400 | Not for any length of time.

00:34:05.380 | Just to round out our earlier discussion,

00:34:07.300 | 'cause I find it fascinating

00:34:08.540 | and I know other people will as well,

00:34:10.560 | talked about that 160 calories,

00:34:13.280 | that's actually 130 at the business end of things,

00:34:15.940 | of almonds.

00:34:17.020 | We talked about the porterhouse steak with butter

00:34:19.380 | and the 25% reduction in what's actually "eaten".

00:34:24.380 | And I'll get back to this 'cause this "issue",

00:34:27.140 | I think the problem is there's a lack of useful language

00:34:30.820 | to dissociate this stuff.

00:34:33.740 | Even just calling fat, fat.

00:34:35.540 | People think it's gonna make you gain body fat.

00:34:37.740 | - Totally.

00:34:38.580 | - If we called it adipose tissue and lipids,

00:34:40.580 | we would have avoided this confusion.

00:34:42.080 | So I don't wanna get there just yet,

00:34:44.080 | but I wanna make sure with-

00:34:45.460 | - The food industry does this on purpose.

00:34:47.580 | - Really?

00:34:48.420 | - Oh, absolutely.

00:34:49.260 | So they tell you a sugar is a sugar, which is not true.

00:34:53.500 | They tell you a calorie is a calorie, which is not true.

00:34:56.540 | And they tell you a fat is a fat, which is not true.

00:34:59.900 | Okay, this is very specifically.

00:35:01.380 | So when you're talking about sugar,

00:35:02.940 | you're talking about dietary sugar,

00:35:05.020 | or are you talking about blood sugar?

00:35:06.600 | 'Cause blood sugar is blood glucose.

00:35:08.540 | - Or cholesterol. - And I never use-

00:35:09.860 | - Dietary cholesterol, or circulating cholesterol, or-

00:35:13.260 | - Absolutely, okay.

00:35:14.820 | So we've done this to ourselves,

00:35:19.180 | but the food industry has really promulgated it

00:35:21.840 | because we farmed out nutrition policy and information

00:35:26.240 | to the food industry.

00:35:27.260 | So they actually use this for their purposes.

00:35:30.100 | It's one of the problems in this field.

00:35:33.540 | As we all know, quality nutrition influences,

00:35:36.100 | of course, our physical health,

00:35:37.260 | but also our mental health and our cognitive functioning,

00:35:39.980 | our memory, our ability to learn new things and to focus.

00:35:42.900 | And we know that one of the most important features

00:35:45.080 | of high quality nutrition is making sure

00:35:47.020 | that we get enough vitamins and minerals

00:35:49.020 | from high quality unprocessed

00:35:50.780 | or minimally processed sources,

00:35:52.620 | as well as enough probiotics and prebiotics and fiber

00:35:55.740 | to support basically all the cellular functions in our body,

00:35:58.800 | including the gut microbiome.

00:36:00.660 | Now, I, like most everybody,

00:36:02.780 | try to get optimal nutrition from whole foods,

00:36:05.840 | ideally mostly from minimally processed

00:36:08.580 | or non-processed foods.

00:36:10.020 | However, one of the challenges

00:36:11.140 | that I and so many other people face

00:36:12.980 | is getting enough servings of high quality fruits

00:36:15.060 | and vegetables per day, as well as fiber and probiotics

00:36:18.020 | that often accompany those fruits and vegetables.

00:36:20.220 | That's why way back in 2012,

00:36:22.240 | long before I ever had a podcast, I started drinking AG1.

00:36:26.060 | And so I'm delighted that AG1

00:36:27.700 | is sponsoring the Huberman Lab podcast.

00:36:29.860 | The reason I started taking AG1

00:36:31.580 | and the reason I still drink AG1 once or twice a day

00:36:34.860 | is that it provides all of my foundational nutritional needs

00:36:37.660 | that is it provides insurance

00:36:39.620 | that I get the proper amounts of those vitamins, minerals,

00:36:42.400 | probiotics, and fiber to ensure optimal mental health,

00:36:46.080 | physical health, and performance.

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00:37:04.460 | For the third category of macronutrients, carbohydrates,

00:37:07.860 | you differentiated glucose and fructose.

00:37:11.100 | If I ingest, let's say, a half a bagel

00:37:16.980 | since we were talking about New York, your city of origin,

00:37:20.220 | they have great bagels on the West Coast.

00:37:22.360 | - Yeah, I know.

00:37:23.200 | - Yeah, it's not the same.

00:37:24.020 | - It's pretty pitiful.

00:37:24.860 | - Same with the pizza dough.

00:37:25.900 | It's like they claim it's the water, whatever it is,

00:37:28.900 | it's different back there and it's better.

00:37:30.660 | - Indeed.

00:37:31.860 | - Half a bagel, let's say 250 calories, mostly carbohydrate.

00:37:36.860 | This is an unlined, no cream cheese, no schmear,

00:37:41.500 | as they call it back there.

00:37:42.500 | No cream cheese, no butter, none of that thing.

00:37:44.260 | Just half a bagel, 250 calories.

00:37:46.380 | So that's what I ate.

00:37:47.540 | You're saying that a calorie eaten is not a calorie eaten.

00:37:49.700 | How much of that carbohydrate,

00:37:50.980 | given that it's probably most,

00:37:52.300 | let's assume it's mostly glucose.

00:37:53.860 | Let's do it this way.

00:37:54.680 | - Yeah, it is.

00:37:55.520 | It's polymerized glucose.

00:37:56.340 | - Okay, polymerized glucose. - That's what it is.

00:37:57.840 | - How much of that is actually utilized or burned

00:38:01.740 | versus the original 250?

00:38:05.700 | - So if you look at what happens to energy in the body,

00:38:10.360 | 65% of that which is ingested

00:38:14.480 | goes to resting energy expenditure, just to power the body.

00:38:18.460 | 10% goes to the thermic effect of food.

00:38:21.300 | And then 25% goes to activity.

00:38:24.060 | That's the breakdown of where the energy goes.

00:38:28.540 | - And that's calories from fat, protein, and carbohydrate.

00:38:31.500 | - Yeah, from everything together.

00:38:33.200 | And glucose is a perfectly good example of how that works.

00:38:37.500 | The point is though that when you ingest glucose,

00:38:40.420 | you're getting a big glucose excursion in your bloodstream.

00:38:44.220 | So you're getting a big glucose spike.

00:38:46.940 | And that glucose spike has to come down.

00:38:50.480 | Well, what makes it come down?

00:38:52.460 | The hormone insulin.

00:38:54.080 | Insulin is the bad guy in this story.

00:38:57.020 | The higher your glucose goes,

00:38:59.060 | the more your pancreas will release insulin

00:39:02.060 | in order to bring that glucose down.

00:39:04.960 | Well, it turns out that glucose rise was not benign.

00:39:08.720 | That glucose rise led to endothelial dysfunction.

00:39:11.600 | Transient, but nonetheless, endothelial dysfunction.

00:39:14.180 | - Could you just remind people

00:39:15.720 | what endothelial cells are?

00:39:16.980 | - The inside of your arteries, okay?

00:39:19.820 | And it will change blood pressure.

00:39:22.660 | We've got plenty of data to demonstrate

00:39:24.660 | how it changes blood pressure.

00:39:25.860 | And over time, that will cause coronary artery disease.

00:39:30.140 | That will cause kidney disease, et cetera.

00:39:33.220 | But it's the insulin response that is really the bad guy.

00:39:37.340 | Now, people think insulin is good

00:39:39.620 | because it lowers blood glucose.

00:39:41.900 | After all, diabetics take insulin

00:39:44.300 | to lower their blood glucose.

00:39:46.060 | Okay, let's take a diabetic.

00:39:49.220 | A patient with diabetes.

00:39:51.140 | Blood sugar's 300, that's bad.

00:39:53.740 | We give him a shot of insulin in the arm.

00:39:55.660 | Blood sugar goes down to 100.

00:39:57.820 | Blood sugar went from 300 to 100.

00:40:00.260 | Okay, where did the 200 points of blood glucose go?

00:40:05.140 | - I'm assuming that the insulin sequestered it to where?

00:40:12.580 | - I'm assuming to the liver.

00:40:13.880 | - To the fat.

00:40:15.660 | - Interesting. - For storage.

00:40:17.580 | That's insulin's job.

00:40:18.860 | Insulin takes whatever you're not burning

00:40:20.380 | and puts it into fat for storage.

00:40:22.460 | Insulin is not the diabetes hormone.

00:40:24.540 | Insulin is the energy storage hormone.

00:40:27.220 | - How quickly does it do that?

00:40:28.780 | - Pretty quick.

00:40:29.620 | - Because if I'm having a very busy day,

00:40:33.220 | or the diabetic person is having a very busy day

00:40:35.460 | and they're moving around a lot,

00:40:37.220 | then you've got insulin-bound glucose in the bloodstream

00:40:41.580 | for how long?

00:40:42.420 | - No, no, insulin doesn't bind glucose.

00:40:44.500 | Insulin binds to its receptor.

00:40:46.260 | - Sure, sorry.

00:40:47.100 | - Insulin allows for glucose transporters to work.

00:40:49.980 | - So, but for some period of time,

00:40:51.900 | while that person is active,

00:40:53.360 | there's an opportunity to utilize that glucose, right?

00:40:56.940 | So how quickly is insulin managing that glucose?

00:41:00.700 | We know that the spike comes down quickly,

00:41:03.140 | but the glucose is not available for energy utilization

00:41:06.660 | after what?

00:41:07.740 | It's sequestered to the adipose, to the fat tissue

00:41:11.740 | within an hour?

00:41:13.500 | Is that about right?

00:41:14.340 | - So about 90 minutes, yeah.

00:41:15.820 | But I mean, if you're active,

00:41:18.420 | if you eat a muffin and you're active,

00:41:23.420 | your muscles are going to take up that glucose

00:41:26.140 | irrespective of insulin.

00:41:27.980 | In fact, muscles are insulin independent.

00:41:32.320 | They have glucose transporters,

00:41:34.020 | but they are insulin independent

00:41:35.260 | because if they weren't,

00:41:36.380 | then every patient in diabetic ketoacidosis

00:41:38.460 | would be paralyzed, okay?

00:41:40.140 | So glucose will end up in muscles

00:41:43.620 | irrespective of energy status and insulin status.

00:41:48.500 | - And in muscles, it's used as immediate fuel

00:41:50.820 | and glycogen?

00:41:52.420 | - Both. - Okay.

00:41:53.480 | - Immediate fuel and glycogen storage in the muscle.

00:41:56.500 | Absolutely, all right?

00:41:58.620 | Now, if you're active,

00:42:01.380 | then you will clear glucose into muscle,

00:42:04.660 | therefore your blood glucose won't rise as much

00:42:06.820 | 'cause it went into muscle,

00:42:08.060 | and therefore your pancreas will put out less insulin

00:42:11.300 | because it doesn't have to clear as much

00:42:13.180 | from the bloodstream, and that's okay, that's good, right?

00:42:16.780 | But let's say you didn't exercise,

00:42:18.620 | so you've got a big glucose excursion,

00:42:20.420 | now you have a big insulin response,

00:42:22.920 | and that insulin is going to take the excess

00:42:26.300 | that's in your blood, it has to clear it,

00:42:28.220 | and it will go to fat for storage.

00:42:31.380 | That insulin rise turns out to be particularly egregious

00:42:35.720 | in terms of metabolic disease, and I can prove it.

00:42:38.280 | There is a mouse, my favorite mouse.

00:42:42.780 | I love this mouse.

00:42:43.820 | This mouse turns medicine on its head

00:42:47.260 | and teaches every doctor why they have to go

00:42:49.940 | back to medical school and learn it right.

00:42:52.320 | This mouse is called the PADERCO mouse, P-O-D-I-R-K-O.

00:42:58.200 | - Is it discovered by PADERCO?

00:42:59.780 | - No. (laughs)

00:43:01.060 | No, it was discovered in Ron Kahn's lab,

00:43:03.500 | it was manufactured in Ron Kahn's lab.

00:43:05.580 | So this is a tissue-specific insulin receptor

00:43:08.460 | knockout mouse, I-R-K-O.

00:43:10.700 | - So it lacks the insulin receptor in the kidney.

00:43:15.260 | - PADERCO, glomerular podocyte

00:43:18.300 | insulin receptor knockout mouse.

00:43:20.380 | - We haven't talked too much about transgenic models

00:43:22.460 | and knock-ins and knock-outs,

00:43:23.560 | so just in 10 seconds or less, basically,

00:43:27.020 | these are mice that are genetically engineered

00:43:29.980 | to lack the receptor for insulin,

00:43:33.220 | specifically in the kidney.

00:43:35.660 | - Glomerular podocyte, the kidney.

00:43:36.980 | - In the kidney, and everywhere else in this mouse,

00:43:40.020 | insulin does its thing normally.

00:43:41.420 | - Exactly, great.

00:43:42.740 | So these animals are euglycemic, normal blood glucose levels.

00:43:47.740 | These animals are normally glucose-tolerant,

00:43:50.820 | so they go up, they go down, just like every other mouse.

00:43:54.320 | These mice are not fat, these mice are not thin.

00:44:00.660 | These mice are mice, except they have

00:44:05.620 | the worst diabetic nephropathy on the planet.

00:44:08.740 | - So their, oh, their kidney is degenerative.

00:44:11.460 | - Their kidneys degenerate to nothing.

00:44:14.020 | - Yikes.

00:44:14.860 | - Now, they have normal blood glucose levels.

00:44:18.180 | They have normal glucose tolerance.

00:44:20.020 | They have normal insulin tolerance whole body,

00:44:24.480 | but their kidneys are dying.

00:44:28.080 | How come?

00:44:30.420 | Can't be the glucose, it's the insulin,

00:44:33.460 | because insulin's the bad guy.

00:44:36.580 | Insulin's actually making the kidney disease.

00:44:40.020 | And so these animals that are insulin-resistant,

00:44:42.220 | they have diabetic nephropathy without diabetes.

00:44:45.780 | - So the insulin is having a negative,

00:44:50.020 | clearly negative effect on the kidneys

00:44:52.080 | without binding to the receptor.

00:44:54.140 | - Exactly.

00:44:54.980 | - So circulating insulin can do stuff

00:44:57.060 | without binding to its receptor.

00:44:58.980 | - Well, no, it binds to its receptor

00:45:01.180 | in different parts of the body.

00:45:02.580 | - Other parts of the body, but in the kidney it can't

00:45:04.540 | 'cause it's a knockout.

00:45:05.380 | - It's a knockout, right.

00:45:06.780 | The point is insulin does stuff by itself.

00:45:10.620 | And it turns out insulin drives growth.

00:45:14.540 | Now, every cell in your body wants to burn

00:45:19.300 | at one time in its life and wants to grow

00:45:25.220 | at another time in its life.

00:45:26.980 | Every cell has those two pathways.

00:45:30.420 | Burning, growth, burning, growth.

00:45:32.860 | What determines whether a cell should be burning

00:45:37.620 | or whether a cell should be growing?

00:45:40.420 | - I don't know what makes it burning,

00:45:42.260 | but presumably it has something to do with mitochondria.

00:45:44.660 | - It has everything to do with mitochondria.

00:45:47.900 | So every cell needs to burn and needs to grow

00:45:52.020 | at a different time in its life.

00:45:53.780 | Here's a way to think about it.

00:45:55.640 | We all start out as a zygote, a single cell.

00:45:58.900 | We end up an adult.

00:46:02.420 | Now, that single cell had to become two cells.

00:46:05.420 | Those two cells had to become four cells.

00:46:08.500 | Those four cells had to become eight cells.

00:46:12.180 | And on and on and on and on.

00:46:13.980 | So every cycle there's a doubling.

00:46:16.420 | How many doublings to get from a zygote to an adult?

00:46:22.380 | - What's an exponential growth?

00:46:25.260 | So I don't know it off the top of my head.

00:46:28.540 | - 41.

00:46:30.380 | - 41, two to the 41 doublings.

00:46:34.380 | - Gives you an organism?

00:46:35.220 | - 10 trillion cells.

00:46:37.220 | - We're 10 trillion cells?

00:46:38.060 | - We're 10 trillion cells.

00:46:38.900 | - Do we know that?

00:46:39.740 | - Yeah.

00:46:40.860 | - Okay.

00:46:42.180 | - Two to the 41.

00:46:43.300 | - Okay.

00:46:44.140 | - Okay, now of those 41 doublings,

00:46:47.980 | some of them had to occur in utero.

00:46:50.260 | Some of them had to occur postnatally.

00:46:53.340 | So I need two numbers that add up to 41.

00:46:57.700 | How many in utero?

00:46:58.780 | How many postnatally?

00:47:00.020 | - Postnatally.

00:47:00.860 | - Well, way more.

00:47:03.820 | You start off with a lot more than you end up with,

00:47:06.460 | but then you have cells that turn over

00:47:08.740 | throughout the lifespan.

00:47:09.660 | So this is a tough one.

00:47:10.780 | - Okay.

00:47:11.620 | - Because skin cells turn over.

00:47:12.460 | - Sure.

00:47:13.580 | - With neurons, it's pretty straightforward

00:47:16.060 | because you're gonna...

00:47:17.580 | - What you get is what you get.

00:47:19.260 | - Right, and you're born with somewhere between three

00:47:21.500 | and 10 X of what you end up with,

00:47:22.860 | depending on the brain structure.

00:47:24.060 | - Yeah.

00:47:24.900 | - So, but for whole body wide,

00:47:26.020 | I don't know how you'd come up with that number.

00:47:27.500 | - 36 and five.

00:47:29.740 | - Okay.

00:47:30.580 | - 36 doublings prenatally, five doublings postnatally.

00:47:34.780 | And I can prove that to you too.

00:47:36.500 | Typical baby weighs seven pounds.

00:47:39.580 | First doubling, 14 pounds.

00:47:40.980 | Second doubling, 28 pounds.

00:47:43.380 | Next doubling, 56 pounds.

00:47:45.140 | Next doubling, 112 pounds.

00:47:46.820 | Next doubling, 224 pounds.

00:47:48.740 | - Hopefully it stops there.

00:47:49.580 | - Obese individuals.

00:47:50.420 | - Hopefully it stops there.

00:47:52.100 | Not all people 212 pounds are obese,

00:47:54.820 | but some people who are certain heights or below

00:47:57.900 | are 212 or obese.

00:47:59.940 | Point is, the cell has to know when to grow

00:48:04.940 | and when to burn.

00:48:07.740 | It turns out that the signal for that is oxygen

00:48:11.860 | because oxygen is necessary for mitochondria

00:48:15.460 | to be able to burn.

00:48:17.020 | In the absence of oxygen, the cell only knows how to grow.

00:48:22.020 | This is actually why Otto Warburg won the Nobel Prize

00:48:25.420 | in 1931 for the Warburg effect.

00:48:27.620 | He asked the question,

00:48:29.020 | how come cancer cells don't need oxygen to grow?

00:48:33.500 | And the answer is because no cell needs oxygen to grow.

00:48:37.060 | In fact, oxygen is the thing that prevents growth.

00:48:40.820 | Famous article from the New England Journal of Medicine,

00:48:45.020 | 1951, Mount Everest in utero,

00:48:48.580 | because every fetus is oxygen deprived.

00:48:53.900 | So normal, partial pressure of oxygen, 100 millimeters

00:48:58.580 | of mercury out here, right?

00:49:00.580 | If I checked your blood, it'd be about 100, right?

00:49:03.300 | - I hope so.

00:49:04.260 | - How about a tumor cell?

00:49:06.100 | - Guess tumor cells probably, is it double?

00:49:11.300 | - About 44.

00:49:12.960 | - Wait, you just told me--

00:49:13.800 | - Partial pressure of oxygen in a tumor cell, it's about 44.

00:49:17.820 | - But you just told me that tumor cells,

00:49:19.580 | which grow like wild.

00:49:20.780 | - Right, they grow like wild

00:49:23.220 | because they don't have oxygen.

00:49:25.120 | - But there are some of the,

00:49:29.260 | so here's what's peculiar about it.

00:49:31.060 | Tumor cells are some of the most vascularized cells,

00:49:35.100 | or tumors are heavily vascularized.

00:49:37.460 | I mean, one way to try and kill one

00:49:39.780 | is to de-vascularize the tumor cell.

00:49:41.860 | - Yes, and angiogenesis inhibition, et cetera,

00:49:44.940 | is a big deal.

00:49:46.380 | Judah Folkman and all that from Harvard, you know.

00:49:49.980 | - So the excess blood to a tumor

00:49:51.920 | is the attempt to bring in oxygen that it's not getting.

00:49:54.320 | - That's right.

00:49:55.160 | - As opposed to delivering lots of oxygen

00:49:56.560 | and that's why it's growing.

00:49:57.520 | - That's right.

00:49:58.360 | - Okay.

00:49:59.500 | - But a fetus, what's the partial pressure in the placenta?

00:50:03.200 | - I don't know.

00:50:04.040 | - Six to 31.

00:50:04.880 | So it's actually like a mile above Mount Everest.

00:50:09.540 | That's how much oxygen the fetus gets.

00:50:12.260 | And it's for that reason that you've got 36 doublings.

00:50:16.400 | And then, as soon as you're out,

00:50:18.740 | you cut the cord and you start breathing

00:50:20.900 | and now your partial pressure's at 100,

00:50:23.140 | that's when growth slows down.

00:50:26.140 | - Has there been any effort to treat tumors

00:50:27.740 | by oxygenating tumors?

00:50:29.220 | - Yes.

00:50:30.060 | - And what does that look like?

00:50:30.900 | - It's hyperbaric oxygen therapy.

00:50:32.960 | It's a thing.

00:50:33.800 | - Oh yeah. - Yeah.

00:50:34.640 | - Yeah, we'll probably do an episode on hyperbaric chambers.

00:50:37.180 | The reason we haven't yet is it's pretty niche,

00:50:41.780 | but there are people who own these things,

00:50:43.760 | who sit in these things.

00:50:45.120 | Okay, so we got here by way of the bagel.

00:50:50.700 | - Right.

00:50:51.540 | - So I just want to orient us.

00:50:54.300 | You just had 250 calories of the bagel.

00:50:58.460 | We talked about glucose excursions.

00:51:00.780 | - But it's that insulin rise that's driving the adiposity

00:51:04.860 | and it's also driving the growth, okay?

00:51:08.140 | In the absence of oxygen.

00:51:10.060 | 'Cause if you have oxygen,

00:51:11.260 | then you don't need that much insulin.

00:51:13.100 | - Okay.

00:51:15.120 | So, because you're gonna burn instead of store.

00:51:19.160 | Got it.

00:51:21.000 | In terms of the raw metabolism of carbohydrate though,

00:51:26.000 | that glucose, if I eat 250 calories of glucose,

00:51:31.480 | how much of that did I quote unquote actually eat?

00:51:33.960 | How much is used?

00:51:35.880 | - How much is used?

00:51:36.760 | - Yeah, let's assume that I'm at my desk working

00:51:39.520 | or I'm walking around a little bit.

00:51:40.920 | I'm not exercising hard in the subsequent hour.

00:51:44.180 | - So used for what is the question?

00:51:46.420 | - I'm getting back to the calories.

00:51:47.800 | Is the calorie a calorie?

00:51:49.140 | Clearly the answer is no.

00:51:50.440 | But based on the processing of different types of calories,

00:51:52.640 | we established it for fat.

00:51:53.840 | The almonds, we established it for protein.

00:51:56.000 | The porterhouse with butter.

00:51:58.060 | And now we're trying to establish that

00:52:00.220 | for the 250 calories of bagel, which is glucose.

00:52:03.180 | - Right.

00:52:04.020 | So the glucose has to be phosphorylated.

00:52:05.700 | So you're gonna lose an ATP in the process.

00:52:09.480 | So ATP goes to ADP.

00:52:12.360 | And then that ADP will go to AMP, adenosine monophosphate,

00:52:16.280 | which will then go to IMP, adenosine monophosphate,

00:52:19.840 | which will then go to uric acid.

00:52:21.840 | - Okay.

00:52:22.680 | - And that uric acid will be then released from the cell,

00:52:25.640 | circulate in the bloodstream,

00:52:26.720 | and hopefully go out in the kidney.

00:52:28.580 | In the process, that uric acid

00:52:30.700 | can inhibit mitochondrial function,

00:52:33.320 | and it can also inhibit endothelial nitric oxide synthase,

00:52:37.360 | which is the enzyme in your vasculature

00:52:41.600 | that is your endogenous blood pressure lower.

00:52:44.960 | - Right, by expanding blood vessels and capillaries.

00:52:47.200 | - Exactly.

00:52:48.040 | - Right, this is the mechanistic foundation

00:52:50.740 | of the drugs that were originally used

00:52:53.200 | for improving prostate function,

00:52:55.480 | but are used to treat erectile dysfunction,

00:52:57.360 | which are the PDE inhibitors,

00:53:00.120 | which allow nitric oxide to be around longer

00:53:03.680 | and more of it, right?

00:53:04.940 | People use it for other purposes too.

00:53:06.920 | Now no one will forget, if I queue it up with that example.

00:53:09.640 | - We, in the neonatal intensive care unit,

00:53:12.840 | it closes patent ductus arteriosus,

00:53:14.840 | which is a big deal in the neonatal world.

00:53:19.320 | - Well, okay, I wanna ask you about that,

00:53:20.940 | but so I heard two things.

00:53:23.040 | One is that glucose and the insulin that goes with it

00:53:27.240 | increases uric acid.

00:53:29.180 | Uric acid, while it has certain important functions

00:53:32.800 | in health, too much of it, you said,

00:53:34.680 | can inhibit nitric oxide.

00:53:36.720 | - Yeah, can inhibit nitric oxide.

00:53:37.880 | - So that means that the blood vessels and capillaries

00:53:39.520 | are gonna stay more constricted,

00:53:40.740 | so blood pressure is gonna be higher

00:53:42.400 | than it would be normally.

00:53:43.240 | - That's right.

00:53:44.080 | - And then uric acid is also inhibiting

00:53:46.480 | mitochondrial function.

00:53:47.760 | - That's right.

00:53:48.600 | - Okay.

00:53:50.240 | But eating half a bagel isn't necessarily a terrible thing

00:53:53.920 | if it's within your caloric requirements.

00:53:56.720 | - And it all depends on how much you clear

00:54:01.720 | and how high your insulin goes.

00:54:04.900 | - Now let's compare that 250 calories of glucose

00:54:09.280 | to 250 calories of fructose.

00:54:11.320 | - Right.

00:54:12.720 | - Let's come up with a food example.

00:54:14.360 | 250 calories of fructose would be trivial to consume

00:54:18.440 | in the form of high fructose corn syrup, right?

00:54:20.360 | - So remember that high fructose corn syrup

00:54:22.220 | is half glucose, half fructose.

00:54:23.800 | - Okay, so let's not use--

00:54:24.640 | - So it'd be 125, 125.

00:54:26.020 | - So let's not use that.

00:54:26.920 | Well, so let's assume, so we can talk about a soda

00:54:30.080 | to get that 250 calories easily,

00:54:34.540 | especially if it's not a can or a European-sized bottle.

00:54:38.200 | - Eight ounce can of soda.

00:54:40.640 | - Okay, so eight ounce can of soda and maybe

00:54:43.520 | let's include a food item.

00:54:44.520 | Let's talk like a store-bought packaged cookie,

00:54:47.360 | couple of Oreos, two Oreos.

00:54:49.120 | - Okay.

00:54:49.960 | - Probably get you to that 250 or maybe four Oreos.

00:54:51.680 | - Maybe three Oreos.

00:54:52.520 | - Okay, Oreo lovers everywhere celebrating.

00:54:55.400 | Three, 250 calories of fructose.

00:54:58.980 | What's the effect on uric acid?

00:55:03.060 | What's the effect on caloric burn?

00:55:05.920 | What's the effect on anything for that matter

00:55:07.520 | that we should be aware of?

00:55:09.080 | - All right, so first of all, the Oreo has plenty

00:55:10.720 | of fructose in it, so keep that in mind.

00:55:12.680 | - Okay.

00:55:13.520 | - Let's say you consumed 250 calories in a bagel

00:55:18.560 | 'cause that's pretty much polymerized glucose

00:55:21.400 | versus say the soda.

00:55:22.760 | So the bagel versus the soda, that's what you're--

00:55:24.680 | - Equivalent calories, right.

00:55:25.880 | - Equivalent calories.

00:55:26.720 | - Or the bagel versus let's say two Oreos

00:55:30.160 | and a little bit of, yeah, two Oreos.

00:55:33.240 | - Okay, so number one, there's only half the glucose

00:55:37.920 | in the soda because the other half is the fructose.

00:55:40.400 | So 125, 125.

00:55:41.960 | So your glucose rise won't be as high.

00:55:45.840 | Your glucose excursion will be lower.

00:55:48.240 | This is actually one of the reasons

00:55:50.120 | why there's this thing called glycemic index.

00:55:55.120 | And glycemic index is a canard.

00:55:56.960 | It's garbage.

00:55:58.160 | It is complete and utter BS.

00:56:00.520 | - The glycemic index.

00:56:01.780 | - Absolute BS.

00:56:03.480 | Nothing is more egregious in terms of argument

00:56:08.480 | than the glycemic index.

00:56:12.480 | And this is one of the things that dieticians

00:56:15.260 | promote and espouse and one of the things that's gotta go.

00:56:18.880 | This is an idea that must die.

00:56:20.420 | - Okay, we'll get back to why the glycemic index

00:56:22.640 | has gotta die.

00:56:23.720 | So 250 calories and actually can we make these equal

00:56:30.240 | just for sake of simplicity?

00:56:33.120 | Can we say 250 calories of glucose from the bagel

00:56:35.960 | versus 250 calories of fructose?

00:56:38.140 | How do we get 250 calories of pure fructose?

00:56:40.760 | - We don't.

00:56:41.580 | - You can't.

00:56:42.420 | Okay, you gotta bring the glucose with you.

00:56:43.260 | - Lab fructose.

00:56:44.360 | You'd have to make it crystalline fructose in the lab.

00:56:45.200 | - Then let's stay with the Oreos,

00:56:46.320 | which is half glucose, half fructose.

00:56:48.000 | - Right.

00:56:48.840 | I mean, there is no fructose alone in nature.

00:56:50.800 | - Even crackers, some of the ones that are salty

00:56:53.040 | are also sweet.

00:56:54.120 | They have fructose in them.

00:56:54.940 | - Yeah, absolutely.

00:56:55.780 | - High fructose corn syrup. - On purpose.

00:56:56.880 | - Yeah, that's why it's impossible to eat just one.

00:56:59.920 | - Indeed.

00:57:01.360 | - So what's happening biochemically

00:57:03.760 | as a consequence of the fructose component specifically?

00:57:06.720 | - So the fructose will, first of all, go into the intestine.

00:57:11.320 | The intestine will metabolize some of that fructose

00:57:15.320 | through what is known as intestinal de novo lipogenesis.

00:57:18.800 | About 10% of that fructose will be turned into fat

00:57:22.520 | right in the intestine.

00:57:24.320 | - And that's 'cause fructose, it just wants to be fat?

00:57:27.680 | - Yeah, fructose wants to be fat.

00:57:29.160 | Fructose is the lipogenic substrate.

00:57:31.680 | - Here, we're not talking about body fat.

00:57:32.880 | We're talking about fat molecules

00:57:35.040 | that can potentially be used as energy.

00:57:36.800 | - That's right, triglyceride molecules.

00:57:38.820 | Okay, so 10% of that fructose will be turned

00:57:41.940 | into triglyceride right in the intestine

00:57:44.480 | and be released into the bloodstream.

00:57:46.080 | And it is the reason

00:57:46.920 | for a postprandial triglyceride response.

00:57:49.560 | - Postprandial is, and I'm including myself in this group,

00:57:52.420 | is the nerd speak for after eating lunch.

00:57:54.920 | Typically it's lunch.

00:57:57.200 | So that's actually one of the drivers

00:57:59.820 | of cardiovascular pathology,

00:58:02.260 | that intestinal de novo lipogenesis,

00:58:04.740 | turning that fructose into triglyceride

00:58:07.080 | right in the intestine.

00:58:08.840 | Now, there's a limit to how fast

00:58:11.180 | and how much the intestine can do that.

00:58:14.000 | The rest of the fructose will be absorbed

00:58:17.240 | into the portal vein,

00:58:19.360 | but not before some of that fructose

00:58:22.560 | will make it further down

00:58:23.760 | and it will nitrate tight junction proteins.

00:58:27.560 | Now, let's talk about that. - Okay, portal vein

00:58:28.520 | of the kidney.

00:58:29.640 | - Portal vein goes to the liver.

00:58:31.840 | Portal vein goes from the visceral,

00:58:34.040 | from the intestine, to the liver.

00:58:35.860 | - No kidney, doesn't feed the kidney.

00:58:36.880 | - No kidney, no kidney.

00:58:38.200 | Intestine to liver.

00:58:41.360 | But fructose nitrates tight junction proteins.

00:58:45.520 | Now, let me explain that to your audience.

00:58:48.120 | Your intestine is a sewer.

00:58:50.340 | Definition of a sewer.

00:58:52.520 | A pipe with shit in it, okay?

00:58:55.120 | That's its sewer.

00:58:56.000 | Our intestines are sewers.

00:58:57.640 | There's junk in the center

00:59:02.120 | and the job of the intestine

00:59:04.200 | is to move the junk through to the anus,

00:59:08.600 | absorbing the good stuff while you can.

00:59:12.520 | The intestine is made up of cells,

00:59:14.320 | intestinal epithelial cells,

00:59:15.840 | that are bound together

00:59:17.640 | and they're bound with proteins

00:59:19.940 | that basically form a barrier.

00:59:23.800 | Those barriers are called tight junction proteins.

00:59:26.800 | - Things like Claudins and things like that?

00:59:29.000 | - Zonulin is the main one.

00:59:30.940 | Okay, there are others,

00:59:31.780 | but zonulin is the one that goes,

00:59:33.400 | is defective in celiac disease.

00:59:35.500 | - What defines a tight junction?

00:59:36.700 | Is it like completely impermeable or semi-permeable?

00:59:40.220 | - Completely impermeable,

00:59:42.120 | unless its function is inhibited.

00:59:45.640 | Turns out if you alter the phosphorylation status

00:59:50.640 | or the nitrate status of that tight junction,

00:59:54.320 | it will become transiently permeable, okay?

00:59:58.940 | And so fructose nitrates tight junction proteins,

01:00:02.280 | causing them to be transiently permeable,

01:00:05.520 | allowing some of the junk in your intestine

01:00:09.860 | to get through into your bloodstream.

01:00:12.740 | - So this is leaky gut.

01:00:13.780 | - This is leaky gut.

01:00:14.880 | This is what causes leaky gut.

01:00:16.920 | Fructose is a driver of leaky gut.

01:00:19.760 | - Got it.

01:00:21.080 | - That causes inflammation at the level of the liver,

01:00:23.840 | which ultimately leads to systemic inflammation,

01:00:25.960 | one of the reasons why high sensitivity CRP

01:00:29.960 | is high in patients who eat ultra-processed food.

01:00:33.320 | - CRP is C-reactive protein,

01:00:35.240 | which is a marker of a,

01:00:36.520 | essentially an inflammatory immune response.

01:00:38.400 | - Exactly.

01:00:39.240 | - You don't want it too high.

01:00:40.400 | - And 93% of Americans today are inflamed.

01:00:44.180 | - Does that mean that 93% of Americans have leaky guts?

01:00:47.780 | - Yeah, it does, 'cause that's where it comes from.

01:00:51.500 | - So in addition to limiting fructose intake,

01:00:55.380 | what are things that support the tight junctions

01:01:01.660 | of the intestinal pathway?

01:01:03.140 | - So there are three barriers in your intestine

01:01:05.580 | to keep the junk where it belongs, in the center,

01:01:09.240 | so that it can get pooped out your behind, all right?

01:01:12.840 | Three separate barriers.

01:01:14.560 | One is a physical barrier called the mucin layer.

01:01:18.720 | So it's a layer of mucus that actually sits

01:01:20.960 | on top of the intestinal epithelial cells.

01:01:23.460 | Now, that mucin is a polysaccharide,

01:01:28.820 | and the bacteria can use that mucin layer

01:01:33.100 | for its own purposes.

01:01:34.860 | It will eat your mucin layer

01:01:36.320 | if you don't feed your bacteria.

01:01:38.060 | You must feed your bacteria,

01:01:39.460 | or your bacteria will feed on you, okay?

01:01:42.720 | So you are in concert with your microbiome.

01:01:46.020 | If you deprive your microbiome of the food that it needs,

01:01:50.360 | it will use you as its food.

01:01:52.740 | And that's one of the reasons why fiber is so important.

01:01:56.100 | - So fiber to build up this mucin layer

01:01:58.100 | is one way to reinforce the fence

01:02:01.540 | that is the tight junctions, et cetera,

01:02:04.780 | between your intestine and the bloodstream.

01:02:07.500 | This raises an interesting point about fasting.

01:02:10.020 | Many people, including myself, do a pseudo intermittent

01:02:13.160 | fasting.

01:02:14.000 | I eat my first meal somewhere between 11 and noon.

01:02:16.120 | I'm not strict about this, the 11 versus noon thing.

01:02:18.960 | And I probably eat my last bite of food

01:02:20.240 | somewhere around 8 p.m.

01:02:21.200 | And occasionally it's outside that window.

01:02:23.320 | I've done this for a long time.

01:02:24.360 | It just feels best to me.

01:02:25.920 | But other people use a shorter eating window.

01:02:28.120 | One thing that I learned from a colleague at Yale

01:02:30.700 | who studies the gut microbiome that was surprising to me

01:02:33.480 | is that when you eat in that way,

01:02:36.940 | there's a long stretch of time, sometimes longer,

01:02:39.100 | for people that have a shorter eating window,

01:02:41.380 | longer fasting window, that is,

01:02:43.380 | where you're actually eating up your own intestinal lining.

01:02:47.680 | So this idea that fasting is so great for us,

01:02:50.040 | on the one hand might be true.

01:02:52.840 | On the other hand, you're actually consuming components

01:02:55.200 | of your, you're not feeding your gut microbiome

01:02:57.480 | and you deplete it.

01:02:58.320 | But then here's where I was positively surprised.

01:03:01.460 | When you do eat, provided that you eat enough fiber

01:03:04.560 | and in particular high quality fermented foods,

01:03:07.240 | low sugar fermented foods,

01:03:08.640 | it seems that the lining of the gut

01:03:11.340 | and the gut microbiome is replenished

01:03:13.460 | to a level that is greater than if you had eaten

01:03:16.600 | for longer periods of the 24 hour cycle.

01:03:18.880 | Do I have that right?

01:03:19.880 | - We do, you do have it right.

01:03:21.040 | And I don't know why that is true,

01:03:22.920 | but it does seem to be the case.

01:03:24.760 | And fermented foods, in part because they've got

01:03:28.920 | already short chain fatty acids in them,

01:03:32.020 | seem to help. - Is that the preferred food

01:03:33.200 | of the microbiome?

01:03:34.040 | - Well, it's what the microbiome actually turns fiber into.

01:03:37.800 | So it's probably helping your intestinal epithelial cells

01:03:42.680 | in the same way the microbiome turning fiber

01:03:45.340 | into short chain fatty acids helps.

01:03:47.200 | So it's what we call a postbiotic.

01:03:49.660 | So you have prebiotic, which is the food for the bacteria.

01:03:53.000 | You have the probiotic, which is the bacteria itself.

01:03:55.560 | And then you have the postbiotic,

01:03:57.000 | which is what the bacteria make in order to heal you.

01:04:01.320 | God, okay.

01:04:02.160 | And so short chain fatty acids are postbiotics.

01:04:04.960 | And there are a lot of people selling short chain fatty acids

01:04:07.940 | you know, drinks and supplements and what have you.

01:04:11.320 | Whether they work or not is another story.

01:04:13.640 | - If I consume fructose in the form of,

01:04:17.660 | let's say a highly processed food,

01:04:19.920 | has minimal antioxidants,

01:04:21.840 | but it's got plenty of calories typically.

01:04:23.920 | And it's disrupting the tight junctions,

01:04:27.040 | making my gut leaky.

01:04:28.640 | But I'm also eating fiber.

01:04:30.680 | You know, I'm having a meal that includes a salad.

01:04:33.880 | I'm having some probiotics.

01:04:35.600 | And then I want like a couple of Reese's peanut butter cups,

01:04:38.400 | like in the dark chocolate ones in particular.

01:04:40.300 | I don't do this anymore,

01:04:41.600 | but I used to eat like that more often.

01:04:43.400 | As time has gone on, I've become,

01:04:45.720 | I don't like to call it stricter,

01:04:46.720 | but more I tend to like healthier foods over time.

01:04:50.640 | And I think you can get away with different things

01:04:52.480 | at different stages of life.

01:04:53.800 | Although you work with young people,

01:04:55.420 | so we'll get to very young people.

01:04:57.280 | So we'll get to this.

01:04:58.300 | But how much damage am I doing by ingesting any fructose

01:05:03.080 | in the form of a highly processed food?

01:05:04.920 | - So I'll make it very simple, Andrew.

01:05:07.300 | I am for dessert.

01:05:10.220 | For dessert.

01:05:13.860 | I am not for dessert for breakfast, lunch,

01:05:16.160 | snacks, and dinner.

01:05:17.080 | So if you wanna have a couple of Reese's peanut butter cups

01:05:22.720 | as your dessert, in the same way as you might have

01:05:26.600 | a cognac for dessert, that's fine.

01:05:31.560 | I have no problem with that.

01:05:33.800 | - The question is, are you gonna eat Reese's peanut butter

01:05:35.800 | cups for breakfast?

01:05:36.800 | - No, I don't eat breakfast, but no.

01:05:39.440 | But I do see your point.

01:05:40.900 | - The National School Breakfast Program,

01:05:43.080 | which 29% of school children today consume,

01:05:47.320 | is a bowl of Froot Loops and a glass of orange juice.

01:05:50.440 | That is 41 grams of sugar.

01:05:53.320 | American Heart Association says that the upper limit

01:05:56.240 | for children should be 12 grams of added sugar per day.

01:06:02.500 | That's 41 grams of added sugar, and it's just breakfast.

01:06:07.500 | - And that's fructose rich.

01:06:10.640 | - Totally, completely.

01:06:12.200 | So the question is, which dessert are we talking about?

01:06:16.280 | - Right, and can we adjust that morning meal

01:06:19.840 | to a different reality?

01:06:21.280 | 'Cause I agree that there are plenty of kids eating that,

01:06:24.080 | or a muffin that might be the equivalent.

01:06:27.360 | But what about the parent who says,

01:06:29.960 | okay, let's come up with a healthier option

01:06:31.740 | that the kid still likes, like,

01:06:34.240 | I'm thinking back to my childhood,

01:06:36.000 | like a Honey Nut Cheerios or something.

01:06:37.760 | So not Froot Loops, which is kind of the extreme.

01:06:41.160 | - Take a look at the side of the package.

01:06:43.160 | No difference.

01:06:44.000 | - Now let's say they go with some waffles that are made.

01:06:49.000 | So with a pre-made mix, some milk, some butter,

01:06:54.060 | so mom or dad is making waffles.

01:06:57.840 | Great, it sounds healthier, but then if you do the breakdown

01:07:00.520 | we're still ending up at very high.

01:07:02.200 | Are we basically eating dessert for breakfast

01:07:03.660 | in that case too? - Are we eating Eggo waffles?

01:07:05.240 | Or are we making waffles de novo

01:07:08.880 | from scratch in your own kitchen?

01:07:10.920 | - Let's say making- - Big difference.

01:07:13.560 | Okay, because the Eggo waffles replete with sugar on purpose

01:07:18.560 | because the food industry knows when they add it,

01:07:20.700 | you buy more because it's addictive.

01:07:23.880 | And we actually have the demographic, the mechanistic,

01:07:30.360 | the imaging, and also the economic data to demonstrate

01:07:35.360 | that sugar's addictive and the food industry knows it.

01:07:38.920 | So have you ever heard of a phenomenon

01:07:40.480 | called price elasticity?

01:07:42.300 | Price elasticity is an economic term that is used

01:07:48.280 | to ask the question, if the price of a given good

01:07:53.280 | goes up by 1%, that should result in reduction

01:07:58.400 | in purchase or consumption

01:08:01.300 | because price influences consumption.

01:08:04.120 | How much does it influence it?

01:08:07.680 | So if something's price elastic, when the price goes up,

01:08:12.680 | consumption goes down equivalently.

01:08:15.240 | A food that is price elastic,

01:08:19.080 | the most price elastic food is eggs.

01:08:22.040 | So when the price of eggs goes up 1%,

01:08:25.520 | consumption of eggs goes down 0.68%,

01:08:30.520 | meaning that eggs have a price elasticity of 0.32.

01:08:34.980 | Got it? - Got it.

01:08:37.480 | - Now, what's the most price inelastic food?

01:08:41.320 | The top three most price inelastic foods are fast food.

01:08:47.280 | - Cereal? - 0.81.

01:08:49.400 | - I like a good quiz.

01:08:51.020 | Fast food, 0.81, soft drinks at 0.79 and juice at 0.77.

01:08:56.020 | - Meaning people will pay not whatever,

01:08:59.940 | but they're willing to pay more,

01:09:01.980 | more readily willing to pay more.

01:09:04.740 | - Because of the sugar, because it's addictive,

01:09:07.540 | because it's hedonic.

01:09:09.120 | So many, many years ago, Andrew,

01:09:12.180 | you probably remember something called Keynesian economics.

01:09:16.300 | And Keynesian economics was based on this concept

01:09:19.180 | of the rational actor.

01:09:21.140 | And the rational actor can determine value,

01:09:25.060 | which is utility over cost.

01:09:27.020 | And if you're a rational actor,

01:09:30.380 | you should be able to say, yeah, I'll buy that,

01:09:32.220 | but I won't buy that, right?

01:09:34.520 | Okay.

01:09:35.360 | In 1979, Daniel Kahneman and Amos Tversky,

01:09:41.140 | Nobel Prize winner, Daniel Kahneman,

01:09:44.980 | described the irrational actor.

01:09:48.140 | Now the irrational actor cannot determine value.

01:09:51.020 | And the reason is because he is risk averse.

01:09:54.140 | So the cost is always too great.

01:09:56.560 | So the utility may be the same,

01:09:58.660 | but the cost goes up because that's why they have,

01:10:02.140 | you know, aversive tendencies, the irrational actor.

01:10:06.340 | Jeffrey Sachs has described the hedonic actor,

01:10:10.180 | who also cannot determine value

01:10:13.780 | because it doesn't matter what it costs.

01:10:15.440 | They need their fix.

01:10:16.660 | And this is what's going on and the food industry knows it.

01:10:21.660 | And that's why every food in the store has been spiked.

01:10:27.120 | - I'd like to take a quick break

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01:11:51.620 | - We talked about dessert for breakfast

01:11:53.460 | in the form of cereals,

01:11:55.100 | some of which are disguised or couched as healthier.

01:12:00.100 | You know, I think of like honey nut Cheerios.

01:12:02.300 | It seems healthier than Froot Loops.

01:12:03.900 | It looks healthier like just by way of color.

01:12:06.020 | It looks kind of weedy, you know, color.

01:12:08.300 | So, but let, and in terms of lunch,

01:12:10.460 | I mean, one of the things that I love about Europe

01:12:13.020 | is that the breads are amazing.

01:12:14.780 | - Yeah, that's a terrific pair.

01:12:16.580 | - And I like them because they're not as sweet.

01:12:18.540 | - Exactly.

01:12:19.380 | - And so a sandwich from not every deli,

01:12:21.420 | but from a typical sandwich shopper

01:12:23.580 | that one makes with store-bought bread, sliced bread

01:12:26.940 | in the US has a lot of fructose.

01:12:29.240 | I looked this up prior to our discussion today.

01:12:32.300 | So in some ways, dessert is being woven into foods

01:12:35.620 | that are, that parents and or kids,

01:12:39.220 | everyone thinks are savory, we're actually eating sweets.

01:12:42.460 | - Exactly right.

01:12:43.300 | - But we can't, but we don't taste them as sweet

01:12:45.380 | at a conscious level necessarily, right?

01:12:47.740 | - But our taste buds do.

01:12:49.200 | - Right.

01:12:50.040 | - That's exactly right.

01:12:50.860 | So the question is why do they do that?

01:12:53.220 | So question for your audience.

01:12:56.100 | You buy a loaf of bread at the local bakery.

01:13:00.140 | How soon before it stales?

01:13:02.260 | - Two days at best.

01:13:03.580 | - Yeah.

01:13:04.420 | - If it's really great bread.

01:13:05.580 | - That's right.

01:13:06.420 | - The better the bread, the quicker it stales.

01:13:09.460 | You buy a loaf of bread at the neighborhood grocery store.

01:13:14.460 | How soon before it stales?

01:13:16.940 | - You've got probably a week and then there's moldy pieces

01:13:21.080 | at the end that you, you know, if you're in college

01:13:23.300 | and you were maybe trying to scrape that off.

01:13:25.100 | (laughing)

01:13:26.300 | - It can last up to three weeks, depending, right?

01:13:28.320 | - You could throw it in the freezer.

01:13:29.640 | You probably do that with the bakery bread,

01:13:31.100 | but it's never the same.

01:13:32.040 | - Never the same.

01:13:32.880 | - It's never the same.

01:13:33.700 | - So the question is why is that?

01:13:34.540 | And the answer is sugar.

01:13:36.260 | The answer is sugar.

01:13:38.480 | So the grocery store bread had sugar added to it on purpose

01:13:43.480 | because when you bake it, the sugar does not evaporate.

01:13:49.360 | It stays in the bread and the sugar is hygroscopic,

01:13:52.820 | meaning it holds on to water.

01:13:55.020 | This is a phenomenon that the food industry uses

01:13:57.180 | called water activity, okay?

01:13:59.380 | And so it will hold on to water and so it will stay spongy

01:14:02.860 | and will not stale as quickly as the bakery store bread,

01:14:06.180 | which did not have that sugar added to it.

01:14:09.660 | So even something as benign as bread has been turned

01:14:13.620 | into something that ultimately leads

01:14:16.220 | to chronic metabolic disease.

01:14:17.740 | - We've pivoted somewhat from carbohydrate divided

01:14:23.300 | into glucose and fructose to a discussion of sugar.

01:14:27.220 | Could you tell us the link between sugar and fructose?

01:14:29.960 | - So table sugar, what percentage of table sugar is fructose?

01:14:33.720 | What percentage of brown sugar is fructose?

01:14:36.040 | What percentage of the sugar that's added to food

01:14:38.400 | is high fructose corn syrup on average?

01:14:40.500 | You know, just because here what we're talking about

01:14:42.320 | is what you're describing as an intentional lacing of food

01:14:47.320 | with something that's addictive,

01:14:48.620 | but that's also processed very differently

01:14:50.940 | at the level of the kidney, at the level of the liver.

01:14:53.600 | And it's bad, it's a bad situation.

01:14:58.880 | - So when we talk about sugar,

01:15:01.320 | I think we need to be as careful

01:15:03.220 | in describing what we really mean

01:15:05.300 | as when we talk about a calorie.

01:15:07.100 | - I completely agree.

01:15:08.580 | So for your audience,

01:15:10.260 | let's be very, very clear on definitions.

01:15:13.560 | Let's not use the word sugar

01:15:17.580 | because it has multiple definitions.

01:15:21.380 | Let's use sucrose.

01:15:24.980 | Sucrose is what you put in your coffee.

01:15:29.720 | It's the crystals, right?

01:15:31.660 | It's cane sugar, beet sugar,

01:15:33.780 | you know, the stuff that you, teaspoons of, right?

01:15:39.060 | This was all that was available for many, many years.

01:15:42.100 | That is one molecule of glucose,

01:15:46.500 | one molecule of fructose bound together

01:15:49.860 | for the chemists out there in O-glycosidic linkage, okay?

01:15:54.740 | The enzyme in your intestine called sucrose

01:15:57.420 | cleaves this O-glycosidic linkage in about a nanosecond.

01:16:01.020 | You absorb the two molecules separately.

01:16:03.300 | The glucose goes to the entire body,

01:16:05.500 | generates an insulin response.

01:16:06.960 | The fructose goes straight to your liver, generates fat.

01:16:09.880 | That's sucrose.

01:16:13.300 | High fructose corn syrup

01:16:15.020 | is essentially one molecule of glucose,

01:16:18.220 | one molecule of fructose, not bound together.

01:16:22.180 | No O-glycosidic linkage.

01:16:24.920 | So they're free.

01:16:26.120 | The enzyme sucrose doesn't care

01:16:30.140 | because the blond's already broken.

01:16:33.020 | Ultimately, they do the same thing,

01:16:36.180 | and that's why high fructose corn syrup and sucrose

01:16:39.180 | are indistinguishable metabolically.

01:16:41.740 | What they are is they're very different economically,

01:16:46.780 | and the reason is because high fructose corn syrup

01:16:48.900 | is half the price of sucrose

01:16:52.020 | because sucrose we get from importing,

01:16:55.980 | and high fructose corn syrup we make at home.

01:16:58.280 | Sucrose is in bags.

01:17:02.260 | High fructose corn syrup is in barrels.

01:17:05.320 | Sucrose you can sell at the store.

01:17:07.800 | High fructose corn syrup you sell

01:17:09.740 | to the ultra-processed food manufacturer.

01:17:13.020 | You can't buy high fructose corn syrup at the grocery store.

01:17:17.740 | So they're very different

01:17:18.900 | in terms of what they're used for.

01:17:22.820 | High fructose corn syrup is particularly egregious

01:17:25.340 | because it's so miscible, because it's already a liquid.

01:17:30.140 | So you probably remember Chips Ahoy cookies in the old days.

01:17:35.020 | They often would seem like the sugar

01:17:38.780 | in the cookie had crystallized

01:17:41.300 | 'cause the sugar content was so high.

01:17:43.660 | - It's been a while since I've had one.

01:17:45.160 | They weren't particularly good.

01:17:46.580 | - Yeah, well now--

01:17:47.900 | - But you eat two of them,

01:17:49.700 | and then you think they're good,

01:17:51.140 | and then you want to eat four.

01:17:52.500 | That's what's so odd.

01:17:53.380 | The first bite is kinda like the,

01:17:55.300 | and then it's bombs away.

01:17:57.300 | - There you go.

01:17:58.760 | Well now it's a chewy Chips Ahoy cookies.

01:18:01.820 | - Oh, I remember the chewy Chips Ahoy cookies.

01:18:03.540 | - Remember chewy chips?

01:18:04.380 | Well that, that's high fructose corn syrup

01:18:06.940 | because the two molecules are free,

01:18:11.820 | they don't crystallize.

01:18:13.700 | So you can actually up the dose.

01:18:16.680 | Several times throughout today's discussion,

01:18:18.440 | you've been talking about the quote unquote food industry.

01:18:22.160 | Okay, so I'm not a conspiracy theorist.

01:18:24.280 | - I am.

01:18:25.120 | - But I understand, you know,

01:18:29.680 | that most businesses exist to make money.

01:18:33.840 | Many businesses start off with good intentions and drift

01:18:36.780 | in order to stay competitive.

01:18:40.140 | And many, many businesses, as we know,

01:18:46.440 | not all of which are entirely bad,

01:18:49.020 | such as the pharmaceutical industry, right?

01:18:51.140 | There are bad, there are instances of like the opioid crisis,

01:18:53.940 | but then there are drugs from the pharmaceutical industry

01:18:56.440 | that help save lives.

01:18:58.480 | I mean, that's my stance.

01:19:00.060 | The food industry, I think there are good actors

01:19:03.060 | and there are bad actors,

01:19:03.920 | but we're talking about the food industry.

01:19:05.940 | Okay, well, we can talk about the exercise industry,

01:19:08.140 | we talk about the podcast industry.

01:19:09.540 | I mean, you got good actors and bad actors,

01:19:11.760 | but what you've alluded to several times here,

01:19:13.500 | and you're more informed than I am,

01:19:15.340 | is a concerted effort to lace food with a form of sugar

01:19:20.340 | that makes people crave more of that food,

01:19:26.860 | and that is causing metabolic illness,

01:19:29.140 | disrupting mitochondria, and on and on.

01:19:32.280 | - Exactly.

01:19:33.120 | - And you're the physician, not me.

01:19:34.820 | You've worked with patients who struggle with obesity

01:19:38.260 | and for various reasons, not me.

01:19:40.980 | And so we could probably spend hours, if not days,

01:19:45.980 | talking about all the terrible things

01:19:48.260 | that the quote-unquote food industry has done,

01:19:49.860 | but what do you think is the pure motivation, right?

01:19:54.100 | I don't think that they want people to be sick,

01:19:57.200 | but they wanna sell product and this sells more product.

01:20:00.220 | So then it raises two questions.

01:20:01.940 | Why is it that more people don't know this information,

01:20:07.940 | although many more will know after today's conversation,

01:20:10.060 | but, and certainly in government, it's a mix,

01:20:14.020 | regardless of what side of the aisle you're on,

01:20:15.660 | or if you're right in between.

01:20:17.380 | There are clearly people that care about

01:20:19.840 | the health of themselves and others.

01:20:21.220 | So I can understand how things

01:20:23.800 | might've gotten to this point,

01:20:25.880 | but what do you think are the barriers

01:20:28.460 | to getting people to appreciate just what a problem this is,

01:20:32.320 | and getting people to change their choices

01:20:34.700 | in terms of what they're eating?

01:20:36.340 | Are they truly addicted to the point where they are sick,

01:20:38.700 | they can't make good decisions?

01:20:40.160 | Like a drug addict who's highly addicted to heroin

01:20:43.100 | is a sick person, they have an illness

01:20:44.700 | and they need treatment, but until they get that treatment,

01:20:47.940 | they can't make good decisions.

01:20:50.860 | - Let's take an analogy, alcohol.

01:20:53.500 | 40% of Americans are teetotalers, never touch this stuff.

01:20:58.460 | - 40% don't drink. - 40% don't drink.

01:21:00.460 | - Great, I'm not a big fan of alcohol.

01:21:02.580 | I've never seen it make anyone better

01:21:04.060 | at anything that really mattered.

01:21:05.180 | - No, because it's- - Except drinking.

01:21:06.380 | And that doesn't really matter.

01:21:07.220 | - It's also completely vestigial.

01:21:08.420 | There's no biochemical reaction in the body

01:21:11.380 | that requires alcohol, okay?

01:21:13.980 | For the same reason, by the way, fructose.

01:21:16.100 | 40% are social drinkers.

01:21:18.980 | Yeah, you can pick up a beer, put it down,

01:21:20.540 | I'm in that category.

01:21:22.380 | 10% are binge drinkers, and 10% are chronic alcoholics.

01:21:26.300 | Okay?

01:21:28.580 | Now, do you deprive the 40% of social drinkers

01:21:35.300 | because of the 20% of binge drinkers and chronic alcoholics?

01:21:40.300 | - Well, I believe people should be in choice,

01:21:43.100 | but I believe people should know what they are doing

01:21:45.580 | so that they can be in choice, right?

01:21:47.540 | Like, do as you, I always say,

01:21:49.220 | and I said this about the alcohol episode,

01:21:51.040 | which turned out to be one of our most prolific episodes,

01:21:53.540 | where I said that more than two drinks,

01:21:55.580 | zero is better than any,

01:21:56.700 | and more than two drinks per week,

01:21:57.940 | you need to do other things to offset that,

01:21:59.700 | and it's problematic.

01:22:01.380 | Those are what the data say.

01:22:02.300 | But I would say, do as you want, but know what you're doing.

01:22:06.200 | - Well, so I would say that that's exactly

01:22:09.100 | what the food industry wants you to think.

01:22:12.340 | That is the food industry's mantra,

01:22:15.860 | is you have your own choice, personal responsibility.

01:22:20.660 | So the question is, does personal responsibility work?

01:22:25.020 | And the answer is, no, it doesn't.

01:22:27.220 | Every public health debacle

01:22:31.660 | in the history of mankind

01:22:33.860 | started out as a personal health issue

01:22:36.060 | before it became a public health crisis.

01:22:38.380 | And you can pick your personal responsibility issue,

01:22:42.700 | whether it be exposures, whether it be addictions,

01:22:45.760 | whether it be infections.

01:22:47.900 | Bottom line is, ultimately,

01:22:50.080 | it required a societal response, okay?

01:22:53.900 | We can talk about syphilis, we can talk about tuberculosis,

01:22:57.820 | ultimately needed a public health response.

01:22:59.980 | We can talk about teen pregnancy, we can talk about--

01:23:03.900 | - Tobacco.

01:23:04.740 | - Tobacco ultimately needs a public health response

01:23:07.860 | because the sheer enormity of it

01:23:10.160 | and the egregiousness of it

01:23:12.820 | requires that public health response.

01:23:15.340 | Well, turns out, this is no different.

01:23:18.280 | In order to exercise personal responsibility,

01:23:22.500 | four criteria have to be met.

01:23:26.060 | Those four criteria are the following.

01:23:28.360 | Number one, knowledge.

01:23:30.380 | You have to have the knowledge

01:23:32.300 | because if you don't have the knowledge,

01:23:33.540 | then how can you exercise personal responsibility?

01:23:36.160 | Well, in fact, the public's being kept from the knowledge.

01:23:39.940 | We're doing this now in part to entrain that knowledge,

01:23:44.640 | to get people to understand what the problem is.

01:23:48.140 | - Yeah, I consider myself pretty informed

01:23:50.220 | about nutrition and health,

01:23:51.500 | but already today I've learned two dozen facts

01:23:56.660 | about processing of fructose in calories generally

01:23:59.820 | that I had no knowledge of prior.

01:24:01.600 | - Well, that's good, okay?

01:24:03.700 | 'Cause it's not about the math, it's about the science, okay?

01:24:07.500 | They want it to be about calories.

01:24:09.440 | So we have this thing called food science,

01:24:11.740 | we have this thing called nutrition,

01:24:13.580 | and we have this thing called metabolic health.

01:24:15.900 | They are not the same.

01:24:17.060 | Food science is what happens to food

01:24:19.580 | between the ground and the mouth.

01:24:21.820 | Nutrition is what happens to food

01:24:23.300 | between the mouth and the cell.

01:24:25.400 | Metabolic health is what happens to food inside the cell.

01:24:28.940 | But all of the chronic diseases that we are suffering from,

01:24:32.140 | type 2 diabetes, hypertension, dyslipidemia,

01:24:34.440 | cardiovascular disease, cancer, dementia,

01:24:36.160 | fatty liver disease, polycystic ovarian disease,

01:24:38.120 | those eight diseases, which make up 75%

01:24:41.540 | of healthcare expenditures in this country today,

01:24:44.160 | are all inside the cell,

01:24:48.620 | because they are all mitochondrial dysfunction,

01:24:52.420 | and there is no medicine that gets to the mitochondria.

01:24:56.860 | - Although you and others at Stanford, Harvard, et cetera,

01:25:00.760 | are starting this with metabolic psychiatry

01:25:02.860 | being one instance, right?

01:25:03.980 | - Indeed. - And UCSF as well,

01:25:05.480 | forgive me, I should have mentioned UCSF up front.

01:25:08.060 | Your home institution, wonderful institution

01:25:10.140 | right up the road from Stanford.

01:25:11.780 | So, you know, things are changing.

01:25:13.260 | People are starting to think about mitochondrial health.

01:25:15.000 | - They are.

01:25:15.840 | - Okay, so you listed off the first thing.

01:25:17.700 | You said there are four things that stand is bare.

01:25:19.440 | First one was knowledge. - Knowledge.

01:25:21.300 | - Second, access, because if you don't have access,

01:25:24.540 | then how can you exercise personal responsibility?

01:25:27.180 | - Access to healthier alternatives.

01:25:29.580 | - Exactly.

01:25:30.500 | - Which means cost-effective.

01:25:31.580 | I mean, I love berries from the farmer's market

01:25:34.420 | more than I love berries from the store.

01:25:35.720 | I love the farmer's markets generally,

01:25:38.500 | but it takes time, energy to go there,

01:25:40.760 | and the cost is actually lower

01:25:43.460 | at the level of what you hand the vendor, typically,

01:25:47.060 | but volume is tough to achieve.

01:25:50.060 | - They actually have me at a quota.

01:25:52.180 | I'm not allowed to buy as many berries as I want

01:25:54.600 | because obviously there are other people who want berries.

01:25:56.740 | So there's that, right?

01:25:57.580 | People have to feed their family that, you know,

01:25:59.620 | and we're used to eating a lot of volume.

01:26:02.280 | - But you're able to at least go there.

01:26:04.520 | - Sometimes, yeah.

01:26:05.820 | - We're talking about people who live in, quote, food deserts.

01:26:08.900 | We're also talking about people who live in food swamps, okay?

01:26:12.300 | When we're talking about food swamps,

01:26:13.560 | we're not talking about a plethora of healthy foods.

01:26:17.180 | We're talking about all the junk.

01:26:19.260 | That's what they, they live in the swamp of junk.

01:26:21.980 | So if you live in the swamp of junk,

01:26:25.100 | how are you supposed to exercise personal responsibility?

01:26:28.380 | Number three, or affordability.

01:26:33.140 | So you have to be able to afford your choice,

01:26:34.900 | and society has to be able to afford your choice.

01:26:37.620 | And right now, we can't afford that choice

01:26:40.040 | because healthcare costs right now

01:26:43.980 | are at $4.1 trillion a year.

01:26:47.880 | - But like so many things in behavioral economics and health,

01:26:52.880 | it's so hard for people to see that the immediate choice

01:26:57.600 | is leading to a higher cost down the road.

01:27:00.520 | There are just too many nodes of separation

01:27:02.660 | for people to realize,

01:27:03.500 | hey, when I'm reaching for this cereal,

01:27:04.840 | as opposed to making waffles for my kids from scratch,

01:27:07.880 | or, you know, they're thinking time efficiency,

01:27:10.000 | cost efficiency, volume, the kid's not throwing tantrums

01:27:13.080 | 'cause they're no longer getting the cereal.

01:27:15.420 | And it's very difficult to see this is the reason

01:27:18.320 | why healthcare costs are going up.

01:27:20.100 | There are just too many nodes of separation.

01:27:21.700 | - Well, couldn't agree more.

01:27:23.020 | But ultimately, it's because the government separates

01:27:26.720 | and silos food industry profits from healthcare costs.

01:27:31.720 | If you actually combine those,

01:27:34.380 | 'cause they ultimately are the same,

01:27:36.620 | you would see the problem.

01:27:38.240 | So globally, the food industry grosses $9 trillion a year.

01:27:44.240 | Healthcare costs globally cost $11 trillion a year,

01:27:49.240 | dietary related healthcare costs.

01:27:52.120 | Environmental costs cost $7 trillion a year,

01:27:57.120 | and productivity costs cost $1 trillion a year.

01:28:01.060 | So when you do the math,

01:28:02.540 | nine minus 11 minus seven minus one

01:28:05.100 | means that there is a $10 trillion a year deficit

01:28:10.260 | because of us cleaning up the mess

01:28:14.800 | that the food industry makes.

01:28:16.600 | - And while numbers like that-

01:28:17.440 | - That's not affordable.

01:28:18.760 | - Right, I agree.

01:28:19.600 | And while numbers like that land really hard,

01:28:22.240 | I find that for myself and for many people,

01:28:25.000 | statistics like that are hard to keep in mind in a way.

01:28:29.040 | There's something about the human brain

01:28:30.120 | that hears that and goes, whoa,

01:28:31.840 | where like that war costs that much

01:28:34.160 | and this food issue costs that much.

01:28:36.380 | And then we go to the store and we're hungry.

01:28:38.800 | And the kids are hungry.

01:28:41.900 | And so those nodes of separation,

01:28:44.280 | it's almost like a neural slash memory

01:28:46.940 | slash prefrontal cortex issue to me.

01:28:48.820 | And of course I look at everything

01:28:49.860 | through the lens of neurobiology.

01:28:51.180 | - Me too.

01:28:52.020 | - Not everything, but most everything.

01:28:53.420 | And so how could I not, how could we not?

01:28:56.440 | But then the issue is,

01:28:59.460 | well, there's still food on the shelves.

01:29:01.380 | And so what do we do to bring closer together these nodes?

01:29:06.380 | What would the government do?

01:29:08.180 | So the question is, is there food on the shelves?

01:29:10.620 | Let me finish the fourth one

01:29:11.840 | and then I wanna come back to that point.

01:29:13.660 | Let me just finish a concept.

01:29:16.360 | So affordability.

01:29:17.540 | And number four, externalities.

01:29:20.880 | Your choice can't hurt anybody else.

01:29:25.020 | But what if your choice does hurt somebody else?

01:29:27.360 | So like for tobacco, secondhand smoke.

01:29:29.900 | - Right.

01:29:30.740 | - Four, alcohol, drunk driving.

01:29:33.020 | - But what's the argument for teen pregnancy

01:29:34.580 | that someone else was gonna have to raise the kids?

01:29:36.400 | - Exactly.

01:29:37.720 | - But what about for food?

01:29:39.780 | Well, how about the fact that your employer,

01:29:43.500 | Stanford University, has to pay $2,750 per year

01:29:48.500 | in obesity-related healthcare expenses

01:29:51.840 | that they have passed on to you

01:29:54.420 | even though you're not obese?

01:29:55.860 | That is affecting you.

01:29:58.820 | So that guy's obesity right there, that is affecting you.

01:30:04.260 | But there, nowadays, it's especially tricky

01:30:07.760 | even to have the conversation.

01:30:09.180 | I'm willing to have it now,

01:30:11.040 | which is that there's this whole concept

01:30:13.360 | of fat-shaming, right?

01:30:14.320 | So if somebody's obese, whose fault is it?

01:30:16.520 | And if we even talk about it,

01:30:18.120 | are we subject to attack, legitimate attack?

01:30:24.360 | So calling someone obese at a clinical level,

01:30:30.440 | like I mean, you're an expert in endocrinology.

01:30:33.820 | Don't talk about obesity.

01:30:35.280 | Let's talk about diabetes.

01:30:37.120 | - Okay, so talk about the consequence of obesity.

01:30:39.160 | - Yeah, let's talk about the metabolic health issue itself.

01:30:42.400 | The fact is that diabetes is now 11.4% of America.

01:30:49.320 | - What was it 20 years ago?

01:30:51.980 | - It was, 20 years ago, it was about 8%.

01:30:55.440 | - I was wondering this earlier.

01:30:56.920 | 20 years ago, there was a lot more margarine

01:30:59.540 | in refrigerators, but people were thinner

01:31:01.780 | and there was less diabetes.

01:31:03.260 | - Everything you told us about margarine and trans fats

01:31:05.080 | is that it's bad, bad, bad.

01:31:06.160 | Now butter is back, as Time magazine and you said.

01:31:09.480 | So clearly can't be the transition away from trans fats.

01:31:13.320 | That's increased obesity.

01:31:14.600 | So it's gonna be the increase in sugar

01:31:17.600 | and these hidden sugars in the foods.

01:31:20.080 | - Exactly, that's right.

01:31:21.580 | The key though is Pakistan and India and China,

01:31:28.500 | they are not fat, but they have 14% diabetes rates

01:31:33.500 | and they're thin and the reason is

01:31:36.680 | because of ultra processed food.

01:31:38.320 | - Are there any countries in the world

01:31:40.560 | that don't allow high fructose corn syrup

01:31:45.160 | or at least not at the level that we do?

01:31:47.160 | - Oh, boat loads, okay.

01:31:48.960 | There are boat loads of countries

01:31:50.960 | that don't import high fructose corn syrup or don't make it.

01:31:54.200 | - So Scandinavian countries?

01:31:55.740 | - Scandinavian countries, most of Europe.

01:31:59.040 | Other than the Asia Pacific Rim, so Japan has it.

01:32:03.280 | In fact, it was invented in Japan,

01:32:04.640 | 1966 Saga Medical School, Takasaki, et al.

01:32:09.300 | Korea has it, but Australia does not have it.

01:32:14.040 | Thailand does not have it,

01:32:15.560 | but they have just as much of obesity

01:32:19.000 | and diabetes problem as we do because they have sucrose.

01:32:22.560 | Because high fructose corn syrup and sucrose

01:32:24.360 | are no different metabolically.

01:32:26.920 | So it doesn't really matter.

01:32:28.260 | - Is that one to one?

01:32:29.500 | - It's the one to one thing, exactly.

01:32:31.240 | - Of glucose and fructose.

01:32:32.300 | - So here's the question, Andrew, okay?

01:32:35.200 | So I wanna go back to that.

01:32:37.720 | You said all this food is still on the shelves.

01:32:41.200 | Is it food?

01:32:42.840 | What is the definition of food?

01:32:44.440 | - Can I give the definition I think most people would give?

01:32:49.080 | That's not necessarily the one I would give,

01:32:51.000 | but something that contains caloric energy.

01:32:54.720 | Or like I could eat this microphone,

01:32:56.740 | but it's not gonna provide much useful energy.

01:33:00.440 | - The definition of food straight from the dictionary,

01:33:03.680 | and believe me, I looked it up and memorized it.

01:33:05.960 | - I believe you.

01:33:07.600 | - Substrate that contributes to either growth

01:33:10.800 | or burning of an organism.

01:33:13.440 | - Interesting.

01:33:14.280 | - That is the definition of food.

01:33:15.320 | - So I'm pretty scientific.

01:33:16.560 | - 100% correct, growth or burning.

01:33:21.160 | So any substrate that passes your lips

01:33:23.960 | that contributes to either growth or burning, that's food.

01:33:27.800 | Okay, let's do it.

01:33:29.800 | Let's do burning first.

01:33:31.360 | I just showed you that sugar,

01:33:33.760 | which is the marker of ultra-processed food,

01:33:35.640 | and 73% of the items in the grocery store

01:33:38.160 | are spiked with sugar, inhibits burning.

01:33:41.160 | It inhibits those three enzymes

01:33:42.780 | involved in mitochondrial function.

01:33:45.520 | Now let's do growth.

01:33:47.240 | My colleague, Dr. Efrat Monsonigo-Ornan,

01:33:50.080 | who is the chairman of nutrition

01:33:51.840 | at Hebrew University Jerusalem,

01:33:53.400 | actually looked at this question

01:33:56.040 | and showed that ultra-processed food

01:33:57.440 | actually inhibits growth.

01:33:58.760 | It inhibits cortical bone growth.

01:34:01.560 | It inhibits trabecular bone growth.

01:34:03.800 | It inhibits cancellous bone growth.

01:34:06.280 | It inhibits linear bone growth.

01:34:09.440 | It hijacks growth for cancer

01:34:12.040 | because it inhibits mitochondria.

01:34:14.920 | And so you have to then grow instead of burn.

01:34:18.800 | - And this was work that was done in in vivo or in vitro?

01:34:21.800 | - In vivo.

01:34:22.640 | - In vivo, so these are people

01:34:23.800 | that are eating high amounts of highly processed food.

01:34:25.960 | - Exactly.

01:34:26.800 | - How did you find those in the Middle East?

01:34:29.400 | - They found, in Israel, they found them.

01:34:32.280 | So bottom line is if a substrate

01:34:35.960 | does not contribute to growth

01:34:37.720 | and does not contribute to burning,

01:34:40.160 | is it a food?

01:34:42.040 | - I see the answer is no.

01:34:44.080 | - Well, that's 73% of what's in the grocery store.

01:34:48.280 | So I would argue, you said the food's there.

01:34:51.120 | No, it's not.

01:34:52.600 | That's not food.

01:34:54.000 | In fact, it's consumable poison.

01:34:55.920 | - So this leads to an important question of what's left.

01:35:00.920 | You remove all that, what's left.

01:35:03.040 | Just anecdotally, and what I sometimes call anecdata,

01:35:07.200 | you know, I've had several friends in their 40s

01:35:12.080 | and early 50s say they wanted to lose weight

01:35:15.200 | and get in shape, and the thing that's worked

01:35:17.800 | every single time for them to lose significant amounts

01:35:21.520 | of weight quickly and keep it off,

01:35:23.640 | and many of them were already exercising,

01:35:25.600 | but then also increase their exercise,

01:35:27.640 | was I just, since I'm not a dietician,

01:35:30.080 | nutritionist, or anything, I just say,

01:35:32.080 | eat meat, fish, eggs, vegetables, fruits,

01:35:37.280 | you're not gonna eat starches.

01:35:38.760 | You're not gonna drink alcohol.

01:35:39.920 | You're not gonna drink soda.

01:35:41.400 | You can still have coffee, tea.

01:35:43.280 | You can still have artificial sweeteners.

01:35:45.200 | I will get to artificial sweeteners in a little bit.

01:35:47.760 | - We have to go there.

01:35:49.480 | - And the reason I say no starches,

01:35:52.760 | even though I personally eat rice, oatmeal, pasta,

01:35:55.880 | things of that sort, some in moderation,

01:35:58.200 | depending on what sort of exercise I'm doing and how much,

01:36:02.240 | is because of the fact that nowadays

01:36:04.560 | many of those things contain fructose,

01:36:07.720 | and inevitably, every one of those people

01:36:10.800 | is blown away by the fact that it, quote unquote, works,

01:36:13.920 | and assumes that it's all because

01:36:15.080 | of reduced calorie intake overall,

01:36:17.200 | and they lose like anywhere from 30 to 55 pounds

01:36:21.840 | and keep it off, and they're like, hey, this is great.

01:36:23.520 | I can actually still eat ribeye steaks and salads,

01:36:26.580 | but they're not eating croutons.

01:36:28.480 | And so in some sense, it looks extreme.

01:36:31.120 | It sounds ketogenic, but it's nothing like that.

01:36:33.540 | You're just saying basically stay away from,

01:36:35.780 | you're eliminating processed foods,

01:36:37.080 | you're eliminating liquid calories in general,

01:36:40.340 | and on and on.

01:36:42.420 | And so there's nothing sophisticated about it.

01:36:44.480 | And my question to you is how much of that weight loss

01:36:47.920 | effect do you think is a calories in

01:36:50.560 | versus calories out effect?

01:36:52.520 | 'Cause they're eating a lot of food, in some cases.

01:36:56.860 | And how much of it do you think is the elimination

01:36:59.580 | or near elimination of this fructose or this glucose,

01:37:04.040 | fructose combination?

01:37:05.440 | - It's nothing to do with the calories.

01:37:08.200 | It has everything to do with the insulin.

01:37:10.240 | If you get the insulin down,

01:37:13.140 | you're not shunting energy to fat.

01:37:16.480 | You can lose weight.

01:37:18.080 | Your fat will give up the triglycerides stored in it

01:37:23.080 | as soon as your insulin goes down.

01:37:28.440 | Insulin is pushing on your fat cell all the time.

01:37:33.020 | And as long as your insulin's up,

01:37:34.980 | your fat cell can't release it.

01:37:36.720 | The minute your insulin goes down,

01:37:38.640 | you can now engage in what we call lipolysis.

01:37:41.880 | Hormone sensitive lipase is an enzyme in the fat cell

01:37:46.180 | that is inhibited by insulin.

01:37:48.980 | As soon as the insulin's gone, hormone sensitive lipase

01:37:52.440 | can turn that stored triglyceride into free fatty acids

01:37:57.680 | and glycerol and release it and you can lose weight.

01:38:01.320 | So get the insulin down and it all works.

01:38:03.960 | So the question is, what makes insulin go up?

01:38:06.560 | Well, two things, refined carbohydrate and sugar.

01:38:08.880 | Those are the two things that make insulin go up.

01:38:10.800 | In addition, branched chain amino acids

01:38:12.560 | make insulin go up as well.

01:38:14.220 | Leucine, isoleucine, valine, which is in corn-fed

01:38:17.040 | beef, chicken and fish, processed food.

01:38:19.660 | All right, here's the deal in one concept.

01:38:26.700 | My colleague, Dr. Carlos Montero,

01:38:29.200 | who is a professor of public health

01:38:31.320 | at the University of São Paulo,

01:38:32.820 | has done the world a great service.

01:38:35.220 | He has developed a system for categorization

01:38:38.660 | of food processing.

01:38:40.960 | It is called the NOVA system, just means new.

01:38:44.520 | But he has basically categorized every food

01:38:48.960 | anywhere in the world into one of four classes.

01:38:54.360 | Easiest way to explain this would be an example.

01:38:57.380 | Let's take an apple.

01:38:58.580 | NOVA class one would be an apple picked off a tree.

01:39:02.560 | NOVA class two would be apple slices.

01:39:06.360 | De-stemmed, de-seeded, de-skinned maybe.

01:39:09.040 | NOVA class three would be apple sauce.

01:39:13.020 | Cooked, macerated, possibly a preservative added,

01:39:16.440 | maybe some extra sugar, maybe not.

01:39:18.540 | NOVA class four would be a McDonald's apple pie.

01:39:23.840 | Now, does that McDonald's apple pie

01:39:26.460 | look anything like that apple?

01:39:28.600 | No.

01:39:29.640 | Is there even any apple in it?

01:39:31.240 | Maybe a tiny bit. Maybe not.

01:39:32.680 | Maybe a tiny bit.

01:39:34.060 | It's all flavor enhanced, et cetera.

01:39:35.880 | Turns out, and this is epidemiologic data,

01:39:40.560 | but nonetheless, prospective epidemiologic data,

01:39:42.920 | so it's not useless.

01:39:44.120 | That NOVA class four, that ultra-processed food category,

01:39:50.460 | which is 73% of the American grocery store,

01:39:54.100 | is the class that is associated

01:39:56.440 | with all of these chronic metabolic diseases.

01:39:58.640 | NOVA class one through three, no problem.

01:40:02.720 | - Now, when you say associated,

01:40:03.820 | what percentage of one's daily total caloric intake

01:40:07.300 | needs to come from NOVA class four

01:40:09.060 | before that statement you just made is true?

01:40:11.980 | Because I love the recommendation you made earlier,

01:40:15.020 | or the, let's just say, the contour of a,

01:40:19.240 | you don't have to avoid dessert.

01:40:22.300 | You can enjoy dessert,

01:40:23.520 | but don't eat dessert at other times of day.

01:40:25.740 | And maybe you don't eat dessert every single night.

01:40:27.820 | I mean, is there a rule that people

01:40:29.380 | have to eat dessert every single night?

01:40:30.780 | - So the answer is about seven to 10%

01:40:34.740 | would be at the upper limit.

01:40:36.660 | - So you can get seven to 10% of your caloric intake,

01:40:40.340 | daily caloric intake, from these NOVA class four foods,

01:40:43.480 | and still- - And still be okay.

01:40:44.860 | - And still be okay.

01:40:45.700 | - Yeah. - So this is, I know-

01:40:47.540 | - But that's not what's happening.

01:40:48.700 | - Right, I know some very healthy physicians

01:40:50.500 | who I used to observe how people, A, moved,

01:40:54.540 | 'cause I would pay attention in our field, right?

01:40:58.480 | I was like, oh, you know, people all around me

01:41:00.900 | at Stanford, UCSF, et cetera, were successful,

01:41:02.820 | or else they wouldn't be there.

01:41:04.200 | I was like, you know, who looks healthy?

01:41:05.380 | Who can make it up the stairs

01:41:06.460 | and doesn't have to take the elevator?

01:41:08.220 | How much exercise are people doing at a given age?

01:41:10.820 | Are they fanatic, you know, like four in the morning runners?

01:41:13.320 | I'm not gonna do that consistently unless I have to.

01:41:16.380 | And I observed that, you know,

01:41:18.820 | many of the healthiest people I know,

01:41:20.820 | they move a lot during the day, they eat very well.

01:41:23.260 | Many of them skip breakfast or lunch, not always.

01:41:26.620 | And then I also noticed that they would drink very little

01:41:30.780 | or no alcohol, but they would enjoy like a,

01:41:34.100 | there's one physician at UCSF in particular I'm thinking of

01:41:36.260 | who really enjoyed his dark chocolate Kit Kat after lunch.

01:41:39.380 | And he's sort of very ceremonial about the unraveling

01:41:42.560 | of the foil and the end of the day.

01:41:44.700 | And I was like, okay, so you're talking about

01:41:46.220 | that small percentage of calories.

01:41:47.820 | If that's all you do, hey, you know, God bless you.

01:41:51.900 | But that's not what people are doing.

01:41:54.260 | That's the problem.

01:41:55.980 | Bottom line, that NOVA class four is where all the action is

01:41:59.780 | in terms of chronic metabolic disease.

01:42:02.380 | So the question is, how can you avoid that?

01:42:05.580 | How do you know which is which?

01:42:07.520 | We have a solution.

01:42:09.940 | So my colleagues and I have developed a web-based tool

01:42:15.540 | that is available to the entire world right now.

01:42:19.640 | And you'll put it in your show notes.

01:42:21.500 | - Yeah, we'll put a link to this.

01:42:22.480 | - Absolutely, it's called PERFECT, P-E-R-F-A-C-T.

01:42:26.280 | And you can find it at PERFECT.CO.

01:42:28.540 | And what it is, is it's a recommendation engine, not AI.

01:42:34.980 | We're gonna talk about AI in a minute.

01:42:38.220 | But it is a recommendation engine based on the science

01:42:42.180 | of human metabolism that categorizes foods

01:42:47.180 | based on not their nutrient content,

01:42:52.340 | but on their metabolic effect.

01:42:54.740 | - Interesting.

01:42:55.580 | - And so there is a NOVA filter,

01:42:57.780 | which will filter out all the NOVA class four stuff.

01:43:00.500 | And it will go to your grocery store

01:43:02.660 | and will tell you what you can buy

01:43:06.300 | that will be in NOVA class one through three,

01:43:08.900 | which turns out to only be 20% of the grocery store.

01:43:13.420 | - It means basically staying on the periphery

01:43:14.920 | of the grocery store, right?

01:43:15.760 | - Well, that's a lot of it. - In general.

01:43:17.060 | - In general, yes.

01:43:17.900 | - Yeah, the produce, the meat, the dairy, the--

01:43:20.260 | - All the things you mentioned, in fact.

01:43:23.260 | So I'm not low carb, I'm low insulin.

01:43:27.500 | And there are a lot of ways to get to low insulin.

01:43:29.760 | Get rid of the refined carbohydrate, get rid of the sugar,

01:43:32.340 | increase the fiber, get rid of the branched chain

01:43:35.500 | amino acids, okay, so eating fish is a good place to be.

01:43:40.460 | Even eating a steak is okay if it's a pasture-fed steak.

01:43:45.460 | So let's talk about your steak.

01:43:48.500 | - Right, which is also better for the animals, right?

01:43:50.380 | - It is, absolutely.

01:43:51.540 | So you mentioned marbling before.

01:43:53.600 | We love our marbling, right?

01:43:55.340 | We can cut our US grade A steaks with a butter knife

01:43:58.540 | because they're so tender, right?

01:44:02.420 | You ever been to Argentina?

01:44:03.940 | - Yeah, my father's Argentina.

01:44:04.900 | - Oh, right, that's right, you're Argentinian.

01:44:06.340 | - Yeah, they only know grass-fed steak.

01:44:09.340 | The idea that cows would eat anything but grass

01:44:12.220 | is sort of like the idea that fish would fly.

01:44:16.060 | - Absolutely, New Zealand, same thing, okay?

01:44:19.740 | The meat is gorgeous, it's homogeneous, it's pink,

01:44:23.120 | it's delightful.

01:44:24.560 | I've been to Argentina, the meat is fantastic,

01:44:27.720 | but you have to use a steak knife.

01:44:28.880 | You can't use a butter knife.

01:44:29.720 | - And it takes more chewing.

01:44:31.460 | - And it takes more chewing because there's sinew.

01:44:33.940 | It's a different experience entirely.

01:44:36.240 | It's delicious, but it is kind of a little bit tougher.

01:44:40.500 | Turns out that marbling is intramyocellular lipid.

01:44:46.580 | That animal has metabolic syndrome.

01:44:50.100 | - The American corn-fed.

01:44:51.580 | - The American corn-fed animal because that corn

01:44:54.920 | is filled with branched-chain amino acids,

01:44:56.980 | leucine, isoleucine, valine.

01:44:58.460 | Branched-chain amino acids are what's in protein powder.

01:45:01.220 | That's what bodybuilders put in their smoothies

01:45:05.540 | to build muscle.

01:45:06.700 | And if you're building muscle, that's okay

01:45:08.780 | because 20% of the amino acids in muscle are branched-chain.

01:45:13.780 | So if you've got a place to put them, have at it.

01:45:18.980 | - Yeah, there's a need there

01:45:20.080 | 'cause they're breaking down muscle.

01:45:21.140 | - Yeah, fine.

01:45:21.980 | But if you're not, if you're, again, a mere mortal like me,

01:45:24.860 | you consume those excess branched-chain amino acids,

01:45:27.740 | they're gonna go to the liver, they're gonna be deamidated

01:45:30.100 | like we talked about earlier,

01:45:31.740 | and they're gonna end up as branched-chain organic acids.

01:45:34.700 | They're gonna flood the mitochondria.

01:45:36.940 | The mitochondria are not gonna be able

01:45:38.500 | to deal with the volume.

01:45:40.540 | And so they're gonna divert the excess

01:45:43.860 | and turn that into fat.

01:45:45.580 | And so now you've got hypertriglyceridemia

01:45:48.600 | and chance for fatty liver disease and insulin resistance.

01:45:53.300 | So what kind of meat you eat has a lot to do

01:45:58.580 | with your metabolic health.

01:46:00.500 | - What about the egg, the whole egg?

01:46:02.460 | Near perfect protein score in terms of its bioavailability.

01:46:06.940 | - Eggs are terrific.

01:46:10.060 | - Okay, great.

01:46:10.880 | - There's nothing wrong with eggs.

01:46:12.180 | Now, there are better eggs than others.

01:46:14.660 | So there are-- - Pasture.

01:46:16.220 | - Well, there's yellow yolk eggs

01:46:18.940 | and there are orange yolk eggs.

01:46:20.700 | What's the difference between a yellow oak egg

01:46:22.500 | and an orange oak egg?

01:46:23.420 | - I'm guessing that something about the feed

01:46:27.620 | of the mother chicken.

01:46:30.200 | And I'm guessing it probably also has something to do

01:46:33.940 | with choline content?

01:46:35.960 | - Omega-3s.

01:46:37.100 | - Ah, interesting.

01:46:38.660 | - The orange yolk egg has a lot of omega-3s in it.

01:46:43.660 | - What are other great sources of omega-3s?

01:46:45.580 | I know some off the top of my head,

01:46:47.220 | but I'd like to hear it from you.

01:46:48.180 | - Okay, so marine life is number one, fish.

01:46:53.100 | - Provided you're not bringing in heavy metals with it.

01:46:55.660 | - Well, yes, so that's always the argument.

01:47:00.420 | The question is, is it the mercury or is it the omega-3s?

01:47:03.860 | Ultimately, I think it's the omega-3s that is more important

01:47:06.900 | but yes, I do understand the mercury issue.

01:47:09.600 | Ultimately, there are three omega-3s.

01:47:14.340 | There's ALA, alpha-linolenic acid,

01:47:17.980 | which you can get in vegetables.

01:47:19.680 | There is EPA, eicosapentaenoic acid,

01:47:25.140 | which you can only get in marine life.

01:47:27.180 | - Fish oil, cod liver oil.

01:47:29.380 | - Right, and finally, DHA, docohexainoic acid,

01:47:34.080 | which you also get from marine life

01:47:36.060 | but you can get from algae.

01:47:38.320 | So you can get algal oil, which the vegans will use.

01:47:42.740 | - Do you personally take anything

01:47:45.100 | to increase your omega-3 intake?

01:47:47.080 | - Yeah, I take fish oil.

01:47:47.920 | - I know that there's even prescription omega-3s.

01:47:49.580 | - I take fish oil.

01:47:50.540 | - You take a fish oil, yeah.

01:47:52.420 | - I only take three supplements.

01:47:55.200 | - Okay, I'd like to know what those are.

01:47:56.180 | I will say that I always, always, always say

01:47:58.340 | behaviors first, right, do's and don'ts.

01:48:00.640 | Behaviors, nutrition, then only if needed

01:48:05.020 | and one can afford it,

01:48:05.860 | then supplementation and prescription drugs.

01:48:07.620 | And I'm a big consumer of supplements

01:48:09.300 | and always have been, frankly.

01:48:10.740 | So what are the three?

01:48:11.580 | So you take--

01:48:12.420 | - Fish oil.

01:48:13.420 | - And do you take to get above a certain threshold of EPA?

01:48:16.580 | - About 1,000 milligrams.

01:48:17.940 | - So you say about a gram a day of EPA, okay.

01:48:20.580 | - Vitamin C.

01:48:21.860 | - How much vitamin C do you take?

01:48:22.700 | - A thousand milligrams a day.

01:48:23.940 | - You and Linus Pauling.

01:48:25.100 | - Yeah, well, it's actually from my rosacea.

01:48:27.680 | I've got a skin issue that helps with that.

01:48:32.680 | - Interesting.

01:48:33.620 | - And finally, vitamin D.

01:48:35.320 | Now I will tell you, vitamin D is a complicated one.

01:48:39.060 | All right, and we can talk about vitamin D

01:48:42.160 | and how either important or non-important it is

01:48:45.740 | 'cause there's a quirk to vitamin D

01:48:48.640 | and it's important for your audience to know about it

01:48:52.560 | 'cause everybody and his brothers, you know,

01:48:55.320 | touting vitamin D as the cure for everything.

01:48:57.640 | - It's sort of funny because you have your supplement,

01:49:00.440 | lovers, haters, and agnostics,

01:49:02.360 | but vitamin D somehow made it through the chute.

01:49:05.200 | Like everyone's like pro vitamin D.

01:49:06.880 | It's really interesting.

01:49:07.720 | Somehow vitamin D,

01:49:09.160 | people are comfortable taking a vitamin D gel cap,

01:49:12.440 | but like other supplements where you say,

01:49:14.240 | oh, like maybe this might be good for, you know,

01:49:17.840 | like Omega-3s and fish oil,

01:49:19.560 | then people are a little bit like more standoffish.

01:49:21.360 | It's really interesting that the kind of

01:49:22.640 | psychosocial stuff around this.

01:49:24.840 | How much vitamin D do you personally take?

01:49:27.360 | - I take 5,000 units a day.

01:49:29.080 | - Okay, so do I.

01:49:29.960 | - Vitamin D is complicated though.

01:49:32.200 | Here's the problem.

01:49:33.680 | If you look at the literature,

01:49:36.400 | vitamin D deficiency is associated

01:49:38.880 | with all of these chronic metabolic diseases.

01:49:41.840 | However, supplementation with vitamin D

01:49:46.480 | has not fixed any of those.

01:49:48.560 | So if you're vitamin D deficient,

01:49:51.800 | why wouldn't supplementation fix it?

01:49:54.520 | Couple of reasons.

01:49:57.360 | One, one of the reasons for vitamin D deficiency

01:50:00.160 | is 'cause everyone's drinking soft drinks.

01:50:02.400 | That's one reason, but there's a more important reason.

01:50:05.400 | - Sugar and artificially sweetened soft drinks?

01:50:08.480 | - Yeah.

01:50:09.320 | - Can deplete vitamin D, utilize it?

01:50:10.720 | - Well, you're not consuming dairy

01:50:12.280 | 'cause you're consuming soft drinks.

01:50:14.200 | - But I can't tolerate milk anymore.

01:50:16.200 | - Well, then you take vitamin D.

01:50:18.200 | But here's the real nugget of truth.

01:50:21.840 | And this is a little complicated,

01:50:23.940 | but the endocrinologists in the audience will get it.

01:50:27.300 | Vitamin D is a pre-pro hormone.

01:50:32.640 | It's not active at all.

01:50:35.380 | Vitamin D is converted in the liver first step

01:50:39.360 | to a compound called 25-hydroxy vitamin D.

01:50:43.680 | That is a pro hormone.

01:50:45.440 | It also is inactive.

01:50:47.360 | It has no activity whatsoever.

01:50:50.180 | From there, 25-hydroxy vitamin D

01:50:54.400 | can be metabolized one of two ways.

01:50:56.380 | It can either be one alpha-hydroxylated in the kidney

01:51:00.920 | to the active form, one alpha,

01:51:04.120 | one 25-dihydroxy vitamin D,

01:51:06.600 | which will then do all of the business of vitamin D,

01:51:10.080 | such as calcium absorption from the gut,

01:51:14.180 | suppression of the immune system

01:51:16.120 | at the toll-like receptor four.

01:51:17.940 | - That sounds like a bad thing.

01:51:19.100 | - No, that's a good thing.

01:51:19.940 | - I know, but I had to bring that up

01:51:21.420 | because when you say suppression of the immune system,

01:51:23.200 | people go, "Oh, I'm immunosuppressed."

01:51:24.800 | That sounds like AIDS.

01:51:26.680 | - It suppresses inflammation.

01:51:28.580 | It's a good thing, okay, suppression of inflammation.

01:51:31.600 | And that's actually the point that we're getting to.

01:51:34.900 | So there are a lot of good things

01:51:37.140 | about one 25-dihydroxy vitamin D.

01:51:41.520 | However, that 25-hydroxy D that came out of the liver

01:51:46.120 | can be metabolized a different way.

01:51:48.800 | It can be 24-hydroxylated in inflammatory tissue,

01:51:53.720 | like tuberculosis, sarcoid, gut inflammation.

01:51:59.600 | And so you will end up taking your 25-hydroxy D,

01:52:04.960 | which is a prohormone,

01:52:06.320 | and turning it into the inactive 24/25-dihydroxy D,

01:52:11.420 | which then just gets excreted out.

01:52:13.800 | So in other words, you consumed all this vitamin D

01:52:16.640 | and it didn't go where you needed it to go.

01:52:19.080 | And the reason was because you're inflamed.

01:52:21.360 | You have to fix the inflammation

01:52:25.400 | before the vitamin D can be effective.

01:52:28.680 | And 93% of Americans are inflamed.

01:52:31.960 | So giving them vitamin D is not gonna do a damn thing.

01:52:36.960 | - Got it, is reducing fructose intake

01:52:39.660 | one of the primary ways to reduce systemic inflammation?

01:52:42.880 | - Absolutely.

01:52:43.980 | - What are some others?

01:52:44.920 | - Reducing oxidative stress in general,

01:52:47.000 | so heavy metals like cadmium.

01:52:49.380 | Cadmium is very high in chocolate,

01:52:51.440 | especially South American chocolate, sorry.

01:52:54.280 | - No, I'm not a fan of chocolate.

01:52:55.740 | I occasionally like a little dark chocolate,

01:52:57.440 | but so if people are going to eat chocolate,

01:53:01.600 | they should be careful how much chocolate they eat.

01:53:03.480 | - Well, especially if it's South American chocolate

01:53:05.760 | and processed chocolate.

01:53:07.080 | I mean, the really good stuff.

01:53:08.580 | - We're gonna be on the hit list of so many industries

01:53:10.680 | after this episode comes out.

01:53:12.720 | - All I can tell you is I've been on the hit list

01:53:14.900 | for a decade and I'm still here.

01:53:16.240 | - You're just one big target.

01:53:17.320 | - Yeah, right.

01:53:18.320 | I gotta, it's on my back, you know, kick me.

01:53:21.720 | I already got that.

01:53:22.680 | There are, the main thing is to make that gut work right.

01:53:29.300 | So fiber, short chain fatty acid production from fiber

01:53:36.840 | is a huge, you know, boon and benefit.

01:53:40.040 | - To reduce inflammation.

01:53:41.140 | - To reduce inflammation.

01:53:41.980 | - How about improving sleep?

01:53:44.060 | Is there any evidence that, you know,

01:53:46.080 | chronic slight sleep deprivation can increase inflammation?

01:53:49.180 | - Well, what it will do is it'll increase cortisol

01:53:51.460 | and chronically increased cortisol

01:53:53.500 | will definitely lead to increased inflammation.

01:53:56.420 | You know, which is funny 'cause cortisol

01:53:57.700 | is usually considered the anti-inflammatory,

01:53:59.660 | but only acutely.

01:54:01.180 | Chronic cortisol elevation does the opposite.

01:54:04.020 | - If we can contribute to,

01:54:05.860 | I have this secret agenda, which is not a secret,

01:54:09.960 | which is that people think cortisol is bad

01:54:13.120 | when in fact acutely cortisol does wonderful things

01:54:15.980 | provided it's happening at the right time of day.

01:54:18.300 | Late shifted cortisol, bad.

01:54:21.140 | Too much or too frequent cortisol, bad.

01:54:23.940 | But cortisol, you need it.

01:54:25.940 | It's so essential.

01:54:27.020 | And I think most people just hear cortisol

01:54:28.620 | and it's been associated with all things bad

01:54:30.320 | and maybe we can help shift that narrative.

01:54:32.140 | - Yeah, I'm very happy.

01:54:33.240 | I mean, as an endocrinologist, you know, this is,

01:54:35.440 | you know, this is my wheelhouse is where I live.

01:54:37.880 | Cortisol is a good news, bad news deal like so many things.

01:54:43.520 | Short-term gain for long-term pain, okay?

01:54:46.520 | So when you are in what we call allostasis,

01:54:51.220 | that is perturbation of homeostasis,

01:54:55.200 | that is a stress, an acute stress,

01:54:59.440 | cortisol is one of the things that helps you manage that

01:55:04.180 | bodily and mental stress.

01:55:06.980 | So an English test, a car accident,

01:55:11.460 | running away from the lion, you know, the famous, you know,

01:55:14.960 | pygmy running away from the lion.

01:55:17.140 | All of those require cortisol in order to manage

01:55:21.080 | and mitigate that stress.

01:55:22.960 | - The upcoming 2024 election.

01:55:25.680 | - That's chronic stress.

01:55:27.100 | That is not acute stress, that's the worst.

01:55:31.780 | - That'll be the only mention of politics on this podcast.

01:55:35.080 | - And we don't have to go there.

01:55:36.940 | But we're all chronically stressed.

01:55:39.460 | And we can talk about why that is and what's going on.

01:55:43.440 | And I'm actually very interested in that.

01:55:45.180 | And a colleague of mine in Paris and I have built

01:55:49.040 | a computational model of the limbic system,

01:55:52.580 | which focuses on the stress center of the brain,

01:55:55.440 | the amygdala, to understand how chronic stress

01:55:59.200 | is different from acute stress and how that chronic stress

01:56:03.000 | ultimately leads to metabolic and mental health disaster.

01:56:07.900 | - Very interested in learning more about that.

01:56:09.680 | Before we touch on that, you've worked a lot with kids.

01:56:12.880 | People age, as you put it, zero to 19.

01:56:16.600 | I don't know about the exact numbers,

01:56:22.080 | but when I was growing up, there were some kids in school

01:56:25.240 | that were overweight, but it was the occasional kid.

01:56:27.700 | - Right.

01:56:28.640 | Now it seems, depending on where one draws the threshold

01:56:32.040 | for overweight, it seems that there are a lot of kids

01:56:34.280 | that are overweight.

01:56:36.080 | - How about 25% obese and 40% overweight?

01:56:41.080 | - Okay, so obviously a serious problem.

01:56:43.740 | - Serious problem.

01:56:44.580 | - Now and going forward.

01:56:45.760 | What about adults in the U.S.?

01:56:47.740 | I remember seeing at a meeting a map of obesity in the U.S.

01:56:51.160 | and over time, and it very quickly filled in

01:56:54.620 | from very few people were obese to very many.

01:56:56.960 | Colorado was this beacon of fit people,

01:57:01.960 | but now it's no longer-

01:57:04.760 | - And that's bullshit too.

01:57:05.800 | - Oh, okay, cool.

01:57:06.840 | - I'll tell you why.

01:57:07.800 | There are four things that can increase

01:57:09.160 | mitochondrial biogenesis.

01:57:12.800 | - Are you gonna tell me altitude is-

01:57:13.920 | - Cold, that's why Colorado is less obese.

01:57:17.120 | Altitude, that's why Colorado is less obese.

01:57:20.280 | And what were the other two?

01:57:23.400 | But those were the reason.

01:57:24.840 | It had nothing to do with being more fit.

01:57:27.400 | It had to do with cold and altitude.

01:57:29.720 | Example, Switzerland compared to Germany,

01:57:32.840 | they got the same crappy food,

01:57:34.680 | but Switzerland has half the obesity that Germany does.

01:57:37.520 | Because Switzerland is higher.

01:57:39.240 | - Oh, I love the food.

01:57:40.120 | When I go to Munich, I love the schnitzels

01:57:42.800 | and the sauerkraut. - Yeah, it's wonderful.

01:57:44.640 | They got that in Switzerland too.

01:57:46.800 | - Okay, so they have great food.

01:57:47.920 | - Switzerland is less obese.

01:57:50.200 | Same way Colorado is less obese.

01:57:52.200 | It's because of the altitude.

01:57:54.100 | - You mentioned cold.

01:57:55.460 | Many listeners of this podcast

01:57:57.040 | are at least interested in some also practice

01:58:00.760 | deliberate cold exposure, cold showers, cold plunges,

01:58:02.980 | mainly for the, I think the best data

01:58:05.840 | are the increase in catecholamines,

01:58:07.680 | epinephrine, norepinephrine, dopamine that are long lasting.

01:58:09.840 | People feel a big state shift.

01:58:11.320 | They feel better.

01:58:12.480 | But when one looks at the effects on metabolism,

01:58:15.700 | they're pretty slight.

01:58:16.960 | - They are slight. - They're slight.

01:58:18.280 | However, studies like that, to me,

01:58:21.160 | always seem short-sighted in the sense

01:58:24.220 | that if there's a longer arc of effect on the mitochondria

01:58:27.980 | that's affecting other things

01:58:29.440 | in terms of how calories are processed

01:58:31.620 | or how calories are feeding into mitochondrial function

01:58:36.660 | or dysfunction, there I could see how it might shift

01:58:39.420 | the scale, so to speak.

01:58:42.420 | I mean, cold is an amazingly powerful stimulus.

01:58:45.700 | And I think of light, cold, food, movement.

01:58:49.780 | It's kind of like the core four ways

01:58:52.340 | in which you can shift physiology easily.

01:58:54.660 | - All of these things are eminently manipulable

01:58:57.780 | and for almost zero dollars, okay?

01:59:00.600 | But you have to know what you're doing.

01:59:02.420 | And right now, we've been actually kept from that knowledge.

01:59:06.380 | And if you're addicted,

01:59:09.180 | it's really hard to unaddict yourself.

01:59:11.980 | - So that brings us back to this thing

01:59:14.380 | about food industry conspiracies, government conspiracies,

01:59:19.740 | and the rest.

01:59:20.740 | Boy, this is going to be an interesting section.

01:59:25.300 | But what do we do?

01:59:28.700 | So if you and I go up to Capitol Hill.

01:59:31.180 | - Which I've done.

01:59:32.020 | - Yeah, which you've done, and maybe I'll join you someday.

01:59:34.780 | And you're at UCSF, I'm down at Stanford.

01:59:39.980 | You're a clinician, I'm a scientist

01:59:41.420 | and a public health advocate, podcaster.

01:59:45.340 | And we explain to people, hey, listen,

01:59:47.820 | the food is laced with a drug, it's not even really food.

01:59:50.820 | - That's right, it's not food.

01:59:51.880 | - It's an aggregate of food and non-food parts

01:59:54.120 | that make you think it's food.

01:59:55.360 | It's sort of like telling people, hey, your kids are,

01:59:57.700 | they're swimming in a swimming pool, looks like water,

02:00:00.000 | but it's actually part poison and it's harming them.

02:00:02.740 | It's giving them, if you say those kinds of things,

02:00:05.140 | I mean, congressmen and women are,

02:00:07.620 | they're like reasonably smart people, right?

02:00:10.640 | I mean, aren't they gonna do something about it?

02:00:12.720 | - No.

02:00:13.560 | - So where is the conflict?

02:00:14.580 | Is it that the food industry has the government

02:00:18.260 | by the short hairs?

02:00:19.140 | - That's exactly right.

02:00:20.180 | - And they have them by the short hairs where?

02:00:22.000 | I mean, is it, are they lining their pockets?

02:00:24.540 | I mean, where is the leverage actually exerted?

02:00:28.540 | - Okay, so they are lining their pockets, that's number one.

02:00:31.180 | That is absolutely true, and we have the data

02:00:33.020 | to support that.

02:00:34.260 | Blanche Lincoln, who was a senator from Arkansas,

02:00:37.180 | who was the chairman of the nutrition committee,

02:00:38.740 | you had to see her campaign contributions

02:00:40.580 | every time she was up for reelection.

02:00:42.060 | - So it's all about getting reelected,

02:00:43.580 | or it's about them having a third home in the Hamptons?

02:00:48.060 | - I think it's the third home in the Hamptons

02:00:49.920 | more than anything.

02:00:50.760 | - Okay, so it's really as bad as some of the documentaries

02:00:53.820 | would make us believe. - Without question.

02:00:55.100 | Without question.

02:00:55.940 | - Goodness.

02:00:56.780 | - And we have the data.

02:00:58.120 | There is an organization that I absolutely wanna call out

02:01:02.720 | because they are the most egregious political organization

02:01:07.500 | on the face of the earth.

02:01:08.840 | They're called the American Legislative Exchange Council,

02:01:11.680 | ALEC, or A-LIC, and they write bills.

02:01:16.640 | They are a bill mill, okay?

02:01:18.840 | And they are for whoever gives them money.

02:01:21.780 | And who gives them money?

02:01:23.960 | Big pharma, big agra, big oil, and big food.

02:01:28.960 | - So you're including big pharma.

02:01:30.620 | You're a physician.

02:01:31.460 | You've written scripts before.

02:01:32.400 | You've written prescriptions for patients before.

02:01:34.380 | Isn't that pharma that provides the drugs

02:01:36.360 | that allows your patients to feel better?

02:01:38.000 | - Well, the question is, do they?

02:01:40.160 | Do they feel better?

02:01:41.260 | This is a big question.

02:01:43.180 | You wanna go there?

02:01:44.020 | We can go there.

02:01:44.860 | - But you're writing the script.

02:01:45.900 | I mean, I'm not trying to challenge you, but I see.

02:01:49.980 | So you don't, there have to be instances

02:01:52.980 | where someone's thyroid deficient

02:01:54.180 | and you give them a drug.

02:01:55.500 | - Absolutely, so if you've got a disease

02:01:58.960 | and a medicine will replace what's missing, sure, okay?

02:02:02.740 | So for deficiency diseases, which as an endocrinologist,

02:02:06.220 | that's what I do, absolutely.

02:02:08.980 | And I did that with no compunction

02:02:12.140 | of impropriety whatsoever.

02:02:15.480 | But that's not what we're talking about here.

02:02:18.260 | Let's talk about what we're really talking about.

02:02:21.060 | Let's start with statins, statins lower LDL.

02:02:26.060 | Okay, do statins reduce heart disease?

02:02:32.480 | Yes or no?

02:02:36.100 | - I seem to be whiffing today on all the quizzes

02:02:39.220 | and it's kind of becoming fun for me at this level.

02:02:41.920 | I'm gonna go with no, but I will say, you know,

02:02:45.080 | my friend and I think his expert physician as well,

02:02:48.500 | you know, Peter Attia and others, you know,

02:02:50.280 | has talked about some of the positive attributes

02:02:52.740 | of statins in certain cases for certain patients.

02:02:54.980 | - In certain cases, that's exactly right.

02:02:56.920 | And I completely agree.

02:02:57.900 | And by the way, Peter's a friend and, you know,

02:03:00.340 | someday we'll, you know, all, you know,

02:03:02.980 | go out drinking together.

02:03:04.260 | - Well, I won't drink, but how about

02:03:06.020 | if we share a steak?

02:03:06.860 | - Share a steak, absolutely.

02:03:08.740 | You got it.

02:03:09.580 | - You guys, I don't know if he drinks a little bit.

02:03:12.580 | - If you're listening, okay.

02:03:13.820 | - He drinks a little bit.

02:03:14.660 | - Porterhouse on me.

02:03:15.500 | - Yeah, I don't do the dessert or the alcohol anymore.

02:03:18.020 | But I'm, and it's not so I can live to be 120.

02:03:20.660 | It's so I can wake up the next morning

02:03:21.940 | and keep up with you guys.

02:03:24.140 | - It's fine, yeah, I get it.

02:03:25.740 | So for primary prevention, that is your LDL's high,

02:03:31.340 | you need a statin.

02:03:32.460 | That's primary prevention.

02:03:33.980 | You haven't declared yourself.

02:03:35.300 | You haven't had an event.

02:03:36.940 | For primary prevention, the mean increase in lifespan

02:03:41.940 | for being on a statin is four days.

02:03:46.100 | - Four days?

02:03:46.940 | - Four days.

02:03:47.780 | - Four days.

02:03:48.620 | Sorry, I have to chuckle.

02:03:49.540 | That's a--

02:03:50.780 | - And the risk for diabetes is 20% increase.

02:03:55.660 | - What about any improvement in quality of life?

02:03:58.460 | - Done.

02:03:59.300 | For primary prevention.

02:04:00.580 | Now for secondary prevention, for secondary,

02:04:03.420 | in other words, you've already declared yourself.

02:04:05.140 | You already have a problem.

02:04:06.820 | For secondary prevention, that's where statins shine.

02:04:10.460 | So there's a value to them.

02:04:12.700 | I'm not arguing that.

02:04:13.700 | And if you have familial hypercholesterolemia,

02:04:16.220 | which is one in 500, okay, not only do you need a statin,

02:04:19.660 | but you need a low-fat diet and a priest, okay?

02:04:23.820 | So there is definitely a value to statins,

02:04:27.860 | but not for primary prevention.

02:04:29.920 | But that's what every doctor's doing.

02:04:33.100 | Oh, your LDL, it's over 80, you need a statin.

02:04:36.620 | That's ridiculous.

02:04:37.460 | That is absolutely a joke.

02:04:39.100 | And the data show that.

02:04:41.940 | In fact, in fact, my colleague Asim Malhotra in the UK

02:04:46.280 | participated in an analysis

02:04:48.340 | where they took the entire UK population,

02:04:52.140 | and they took out everybody under age 65.

02:04:55.900 | So you're looking at people 65 to 90.

02:04:58.260 | And it turned out that the LDL level

02:05:01.300 | correlated with longevity.

02:05:03.400 | The higher the LDL, the longer they lived

02:05:06.900 | when you took out all the people who had problems.

02:05:10.800 | So LDL is not really the problem.

02:05:13.420 | And the reason is 'cause there are two LDLs.

02:05:15.500 | There's one called large buoyant.

02:05:16.860 | There's one called small dense.

02:05:18.800 | Turns out dietary fat raises your large buoyant.

02:05:21.300 | Your large buoyant is irrelevant.

02:05:24.020 | It is cardiovascularly neutral.

02:05:28.220 | But that's the one that statins affects.

02:05:31.140 | The small dense, that's the atherogenic particle.

02:05:34.680 | When your small dense LDL is high,

02:05:36.920 | that means you are not clearing triglyceride peripherally

02:05:41.260 | because that's what small dense show you.

02:05:43.820 | That's what happens to triglyceride,

02:05:47.260 | they become small dense.

02:05:48.620 | - Can I take a guess and say

02:05:51.900 | that the best way to reduce small dense

02:05:54.540 | is to reduce insulin?

02:05:56.780 | - Yes, by reducing sugar.

02:06:00.180 | Because that triglyceride is made in the liver.

02:06:03.340 | It's all palmitate and that's the only fat

02:06:06.860 | that the liver knows how to make.

02:06:08.900 | And so triglyceride is your liver output of carbohydrate.

02:06:13.900 | That's how you have to look at triglyceride.

02:06:16.800 | So triglyceride turns out to be much more important

02:06:19.860 | as a cardiovascular risk factor than LDL ever was.

02:06:23.140 | - So does big pharma and big food,

02:06:26.380 | do they know all of this?

02:06:28.140 | - Yes, I know they know 'cause they've told me so.

02:06:31.480 | But they have statins to sell.

02:06:33.980 | - And foods in the NOVA class four.

02:06:38.900 | - They know this too.

02:06:40.780 | - So I'm an optimist or what's it gonna take

02:06:45.780 | to really move the needle?

02:06:47.900 | I mean, you described the four barriers.

02:06:49.900 | We're trying to add to the knowledge component now.

02:06:53.600 | What's it gonna take?

02:06:55.900 | Going to take having a president in office

02:06:59.260 | or congress people in office that really understand

02:07:02.820 | and care about this stuff?

02:07:04.700 | - Yeah.

02:07:05.620 | - I mean, to really revamp the whole system.

02:07:07.860 | - So right now, the system is completely and utterly broken.

02:07:13.540 | Completely and utterly broken.

02:07:14.860 | And there's a reason why it's completely and utterly broken

02:07:17.220 | 'cause the food industry likes it that way.

02:07:19.380 | - Well, it's profitable for them, obviously.

02:07:21.740 | - There are 51 different federal agencies

02:07:24.940 | that manage our food, 51.

02:07:27.820 | And none of them know what the other one's doing.

02:07:30.220 | And the food industry likes it that way.

02:07:33.380 | - So communication across these 51 organizations would help?

02:07:38.100 | - Well, if we had a centralized food czar or food,

02:07:43.100 | if we split the food off the FDA,

02:07:47.860 | because it's not the FDA, it's the DA,

02:07:52.460 | or the FDA is not the Food and Drug Administration,

02:07:55.100 | it's the Federal Drug Administration.

02:07:56.740 | They spend a lot of time on drugs.

02:07:58.500 | They spend almost no time on food.

02:08:00.660 | - Well, let's think about where there's been success.

02:08:02.300 | So I can recall when people smoked on planes.

02:08:04.540 | I actually recall going to a gym in Europe

02:08:08.380 | and there was an ashtray molded into the squat rack.

02:08:11.060 | - Yep.

02:08:11.900 | - That was telling.

02:08:12.900 | - Yep.

02:08:13.780 | - I don't see people smoking cigarettes

02:08:16.180 | around Stanford Hospital anymore.

02:08:17.740 | But I remember when they initially said

02:08:19.940 | that people couldn't smoke anywhere

02:08:21.820 | except in this one little designated area.

02:08:24.340 | And that's typically what you see nowadays.

02:08:26.020 | And my understanding of the anti-smoking campaign,

02:08:29.260 | at least for kids, for people 18 and younger,

02:08:31.460 | was that telling people it was bad for their health

02:08:34.300 | didn't work.

02:08:35.300 | Showing them lungs that were decrepit didn't work.

02:08:38.500 | What worked was showing them commercials

02:08:41.260 | of cackling, hand writhing white guys

02:08:45.060 | who were talking about how much money they were making

02:08:49.940 | off of these naive kids who were buying cigarettes

02:08:54.820 | and other tobacco products.

02:08:55.860 | So it became the effective campaign

02:08:59.220 | to end smoking in young people

02:09:01.000 | was to hijack their inherent rebelliousness of youth.

02:09:06.000 | And then they were like, "No, we're not gonna smoke.

02:09:09.140 | "Stick it to them."

02:09:10.240 | Like, you know, as my friend calls it,

02:09:12.340 | like the two-finger business card, like no.

02:09:15.800 | And so that worked.

02:09:18.460 | That worked.

02:09:19.300 | - Vaping's making a comeback.

02:09:20.780 | Vaping is a separate episode.

02:09:21.960 | We won't get into that.

02:09:22.800 | But because nicotine is still addictive.

02:09:25.120 | But you don't see a lot of people smoking cigarettes.

02:09:28.380 | So it worked.

02:09:29.220 | Like something that you would never imagine

02:09:31.020 | could ever work, worked.

02:09:32.460 | - Well, so yes, no.

02:09:34.260 | I mean, that's part of it.

02:09:35.420 | I'm not gonna tell you that it's not.

02:09:36.840 | It is part of it.

02:09:38.060 | And we actually have an example

02:09:40.620 | of how that could be applied

02:09:41.860 | to another toxic substance, sugar.

02:09:46.020 | We had Berkeley versus Big Soda.

02:09:48.600 | You know, that's how Berkeley ended up with its soda tax.

02:09:51.780 | That dates back to 2015.

02:09:54.240 | - The city of Berkeley.

02:09:55.080 | - City of Berkeley.

02:09:56.420 | We just celebrated the five-year anniversary

02:09:59.040 | of the Berkeley soda tax.

02:10:01.040 | And we've been able to actually look.

02:10:03.140 | Gestational diabetes, way down.

02:10:07.360 | Obesity, down slightly.

02:10:09.460 | Not a lot, but a little bit.

02:10:10.980 | Cardiovascular disease, down.

02:10:14.060 | Dean Schillinger and Chris Madsen at UCSF and UC Berkeley

02:10:18.620 | just presented at San Francisco General

02:10:20.500 | just three weeks ago.

02:10:22.120 | - So a soda tax like the cigarette tax.

02:10:24.160 | - Like this-- - Just makes soda expensive.

02:10:25.800 | - Exactly.

02:10:26.640 | - So you're telling me that a can of Coke

02:10:28.240 | that I buy on Shattuck Avenue in Berkeley

02:10:31.480 | costs more than a can of Coke that I buy

02:10:34.320 | on University Avenue in Palo Alto?

02:10:36.640 | - It does.

02:10:37.600 | - Huh, okay.

02:10:38.600 | - Buy a dime.

02:10:40.160 | - And that was sufficient enough

02:10:42.080 | to create this kind of change?

02:10:43.880 | - Well, yes, it is.

02:10:45.480 | - 'Cause money hurts.

02:10:46.320 | - 'Cause money hurts, exactly.

02:10:47.960 | So, Andrew, there have been four, count 'em,

02:10:52.260 | four cultural tectonic shifts in America

02:10:55.840 | in the last 30 years.

02:10:57.400 | And they're all undeniable, here they are.

02:11:00.640 | Number one, bicycle helmets and seat belts.

02:11:04.200 | - Everybody uses those.

02:11:05.760 | - Two, smoking in public places.

02:11:08.600 | - Nobody does that.

02:11:09.980 | - Three, drunk driving.

02:11:13.420 | - Hopefully fewer people are doing that.

02:11:15.280 | - Four, condoms in bathrooms.

02:11:17.400 | - Condoms in bathrooms?

02:11:19.560 | - In bathrooms, in public bathrooms.

02:11:21.260 | - Yeah, you see those more available.

02:11:22.880 | - Okay, all right.

02:11:24.360 | 30 years ago, if a legislator stood up in a state house

02:11:29.360 | and proposed legislation for any one of those four,

02:11:33.120 | and I don't care if it's in a state house

02:11:34.560 | or in Congress or in Parliament or in the Duma

02:11:37.560 | or anywhere else in the world,

02:11:39.200 | they'd have gotten laughed right out of town.

02:11:41.360 | Nanny state, liberty interest, get out of my kitchen,

02:11:45.920 | get out of my bathroom, get out of my car.

02:11:48.260 | Okay, today, they're all facts of life.

02:11:50.260 | All right, nobody's bellyaching about any of those.

02:11:54.780 | The point is, we were able to solve those

02:11:59.100 | for public health tobaccos.

02:12:03.440 | How did we do it?

02:12:05.320 | How did we solve those four?

02:12:07.600 | No one could imagine that we would ever solve smoking, right?

02:12:11.600 | But we did, sort of.

02:12:13.200 | I mean, we brought consumption down by half.

02:12:16.320 | Okay, that's pretty good when you think about it.

02:12:18.480 | For an addictive substance--

02:12:19.320 | - How many fewer people are dying

02:12:20.560 | of lung cancer nowadays in the US?

02:12:22.200 | - It's like 80% lower.

02:12:25.400 | - Well, there's also been improvements in treatment, but--

02:12:27.480 | - Yeah, but no, it's the incidence--

02:12:29.480 | - But diagnosed with the incidence.

02:12:31.320 | - Incidence has gone down.

02:12:32.140 | - Amazing.

02:12:32.980 | - Okay, because tobacco's gone down.

02:12:35.400 | So the question is, how did that happen?

02:12:37.960 | The answer is very, and why did it take 30 years to do it?

02:12:41.440 | We taught the children, the children grew up,

02:12:45.460 | and they voted, and the naysayers are dead.

02:12:50.460 | That's how you make a cultural tectonic shift.

02:12:56.460 | So, we now have this real food movement.

02:13:02.160 | We have people who are arguing against ultra-processed food.

02:13:06.040 | We have kids who are demanding different in their schools.

02:13:10.600 | And by the way, what is the biggest fast food franchise

02:13:15.000 | in the United States?

02:13:17.840 | - I'm gonna get this wrong, so--

02:13:19.460 | - Try me again.

02:13:20.300 | - I don't know, I've never tried it,

02:13:21.640 | but I've heard of, is it Chick-fil-A?

02:13:24.940 | - Nope.

02:13:25.780 | - Is it McDonald's?

02:13:26.600 | I don't know.

02:13:27.760 | - It is this nation's public schools.

02:13:30.720 | - Ah.

02:13:32.240 | - You can add up McDonald's, Subway, Burger King, Chick-fil-A,

02:13:37.240 | and Wendy's, and every other fast food franchise,

02:13:44.400 | Jack in the Box, every fast food franchise

02:13:48.000 | in the entire country, and it would only be half

02:13:50.840 | our nation's public schools.

02:13:53.400 | - Wow, so could you imagine a world

02:13:56.600 | where there were no class three or class four NOVA foods

02:14:01.600 | allowed in public schools?

02:14:04.400 | - And we're doing it.

02:14:06.180 | So I am the chief science officer of a nonprofit,

02:14:09.380 | and put this in the show notes, called Eat Real,

02:14:12.920 | eatreal.org, and we have a new business model

02:14:17.760 | for public schools.

02:14:18.920 | So in 1971, the Department of Education

02:14:25.320 | issued an administrative ordinance called Resolution 242,

02:14:29.940 | and they did this purely on monetary reasons.

02:14:34.000 | This was under Nixon, and what this Resolution 242 said

02:14:38.080 | was that all school cafeterias all throughout the country

02:14:42.800 | had to make book.

02:14:44.120 | They had to basically cover their costs.

02:14:48.400 | They couldn't be loss leaders for the school.

02:14:51.200 | They had to fend for themselves.

02:14:54.840 | Well, this sent every food service director

02:14:57.120 | in the country scurrying for how am I gonna do this,

02:15:00.760 | 'cause I got all these lunch ladies,

02:15:04.520 | which personnel and food preparation equipment

02:15:08.160 | and costs that they're mounting,

02:15:11.600 | how am I going to break even?

02:15:15.440 | They couldn't do it.

02:15:16.480 | So in walks Aramark and Cisco and Guggenheim and McDonald's,

02:15:23.960 | and they say, "Hey, we'll do it for you.

02:15:26.440 | "We'll provide every kid in America

02:15:29.060 | "with a nutritious meal every single day."

02:15:32.600 | - Hot lunch.

02:15:33.560 | - Well, they didn't say hot.

02:15:35.520 | They just said lunch.

02:15:36.740 | Nutritious, they said nutritious,

02:15:38.400 | and I put that in air quotes too,

02:15:40.000 | 'cause it wasn't nutritious.

02:15:42.200 | And here's the added benefit.

02:15:45.740 | You can take your food preparation facilities

02:15:48.720 | and your footprint in the school,

02:15:52.080 | and you can turn that into classrooms

02:15:54.160 | 'cause you're gonna need 'em.

02:15:56.320 | And that was the goal.

02:15:58.140 | Because as soon as you've moved

02:15:59.760 | the food preparation facilities out of the school,

02:16:01.980 | you are now hostage to the food industry

02:16:03.880 | for the rest of your life.

02:16:05.360 | - And I could also see how that allows room for them

02:16:08.360 | to use these commoditized foods,

02:16:10.400 | foods that have very long shelf life.

02:16:12.120 | - Exactly.

02:16:12.960 | - Right, because you wanna make sure

02:16:14.400 | that if you only sold 2/3 of the lunches

02:16:18.120 | that were prepared that on next Tuesday after the weekend,

02:16:21.640 | that you could still give them food that isn't moldy.

02:16:23.600 | - Exactly right.

02:16:24.720 | And I will tell you, so that's how it happened.

02:16:28.480 | And you can actually trace IQ scores

02:16:31.960 | and reading and math scores in this country

02:16:35.520 | down from 1971 to today.

02:16:38.420 | - When I went to school, I was allowed to get,

02:16:42.760 | I called it hot lunch 'cause it was usually hot.

02:16:44.940 | I was allowed to get the school lunch one day a week.

02:16:48.820 | - One day a week.

02:16:49.660 | - Two days, I had to bring my lunch.

02:16:51.940 | That one day was pretty special,

02:16:53.420 | like you felt like you were getting a treat.

02:16:55.040 | It was usually like corn dog or a hamburger.

02:16:58.460 | The hamburger was pretty paltry, but the-

02:17:00.540 | - It's a commoditized hamburger.

02:17:01.700 | - Yeah, a commoditized hamburger.

02:17:03.580 | You had to go looking for the patty portion

02:17:05.620 | and the bread was sweetened.

02:17:07.560 | And so it was different,

02:17:09.140 | but I don't remember nearly as much obesity.

02:17:11.460 | I went to high school in the early '90s.

02:17:14.620 | So you're saying that now, if I went to a high school,

02:17:18.120 | it would be a lot more sodas and donuts and pizza and-

02:17:23.120 | - Got it.

02:17:24.100 | Yeah, pizza's a vegetable, didn't you know?

02:17:26.720 | - They claim it's a vegetable.

02:17:27.640 | - Congress said pizza's a vegetable.

02:17:29.160 | Amy Klobuchar made pizza a vegetable.

02:17:31.100 | - Maybe they need their eyes checked.

02:17:31.940 | - Because the biggest frozen pizza producer is in Minnesota.

02:17:36.680 | - I mean, the ketchup is a vegetable was a stretch,

02:17:41.760 | but at least it made sense on the Nova system

02:17:44.300 | of going from tomato all the way to ketchup.

02:17:47.960 | - To ketchup.

02:17:48.800 | - Since high fructose corn syrup

02:17:49.940 | is the primary ingredient in ketchup.

02:17:53.600 | - Indeed.

02:17:54.440 | - So the point is that our kids are suffering

02:17:58.500 | under the weight, the burden of this chronic disaster

02:18:03.500 | of ultra processed food, which is not food.

02:18:07.300 | And no wonder they're all obese

02:18:09.760 | and sick and doing so poorly in school.

02:18:16.360 | And by the way, also depressed.

02:18:18.400 | Ultra processed food has now been shown

02:18:20.320 | in three separate studies to correlate

02:18:23.100 | with depression in teenagers.

02:18:25.320 | - So what is the relationship between processed food

02:18:28.280 | or maybe we call it Nova system level three, four foods

02:18:31.960 | and depression and other psychiatric challenges?

02:18:35.840 | And if you could, you separate out metabolic syndrome

02:18:40.840 | from obesity in answering that.

02:18:44.400 | Like, is there something inherently depressing

02:18:47.520 | about carrying excess adipose tissue,

02:18:50.680 | setting aside any kind of aesthetic stuff,

02:18:55.020 | you know, how people want to look or perceived,

02:18:57.640 | you know, just, is there anything bad

02:18:59.080 | about carrying a lot of body fat

02:19:01.040 | independent of the metabolic syndrome

02:19:02.680 | for mood and overall sense of wellbeing?

02:19:05.880 | - No, I'm really glad you asked that, Andrew.

02:19:07.600 | And we should have actually covered this earlier.

02:19:09.800 | Everyone thinks fat is fat.

02:19:12.900 | As we've learned, fat is not fat.

02:19:15.280 | And a fat is not a fat, but body fat is not body fat.

02:19:20.280 | There are three fat depots

02:19:22.560 | and they are metabolically different.

02:19:26.720 | The first is the,

02:19:29.000 | does this bathing suit make me look fat fat?

02:19:32.520 | By the way, never answer that question.

02:19:34.600 | That's called subcutaneous fat or big butt fat, if you will.

02:19:41.040 | So here's the question.

02:19:42.180 | How many pounds or kilos of subcutaneous fat

02:19:46.920 | do you have to gain before you become metabolically ill?

02:19:50.920 | - I have no idea.

02:19:52.280 | - About 10 kilos, about 22 pounds.

02:19:55.160 | - Okay. - Why?

02:19:57.320 | The reason is because that subcutaneous fat

02:20:00.200 | drains into the systemic circulation.

02:20:03.520 | So you have to have a lot of cytokines

02:20:08.440 | coming from those subcutaneous adipocytes

02:20:12.040 | to raise the blood level of cytokines

02:20:16.860 | to the point where it starts doing damage

02:20:19.000 | at the level of the liver.

02:20:20.220 | - So fats are releasing cytokines,

02:20:21.940 | which are pro-inflammatory?

02:20:23.140 | - Exactly.

02:20:23.980 | - And they're doing that at rest.

02:20:25.120 | Any fat cell?

02:20:26.360 | - Any fat cell.

02:20:27.520 | - Okay. - Any fat cell.

02:20:28.640 | But if it's going to the systemic circulation,

02:20:31.460 | you have a volume of distribution of six liters.

02:20:34.420 | So you have to lose, you have to have a lot of cytokines

02:20:37.920 | to get the concentration up.

02:20:39.560 | - Now, just out of fairness to the fat,

02:20:42.380 | how many cytokines does a muscle cell release?

02:20:46.520 | I mean, are we unfairly picking on adipose tissue?

02:20:49.360 | 'Cause why would adipose tissue be pro-inflammatory?

02:20:52.800 | I mean, a single fat cell.

02:20:54.320 | I've got a fat cell sitting in my shoulder someplace, right?

02:20:59.160 | I mean, I'm not zero fat at my shoulder.

02:21:01.820 | Why would it be pro-inflammatory?

02:21:03.560 | - So in fact, the fat cell itself is not.

02:21:07.640 | Here's what happens.

02:21:09.520 | The fat cell has a fat vacuole.

02:21:12.040 | It has a storage place for this lipid droplet.

02:21:16.180 | You stuff it, you stuff it, you stuff it,

02:21:19.320 | the fat vacuole gets bigger, bigger, bigger.

02:21:22.100 | The perilylipin border that encompasses that fat vacuole,

02:21:26.520 | that borders the space,

02:21:30.080 | ultimately can't get any bigger,

02:21:33.560 | and it starts breaking down.

02:21:35.660 | When that happens, it spills the grease

02:21:38.860 | into the fat cell.

02:21:41.120 | The fat cell dies, becomes necrotic.

02:21:45.560 | That calls macrophages in to clean up the grease,

02:21:49.880 | and it's the macrophages that release the cytokines.

02:21:53.800 | So in fact, the fat cell is not the problem.

02:21:58.120 | It's the breakdown of the grease

02:22:03.120 | that leads to the macrophage activation.

02:22:06.280 | That's the problem.

02:22:07.720 | But when you do it in subcutaneous fat,

02:22:10.780 | it's going into this six-liter tank,

02:22:14.040 | and so the concentration doesn't go up very much.

02:22:17.480 | So 10 kilos before you start seeing some effect.

02:22:22.400 | Fat depot number two,

02:22:25.380 | visceral or big belly fat.

02:22:29.340 | Now, how many pounds or kilos of big belly fat

02:22:34.680 | do you have to gain before you get metabolically ill?

02:22:38.120 | - I don't know, but I'm guessing it's less than 22 pounds.

02:22:40.380 | - It's way less.

02:22:41.560 | - Oh, for once I got an answer right today.

02:22:43.000 | - Yeah, that's right. (laughs)

02:22:44.720 | About five, about five pounds.

02:22:48.040 | Now, the question is why?

02:22:49.780 | Number one, the visceral fat does not drain

02:22:54.240 | into the systemic circulation.

02:22:56.960 | It drains into the portal vein,

02:22:58.720 | which goes straight to the liver.

02:23:00.240 | So you're getting a bigger load

02:23:02.000 | going straight to the liver of cytokines.

02:23:04.000 | - Not to the kidney.

02:23:05.300 | - Not to the kidneys.

02:23:06.140 | - The good thing about getting an answer wrong, folks,

02:23:07.480 | is that you never forget the correct answer.

02:23:10.040 | That's what I always tell my students, right?

02:23:11.760 | So I'll never forget that.

02:23:13.200 | - Indeed.

02:23:14.080 | - Got it.

02:23:15.160 | - And the question is what made the visceral fat

02:23:18.800 | in the first place?

02:23:20.140 | Was it calories?

02:23:21.760 | Nope.

02:23:23.200 | It's cortisol.

02:23:24.700 | It's stress.

02:23:26.440 | It's the combination

02:23:27.400 | of the sympathetic nervous system and cortisol.

02:23:29.720 | And the reason we know this is because you can take patients

02:23:32.620 | with major depressive disorder,

02:23:34.400 | with endogenous depression, who are suicidal,

02:23:37.160 | who have to be admitted to the hospital

02:23:39.100 | to keep themselves from killing themselves,

02:23:42.500 | stick them in a scanner,

02:23:44.400 | and they are losing subcutaneous fat like crazy

02:23:47.200 | 'cause they're not eating,

02:23:48.940 | but they're gaining visceral fat

02:23:50.840 | because of the high cortisol and the stress.

02:23:54.460 | - So there's something about the adrenocorticoid receptors

02:23:57.440 | in that area that just preferentially depot fat there

02:24:00.640 | when cortisol is high?

02:24:02.380 | - Indeed.

02:24:03.880 | Because that's the metabolically active fat, right?

02:24:07.760 | And five pounds will do it.

02:24:09.880 | And then finally the third fat depot, the liver.

02:24:13.160 | Now, how many pounds of fat can the liver store

02:24:17.760 | before you become metabolically ill?

02:24:20.500 | - Oh, I gotta be even less

02:24:24.000 | because the liver's not nearly as large

02:24:26.240 | as the sort of abdominal region.

02:24:28.840 | - Half a pound, quarter of a kilo.

02:24:31.160 | How much does a healthy liver weigh?

02:24:33.820 | - Healthy liver weighs 1,500 grams, okay?

02:24:38.100 | So it's not very--

02:24:43.160 | - I'm trying to translate quickly to pounds,

02:24:44.740 | so we're going metric, we're going as standard to metric.

02:24:47.040 | - So 1,500 grams would be three pounds.

02:24:50.000 | So basically half a pound, okay?

02:24:53.860 | So not very much.

02:24:55.240 | Because that's where the action is.

02:24:58.980 | And so when you have fat in your liver,

02:25:02.120 | it causes metabolic dysfunction right away.

02:25:05.720 | And the question is where did that fat come from?

02:25:08.700 | That came from alcohol or sugar.

02:25:10.540 | So alcohol and sugar, most metabolically egregious

02:25:15.280 | 'cause it affects the liver directly.

02:25:17.600 | Stress, second most because it affects the visceral fat.

02:25:22.600 | And subcutaneous fat, the least important

02:25:26.720 | in terms of metabolic derangement.

02:25:29.040 | So yes, it may not look good in a bathing suit,

02:25:32.140 | but from a metabolic standpoint,

02:25:33.920 | it is actually the least important.

02:25:36.020 | So the question then becomes, all right,

02:25:39.740 | what are you trying to fix?

02:25:42.380 | If you're trying to fix liver fat, it's really easy.

02:25:46.280 | Get rid of the alcohol and the sugar,

02:25:47.360 | except of course they're both addictive.

02:25:49.360 | - Will that also liberate any fat

02:25:51.520 | that's already in the liver?

02:25:52.680 | - Absolutely, and that's one of the reasons

02:25:54.000 | why intermittent fasting works

02:25:56.080 | is because it gives your liver a chance

02:25:57.760 | to basically offload what it's already stored.

02:26:02.720 | That's one of the things that intermittent fasting

02:26:05.320 | will buy you is a little less liver fat.

02:26:10.080 | So that's a good thing.

02:26:11.880 | All right, now stress on the other hand, as you know,

02:26:14.960 | and as we've talked about and as you know,

02:26:17.360 | you've had Dr. Les Appel on your podcast before,

02:26:21.960 | stress is tough, trying to mitigate stress,

02:26:25.120 | especially in today's environment,

02:26:27.080 | and I hope you'll invite me back some time

02:26:29.140 | to talk about the role of stress on the amygdala.

02:26:33.640 | - Yeah, gladly.

02:26:34.480 | - And then finally, the subcutaneous fat.

02:26:39.200 | So when people go on diet sweeteners, what are they doing?

02:26:44.200 | Are they really reducing the fat?

02:26:51.320 | And the answer is no.

02:26:53.600 | - When are you talking about artificial sweeteners?

02:26:55.460 | - Diet sweeteners of any sort.

02:26:57.120 | You can pick your artificial sweetener.

02:26:59.320 | So aspartame or sucralose, stevia, monk fruit,

02:27:04.320 | the new ones, you know.

02:27:08.400 | - Yeah, the one that people are more excited about nowadays

02:27:10.640 | is Allulose, it's expensive, it tends to have less

02:27:13.460 | of an artificial sweetener taste that people can detect.

02:27:16.520 | So you're saying that regardless of, oh, and we should,

02:27:21.100 | I'm remembering from the comment section, I do read them,

02:27:25.500 | artificial sweeteners and non-caloric sweeteners.

02:27:29.860 | Because the moment you say artificial, people say,

02:27:31.500 | what about stevia, what about Allulose?

02:27:33.180 | So let's just say non-caloric sweeteners

02:27:37.200 | can wrap our arms around that entire category

02:27:40.100 | unless we need to distinguish among the different

02:27:42.460 | participants in that category.

02:27:44.140 | So you're saying that even though people can lower

02:27:48.460 | their total caloric intake, pretty effectively,

02:27:50.960 | I've seen the studies that show if, you know,

02:27:53.100 | dieters who consume water only as their main liquid

02:27:58.100 | versus diet sodas with aspartame typically or stevia,

02:28:04.140 | the diet soda drinkers actually lose more weight.

02:28:08.340 | We know that, but you're saying there may be deposition

02:28:11.220 | of fat in the liver in those individuals,

02:28:14.820 | specifically because of the artificial sweetener.

02:28:16.900 | - Because of the insulin.

02:28:18.460 | Turns out there's still an insulin response.

02:28:20.820 | So a very famous study done in Copenhagen,

02:28:24.540 | 100 normal individuals, 25 in four different groups.

02:28:29.540 | One group, one liter of sugared soda per day for six months.

02:28:35.680 | - One liter, that's a lot of sugared soda.

02:28:39.520 | - Yeah, one group, one liter of diet soda per day

02:28:43.220 | for six months.

02:28:44.180 | - I probably did that in graduate school.

02:28:46.400 | - One group, one liter of milk per day for six months.

02:28:50.180 | - I probably did that when I was an infant.

02:28:52.060 | - And finally, one final group,

02:28:54.220 | one liter of water per day for six months.

02:28:56.540 | - I do that now.

02:28:57.380 | I do more than that, but yeah.

02:29:00.260 | - The one liter of soda per day in six months

02:29:04.540 | gained 10 kilos.

02:29:05.620 | - The sugary soda.

02:29:06.540 | - The sugary soda.

02:29:07.380 | - 10 kilos.

02:29:08.380 | - 10 kilos, no surprise.

02:29:10.540 | The one liter of water per day lost two kilos.

02:29:14.940 | Also no surprise, those were the easy ones.

02:29:18.060 | Now let's do the ones in the middle.

02:29:20.340 | One liter of milk per day, no change.

02:29:25.020 | - Presumably that was full fat milk.

02:29:26.660 | We're talking about Europe.

02:29:28.100 | - Full fat milk.

02:29:28.940 | - Yeah, they like their full fat milk.

02:29:31.100 | - No change, why is that?

02:29:33.420 | They're taking on an enormous increase

02:29:37.860 | in total caloric intake.

02:29:39.580 | - I'm guessing that there was a blunted insulin response

02:29:42.860 | due to the fat in the milk.

02:29:44.460 | - And also because lactose is not a very big driver

02:29:49.060 | of insulin response.

02:29:50.540 | And because there's a satiety effect.

02:29:53.760 | - That's like food.

02:29:54.600 | - They eat less.

02:29:55.420 | - Yeah, it's like food.

02:29:56.260 | - Like food.

02:29:57.880 | And finally, the key, the kicker to the whole thing,

02:30:01.940 | diet soda, the one liter of diet soda.

02:30:04.880 | What would you predict their weight would do?

02:30:08.020 | - More weight loss than in the water group

02:30:09.940 | based on my understanding of the literature.

02:30:12.300 | - They gain two kilos.

02:30:14.160 | - A child, because they ate more.

02:30:16.040 | - Well, you tell me, why did they gain two kilos

02:30:21.900 | if they were consuming a liter of diet soda,

02:30:24.600 | which are zero calories?

02:30:26.580 | The answer is because they still generated

02:30:28.340 | an insulin response.

02:30:29.460 | - And that insulin response generated more hunger?

02:30:31.920 | - More weight and more hunger, exactly.

02:30:35.980 | And that's the key.

02:30:36.900 | So they didn't gain the 10 kilos, they gained two kilos.

02:30:40.620 | So it looks better compared to the sugared version,

02:30:44.300 | but it looks like a problem compared to the water version

02:30:50.760 | or even the milk version.

02:30:51.940 | - So unless you bootstrap calories and hold that constant,

02:30:54.740 | you're gonna see a weight gain

02:30:55.800 | due to artificial sweetener intake.

02:30:57.620 | - Exactly right.

02:30:58.460 | And that's been shown 50 ways from Sunday

02:31:00.520 | at a whole bunch of different studies.

02:31:02.500 | So compared to sugar, yeah, it's better.

02:31:06.000 | But compared to water, it's way worse.

02:31:08.640 | And the reason is the insulin response.

02:31:11.380 | You put something sweet on the tongue,

02:31:13.080 | message goes, tongue to brain, sugar's coming,

02:31:15.720 | message goes, brain to pancreas through the vagus nerve,

02:31:19.040 | sugar's coming, release the insulin.

02:31:22.040 | And so tongue doesn't know if it's sugar or not.

02:31:26.040 | It releases the, the pancreas releases the insulin,

02:31:28.600 | which drives energy into fat,

02:31:30.620 | whether it was from the diet sweetener or not.

02:31:34.300 | - I saw some really interesting data

02:31:35.840 | from Dana Small's group at Yale

02:31:37.900 | showing that when people have a diet soda with food,

02:31:40.920 | so this is like the Diet Coke with the sandwich

02:31:42.720 | or with the burger, maybe even with the pasta,

02:31:45.620 | the insulin response from the food

02:31:48.000 | and the insulin response from the diet soda are compounded,

02:31:50.840 | but there's a classical conditioning effect,

02:31:52.440 | Pavlovian effect, such that then later,

02:31:56.040 | if they just drink the diet soda,

02:31:58.640 | they get an even bigger insulin response

02:32:00.760 | just to the diet soda than they would have originally

02:32:03.800 | if they'd only had the diet soda separate from food.

02:32:06.240 | So in other words, the insulin,

02:32:08.120 | the food-induced insulin response

02:32:09.980 | is conditioning a greater insulin response

02:32:12.200 | from the diet soda.

02:32:13.220 | - And we actually have another study

02:32:14.640 | that demonstrates the same thing out of Singapore,

02:32:17.620 | Tay et al in American Journal of Clinical Nutrition,

02:32:21.540 | 2018, I believe, that looked at a similar paradigm.

02:32:26.540 | Here's what they did.

02:32:28.620 | They took a bunch of people and they admitted them

02:32:31.860 | to their clinical research center four times a week apart,

02:32:35.540 | and they did them in random order.

02:32:37.400 | And each time they started the morning, they're fasting,

02:32:42.400 | and they did either a sucrose tolerance test

02:32:46.640 | or an aspartame tolerance test or a sucralose tolerance test

02:32:51.640 | or a monk fruit tolerance test.

02:32:55.960 | So two hours, ingesting one of the four

02:33:00.960 | and measuring glucose and insulin

02:33:03.500 | over the course of the next two hours.

02:33:05.360 | - Fasted.

02:33:06.340 | - Fasted, okay.

02:33:07.820 | Then it was time for lunch,

02:33:10.360 | and they let them have whatever lunch they want.

02:33:13.060 | It was a metabolic buffet.

02:33:14.980 | They could eat whatever they wanted off the buffet

02:33:17.520 | except that they were being clocked,

02:33:21.600 | and the same for dinner.

02:33:23.180 | They were being clocked,

02:33:24.380 | but they could eat whatever they wanted.

02:33:25.640 | - In a given period of time.

02:33:26.700 | - In the 24 hours, or from 7 a.m. to 7 p.m.

02:33:30.860 | whenever they went home.

02:33:32.740 | Turned out the sucrose tolerance test

02:33:35.960 | generated an insulin response as you'd expect.

02:33:38.960 | The monk fruit, the sucralose, and the aspartame did not.

02:33:43.960 | But then when they ate lunch,

02:33:49.320 | if they had had one of the three diet sweeteners

02:33:53.460 | in the morning, they ate more at lunch and more at dinner

02:33:57.600 | and generated an increased insulin response

02:34:00.120 | both at lunch and dinner

02:34:01.160 | so that the area under the curve for the whole day

02:34:03.360 | was exactly the same.

02:34:05.060 | - So they ate significantly more.

02:34:07.920 | - Yeah, yeah, because they had the diet soda in the morning.

02:34:11.980 | - Wild, well I drink drinks that contain stevia,

02:34:17.960 | and I don't worry about it too much,

02:34:20.460 | but what you're saying is even if I bootstrap my calories,

02:34:25.300 | there's a possibility that the insulin response

02:34:27.280 | could have direct effects on the liver.

02:34:29.600 | - Exactly right.

02:34:30.440 | - And not for the better.

02:34:31.320 | - And not for the better.

02:34:32.360 | Now, having said that,

02:34:33.820 | we have undertaken an interesting project,

02:34:39.380 | which I don't know if you know about.

02:34:41.280 | In 2020, during the pandemic,

02:34:46.000 | I was approached by a food company in the Middle East

02:34:50.420 | called Kuwaiti Danish Dairy Company, KDD.

02:34:54.000 | It's the Nestle of the Middle East.

02:34:56.040 | Now they make all sorts of junk.

02:34:58.920 | Frozen yogurt, flavored milks, ice cream,

02:35:03.360 | confectionery, biscuits, tomato sauce, okay?

02:35:06.720 | Kuwait has an 18% diabetes rate and an 80% obesity rate.

02:35:14.280 | - Eight zero. - Eight zero.

02:35:16.960 | - Wow. - In the adults, all right?

02:35:19.240 | Now, the company recognized that they wanted

02:35:24.680 | to be a metabolically healthy company

02:35:27.600 | and they knew they weren't.

02:35:28.900 | They contacted me and said,

02:35:31.660 | would you put together a scientific advisory team

02:35:34.280 | to advise us what we need to do to change the food

02:35:39.280 | in order to be a metabolically healthy company?

02:35:42.220 | And we wanna lead.

02:35:43.360 | And I said, I'd be happy to do that with one proviso.

02:35:47.760 | We get to publish what we did

02:35:50.800 | so that it can serve as a roadmap

02:35:53.200 | for the rest of the food industry.

02:35:55.080 | And they said, fine.

02:35:56.560 | And so I convened a scientific advisory team

02:35:59.840 | with my colleague, Wolfram Alderson,

02:36:01.840 | who started the very first farmer's market in Los Angeles

02:36:05.680 | and is now actually the director

02:36:06.880 | of sustainability and nutrition for KDD.

02:36:08.920 | Tim Harlan, who is the head of culinary medicine

02:36:13.280 | at George Washington University.

02:36:15.480 | Rachel Gao, who is a fatty acid expert

02:36:18.040 | who ran the omega-3 for ADD trial at the NIH.

02:36:21.920 | And Andreas Kornstadt,

02:36:23.160 | who's actually a computer scientist from Stanford.

02:36:26.280 | And we basically stripped down every single thing

02:36:31.280 | that KDD did in terms of procurement,

02:36:36.640 | in terms of ingredients, in terms of packaging.

02:36:39.560 | We submitted every single ingredient

02:36:41.480 | to biochemical analysis because you couldn't trust

02:36:44.440 | what the vendors were basically telling KDD

02:36:47.720 | was in the food.

02:36:48.760 | We had to actually know what was in the food.

02:36:51.480 | And that was a half a million dollars all by itself.

02:36:53.820 | I mean, this was not a cheap little sojourn into the woods.

02:36:58.820 | This was a big deal.

02:37:00.080 | We basically re-engineered their entire 180 item portfolio.

02:37:05.080 | And they have now turned over 10% of their products

02:37:10.260 | to be metabolically healthy.

02:37:12.300 | And the precepts that we set in this paper,

02:37:17.820 | which is in Frontiers in Nutrition

02:37:19.640 | in March of this year, 2023,

02:37:22.720 | three things, three principles.

02:37:24.440 | If you adhere to these three principles,

02:37:26.200 | you can turn any food healthy,

02:37:29.440 | including ultra-processed food.

02:37:31.460 | Number one, protect the liver.

02:37:34.660 | Number two, feed the gut.

02:37:36.720 | Number three, support the brain.

02:37:38.600 | If you have a food that does all three of those,

02:37:43.200 | it is healthy.

02:37:44.700 | If you have a food that does none of those three,

02:37:47.240 | then it's poison because it's not food.

02:37:49.020 | - It's not, I was gonna say,

02:37:50.060 | it doesn't sound like food is the right descriptor

02:37:53.560 | in that case.

02:37:54.400 | - Exactly.

02:37:55.220 | And if it does one or two but not all three,

02:37:57.280 | then it's gonna be somewhere in between.

02:37:59.180 | So the goal was to take all of KDD's products

02:38:01.640 | and move them from the lowest tier up to the highest tier

02:38:06.600 | by adhering to these three principles.

02:38:09.740 | And we came up with some very simple things.

02:38:12.940 | Number one, gotta get rid of the sugar.

02:38:15.520 | Number two, gotta add fiber.

02:38:19.220 | Number three, gotta add omega-3s.

02:38:21.940 | Number four, gotta do something about the emulsifiers

02:38:26.000 | because the emulsifiers are causing the gut inflammation

02:38:29.400 | because after all, emulsifiers are detergents.

02:38:31.920 | They hold fat and water together.

02:38:33.240 | They burn a hole in the mucin layer.

02:38:35.300 | So they're actually contributing to that gut inflammation

02:38:38.200 | and emulsifiers are strewn throughout

02:38:41.080 | ultra-processed food-dom.

02:38:43.120 | - We've heard about hidden sugars a lot

02:38:46.200 | during today's episode and elsewhere,

02:38:47.820 | but based on everything you told us about artificial,

02:38:51.760 | excuse me, low-calorie sweeteners,

02:38:53.940 | it makes more sense to me now

02:38:57.080 | why foods that are not touted as diet foods

02:39:00.280 | would be laced with things like sucralose

02:39:02.500 | because it should drive the craving for that food

02:39:05.780 | through increases in insulin and craving of other foods

02:39:09.540 | later that day and later that evening.

02:39:11.460 | Is that why non-caloric sweeteners

02:39:14.980 | are added to all sorts of foods now

02:39:17.120 | that because typically one thing's non-caloric sweeteners

02:39:19.840 | probably only added to quote-unquote diet foods,

02:39:22.280 | low-calorie foods, but that's not--

02:39:24.520 | - You're right, that's not the case.

02:39:26.660 | And they are adding diet sweeteners to foods

02:39:30.020 | that you didn't know had diet sweeteners in them.

02:39:31.960 | That's right.

02:39:32.800 | There are two reasons that this happens.

02:39:36.180 | One is insulin because insulin blocks leptin signaling

02:39:39.320 | at the level of the hypothalamus and the nucleus accumbens.

02:39:43.120 | So if it blocks leptin,

02:39:44.760 | leptin is the hormone that your fat cells make

02:39:47.240 | that tells your brain you've had enough.

02:39:49.480 | So if insulin blocks leptin, it makes you hungrier

02:39:53.300 | and it also extinguishes,

02:39:55.440 | it stops the extinguishing of reward by that food

02:39:58.700 | so that you want more of it.

02:40:00.520 | So it does both because leptin normally

02:40:03.520 | suppresses food intake and reduces craving.

02:40:08.100 | - The analogy that comes to mind is a slot machine

02:40:12.180 | that encourages you to feed more money

02:40:15.300 | and hit go to pull the lever,

02:40:17.660 | but that also blinds you to the outcome.

02:40:19.900 | So even if you win, you don't even know that you have wins.

02:40:22.660 | It's also blinding you to your losses.

02:40:24.580 | You're effectively becoming an automaton

02:40:27.460 | of just eating without any kind of conscious understanding

02:40:32.460 | of what you're bringing in or tasting the food any longer.

02:40:35.920 | - Exactly.

02:40:36.760 | - Right, it's not this like,

02:40:37.860 | Anna Lemke when she came on the podcast,

02:40:39.740 | author of "Dopamine Nation"

02:40:40.980 | and obviously head of our dual diagnosis addiction clinic

02:40:43.940 | at Stanford, talked about these consumptive behaviors

02:40:48.940 | where people are scrolling social media or consuming porn

02:40:52.420 | or consuming drugs or alcohol in a way that like,

02:40:55.560 | they're not in touch with the pleasure

02:40:57.520 | of the substance or behavior anymore.

02:40:59.980 | They become automatons.

02:41:01.520 | But if they don't do it, they feel lousy.

02:41:04.500 | So the pleasure is gone, the pain is definitely awaiting.

02:41:07.140 | - Tolerance and dependence,

02:41:08.840 | that's the definition of addiction.

02:41:10.960 | So dopamine is an excitatory neurotransmitter.

02:41:14.620 | It excites the next neuron always.

02:41:16.940 | There is no such thing as dopamine inhibiting

02:41:19.980 | a post-synaptic neuron.

02:41:21.500 | Dopamine stimulates the next neuron.

02:41:23.880 | And it doesn't matter which dopamine receptor it is,

02:41:26.000 | one through five, it's always excitatory.

02:41:28.980 | Now, neurons like to be excited.

02:41:30.780 | That's why they have receptors.

02:41:32.700 | But neurons like to be tickled, not bludgeoned.

02:41:35.680 | Chronic overstimulation of any neuron, and you know this,

02:41:39.780 | leads to neuronal cell death.

02:41:41.920 | And the reason is because the neuron needs energy.

02:41:46.260 | The neuron is the most energy-dependent tissue in the body.

02:41:51.260 | It needs those mitochondria to be pumping out ATP

02:41:57.080 | like crazy to engage in neurotransmission.

02:42:00.700 | Well, when you're firing nonstop, you risk cell death.

02:42:07.780 | So the excitatory neuron, the post-synaptic neuron,

02:42:11.740 | has a plan B.

02:42:14.180 | It down-regulates the receptor.

02:42:16.900 | It down-regulates the dopamine receptor.

02:42:19.060 | So there's less chance that any stray dopamine molecule

02:42:22.540 | will find a receptor to bind to.

02:42:24.760 | And this is its plan B in order to try to mitigate

02:42:28.940 | the risk of dying.

02:42:30.000 | Well, what does that mean in human terms?

02:42:33.660 | It means you get a hit, you get a rush,

02:42:36.420 | receptors go down, next time you need a bigger hit

02:42:39.260 | to get the same rush, and receptors go down,

02:42:41.860 | and you need a bigger hit and a bigger hit and a bigger hit

02:42:43.540 | until finally you need a huge hit to get nothing.

02:42:46.300 | That's called tolerance.

02:42:48.100 | And then when the neurons do start to die,

02:42:51.060 | that's called addiction.

02:42:52.260 | That's what we've got.

02:42:55.660 | And that's what's happened in terms of food addiction.

02:42:59.180 | So the question is, what's addictive?

02:43:02.740 | Is fat addictive?

02:43:04.820 | No, because if fat was addictive,

02:43:07.080 | then all the people on the Atkins diet

02:43:09.780 | or on the ketogenic diet would be gaining weight,

02:43:11.520 | not losing it.

02:43:12.360 | - And I'd be craving rib-eyes all day.

02:43:14.340 | I like a rib-eye pretty often, actually.

02:43:16.460 | But I know, I know, people say no.

02:43:18.300 | But hey, look, my lipids are in line

02:43:20.580 | and I don't eat many starches and I certainly avoid sugar.

02:43:23.540 | Although now I'm thinking I might want to really reduce

02:43:25.920 | my low-calorie sweetener intake.

02:43:29.260 | I don't see myself reducing my stevia intake to zero

02:43:32.700 | 'cause it's in some things I really like.

02:43:34.440 | - Andrew, I am not the food police, you know?

02:43:37.620 | - I always say that to people, I'm not a cop.

02:43:39.780 | But data are data and health data are interesting.

02:43:44.780 | - The data say that that's not helping you any.

02:43:48.620 | That's what the data say.

02:43:50.000 | Point is that the fat's not the problem.

02:43:55.720 | The salt's not the problem.

02:43:58.380 | The caffeine's a problem.

02:44:00.260 | - Really?

02:44:01.100 | - It's a classic addictive substance at every level.

02:44:04.880 | - Yeah, but in terms of-- - And the sugar's a problem.

02:44:06.640 | - But if one can cut out caffeine by the early afternoon

02:44:10.280 | or even sooner in the day and it's not consumed to excess

02:44:13.520 | and it's in the form of coffee, yerba mate,

02:44:17.920 | some other form that's healthy,

02:44:19.600 | is it really that much of a problem?

02:44:23.480 | I love coffee and yerba mate. - Me too.

02:44:25.440 | That's my addiction.

02:44:26.260 | - Like with a capital L underlined boldface highlight.

02:44:30.520 | - I feel your pain.

02:44:33.500 | And the answer is no one has shown that coffee is toxic.

02:44:38.360 | It is addictive, but it's not toxic.

02:44:40.560 | Now, if you mix the coffee with alcohol,

02:44:42.660 | now you got four loco, now it's toxic.

02:44:44.980 | But in and of itself, caffeine is not toxic.

02:44:49.200 | And that's why there's a Starbucks on every street corner.

02:44:51.640 | - But it is highly reinforcing.

02:44:53.060 | I did an episode on caffeine where it covered some data

02:44:55.960 | that was published in the journal Science,

02:44:57.560 | one of the three apex journals.

02:44:59.920 | And if you put caffeine, unbeknownst to the consumer,

02:45:04.360 | into plain yogurt, people will crave plain yogurt much more.

02:45:09.000 | I mean, people like the feeling of being caffeine

02:45:11.160 | as long as it's not creating anxiety levels of energy.

02:45:14.160 | - Exactly.

02:45:15.000 | - I'm gonna stick with caffeine.

02:45:16.180 | - That's fine, and so will I.

02:45:18.520 | - We've been talking a little bit about the hypothalamus

02:45:20.660 | as well as some peripheral gut-based mechanisms

02:45:23.640 | for hunger and satiety.

02:45:25.580 | This is a great opportunity to talk about

02:45:28.440 | some of the GLP-1 agonists that are now widely used.

02:45:33.440 | So typically called ozempic,

02:45:35.560 | but GLP-1, glucagon-like peptide-1,

02:45:39.040 | originally discovered in the Gila monster,

02:45:41.300 | which eats very seldom.

02:45:42.320 | And some really smart biologist, I love biology like this,

02:45:45.360 | said, "How come they don't have to eat very much?"

02:45:46.680 | Well, their blood is loaded with GLP-1.

02:45:49.720 | - Right.

02:45:50.560 | - And so they only have to eat one,

02:45:52.320 | whatever Gila monsters delight in,

02:45:55.560 | per year or something outrageous like that.

02:45:57.560 | Humans make GLP-1 as well.

02:45:59.240 | My understanding is that GLP-1,

02:46:00.960 | not that it's injected, but that one makes naturally,

02:46:06.060 | is acting on both the brain and the gut

02:46:10.200 | to increase satiety.

02:46:11.720 | - So it is acting on the brain, no argument,

02:46:16.400 | but the primary action is on the gut.

02:46:19.320 | GLP-1 decreases the rate of gastric emptying.

02:46:26.280 | - That is its primary driver.

02:46:28.840 | Yes, it does affect the brain.

02:46:30.320 | I'm not arguing that it does,

02:46:31.680 | but the primary effect is to reduce

02:46:34.880 | the rate of gastric emptying.

02:46:36.160 | So you stay fuller longer because the food doesn't move

02:46:41.160 | through the stomach and the intestine.

02:46:43.360 | - Interesting, in South America, in Uruguay and Argentina,

02:46:46.080 | it was long thought that yerba mate consumption,

02:46:50.200 | which we know very modestly increases GLP-1,

02:46:53.720 | and by the way, a lot of other things do too,

02:46:56.700 | that people were taking it after meals

02:46:59.120 | for its laxative effect, partially,

02:47:01.000 | but that's, you know, it's not pleasant for-

02:47:03.040 | - But that's also at the colon.

02:47:05.040 | - That's at the level of the colon.

02:47:06.200 | - Rather than the stomach.

02:47:07.040 | - But it is used fairly effectively

02:47:09.320 | for people to space their meals without snacking.

02:47:11.800 | And maybe it's the GLP-1, maybe it's something else,

02:47:15.500 | but people are injecting themselves

02:47:16.920 | with GLP-1 analogs now.

02:47:19.960 | - And it's $1,300 a month, yeah.

02:47:21.800 | - Is that what it costs?

02:47:22.640 | - That's what it costs right now.

02:47:24.280 | - And it seems to be pretty effective

02:47:26.060 | at inducing weight loss, although a significant amount

02:47:28.400 | of that weight loss seems to be

02:47:29.320 | from skeletal muscle tissue.

02:47:31.600 | - And we need to talk about that.

02:47:33.040 | - So what are your thoughts on ozempic as a primary,

02:47:36.200 | earlier you talked about primary and secondary control.

02:47:39.260 | You referred to it a little bit differently

02:47:40.600 | in the context of statins.

02:47:42.040 | So a kid comes in who's obese, who's slightly overweight,

02:47:46.120 | and it's like, "Mm, I don't know what to do.

02:47:47.620 | "I'm trying to eat better exercise."

02:47:49.080 | Or a person comes in and says,

02:47:50.120 | "Hey, I've had a really hard time getting

02:47:52.100 | "that last 29 pounds off for so many years.

02:47:56.260 | "Will you prescribe me ozempic?"

02:47:57.760 | - So the short answer is number one, I'm retired,

02:48:00.900 | so I'm not prescribed on anything.

02:48:02.640 | But let's go there.

02:48:05.280 | The data show that GLP-1 analogs like semaglutide

02:48:11.140 | and now terzepatide, which is Lily's version,

02:48:16.600 | Monjaro is the diabetes version,

02:48:18.560 | Zepbound is the obesity version in the same way

02:48:21.600 | that Ozempic is the diabetes version for Novo Nordisk

02:48:26.180 | and Wegovy is the obesity version.

02:48:28.660 | - But they're all GLP-1 analogs.

02:48:29.880 | - They're all GLP-1 analogs.

02:48:31.360 | - They're synthesized in a lab.

02:48:32.540 | It looks like GLP-1, smells like GLP-1,

02:48:34.460 | acts like GLP-1 when injected.

02:48:36.340 | - Terzepatide, the Lily one, actually has a dual function.

02:48:40.900 | It binds to the GIP receptor, so it might have double duty.

02:48:45.900 | And the data show that it's actually even slightly

02:48:50.280 | more effective at weight loss than the Novo Nordisk version.

02:48:53.600 | So we'll be seeing a shift in terms

02:48:55.960 | of consumer preference soon, no doubt.

02:48:59.940 | But here's the thing.

02:49:02.900 | You look at the data, one year of treatment,

02:49:07.900 | 16% weight loss.

02:49:10.320 | Now that sounds great.

02:49:11.840 | And I'm not saying it's bad.

02:49:12.840 | It's good.

02:49:13.680 | - And people are not craving food all the time.

02:49:14.680 | Is that because people are feeling full longer?

02:49:18.520 | - Right.

02:49:19.360 | - So they're eating less.

02:49:20.180 | - They're eating less.

02:49:21.200 | - This is the calorie in, calorie out model.

02:49:23.180 | - They're eating less.

02:49:24.500 | And so they are losing weight.

02:49:26.440 | I'm not arguing that.

02:49:27.480 | - And they might be craving alcohol less,

02:49:29.080 | according to some recent reports.

02:49:30.000 | - Yes, yeah.

02:49:30.960 | Well, we can go there for a minute too, in a second.

02:49:34.240 | Here's the problem.

02:49:36.940 | When you look at that 16% weight loss,

02:49:38.840 | as you just said, when you put people in a DEXA scanner,

02:49:42.440 | they have lost equal amounts of fat and muscle.

02:49:45.960 | Now, is it good to lose muscle?

02:49:49.180 | No.

02:49:50.020 | It is not good.

02:49:50.880 | Ask any little old lady who breaks her hip

02:49:52.720 | if she wishes she had a little bit more muscle.

02:49:54.760 | - Or somebody who dieted lost a lot of muscle

02:49:56.720 | 'cause they weren't offsetting the weight loss

02:49:58.260 | with resistance training or some other form of exercise.

02:50:01.060 | And the amount of food that they can eat

02:50:03.600 | in order to maintain that weight,

02:50:05.520 | to put it in scientific terms, sucks.

02:50:08.360 | - And we mentioned Peter Atiyah earlier.

02:50:12.360 | In Outlive, he's made it very clear

02:50:14.320 | that sarcopenia, lack of muscle mass,

02:50:17.600 | is one of the drivers of mortality.

02:50:20.200 | So losing muscle is not a good idea.

02:50:25.200 | But you lose equal amounts of fat and muscle.

02:50:29.260 | What else causes loss of equal amounts

02:50:31.820 | of fat and muscle?

02:50:32.940 | Starvation.

02:50:34.380 | In fact, the reason that all these GLP-1 analogs work

02:50:38.620 | is because you stop eating.

02:50:40.020 | - Like the Gila monster. - It's starvation.

02:50:41.300 | Yeah, just like the Gila monster.

02:50:42.140 | - Although the Gila monsters look pretty chubby to me.

02:50:44.300 | - Well, ask another Gila monster.

02:50:48.000 | - I did, but unfortunately whatever answer it provided

02:50:50.640 | was not interpretable. - Indeed.

02:50:52.440 | The point is that starvation is not so good.

02:50:56.280 | And if you think about why it's working,

02:51:00.040 | it's reducing the rate of gastric emptying, all right?

02:51:04.320 | Well, it turns out that that's the reason

02:51:07.160 | for its side effects, the reduction in gastric emptying.

02:51:10.520 | That's why you get nausea.

02:51:11.880 | That's why you get vomiting.

02:51:13.520 | That's why you get pancreatitis.

02:51:16.260 | And most importantly now, gastroparesis.

02:51:20.700 | Your stomach turns to stone.

02:51:23.520 | And you can't move any food through your intestine at all.

02:51:29.480 | And worse yet, when you stop the medicine,

02:51:33.680 | the gastroparesis doesn't get better.

02:51:36.080 | This is not a good idea.

02:51:38.080 | - This is like the opposite

02:51:39.000 | of the Yerba Monte induced effect,

02:51:40.520 | which has a sort of prolaxative gastric emptying,

02:51:42.740 | maybe GLP-1 agonism.

02:51:44.840 | Gosh, okay.

02:51:45.840 | So it's obvious why people

02:51:48.820 | who've struggled to lose weight like it,

02:51:51.180 | especially if their struggle to lose weight was,

02:51:53.280 | at least in their mind,

02:51:54.120 | the consequence of being hungry all the time

02:51:56.020 | and needing to eat more.

02:51:57.560 | - Or was it because of the reward and their dependence?

02:52:02.420 | Because in fact, yes, these GLP-1 analogs reduce reward.

02:52:07.420 | And that's one of the reasons why they've noticed

02:52:12.240 | that reduction in alcohol consumption as well.

02:52:17.240 | And that sounds like a good thing,

02:52:20.220 | except there are also numerous cases now

02:52:25.220 | of major depressive disorder in response to these drugs.

02:52:28.880 | - It's almost like naltrexone or something

02:52:30.660 | for the treatment of addiction,

02:52:32.060 | which sometimes can be useful,

02:52:33.360 | but attempting to remove the amplitude

02:52:37.360 | of that reward signal.

02:52:39.820 | I mean, on paper it makes sense,

02:52:41.660 | but it doesn't always play out.

02:52:43.100 | - And in practice it doesn't play out, that's right.

02:52:45.220 | And so I'm gonna refer you now to an old literature

02:52:50.220 | that was from 2006.

02:52:53.220 | There was a drug that was approved in Europe

02:52:57.540 | called Romanabant, okay, a trade name Acomplia.

02:53:02.540 | And it was approved in Europe for weight loss.

02:53:06.160 | And it was pretty good at weight loss.

02:53:07.820 | It caused about 20% weight loss.

02:53:10.480 | It also caused severe depression and 21 suicides.

02:53:15.060 | - So it's no longer available.

02:53:16.260 | - Because it was pulled from the European market,

02:53:19.700 | never approved in the United States.

02:53:22.020 | And the reason this happened

02:53:23.100 | was because this was the anti-marijuana drug.

02:53:26.260 | This was the anti-munchies drug.

02:53:28.420 | This was an endocannabinoid antagonist.

02:53:32.220 | Well, when you reduce reward,

02:53:34.940 | you also reduce your desire to live.

02:53:38.060 | And that's why this concern about reduction

02:53:41.240 | in alcohol consumption,

02:53:42.400 | we've already seen major depressive disorder

02:53:45.320 | in patients receiving Ozempic.

02:53:48.440 | So are we gonna see the same thing play out

02:53:51.020 | as we did for Romanabant?

02:53:52.840 | I'm worried about it.

02:53:53.920 | - Or Fen-Fen.

02:53:54.940 | - Well, Fen-Fen didn't have--

02:53:56.600 | - No, it was cardiac.

02:53:58.520 | - It was cardiac, right.

02:53:59.440 | We had cardiac problems due to the fenfluramine

02:54:02.820 | because of the serotonin 1B receptor agonism.

02:54:06.620 | - Right, I'm just referring to the fact

02:54:07.760 | that these quote-unquote blockbuster drugs for obesity,

02:54:11.300 | they tend to follow a contour of very promising,

02:54:14.640 | very exciting, a lot of people losing weight suicides,

02:54:18.220 | or very promising, a lot of people losing weight,

02:54:20.720 | cardiac issues, very promising, losing weight.

02:54:23.760 | And now you're saying the stomach turns to stone.

02:54:25.960 | It sounds so biblical.

02:54:27.520 | - Well, indeed.

02:54:28.760 | So that's the question.

02:54:29.760 | And then finally, we can really talk biblical.

02:54:33.460 | If everyone in America who qualified for Ozempic

02:54:37.520 | got it, that would be 2.1 trillion to the healthcare system,

02:54:42.420 | which is currently at 4.1 trillion.

02:54:44.400 | So that would be a greater than 50% increase

02:54:46.900 | in healthcare costs at 1,300 a month.

02:54:51.120 | Conversely, if we just got sugar consumption

02:54:57.480 | down to USDA guidelines by basically putting some limits

02:55:02.480 | on how much added sugar the food industry can put

02:55:06.440 | into any given product, like Froot Loops,

02:55:08.480 | we could reduce weight by 29% and save $3.0 trillion.

02:55:14.440 | So we'd get better weight loss and we'd save $5.1 trillion,

02:55:23.260 | which makes more sense to the U.S. government.

02:55:28.660 | - Well, earlier you were alluding to government,

02:55:31.600 | big food, big pharma relationships.

02:55:34.760 | I mean, there's a huge win here

02:55:36.520 | for whoever's manufacturing these GLP-1 analogs.

02:55:39.800 | - Indeed.

02:55:41.000 | - But the question is, who's paying the tab?

02:55:42.720 | - Well, we are.

02:55:43.560 | Now, the question is, why can't the government see that?

02:55:47.720 | And the answer is because the government's on the dole too.

02:55:50.680 | Because the government, through tariffs on U.S.-made foods,

02:55:55.680 | okay, grosses $56 billion a year.

02:56:02.920 | So they're a player.

02:56:05.120 | They're not just a regulator, they're an actor.

02:56:08.280 | - To play devil's advocate a little bit,

02:56:10.200 | listen, I'm gonna be the last person to step in

02:56:11.880 | and try and defend government as a unified body.

02:56:15.800 | I'm not qualified to do that, but you could see how

02:56:18.700 | if you looked at it like checkers instead of chess,

02:56:21.980 | you'd say, okay, here's a drug that's going to allow

02:56:25.160 | many millions of people to reduce their overall body weight.

02:56:29.480 | Overall body weight is a risk factor for a number of things.

02:56:33.420 | And there will be savings on the back end

02:56:35.800 | as a consequence of that weight loss.

02:56:37.500 | I mean, so that's the checkers version.

02:56:39.740 | The chess version is how you're describing it.

02:56:42.060 | And I think that, I mean, clearly people in government

02:56:47.060 | are, well, most, some perhaps are smart enough

02:56:50.980 | to play chess, not checkers, or to at least understand it,

02:56:53.720 | but there's very little incentive for the chess model.

02:56:56.460 | So what would quote unquote solve this problem

02:57:00.640 | is the same thing that happened to Fen-Fen

02:57:02.180 | or this romantic, which is if suddenly there's a major issue

02:57:07.180 | with the drug, then everyone stops taking it.

02:57:09.620 | And traditionally that's how it's gone.

02:57:10.880 | It sounds like these GLP-1 analogs

02:57:12.980 | are gonna make it through the chute though.

02:57:14.700 | - Yeah, I mean, there is a very clear downside

02:57:19.700 | to these medicines.

02:57:21.380 | On the other hand, you know, there's an upside.

02:57:24.260 | And so I'm not sad that these medicines exist.

02:57:28.960 | I'm for them, I'm not against them.

02:57:32.260 | I'm for them for the right patient.

02:57:34.360 | And right now it's not the right patient who's getting them.

02:57:37.400 | - Just like the statins.

02:57:38.520 | So what if somebody who's taking one of these analogs

02:57:41.380 | makes it a point to do resistance training?

02:57:43.800 | And here, you know, you mentioned bodybuilders early.

02:57:45.960 | I'm not suggesting they become bodybuilders,

02:57:47.880 | but we now know, and I think Peter or Atiya and others

02:57:50.360 | would agree that everybody should be doing some form

02:57:53.280 | of muscle loss offsetting resistance exercise.

02:57:56.400 | - I agree.

02:57:57.240 | - At least past, you know,

02:57:58.160 | they're reaching their adult height or something.

02:58:00.440 | You know, I know there are those that say

02:58:01.960 | weight training doesn't blunt your height,

02:58:03.560 | but anyway, let's just say that from early twenties onward,

02:58:07.760 | doing something.

02:58:08.600 | - Especially if you're on these medicines

02:58:11.040 | in order to maintain muscle mass.

02:58:13.160 | - So that's a different picture, right?

02:58:15.300 | People are drinking less alcohol.

02:58:16.840 | Again, I'm playing devil's advocate here.

02:58:19.380 | So if we look at these compounds, not in a vacuum,

02:58:22.380 | but okay, the person who's been carrying that extra 30 pounds

02:58:25.460 | is now only carrying a few extra pounds of adipose tissue.

02:58:29.280 | They've lost a lot of muscle,

02:58:31.300 | but now they feel well enough to exercise.

02:58:33.400 | The depression part worries me,

02:58:36.180 | but anyway, I'm just trying to round the contour of it.

02:58:38.960 | - What we've seen in children,

02:58:42.040 | 'cause that's who I took care of,

02:58:43.880 | was that often they needed a jumpstart, okay?

02:58:47.700 | And there were different ways to get them to jumpstart.

02:58:50.240 | - Stomach stapling.

02:58:51.280 | - Well, that's not jumpstart.

02:58:52.760 | That's way down the line. - But that was what

02:58:53.760 | a lot of people did.

02:58:54.880 | I have a friend, he was and sadly still is really big.

02:58:59.200 | And he always talked about the stomach stapling,

02:59:00.980 | like if I could just get 50 pounds down quickly,

02:59:04.960 | then I could exercise, but exercise is painful,

02:59:07.680 | this kind of thing.

02:59:08.520 | And sadly, he's continued to maintain or creep up

02:59:11.140 | in a very excessive weight.

02:59:12.600 | - And that's the point, is that this concept of jumpstart,

02:59:16.800 | actually, if you're only doing it yourself,

02:59:20.040 | doesn't really work.

02:59:21.120 | And the question is, why is his weight creeping up

02:59:24.360 | if he's had the stomach stapling?

02:59:25.760 | The answer is 'cause he's a sugar addict.

02:59:28.840 | - Yeah, he's definitely addicted

02:59:30.160 | to the super big gulp soda.

02:59:32.840 | - If you drink your calories,

02:59:35.040 | it doesn't really matter, does it?

02:59:37.280 | - No, and he's got such terrible psoriasis

02:59:39.600 | and joint pain and all this,

02:59:41.000 | that the prospect of exercising is like a,

02:59:43.440 | you might as well tell him to like flap his wings

02:59:45.800 | and go to Mars.

02:59:46.920 | - You know, fructose is a driver of immune dysfunction.

02:59:50.140 | If he got off, you can tell him from me,

02:59:53.040 | if he got off the sugar, his psoriasis would get better,

02:59:56.080 | his weight would get better, his arthritis would get better,

02:59:59.080 | and he could have then that jumpstart.

03:00:02.360 | - This is a perfect example to bridge

03:00:04.180 | to the brain component of all this,

03:00:05.880 | because I've long wondered,

03:00:07.820 | based on what I understand about neural circuitry

03:00:10.240 | and neuroplasticity, I know we share in this knowledge

03:00:13.640 | that at some point, carrying a lot of adipose tissue

03:00:17.560 | means that the brain sort of represents

03:00:19.680 | the body differently.

03:00:20.860 | I mean, we know there are these somatotopic maps of self,

03:00:25.720 | but that the neural machinery and the hypothalamus, sure,

03:00:28.760 | which is responsible for motivated states, et cetera,

03:00:31.640 | but also just the entire mapping of the self changes.

03:00:36.640 | In other words, if one is fat long enough,

03:00:39.860 | that it becomes increasingly hard to get to a healthy weight

03:00:45.760 | because of the way that the neural circuitry is impacted.

03:00:49.660 | It basically remaps to maintain that fat person,

03:00:53.600 | not necessarily even just at the level of appetite,

03:00:56.280 | but just in terms of what do big animals do?

03:00:58.860 | I had a bulldog that weighed 90 pounds, bulldog mastiff.

03:01:01.800 | He was very economical with his movement, right?

03:01:04.440 | He was extremely powerful. - Indeed.

03:01:05.800 | - He could run, at least when he was younger,

03:01:07.920 | but if he could be still, he was still,

03:01:10.640 | as opposed to certain smaller animals

03:01:13.320 | that are peripatetic, right?

03:01:14.920 | - Because he was leptin resistant.

03:01:18.080 | So leptin, as we talked about briefly,

03:01:21.600 | is the hormone that tells your brain you've had enough.

03:01:25.600 | If you are leptin sensitive, you are happy to burn.

03:01:30.060 | If you are leptin resistant,

03:01:31.360 | your brain thinks you're starving,

03:01:33.080 | and if your brain thinks you're starving,

03:01:34.480 | it's going to affect your behavior in two ways.

03:01:37.280 | It's gonna make you wanna eat,

03:01:38.680 | and it's also gonna make you wanna conserve

03:01:41.080 | because the goal is to try to increase the leptin levels

03:01:45.080 | in order to overcome that resistance,

03:01:46.860 | which, of course, you can never do

03:01:49.000 | because all you're gonna do is lay down more fat

03:01:50.680 | and make more leptin.

03:01:51.740 | - That makes so much sense

03:01:52.580 | because leptin comes from the adipose tissue.

03:01:54.240 | - Exactly.

03:01:55.080 | So that leptin resistance

03:01:58.160 | is what you have to be able to break through.

03:02:01.800 | You have to fix the leptin sensitivity.

03:02:03.800 | Well, what's the driver of the leptin resistance?

03:02:07.000 | Insulin.

03:02:08.620 | Insulin inhibits leptin signaling,

03:02:12.080 | and it does it at three separate places in the POMC neuron,

03:02:16.060 | the pro-opium melanocortin neuron in the hypothalamus.

03:02:19.480 | It does it at IRS2, insulin receptor substrate two.

03:02:24.040 | It does it at SOX3, suppressor of cytokine signaling three,

03:02:27.080 | and it does it at PIP3, phosphatidylinostole triphosphate.

03:02:32.080 | Those three separate arms of the leptin receptor

03:02:37.120 | are all basically put to sleep by high insulin.

03:02:42.040 | Insulin blocks leptin signaling.

03:02:45.040 | So the higher the insulin goes,

03:02:47.560 | the more your brain thinks you're starving,

03:02:50.160 | and the more your brain thinks you're starving,

03:02:52.320 | the hungrier you get and the less you wanna move.

03:02:55.440 | So the gluttony and sloth that we've been talking about

03:03:00.440 | all in our podcast is really biochemical.

03:03:05.080 | It is secondary to this phenomenon

03:03:08.080 | of insulin blocking leptin signaling.

03:03:11.160 | You gotta fix that first.

03:03:12.360 | Get the insulin down any way you can,

03:03:16.720 | and the best way, get rid of the refined

03:03:19.760 | carbohydrate and sugar.

03:03:20.880 | That's where you start.

03:03:23.360 | - It makes so much sense.

03:03:26.280 | - It works too, how about that?

03:03:28.680 | - That's always good.

03:03:29.640 | - It is.

03:03:30.840 | - I once heard you say, I think it was in a conversation

03:03:32.960 | with Peter Attia on his podcast,

03:03:35.300 | and this really stuck in my mind,

03:03:37.620 | that when a person consumes glucose,

03:03:42.620 | that it activates a number of different brain sites.

03:03:46.440 | You know, neurons loving glucose,

03:03:49.640 | but that when one ingests fructose,

03:03:53.000 | that it preferentially activates neurons

03:03:55.160 | in the reward pathway.

03:03:57.120 | At maybe seven times the magnitude or something like that.

03:04:02.080 | - Glucose activates the basal ganglia.

03:04:04.700 | This is work from Wollner House in Switzerland,

03:04:09.280 | and also Eric Stice at Oregon Health Sciences.

03:04:11.440 | - It's for movement and planning and execution.

03:04:12.960 | - Exactly, okay.

03:04:14.720 | Fructose basically stimulates the nucleus accumbens,

03:04:18.320 | the reward center.

03:04:19.200 | It is just like heroin, just like cocaine,

03:04:21.840 | just like nicotine.

03:04:23.800 | It activates the reward center.

03:04:25.680 | It doesn't do anything for the basal ganglia.

03:04:28.620 | So it is addictive.

03:04:31.760 | Anything that stimulates the reward center

03:04:34.280 | in the extreme is addictive.

03:04:36.560 | So we have chemical addictions, heroin, cocaine,

03:04:38.960 | nicotine, alcohol, sugar.

03:04:40.480 | We have behavioral addictions, shopping, gambling,

03:04:42.800 | internet gaming, social media, pornography.

03:04:45.720 | Doesn't matter.

03:04:46.640 | They all stimulate dopamine in the reward center,

03:04:50.720 | and in the extreme, they are all addictive.

03:04:53.440 | So the question is, if you are addicted,

03:04:56.940 | is that personal responsibility?

03:05:01.440 | - Well, it's a very,

03:05:03.700 | it's a question I think about a lot,

03:05:08.060 | because I know a lot of people

03:05:10.600 | in the addiction recovery community,

03:05:13.280 | both from the treatment end and the addict end,

03:05:16.120 | and this always comes down to this question

03:05:18.040 | when somebody is suffering from an addiction of any kind

03:05:20.400 | and they're resistant to getting treatment.

03:05:22.560 | If you look at them as being sick,

03:05:27.480 | at least in that moment,

03:05:29.400 | is a sick person in the best or worst

03:05:32.200 | or at least diminished position to guide their own treatment?

03:05:36.240 | So for instance, somebody with dementia,

03:05:37.600 | would you ask them, do you wanna go see a neurologist?

03:05:40.560 | You might ask them that,

03:05:41.940 | but are they the best person to make that decision?

03:05:44.040 | - Well, this is the problem.

03:05:45.280 | So this is where personal responsibility falls down.

03:05:49.660 | So personal responsibility,

03:05:51.740 | as we talked about four criteria have to be met,

03:05:54.400 | none of them are met.

03:05:55.360 | That's the first issue.

03:05:57.160 | Second one is a little bit, shall we say cheekier.

03:06:00.160 | Who invented personal responsibility?

03:06:04.520 | Any idea?

03:06:05.440 | - I'm definitely gonna get this one wrong.

03:06:07.280 | - Yeah, you're gonna get this one wrong.

03:06:08.840 | Are you ready?

03:06:09.680 | - Yeah, I don't know.

03:06:10.520 | - The tobacco industry.

03:06:12.560 | - The notion of personal responsibility?

03:06:14.240 | - They invented it.

03:06:15.720 | There was no personal responsibility until tobacco in 1962,

03:06:20.080 | 'cause they were getting killed on the science

03:06:22.640 | and they needed to invent another reason for you to smoke.

03:06:26.480 | In fact, there's a paper that came out, Dorfman et al,

03:06:29.860 | that looked at the New York Times and the Washington Post

03:06:33.360 | and they did an entire lit search of the entire,

03:06:38.360 | all of the output of those two newspapers for decades

03:06:46.160 | to look for the term personal responsibility.

03:06:49.000 | And the very first time it was ever mentioned was 1962.

03:06:54.000 | And it didn't pick up in speed until 1986,

03:06:58.940 | which was the same year as Cipollone v. Liggett

03:07:02.160 | at the Supreme Court,

03:07:04.000 | which basically said that the cigarette industry

03:07:09.000 | was guilty of plying people with an addictive substance.

03:07:14.280 | So this is very specifically industry-driven

03:07:21.120 | and we have the data to prove it.

03:07:24.160 | - Amazing.

03:07:25.320 | Well, I wonder, along the lines of personal responsibility,

03:07:31.740 | given that many listeners to this conversation

03:07:34.560 | are going to be thinking about their own food intake

03:07:37.480 | and food choices and that of their children

03:07:39.800 | and other relatives,

03:07:41.800 | that we could play a little, not a game,

03:07:44.680 | but a little rapid-ish fire Q&A.

03:07:48.440 | Never done this before in this podcast,

03:07:50.040 | but I think it's particularly appropriate

03:07:51.720 | for a discussion like this that weeks out into so many areas

03:07:55.000 | and I absolutely will invite you back

03:07:56.600 | and perhaps along with Alyssa Eppold

03:07:59.560 | to talk about some of the exciting work you guys are doing,

03:08:01.300 | 'cause there's so much we could cover,

03:08:02.520 | but people are going to wonder in a very practical sense

03:08:05.720 | whether or not they should

03:08:08.000 | or should not be consuming certain things.

03:08:09.520 | And I know you're not the food police.

03:08:11.200 | - I'm not the food police.

03:08:12.040 | - And I'm not a cop and I do believe people

03:08:14.360 | should be in choice about these matters.

03:08:18.620 | But I also believe that,

03:08:20.580 | because you're a guest on the podcast

03:08:21.840 | and you're highly informed

03:08:23.000 | and I've done clinical work and research

03:08:25.480 | for so many years in this area,

03:08:27.920 | and you have such a clear stance on the role of big food

03:08:30.680 | and we really, really appreciate your honesty

03:08:34.220 | and directness,

03:08:35.060 | but now you'd be willing to provide a comment

03:08:37.160 | about a couple of different terms that I'll throw out.

03:08:39.420 | And if you choose to say really nothing to say about that,

03:08:42.220 | fine, that would be a quick pass.

03:08:43.520 | So here we go.

03:08:45.520 | And we covered a little bit of this earlier,

03:08:47.320 | but fruit in whole form.

03:08:49.360 | So has fructose, but has fiber.

03:08:54.040 | So thumbs up, thumb sideways

03:08:56.160 | or thumbs down for fruit consumption.

03:08:58.080 | - Fruit is fine.

03:08:59.520 | - Fruit juice is not.

03:09:01.320 | - Great, thank you.

03:09:02.420 | White rice versus brown rice.

03:09:05.560 | And among the white rice is the sticky rice

03:09:08.120 | and the rice is with added sugars,

03:09:10.540 | which you find in a lot of restaurants.

03:09:14.140 | - Brown rice because of the fiber.

03:09:16.760 | White rice, polished, you know, number one,

03:09:20.120 | all the vitamin B1 gone.

03:09:22.160 | And of course, a much larger glucose excursion.

03:09:25.740 | That glycemic index thing, which of course I hate,

03:09:28.760 | it's glycemic load that matters.

03:09:31.720 | And that is a very high glycemic load.

03:09:34.480 | So brown rice.

03:09:35.720 | - So brown rice is better than white rice.

03:09:38.220 | - Yes.

03:09:39.060 | - Okay, in a meaningful way.

03:09:40.020 | - In a meaningful way.

03:09:40.960 | - Okay.

03:09:42.280 | Earlier you mentioned tomato sauce.

03:09:44.180 | I love tomato sauce that's made from just tomatoes.

03:09:48.200 | Can tomato, so are most tomato sauces filled with sugar?

03:09:51.940 | - Perfect.

03:09:53.200 | Our little recommendation engine looked at this question

03:09:57.440 | and it turns out that only 10%

03:10:00.240 | of the available tomato sauces out on the market

03:10:03.920 | don't have added sugar.

03:10:06.180 | So you have to know which ones.

03:10:07.440 | Well, you can look yourself or you can look up perfect

03:10:09.640 | and it will tell you which ones you can buy.

03:10:12.460 | - If people chose to consume bread, which many people do,

03:10:17.060 | is there a way to just across the board

03:10:20.440 | without just baking your own

03:10:21.820 | or looking at the ingredients list to make a better choice?

03:10:24.560 | Is it like sourdoughs tend to have less sugar

03:10:26.680 | than blank?

03:10:29.320 | - Well, sourdough has been fermented

03:10:31.200 | so it will have actually consumed some of the sugar

03:10:33.840 | so it would be a better choice.

03:10:35.400 | But really the best choice is the highest fiber breads.

03:10:39.200 | Now, if you look at a wheat berry,

03:10:42.720 | it is 25% of fiber.

03:10:46.980 | The husk is 25% of the weight of that wheat berry.

03:10:50.880 | That means that the carbohydrate to fiber ratio

03:10:54.280 | of a wheat berry is three to one.

03:10:56.440 | So a good bread should have a carbohydrate to fiber ratio

03:11:02.960 | of somewhere between three to one to five to one tops.

03:11:07.060 | Anything above that means that they've stripped

03:11:09.540 | the fiber away.

03:11:11.080 | So that's something you could do.

03:11:12.720 | But the easier way is to actually look it up on perfect.

03:11:15.660 | - You mentioned meat and meat sourcing,

03:11:19.280 | egg and chicken sourcing earlier.

03:11:21.620 | Maybe we just revisit that.

03:11:23.700 | Meat, fish and eggs, thumbs up, thumb sideways,

03:11:26.140 | thumbs down, or it depends?

03:11:27.580 | - It depends.

03:11:28.420 | It depends on where the meat came from.

03:11:31.140 | It depends on whether it was pasture raised.

03:11:33.380 | Depends on whether it's organic or not.

03:11:36.180 | If the animal was injected with antibiotics,

03:11:39.600 | stay away from it because those antibiotics are in the meat.

03:11:42.480 | They're gonna basically sterilize your gut

03:11:44.740 | and then the bad bacteria are gonna take over.

03:11:47.660 | We haven't really talked much about the microbiome today,

03:11:50.580 | but that's a whole podcast all by itself.

03:11:53.500 | - We can touch on it a little bit more.

03:11:56.460 | Low sugar fermented foods, thumbs up,

03:11:58.420 | thumb sideways, thumbs down.

03:11:59.260 | - Fermented foods, short chain fatty acids, all good.

03:12:03.500 | - What are your favorite sources of fermented foods?

03:12:05.700 | - I like kimchi.

03:12:06.860 | - Yeah, I like kimchi too.

03:12:08.860 | I like some of the live sauerkrauts.

03:12:11.140 | - Yeah, that's also good, but with the right accoutrement.

03:12:15.920 | The one thing I would be careful about is yogurt, okay?

03:12:21.940 | So there are yogurts with live cultures

03:12:24.940 | and there are a whole lot of yogurts with dead cultures.

03:12:27.620 | And if it's a yogurt with dead cultures,

03:12:29.760 | it's kind of irrelevant and the chances are

03:12:32.180 | they've actually covered up the sourness with sugar.

03:12:36.300 | So large commercially available yogurt,

03:12:40.640 | be very, very careful, okay?

03:12:42.820 | If it's an artisan yogurt made by people you know or trust,

03:12:49.340 | that's a very different story, yogurts with live cultures.

03:12:54.340 | - Intermittent fasting, do you practice it

03:12:56.900 | and what do you think about it?

03:12:58.340 | - I don't practice it, but I am for it,

03:13:01.600 | for the right patient.

03:13:02.940 | Turns out who's the right patient?

03:13:04.620 | The patient with liver fat because the reason it works

03:13:08.140 | is 'cause it gives the liver a chance

03:13:09.660 | to basically burn off the fat that it's stored.

03:13:13.120 | - Zero calorie soda, got it, definitely no.

03:13:17.780 | And I don't even have to ask about sugary soda

03:13:20.900 | because that's basically just poison in a can.

03:13:25.300 | - Food combinations, I have a feeling

03:13:27.740 | I know what your answer is,

03:13:28.580 | but the glycemic index, which we know your feelings on now,

03:13:31.760 | asserts that if you combine some fat with a sugary,

03:13:35.800 | like eating ice cream,

03:13:36.980 | you have a more blunted insulin response

03:13:39.020 | than if you were to eat pure sugar of equivalent calories.

03:13:41.700 | But what are your thoughts on food combinations

03:13:45.680 | as a way to blunt the insulin response?

03:13:48.000 | - Food combinations are great

03:13:49.100 | if there's some fiber associated with it.

03:13:51.200 | - Comes back to fiber again.

03:13:53.980 | - And by the way, and by the way,

03:13:55.580 | full disclosure, I am the chief medical officer

03:14:00.180 | of a fiber company.

03:14:01.340 | - What is it?

03:14:02.180 | - It is called biolumen and it is a proprietary fiber.

03:14:06.100 | It is a microcellulose sponge, seven microns in diameter,

03:14:11.100 | so the size of a red blood cell.

03:14:14.800 | You swallow it, it goes to your stomach,

03:14:18.020 | it expands 70-fold over its original size,

03:14:22.020 | and so it'll give you a feeling of fullness

03:14:23.980 | 'cause it's taking up space in the stomach,

03:14:26.200 | but more importantly, when it expands,

03:14:29.540 | the nooks and the crannies in the sponge become available,

03:14:33.960 | and embedded in those nooks and crannies

03:14:35.820 | are a set of proprietary hydrogels, soluble fiber,

03:14:39.060 | which sequester glucose, fructose, sucrose, simple starches,

03:14:43.060 | and render them unavailable for early absorption

03:14:45.820 | in the duodenum, thus reducing the glucose response,

03:14:48.840 | reducing the insulin response, protecting the liver,

03:14:52.940 | and moving it through the intestine

03:14:55.240 | so that microbiome can chew it up for its own purposes,

03:14:58.540 | feeding the gut.

03:14:59.980 | We can reduce glucose absorption by 36%,

03:15:03.580 | fructose absorption by 38%, sucrose absorption by 40%,

03:15:08.100 | simple starch absorption by 9%,

03:15:10.660 | and increase short-chain fatty acid production by 60%

03:15:15.660 | without an increase in gas.

03:15:19.260 | - When do people take this?

03:15:22.000 | - With meals.

03:15:23.420 | - Okay.

03:15:24.260 | - So it comes as a sachet, one teaspoon,

03:15:28.180 | sprinkle it on your food or take it in a drink,

03:15:31.980 | just mix it in and slug it down,

03:15:34.540 | and then eat breakfast, lunch, or dinner,

03:15:37.240 | and it will basically act like you ate real food.

03:15:42.240 | It will turn processed food into real food in the intestine.

03:15:47.880 | And we have clinical trial data that demonstrates that.

03:15:51.000 | - Is it available as a commercial product?

03:15:52.340 | - It is available.

03:15:53.180 | It is called Munch Munch.

03:15:55.280 | Now, I hate that name.

03:15:56.360 | I didn't make it up.

03:15:57.520 | - Well, I'm gonna--

03:15:58.360 | - The marketers did that.

03:16:00.680 | - Your marketing team sucks,

03:16:01.860 | but the product sounds amazing.

03:16:03.240 | - Yes, biolumin.tech.

03:16:05.560 | - Great, thank you for that.

03:16:07.420 | Sorry, Munch Munch marketing team,

03:16:09.060 | but you got a Munch Munch to a new product name.

03:16:12.060 | But it sounds like a very interesting product,

03:16:15.740 | and it actually answered my next question,

03:16:18.140 | which was about fiber supplements.

03:16:21.240 | - Fiber is good, but there are two kinds of fiber.

03:16:24.740 | There's soluble and there's insoluble,

03:16:27.260 | and they are not the same.

03:16:28.620 | So soluble is what goes into fiber one bars,

03:16:32.180 | you know, that's psyllium, inulin, pectin,

03:16:35.900 | like what holds jelly together.

03:16:40.940 | That's good.

03:16:43.060 | I'm not saying it's bad,

03:16:44.640 | but you need the insoluble fiber, the cellulose,

03:16:47.740 | the stringy stuff in celery, the cardboard, if you will.

03:16:51.380 | Together, they form this gel that we talked about earlier.

03:16:55.380 | If you only consume the soluble fiber,

03:16:57.400 | which is what the food industry will add to food,

03:17:00.580 | 'cause the insoluble fiber is not miscible.

03:17:03.260 | If you only add the soluble fiber back,

03:17:05.740 | you're not getting the benefits

03:17:07.860 | of the entire fiber complement.

03:17:10.020 | - Earlier, when talking about the Nova system

03:17:13.000 | and how most all of our foods are nine,

03:17:17.220 | let's say, I know it was seven to 10%,

03:17:19.000 | let's say 95%, let's say are on the side of better.

03:17:22.620 | 95% of our foods should come from Nova system

03:17:24.940 | class one or class two foods.

03:17:26.340 | - Or three.

03:17:27.180 | - Or three, okay, staying away

03:17:28.560 | from those Nova class four foods.

03:17:30.620 | Could you give us some examples of Nova class one

03:17:32.940 | and class two foods, just broadly speaking?

03:17:37.020 | - Okay, Nova class one is any food without a label, period.

03:17:41.760 | If you see a label on a food, it's a warning label.

03:17:47.000 | - Well, there's ground beef has a label.

03:17:49.740 | Okay, so that's--

03:17:50.580 | - Well, does it?

03:17:51.420 | - So you're talking about apple.

03:17:53.120 | Well, when I buy it, it has a label.

03:17:54.660 | I'm asking this because people are gonna wonder.

03:17:56.180 | - Well, it doesn't have a nutrition facts label.

03:17:58.700 | Is there a nutrition facts label on a thing of ground beef?

03:18:00.980 | - I buy that ground beef where I consume venison

03:18:05.980 | where if you flip it over, it says how many calories,

03:18:08.020 | how many protein.

03:18:08.860 | So there's a label, but it's just B for venison.

03:18:12.900 | - Okay, and that's class one.

03:18:14.920 | - Okay, egg?

03:18:16.040 | - Egg is class one.

03:18:17.460 | - So, and then of course, fruit, apples, orange.

03:18:19.440 | Okay, so it doesn't matter if it has a name tag

03:18:22.400 | as long as it doesn't have an ingredients list.

03:18:25.780 | - Got it.

03:18:27.420 | - Real food does not need a label.

03:18:29.660 | It's only if they did something to it

03:18:32.340 | that it needs a label.

03:18:33.620 | So you have to look at every label as a warning label.

03:18:36.220 | Now, the problem with the label

03:18:37.520 | is it only tells you what's in the food.

03:18:39.240 | What you really need to know

03:18:40.300 | is what's been done to the food

03:18:42.420 | because it's the ultra processed food that's the problem.

03:18:45.180 | They don't wanna tell you that.

03:18:47.060 | That's secret.

03:18:49.020 | Okay, secret from a proprietary standpoint,

03:18:51.220 | but also secret because if you knew what they did to it,

03:18:53.880 | you wouldn't eat it, you would never buy it.

03:18:56.340 | And they don't want you to know.

03:18:57.940 | So they only tell you what's in the food.

03:19:00.580 | That's not what's important.

03:19:02.180 | It's what's been done to the food that's important.

03:19:04.380 | And that's why this NOBA class four is so important

03:19:07.080 | and that's why perfect is so important

03:19:09.480 | because it'll do the work for you.

03:19:11.700 | - Great, we'll definitely provide links to all of these.

03:19:14.760 | So if you could pick one thing to recommend to people

03:19:19.760 | that want to improve their health.

03:19:23.640 | - Get rid of the sugar, period.

03:19:25.740 | - Very clear.

03:19:26.580 | - That's number one.

03:19:27.520 | Number two, go for a walk.

03:19:30.780 | - The exercise piece.

03:19:32.620 | - Go for a walk.

03:19:33.820 | - And if you could recommend one thing

03:19:36.620 | that the general public can do to try and assist

03:19:40.820 | in this advocacy for not redefining,

03:19:46.260 | but actually clearly defining what is food and what isn't

03:19:49.040 | and making people aware at the level of policy and change

03:19:53.380 | and school lunches.

03:19:54.240 | I mean, if there were one thing, what can we do?

03:19:56.240 | I mean, you've clearly activated my neurons surrounding

03:19:59.280 | like the set of problems that exist

03:20:01.420 | and the paths to correct them,

03:20:03.160 | but should we be writing to our Congress people?

03:20:06.060 | Should we be getting angry at hospitals

03:20:09.220 | because they've got all these fast food machines

03:20:11.160 | and that the cafeteria food is like illness promoting?

03:20:15.060 | - At UCSF, we've gotten rid of all sugar beverages.

03:20:17.760 | We have the healthy beverage initiative.

03:20:19.800 | So you can-- - No Coke machines at UCSF?

03:20:21.400 | - No Coke machines at UCSF.

03:20:22.940 | - Oh, Stanford, check that out,

03:20:24.380 | 'cause people always send me pictures of the Coke machines

03:20:27.320 | in the school of medicine.

03:20:28.180 | I'm like, listen, I didn't put them there, but I--

03:20:31.980 | - We have to model for the public.

03:20:34.680 | I mean, where was the first place

03:20:37.020 | that smoking was banned?

03:20:38.220 | Hospitals, okay?

03:20:40.320 | Because we knew.

03:20:41.600 | So if you get rid of the soda,

03:20:46.600 | if you get rid of the sugared soda at the hospital,

03:20:49.300 | you're telling people something.

03:20:51.540 | So yeah, I think that every hospital

03:20:53.840 | and really every public venue in America

03:20:57.300 | needs to clear out the junk.

03:21:00.280 | - So post photos of junk that are supposed to be

03:21:02.780 | in health promoting institutions,

03:21:05.180 | and I guess we're trying to cancel junk food.

03:21:07.760 | - Shame, shame. - We're trying

03:21:08.720 | to cancel junk food.

03:21:10.260 | I'm pretty opposed to cancel culture, but here we go.

03:21:12.660 | We're gonna cancel.

03:21:14.500 | Marvelous, it's actionable, it's straightforward,

03:21:16.520 | it's low cost, low time investment.

03:21:18.360 | Zero cost, very low time investment.

03:21:20.740 | So thank you for that.

03:21:21.700 | - And look up Eat Real,

03:21:23.700 | because we're doing it for your kids.

03:21:26.500 | So you need to help support it.

03:21:29.500 | Any school district in America can do it.

03:21:33.140 | So what do we do?

03:21:34.420 | We have a business model whereby

03:21:37.220 | the food services director either purchases or rents

03:21:42.220 | a dilapidated factory in the center of the district,

03:21:45.180 | repurposes it into a food preparation facility.

03:21:48.360 | They can make 27 to 30,000 meals a day, okay,

03:21:52.220 | with a skeleton crew, and you control what's in it.

03:21:57.220 | And because you're buying in volume,

03:22:01.160 | it actually reduces the cost, so it's cheaper

03:22:04.560 | than buying it from Cisco or Aramark or Sodexo or wherever.

03:22:08.400 | And then you farm it out via truck or bus

03:22:11.800 | to all the different schools.

03:22:13.000 | So every kid gets a hot meal made from scratch,

03:22:18.360 | each day, and we can solve this problem.

03:22:22.720 | - Can't help but ask this one last question.

03:22:28.060 | For people that want to cut out sugar,

03:22:29.820 | which you clearly stated is the most important thing to do

03:22:32.300 | for one's health, how do we know

03:22:37.120 | how much sugar is in something?

03:22:39.020 | So should people be looking at labels

03:22:40.820 | and just looking for how much sugar, how much carbohydrate,

03:22:43.500 | or could we even go so far as to say,

03:22:45.880 | if it says high fructose corn syrup,

03:22:49.140 | then it's on the no-fly list.

03:22:51.500 | Don't eat it.

03:22:52.780 | - So the problem is that there are 262 names for sugar,

03:22:57.340 | and the food industry uses all of them.

03:23:00.540 | And the reason they use all of them

03:23:01.780 | is because they can include a different sugar

03:23:04.820 | as number five, number six, number seven,

03:23:06.500 | number eight, number nine on the list,

03:23:08.180 | and when you add it up, it becomes number one.

03:23:11.220 | They hide it in plain sight, and they do it on purpose.

03:23:15.740 | Now, do I expect everybody to memorize all 262 names?

03:23:20.740 | No, of course not.

03:23:22.100 | Can you figure it out yourself?

03:23:25.520 | Well, the answer is no, unless they have the line

03:23:30.040 | where it says added sugars.

03:23:32.520 | If it says added sugars, it is either sucrose

03:23:35.800 | or high fructose corn syrup.

03:23:36.880 | No one's adding lactose, okay?

03:23:39.380 | That's not-- - Or glucose.

03:23:41.140 | - They're not even adding glucose,

03:23:42.480 | because glucose isn't that sweet.

03:23:44.560 | Glucose is not that interesting.

03:23:46.220 | You don't see people going around

03:23:47.380 | chugging carose syrup, do you?

03:23:49.300 | Okay, that's glucose.

03:23:50.480 | Who cares?

03:23:51.460 | Yeah, it might be good in the molasses cookie,

03:23:52.960 | but that's it, all right?

03:23:54.800 | So it's fructose.

03:23:57.180 | So you need to know what's been added.

03:23:59.940 | So if it says added sugars, that's a good place to start.

03:24:03.960 | No greater than one teaspoon per serving.

03:24:08.120 | No greater than four grams per serving of added sugars.

03:24:13.160 | Anything greater than that, leave it at the store.

03:24:16.120 | - And aim for those Nova type 1, type 2.

03:24:19.680 | - Aim for Nova types 1, 2, and 3.

03:24:21.840 | And if you don't know whether it's Nova type 1, 2, or 3,

03:24:25.040 | you can use perfect, and if you don't look at that,

03:24:27.880 | then go look at the Nutrition Facts label,

03:24:31.320 | and anything that has more than four ingredients

03:24:34.880 | is Nova Class 4.

03:24:36.640 | - Robert Lustig, thank you so much.

03:24:39.160 | You've provided such an incredible education

03:24:42.120 | in nutritional biochemistry,

03:24:43.880 | the processing of fat, protein, carbohydrate, sugar,

03:24:47.620 | fructose in particular,

03:24:49.200 | the clear detriments of consuming fructose

03:24:51.920 | on so many different organ systems.

03:24:53.800 | I love, love, love that you separated out food science,

03:24:58.220 | nutrition, and metabolic health.

03:25:01.480 | That's a gazillion dollar delineation

03:25:07.080 | for people to understand and to shape their understanding

03:25:10.000 | of all the information that's out there

03:25:12.560 | and bins into these different categories.

03:25:14.840 | You've given us so many actionable tools,

03:25:16.960 | new conceptual frameworks.

03:25:19.960 | You've given us a real tour de force today

03:25:22.180 | in just oh so clear language.

03:25:25.600 | So I want to thank you.

03:25:27.560 | I've learned a ton, and I know everyone else has as well.

03:25:32.560 | And if people have questions,

03:25:33.720 | they can of course put them in the comment section

03:25:36.320 | on YouTube, that's the best place.

03:25:37.660 | We'll provide links to all the companies

03:25:40.380 | and websites that you referenced

03:25:42.820 | and some of your other work.

03:25:44.360 | And listen, I'm so grateful that you exist

03:25:49.360 | and that you've done the work that you've done

03:25:51.020 | and your passion and your advocacy for health

03:25:54.900 | is just oh so clear.

03:25:57.000 | So thank you so much.

03:25:58.300 | - So I want to thank you.

03:26:00.620 | And the reason I want to thank you is first of all,

03:26:02.960 | inviting me, that's nice, that's good.

03:26:04.680 | But the reason is because people need to understand science.

03:26:09.440 | I am completely in agreement with you.

03:26:13.660 | The public needs to understand science.

03:26:16.160 | They listen to you because you number one,

03:26:19.200 | provide the science and number two,

03:26:21.400 | you don't talk down to them.

03:26:23.540 | You treat them as equals.

03:26:25.480 | And that is truly remarkable.

03:26:28.200 | And so I want to thank you for your service.

03:26:31.600 | - Well you're most welcome.

03:26:33.280 | It's a labor of love and I think it was the great

03:26:36.320 | Max Delbrück that said when teaching assume zero knowledge

03:26:40.640 | and infinite intelligence.

03:26:42.020 | And I do believe that humans are infinitely intelligent,

03:26:44.460 | although sometimes as a whole we mask it.

03:26:46.840 | People deserve the knowledge.

03:26:49.320 | So thank you so much for sharing that knowledge today

03:26:51.580 | and let's absolutely have you back.

03:26:53.340 | - My pleasure, thank you.

03:26:54.940 | - Thank you for joining me for today's discussion

03:26:56.680 | with Dr. Robert Lustig about nutrition

03:26:58.720 | and how sugar impacts the health of our brain and body.

03:27:02.260 | To learn more about Dr. Lustig's work

03:27:04.200 | and to find links to the many books that he's written

03:27:06.560 | on this and other topics,

03:27:08.200 | please see the show note captions.

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03:27:40.520 | Not so much on today's episode,

03:27:41.940 | but on many previous episodes of the Huberman Lab podcast,

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03:28:34.100 | as well as protocols in the form of short PDFs

03:28:36.660 | of maybe just one to three pages,

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03:29:08.000 | Thank you once again for joining me

03:29:09.340 | for today's discussion with Dr. Robert Lustig.

03:29:12.020 | And last, but certainly not least,

03:29:14.180 | thank you for your interest in science.

03:29:16.020 | [upbeat music]

03:29:18.600 | (upbeat music)

Dr. Robert Lustig: How Sugar & Processed Foods Impact Your Health

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