How to Improve Serotonin Levels for Depression

00:00:00.000 | - How does serotonin have adequate levels of serotonin?

00:00:02.440 | - Having adequate levels of serotonin

00:00:04.480 | is absolutely critical for people depressed,

00:00:07.160 | as well as people who are not depressed,

00:00:08.880 | to feel a sense of wellbeing,

00:00:10.440 | just overall sense of wellbeing,

00:00:12.120 | being okay with who they are and where life is at,

00:00:15.520 | being able to lean into effort and all these things.

00:00:17.400 | It's absolutely critical that we have adequate levels

00:00:19.720 | of serotonin in the brain.

00:00:21.700 | Now, you may have heard, and it is absolutely true,

00:00:24.340 | that 90% of the serotonin manufactured in your body

00:00:28.080 | is in the gut.

00:00:29.560 | Now, what you don't often hear

00:00:31.500 | is that serotonin stays in the gut, right?

00:00:34.580 | We hear these days, oh, you know,

00:00:36.160 | most of your serotonin is manufactured in your gut,

00:00:39.060 | which has given millions of people the false impression

00:00:42.200 | that if you get your gut serotonin right,

00:00:44.820 | somehow it's traveling up to your brain

00:00:47.580 | and performing all the important roles

00:00:49.220 | that serotonin plays in your brain.

00:00:50.860 | That's not how it works at all.

00:00:53.080 | Fortunately, however, there are ways

00:00:55.220 | that you can modify the levels of serotonin in your gut,

00:00:58.460 | and indeed the levels of serotonin in your gut powerfully impact

00:01:02.420 | the levels of serotonin in your brain.

00:01:04.320 | And this occurs, you guessed it, by way of the vagus.

00:01:07.760 | It's a super cool mechanism,

00:01:09.220 | and it's one that you can exert some positive control over,

00:01:12.460 | in order to, for instance, increase your baseline levels

00:01:15.800 | of mood in order to increase levels of serotonin,

00:01:19.100 | if that's something that you seek.

00:01:20.760 | Here's the pathway and the mechanism,

00:01:22.240 | and I'm going to provide this in kind of top contour form.

00:01:25.300 | In the future, I'll do an entire episode about serotonin,

00:01:28.060 | but here's the idea.

00:01:29.000 | In your gut, you have cells, including neurons,

00:01:33.700 | but you also have a lot of other cells,

00:01:35.200 | mostly other cells, frankly.

00:01:37.200 | And there's a particular category of cells

00:01:39.540 | called the enterochromafin cells.

00:01:41.900 | You don't need to know that name,

00:01:42.860 | but if you want, they're the enterochromafin cells,

00:01:44.780 | and they manufacture serotonin.

00:01:47.500 | They do that through a beautiful pathway

00:01:49.440 | involving an enzymatic reaction

00:01:51.380 | that converts tryptophan from the food you eat,

00:01:53.580 | tryptophan's an amino acid,

00:01:55.080 | gets converted eventually into serotonin.

00:01:57.240 | There are a bunch of steps in there in the biochemistry,

00:01:59.300 | gets converted into serotonin.

00:02:00.980 | That serotonin binds to the ends of neurons,

00:02:04.900 | the axons of neurons in the vagus nerve

00:02:06.980 | that innervate your gut, not just your stomach,

00:02:09.800 | but your large intestine and your small intestine.

00:02:12.980 | Remember, those sensory afferents,

00:02:14.860 | those sensory axons that extend into the body

00:02:18.760 | have receptors on them, right?

00:02:21.540 | The serotonin in the gut,

00:02:23.380 | assuming you're getting enough tryptophan,

00:02:25.780 | and assuming the milieu of your gut is correct,

00:02:27.900 | we'll talk about what that means

00:02:28.780 | and how you can exert control over it,

00:02:30.180 | get the milieu right,

00:02:31.840 | that serotonin binds to the ends of those axons in the gut

00:02:35.960 | and stimulates a particular category of them

00:02:39.880 | that then relays the signal up and through nodos ganglion,

00:02:44.040 | you now are familiar with these names,

00:02:45.940 | up into the brain to the nucleus tractus solitaris,

00:02:50.660 | okay, that NTS again,

00:02:52.960 | and then the nucleus tractus solitaris,

00:02:55.520 | doesn't just communicate with locus coeruleus

00:02:57.400 | and with nucleus basalis,

00:02:58.400 | it also sends a powerful signal

00:03:00.520 | to what's called the dorsal raphe nucleus.

00:03:02.660 | The dorsal raphe nucleus in your brain

00:03:05.460 | is responsible for the release

00:03:07.280 | of the majority of the serotonin in your brain.

00:03:10.320 | So when you hear that most of the serotonin in your body

00:03:13.120 | is made in your gut,

00:03:15.000 | that's true and it stays in your gut,

00:03:17.600 | but the levels of serotonin are communicated

00:03:20.020 | to the brain by the vagus

00:03:23.000 | and then stimulates the release of serotonin

00:03:25.200 | from the dorsal raphe nucleus.

00:03:27.380 | So the question therefore becomes,

00:03:29.760 | if we want to increase levels of serotonin in the brain

00:03:32.920 | or simply to maintain healthy levels of serotonin in the brain

00:03:36.080 | for somebody who's not depressed

00:03:37.220 | or maybe somebody who's having low mood,

00:03:38.800 | just to keep elevated levels of mood

00:03:40.620 | and proper levels of serotonin overall,

00:03:42.780 | because it's involved in lots of things, not just mood,

00:03:46.380 | we need to make sure that we're getting adequate production

00:03:48.800 | of serotonin in the gut.

00:03:50.680 | And again, adequate production of serotonin in the gut

00:03:53.400 | has a bunch of other positive effects

00:03:54.900 | on the immune system, on gut motility.

00:03:56.820 | In fact, having adequate levels of serotonin in the gut

00:03:59.640 | is powerfully associated with having a healthy gut

00:04:01.900 | and not having irritable gut.

00:04:03.820 | Irritable bowel syndrome is something that vexes many people.

00:04:07.520 | You know, it might sound kind of funny

00:04:08.720 | to those of you that don't have,

00:04:09.560 | oh, you have an irritable bowel.

00:04:11.120 | People with IBS, irritable bowel syndrome,

00:04:13.500 | oftentimes suffer tremendously.

00:04:16.040 | They can't go out to dinner.

00:04:17.020 | They can't eat foods that other people offer them.

00:04:19.600 | They'll eat a bunch of foods for a while and feel fine.

00:04:21.880 | Then they feel terrible.

00:04:23.160 | It's not just about having diarrhea.

00:04:24.880 | Often they have a bunch of other gut issues

00:04:26.740 | and it's correlated with a bunch

00:04:27.740 | of other major problems over time.

00:04:31.400 | We're going to do an entire episode about gut health

00:04:33.280 | as it relates to IBS.

00:04:34.900 | There are things that you can do to improve IBS.

00:04:36.840 | One of them is to keep your,

00:04:38.640 | or get your gut levels of serotonin right.

00:04:42.280 | How do you do that?

00:04:43.540 | Well, one way to do that is to make sure

00:04:45.700 | that the microbiota of your gut are healthy

00:04:48.380 | and that they are diverse.

00:04:49.860 | The best way to do that,

00:04:51.660 | not using any kind of supplementation,

00:04:53.820 | is to make sure that you're ingesting one to four servings

00:04:56.880 | of low sugar fermented foods per day.

00:04:58.600 | I've talked about this before on the podcast.

00:05:00.220 | This is based on beautiful data

00:05:01.740 | from my colleague, Justin Sonnenberg,

00:05:03.900 | and Christopher Gardner at Stanford,

00:05:06.120 | showed that the ingestion of one to four servings

00:05:08.320 | of low sugar fermented foods per day.

00:05:10.420 | So these would be things like kimchi, sauerkraut,

00:05:13.540 | again, low sugar.

00:05:14.420 | Look at the labels.

00:05:15.180 | This is the stuff that would need to be refrigerated.

00:05:17.700 | We're not talking about pickles kept on the non-refrigerated

00:05:20.440 | shelf and the non-refrigerated section of the grocery store,

00:05:23.020 | but rather the brine and the pickles

00:05:25.100 | that don't have a ton of sugar.

00:05:26.920 | So the sour pickles, that is,

00:05:28.640 | that are kept in the refrigerator, things like kimchi,

00:05:31.580 | things like kombucha.

00:05:33.520 | Keep in mind, some kombucha has alcohol.

00:05:35.900 | So keep that in mind if you're giving this to kids

00:05:38.180 | who shouldn't be ingesting alcohol.

00:05:40.020 | Any adults probably shouldn't be ingesting alcohol.

00:05:42.300 | Kombucha has very little alcohol,

00:05:43.600 | but if you're an alcoholic

00:05:44.480 | and you're completely avoiding alcohol,

00:05:45.800 | you should know that.

00:05:46.840 | Kombucha contains some alcohol.

00:05:48.480 | Things like kefir, quality yogurts, low sugar yogurts.

00:05:53.860 | You can look up online,

00:05:55.000 | what are different low sugar fermented foods?

00:05:56.720 | These things are going to improve the gut microbiota

00:05:59.600 | that in turn promote the production of serotonin,

00:06:03.380 | if and only if, this is important,

00:06:05.560 | if and only if there's also sufficient levels of tryptophan

00:06:08.900 | in your dietary intake.

00:06:10.420 | So you're going to want to take a look at what you're eating

00:06:12.280 | and just through a simple online search,

00:06:14.220 | you can figure out whether or not

00:06:15.840 | you're getting sufficient levels of tryptophan.

00:06:18.300 | Many people are familiar with the idea,

00:06:20.280 | because it's true,

00:06:21.240 | that turkey contains high levels of tryptophan.

00:06:23.760 | This is thought to be responsible

00:06:25.740 | for the post Thanksgiving dinner effect,

00:06:27.480 | although that's probably due to just eating a lot of food.

00:06:30.380 | And when the gut is distended,

00:06:32.340 | the distension of the gut is communicated

00:06:34.140 | by mechanosensors up the vagus nerve sensory neurons

00:06:37.780 | and set in motion the so-called rest and digest,

00:06:41.340 | or I guess it would be like collapse and pass out.

00:06:44.300 | And in the case of Thanksgiving,

00:06:45.860 | collapse and pass out effect

00:06:48.820 | of having a lot of food in your gut,

00:06:50.400 | doesn't matter what the food is,

00:06:51.420 | but you're going to want to make sure

00:06:52.460 | that you're ingesting foods

00:06:53.520 | with sufficient levels of tryptophan.

00:06:55.220 | So dairy products will do that.

00:06:57.260 | White turkey meat will do that.

00:06:58.520 | There are other foods that have tryptophan in them.

00:07:00.560 | I'm not going to bother to list those off now.

00:07:02.060 | You can simply look those up.

00:07:03.020 | So make sure you're getting enough tryptophan in your diet.

00:07:05.340 | Make sure that you're getting

00:07:06.180 | enough low sugar fermented foods,

00:07:07.940 | or if you're not doing that,

00:07:09.280 | and perhaps even if you are,

00:07:10.560 | you might think about supplementing your diet

00:07:12.640 | with probiotic on occasion, right?

00:07:14.860 | I'm not talking about constantly taking

00:07:16.400 | high doses of probiotics.

00:07:18.040 | I actually don't recommend that,

00:07:19.740 | but for many people who are suffering low mood,

00:07:22.260 | supplementing with a quality probiotic

00:07:24.080 | can actually improve mood.

00:07:25.640 | And the purported mechanism by which that happens

00:07:28.080 | is the increase in serotonin that is allowed

00:07:30.880 | by improving the gut microbiota

00:07:32.920 | and including foods with enough tryptophan,

00:07:34.660 | which is the precursor to serotonin.

00:07:36.720 | So what I've done here is I've created

00:07:38.460 | the real conceptual link, the anatomical link,

00:07:42.340 | and the chemical link between the production of serotonin

00:07:44.700 | in the gut and serotonin in the brain.

00:07:46.900 | And I wouldn't be talking about this

00:07:48.220 | if there wasn't actually data on this,

00:07:50.440 | I'll include links to a few papers about the,

00:07:53.140 | and here I'm quoting the title of a great paper,

00:07:54.820 | the interaction of the vagus nerve and serotonin

00:07:56.940 | in the gut brain axis.

00:07:58.840 | There's also been at least one clinical trial study

00:08:02.160 | exploring how taking probiotics,

00:08:04.140 | and in this case,

00:08:04.980 | it was actually probiotics plus magnesium.

00:08:07.920 | It was magnesium orotate,

00:08:09.900 | which is just one form of magnesium,

00:08:11.720 | as well as I would say a low-ish dose of coenzyme Q10.

00:08:16.860 | Combining those three things in this paper entitled,

00:08:19.580 | Probiotics and Magnesium Orotate,

00:08:21.780 | it should have said probiotics and Magnesium Orotate

00:08:24.580 | and coenzyme Q10,

00:08:25.580 | but the title is Probiotics and Magnesium Orotate

00:08:28.580 | for the Treatment of Major Depressive Disorder,

00:08:30.840 | a Randomized Double Blind Control Trial.

00:08:32.780 | And I want to emphasize that the results of this paper show

00:08:36.780 | that in the short term,

00:08:38.580 | there's an improvement in symptoms of major depression.

00:08:42.540 | That is symptoms of major depression were reduced

00:08:45.260 | through the administration of this combination of probiotics,

00:08:50.260 | magnesium orotate, and coenzyme Q10.

00:08:54.260 | However, it was a short-lived effect.

00:08:56.260 | Now, it was also a short-lived treatment,

00:08:58.260 | but it was a short-lived effect that showed up in the,

00:09:02.260 | essentially starting about the four-week mark,

00:09:05.260 | and then carried out to 10 and 15 weeks,

00:09:09.580 | the effect disappeared.

00:09:11.060 | Now, this is important because what it suggests

00:09:13.300 | is that in the short-term,

00:09:14.900 | if you're seeking to improve your mood,

00:09:17.040 | or if you're suffering from major depression,

00:09:19.060 | please seek help for major depression.

00:09:20.560 | This, of course, wouldn't be the only approach.

00:09:22.300 | You don't want to, you know,

00:09:24.140 | start being your own psychiatrist.

00:09:25.860 | This treatment very well could be combined with things,

00:09:28.380 | and should be combined probably with things like exercise,

00:09:30.660 | maybe with pharmacologic treatment,

00:09:32.140 | with antidepressant drugs.

00:09:33.400 | It really depends on the situation.

00:09:35.200 | But if you are somebody who's suffering

00:09:36.780 | from major depression or just mild depression,

00:09:38.700 | or if you're just seeking to maintain healthy serotonin levels,

00:09:42.120 | or improve your mood slightly,

00:09:44.200 | the consumption of things that are going to improve

00:09:47.180 | your gut microbiome absolutely is going to support that process.

00:09:51.260 | This has been shown over and over again,

00:09:52.800 | because the gut microbiota create these short chain fatty acids

00:09:56.780 | that are critically involved in this biochemical pathway

00:09:59.680 | that converts tryptophan into serotonin.

00:10:02.480 | I'm going to repeat that because it's very important.

00:10:04.680 | The microbiota of the gut,

00:10:05.920 | if they're diverse and you have enough of them,

00:10:08.000 | are going to produce the short chain fatty acids

00:10:10.500 | that are critically required for the conversion of tryptophan,

00:10:13.540 | which again is going to come from your diet,

00:10:15.620 | into the serotonin of your gut,

00:10:17.220 | which in turn is going to be relayed.

00:10:19.920 | And it's not the actual serotonin that's relayed,

00:10:21.980 | but the presence of serotonin at sufficient levels in the gut

00:10:25.900 | is communicated by the vagus nerve

00:10:28.200 | up to the dorsal raphe nucleus.

00:10:29.760 | Remember there's some stations in between,

00:10:31.120 | but it's communicated up to the dorsal raphe,

00:10:33.460 | and your dorsal raphe then releases serotonin in the brain.

00:10:36.620 | Again, a beautiful coordination of the body and the brain,

00:10:41.080 | just as activity levels in the body and the brain

00:10:43.540 | are matched through the vagus,

00:10:44.840 | or from the brain to the body,

00:10:46.120 | depending on the direction of flow, right?

00:10:47.640 | Alertness in the brain, body becomes alert.

00:10:49.400 | alertness in the body, brain becomes alert.

00:10:51.780 | Serotonin elevated in the gut, serotonin elevated in the brain.

00:10:56.740 | All of that happens by way of vagal signaling.

00:10:59.720 | alertness in the brain.

How to Improve Serotonin Levels for Depression | Dr. Andrew Huberman

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