Dr. Sara Gottfried: How to Optimize Female Hormone Health for Vitality & Longevity

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,

00:00:10.080 | and I'm a professor of neurobiology and ophthalmology

00:00:12.920 | at Stanford School of Medicine.

00:00:14.760 | Today, my guest is Dr. Sarah Gottfried.

00:00:17.080 | Dr. Sarah Gottfried is an obstetrician gynecologist

00:00:20.160 | who did her undergraduate training in bioengineering

00:00:22.960 | at the University of Washington in Seattle.

00:00:25.400 | She then completed her medical training

00:00:27.040 | at Harvard Medical School,

00:00:28.440 | and she currently is a clinical professor

00:00:30.320 | of integrative medicine and nutritional sciences

00:00:32.680 | at Thomas Jefferson University.

00:00:34.800 | She has also been a clinician treating men and women

00:00:38.440 | in various aspects of hormone health and longevity

00:00:41.220 | for more than 20 years.

00:00:43.200 | She is an expert in not just traditional medicine

00:00:45.760 | as it relates to hormones and fertility,

00:00:47.880 | but also nutritional practices,

00:00:49.960 | supplementation and behavioral practices,

00:00:52.280 | and combining all of that expertise

00:00:54.440 | in order to help women navigate every aspect and dimension

00:00:57.600 | of their hormones, longevity, and vitality,

00:01:00.000 | ranging from puberty to young adulthood,

00:01:03.360 | adulthood, perimenopause, and menopause.

00:01:06.080 | And nowadays, she's also treating men across the lifespan

00:01:09.300 | in terms of longevity, vitality, and hormone health.

00:01:12.080 | During today's discussion,

00:01:13.100 | Dr. Gottfried shares an enormous amount of information

00:01:15.920 | and tools that women can apply toward their hormone health,

00:01:19.080 | fertility, vitality, and longevity.

00:01:22.240 | We discussed the gut microbiome,

00:01:23.800 | which many people have heard about,

00:01:25.400 | but Dr. Gottfried points out the specific needs

00:01:27.500 | that women have in terms of managing their gut microbiome

00:01:30.120 | and the ways that that influences things

00:01:32.100 | like estrogen levels and metabolism,

00:01:34.080 | testosterone, thyroid, and growth hormone, and much more.

00:01:37.440 | We also discussed nutrition and exercise.

00:01:40.120 | We touch on how the omega-3 fatty acids

00:01:42.360 | play a particularly important role

00:01:44.120 | in managing female hormone health.

00:01:45.800 | Dr. Gottfried points out why women have particular needs

00:01:48.840 | when it comes to essential fatty acids

00:01:50.680 | and how best to obtain those essential fatty acids

00:01:53.440 | for hormone health.

00:01:54.960 | We also discuss exercise, and she offers

00:01:57.820 | some surprising information about the types and ratios

00:02:00.960 | of resistance training to cardiovascular training

00:02:03.460 | that women ought to use

00:02:04.600 | in order to maximize their hormone health.

00:02:07.160 | We also talk a lot about the digestive system.

00:02:09.280 | This was a surprising aspect of the conversation

00:02:11.420 | I did not anticipate.

00:02:12.580 | Dr. Gottfried shared with us, for instance,

00:02:14.560 | that women suffer from digestive issues

00:02:16.420 | at more than 10 times the frequency that do men,

00:02:18.940 | and fortunately, that there are tools specific to women

00:02:21.820 | that they can use in order to overcome

00:02:23.660 | those digestive issues, and that in overcoming

00:02:26.480 | those digestive issues, they can overcome

00:02:28.480 | many of the related hormone issues that so many women face.

00:02:31.840 | Dr. Gottfried also shares with you tremendous knowledge

00:02:34.640 | about the specific types of tests, not just blood tests,

00:02:37.160 | but also urine and microbiome tests that women can use

00:02:40.760 | in order to really get a clear understanding

00:02:43.160 | of their hormone status, not just of present,

00:02:46.320 | but also where the trajectory of their hormones

00:02:49.040 | is taking them.

00:02:49.980 | So we have an avid discussion about puberty,

00:02:52.880 | about young adulthood, adulthood, perimenopause,

00:02:55.880 | and how best to manage and navigate perimenopause

00:02:58.900 | and menopause, including a discussion

00:03:01.320 | about hormone replacement therapy.

00:03:03.080 | In addition to her academic and clinical expertise,

00:03:05.400 | Dr. Gottfried has authored many important books

00:03:07.560 | on nutrition, hormones, and supplementation

00:03:10.020 | as it relates to women and to people generally.

00:03:13.200 | The two books that I'd like to highlight

00:03:14.560 | and that we've provided links to in the show note captions

00:03:17.200 | are "Women, Food, and Hormones" and "The Hormone Cure."

00:03:20.600 | I read "The Hormone Cure" and found it

00:03:22.160 | to be tremendously interesting and informative,

00:03:24.440 | not just in terms of teaching me about female hormone health

00:03:26.880 | and various treatments for female hormone health,

00:03:29.080 | but also as a man trying to understand

00:03:31.560 | how the endocrine system interacts with mindset,

00:03:34.400 | nutrition, and supplementation more generally.

00:03:36.320 | So I highly recommend "The Hormone Cure"

00:03:38.320 | for anybody interested in hormones and hormone health,

00:03:40.920 | and "Women, Food, and Hormones" in particular for women,

00:03:43.360 | although again, both books are going to be

00:03:45.660 | strongly informative for women wishing to optimize

00:03:48.200 | their hormone health, vitality, and longevity.

00:03:50.880 | Before we begin, I'd like to emphasize that this podcast

00:03:53.480 | is separate from my teaching and research roles at Stanford.

00:03:56.200 | It is, however, part of my desire and effort

00:03:58.440 | to bring zero cost to consumer information about science

00:04:01.100 | and science-related tools to the general public.

00:04:03.780 | In keeping with that theme,

00:04:04.940 | I'd like to thank the sponsors of today's podcast.

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00:07:46.760 | And now for my discussion with Dr. Sarah Gottfried.

00:07:49.840 | Dr. Gottfried, Sarah, welcome.

00:07:52.120 | - Thank you, so happy to be here.

00:07:53.640 | - Yeah, I'm delighted and very excited to ask you

00:07:55.940 | about an enormous number of topics.

00:07:57.780 | You are expert in so many things.

00:08:00.400 | So the challenge for me is going to be

00:08:02.560 | to constrain this walk, as it were,

00:08:05.480 | but I'm hoping that we can touch on

00:08:07.580 | a great number of things today.

00:08:09.540 | The first of which is really about hormones

00:08:14.460 | and female hormones in particular.

00:08:16.860 | And I have a question, which is,

00:08:18.700 | is it ever informative for a woman,

00:08:22.440 | regardless of age, to know something about her mother's,

00:08:26.560 | perhaps even her grandmother's experience

00:08:29.160 | vis-a-vis hormones, not just pregnancy challenges with,

00:08:33.820 | or ease with pregnancy and child, rearing childbirth,

00:08:38.740 | this sort of thing, but what sorts of conversations

00:08:41.900 | should women be having with themselves

00:08:44.360 | and with family members to get a window

00:08:46.240 | into what their specific needs might be?

00:08:49.780 | - Love this question.

00:08:51.580 | So my work is really at the interface

00:08:54.120 | between genetics and environment.

00:08:56.360 | So your question gets to both.

00:09:00.260 | And I think it's essential that you understand

00:09:03.920 | what your grandmother went through.

00:09:06.900 | I'd even say your great-grandmother,

00:09:08.140 | depending on longevity in your family.

00:09:09.980 | So I grew up with my great-grandmother, I get that.

00:09:12.940 | And especially your mother.

00:09:14.940 | So I would probably start first with trauma,

00:09:19.500 | an intergenerational trauma,

00:09:21.300 | because I think that affects the endocrine system so hugely,

00:09:25.340 | especially cortisol signaling,

00:09:27.260 | but the broader pine system,

00:09:30.720 | psycho-immuno-neuro-endocrine system.

00:09:34.180 | And then there's, you know, if I think about the stages,

00:09:38.220 | the life cycle that a woman goes through,

00:09:40.360 | if you think about puberty, I think,

00:09:44.460 | I don't know how genetically determined

00:09:47.360 | the age of puberty is.

00:09:48.500 | Certainly there's a lot of environmental influences,

00:09:51.260 | like toxins can affect it.

00:09:53.380 | But pregnancy, the age at which you start to go through,

00:09:59.220 | perimenopause, menopause,

00:10:02.100 | many of those have a genetic component.

00:10:05.940 | So with pregnancy, I mean,

00:10:06.900 | you can certainly think the shape of the pelvis,

00:10:10.380 | your ability to have a vaginal birth,

00:10:13.660 | some of that is genetically determined.

00:10:15.200 | I mean, you do have, you know,

00:10:16.580 | the sperm donor affecting some of that.

00:10:20.300 | But, you know, in my family, for instance,

00:10:22.460 | we have no cesarean sections.

00:10:24.420 | So everyone goes through this process

00:10:27.620 | of a relatively easy vaginal birth.

00:10:30.140 | I was a forceps baby, but, you know, for the most part,

00:10:33.600 | you can find out about that.

00:10:35.820 | And then there's certain female conditions

00:10:39.260 | that have a very strong component genetically,

00:10:43.300 | most of which run in my family.

00:10:45.300 | So that includes endometriosis, fibroids,

00:10:49.180 | I just had a hysterectomy.

00:10:51.060 | I had 50 plus fibroids and polycystic ovarian syndrome.

00:10:56.060 | - And of those three, how frequent are those?

00:11:00.100 | And maybe I can constrain the question a little bit

00:11:02.600 | by saying today's discussion,

00:11:04.860 | I imagine is going to be heard by men and women

00:11:06.760 | of all sorts of ages.

00:11:07.840 | So maybe I'll direct the question a little bit toward,

00:11:11.260 | you know, at what age should these discussions start?

00:11:14.300 | You know, we always imagine that women in their 30s

00:11:19.780 | and 40s and 50s and onward should be getting certain tests

00:11:22.820 | and addressing things like ovarian reserve

00:11:26.220 | and other sorts of things.

00:11:27.860 | But, you know, maybe we could march through and just say,

00:11:31.140 | for a woman in her teens who's already hit puberty,

00:11:35.180 | what sorts of biomarkers,

00:11:37.140 | whether or not they're blood-based or phenotyping,

00:11:40.700 | you know, the outward appearance of,

00:11:42.800 | should those young women be paying attention to,

00:11:46.820 | likewise for women in their 20s, 30s,

00:11:48.660 | maybe we could take it more or less by decade,

00:11:51.260 | starting at puberty, assuming that woman hits puberty

00:11:54.580 | sometime between what is it now?

00:11:56.260 | The average in the U.S. is somewhere between 12

00:11:58.480 | and 16 years old, do I have that right?

00:12:00.420 | - No, you do not.

00:12:01.380 | - Oh, great, I love to be wrong, so.

00:12:03.960 | - So it used to be 12 to 16, I would say 50 years ago.

00:12:08.580 | It's been moving younger.

00:12:11.800 | And we think some of that is related to toxin exposure,

00:12:15.700 | as I mentioned, but I was 10 when I went through puberty.

00:12:20.220 | So, well, I should say men are key.

00:12:22.860 | And I started growing breasts much before that.

00:12:26.300 | So I think now I'm gonna step away

00:12:30.580 | from the science for a moment.

00:12:31.640 | I'm gonna do that pretty fluidly and I'll try to call it out.

00:12:35.140 | I think there's also a huge influence from stress

00:12:39.200 | and like the development of the adrenal glands.

00:12:42.480 | So going back to the science,

00:12:44.000 | the issue in teenage years is that the hypothalamic,

00:12:51.420 | pituitary, adrenal axis, and I like to think of it broader.

00:12:56.420 | So stay with me, hypothalamic, pituitary, adrenal,

00:13:01.420 | gonadal of recent women, testes men, thyroid, gut axis.

00:13:06.420 | So that to me is the control system.

00:13:10.320 | So I'm kind of expressing my bioengineering side here.

00:13:14.300 | - Well, I think it's great to include the other organs

00:13:16.140 | and tissue systems of the body, because as we both know

00:13:19.140 | that the narrow definition of just hypothalamic,

00:13:22.140 | pituitary, adrenal, it can't be just that, right?

00:13:24.940 | - No. - It can't.

00:13:26.020 | - No. - Yeah.

00:13:27.100 | - It doesn't tell the whole story.

00:13:29.080 | So if you look at the main sex hormones

00:13:34.080 | in a young woman who's in her teenage years,

00:13:38.060 | the hypothalamic, pituitary, adrenal, gonadal part of that

00:13:42.140 | is not fully mature.

00:13:44.100 | So they're more likely to skip periods,

00:13:46.340 | especially under stress.

00:13:48.340 | They have a lot of influences.

00:13:49.940 | It really doesn't get well-established

00:13:52.100 | until you're done with adolescence.

00:13:54.240 | And I'm told that adolescence now is till like age 25 to 26.

00:13:58.580 | I heard that and I was like, "I've got two daughters."

00:14:00.860 | And I was thinking, "That's a really long time."

00:14:03.300 | - And not just psychologically defined or biopsychosocial?

00:14:08.180 | - Mostly psychologically defined.

00:14:10.340 | I heard that from a psychologist.

00:14:12.340 | So biomarkers you asked about.

00:14:17.220 | In your teenage years, what I think is really interesting

00:14:19.900 | is to look at cortisol.

00:14:21.520 | To look at the dance between estrogen and progesterone

00:14:25.900 | in those years is less helpful

00:14:28.700 | because I think there's a lot of variability

00:14:30.660 | due to the immaturity of the system.

00:14:33.140 | If you've got someone who's got really regular periods,

00:14:35.780 | it's probably better to do some benchmarking at that age.

00:14:38.860 | But generally I find that benchmarking

00:14:40.820 | is best performed in your 20s or 30s.

00:14:44.360 | - Are periods not that regular in terms of duration

00:14:48.360 | of the menstrual cycle when the menstrual cycle first sets in?

00:14:52.840 | - It depends.

00:14:54.240 | So I was like clockwork every 28 days

00:14:57.180 | until I had my hysterectomy in August.

00:15:00.200 | Same thing with my daughters.

00:15:01.840 | I've got two daughters, one's 17, the other's 23.

00:15:05.220 | For a lot of women, they're not regular.

00:15:09.280 | And then there's the whole piece of oral contraceptives

00:15:12.880 | and other forms of contraception

00:15:14.920 | where you have no idea what the normal cycle is.

00:15:17.920 | And I hope we'll have some time

00:15:19.460 | to talk a little bit about oral contraceptives

00:15:21.480 | because I think this is now opinion again and not science.

00:15:26.280 | I think it is the number one endocrinopathy

00:15:28.800 | that is iatrogenic for women.

00:15:32.900 | - We will definitely talk about it.

00:15:34.080 | I get a lot of questions about oral contraceptives

00:15:36.480 | in the social media space

00:15:39.240 | and also questions about IUDs quite a lot.

00:15:43.160 | - Totally.

00:15:44.000 | - In particular, copper IUDs, non-hormonal IUDs.

00:15:46.840 | So we will definitely touch on that.

00:15:48.880 | - I'm an IUD crusader,

00:15:50.440 | so I just want to give you that warning.

00:15:52.640 | - You're a fan, do I have that right?

00:15:54.600 | Or you're anti-

00:15:55.560 | - I am a huge fan.

00:15:56.760 | - Uh-huh, which IUDs in particular?

00:15:59.280 | - So I like copper because it's non-hormonal.

00:16:03.520 | It's as effective as getting your tubes tied.

00:16:06.300 | - Who would have thought?

00:16:07.140 | - Right.

00:16:07.960 | - Is that toxic to the sperm mobility?

00:16:09.440 | Is that how it works?

00:16:10.940 | That's my understanding of it is that it basically,

00:16:13.520 | it's like more or less an electric fence

00:16:17.080 | to the sperm cap and just that's it.

00:16:19.720 | - Electric fence is a bit of a harsh analogy,

00:16:22.160 | but I'll work with that.

00:16:24.140 | But it's, you know, to have something

00:16:26.120 | that can last for 10 years

00:16:27.720 | so that you really have complete autonomy

00:16:31.360 | and sovereignty over your sexual life, that's profound.

00:16:35.840 | And to not get all those downstream risks

00:16:38.000 | that are associated with a birth control pill.

00:16:39.740 | The other thing that's important to know about it,

00:16:41.280 | I know this is a sidebar,

00:16:42.580 | women who use the copper IUD

00:16:46.680 | have the highest satisfaction rate

00:16:49.220 | of anyone on contraceptives, the highest satisfaction rate.

00:16:54.220 | And yet it is the least used of all forms of contraception.

00:16:59.280 | Now my favorite is vasectomy, but short of vasectomy,

00:17:04.760 | I think the IUD is a really great choice.

00:17:06.520 | There are some risks associated with it.

00:17:08.000 | I'm not saying it's risk-free, but I love the IUD.

00:17:11.920 | And I love it for younger women too.

00:17:14.060 | 'Cause it used to be that when I went through my training,

00:17:16.520 | which was 30 years ago, we were told, you know,

00:17:20.200 | don't put it in someone who hasn't had a baby.

00:17:23.240 | And that is patriarchal messaging.

00:17:25.960 | But getting back to your original question,

00:17:27.720 | which is about biomarkers per decade.

00:17:32.000 | In your 20s, that's when you want to do some base casing

00:17:37.000 | with estrogen, progesterone, and testosterone.

00:17:40.200 | So I think it's really helpful to know about this tango.

00:17:44.640 | You're from Argentina or your father.

00:17:46.480 | - I have Argentine lineage.

00:17:47.920 | - Yes.

00:17:48.760 | - My grandparents did tango into their late 80s.

00:17:52.600 | I am, I'm in my late 40s and I still haven't started.

00:17:56.220 | So I suppose there's time.

00:17:57.300 | - It might be time for you to do that.

00:17:59.780 | - Okay.

00:18:00.620 | - There might be a factor in their longevity.

00:18:03.280 | Did they have good health span?

00:18:04.460 | Not just life span?

00:18:05.460 | - And my grandfather smoked cigarettes daily,

00:18:08.660 | remained mentally sharp until he died in his late 90s,

00:18:11.320 | but almost burned down their apartment several times,

00:18:14.020 | falling asleep with a cigarette in his mouth.

00:18:15.440 | So I don't recommend anyone smoke by the way,

00:18:17.980 | but it was a coffee, mate, red meat and cigarettes.

00:18:21.180 | And they lived into their 90s.

00:18:22.220 | So that side of my family has the genetic advantage.

00:18:25.540 | The other side, less so, but in any event,

00:18:29.020 | tango is a 2023 goal.

00:18:32.200 | It has been every year.

00:18:33.300 | - I'm going to hold you accountable to that.

00:18:37.140 | - Okay, will do.

00:18:37.980 | And no, there will be no YouTube video of me doing tango.

00:18:41.220 | - At least not initially.

00:18:42.380 | - Tim Ferriss, actually, a phenomenal podcaster,

00:18:44.960 | as we know, he's a bad-ass tango dancer.

00:18:48.980 | I know this through various sources.

00:18:50.740 | - Yes, I've seen.

00:18:52.340 | Yeah, so this tango between estrogen and progesterone

00:18:54.960 | is incredibly important.

00:18:56.660 | You want to have the right lead.

00:18:58.500 | You want to have the right follow between the two hormones.

00:19:01.820 | Again, I'm stepping away from my science hat.

00:19:04.540 | But what happens a lot of the time

00:19:06.860 | is that estrogen dominates in that tango.

00:19:10.460 | And when that happens, it sets you up

00:19:12.820 | for greater risk of fibroids, endometriosis, breast pain,

00:19:17.820 | probably in association with the microbiome

00:19:23.020 | and the estrobilome.

00:19:25.100 | - Can you familiarize me with the estrobilome?

00:19:26.980 | - Yeah. - I'm delighted to know

00:19:28.980 | that I don't recognize the term.

00:19:30.700 | - Yeah, so the estrobilome is the set of microbes

00:19:34.460 | in, and their DNA, their DNA mostly,

00:19:38.600 | in the gut microbiome, that set of microbes in their DNA.

00:19:42.980 | So it's in the, if you look at the totality,

00:19:46.900 | the subset of particular bacteria modulate estrogen levels.

00:19:55.100 | So a lot of this work was spearheaded by Martin Glaser.

00:19:58.080 | And what we know is that there are some women

00:20:03.580 | who have an estrobilome that makes them have a greater risk

00:20:08.580 | of certain estrogen-mediated conditions like breast cancer,

00:20:13.780 | endometrial cancer, and in men, prostate cancer.

00:20:18.380 | So the estrobilome is incredibly important.

00:20:20.700 | There's not a lot of attention paid to it.

00:20:23.140 | But I always think in terms of my patients,

00:20:26.660 | could this be someone who's got a faulty estrobilome,

00:20:30.580 | and we need to adjust it with some of the microbiome

00:20:35.580 | modulating nutrients, nutraceuticals that we have,

00:20:41.360 | so that they're less likely to have that tango

00:20:44.420 | that's not working with estrogen or testosterone.

00:20:46.940 | So getting back to the biomarkers,

00:20:50.900 | if you gave me an unlimited budget,

00:20:53.900 | which I kind of have with some of my clients

00:20:57.180 | that I work with now, what I would wanna know

00:21:00.020 | is estrogen, progesterone, testosterone,

00:21:03.860 | and I want the timing right for that.

00:21:06.600 | I'd wanna know about DHEA

00:21:08.060 | and sort of the whole androgen pathway.

00:21:10.540 | I'd wanna know about the metabolites of estrogen

00:21:13.280 | because some of them are protective and very helpful.

00:21:18.260 | Others are a bit like Homer Simpson.

00:21:21.660 | I mean, they are just like causing all kinds of problems

00:21:23.980 | in your body, increasing the risk of quinones,

00:21:28.200 | like DNA damage, and potentially an increased risk

00:21:32.420 | of breast cancer, although that data I think is mixed.

00:21:36.040 | I'd also like to know about their stool.

00:21:39.200 | So I wanna know about the microbiome.

00:21:41.300 | So the best that we have right now is to look

00:21:43.940 | when we do stool testing, and I do a lot of stool testing.

00:21:47.300 | We can look at things like beta-glucuronidase.

00:21:51.020 | Are you familiar with BG?

00:21:52.600 | - I'm familiar with it as a term.

00:21:54.340 | And so for those listening, very often,

00:21:57.060 | not always when you hear an ACE, A-S-E,

00:21:58.860 | you're dealing with an enzyme.

00:21:59.940 | So we can take a stab there.

00:22:02.100 | And it sounds like it's somehow involved

00:22:04.660 | in glucose metabolism of some sort, or is it?

00:22:08.620 | - Glucuronidation.

00:22:10.140 | So it's involved in, when you produce estrogen in the body,

00:22:13.760 | this is like the simplified version,

00:22:16.600 | but when you produce estrogen, you are meant to use it,

00:22:21.460 | like send it to the receptors where it's meant to go,

00:22:24.660 | and then lose it.

00:22:26.300 | You don't wanna keep recirculating the estrogen,

00:22:28.480 | like bad karma.

00:22:29.980 | And that's what happens with people

00:22:31.540 | who have high beta-glucuronidase.

00:22:35.140 | So it's this enzyme that's produced

00:22:36.660 | by three bacteria in particular in the gut.

00:22:39.400 | And I see a lot of men and women

00:22:41.940 | who have elevated beta-glucuronidase,

00:22:45.140 | and then they have some estrogen dominance related to that.

00:22:47.960 | Is that the total reason?

00:22:49.620 | We don't really know.

00:22:50.860 | But it's one of the drivers, it's one of the levers.

00:22:53.260 | - And it can be detected from a microbiome,

00:22:55.720 | AKA stool sample.

00:22:56.900 | - That's right.

00:22:57.800 | - And in terms of blood testing or various tests

00:23:01.040 | for these other biomarkers,

00:23:02.080 | getting estrogen, testosterone, and other ratios,

00:23:05.280 | I realize people have different means, financial means,

00:23:09.180 | but in general, people wanting to do a blood test,

00:23:12.280 | it sounds like they're going to need to do it,

00:23:13.680 | women will need to do it at different stages

00:23:15.480 | of their menstrual cycle if they had to pick one,

00:23:18.640 | either in the follicular phase

00:23:21.120 | or in the luteal stage of their ovarian menstrual cycle,

00:23:25.360 | excuse me, ovulatory menstrual cycle.

00:23:27.720 | When would you suggest they do that if they had to pick one?

00:23:30.940 | - So if you forced me to pick one,

00:23:33.060 | I would say probably day 21 to 22 for someone in her 20s.

00:23:38.060 | So we're focused right now on that decade.

00:23:42.300 | So for most women, they've got a menstrual cycle date

00:23:45.120 | that averages out at 28 days.

00:23:47.260 | So this is about a week before they start their period.

00:23:51.480 | For women who are more irregular, it's harder to do that.

00:23:54.360 | As women get older, and we'll talk about this in a moment,

00:23:57.940 | usually the cycle gets a little shorter.

00:24:00.120 | So as they start to decline in their progesterone production

00:24:04.080 | their period gets a little closer together.

00:24:05.960 | Like mine before August was about every 26 days.

00:24:09.920 | So at that point you want to test sooner, like day 19, 20.

00:24:14.920 | And I'm not talking about blood tests.

00:24:17.660 | So a blood test is the cheapest thing.

00:24:19.040 | It's usually what's covered by insurance.

00:24:21.320 | But my preference would be to do dried urine.

00:24:24.660 | I like to use saliva for cortisol.

00:24:27.100 | I like to use dried urine so that I get metabolomics

00:24:29.780 | in addition to the levels of these hormones.

00:24:32.680 | And if I'm forced to, I'll use blood testing.

00:24:35.200 | And that's certainly the gold standard

00:24:37.580 | for all of these hormones that we're talking about.

00:24:40.180 | But it's not as comprehensive.

00:24:43.920 | And as you know, it's a quick little snapshot

00:24:45.960 | while the needle's in your vein for 30 seconds.

00:24:49.100 | - Yeah, the salivary cortisol makes sense to me

00:24:51.200 | 'cause my understanding is that you get free cortisol

00:24:53.100 | which is the active cortisol.

00:24:54.600 | You said with urine, you're also getting the metabolites.

00:24:56.680 | - That's right.

00:24:57.520 | - And then for blood testing,

00:25:00.200 | you're getting sort of a crude window into the averages.

00:25:03.200 | - A static, total level.

00:25:06.840 | So let me go back and say one other thing about biomarkers.

00:25:11.280 | A big part of the testing that I do

00:25:13.100 | in phenotyping my patients, I practice precision medicine.

00:25:16.540 | So I like to almost start with nutritional testing.

00:25:21.540 | I don't think I've ever had a teenager.

00:25:26.880 | I've got some NBA players that are 19, 20, 21.

00:25:30.140 | So maybe those count, but those are men, obviously.

00:25:34.580 | But for nutritional testing,

00:25:38.100 | that would be potentially a helpful thing

00:25:39.900 | to do in your 20s.

00:25:41.380 | Becomes less important as you get older

00:25:43.140 | and you develop more micronutrient deficiencies,

00:25:46.060 | but micronutrients play a huge role

00:25:48.620 | in terms of hormone production.

00:25:50.380 | Magnesium, the magnesium is hugely involved

00:25:53.820 | in the way that you get rid of estrogen, as an example.

00:25:57.340 | So micronutrient testing, what I usually do

00:25:59.400 | is a combination of blood and urine.

00:26:02.300 | And so I'm looking at all of the micronutrients

00:26:04.780 | that we can measure that have some clinical

00:26:08.780 | scientific basis behind them.

00:26:10.760 | If I could do that for a teenager,

00:26:14.020 | I think it might be helpful

00:26:15.340 | because I recently gave a lecture

00:26:18.960 | on breast cancer risk reduction, another quick sidebar.

00:26:22.960 | And I was sad to find that intake of vegetables,

00:26:30.940 | polyphenols is such an important predictor

00:26:34.540 | of future risk of breast cancer,

00:26:36.040 | like when you're 50, 60 plus.

00:26:38.760 | And the most important time is when you're a teenager.

00:26:42.340 | Now I have one daughter that eats vegetables, she loves them

00:26:45.220 | and I have another daughter who eats food that's beige.

00:26:48.300 | And it's very hard to get her to eat the volume

00:26:51.600 | of vegetables, five colors a day, which is what I do.

00:26:55.540 | And if you have evidence that you could show

00:27:01.300 | a 17 year old that they've got micronutrient gaps,

00:27:05.620 | I think that would be a motivator

00:27:08.620 | for them to eat differently at a time when it's so critical,

00:27:13.160 | even though it's 25 years in the future,

00:27:15.520 | that it's going to potentially change

00:27:17.140 | this arc that they're on.

00:27:19.080 | - What do you do for a young woman

00:27:21.360 | who doesn't like vegetables or is not somehow able

00:27:25.640 | or willing to get those five colors a day of vegetable

00:27:29.540 | to help support the microbiome?

00:27:32.260 | Are supplements a useful tool in that case?

00:27:37.180 | What other sorts of tools, behavioral or otherwise,

00:27:39.500 | are useful?

00:27:40.600 | - Such a good question.

00:27:41.620 | So here I'm going to invoke Rob Knight at UCSD.

00:27:45.320 | So I think his gut project has really been helpful

00:27:50.320 | in terms of understanding what kind of modulators

00:27:53.380 | are going to be important.

00:27:55.500 | So what I try to get that person to do,

00:27:57.860 | and I don't see many teens anymore other than NBA players,

00:28:01.900 | what I try to get them to do is to have a smoothie.

00:28:05.060 | Very hard to get them to have a smoothie every day,

00:28:07.140 | but if I could get them to have a smoothie

00:28:08.660 | three times a week and to throw some of these vegetables in,

00:28:12.500 | that makes a huge difference.

00:28:13.900 | I mean, we know that makes a difference

00:28:15.340 | in terms of microbiome change.

00:28:17.300 | - To be blending up broccoli or kale.

00:28:19.740 | - Cauliflower.

00:28:20.580 | So cauliflower is great. - Yellow peppers even,

00:28:22.220 | they're putting things into the smoothie.

00:28:24.060 | - Yeah, I don't know if you can get a teenager to do that,

00:28:26.060 | but they often will use,

00:28:27.600 | like I have them do steamed broccoli that's in the freezer

00:28:30.480 | because it's got very little taste.

00:28:32.900 | So they could do that in a chocolate smoothie.

00:28:35.500 | They could add some greens.

00:28:36.780 | I like greens.

00:28:37.860 | Powders are super convenient.

00:28:40.700 | So that with kind of a taste that they like,

00:28:43.700 | whether that's chocolate,

00:28:45.260 | which is what most of my clients want,

00:28:47.380 | or vanilla with berries and that sort of thing.

00:28:50.660 | So that can go a long way if you don't like vegetables.

00:28:53.940 | And short of that, I would say some supplements,

00:28:56.080 | but I would say that's a distant second

00:28:58.100 | to making a smoothie.

00:28:59.460 | I've got one patient that I have to mention

00:29:02.140 | because he took this to the extreme.

00:29:07.140 | So he is a retired physicist professor at UCSD.

00:29:12.420 | He found out that his microbiome was a hot mess

00:29:15.460 | and developed autoimmune disease.

00:29:19.020 | And so he became hell bent,

00:29:20.820 | like only a physicist could on changing his microbiome.

00:29:25.540 | And he dramatically shifted it

00:29:27.660 | by having a smoothie every day

00:29:31.040 | with 57 vegetables and fruits in it.

00:29:34.900 | - 57 independent.

00:29:36.580 | - 57 independent.

00:29:38.260 | So, I mean, this just warms my heart

00:29:42.700 | the way that he did this.

00:29:44.220 | But he would go to the farmer's market.

00:29:45.980 | He would just get a bunch of this, a bunch of that.

00:29:48.980 | And he would go home, make the smoothie,

00:29:51.520 | and then stick it in the freezer.

00:29:52.860 | So he'd have a serving every day.

00:29:55.120 | And he became a completely different person

00:29:58.680 | based on this microbiome change.

00:30:00.800 | His autoimmune disease is in remission.

00:30:05.800 | He dropped a huge amount of weight.

00:30:10.820 | He went from being kind of this phenotype

00:30:13.040 | that I know you know well of a professor,

00:30:16.360 | high performing, traveling around the world

00:30:18.220 | on so many boards, so much innovation,

00:30:20.960 | so many great ideas, super computer guy,

00:30:23.520 | to being someone who gets up in the morning,

00:30:26.140 | gets in his hot tub, exercises for one to two hours a day,

00:30:31.100 | and then does a little work.

00:30:33.100 | He completely shifted the way that he lives.

00:30:35.500 | And his microbiome shift, who knows what's the chicken

00:30:39.140 | and what's the egg there?

00:30:40.780 | But he had a huge change in his physiology.

00:30:43.820 | Glucose went from being quite high.

00:30:45.780 | He had, and he tracks all of this, of course.

00:30:48.720 | It's like on a Jupiter. - Scientist after all.

00:30:51.460 | - Right. - Yeah.

00:30:52.300 | - Retired, I suppose, might've had.

00:30:53.660 | - And he's retired, but he's got the longest time series

00:30:57.980 | of anyone I know.

00:31:00.000 | And he's tracked his glucose and insulin

00:31:02.000 | going back 20 years.

00:31:04.000 | So he can show you, okay,

00:31:06.140 | here's where I started having my smoothie,

00:31:08.960 | and here's how my glucose and insulin changed

00:31:11.560 | as a result of that.

00:31:12.900 | - I'd like to take a quick break

00:31:14.300 | and acknowledge one of our sponsors, Athletic Greens.

00:31:17.340 | Athletic Greens, now called AG1,

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00:31:22.160 | that covers all of your foundational nutritional needs.

00:31:25.060 | I've been taking Athletic Greens since 2012,

00:31:27.740 | so I'm delighted that they're sponsoring the podcast.

00:31:29.960 | The reason I started taking Athletic Greens

00:31:31.560 | and the reason I still take Athletic Greens

00:31:33.620 | once or usually twice a day

00:31:35.620 | is that it gets me the probiotics that I need for gut health.

00:31:39.220 | Our gut is very important.

00:31:40.300 | It's populated by gut microbiota

00:31:42.860 | that communicate with the brain, the immune system,

00:31:44.620 | and basically all the biological systems of our body

00:31:47.020 | to strongly impact our immediate and long-term health.

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00:32:01.700 | nutritional needs are met, and it tastes great.

00:32:05.160 | If you'd like to try Athletic Greens,

00:32:06.620 | you can go to athleticgreens.com/huberman,

00:32:10.020 | and they'll give you five free travel packs

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00:32:14.300 | while you're on the road, in the car, on the plane, et cetera.

00:32:16.880 | And they'll give you a year's supply of vitamin D3K2.

00:32:20.300 | Again, that's athleticgreens.com/huberman

00:32:22.980 | to get the five free travel packs

00:32:24.340 | and the year's supply of vitamin D3K2.

00:32:27.520 | - Is there a case for, I'll say young women,

00:32:30.060 | but young women and men using over-the-counter probiotics

00:32:34.580 | as a way to enhance the microbiome?

00:32:36.020 | This is something I hear about a lot.

00:32:37.180 | I've heard that excessive doses of capsule probiotics

00:32:39.920 | can give a brain fog-like condition.

00:32:42.660 | I personally don't use capsule probiotics

00:32:45.540 | unless I feel like my system

00:32:47.300 | is under a significant amount of stress,

00:32:49.060 | in which case I might add that in for brief periods of time,

00:32:51.660 | or if I've just taken antibiotics for a period of time.

00:32:55.200 | Do you ever recommend that the college student

00:32:57.660 | or the high school student,

00:32:59.120 | that she or he take capsule probiotics?

00:33:02.560 | Assuming that they're getting,

00:33:04.220 | let's say three to five servings of vegetables per day,

00:33:07.380 | either in smoothie form or some other form,

00:33:09.980 | what are your thoughts on supplementing probiotics?

00:33:12.940 | - It sounds like such a simple question.

00:33:16.280 | It is such a complex answer.

00:33:18.380 | And I don't think we really have the answer.

00:33:20.820 | So I'll tell you the way that I approach it.

00:33:23.100 | I look for randomized trials to support my use of probiotics

00:33:27.180 | and frankly, I'm underwhelmed.

00:33:29.600 | So I've seen some data,

00:33:31.700 | if I invoke my NBA players for a moment,

00:33:35.460 | almost every player I've tested

00:33:38.420 | has increased intestinal permeability.

00:33:40.420 | They just have such a high training load,

00:33:42.760 | probably mediated by cortisol,

00:33:44.900 | very high glucoses when they drain,

00:33:47.060 | that they have increased intestinal permeability.

00:33:50.060 | So those tight junctions in their intestine become loose.

00:33:53.980 | They develop a lot of inflammation as a result of that.

00:33:56.500 | And when you're a professional NBA player

00:33:59.060 | and you're making 20 million a year,

00:34:01.580 | like you don't want a lot of inflammation.

00:34:03.180 | You want a little bit to like help your muscles recover,

00:34:05.620 | but you don't want it to be adding to problems

00:34:09.580 | when you develop an injury.

00:34:10.980 | - So this is leaky gut.

00:34:12.180 | - Leaky gut.

00:34:13.460 | I don't love that term, but yeah, we'll use it here.

00:34:16.940 | So there's a particular probiotic

00:34:20.340 | that is helpful in athletes with leaky gut.

00:34:23.500 | So that's the kind of specificity

00:34:25.340 | and randomized trial that I'm looking for.

00:34:28.020 | The rest of it,

00:34:29.040 | I think there's support if you find help from it,

00:34:34.300 | as you described, if you take a course of antibiotics.

00:34:37.500 | I mean, first of all, I would question whether you need them,

00:34:39.700 | but there's a ton of ways. - Yeah, I try and avoid them.

00:34:41.420 | There have been instances where they've been prescribed

00:34:43.740 | and I took them mostly in the past, like it was in college.

00:34:45.660 | They seemed like they kind of gave them out.

00:34:46.840 | You had a science infection, they give you antibiotics.

00:34:50.300 | - Yeah, the worst treatment ever.

00:34:52.020 | Yeah, so if you're coming off of antibiotics,

00:34:54.680 | I think that's a good time to do

00:34:55.980 | what we call replacement dose probiotics.

00:34:58.620 | I think what's far more interesting is prebiotics.

00:35:03.620 | I think the data is much better for prebiotics

00:35:07.180 | and the selective use of polyphen.

00:35:11.740 | - How would a person in their teens and twenties

00:35:15.460 | or any age for that matter,

00:35:16.720 | know whether or not they have nutritional deficiencies?

00:35:20.780 | What is the best way to analyze

00:35:22.540 | if one is getting enough magnesium?

00:35:24.840 | And for that matter,

00:35:26.020 | what is going to be the best way to test the microbiome?

00:35:29.060 | You said stool sample,

00:35:30.700 | and I'll come right back with the same question

00:35:32.860 | I asked about a blood test.

00:35:34.500 | What time of day, when during the month

00:35:38.420 | to establish a baseline?

00:35:40.900 | So this would be prior to embarking on 97 vegetables

00:35:44.480 | or however many per day.

00:35:46.020 | - I was only 57.

00:35:47.120 | - Well, I love the idea that you're telling us,

00:35:49.920 | if I'm gathering correctly,

00:35:51.220 | is that yes, there's a case for probiotics,

00:35:52.840 | but for the typical person, regardless of age,

00:35:55.040 | eating more vegetables or drinking more vegetables,

00:35:57.760 | as the case may be,

00:35:59.060 | is going to be beneficial for the gut microbiome,

00:36:01.760 | perhaps without the need to go test whether or not

00:36:04.400 | one is making a certain number

00:36:05.540 | of estrogen-related metabolites or not.

00:36:07.640 | Just that that's a great starting place,

00:36:09.180 | eat or consume more vegetables.

00:36:12.600 | But if one wants to analyze their gut microbiome,

00:36:15.000 | are there good tests available to the general public?

00:36:17.380 | This has been, I'm not going to name companies,

00:36:18.840 | but I've been tracking this over the years,

00:36:20.860 | and it's never been clear to me that we know

00:36:23.100 | what constituents of the gut microbiome are best.

00:36:26.620 | You know, we know that dysbiosis is bad,

00:36:28.980 | and we know that diversity of the microbiome is good.

00:36:31.540 | We hear this, but no one's ever told me that you want

00:36:34.580 | a particular ratio of one microbiota to another

00:36:38.740 | in a way that has made any sense to me at least.

00:36:41.620 | I'm not a microbiologist,

00:36:43.020 | but whereas with, you know, with testosterone in men,

00:36:46.540 | we hear, okay, you want your free testosterone

00:36:48.260 | to be about 2% of your total, perhaps.

00:36:50.920 | With women, women are going to have more testosterone

00:36:53.220 | than estrogen on average, but still less than men

00:36:56.100 | when you look at testosterone, et cetera, et cetera.

00:36:58.260 | But you can kind of get some crude measures,

00:37:00.300 | but for the microbiome, it just seems like long lists

00:37:02.720 | of microbiota for which I just get dizzy.

00:37:05.600 | I just, if you just wrote out a bunch of Is and Ls and Ss,

00:37:08.620 | you'd kind of halfway,

00:37:10.160 | you're getting a bit the same information.

00:37:12.580 | I'm not trying to poke at that field as a beautiful field,

00:37:14.760 | but they haven't told me what my microbiota ought to look

00:37:19.600 | like, like what's a healthy microbiome chart.

00:37:22.100 | - Well, that's because we don't know.

00:37:24.640 | I mean, the best we have is Rob Knight's work,

00:37:27.300 | but even that is limited in terms of, you know,

00:37:30.640 | can I tell you that a woman in her 20s should have

00:37:33.800 | this particular pattern with her microbiome?

00:37:36.560 | No, I can't.

00:37:38.220 | So let me go to your first question,

00:37:40.780 | 'cause I think you just asked about six.

00:37:43.460 | Your first question is about nutritional testing.

00:37:46.460 | What I like to do with nutritional testing is run a panel

00:37:51.460 | that's looking at antioxidants, so like vitamin A,

00:37:55.860 | vitamin C, alpha lipoic acid, plant-based antioxidants,

00:38:00.820 | 'cause you can measure that in the blood.

00:38:03.000 | I like to look at some of the key vitamins,

00:38:06.660 | especially the B vitamin range,

00:38:08.780 | because as you probably know,

00:38:10.420 | if you've got particular genetic polymorphism,

00:38:14.780 | so you might be less likely to be absorbing the right level

00:38:17.960 | of vitamin B9, folate, vitamin B12, et cetera.

00:38:21.600 | I'm also looking, going back to the antioxidants

00:38:24.760 | at glutathione, because I think that's such

00:38:26.700 | an important lever when it comes to detoxification,

00:38:29.500 | which we haven't talked about yet.

00:38:31.540 | And then I'm looking at some of the minerals.

00:38:33.480 | Magnesium is really the most important,

00:38:35.220 | and we know that somewhere around 70 to 80% of Americans

00:38:37.900 | are deficient in magnesium.

00:38:39.260 | That's like the lowest hanging fruit.

00:38:41.980 | - I would be curious, for instance, like with magnesium,

00:38:43.940 | if that number of people are deficient,

00:38:46.500 | does that mean that that number of people

00:38:47.860 | should be targeting their nutrition towards foods

00:38:50.400 | that contain magnesium and or supplementing with magnesium?

00:38:53.260 | And if so, what forms of magnesium?

00:38:55.700 | We've talked about Mag-3 and 8 for sleep.

00:38:58.180 | There's a Mag-Citrate.

00:38:59.020 | There's so many forms.

00:39:00.320 | It can be a little bit of overwhelming to people.

00:39:01.640 | So any detail in sourcing, I would appreciate it.

00:39:05.140 | - Great, so first, in terms of testing,

00:39:07.980 | what I prefer to do is to mention more than one lab

00:39:12.460 | and more than one brand.

00:39:13.660 | And I'm speaking mostly from experience.

00:39:17.860 | So for testing, I do a lot of Genova NutriVols.

00:39:22.860 | During the pandemic, they developed an at-home test.

00:39:28.300 | Normally with a NutriVol, you have to get your blood drawn

00:39:30.420 | and you have to do a urine sample.

00:39:32.540 | So a lot of people can't do that.

00:39:34.240 | The great thing about this test is your insurance

00:39:36.720 | usually pays for most of it.

00:39:38.880 | And so the copay is about $150.

00:39:42.360 | So during the pandemic, they developed another test

00:39:44.480 | called Metabolomics, which does much of the same testing,

00:39:48.600 | but it's a finger prick.

00:39:49.900 | So most of my patients prefer that.

00:39:53.020 | In fact, they haven't gone back to the NutriVol.

00:39:56.020 | Second lab is SpectraCell.

00:39:58.220 | I use SpectraCell occasionally.

00:40:01.020 | I find it not quite as easy in terms of fitting

00:40:03.700 | into my practice, but I've got friends and mentors

00:40:07.180 | like Mark Houston, who does a lot of kind of precision

00:40:12.180 | cardiometabolic health.

00:40:15.400 | He thinks SpectraCell is the best test out there.

00:40:18.820 | So you asked about magnesium.

00:40:21.280 | You have to measure red blood cell magnesium,

00:40:23.740 | like whole blood.

00:40:25.460 | And with deficiency, it's interesting with supplementation.

00:40:31.680 | For my patients who tend toward constipation,

00:40:34.960 | and that's frankly about 80% of the women

00:40:37.080 | that I take care of.

00:40:38.040 | - Really?

00:40:38.880 | - Yes.

00:40:39.800 | - Wow, I'd be curious as to why that is.

00:40:42.460 | I can guess, diet, stress.

00:40:46.260 | - Patriarchy, rage.

00:40:50.120 | - So psycho-- - That they may not know about.

00:40:52.820 | - So the pine.

00:40:54.440 | - The pine system.

00:40:55.480 | - Right, psychology, immunology,

00:40:58.920 | neural and endocrine factors combined.

00:41:01.380 | - Yes.

00:41:02.220 | And then I would say there's another factor,

00:41:04.940 | which is being female is a health hazard.

00:41:09.940 | So we have twice the rate of depression, insomnia.

00:41:16.580 | We've got three to four X increased risk

00:41:19.300 | of multiple sclerosis.

00:41:21.260 | We've got five to eight times the risk

00:41:23.500 | of thyroid dysfunction.

00:41:25.240 | So if you just look at that, and you look at subtle

00:41:29.380 | pre-clinical thyroid dysfunction,

00:41:32.060 | a huge number of the women that I take care of,

00:41:34.420 | well, let me back off.

00:41:35.980 | A large number of the women that I take care of

00:41:38.380 | have thyroid dysfunction that's contributing

00:41:40.940 | to constipation.

00:41:42.900 | And if we go back to that control system,

00:41:44.740 | the hypothalamic, pituitary, adrenal, thyroid,

00:41:46.600 | canal, gut axis, and they have a lot of perceived stress,

00:41:51.600 | together with this borderline thyroid function

00:41:54.500 | that no mainstream medicine doctor has told her

00:41:57.260 | is a problem.

00:41:58.500 | And then she's got a problem with the tango

00:42:00.460 | between estrogen and progesterone.

00:42:02.340 | She's gonna tend toward constipation.

00:42:06.020 | Women have a lot more constipation than men.

00:42:08.660 | The gut is about 10 feet longer in women compared to men.

00:42:12.900 | We should talk about some sex and gender differences

00:42:15.140 | and define those.

00:42:16.580 | And they are much more likely to have a torturous colon.

00:42:21.180 | And the way you know that is you get a colonoscopy

00:42:23.700 | and they tell you, yeah, it was really hard.

00:42:26.420 | Like, get in there and do what we need to do.

00:42:28.900 | - As a brief tangent, but I think this is the time to ask,

00:42:31.740 | at what age now do physicians insist

00:42:36.000 | their female patients get colonoscopies?

00:42:39.200 | For men, I think the age used to be 50.

00:42:41.180 | Now it's getting ratcheted back to 45 or 40.

00:42:45.040 | Again, these are recommendations, not requirements,

00:42:46.900 | but they're pretty strong recommendations

00:42:48.500 | from depending on where you live, et cetera.

00:42:50.700 | For women, how early do you think they should get

00:42:53.900 | a colonoscopy to explore for possible polyps

00:42:57.700 | and/or colon cancer?

00:42:59.780 | - Yeah, it's a really good question.

00:43:00.900 | I don't know the answer.

00:43:01.940 | So what I've always operated with is 50.

00:43:04.860 | The way that I answer that is to go

00:43:06.500 | to the U.S. Preventive Task Force rating

00:43:09.400 | to determine based on their synthesis of the data

00:43:12.780 | what age is the most appropriate.

00:43:14.660 | Has it changed, as you just described from men,

00:43:17.460 | from 50 to younger?

00:43:18.820 | I don't know, so we should fact check that.

00:43:21.500 | All these additional health hazards for women.

00:43:25.460 | You mentioned some of the,

00:43:28.340 | you broadly mentioned psychological impact, right?

00:43:31.140 | And of course these things are all related,

00:43:33.220 | psychology, immunology.

00:43:34.540 | And then one of the, I think, wonderful things

00:43:36.180 | about neuroscience and science in general and medicine

00:43:40.140 | is that there's now an understanding

00:43:42.280 | that all the organs are connected to one another.

00:43:44.440 | - It's a network.

00:43:45.280 | - It's a network.

00:43:46.100 | And that the microbiome sits at a key node

00:43:49.700 | within that network.

00:43:51.720 | And I think most people accept that now.

00:43:54.040 | - Yes.

00:43:55.160 | - That seems to be a theme

00:43:56.120 | that at least in the last 10 years is really wonderful

00:43:58.280 | because certainly for neuroscience,

00:44:00.600 | it was thought that unless it's in the cranial vault,

00:44:03.860 | it's not neural, which is ridiculous

00:44:05.880 | 'cause there's lots of nervous system outside the skull.

00:44:08.600 | But in any case-

00:44:09.820 | - Can I interrupt for a second?

00:44:10.840 | - Yes, please.

00:44:11.680 | - So I think you're right

00:44:12.800 | that there's an understanding about the network effect.

00:44:16.400 | But I think that as much as I love mainstream medicine

00:44:21.400 | and I trained in it, and I'm so grateful for my education,

00:44:25.360 | I still think it is a silo-based way

00:44:27.840 | of taking care of patients.

00:44:29.160 | So even if there's an understanding of the network effect

00:44:31.460 | more at the science level,

00:44:33.460 | or as you described in neuroscience,

00:44:35.840 | there's still, you know, if you are a woman

00:44:39.700 | who has constipation, fatigue,

00:44:44.180 | maybe an autoimmune condition, feel stressed out all the time

00:44:49.180 | feel like your hormones are out of whack,

00:44:51.240 | you get sent to the gastroenterologist for the constipation.

00:44:55.360 | You get sent to the rheumatologist

00:44:57.880 | for your autoimmune issues.

00:44:59.620 | You maybe get sent to an endocrinologist

00:45:02.440 | if you've got thyroid problems.

00:45:04.560 | And there's very little collaboration between these groups.

00:45:08.820 | So even though there's an understanding

00:45:10.620 | of the network effect, in real life,

00:45:13.840 | it's not happening.

00:45:15.040 | - Let's go deeper down that path

00:45:19.840 | 'cause you point out something really important

00:45:21.680 | and you've mentioned constipation a few times.

00:45:24.500 | Can we view constipation as a serious enough symptom

00:45:27.360 | that it warrants an immediate intervention?

00:45:29.200 | That is, does it flag or signal problems

00:45:33.120 | that are severe enough that that should be the issue

00:45:34.960 | that's dealt with for anybody that's experiencing it?

00:45:38.560 | And I mean, it's sort of an odd topic for many people

00:45:40.560 | 'cause they think, oh, you know, bowel movements

00:45:41.980 | or there's that kind of pre-adolescent humor around this.

00:45:45.580 | But I think it's so important.

00:45:47.240 | What I'm hearing you say is that constipation

00:45:49.960 | is far more common in women

00:45:51.240 | and it signals many problems occurring.

00:45:55.180 | Does that mean that women should address constipation?

00:45:58.440 | And if so, what's the best way to address constipation?

00:46:01.600 | - Yeah, I love this question because you're doing,

00:46:05.560 | can we have a quick little meta conversation?

00:46:07.600 | So you're doing something that I knew you would do,

00:46:10.120 | which is you're teaching me something and you're changing,

00:46:14.040 | like there's a social genomics thing happening

00:46:16.120 | where you're changing my thought about this.

00:46:18.280 | So I just wanted to acknowledge that.

00:46:19.640 | Thank you. - Thank you.

00:46:20.480 | Well, I think for me, when I hear that there's a kind of,

00:46:23.800 | you're talking about a phenotype,

00:46:25.240 | constipation is a phenotype.

00:46:26.460 | It's one that people generally don't wear a T-shirt

00:46:29.160 | explaining it to people, but that I'm guessing

00:46:31.660 | anything to do with sexual health, bowel health, urology,

00:46:36.260 | people just don't talk about for all sorts of reasons.

00:46:40.020 | And those reasons are probably so obvious

00:46:42.100 | that they're not even worth discussing.

00:46:43.960 | And also because we won't change them

00:46:45.600 | except by talking about them.

00:46:47.360 | So if you say women are far more constipated

00:46:51.560 | and that's signaling a larger set of problems,

00:46:54.560 | then my immediate thought is,

00:46:55.960 | well, will relieving constipation,

00:46:57.920 | pun intended retroactively,

00:47:01.920 | will that assist in a great number of issues

00:47:07.400 | and/or will it get them down the road

00:47:08.980 | of thinking about those other issues more specifically?

00:47:11.120 | Like, do I need more magnesium

00:47:12.520 | or should I be putting vegetables in my smoothie?

00:47:15.040 | So I'm curious about constipation as a target

00:47:18.360 | for intervention that then opens up

00:47:20.440 | a bunch of other discussions.

00:47:21.520 | 'Cause there are these certain nodes

00:47:22.800 | in the mental health, physical health space

00:47:25.820 | that when someone, like we talk a lot

00:47:27.880 | of deliberate cold exposure, do I think it's magic?

00:47:30.280 | No, but I think that if someone's getting themselves

00:47:32.100 | into a cold shower once a day,

00:47:33.680 | it opens up a number of questions about themselves

00:47:36.460 | and reveals a number of things to themselves.

00:47:38.320 | I'm like, how do I buffer stress?

00:47:40.360 | What sorts of levels of control do I actually have?

00:47:42.440 | And on and on.

00:47:43.280 | So perhaps not the best example, but-

00:47:46.160 | - Some of us hate cold exposure.

00:47:47.940 | - Right, which is-

00:47:48.780 | - And we have like a gene that makes us stress out

00:47:51.620 | like you wouldn't believe with cold exposure.

00:47:53.400 | - Which I would argue makes it very likely

00:47:56.380 | that even 10 seconds of cold exposure

00:47:58.260 | gets you the effect that you want.

00:47:59.780 | As opposed to someone who adores cold exposure

00:48:01.600 | like a penguin, needs a lot more cold exposure

00:48:03.920 | for it to have the adaptive response.

00:48:05.820 | Anyway, that's my way of gumbing through that.

00:48:09.220 | Quite, you're quite correct.

00:48:12.320 | So-

00:48:13.160 | - So let's answer this question.

00:48:14.220 | - The constipation issue.

00:48:15.260 | - Yeah, so this is how you're changing

00:48:17.460 | the way I think about this.

00:48:19.260 | So you're asking, okay, instead of looking at constipation

00:48:22.180 | as a constellation of symptoms,

00:48:24.280 | what about if you just used it on its own

00:48:26.620 | as sort of a key indicator or signal of dysfunction

00:48:35.780 | with my network or maybe something broader?

00:48:38.860 | And I think that's right.

00:48:40.360 | So it makes me think of a few things.

00:48:43.420 | It makes me, you're also changing this book

00:48:45.600 | that I'm writing on autoimmunity and trauma.

00:48:47.780 | So thank you for that.

00:48:49.060 | So women experience more trauma than men.

00:48:53.380 | This is well-established.

00:48:54.660 | If you look at the ACE studies that were done

00:48:57.220 | by the CDC and Kaiser in 1998,

00:49:00.100 | we know that men for the most part,

00:49:02.200 | middle-aged men have about 50% of them

00:49:07.200 | experience significant trauma

00:49:09.540 | as defined by the ACE questionnaire.

00:49:11.780 | Women are at 60% and that's pretty durable since 1998.

00:49:16.220 | So women have more, they have different forms of abuse,

00:49:20.220 | much more likely to have sexual abuse.

00:49:22.260 | They have a different HPA response than men.

00:49:27.200 | Their perceived stress tends to be higher

00:49:31.100 | and I'm generalizing for a population.

00:49:33.120 | Side note, in precision medicine, we don't do that.

00:49:36.940 | We do medicine for the individual, not the population,

00:49:40.060 | not medicine for the average.

00:49:41.600 | And so if you look at the physiology of a female,

00:49:47.480 | I think that constipation and that need to control

00:49:52.240 | and restrain and hold things in,

00:49:54.760 | tighten the anal sphincter,

00:49:58.100 | I think that's part of the physiology.

00:50:00.380 | So I'm veering away from the science,

00:50:02.240 | but I do think that it is a really important signal

00:50:06.220 | to pay a lot of attention to.

00:50:08.340 | Now, you also asked about microbiome testing.

00:50:10.940 | Should we do that or do you-

00:50:11.780 | - Yeah, well, I have a couple more questions

00:50:13.420 | about constipation.

00:50:14.400 | I never thought I'd ask this many questions

00:50:15.780 | about constipation, but now I'm fascinated.

00:50:17.620 | By the way, also this morning,

00:50:18.620 | I taught medical students at Stanford

00:50:19.840 | about the fact that we are basically a series of tubes.

00:50:21.940 | So you talked about the anal sphincter.

00:50:23.700 | We are a set of sphincters from one end to the other.

00:50:26.140 | I mean, we are a set of tubes,

00:50:27.420 | our nervous system being one of those tubes.

00:50:29.100 | And I think in Eastern medicine,

00:50:31.060 | they talk about the various locks

00:50:32.380 | between those tubes and chambers,

00:50:33.840 | and it's not without coincidence.

00:50:35.860 | There's some real wisdom there, of course.

00:50:37.840 | - Wait, did you just talk about energetic anatomy?

00:50:41.020 | - More or less.

00:50:41.860 | I didn't say the word chakras,

00:50:42.700 | but I might in passing.

00:50:44.700 | - Well, it's the bandhas that you work with.

00:50:46.100 | - The bandhas, right, are the sphincters, right?

00:50:49.460 | Yes, that's right.

00:50:50.620 | Thank you for that.

00:50:51.840 | So what defines constipation?

00:50:55.140 | I mean, in other words, let's think about the healthy,

00:50:57.140 | rather than thinking about the unhealthy,

00:50:58.340 | is how many bowel movements

00:51:00.700 | should a woman or a man have per day,

00:51:05.100 | assuming, and this is where it gets tricky,

00:51:07.220 | because some people are doing time-restricted feeding,

00:51:09.100 | some people are eating more,

00:51:09.940 | some people are eating more fiber, more bulk,

00:51:11.420 | larger meal at the end of the day,

00:51:12.460 | a larger meal at the beginning of the day.

00:51:13.860 | We will never be able to sort out all those variables,

00:51:16.980 | but on average, how many bowel movements

00:51:21.220 | and is timing during the day for bowel movements

00:51:24.420 | at all informative?

00:51:26.440 | - What works for you?

00:51:28.300 | - Well, when I'm asleep,

00:51:30.020 | generally I don't want a bowel movement,

00:51:31.500 | so I'm going to be like most people, right?

00:51:33.020 | - Well, sleep is primary for you.

00:51:34.340 | - Right, exactly.

00:51:35.740 | I always assumed that morning time

00:51:38.140 | was a healthy time for bowel movements,

00:51:41.780 | and I think almost everybody, babies included,

00:51:47.040 | recognize the feeling of being lighter and more energetic

00:51:51.120 | when they've evacuated their colon.

00:51:54.480 | In fact, so much so that I'm obsessed

00:51:56.380 | with Jungian and Freudian psychology

00:51:58.460 | that the first thing we learn when we come into this world

00:52:00.700 | is that we want something,

00:52:01.820 | we feel some sort of autonomic arousal, stress,

00:52:06.020 | whether or not it's food or warmth

00:52:07.980 | or the need to have a bowel movement.

00:52:09.500 | And one of the first things that parents learn

00:52:11.020 | is how to recognize that,

00:52:12.580 | not by the odor coming from the diaper,

00:52:15.020 | but by the look on the baby's face or their agitation.

00:52:17.620 | Agitation signals the need for some sort of relief,

00:52:21.500 | temperature relief, food relief,

00:52:23.740 | evacuating the bowel relief.

00:52:25.020 | So my understanding is that as autonomic arousal increases

00:52:28.900 | in the early part of the day,

00:52:29.820 | ideally after a good night's sleep,

00:52:31.820 | that bowel movements become more likely,

00:52:33.380 | unless that arousal becomes so great

00:52:35.340 | that then people feel sort of quote unquote locked up

00:52:38.860 | because of the balance of the autonomic features.

00:52:42.060 | So early day, I'm guessing,

00:52:44.100 | and again in the second half of the day,

00:52:45.600 | and here I'm totally guessing,

00:52:47.260 | and certainly not having to wake

00:52:49.020 | in the middle of the night.

00:52:50.420 | Yeah, those are my best guesses.

00:52:53.740 | - That's great.

00:52:54.820 | So I would agree with that.

00:52:56.580 | When I was at Harvard Medical School in UCSF for residency,

00:53:00.140 | I was taught that constipation

00:53:01.820 | is having a bowel movement less frequently

00:53:05.180 | than once every three days.

00:53:06.980 | - Sorry, I don't think I've ever laughed out loud

00:53:10.260 | on this podcast as a consequence

00:53:11.940 | of textbook medical knowledge.

00:53:14.060 | Are you kidding me?

00:53:15.140 | - Is that ridiculous?

00:53:15.980 | - Well, that sounds like, and here, pun intended,

00:53:18.060 | that sounds like the conclusion of some very-

00:53:22.020 | - Constipated person. - Emotionally

00:53:23.460 | and in other ways constipated individuals.

00:53:27.440 | And again, this might seem like an odd conversation,

00:53:29.820 | but the discussion around constipation

00:53:32.180 | is present in psychological literature

00:53:35.920 | because of this relationship to the autonomic system.

00:53:38.660 | - Well, it's a metaphor in literature.

00:53:41.060 | It's crucial.

00:53:42.340 | So you spoke to a number of different threads

00:53:45.200 | that I think are important here.

00:53:46.900 | So that's the definition that I learned.

00:53:48.780 | And I heard that and I was like, hell no,

00:53:51.060 | that doesn't work for me.

00:53:52.340 | It doesn't work for anyone I know.

00:53:54.820 | And I spent a lot of time, especially in medical school

00:53:59.020 | and in my internship where you rotate on medicine,

00:54:02.660 | dis-impacting women, like older women who come in

00:54:06.660 | who haven't had a bowel movement in a month.

00:54:08.940 | - Whoa.

00:54:09.780 | - And let me tell you, that is not nice for anybody.

00:54:13.120 | - Believe me, I became a scientist and a physician

00:54:15.500 | for a number of reasons, both positive and negative.

00:54:18.700 | That's one of them.

00:54:19.820 | - Yeah, so my definition of constipation

00:54:23.740 | as a Western, mostly white girl is that

00:54:28.740 | if you're not having a bowel movement every single morning

00:54:32.580 | and you have a feeling of complete evacuation,

00:54:36.500 | anything less than that is constipation.

00:54:39.820 | So that's how I define it.

00:54:41.440 | If you're in India and you're eating food

00:54:45.380 | that's got a fair amount of microbes in it,

00:54:47.780 | it's less sanitary, I'm using that word,

00:54:51.560 | as carefully as I can.

00:54:54.900 | Generally, they have a bowel movement after every meal.

00:54:58.820 | But they've got a different microbiome,

00:55:00.260 | they're exposed to different microbes.

00:55:01.900 | Here in the US, I would say Wednesday,

00:55:03.940 | you also spoke to something very important,

00:55:08.120 | which is the balance between

00:55:11.100 | the parasympathetic nervous system,

00:55:13.000 | rest and digest and poop,

00:55:15.180 | versus the sympathetic nervous system,

00:55:17.420 | kind of the on button, you know,

00:55:20.100 | fight, flight, freeze, fawn.

00:55:23.100 | So I think for those of us who've got issues

00:55:28.460 | with autonomic balance, it can lead to constipation.

00:55:33.460 | And I like that constipation could be pulled out

00:55:37.220 | and kind of writ larger as an important signal.

00:55:40.740 | - What sorts of tools do you recommend people use

00:55:43.260 | to relieve constipation in eating more fiber?

00:55:48.260 | Sounds like reducing stress is going to be a huge one.

00:55:52.220 | - Yes.

00:55:53.060 | - What are your favorite stress reduction tools?

00:55:56.060 | I like to divide these into real-time tools.

00:55:59.780 | So a big proponent of like physiological sighing,

00:56:03.220 | real-time, you know, these sorts of things,

00:56:04.680 | but things that can really lower the baseline

00:56:07.960 | on stress overall to facilitate constipation

00:56:11.980 | and other broad indicators of health.

00:56:15.780 | - So I'm not a fan of lowering stress.

00:56:21.180 | I'm a fan of lowering perceived stress.

00:56:23.660 | And I think the distinction is really important.

00:56:26.060 | I learned when I was in my 30s

00:56:30.740 | that I was a massive stress case and I didn't know it.

00:56:35.620 | It was just sort of, I think I, through residency,

00:56:39.420 | through working 120 hours a week,

00:56:41.000 | I just was so accustomed and sort of entrained.

00:56:44.620 | - That was 120, not under 20 folks.

00:56:48.220 | Not unusual in medicine.

00:56:50.300 | - Well, they've changed training

00:56:52.200 | so that you work no more than 80 hours a week now,

00:56:55.100 | but that was before my time.

00:56:57.460 | So I became accustomed to a massive amount of cortisol,

00:57:02.460 | massive, and I would say I've spent the past 20 years

00:57:10.480 | really working on perceived stress to find,

00:57:13.500 | I think all of us need an a la carte menu

00:57:16.460 | of what is most effective.

00:57:18.940 | So what works for me now at my age is different than,

00:57:23.080 | you know, the TM I did as a college student,

00:57:25.900 | transcendental meditation, it's different than the,

00:57:28.860 | I became a certified yoga teacher when I was in my 30s.

00:57:31.460 | That is very effective for a lot of people.

00:57:34.220 | It wasn't enough for my matrix.

00:57:37.660 | I do holotropic breath work.

00:57:40.080 | I didn't read it, but I saw that she just had a paper

00:57:43.120 | in cell on your sign and it kind of,

00:57:47.340 | it made me think like, teach me how to sigh,

00:57:50.800 | teach me how to sigh, like,

00:57:52.580 | can you say a little bit about that?

00:57:54.120 | Like, how do you do it?

00:57:55.160 | - Yeah, very briefly, that study was,

00:57:56.880 | we wanted to find a minimal effective dose intervention.

00:58:00.120 | - Yeah, five minutes.

00:58:00.960 | - So I just wanted, yeah, so five minutes a day.

00:58:02.360 | We needed to figure out what people would do every day.

00:58:04.360 | And we were monitoring subjective mood, et cetera,

00:58:07.680 | but also biometrics remotely.

00:58:09.600 | So it was kind of a nice study.

00:58:10.440 | - Which biometrics?

00:58:11.520 | HRV?

00:58:12.360 | - HRV, nighttime sleep.

00:58:14.700 | - Portisol?

00:58:15.820 | - I wish.

00:58:16.880 | So this was done during the pandemic,

00:58:18.880 | more than a hundred subjects.

00:58:20.220 | The advantage was that we got data 24 hours a day

00:58:23.060 | 'cause they're pinging us in their data wearing-

00:58:25.640 | - HRV 24?

00:58:26.840 | - Yeah.

00:58:27.680 | - Nice.

00:58:28.500 | - So that was nice.

00:58:29.340 | Resting heart rate, subjective mood,

00:58:31.040 | we would get in touch with them daily.

00:58:32.780 | So when people were swapped between groups,

00:58:35.460 | like any good study,

00:58:36.300 | but five minutes a day of sort of standard, if you will,

00:58:39.760 | forgive me, meditations or just sitting,

00:58:41.560 | no instructions about how to breathe,

00:58:42.940 | just focusing on closing their eyes

00:58:45.600 | and focusing on focusing.

00:58:47.520 | Another group did box breathing.

00:58:50.820 | Inhale, hold, exhale, hold for equal durations.

00:58:53.200 | The duration of each of those inhales and holds

00:58:55.680 | was set by their carbon dioxide tolerance.

00:58:58.280 | So somewhere between three and eight seconds,

00:59:01.500 | depending on how well they regulate to carbon dioxide.

00:59:04.440 | Another group did cyclic sighing.

00:59:06.700 | So this would be double inhale through the nose.

00:59:08.660 | So big inhale through the nose.

00:59:10.180 | [inhales and exhales]

00:59:13.260 | Followed by a, to lungs, empty exhale.

00:59:17.620 | That second inhale after the first big long inhale

00:59:20.700 | through the nose is really important

00:59:21.780 | because it makes sure that all the collapsed avioli

00:59:24.820 | of the lungs snap open. - Totally.

00:59:26.520 | - And then the exhale,

00:59:27.360 | you offload a lot of the carbon dioxide.

00:59:29.260 | - That's very similar to holotropic breath work.

00:59:31.660 | - Yes, not unlike holotropic breath work.

00:59:35.360 | Little bit pranayama-ish,

00:59:37.860 | but the exhale is rather passive as opposed to active.

00:59:42.100 | And then the fourth category was cyclic hyperventilation,

00:59:45.120 | which is a lot like Tummo, AKA Wim Hof-ish breathing,

00:59:48.800 | different than Wim Hof breathing.

00:59:50.200 | So this would be, [inhales and exhales]

00:59:51.900 | so very active inhales and exhales.

00:59:54.960 | Every 25 cycles of inhale exhale, that would be one cycle.

00:59:58.100 | Long exhale, hold lungs empty.

01:00:00.820 | 15 to 30 seconds.

01:00:03.180 | Then repeat for about five minutes.

01:00:05.980 | Everyone did that for five minutes.

01:00:07.300 | And what we found was that the cyclic sighing

01:00:09.100 | led to the greatest improvements in mood around the clock,

01:00:12.220 | not just around the practice or during the practice,

01:00:15.060 | as well as lowered resting heart rate,

01:00:17.740 | improvements in sleep, et cetera.

01:00:20.020 | - And you got it published in Cell.

01:00:21.700 | That's so amazing. - Yeah, we were very fortunate.

01:00:22.940 | Yeah, we were very fortunate.

01:00:23.780 | I think that, thankfully, the reviewers and editors

01:00:28.220 | understood that these minimal intervention things

01:00:31.140 | hopefully are going to be of use to people.

01:00:33.100 | - So useful to people.

01:00:34.660 | I mean, how often do you read a paper like that

01:00:37.280 | that could offer a behavior change

01:00:40.940 | that is so easy to implement?

01:00:43.300 | I mean, I love that question.

01:00:45.680 | - Thank you.

01:00:46.520 | - So what about, did you tell them not to drink?

01:00:49.400 | Because alcohol has such a huge effect on HIV.

01:00:51.820 | - Yeah, so in this case, we didn't tell them

01:00:53.360 | to alter anything else about their behavior.

01:00:55.420 | - Just hoping it was background kind of across the same--

01:00:57.660 | - All groups.

01:00:58.500 | - Yes, and some were Stanford students.

01:01:00.120 | Others were from the general population.

01:01:02.700 | - Any frat boys that were drinking heavily?

01:01:05.780 | - Probably not.

01:01:06.620 | Well, during the pandemic, I think alcohol intake

01:01:08.620 | went way up across the board.

01:01:11.420 | I mean, if I had a magic wand,

01:01:13.140 | I would ask that people either not drink

01:01:15.140 | or drink two drinks per week maximum.

01:01:17.260 | At least that's my understanding of the literature.

01:01:19.960 | - Are you familiar with the WHOOP data with alcohol?

01:01:22.420 | - No, but we have a collaboration with WHOOP

01:01:24.220 | through that paper.

01:01:25.740 | And it certainly disrupts patterns of nighttime sleep.

01:01:28.740 | In particular, from my understanding,

01:01:30.840 | that first phase of sleep that's related

01:01:33.280 | to the massive growth hormone release

01:01:34.980 | that we all really need and want in the first--

01:01:37.020 | - And you didn't measure growth hormone.

01:01:38.420 | - We did not, no.

01:01:39.460 | The second iteration of this study

01:01:40.980 | will certainly include free cortisol by saliva.

01:01:43.460 | - A hormone panel?

01:01:44.300 | - Yeah, hormone panels.

01:01:45.140 | Well, I'm beginning to think that we should also

01:01:47.380 | be asking people how often they're going to the bathroom

01:01:49.200 | and what time of day.

01:01:50.040 | - Yes.

01:01:50.860 | - I mean, this thing around constipation

01:01:52.220 | is super interesting.

01:01:54.060 | And I think that plus blood markers,

01:01:56.740 | and then I'm very excited to learn

01:01:58.600 | that urine contains additional markers

01:02:02.280 | that could be informative.

01:02:03.260 | So yeah, it was a fun study,

01:02:05.800 | not easy study to do with that number of subjects.

01:02:09.440 | - Takes a lot of training for your research assistants.

01:02:12.220 | - Yeah, it was a big group.

01:02:13.060 | It was nine people in our group and three clinicians

01:02:15.860 | and a lot of phone calls and a lot of back and forth.

01:02:18.340 | But, you know, and thank you to the subjects

01:02:20.300 | who served as the real life guinea pigs.

01:02:22.800 | So yeah, I think that stress, you know,

01:02:24.440 | people's, I think people are starting to appreciate

01:02:26.900 | that there are ways that they can relieve their stress

01:02:28.800 | that don't only fall under the categories of vacation

01:02:33.620 | and meditation.

01:02:34.460 | But I want to say that meditation

01:02:36.080 | is obviously a wonderful tool.

01:02:38.460 | It's just, it's a tool not unlike any other tool

01:02:42.100 | that is great for some people and less great for others.

01:02:45.100 | - Well, certainly it's a great tool

01:02:46.380 | and it's got such a scientific basis behind it.

01:02:49.480 | But there's so many things on this a la carte menu.

01:02:52.760 | Sex, orgasm, connection, feeling heard and seen and loved.

01:02:57.760 | - Yeah, let's talk about that.

01:03:01.940 | You know, you mentioned earlier that all these stress

01:03:03.540 | factors, you said patriarchy, right?

01:03:05.940 | But I think what, if I may, at risk of just strengthening

01:03:10.940 | that statement, I mean, that to me is signaling

01:03:15.140 | a bunch of other factors around, as you said,

01:03:17.640 | like keeping things in.

01:03:20.560 | What do you think explains, let's talk about that.

01:03:25.560 | Because I think that that's likely to have raised

01:03:27.640 | a certain flag in people's minds.

01:03:28.800 | Like what exactly is she talking about?

01:03:30.360 | Are you talking about less opportunity?

01:03:32.560 | Are you talking about less opportunity to vocalize?

01:03:37.200 | Are you talking about less opportunity

01:03:38.560 | to vocalize and be heard?

01:03:40.080 | I mean, I realize that there are an infinite number

01:03:41.520 | of variables, but given that it sounds

01:03:43.200 | like a really strong input to the system,

01:03:47.800 | what I mean by that is that psychology is influencing

01:03:50.700 | biology and you're saying that these power dynamics,

01:03:55.700 | structures and dynamics are impacting.

01:03:59.420 | I'd love to, let's hear your thoughts on that.

01:04:00.960 | Because I hate to let a flag like that go by

01:04:04.860 | without fleshing it out.

01:04:05.900 | - Never waste a good flag.

01:04:07.460 | - Well, and let's preface it by just saying that like,

01:04:10.020 | people will have different opinions on this and that's,

01:04:11.980 | and I think that's healthy.

01:04:12.860 | And like with the discussion about constipation,

01:04:14.940 | let's talk about what people aren't willing to talk about

01:04:16.920 | when it comes to health.

01:04:17.860 | - Love it.

01:04:18.940 | So we might need to talk about patriarchy on part two,

01:04:22.700 | but I'll give you some material that I've been working with.

01:04:25.700 | I started, I did not even understand the existence

01:04:30.740 | of patriarchy until I was a bioengineering undergraduate.

01:04:34.440 | - At MIT, I should mention,

01:04:36.020 | which has always had a bit of a skewed mail

01:04:40.780 | in terms of faculty numbers.

01:04:42.820 | - Well, that's true at most universities.

01:04:44.920 | - That's true, well, my postdoc advisor was the late

01:04:46.940 | Ben Barris, who was a female to male transition,

01:04:51.100 | transgender, first transgender member

01:04:53.160 | of the National Academy of Sciences,

01:04:54.340 | one of my closest friends.

01:04:55.240 | Unfortunately, he died of pancreatic cancer.

01:04:57.780 | We were very, very close.

01:04:58.780 | They're actually making a documentary about Ben.

01:05:00.900 | But Ben, this is interesting,

01:05:02.340 | Ben went to MIT because he wanted to be around a lot of men.

01:05:06.780 | That's a lesser known fact,

01:05:08.040 | but then he was a very strong advocate for women.

01:05:11.500 | He went as Barbara when he was Barbara.

01:05:14.140 | And by the way, he's given me permission to share all this.

01:05:17.780 | Prior to his death,

01:05:18.720 | I recorded a lot of conversations with Ben.

01:05:21.820 | I only ever knew him as Ben, by the way.

01:05:23.680 | But when he was at MIT, he was identified female.

01:05:28.680 | And he later talked about the intense suppression oppression,

01:05:33.740 | literally is how he described it,

01:05:37.120 | especially given that he was performing so well.

01:05:40.040 | - Yes, so you just defined patriarchy.

01:05:43.420 | You did it yourself.

01:05:44.700 | A couple things.

01:05:46.900 | When I was in bioengineering,

01:05:50.160 | I took a women's studies class.

01:05:53.220 | And it was all about teaching undergraduates

01:05:56.340 | about the existence of patriarchy,

01:05:58.700 | which I would define maybe at its simplest as power over.

01:06:02.840 | I'm not saying men are patriarchy.

01:06:06.660 | I'm saying something very different, which is power over.

01:06:11.420 | Let me correct one thing that you said.

01:06:13.720 | I didn't go to MIT as an undergraduate.

01:06:16.440 | So I was in Alaska,

01:06:19.060 | and I went to the University of Washington

01:06:21.060 | for bioengineering.

01:06:22.340 | - In Seattle. - In Seattle.

01:06:24.220 | I dropped out of a graduate program in bioengineering

01:06:28.380 | to go to the Harvard MIT program

01:06:32.260 | for health sciences and technology in Boston.

01:06:35.380 | - Thanks for that clarification.

01:06:36.680 | University of Washington, also a wonderful place.

01:06:39.060 | I have many, many, many, many, many

01:06:41.780 | wonderful close colleagues there.

01:06:43.220 | It's an incredible place, especially for vision science.

01:06:46.320 | - It's especially good for engineering, bioengineering.

01:06:49.540 | But yeah, so my MD is jointly between MIT and Harvard,

01:06:54.540 | and it's the oldest, maybe largest,

01:06:59.780 | although Harvard says this a lot,

01:07:01.620 | program for biomedical engineers

01:07:04.220 | and MD PhD's physician scientist training program.

01:07:09.220 | - Great, thanks for that clarification.

01:07:12.260 | I'm going to blame the internet for this one.

01:07:14.420 | I am, I think we need to send our Wikipedia editors out.

01:07:18.180 | - I think LinkedIn is correct.

01:07:19.660 | - Okay, great.

01:07:20.620 | Well, Wikipedia editors, note,

01:07:23.580 | get out there and make the correction, now you heard it.

01:07:27.020 | So stress, what you're really talking about

01:07:30.480 | is systemic stress in the body as a consequence,

01:07:34.520 | excuse me, of systemic stress of environment.

01:07:37.200 | - That's right.

01:07:38.240 | But there's, you know, there's particular forms of it.

01:07:40.680 | I would say this also relates to white privilege.

01:07:44.680 | It relates to racism.

01:07:48.980 | And when you look at, you know,

01:07:51.300 | kind of the way that systems, including my beloved MIT,

01:07:56.300 | the way that they're set up is that might makes right.

01:08:00.200 | And generally the people that are the strongest,

01:08:03.440 | you know, big men, strong men,

01:08:05.180 | they're the ones who tend to be the most successful.

01:08:08.300 | So for people who are BIPOC,

01:08:10.940 | for people who don't have white privilege,

01:08:14.220 | for women, it's a different experience.

01:08:16.780 | And so I'm using patriarchy as kind of a umbrella here,

01:08:21.140 | but it connects to many other things.

01:08:24.580 | - I'd like to take a brief break

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01:08:47.460 | The problem with a lot of blood and DNA tests out there,

01:08:49.520 | however, is that you get data back about metabolic factors,

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01:09:07.460 | in order to adjust the numbers of those metabolic factors,

01:09:10.060 | hormones, lipids, and other things

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01:09:27.820 | to get 20% off.

01:09:29.400 | I want to use this as an opportunity

01:09:30.860 | to A, keep this in mind as we turn to a question

01:09:34.820 | that I didn't close the hatch on earlier,

01:09:37.700 | and it's my fault, which is I'm now clear on the fact

01:09:40.700 | that a woman in her late teens, early 20s

01:09:44.180 | ought to know something

01:09:45.000 | about her testosterone, estrogen, thyroid, cortisol levels,

01:09:47.900 | should start at least thinking about her microbiome,

01:09:51.780 | should be thinking about how many bowel movements

01:09:56.220 | and the timing of those bowel movements per day, really.

01:10:00.060 | And I'm assuming that what I just described

01:10:03.820 | is also true for women in their 20s, 30s, 40s, 50s,

01:10:08.580 | on up to hundreds, is that correct?

01:10:11.660 | - That's correct, but I would say

01:10:12.740 | that there are differential opportunities by decade.

01:10:17.740 | So I'm glad she's circled it back

01:10:21.820 | to teenagers and testosterone,

01:10:24.820 | because I think if you know, for instance,

01:10:28.020 | in your teenage years, that you have high androgens

01:10:32.640 | and that you've got this potential phenotype

01:10:35.380 | way into the future that you may not even notice,

01:10:37.380 | I mean, maybe you notice you've got a few extra hairs

01:10:39.640 | on your chin or something,

01:10:41.800 | if you know that your testosterone is elevated

01:10:43.900 | or some other androgen, it might change the arc

01:10:47.020 | of how you take care of yourself.

01:10:48.740 | So I think that could be very helpful in your teenage years.

01:10:52.100 | In your 20s, for people who are a stress case like me,

01:10:55.820 | so age 27 on the wards at UCSF,

01:11:00.820 | if I had known that I was such a high cortisol person,

01:11:03.700 | I think I would have done things differently.

01:11:06.500 | I would have changed my behavior.

01:11:08.700 | And I don't know because I didn't base case these,

01:11:11.560 | but your testosterone can decline starting in your 20s,

01:11:16.560 | kind of depending on how much stress your matrix is under.

01:11:21.740 | So for women that can start as early as 28,

01:11:24.580 | usually your testosterone declines by about 1% per year.

01:11:28.740 | - What level of testosterone do you like to see in a woman

01:11:31.340 | once she's sort of post, let's say after age 25?

01:11:34.520 | What kind of range is healthy?

01:11:35.780 | I know what the reference range is only

01:11:37.980 | because I know one could look it up.

01:11:39.540 | I don't know off the top of my head, admittedly.

01:11:41.960 | But what's a kind of a nice reference point there?

01:11:46.960 | - So the way I tend to describe this on podcasts

01:11:49.580 | is the top half of the normal range.

01:11:52.260 | - Great.

01:11:53.360 | - So that I think is a good benchmark.

01:11:56.300 | For PCOS, generally it's much higher than that.

01:12:01.300 | I've seen patients with PCOS

01:12:03.020 | where their total testosterone is 100 to 200.

01:12:05.780 | - Do they always have peripheral manifestations of that?

01:12:08.160 | A little bit of hair, the skin plaques I've heard about,

01:12:10.940 | so darkened skin plaques.

01:12:11.940 | - Irregular periods.

01:12:13.140 | - Regular periods.

01:12:13.980 | I get a lot of questions about PCOS.

01:12:17.300 | - Yeah.

01:12:18.580 | - And you're the first person we've had on this podcast

01:12:21.540 | that's really qualified to talk about PCOS in a real way.

01:12:25.260 | So here we're talking about too many androgens,

01:12:27.740 | cysts on the ovary, irregular ovarian,

01:12:30.740 | excuse me, I keep saying that,

01:12:32.820 | ovulatory/menstrual cycle.

01:12:35.020 | What are some other indicators?

01:12:38.920 | And do you recommend that women

01:12:41.580 | start taking androgen blockers?

01:12:43.380 | Or, I mean, how do,

01:12:45.220 | it seems to be a lot of PCOS out there.

01:12:46.780 | I'm hearing about it a lot.

01:12:48.980 | - So glad you asked about this.

01:12:50.640 | So PCOS is one of those really poorly understood conditions

01:12:55.640 | that gets, it kind of flies below the radar

01:12:59.020 | until a woman wants to get pregnant

01:13:01.260 | or she's got some other issue that drives her to a physician.

01:13:05.080 | The problem is that it is a syndrome, right?

01:13:09.540 | So polycystic ovary syndrome,

01:13:12.280 | sometimes polycystic ovarian syndrome.

01:13:15.540 | And syndromes don't necessarily fit together

01:13:18.340 | into a really clear diagnostic criteria.

01:13:22.540 | So in this instance,

01:13:24.580 | there are three different criteria that we look for.

01:13:27.080 | So cysts on the ovaries,

01:13:28.780 | having clinical manifestations of hyperandrogenism,

01:13:33.540 | so that could be hirsutism, acne, other things,

01:13:36.780 | and then usually irregular periods.

01:13:39.140 | And the way that that's defined,

01:13:40.540 | at least by the latest criteria,

01:13:43.500 | is having a period every 35 days or less.

01:13:47.740 | So typical cycle length, 28 days, 35 days,

01:13:51.180 | you're skipping a period here and there.

01:13:53.520 | So those are the criteria that we use to diagnose PCOS.

01:13:57.660 | There are about four different systems out there

01:14:00.860 | in the literature for diagnosing PCOS,

01:14:02.900 | which is where it starts to get confusing.

01:14:05.580 | So there's some women who have no cysts on their ovaries,

01:14:10.060 | but they've got hirsutism

01:14:12.000 | and they've got irregular periods.

01:14:13.920 | - Could you define hirsutism?

01:14:15.300 | - Hirsutism is increased hair growth,

01:14:17.360 | usually in places that you don't want it.

01:14:19.460 | So for women, it can be kind of male pattern.

01:14:21.960 | They might notice it on their breasts, on their chest.

01:14:24.660 | And then there's, of course, a familial quality to that.

01:14:30.280 | Like I was just looking at a paper last night

01:14:31.900 | looking at Israelis and how much hirsutism they have

01:14:35.480 | and whether this is related to CAG repeats

01:14:38.660 | on the androgen receptor.

01:14:40.700 | - Do they get, not Israelis,

01:14:42.240 | but do women who might have PCOS

01:14:45.800 | experience androgenic alopecia, so hair loss,

01:14:49.000 | that sort of of the quote unquote male pattern baldness?

01:14:51.720 | Of course, it's androgen pattern baldness

01:14:53.720 | as opposed to male.

01:14:54.940 | We're talking about testosterone, DHT related.

01:14:57.220 | - Sometimes, you know,

01:14:58.680 | this is where I'm going to invoke clinical experience

01:15:01.160 | rather than what I've seen in the literature.

01:15:04.360 | Women definitely can have some androgenic alopecia.

01:15:08.960 | I tend to see it later in life.

01:15:11.660 | But this is an important point

01:15:12.980 | because we think of PCOS as, you know,

01:15:15.800 | I was just talking about it in teenage years.

01:15:17.700 | Like wouldn't it be nice to know

01:15:19.460 | that you have this phenotype and you're at risk

01:15:21.680 | for all the things that people are at risk for?

01:15:23.540 | And we haven't talked about glucose and insulin yet.

01:15:25.340 | We should.

01:15:26.180 | What we know is that PCOS is not just a problem

01:15:31.440 | in terms of irregular periods

01:15:33.580 | and then difficulty getting pregnant.

01:15:36.120 | So those are mostly problems in your 20s, 30s, early 40s,

01:15:40.660 | but it is a massive risk factor

01:15:44.100 | for cardiometabolic disease as you get older.

01:15:47.120 | So many people tend to pitch and hole PCOS

01:15:50.280 | as a problem of reproductive age.

01:15:52.380 | We have to be thinking of it

01:15:53.540 | over the entire female life cycle.

01:15:56.740 | And I would say it's even more important

01:15:59.140 | to consider it over the age of 50,

01:16:01.480 | you know, average age of menopause is 51 to 52,

01:16:04.360 | because we know that that elevated testosterone,

01:16:07.620 | the high androgens, are probably the greatest

01:16:11.460 | cardiometabolic driver of disease for women with PCOS.

01:16:16.460 | Now, one other thing I wanna mention,

01:16:19.300 | and I still have my notes

01:16:20.580 | that we're gonna talk about microbiome testing

01:16:22.180 | 'cause that's such a fun subject.

01:16:23.820 | What I was taught to do, again,

01:16:28.700 | saying this with so much love

01:16:30.060 | for the people who have taught me how to do medicine.

01:16:32.780 | What I was taught to do is that

01:16:34.220 | if you have a woman with PCOS,

01:16:35.580 | you make the diagnosis, you measure her testosterone,

01:16:38.140 | you see if she has acne, blah, blah, blah.

01:16:40.240 | You ask that woman one question.

01:16:43.460 | Do you wanna get pregnant or not?

01:16:47.280 | So then you have these women with PCOS

01:16:50.960 | who get started on a birth control pill

01:16:52.920 | if they don't wanna get pregnant.

01:16:54.460 | If they wanna get pregnant,

01:16:55.920 | then you help them get pregnant

01:16:57.640 | by addressing some of these PCOS issues.

01:17:00.020 | Like maybe you give them Clomid,

01:17:01.500 | or you do something to make them ovulate more frequently.

01:17:04.720 | That is the way that

01:17:06.740 | most conventional medicine approaches this,

01:17:09.020 | and it does women a gigantic disservice.

01:17:11.220 | So one of the things I'm speaking into

01:17:13.180 | is the gender gap that exists.

01:17:16.160 | So my feeling is that the research money

01:17:20.540 | that goes into women's health is abysmal

01:17:23.200 | compared to what goes into men's health.

01:17:25.300 | - Really?

01:17:26.120 | - And I think that's changing,

01:17:27.280 | but there's also a huge lack of awareness

01:17:29.700 | of sex and gender differences

01:17:31.320 | when it comes to the way that we construct clinical trials

01:17:35.080 | and other experiments.

01:17:36.200 | - Well, that's absolutely true.

01:17:37.160 | I mean, I've sat on NIH review panels

01:17:39.640 | for more than a decade now.

01:17:41.320 | I'm a regular standing member,

01:17:42.280 | which is only to say that I see the research

01:17:44.480 | as it's being proposed.

01:17:45.800 | - Yes.

01:17:46.620 | - And now it's required.

01:17:49.440 | No grant will get funded

01:17:50.680 | without sex as a biological variable.

01:17:53.200 | And here I'm, by the way, folks,

01:17:54.800 | this is sex, biological sex, the noun, not sex, the verb.

01:17:58.880 | Both are super interesting, obviously,

01:18:00.800 | but when we say sex as a biological variable,

01:18:03.520 | meaning even if it's a study on mice.

01:18:06.080 | - Where did that start though?

01:18:07.520 | - That didn't start that long ago.

01:18:08.520 | It must've been, I think we can thank,

01:18:11.160 | I don't want to miss attribute here.

01:18:12.200 | I think we can thank Francis Collins for insisting on this.

01:18:14.560 | - Amen, Francis and Bernadine Healy.

01:18:16.760 | Bernadine Healy has done so much to help us,

01:18:19.280 | but she made the Women's Health Initiative,

01:18:22.440 | which I hope we'll get to, which is a hot mess.

01:18:25.640 | Like so confusing, the data that came out of that.

01:18:28.560 | - Yes, and these trials are long.

01:18:29.980 | And so the data are only now starting to emerge.

01:18:32.200 | So just to be clear, I mean, I have a question

01:18:35.280 | that I don't think is going to take us off track,

01:18:36.720 | but this is, I'm going to pose this question as a hypothesis

01:18:39.420 | because I think it's likely to be a little bit

01:18:41.940 | of a, not a barbed wire question,

01:18:44.800 | but maybe like a prickly question when people first hear it,

01:18:47.920 | but it's posed as a hypothesis.

01:18:49.360 | You mentioned some of the psychosocial stress issues

01:18:52.960 | based on at the organizational level, institutional level,

01:18:56.380 | societal level, maybe right down to the family

01:18:59.140 | and just life that are biasing health outcomes

01:19:03.600 | for the worse in female populations, okay?

01:19:06.400 | You referred to as the patriarchy.

01:19:07.680 | I'm just trying to put,

01:19:09.360 | make sure that we're both talking about the same thing.

01:19:11.040 | And that's non-exhaustive, I realize.

01:19:13.220 | That's just a subset of the issues.

01:19:14.960 | I'm also hearing there's a lot more PCOS,

01:19:18.680 | which is hyperandrogenization of the ovary.

01:19:23.120 | In there, we're talking about, you mentioned it,

01:19:26.280 | excess testosterone, which females naturally

01:19:29.360 | have more testosterone than they do estrogen anyway,

01:19:32.000 | but we're talking about elevated levels.

01:19:34.120 | Here's a hypothesis.

01:19:37.180 | One hypothesis would be that the increased androgens

01:19:40.920 | and the PCOS are a consequence

01:19:43.640 | of the psychosocial conditions that are,

01:19:46.860 | I don't want to say forcing,

01:19:48.640 | but are biasing the need for females to think, behave,

01:19:55.020 | react, act in certain ways to survive, let alone thrive.

01:20:00.020 | Is that a, I don't say this

01:20:02.120 | for any kind of political correctness hypothesis.

01:20:04.980 | This is a, in my, this would be a fun, interesting,

01:20:08.320 | and I think important study to run, right?

01:20:10.680 | Depending on stress and the conditions,

01:20:12.800 | the specific type of stress,

01:20:15.800 | do females underproduce or overproduce androgens,

01:20:20.800 | or is it a neutral effect?

01:20:23.240 | Does that make sense?

01:20:25.120 | - I love this question.

01:20:26.640 | So let me just paraphrase the last part of it

01:20:29.140 | to make sure I got it.

01:20:30.860 | It sounds like what you're asking is,

01:20:32.860 | could PCOS or at least some phenotypes of PCOS

01:20:36.820 | be a response to what I'm calling patriarchy?

01:20:40.340 | And then you add a second part to it,

01:20:43.780 | which is do healthy women,

01:20:46.360 | like what is their production of testosterone like?

01:20:48.480 | Is that right?

01:20:49.320 | - Yes, and with the acknowledgement,

01:20:50.900 | I mean, you're the expert here.

01:20:53.160 | You're the physician clinician and expert in hormones,

01:20:55.540 | and I'm not, but with the understanding

01:20:58.440 | that absolute levels of hormones are interesting,

01:21:01.060 | but perhaps not as interesting

01:21:03.260 | as the ratios of testosterone to estrogen.

01:21:05.680 | So when we're talking about excess testosterone,

01:21:07.720 | we're really not talking about,

01:21:08.600 | oh, women making a lot of testosterone,

01:21:10.380 | because frankly, they already make a lot.

01:21:12.440 | Then most people that weren't aware of that,

01:21:14.980 | I wasn't aware that women make more testosterone

01:21:16.840 | than estrogen. - And we need it.

01:21:17.920 | - Right, and so it's not saying that testosterone in women

01:21:20.440 | is bad or is always a reaction to the environment,

01:21:23.120 | but when it becomes super physiological or hyper-elevated,

01:21:28.120 | I could imagine all sorts of social conditions

01:21:31.500 | that would create that, so in males and females,

01:21:36.020 | but here we're talking about PCOS in females in particular.

01:21:38.380 | So I'd love for you to speculate.

01:21:40.960 | Should we run the study?

01:21:41.960 | - We should totally run the study,

01:21:43.220 | because I don't know the answer.

01:21:47.560 | I suspect that you're onto something.

01:21:51.200 | It may not explain all of the women with PCOS,

01:21:53.920 | because as I mentioned,

01:21:54.780 | there's a lot of different phenotypes,

01:21:56.720 | but I think it could explain a significant portion,

01:22:01.060 | and you're almost, you're seeing,

01:22:04.400 | if we look at the gene-environment interface,

01:22:07.440 | this environmental influence of being someone

01:22:11.160 | who's got power over you, if PCOS was a response to that,

01:22:17.100 | the way that we treat it would be completely different.

01:22:20.260 | So on the one hand, I wanna be careful

01:22:23.880 | not to dismiss the suffering and experience

01:22:27.020 | of women with PCOS.

01:22:28.180 | I've got a lot of women with PCOS in my family,

01:22:31.060 | and it is, there's so much pain and suffering,

01:22:36.060 | especially if you wanna have a baby,

01:22:37.880 | and you try for years, and you just can't ovulate.

01:22:44.120 | On the other hand, I read a paper recently,

01:22:49.120 | and maybe we could cite this,

01:22:51.500 | that compares the phenotype of a woman with PCOS

01:22:55.120 | to a man who is hypoandrogenic,

01:22:58.500 | and I think that's a really interesting way to look at this,

01:23:02.040 | because the thread we haven't talked about with PCOS

01:23:07.040 | is the role of insulin and glucose.

01:23:11.240 | So for some of the phenotypes of PCOS,

01:23:15.460 | the problem is hyperinsulinemia, high insulin in the blood,

01:23:19.520 | is driving those theca cells in the ovaries

01:23:21.600 | to overproduce testosterone.

01:23:23.520 | - These women are insulin insensitive,

01:23:25.020 | so more insulin's being cranked out,

01:23:27.640 | and these cells in the ovary

01:23:29.620 | are therefore making more androgen.

01:23:31.580 | - You don't like to say insulin resistant?

01:23:33.540 | - Oh, I can, I don't have a problem saying insulin resistant.

01:23:36.540 | - Okay, I like the way that's used.

01:23:37.900 | - I'm just a little bit outside the lane lines

01:23:39.740 | of my expertise, so I was trying to use

01:23:41.220 | what is the correct nomenclature

01:23:42.760 | so that we can make sure they don't hear something.

01:23:44.020 | - Well, what I like about insulin insensitive,

01:23:45.820 | the way that you just said it,

01:23:46.840 | is that I think that offers people a way in,

01:23:49.760 | and I love to do that in terms of messaging.

01:23:52.600 | Insulin resistance starts to lose people

01:23:54.980 | 'cause they don't really get what that means

01:23:56.540 | at a receptor level.

01:23:57.580 | - I think I say insulin insensitive

01:23:59.380 | because when people hear insulin sensitive,

01:24:02.520 | it almost sounds like a bad thing,

01:24:03.760 | but that's actually what you want.

01:24:05.080 | So I think that's how I defaulted to insulin insensitive.

01:24:07.440 | - What's your insulin?

01:24:09.080 | - I don't know.

01:24:10.000 | - What?

01:24:10.840 | - I'm doing a blood test.

01:24:11.680 | - Yes, you are.

01:24:12.500 | - I'm due for a blood test.

01:24:13.480 | I had blood work done about eight months.

01:24:15.540 | Sure, that'd be great.

01:24:16.500 | I'm always experimenting with different supplements

01:24:20.020 | and different behavioral regimens,

01:24:21.520 | and I've kept charts since I was 19.

01:24:24.100 | - Oh, you're like my patient.

01:24:25.340 | - I've been sort of obsessed by this,

01:24:27.320 | and I would say everybody, if you can afford it,

01:24:30.800 | and at the time actually I had to save up insurance,

01:24:33.020 | wouldn't cover it, get some basic blood work done

01:24:36.700 | so that you have a reference.

01:24:37.780 | - Do it as soon as possible,

01:24:39.040 | because even, we've been talking about these women

01:24:42.820 | over the life cycle.

01:24:44.520 | I wish I knew what my insulin was when I was a teenager.

01:24:48.020 | I wish I knew what my fasting insulin was.

01:24:50.340 | I really wish I knew my postprandial insulin,

01:24:53.720 | like in my teenage years, in my 20s, in my 30s.

01:24:57.180 | Well, I knew it in my 30s, starting at 35.

01:24:59.700 | - Are you a fan of continuous glucose monitors?

01:25:02.540 | - The hugest, most gigantic fan of CGMs.

01:25:05.140 | I've never seen any tool that I've ever used in medicine

01:25:08.660 | change behavior the way that CGMs do.

01:25:11.040 | - Wow, why do you think they are so effective

01:25:14.140 | at changing behavior?

01:25:14.980 | I've tried one and I really liked it.

01:25:16.720 | I learned that in the sauna, my insulin,

01:25:19.740 | my blood glucose goes up probably by a bit of dehydration.

01:25:22.140 | I learned what kind of foods work for me, which don't.

01:25:24.780 | I thought it was fascinating.

01:25:26.720 | I learned how every behavior you could possibly imagine,

01:25:28.960 | use your imagination, impacts blood glucose.

01:25:31.280 | - Totally.

01:25:32.120 | - It was totally fascinating to me,

01:25:33.280 | including how two wake ups during the middle of the night

01:25:36.280 | versus one versus none impacted blood glucose

01:25:39.180 | the next morning.

01:25:40.020 | Fascinating.

01:25:40.840 | For a data junkie like me, it was like I was in heaven.

01:25:43.860 | Why do you think they are so effective in changing behavior?

01:25:47.060 | Is it because of that,

01:25:47.900 | that people can see that real-time control,

01:25:49.500 | like scan in and like, oh, that's the sandwich glucose?

01:25:53.900 | - I think it's many things.

01:25:54.940 | I think it's generally the enchantment

01:25:59.940 | of learning about your own chemistry and biology.

01:26:02.940 | - I love that.

01:26:03.780 | - And I think for me, what I've seen,

01:26:06.100 | I feel like doctors are basically marketers,

01:26:09.340 | like the secret marketing.

01:26:10.860 | Like our job as a physician is to convince people

01:26:15.240 | to do something that we think is good for them

01:26:17.240 | based on the best science.

01:26:19.560 | But we can't just say,

01:26:21.140 | here, why don't you fill this prescription for a CGM?

01:26:23.580 | You have to market it.

01:26:24.840 | You have to say, I think this completely changes

01:26:29.000 | the way that you approach your prediabetes.

01:26:30.900 | I think this could dramatically affect

01:26:34.340 | your risk of Alzheimer's disease.

01:26:35.740 | Which you're so worried about that your mother has.

01:26:38.300 | So our job as physicians is to be that sacred marketer.

01:26:42.660 | So CGMs are one of my tools that I think are so crucial.

01:26:45.800 | So enchantment number two, yeah, it's the real-time effect.

01:26:50.400 | So if you go get your glucose and insulin measured,

01:26:53.140 | or maybe you do like a two hour glucose challenge test,

01:26:56.620 | where you look at glucose and insulin at the fasting point,

01:26:59.660 | one hour later, two hours later, or more frequently,

01:27:03.160 | that does not have the same kind of behavior effect

01:27:06.780 | as having continuous data where you can say,

01:27:09.840 | okay, I drove to see you, Andrew, from my place in Berkeley,

01:27:13.800 | and it was stressful, it was torrentially raining,

01:27:17.820 | and I know my glucose was elevated.

01:27:20.340 | Like I think really understanding

01:27:22.900 | what the mediators are of your glucose control is essential.

01:27:27.900 | Now that said, it's also kind of a later effect.

01:27:31.600 | I mean, I'd rather know your insulin.

01:27:33.820 | And we know from the Whitehall study that insulin,

01:27:38.820 | especially postprandial insulin, fasting insulin too,

01:27:42.180 | can change years and years

01:27:44.220 | before you get a change in glucose.

01:27:46.940 | So that's more for pre-diabetes and diabetes.

01:27:51.340 | So I think those are the main reasons

01:27:52.700 | why I think it's such an important tool.

01:27:54.760 | Third thing is it democratizes data, which you do too.

01:28:00.620 | I mean, incredible how you do that with your podcast.

01:28:04.020 | But I think one of the most hopeful and exciting things

01:28:07.920 | that I'm seeing right now in the health space

01:28:12.680 | is that we're going from this patriarchal relationship

01:28:16.580 | where doctors hold the power and are the gatekeepers of data

01:28:21.320 | to patients and clients having much more access

01:28:26.320 | to that enchantment about their own chemistry

01:28:29.880 | and their own biology.

01:28:31.460 | So to me, that is so exciting.

01:28:33.980 | For me to be able to, I've got probably 100 patients

01:28:38.900 | that are in a data stream with me

01:28:41.220 | where we're looking at their glucose, and I can,

01:28:43.620 | I mean, I'm on sabbatical,

01:28:44.560 | so I'm not doing this so much anymore,

01:28:45.920 | but I can call a patient and be like,

01:28:47.780 | "Why is your glucose so high?

01:28:49.420 | "What did you do?"

01:28:50.260 | "Oh, it was my birthday.

01:28:51.080 | "I had a piece of birthday cake."

01:28:52.780 | That kind of collaboration,

01:28:57.860 | that also is teaching the patient to be their own clinician.

01:29:02.860 | To me, that is a loop of benevolence and integrity

01:29:07.720 | that I think is essential to creating health.

01:29:11.600 | We've got a disease care system.

01:29:13.760 | We need the democratization of data

01:29:16.060 | to become a health-based system.

01:29:19.520 | - Amen to that.

01:29:20.360 | A million times over, we share that sentiment,

01:29:23.840 | I can tell it at a deep level.

01:29:25.840 | I think the pandemic actually assisted in,

01:29:29.000 | well, it harmed many things,

01:29:30.220 | but it assisted in people's understanding

01:29:32.280 | that no magic fairy, nor the government,

01:29:35.960 | nor anyone was going to arrive at their door

01:29:38.720 | with a kit of things to make them healthy,

01:29:41.040 | that provide sunlight, movement, sleep,

01:29:42.740 | and all the various aspects of nutrition.

01:29:44.760 | No, nothing.

01:29:46.400 | Nothing that everyone has to have access to,

01:29:49.620 | first and foremost,

01:29:50.600 | and then implement those things as best they can.

01:29:53.920 | Speaking of which, and circling back to this idea

01:29:56.560 | of people in their late teens, 20s, 30s, and onward,

01:29:59.620 | if you had a magic wand,

01:30:01.640 | and you could give two or three don'ts,

01:30:05.440 | or to make it personal,

01:30:06.560 | if you could go back in time and erase certain behaviors,

01:30:10.860 | what would the don'ts category be?

01:30:14.720 | You can tell us more than two or three,

01:30:17.960 | but if the goal is to maximize vitality and longevity,

01:30:23.080 | and those are not always parallel to one another,

01:30:27.160 | they're certainly not the same thing,

01:30:28.240 | sometimes orthogonal, but let's just say fertility

01:30:32.400 | being a proxy for vitality and longevity.

01:30:34.640 | I think people will sometimes forget this,

01:30:35.760 | that fertility isn't just about

01:30:36.840 | people who want to conceive children,

01:30:38.000 | it's also, it can serve as a proxy

01:30:40.520 | for vitality and longevity.

01:30:41.980 | So what would you like to see patients,

01:30:45.480 | let's focus first on female patients,

01:30:47.020 | but if it extends to male patients as well,

01:30:50.420 | what would you like to see them not do, or do far less of?

01:30:54.100 | - I really like that.

01:30:55.220 | So I would say a few things, I'll just headline them,

01:30:58.340 | and then we can go into detail.

01:31:00.020 | Number one, sleep.

01:31:01.660 | I do want to diverge from you a little bit on some things,

01:31:04.480 | but sleep is probably not one of them.

01:31:06.500 | - No, well, feel free.

01:31:07.380 | I mean, you're the one that worked 120 hours a week.

01:31:11.300 | - I was not sleeping much then,

01:31:12.180 | let's just put it that way. - I can't imagine,

01:31:13.380 | unless you lived in a different reality than I do.

01:31:15.820 | And there are times in my career

01:31:18.420 | where I was pulling all-nighters and sleep-deprived,

01:31:20.260 | there's just, I don't recommend it, but I did it.

01:31:23.520 | - Yeah, I hope you don't do that anymore.

01:31:24.960 | - No longer if I can avoid it, but there were years,

01:31:27.820 | many years where it was like, all right, here we go.

01:31:30.020 | And I'm quite adept at it for one cycle,

01:31:35.020 | but two nights I kind of start to fall apart.

01:31:37.420 | - Totally. - Yeah.

01:31:38.500 | - So I would say sleep, alcohol, high perceived stress.

01:31:42.900 | And I'd love to talk about maybe the data on telomeres

01:31:46.540 | and what we know.

01:31:47.380 | - So you'd like to see people get enough sleep,

01:31:49.500 | so don't, don't.

01:31:51.300 | - Yeah, not all of these are concordant.

01:31:53.180 | So not enough sleep, too much alcohol,

01:31:56.860 | too much perceived stress, eating the wrong foods,

01:32:01.780 | toxic relationships, and isolation.

01:32:08.620 | And then number six, not moving enough

01:32:11.820 | or not moving and exercising in a way

01:32:18.240 | that really fits with your body.

01:32:20.580 | - Can we start with that one actually?

01:32:22.100 | - Sure. - Just 'cause it's such a,

01:32:23.060 | and then work backwards.

01:32:24.260 | That's interesting.

01:32:26.320 | I think nowadays people appreciate the need

01:32:29.560 | for quote unquote cardio.

01:32:31.280 | I know that the exercise physiologists cringe

01:32:33.780 | and dissolve into a puddle of tears when I say that,

01:32:36.420 | but getting the heart rate up over some period of time,

01:32:39.980 | longer than 10 minutes in order

01:32:42.380 | to generate cardiovascular health circulation.

01:32:44.960 | So, and resistance training of some kind, maybe flexibility.

01:32:47.820 | What do you mean by body phenotype and exercise?

01:32:52.100 | - I'll speak from personal experience.

01:32:53.600 | So what I did through,

01:32:56.020 | I mean, I gave up my 20s to medicine.

01:32:58.040 | And during that time, I occasionally got to the gym,

01:33:02.860 | you know, at UCSF on Parnassus, you could go to the gym,

01:33:06.240 | and then as soon as your beeper went off,

01:33:07.620 | you're back into the hospital.

01:33:10.680 | But I didn't exercise much.

01:33:11.840 | I had, do you remember Nordic tracks?

01:33:13.900 | I had a Nordic track in my house,

01:33:15.580 | and that was like it.

01:33:17.900 | What I believe, because for me,

01:33:20.980 | the primary outcome that I'm interested in

01:33:24.300 | is cardio metabolic health.

01:33:26.400 | So when it comes to exercise, what I really feel,

01:33:29.380 | if we're gonna be at a population level,

01:33:31.800 | I feel that about a third cardio,

01:33:35.660 | two thirds resistance training

01:33:37.980 | is based on my synthesis of the literature,

01:33:41.420 | the best combination.

01:33:43.380 | And I think there's, you know,

01:33:44.660 | as you described with your sign study,

01:33:49.140 | I think there's a minimal effective dose,

01:33:51.660 | which for a population is about 150 minutes.

01:33:55.460 | I think most of us need a lot more than that.

01:33:58.460 | - Per week of- - Per week.

01:34:00.260 | But I think, you know, for me,

01:34:02.780 | because I have a phenotype that produces a lot of insulin,

01:34:07.780 | kind of depending on how I'm on my game,

01:34:11.780 | I have a lot of glucose.

01:34:13.280 | So I have to exercise a lot more to dispose that glucose.

01:34:17.240 | So I think you then have to move from medicine

01:34:20.220 | for the population or prescriptions for the population

01:34:23.480 | to what works for the individual.

01:34:26.060 | - I think that recommendation is fantastic.

01:34:30.020 | I think resistance training, well, let me put it this way.

01:34:32.700 | I'm neither a trainer nor a physician,

01:34:34.560 | but I've seen in family members that were doing,

01:34:36.960 | I wouldn't say a lot of cardio, but just cardio,

01:34:40.420 | when they add resistance training,

01:34:42.380 | everything in terms, including their biomarkers,

01:34:45.160 | have improved dramatically.

01:34:48.000 | - Yes. - This is in particular

01:34:48.960 | for female members of my family.

01:34:51.500 | - Well, one of the mediators that I think is important,

01:34:54.500 | especially for people who do what I call chronic cardio,

01:34:57.020 | which is what I did, is cortisol.

01:35:01.000 | So we know that runners, especially marathon runners,

01:35:05.560 | people who do a lot of cardio

01:35:08.200 | and don't do much resistance training,

01:35:09.940 | they tend to have much high cortisol levels.

01:35:11.860 | And you can buffer that with vitamin C.

01:35:13.700 | Vitamin C can decrease the effect.

01:35:16.060 | But chronic cardio doesn't always serve people.

01:35:20.100 | So quick personal example.

01:35:22.140 | When I first started measuring hormone panels in myself,

01:35:25.740 | I went to my physician and I said, "I'm 35.

01:35:29.840 | "I've had one kid, I wanna have another kid.

01:35:32.720 | "I've never been so exhausted in my life.

01:35:34.820 | "I just feel like I'm pushing a rock up the hill.

01:35:38.220 | "I've got this belly fat that I don't like."

01:35:40.620 | And I don't wanna have sex with my husband.

01:35:44.420 | So what do you think?

01:35:46.620 | What could we do about this?

01:35:48.360 | And he offered a birth control pill and an antidepressant.

01:35:53.180 | - Oh, goodness.

01:35:54.020 | - So I left him and I went to the lab

01:35:56.140 | and I ran a hormone panel and my cortisol

01:35:58.780 | was three times what it should have been.

01:36:00.940 | My insulin was in the 20s.

01:36:02.780 | I was fasting.

01:36:04.060 | My glucose was 105.

01:36:06.700 | My thyroid was mildly abnormal.

01:36:10.020 | My progesterone was low.

01:36:12.100 | And that set me on this course of realizing

01:36:15.420 | that what I was doing as a physician,

01:36:18.240 | taking care especially of women,

01:36:20.880 | was not getting to some of these root causes

01:36:23.380 | that are so essential.

01:36:24.620 | And I would say I had to start first with cortisol.

01:36:28.260 | At that time, I was running four miles,

01:36:30.580 | three times a week, four times a week.

01:36:32.460 | That was just raising my cortisol further.

01:36:35.060 | So that was not the right exercise for me.

01:36:36.780 | I needed more adaptive exercise.

01:36:38.580 | I started doing Pilates, more yoga.

01:36:41.060 | That helped to lower my cortisol.

01:36:42.700 | I mean, it started me on changing the way

01:36:45.780 | I was managing perceived stress

01:36:47.580 | and it also changed my supplement regimen.

01:36:50.300 | - Can we talk about that?

01:36:51.140 | With the moment you said lowering cortisol,

01:36:53.820 | thought of the two supplements that come to mind

01:36:56.620 | are ashwagandha, which I think can potently reduce cortisol,

01:37:01.100 | but I've heard some recommendations about cycling it.

01:37:04.780 | And I've always wondered about time of day

01:37:06.500 | for ashwagandha intake because sort of, quote-unquote,

01:37:09.220 | want cortisol elevated in the early part of the day.

01:37:12.140 | We know this.

01:37:12.980 | We know you do not want cortisol peaking later in the day.

01:37:17.100 | - No, you do not.

01:37:17.940 | Interferes with sleep.

01:37:19.420 | - Interferes with sleep.

01:37:21.340 | And then the other supplement is rhodiola rosacea.

01:37:24.860 | Am I pronouncing that correctly?

01:37:26.260 | - Yeah, so rhodiola is very effective.

01:37:28.140 | It's been shown in multiple randomized trials

01:37:30.400 | to lower cortisol, so that could be very effective.

01:37:32.860 | - What sort of dose?

01:37:33.820 | I've started taking it recently, by the way,

01:37:35.540 | and I made a huge mistake.

01:37:36.940 | I like to make the mistakes first

01:37:38.140 | so then my audiences don't make them.

01:37:41.100 | As I was taking it, I heard it was an adaptogen,

01:37:43.300 | so I thought, oh, I'll take it before resistance training.

01:37:45.900 | But of course you want the cortisol peak

01:37:47.460 | during resistance training

01:37:48.460 | because that's going to set in motion the adaptive response.

01:37:50.740 | So I started taking it later in the day

01:37:52.060 | and it's really improved.

01:37:53.260 | I would say my late day, second half of the day cognition,

01:37:57.260 | this is subjective, to be fair.

01:37:59.300 | I just feel like I'm in a more even plane of attention

01:38:01.940 | in the second half of the day.

01:38:03.540 | - So you're describing an end-of-one experiment.

01:38:05.520 | - Right, anecdotal.

01:38:07.100 | - Well, it is not anecdotal.

01:38:10.180 | So I was taught at Harvard Medical School

01:38:12.620 | that the hierarchy of evidence

01:38:14.720 | starts at the lowest with expert opinion, case studies,

01:38:19.720 | then you've got cohort studies,

01:38:22.100 | then you've got observational data that's prospective,

01:38:25.680 | then you have randomized trial.

01:38:27.040 | But the highest quality evidence of all

01:38:29.300 | is the end-of-one experiment,

01:38:31.260 | where you serve as your own control.

01:38:33.340 | So what you're describing with rhodiola,

01:38:34.940 | I would frame that as an end-of-one experiment,

01:38:37.460 | where you have a washout period

01:38:38.640 | and you compare before and after.

01:38:40.500 | And I'd like to measure some other metrics

01:38:42.380 | to see if there's an effect, including your cortisol.

01:38:45.520 | So rhodiola has been shown in multiple randomized trials

01:38:47.980 | to reduce cortisol.

01:38:49.400 | The other thing that I think is super effective

01:38:52.380 | is phosphatidylserine, PS for short.

01:38:56.040 | Fish oil also more modestly reduces cortisol.

01:39:02.160 | Ashwagandha is interesting.

01:39:03.800 | So in my first book, "The Hormone Cure."

01:39:06.920 | - Which I read by the way.

01:39:08.860 | - You did? - I did.

01:39:09.840 | - I was hoping that was the one you read.

01:39:11.080 | - I did, I read it and it's spectacular.

01:39:12.980 | And I thought going into it, I had this like,

01:39:15.200 | let's just call it what it was.

01:39:16.980 | It's kind of male bias.

01:39:17.820 | Like, is there going to be anything in here for me?

01:39:19.300 | Because I don't have ovaries and is this going to be,

01:39:22.480 | and it was immensely informative.

01:39:25.400 | So thank you.

01:39:26.320 | Yeah, I have very fond recollections

01:39:28.240 | of the walks I took listening to it.

01:39:29.780 | And then I own the print version too.

01:39:31.180 | So I like to switch back and forth.

01:39:32.880 | So thank you for that.

01:39:33.800 | It's a superb book for anyone to read.

01:39:36.080 | - Thank you. - Yeah.

01:39:36.920 | - I so appreciate that.

01:39:37.960 | So in chapter four, you may or may not remember

01:39:42.720 | that Ashwagandha, at least the time that I wrote that book,

01:39:46.560 | Ashwagandha's data is not great,

01:39:48.880 | but lack of proof is not proof against.

01:39:51.040 | So with Ashwagandha, most of the data comes

01:39:53.960 | from thousands of years of using it in diabetic medicine.

01:39:57.360 | And it's considered, again, not my science hat.

01:40:00.800 | It's considered a double adaptogen

01:40:02.580 | so that it's potentially helpful

01:40:04.840 | when you are a high cortisol phenotype like I was,

01:40:09.400 | like I sometimes still am, or low cortisol.

01:40:13.060 | I haven't found that in my patients,

01:40:16.660 | although I'll give you one exception.

01:40:18.900 | So Ashwagandha is mostly based on animal studies.

01:40:21.820 | There's not as much human data,

01:40:23.620 | but it is used a ton in integrative medicine.

01:40:29.020 | There's one supplement that I found to be incredibly helpful

01:40:32.920 | for people who tend to have high cortisol at night,

01:40:36.000 | and that's called a cortisol manager.

01:40:37.640 | It's by Integrative Therapeutics.

01:40:39.980 | I don't have a second supplement manufacturer

01:40:43.520 | that makes something similar.

01:40:44.680 | It's their number one selling supplement

01:40:46.520 | because it's so effective.

01:40:47.680 | - Is it a cocktail of several things?

01:40:49.120 | - It's a combination of phosphatidylserine and Ashwagandha.

01:40:52.580 | - Tell me more about phosphatidylserine.

01:40:54.320 | I am familiar with it for,

01:40:56.580 | it's been mentioned by some guests

01:40:58.880 | that were on the Tim Ferriss podcast long ago

01:41:00.700 | for other reasons, I think, related to sleep.

01:41:03.840 | And maybe that's another reason why you like it.

01:41:07.060 | But before we move on from rhodiola,

01:41:08.700 | is there a dosage of rhodiola rosacea that you-

01:41:11.640 | - So I would refer people to my book

01:41:13.620 | because the randomized trials

01:41:15.520 | and the doses that were used are in there.

01:41:18.360 | So I can't remember with rhodiola,

01:41:19.800 | although I took it this morning to prepare to be with you.

01:41:22.500 | - We can look it up and put a show note caption

01:41:24.760 | so people can link it. - I can remember the dose

01:41:25.800 | with phosphatidylserine 'cause I take that regularly.

01:41:28.560 | So 400 to 800 milligrams is the typical dose for PS.

01:41:32.320 | And what's interesting is that

01:41:34.560 | in the randomized trials that were done,

01:41:37.020 | 400 milligrams was more effective than 800 milligrams.

01:41:40.040 | - Interesting.

01:41:40.880 | I've found that for several supplements

01:41:42.280 | that the lower dose was more effective.

01:41:44.640 | - Yes.

01:41:46.040 | - Yeah, it doesn't matter what those were.

01:41:47.880 | And so when you say PS, you were referring to,

01:41:49.760 | by the way, folks, not PCOS, just 'cause-

01:41:51.880 | [laughing]

01:41:52.920 | Scientists and clinicians are familiar with,

01:41:54.440 | and military, very familiar with acronyms,

01:41:56.400 | phosphatidylserine, PS, so 400 to 800 milligrams,

01:41:59.000 | 400 being more effective.

01:42:00.160 | Taken later in the day or early day, does it matter?

01:42:03.400 | - It depends on when your cortisol is high.

01:42:06.220 | So for me, I tend to, what's the pattern for cortisol?

01:42:10.880 | Typically, it rises to its peak

01:42:13.960 | 30 to 60 minutes after you get up.

01:42:16.160 | Then it has this gradual kind of asymptotic decline

01:42:19.360 | until you go to bed.

01:42:21.080 | So if you're someone like me who peaks way crazy high,

01:42:26.280 | I don't do that anymore, but that's what I used to do,

01:42:28.640 | I need a phosphatidylserine in the morning.

01:42:31.320 | For people who are high at night,

01:42:33.520 | who have what's known as a flat cortisol pattern

01:42:37.720 | or a inverted pattern, you wanna take it at night.

01:42:42.040 | And the flat pattern, just quick sidebar,

01:42:44.280 | is that that's associated with a number of conditions

01:42:48.520 | that most mainstream physicians don't know about.

01:42:51.220 | So a flat pattern where it's low in the morning

01:42:53.860 | and it's high at night is associated with anxiety,

01:42:56.660 | depression, decreased survival from breast cancer.

01:43:00.240 | That was studied at Stanford by David Spiegel.

01:43:03.780 | - He was my close even collaborator,

01:43:07.500 | even on the breath work study that we just did.

01:43:10.220 | - Oh, interesting.

01:43:11.100 | - Yeah, he's our associate chair of psychiatry now.

01:43:13.300 | So a wonderful human being has been a guest on this podcast.

01:43:17.240 | And I'm now fantasizing about a conversation

01:43:19.420 | that includes a panel of incredible minds

01:43:23.780 | like you and David from the clinical side.

01:43:25.400 | So in any case, yeah, the late shifted cortisol, not good.

01:43:29.440 | - Not good.

01:43:30.600 | And it seems to have the worst immune downstream issues

01:43:35.600 | of any of the cortisol patterns.

01:43:41.580 | So that's really important to know about

01:43:43.080 | because it then maps to things like it's related to PTSD.

01:43:48.080 | So that's the pattern we see like in vets

01:43:51.440 | who've got PTSD as well as others.

01:43:54.120 | It maps to autoimmunity.

01:43:56.860 | It maps to fibromyalgia.

01:43:58.700 | - I was told that one in 12 people

01:44:02.260 | have our heterozygous, so one mutant copy

01:44:08.740 | or hypomorphic for some mutation in adrenal related genes.

01:44:13.740 | So congenital adrenal hyperplasia.

01:44:16.180 | Is that true?

01:44:17.300 | And if so, that means that one in 12 people walking around

01:44:20.380 | are cranking out far too much cortisol

01:44:22.220 | or not enough cortisol or the cortisol system

01:44:24.920 | is already skewed in a direction

01:44:26.320 | that makes life more challenging

01:44:27.860 | at the levels we're talking about.

01:44:29.560 | Did I hear that correctly?

01:44:31.660 | 'Cause that one in 12 is not a small number.

01:44:33.700 | - It's not a small number.

01:44:34.840 | It fits with what I see clinically.

01:44:37.600 | I mean, I want to see that data

01:44:39.300 | just to see what does that mean?

01:44:42.340 | And could you modulate it with environmental influences?

01:44:46.260 | But it certainly fits with what I see.

01:44:48.820 | I was taught once again in mainstream medicine

01:44:50.900 | that in terms of adrenal function,

01:44:53.560 | it's very binary how most clinicians think about it.

01:44:59.780 | You either have Addison's disease

01:45:02.300 | and you don't make enough cortisol

01:45:03.980 | or you've got Cushing's or Cushingoid pattern

01:45:06.900 | and you make too much cortisol.

01:45:08.460 | And anything in the middle is normal.

01:45:10.820 | And my experience is that hell no.

01:45:13.540 | There are those of us like me who make a lot of cortisol.

01:45:16.340 | I don't have Cushing's.

01:45:17.760 | Maybe I've got one of these.

01:45:19.620 | I wouldn't call it a mutant gene.

01:45:21.220 | I would call it more of a vulnerable gene.

01:45:25.540 | So maybe I have one of those.

01:45:26.660 | Maybe that's part of the reason why

01:45:28.100 | I make two to three times what I should be.

01:45:30.840 | - I'm aware of certain groups of individuals

01:45:34.500 | from within the military sector

01:45:36.060 | that there's a more frequent occurrence

01:45:40.400 | of some mutation in CAH, congenital adrenal hyperplasia,

01:45:45.400 | not necessarily two copies,

01:45:46.900 | which if people look that up, they're going to go,

01:45:48.480 | oh, wow, there's all these phenotypes

01:45:50.820 | and sort of hypomorphic type things.

01:45:55.800 | Less than or too much cortisol.

01:45:58.200 | And they are very good at staying up

01:46:00.300 | multiple days per night, multiple nights in the series.

01:46:04.140 | So they can pull all nighters very easily.

01:46:06.140 | They can push harder when most people would quit.

01:46:08.340 | And everyone thinks, well, that's a great phenotype to have,

01:46:10.380 | but guess what?

01:46:11.220 | It's because they hyperproduce cortisol.

01:46:13.240 | And so that's interesting.

01:46:16.540 | And I think if we were to panel medical students

01:46:19.900 | and graduate students, and you were to look at,

01:46:21.800 | who's pulling excessively long hours,

01:46:24.120 | who's stressed out a lot,

01:46:25.960 | even outside of academia and medicine,

01:46:28.300 | and pushing, pushing, pushing really hard,

01:46:29.940 | I think the ability to push and not crash,

01:46:32.820 | we think of it as adaptive,

01:46:34.060 | but in some sense it's maladaptive over a series of years,

01:46:36.660 | which is sort of what you described earlier.

01:46:38.980 | - Yeah, it's such a good point,

01:46:40.140 | because in some ways you want to select for that

01:46:44.800 | in certain professions, like in the military,

01:46:47.620 | like in medicine.

01:46:49.020 | But I would wonder for those folks

01:46:54.260 | about the downstream consequences

01:46:56.220 | of producing so much cortisol.

01:46:58.100 | - No, it's got to be detrimental for their health

01:47:00.300 | in the long run. - It's got to be.

01:47:01.140 | - And you see that.

01:47:02.380 | - But even the data shows that if you're someone like me

01:47:05.300 | who makes a lot of cortisol, higher rates of depression,

01:47:08.420 | like 50% of people with major depression

01:47:10.700 | have high cortisol levels, higher rates of suicide.

01:47:14.860 | Much more metabolic dysfunction.

01:47:17.660 | We know that trauma, as an example,

01:47:19.860 | maps to an increased risk of glucose, metabolism issues,

01:47:24.420 | and certainly high cortisol does that,

01:47:26.320 | 'cause it's, one of the jobs of cortisol

01:47:28.460 | is to manage glucose.

01:47:30.400 | And it kind of sets you up for this one,

01:47:35.400 | number five, which is toxic relationships.

01:47:39.780 | You know, someone who hyper-produces cortisol,

01:47:41.880 | it's hard to live with someone like that.

01:47:44.520 | - It's also, I would say people that have this,

01:47:47.540 | let's just call it biological resilience,

01:47:50.820 | it's not always adaptive

01:47:51.880 | because you can stay in bad circumstances longer.

01:47:54.260 | The ability to crash, provided it's not suicide

01:47:58.260 | or life destroying or, you know, long arc of pause

01:48:03.260 | and the requirement to take two years off

01:48:05.540 | from work or school or something,

01:48:07.180 | the ability to keep pressing on is a double-edged sword.

01:48:10.580 | Let's put it that way. - Yes, it is.

01:48:12.960 | - I want to make sure in staying within this conversation,

01:48:16.400 | because you mentioned phosphatidylserine,

01:48:17.880 | we talked about rhodiola, rosacea,

01:48:20.820 | we talked a bit about ashwagandha.

01:48:21.980 | You've also talked about omega-3s

01:48:23.860 | and fish oil in particular.

01:48:25.440 | I'd love to know your favorite sources of these.

01:48:27.160 | I think nowadays there's more general acceptance

01:48:30.680 | that getting these essential fatty acids is important.

01:48:34.360 | Do you have a threshold level of sort of grams?

01:48:37.000 | I've encouraged podcast listeners

01:48:40.260 | to consider, depending on what they're eating,

01:48:42.740 | to try and get a gram of EPA or more per day.

01:48:46.280 | Does that seem excessive?

01:48:47.780 | And what are the real data on EPAs?

01:48:49.980 | Because then the cardiovascular experts always hit back

01:48:54.180 | and say, "Oh no, you know,

01:48:55.220 | it's not good for cardiovascular health."

01:48:56.780 | And then you go, "Well, it's better than antidepressants

01:48:59.140 | and other studies."

01:48:59.960 | And they go, "No."

01:49:00.800 | So I feel like if you really want to make your life

01:49:03.020 | difficult, if you want to raise your cortisol,

01:49:04.900 | you go on Twitter and you say something positive

01:49:06.660 | about omega-3s and fish oil.

01:49:08.140 | [laughing]

01:49:09.260 | And you learn a lot.

01:49:11.200 | What are your thoughts on omega-3s?

01:49:13.660 | I take a lot of them.

01:49:14.500 | I've always been a big fan.

01:49:15.640 | - Yeah.

01:49:16.480 | So this is where I personalize.

01:49:18.360 | I think some people need more than others.

01:49:21.100 | And what I do is I measure your level.

01:49:24.500 | So this gets back to nutritional testing.

01:49:26.860 | So for you, I would suggest an omega quant

01:49:29.480 | or one of my favorite cardiometabolic panels

01:49:32.820 | is to do a Cleveland heart lab.

01:49:35.040 | So I think they give me the most reliable information,

01:49:37.880 | not just for lipids and subclasses

01:49:40.980 | and NMR fractionation,

01:49:43.420 | but it also gives me an insulin resistant score.

01:49:46.100 | It gives me levels of omega-3s.

01:49:50.180 | - Great.

01:49:51.020 | We'll provide links to these different sites

01:49:52.520 | so that people can look at them.

01:49:53.420 | - But one quick thing about that,

01:49:55.620 | the whole story is not omega-3s and taking fish oil.

01:49:59.820 | So the work of Charlie Surhan at the Brigham

01:50:03.180 | is showing that the way that we resolve inflammation,

01:50:07.760 | our understanding of it is really,

01:50:12.840 | I think in the learning to crawl stage.

01:50:15.320 | And so if you look at the omega-3-6 pathway in the body,

01:50:19.980 | fish oils can help kind of push the reactions

01:50:25.640 | in a particular direction,

01:50:27.280 | but typically they're not enough

01:50:29.160 | for the resolution of inflammation.

01:50:31.240 | Now, what most people do, including my MBA players,

01:50:34.560 | is they pop an ibuprofen or something like that

01:50:38.280 | when they've got inflammation,

01:50:39.860 | that's got lots of other side effects

01:50:42.220 | that are not so good for you.

01:50:43.860 | And we know in terms of the resolution of inflammation

01:50:47.800 | that taking something like ibuprofen

01:50:50.660 | reduces the amplitude of inflammation by about 50%,

01:50:54.000 | but then it potentially blocks

01:50:56.340 | the complete resolution of inflammation.

01:50:59.280 | So there's these new supplements that you may have heard of

01:51:02.040 | called Specialized Pro-Resolving Mediators.

01:51:04.520 | There's a lot of different supplement companies

01:51:06.200 | that make them.

01:51:07.440 | And that combined with fish oil

01:51:10.040 | seems to be the best combination.

01:51:11.860 | And what I do for athletes who've got

01:51:14.280 | kind of the normal aches and pains

01:51:16.400 | of the training load they have

01:51:19.040 | is I'll combine a little aspirin,

01:51:21.800 | small dose, just like 81 milligrams

01:51:24.480 | or two of those baby aspirin,

01:51:26.320 | together with fish oil plus

01:51:29.120 | Specialized Pro-Resolving Mediators.

01:51:30.760 | And there's some that are NSF,

01:51:32.020 | they're certified for sports.

01:51:33.900 | But the dose, I would say with my patients,

01:51:38.360 | some of them only need 1,000 milligrams,

01:51:41.600 | your gram that you mentioned for the population.

01:51:44.160 | Some of them need six grams together with SPMs.

01:51:48.620 | So I think it has to be personalized.

01:51:51.560 | - How young is it okay for people

01:51:56.560 | to start taking omega-3s?

01:51:59.000 | For instance, young women in their teens,

01:52:02.720 | in their 20s and their 30s,

01:52:04.040 | young guys in their 20s and 30s,

01:52:06.440 | should they take fish oil?

01:52:08.000 | Just as a, assuming they're not going to get anything tested.

01:52:10.360 | I'm thinking about the college student

01:52:11.640 | who is really into biomarkers and that sort of thing.

01:52:14.080 | We'll go do some of this.

01:52:15.400 | But many people won't, but they want to do the right thing.

01:52:19.540 | So they'll try and drink a little less, hopefully.

01:52:21.040 | Hopefully they won't smoke or vape.

01:52:22.360 | Please don't smoke or vape.

01:52:24.000 | The idea that vaping is okay.

01:52:25.480 | It's like, we had it the whole episode, it's so bad.

01:52:27.760 | So bad for everything we're talking about.

01:52:29.040 | - Let's end that chapter.

01:52:30.480 | - Exactly.

01:52:31.320 | So just, hopefully they'll try and avoid those things.

01:52:34.840 | Hopefully they'll avoid hard drugs.

01:52:37.360 | Hopefully they'll avoid getting any STIs.

01:52:39.840 | If they do, they'll resolve them quickly, hopefully.

01:52:42.800 | So, but they might say, oh, well, okay.

01:52:45.200 | I'm willing to take some magnesium

01:52:47.440 | or take some phosphidylserine, buffer my cortisol,

01:52:49.560 | eat some vegetables.

01:52:51.560 | Should they consider taking fish oil

01:52:53.080 | as a kind of across the board inoculatory thing?

01:52:55.760 | - So I'd like to rank order these.

01:52:57.200 | I would say fish oil, yes.

01:53:00.080 | I think a thousand milligrams

01:53:01.280 | as a general recommendation is good,

01:53:03.000 | but I also have a food first philosophy.

01:53:05.400 | So my preference would be that they're having salmon

01:53:07.800 | or some kind of smashed fish.

01:53:09.880 | And they're getting that as the primary source

01:53:12.560 | of their omega-3s.

01:53:13.840 | And then the days that they don't have fish,

01:53:15.960 | I recommend it probably twice a week

01:53:17.820 | that they take fish oil.

01:53:19.240 | Then I would put magnesium next,

01:53:21.000 | since so many people are deficient.

01:53:22.780 | Then I'd probably put vitamin D.

01:53:24.440 | - How many IU of vitamin D per day?

01:53:27.240 | - Well, you keep asking me this, like for the population.

01:53:30.240 | - Well, let me put it this way.

01:53:31.680 | For the lazy person or, and this is an or, not an and,

01:53:36.680 | or the person who just doesn't have the finances

01:53:42.080 | to go get levels measured,

01:53:44.120 | 'cause our audience has a huge range.

01:53:45.920 | We've got people who can have tons of disposable income

01:53:48.160 | that lives in this body.

01:53:49.000 | You have no disposable income.

01:53:50.600 | - So 1,000 to 2,000 international units.

01:53:52.720 | But my, what I do is I dose to a serum level

01:53:57.200 | that's between about 50 and 90.

01:53:59.720 | - Great.

01:54:00.540 | - And so I have a vitamin D receptor snip.

01:54:03.880 | And so I need to take about 5,000 a day

01:54:06.280 | to get to what I need.

01:54:07.720 | A lot of people don't need that.

01:54:09.960 | And there's some supplements that I don't know if they need.

01:54:14.960 | So you mentioned phosphatidylserine.

01:54:17.100 | For someone who's a college student

01:54:19.060 | and their cortisol is completely normal,

01:54:20.900 | they're wasting their money on PS.

01:54:22.380 | They don't need it.

01:54:23.220 | They might need it later, but they don't need it now.

01:54:25.600 | - I'd like to make sure that we circle back

01:54:27.180 | to birth control.

01:54:28.940 | In particular, oral contraceptive birth control.

01:54:32.200 | And we should touch on IUDs perhaps a little bit more.

01:54:37.580 | But what are your thoughts on sort of pure estrogen

01:54:41.400 | birth control?

01:54:42.240 | This is what I learned when I was in college,

01:54:43.780 | is that birth control is basically tonic estrogen.

01:54:46.840 | So constantly taking estrogen,

01:54:48.140 | estrogen women are taking estrogen

01:54:49.840 | so that they don't get the estrogen priming of progesterone.

01:54:54.840 | You're not getting any ovulation.

01:54:57.480 | And I've known women that have been taking oral,

01:55:01.560 | or that took oral contraception as like estrogen pills,

01:55:05.800 | basically for five, 10, 15 years.

01:55:09.220 | Are there long-term consequences of this

01:55:11.180 | as it relates to pregnancy, PCOS, menopause?

01:55:15.940 | If so, what are some of those consequences?

01:55:18.380 | What are your concerns?

01:55:20.900 | What do you like about oral contraceptives?

01:55:22.660 | What do you dislike about them?

01:55:24.940 | - I like how balanced you asked that question.

01:55:27.060 | So women who take oral contraceptives,

01:55:30.580 | as long as you're describing like 10 years or longer,

01:55:33.860 | we call those Olympic oral contraceptive users.

01:55:38.420 | In terms of benefit, I think that,

01:55:40.640 | especially when they first came out and even now,

01:55:42.860 | it gives women reproductive choice, and that's essential.

01:55:46.980 | As you may know, our reproductive choice

01:55:48.860 | has been declining recently.

01:55:51.060 | So I'm a big fan in that regard,

01:55:52.580 | and we've got a lot of data to show both the risks

01:55:56.540 | and also the benefits of it.

01:55:58.560 | So I'll speak first into the benefits

01:56:00.740 | because I'm gonna get on a soapbox

01:56:05.620 | a little bit about the risks.

01:56:07.420 | So we know that it reduces the risk of ovarian cancer.

01:56:11.120 | So there's something about this idea of incessant ovulation

01:56:15.500 | that is not good for the female body.

01:56:18.060 | So if you look at, for instance, women who are nuns,

01:56:23.060 | who don't take oral contraceptives,

01:56:26.900 | and they have a period every single month

01:56:28.720 | of their reproductive lives,

01:56:30.540 | they have a greater risk of ovarian cancer.

01:56:33.000 | So if you look then at women who have several babies,

01:56:38.000 | and they've got a period of time when they're pregnant

01:56:41.040 | but they're not ovulating,

01:56:42.140 | and then they breastfeed for some period of time,

01:56:44.340 | they have a lower risk of ovarian cancer.

01:56:46.540 | So oral contraceptives help with reducing ovulation

01:56:51.340 | and reducing risk.

01:56:53.080 | We know that if you take the oral contraceptive

01:56:56.580 | for about five years,

01:56:57.580 | it reduces your risk of ovarian cancer by 50%.

01:57:00.260 | And that's significant because we're so poor

01:57:04.320 | at diagnosing ovarian cancer early.

01:57:07.060 | There's really no method that's really effective.

01:57:09.480 | We use CA-125 and ultrasound screening,

01:57:13.020 | especially in women who are at greater genetic risk.

01:57:15.900 | But even that, often we diagnose it in a later stage.

01:57:19.460 | - Maybe just because that statement is going to highlight

01:57:22.300 | for a number of people the question of

01:57:24.780 | what are some of the earliest symptoms

01:57:27.800 | that people can recognize without a blood test?

01:57:29.660 | So is ovarian cancer, is it going to be pain?

01:57:32.820 | - So the problem is the symptoms are so vague

01:57:35.380 | and they're so nonspecific.

01:57:37.820 | One of the most common symptoms is bloating.

01:57:40.820 | And we've already talked about constipation.

01:57:42.380 | We've talked about how women have this longer track,

01:57:45.620 | GI track, and so bloating is a really common experience

01:57:48.660 | for most women.

01:57:50.100 | You can have bulk symptoms,

01:57:51.680 | feeling like your lower belly is kind of pressed out.

01:57:55.720 | So the way that we inform women

01:58:00.720 | in terms of watching for this

01:58:02.420 | is to get regular gynecologic exams

01:58:07.020 | for women who are at high risk

01:58:08.340 | where they have, for instance, an ultrasound for some reason

01:58:10.820 | and it shows a mass that we're concerned about.

01:58:13.140 | There's a way to triage that

01:58:14.420 | in terms of what kind of evaluation that they need.

01:58:17.100 | And that's a situation where you might get a blood test

01:58:19.620 | called the CA-125.

01:58:22.780 | Yeah, the problem is the symptoms are so vague.

01:58:28.100 | It could be, it depends on how big the tumor is,

01:58:30.860 | how much bulk you have, what it's pressing on.

01:58:34.780 | So if taking estrogen

01:58:37.260 | and thereby reducing the frequency of ovulation

01:58:40.980 | lowers the risk of ovarian cancer,

01:58:43.820 | should women that are,

01:58:45.420 | even women who are not sexually active,

01:58:47.060 | so they're not actively trying to get pregnant

01:58:49.540 | or avoid getting pregnant,

01:58:51.020 | but if they're not sexually active,

01:58:52.260 | then the probability of conceiving

01:58:54.120 | unless they go through some IUI or some other route

01:58:57.380 | is very low, as far as I know.

01:58:59.460 | That's what I was taught in high school anyway.

01:59:03.660 | - Would they be wise to suppress ovulation

01:59:06.160 | for periodically using hormone-based contraception

01:59:09.660 | just so that they can offset the risk of ovarian cancer?

01:59:13.340 | - That's a very rational question.

01:59:15.000 | And I would say that's what mainstream medicine

01:59:17.600 | has had at its back to recommend oral contraceptives,

01:59:22.560 | not just for women who are seeking contraception,

01:59:24.780 | but for acne, for painful periods,

01:59:29.260 | for really kind of the drop of a hat

01:59:32.060 | they're prescribing oral contraceptives.

01:59:33.620 | That's what I was taught to do.

01:59:35.380 | But there are so many consequences.

01:59:37.340 | And I think the issue here is more about consent,

01:59:40.760 | because in OB/GYN,

01:59:44.400 | and I started out as a board certified OB/GYN,

01:59:47.580 | and I now mostly see men,

01:59:49.220 | but I was taught as an OB/GYN

01:59:52.420 | to convince women to go on the oral contraceptive.

01:59:55.060 | And I think a lot of that is pharmaceutical influence.

01:59:57.980 | So maybe we could talk about the risks

02:00:00.780 | and why the answer is no to your question.

02:00:04.220 | - As we do that, could I just ask,

02:00:05.820 | is the so-called ring,

02:00:07.700 | it used to be called the NuvaRing,

02:00:09.940 | maybe that's a brand name,

02:00:10.780 | but when I was in college,

02:00:11.860 | there was all this discussion about the ring, right?

02:00:13.940 | By both men and women for reasons that don't belong

02:00:16.980 | on the podcast.

02:00:17.900 | Use your imagination, folks.

02:00:20.160 | So is the ring, obviously,

02:00:22.740 | it's not oral hormone contraception,

02:00:25.460 | but it's hormone-based, right?

02:00:26.760 | The ring is releasing estrogen locally

02:00:29.000 | as opposed to taking it orally.

02:00:30.100 | But would you slot it under what you're about to tell us

02:00:32.900 | in terms of the concerns?

02:00:34.140 | - So we have less data about the ring.

02:00:37.820 | So the oral contraceptive is two hormones.

02:00:41.580 | It's ethinyl estradiol,

02:00:43.600 | and it's a progestin.

02:00:47.280 | So it's not the normal progesterone that your body makes,

02:00:51.900 | that your ovaries make and your adrenals make.

02:00:53.720 | It is a synthetic form of progesterone.

02:00:59.280 | And it is the same progestin, similar,

02:01:03.380 | same class that was shown to be dangerous and provocative

02:01:06.980 | in the Women's Health Initiative.

02:01:08.740 | So I'm not a fan of progestins.

02:01:11.520 | I do not recommend them for any woman,

02:01:14.700 | unless the consequence of not taking them is surgery

02:01:18.580 | or some other,

02:01:20.240 | unless it gives them some freedom in some way.

02:01:25.520 | So I don't like progestins.

02:01:28.180 | The NuvaRing is estrogen plus progestin,

02:01:33.180 | but it's released transdermally through the vagina.

02:01:36.920 | So given the way that it's delivered to the vagina,

02:01:41.920 | the doses are lower than what's taken orally.

02:01:47.500 | But in terms of some of the risks

02:01:49.080 | that I'm about to talk about,

02:01:50.080 | we don't know about much of the data.

02:01:52.660 | We think that it's similar.

02:01:53.920 | There's probably a spectrum of risk,

02:01:56.300 | and the NuvaRing is a little more towards the middle

02:01:59.560 | than what I'm talking about with oral contraceptives.

02:02:03.200 | Are you ready for that?

02:02:04.120 | - Yeah, I'm ready for the risks.

02:02:05.520 | - Okay, so like with almost any pharmaceutical,

02:02:10.220 | the oral contraceptive depletes certain micronutrients.

02:02:14.240 | So magnesium, there's certain vitamin Bs that are depleted.

02:02:17.980 | It also affects the microbiome.

02:02:23.760 | That data is not as strong,

02:02:25.340 | but there seems to be some effect,

02:02:26.720 | and there's also an increased risk

02:02:28.340 | of inflammatory bowel disease and autoimmune condition.

02:02:31.800 | It increases inflammatory tone.

02:02:34.480 | So the studies that I've seen increase

02:02:37.360 | one of the markers of inflammatory tone,

02:02:40.680 | high sensitivity CRP, by about two to three X.

02:02:43.960 | It seems to make the hypothalamic-pituitary-adrenal axis

02:02:49.120 | more rigid so that you can't kind of roll with the punches

02:02:54.000 | and wax and wane in terms of cortisol production

02:02:56.520 | the way that you can off the birth control pill.

02:02:58.980 | It can affect thyroid function.

02:03:02.560 | I'm thinking of the slide that I have

02:03:05.580 | that has like 10 problems associated

02:03:08.540 | with the oral contraceptive,

02:03:09.560 | but that's what I can remember right now.

02:03:11.560 | - That's very helpful,

02:03:12.620 | and it makes me wonder whether or not,

02:03:14.860 | if on the one hand oral contraceptives are protective

02:03:18.320 | in women against ovarian cancer,

02:03:19.920 | but then they have these other issues.

02:03:21.300 | - Yeah, there's one other I want to mention.

02:03:22.680 | - Please.

02:03:23.840 | - Anytime you take oral estrogen,

02:03:26.240 | it raises sex hormone binding globulin,

02:03:28.680 | and you've talked to other podcast guests about this,

02:03:31.160 | Kyle, I think.

02:03:32.600 | Sex hormone binding globulin, I think of it as a sponge

02:03:36.020 | that soaks up free estrogen and free testosterone.

02:03:40.700 | So when you go on the birth control pill,

02:03:42.500 | you raise your sex hormone binding globulin.

02:03:44.800 | It soaks up especially free testosterone,

02:03:48.200 | and for some women, it's not a big deal.

02:03:51.560 | They don't notice much of a difference,

02:03:53.540 | but then there's a phenotype,

02:03:55.320 | maybe related to CAG repeats on the androgen receptor,

02:03:59.840 | who are exquisitely sensitive

02:04:01.960 | to that decline in free testosterone.

02:04:04.940 | So this then opens the portal of talking a little bit

02:04:07.720 | about testosterone in women.

02:04:09.740 | So we've mentioned already that it's the most abundant,

02:04:13.080 | biologically the most abundant hormone in the female system.

02:04:16.680 | Even though men make almost 10 times as much,

02:04:19.180 | or even more than 10 times, it is so important for women.

02:04:23.060 | It is essential to so many things,

02:04:25.080 | not just sex drive and muscle mass

02:04:27.340 | and seeing a response to resistance training,

02:04:30.220 | but also confidence in agency.

02:04:33.040 | And so those women who are so sensitive

02:04:36.000 | to their testosterone level,

02:04:37.160 | they've got this high sex hormone binding globulin,

02:04:39.680 | their testosterone declines,

02:04:42.100 | what they describe is vaginal dryness,

02:04:45.980 | maybe a decline in sex drive,

02:04:48.320 | but there's also this bigger issue

02:04:50.540 | related to confidence in agency, even risk-taking

02:04:53.600 | from studies that we've done with MBA students

02:04:56.120 | that I think is a serious problem.

02:04:57.820 | Maybe the most important out of all of these things

02:05:01.320 | is that it can shrink the clitoris by up to 20%, 20%.

02:05:06.320 | - And that includes a regression of the nerves

02:05:09.400 | that innervate the clitoris, is that, I mean-

02:05:12.160 | - That's a very good question as a neuroscientist.

02:05:14.320 | - Yeah, I would think you used to teach

02:05:16.680 | the neural side of reproductive health.

02:05:18.740 | We need to do a series on sexual health.

02:05:20.180 | Maybe you would co-host that with me.

02:05:21.520 | - Sure.

02:05:22.820 | - We could certainly use your expertise.

02:05:24.920 | I think, yeah, that's a dramatic number.

02:05:28.960 | - Yeah, but then let's go back to the sacred marketing.

02:05:31.440 | If I've got a woman that I think

02:05:33.240 | should not be on the birth control bill,

02:05:34.640 | maybe she's taking it for acne

02:05:35.960 | or she's taking it 'cause her periods were a little painful.

02:05:38.680 | What I'm going to do is say,

02:05:40.820 | let's leverage these other ways

02:05:42.920 | of making your period less painful.

02:05:45.140 | Let's take the message of your painful periods

02:05:48.400 | and figure out, okay, is it your inflammatory tone?

02:05:51.840 | And we give you some fish oil and SPMs,

02:05:53.740 | maybe a little aspirin when you've got your period.

02:05:56.000 | Let's find some other ways to deal with it

02:05:57.980 | than to take the oral contraceptive,

02:06:00.060 | which you have not received informed consent about,

02:06:03.200 | because it can trick your clit by up to 20%.

02:06:06.500 | Now, that usually convinces most people to come off of it.

02:06:08.720 | - Is that reversible?

02:06:09.720 | - The elevation in sex hormone-abiding globulin

02:06:14.420 | does not seem to go away

02:06:16.520 | when you come off the birth control pill.

02:06:19.200 | To me, that is the biggest problem

02:06:22.240 | with prescribing oral contraceptives.

02:06:24.660 | Now, the data that we have is limited.

02:06:26.680 | There's one woman who, Claudia something something,

02:06:30.360 | who looked at sex hormone-binding globulin

02:06:33.360 | a year out from stopping the birth control pill,

02:06:36.040 | and it was still elevated.

02:06:37.280 | It wasn't as high as it was when they were on the pill,

02:06:39.880 | but it was still elevated.

02:06:41.520 | So your question about reversibility,

02:06:43.800 | I don't know if we know the answer to that.

02:06:46.440 | - Wow, okay.

02:06:47.540 | That's, yeah, that's a significant statement

02:06:52.200 | and something that for consideration.

02:06:54.280 | Related to this, although this might seem not related,

02:06:58.160 | it is, how early do you recommend

02:07:02.160 | that women go get their follicle number assessed?

02:07:07.160 | In other words, to get a sense of the size

02:07:09.740 | of the ovarian reserve and their AMH levels measured?

02:07:15.080 | I'm an amateur outsider as I say this,

02:07:17.080 | but we have an episode on fertility

02:07:19.080 | where I just described the ovulatory menstrual cycle.

02:07:22.120 | - I'm not the best person to answer that.

02:07:25.320 | - Yeah, well, we can- - I'm too far out from it.

02:07:27.200 | - Okay, well, I suppose then from taking the perspective

02:07:30.420 | of somebody who thinks about fertility

02:07:33.280 | in terms of at least congruent with vitality and longevity,

02:07:37.300 | given that it's fairly noninvasive,

02:07:40.240 | it's an ultrasound or a blood draw for AMH or both,

02:07:43.940 | is there any reason why a woman would not want

02:07:46.320 | to get her follicle number assessed

02:07:47.860 | or her AMH levels assessed?

02:07:50.040 | Is there any reason why?

02:07:52.240 | Because I was shocked to learn that most women don't do this

02:07:54.860 | until they're hitting their late 30s or early 40s

02:07:58.120 | and they either haven't conceived

02:08:00.180 | or they suddenly decide that they want to conceive.

02:08:02.240 | And I thought, why doesn't every doctor insist

02:08:05.540 | that their female patients have their AMH level addressed

02:08:09.800 | so that if they need to freeze eggs, they can?

02:08:13.380 | - It's cost?

02:08:14.220 | - Yeah, so I think if you've got the disposable income

02:08:16.180 | to do it, go for it.

02:08:17.880 | - It's not included in a standard blood panel?

02:08:19.620 | - No. - Wow.

02:08:21.060 | - The only women in my practice who've had AMHs done

02:08:24.580 | and have looked at their follicle count

02:08:26.740 | are women who want to freeze their eggs

02:08:29.640 | and that requires disposable income,

02:08:33.440 | or they are having trouble getting pregnant,

02:08:37.740 | so they are in the reproductive endocrinology system

02:08:41.380 | and they're getting an evaluation.

02:08:43.840 | And then there are also the women who have symptoms

02:08:48.040 | of early menopause, so premature ovarian insufficiency,

02:08:51.780 | which is before age 40.

02:08:53.360 | Those are the women that I see getting attested

02:08:56.940 | and I think you're right

02:08:58.380 | that it should be offered more broadly.

02:09:01.020 | It speaks to the democratization of data again

02:09:04.220 | and I think most women don't know that.

02:09:06.500 | So you're doing a huge service, I think,

02:09:08.080 | to be speaking into this.

02:09:10.500 | One other point related to that

02:09:14.820 | is that what I see in conventional medicine

02:09:19.820 | is that when a woman asks for a hormone panel

02:09:22.820 | and she's not trying to get pregnant,

02:09:26.020 | she usually gets told that hormones vary too much,

02:09:31.020 | it's a waste of money, you don't need it.

02:09:33.420 | Or if you're feeling hormonal,

02:09:36.740 | why don't you go on a birth control bill?

02:09:39.540 | Unless she's trying to get pregnant.

02:09:42.420 | If she's trying to get pregnant,

02:09:43.900 | suddenly those same tests are very reliable

02:09:46.700 | and they get their free testosterone,

02:09:50.660 | their thyroid panel, they get their estrogen and progesterone,

02:09:54.260 | maybe they get their cortisol, they get their AMH.

02:09:57.780 | So there's a double standard

02:10:00.300 | between those who want to get pregnant and those who don't

02:10:02.820 | and that needs to end.

02:10:04.260 | - Yeah, I totally agree.

02:10:05.420 | As I've learned more about ovulatory cycle

02:10:08.660 | and AMH and the antral population of follicles,

02:10:12.380 | it's fascinating, it just seems to me, wow,

02:10:14.740 | a relatively straightforward test,

02:10:16.220 | one definitely invasive ultrasound, but-

02:10:20.100 | - I don't consider that.

02:10:21.020 | That's not invasive. - Yeah, not terribly invasive,

02:10:22.940 | but invasive, at least,

02:10:24.820 | but the other one, just pure blood test,

02:10:26.840 | just seems like why wouldn't this be offered

02:10:29.100 | or covered by insurance or that anyone that wanted it?

02:10:31.600 | But now I understand why.

02:10:34.140 | You mentioned menopause, huge topic,

02:10:37.940 | enormous topic.

02:10:39.460 | We had a guest on the podcast who's not a clinician

02:10:43.300 | who said something in passing,

02:10:45.860 | so I'm likely to get this wrong,

02:10:48.100 | but what they said was that the results

02:10:51.100 | of the large-scale trials on hormone replacement therapy

02:10:54.920 | for women for menopause said something to the effect of,

02:10:58.140 | if the hormone therapy was started early enough,

02:11:00.900 | it was very beneficial for vitality and health outcomes.

02:11:04.340 | Whereas if women went through menopause

02:11:06.940 | and then initiated the hormone therapy,

02:11:08.860 | hormone replacement therapy,

02:11:11.500 | that it could be detrimental to their health.

02:11:14.980 | So first of all, do I recall that statement correctly?

02:11:18.580 | And then second of all,

02:11:20.100 | what sorts of hormones are being replaced?

02:11:22.220 | Is it just estrogen?

02:11:23.580 | And how is that done?

02:11:24.720 | Is it done through birth control?

02:11:26.380 | So oral contraceptives, NuvaRings,

02:11:28.980 | what are your thoughts on menopause?

02:11:30.520 | When should people start thinking about it?

02:11:32.820 | And what is the palette of things available

02:11:36.320 | so that we can do an entire episode with you

02:11:38.260 | on this topic in the future?

02:11:40.420 | But just to, I get a lot of questions about this

02:11:42.760 | and I'm guessing based on everything you've told me today

02:11:45.820 | that there are women in their 30s

02:11:47.940 | that while they may be 20 years out from menopause,

02:11:51.600 | probably should be doing things now

02:11:52.880 | in anticipation of that.

02:11:54.140 | - Yes, so we haven't talked about the 30 something,

02:11:56.400 | but I totally agree with you.

02:11:58.140 | The more you know about your phenotype,

02:12:00.480 | your hormonal phenotype when you're in your 30s,

02:12:03.320 | you're set up in terms of what to do in the future,

02:12:07.420 | especially things like your thyroid,

02:12:09.260 | your estrogen and progesterone levels,

02:12:10.820 | 'cause you can replace to a state of you thyroid,

02:12:15.820 | whatever that is for you.

02:12:18.600 | You can replace, I don't usually go exactly back

02:12:21.460 | to where the estrogen and progesterone levels were,

02:12:23.940 | but we can get pretty close.

02:12:25.920 | So in your 30s, having a base case,

02:12:27.920 | I think is really essential.

02:12:29.740 | So you spoke to the Women's Health Initiative,

02:12:32.660 | which was published in 2002.

02:12:35.140 | And we went from a huge number of women

02:12:37.300 | taking hormone therapy to a very small percentage,

02:12:40.600 | like in the range of 5%.

02:12:42.780 | And that means we've got millions and millions of women

02:12:45.960 | who are suffering needlessly with things like insomnia,

02:12:50.820 | difficulty with their mood, difficulty with sex drive,

02:12:55.740 | feeling like they are closing the store in terms of sex,

02:12:59.900 | because they're not on hormone therapy.

02:13:02.660 | I would agree with the statement that you made

02:13:04.580 | that hormone therapy,

02:13:06.180 | particular forms that are similar

02:13:08.020 | to what your body always made,

02:13:09.660 | when it's given judiciously at the right time,

02:13:13.320 | typically within five to 10 years of menopause,

02:13:16.220 | which is 51 to 52, that it is incredibly safe.

02:13:20.820 | So it's a complicated study, the Women's Health Initiative,

02:13:24.980 | but it was the wrong study in the wrong patients

02:13:29.280 | with the wrong medications

02:13:31.880 | and with some of the wrong outcomes.

02:13:35.420 | So it was powered to look at cardiovascular outcomes.

02:13:38.500 | It was not powered to look at breast cancer.

02:13:40.740 | It was stopped because of breast cancer risk.

02:13:43.700 | But what happened in the control arm of the study

02:13:46.740 | was that they had an incredibly low rate of breast cancer.

02:13:51.060 | And so as a result, they ended up having

02:13:53.420 | this increased risk of breast cancer at five years,

02:13:58.000 | and they stopped the study.

02:14:00.100 | Now, the study was done with synthetics.

02:14:01.980 | It was done with conjugated equine estrogen,

02:14:04.580 | known as Premarin, and midroxyprogesterone acetate.

02:14:07.900 | Those were the so-called estrogen and progesterone.

02:14:11.520 | Those are synthetic hormones.

02:14:14.100 | We think especially the progesterone is associated

02:14:16.540 | with the greater risk of breast cancer,

02:14:18.620 | although the subsequent re-evaluations of the data,

02:14:23.520 | now 18 years out, have shown that

02:14:27.760 | this problem with the control group

02:14:30.220 | and no increased risk of breast cancer.

02:14:32.920 | And for the women who got estrogen only,

02:14:36.720 | those who had a hysterectomy, the Premarin,

02:14:39.680 | they actually had a decreased breast cancer risk

02:14:43.040 | and decreased breast cancer mortality.

02:14:45.360 | So there's a lot to be said about this.

02:14:49.000 | I'm trying to keep it really brief.

02:14:52.080 | But if you look at the women 50 to 60,

02:14:56.040 | so within 10 years of menopause,

02:14:58.320 | they're the ones who seem to have the greatest benefit.

02:15:01.120 | So they had decreased subclinical atherosclerosis,

02:15:05.080 | so less cardiovascular disease.

02:15:07.360 | They had an improvement in terms of bone health,

02:15:11.640 | less progression to diabetes.

02:15:16.680 | And then over the age of 60,

02:15:19.040 | they started to have greater risk of certain outcomes,

02:15:22.300 | such as cardiovascular disease,

02:15:23.680 | myocardial infarction, and so on.

02:15:26.120 | You asked about what do I do?

02:15:32.700 | And to me, this problem is not just menopause.

02:15:38.560 | What's more interesting is to talk about perimenopause.

02:15:42.600 | So perimenopause is the period of time

02:15:45.660 | before your final menstrual cycle.

02:15:48.320 | And for most women,

02:15:49.600 | depending on how attuned you are to the symptoms,

02:15:52.520 | it can last for 10 years.

02:15:55.360 | So I'm still in perimenopause.

02:15:56.640 | It's been like 20 years

02:15:58.640 | because I've been tracking it so carefully.

02:16:00.800 | It usually gets kicked off

02:16:03.020 | by having your cycle get closer together.

02:16:04.980 | So that could happen in your 30s or your 40s.

02:16:08.000 | You go from 28 days to 25 days, that sort of thing.

02:16:11.560 | You may notice that you start sleeping more poorly

02:16:13.660 | because progesterone is so important.

02:16:15.200 | You talked about that with Kyle.

02:16:17.520 | You may notice it as more anxiety, difficulty sleeping,

02:16:20.720 | and that probably is related to the estrogen receptor.

02:16:24.480 | So ER alpha is estrogen receptor.

02:16:27.620 | Alpha is angio, it increases anxiety.

02:16:32.360 | ER beta is associated with an anxiolytic activity.

02:16:36.960 | And then there's a total

02:16:38.080 | of about six estrogen receptors now.

02:16:40.360 | There's the G protein coupled estrogen receptors,

02:16:44.000 | and those are mixed, anxiolytic, anxiogenic.

02:16:47.680 | So there's this whole period of perimenopause.

02:16:51.040 | And what's most fascinating to me,

02:16:53.400 | and we've got to talk about this

02:16:54.960 | either today or another time,

02:16:57.000 | is that there is this massive, massive change

02:17:00.020 | that happens in the female brain

02:17:01.720 | that people are not talking about enough.

02:17:05.200 | And so looking at the work of Lisa Moscone at Cornell,

02:17:09.400 | from starting around age 40,

02:17:13.560 | there is this massive change in cerebral metabolism.

02:17:17.000 | So you can do FDG PET scans,

02:17:19.000 | you can look at glucose uptake,

02:17:20.920 | and there's about, on average, a 20% decline

02:17:25.240 | from premenopause, up to like age 35,

02:17:30.200 | to perimenopause, to postmenopause.

02:17:34.080 | The women who are having the most symptoms

02:17:36.600 | in perimenopause to menopause,

02:17:37.920 | the hot flashes, the night sweats,

02:17:39.320 | the difficulty of sleeping,

02:17:40.720 | those are the ones who have the most significant

02:17:43.280 | cerebral hypometabolism.

02:17:46.600 | So it's almost like a,

02:17:47.920 | I don't want to scare people with this language,

02:17:50.880 | but it's a low level,

02:17:53.760 | or let's call it pseudo dementia of sorts.

02:17:56.640 | - Yes, it seems to be a phenotype

02:17:59.840 | that you can then map to Alzheimer's disease,

02:18:03.160 | because that's Lisa Moscone's work.

02:18:04.960 | She's looking at, okay,

02:18:07.440 | Alzheimer's disease is not a disease of old age,

02:18:09.580 | it is disease of middle age.

02:18:11.180 | What are some of the biomarkers that we can define

02:18:14.240 | that can tell you what your risk is?

02:18:16.880 | I've got a mother and a grandmother

02:18:18.580 | with Alzheimer's disease,

02:18:19.540 | you can believe I am all over this data.

02:18:21.840 | - And insulin resistance.

02:18:23.800 | - Huge part of it. - Insensitivity,

02:18:24.920 | as we talked about it before,

02:18:26.760 | seems to be somewhere in there,

02:18:28.520 | which I think when that idea first surfaced,

02:18:32.080 | a few people were like, "Really?"

02:18:33.100 | But then of course, right?

02:18:34.080 | I mean, the brain is this incredibly

02:18:35.480 | metabolically demanding organ.

02:18:37.720 | You deprive neurons of fuel sources,

02:18:41.040 | or you make them less sensitive to fuel sources.

02:18:43.680 | They start dying, they certainly start firing less.

02:18:45.880 | It makes perfect sense.

02:18:46.980 | And I think now it's, thanks to Lisa's work,

02:18:49.420 | work that you've done and talked about quite a lot

02:18:52.500 | is in your books and elsewhere,

02:18:54.280 | I think has really highlighted for people

02:18:56.960 | that metabolism and metabolomics

02:19:00.840 | is going to be as important as genes and genomics

02:19:03.960 | when it comes to dementia. - That's right.

02:19:06.320 | - Perhaps, especially in women, is it safe to say that?

02:19:09.360 | - I think so, because,

02:19:11.880 | we believe that the system is regulated by estrogen.

02:19:16.880 | So the decline in estrogen, starting around age 40,

02:19:22.440 | 43 is kind of the average,

02:19:24.540 | seems to be the driver behind cerebral hypometabolism.

02:19:28.080 | The way I describe it to my patients is,

02:19:30.800 | it's like slow brain energy.

02:19:33.160 | So you walk into a room, you can't remember why,

02:19:35.360 | like you just notice that you can't manage all the tasks

02:19:38.400 | the way that you once could.

02:19:39.720 | Like things are just a little slower.

02:19:41.960 | And I say that to women and they're like,

02:19:44.360 | "I have that, like help me."

02:19:47.520 | So this is then circling back to WHI,

02:19:50.980 | where women are scared to death of taking hormone therapy.

02:19:55.040 | And we've got all of these women

02:19:56.600 | that are marching toward potentially a greater risk

02:19:59.680 | of Alzheimer's disease.

02:20:01.600 | And they have this opportunity in their 40s and their 50s

02:20:04.720 | to take hormone therapy and they may not be offered it.

02:20:08.440 | Because the typical conventional approach based on WHI

02:20:11.880 | is to say, unless you're having hot flashes and night sweats

02:20:15.480 | that are severe, I'm not gonna give you hormone therapy.

02:20:18.100 | And I just wanna call that out.

02:20:19.600 | I would say, no, that is not the way to approach it.

02:20:22.360 | Further, the concept right now in conventional medicine

02:20:28.440 | is that hot flashes and night sweats

02:20:30.840 | are these nuisance symptoms

02:20:32.180 | that we will take care of temporarily,

02:20:34.760 | maybe with a little bit of estrogen progesterone

02:20:37.200 | or a birth control pill, 'cause it's given a lot.

02:20:39.440 | - Or that they pass.

02:20:40.640 | - Or that you just suck it up, suck it up.

02:20:44.180 | Doesn't matter that you're not sleeping anymore.

02:20:47.080 | Turn down the temperature in your room.

02:20:49.580 | And that's not right because hot flashes and night sweats

02:20:53.720 | are a biomarker of cardiometabolic disease.

02:20:57.320 | They are a biomarker of increased bone loss.

02:21:00.380 | They are a biomarker of changes in the brain.

02:21:05.200 | So many of these symptoms that occur in perimenopause

02:21:07.920 | are not driven by the ovaries.

02:21:09.680 | They are driven by the brain.

02:21:11.660 | - Yeah, it's the bi-directional crosstalk

02:21:14.400 | between the body and the brain keeps,

02:21:16.720 | I think is this resounding theme.

02:21:18.880 | We had Chris Palmer on here, a psychiatrist,

02:21:20.760 | who's talking about ketogenic diet

02:21:22.200 | for treatment and mental health.

02:21:23.240 | I know we could have a whole other discussion,

02:21:26.320 | and we will, I hope, if you'll agree to it about nutrition

02:21:29.520 | and as it relates to hormones, specific diets and so forth.

02:21:34.240 | But the- - And that's a question too,

02:21:36.480 | whether this problem of cerebral hypometabolism,

02:21:41.480 | could we solve it with estrogen

02:21:44.520 | and/or increase metabolic flexibility?

02:21:47.480 | So I just wanted to footnote that.

02:21:49.280 | Sorry to interrupt you. - No, please, please interrupt.

02:21:51.980 | I know you're, as long as we're there,

02:21:54.840 | I know you are a fan in some instances

02:21:57.240 | of intermittent fasting, time-restricted feeding,

02:21:59.880 | and/or ketogenic diet. - Yes.

02:22:02.600 | - To get cells sensitive to insulin,

02:22:06.200 | which is not to say, if I understand correctly,

02:22:08.200 | which is not to say that women need to stay

02:22:11.160 | on the ketogenic diet for long periods of time

02:22:14.700 | or intermittent fast for my only time-restricted feeding

02:22:16.940 | for eight hours or six hours a day,

02:22:18.320 | but that by increasing, you said metabolic flexibility,

02:22:21.520 | excuse me, but by increasing cells' sensitivity to insulin

02:22:27.460 | and then maybe returning to a more typical eating pattern

02:22:30.800 | and periodically switching back and forth,

02:22:32.260 | that might actually be beneficial.

02:22:34.180 | Do I have that right?

02:22:35.480 | - Yeah, I love the pulse.

02:22:37.000 | So I feel like it's much more physiologic

02:22:39.320 | than, say, going on a ketogenic diet

02:22:41.420 | and staying there for years.

02:22:43.220 | All of the data that we have on the ketogenic diet,

02:22:46.340 | it's pretty limited in terms of duration.

02:22:49.300 | The longest players that we have in terms of the data

02:22:52.320 | are the folks with epilepsy,

02:22:54.660 | and that's just a different phenotype.

02:22:56.860 | So I think in terms of microbiome effects,

02:23:00.100 | diversity, dysbiosis, some of those issues,

02:23:02.960 | we really don't know in terms of long-term effects.

02:23:06.240 | So I prefer with a ketogenic diet

02:23:08.560 | that it's used as an end-of-one experiment

02:23:11.160 | and that you do it for four weeks.

02:23:12.980 | Maybe you measure biomarkers before and afterwards.

02:23:15.800 | Maybe you look at your stool before and afterwards,

02:23:17.740 | and we still haven't talked about stool tests yet,

02:23:19.900 | but you could measure your fasting insulin and your glucose.

02:23:23.660 | You could just start there, do four weeks of keto,

02:23:26.700 | clean keto, including vegetables.

02:23:28.980 | It doesn't have to be 57 a day,

02:23:31.020 | and then measure it again afterwards.

02:23:33.580 | - Since you mentioned stool testing,

02:23:36.140 | what is your recommendation about stool testing?

02:23:40.720 | - So my recommendation, this is again in the field

02:23:46.180 | of if you have the disposable income.

02:23:48.460 | So I usually start with Genova

02:23:49.900 | because they've got a good copay system with insurance.

02:23:53.500 | That's what I typically use.

02:23:54.980 | So I usually do their one-day stool test

02:23:57.500 | where you have to go digging through your stool

02:24:00.740 | and send it off to this lab that's in North Carolina.

02:24:04.580 | I usually do the one-day

02:24:05.660 | unless I'm concerned about parasites.

02:24:07.660 | In that case, I tend to do three days.

02:24:09.360 | I do that for people who travel a fair amount

02:24:11.580 | and go to places where there's greater risk

02:24:13.520 | or they just have gut symptoms.

02:24:15.820 | Another test that I do a lot is,

02:24:19.860 | 'cause I always like to mention two labs,

02:24:22.200 | is a test by Wangeviti.

02:24:24.740 | And this is much more of a data wonk type of test

02:24:29.680 | 'cause it's powered by AI.

02:24:30.860 | It was designed by a guy who's got inflammatory bowel disease

02:24:35.860 | and he's a PhD deep phenotyping bioinformatics guy

02:24:41.700 | who wanted to make this really easy.

02:24:48.140 | So the test is under the umbrella of Thorne

02:24:52.360 | and they used to call it gut bio.

02:24:54.660 | They might have another name for it.

02:24:55.840 | And they just improved it so that it's a wipe

02:24:59.040 | instead of digging through your stool.

02:25:01.100 | And so my athletes will do it now.

02:25:02.820 | They were not so into digging through their stool before.

02:25:05.540 | - Is anybody?

02:25:07.220 | - Really, no one is.

02:25:08.100 | - I don't want the answer to that.

02:25:10.420 | I know the answer, I prefer to that.

02:25:12.540 | - But that's a super interesting test

02:25:14.240 | because you get much more dense data.

02:25:19.140 | The issue is, with apologies to my friends at Thorne,

02:25:23.660 | the issue is that their recommendations

02:25:25.980 | end up being Thorne supplements.

02:25:28.300 | So that can be very easy for people

02:25:30.280 | who want to connect the dots.

02:25:33.100 | That's not always the way that I like to do it.

02:25:37.480 | - First of all, three things.

02:25:40.200 | You've shared with us an immense amount of knowledge.

02:25:45.860 | And in that first statement, I also want to apologize

02:25:49.780 | because I threw at you the entire lifespan of,

02:25:52.900 | female lifespan, reproductive health, contraception,

02:25:56.300 | diet, microbiome, so many things.

02:25:58.980 | But I first, I just want to say,

02:26:02.260 | you've taught me a tremendous amount,

02:26:04.060 | including I think something that most people,

02:26:08.980 | including myself, have not thought about enough,

02:26:11.240 | which is the psychosocial impact

02:26:14.140 | on things that we're all familiar with.

02:26:17.200 | Constipation, bowel movements, what we eat, what we avoid.

02:26:21.380 | I have to say really a huge thank you for that

02:26:25.580 | because it's not something that's been discussed

02:26:28.180 | on this podcast before.

02:26:29.660 | Sort of know that brain communicates with body,

02:26:32.220 | psychology and biology are linked.

02:26:33.880 | But I think this is the first time

02:26:35.020 | that anyone's ever directly linked circumstances

02:26:39.520 | and biology and psychology in such a concrete way.

02:26:42.620 | So that's the first thing.

02:26:44.300 | And I know I speak for many people on that.

02:26:46.540 | Second of all, we barely scratched the surface

02:26:49.780 | of your knowledge, which is both frustrating for me

02:26:54.040 | because I always want to learn more

02:26:56.900 | and I know many other people do as well,

02:26:58.620 | but also very, very exciting because hopefully

02:27:01.500 | without much persuasion, we can have you back

02:27:03.380 | on to talk about things. - No persuasion at all.

02:27:06.620 | - I know you're working with men now.

02:27:07.700 | Men's health, some particulars around,

02:27:11.060 | I think there's more for us to explore

02:27:13.360 | in terms of PCOS, menopause, contraception

02:27:15.660 | and all of the above, but then something that you and I

02:27:17.900 | were talking about off camera before we started,

02:27:20.960 | which I think is a really important factor

02:27:23.460 | that ties back to this issue of trauma and stress

02:27:27.700 | and the bi-directional relationship

02:27:29.960 | between biology and psychology.

02:27:31.620 | Hopefully someday we won't even separate those two,

02:27:34.780 | which is the use of specific medicines,

02:27:37.460 | including plant medicines and how that can influence

02:27:40.620 | overall health, which no doubt will include hormone health.

02:27:43.820 | So I say all of that for two reasons.

02:27:46.360 | First of all, to queue up the,

02:27:48.420 | we won't even call it a part two, but a sequel to this,

02:27:51.580 | which I'm gratified to hear that you'll join us for that.

02:27:55.260 | And then also to just really extend a huge thank you,

02:27:57.900 | the amount of knowledge that you shared is immense

02:28:01.260 | and is going to be very, very useful and actionable

02:28:05.420 | for men in terms of their thinking and their actions

02:28:08.940 | and for women in particular, today's discussion

02:28:13.100 | in particular for women in terms of how to think

02:28:15.300 | about their health and biology,

02:28:16.660 | how to think about their psychology and the environment

02:28:18.600 | that all of that is embedded in.

02:28:20.180 | So I just want to say an enormous thank you.

02:28:23.020 | - Thank you, Andrew.

02:28:23.940 | I so appreciate that.

02:28:25.180 | And I so appreciate what you offer to the world

02:28:28.560 | in terms of a way in, a way to understand physiology

02:28:32.760 | and how to craft a architect, a better life.

02:28:37.700 | - Can I just add one last thing?

02:28:39.620 | 'Cause I didn't talk about it since we didn't get

02:28:41.700 | to the forties and the fifties in this list of biomarkers.

02:28:45.560 | So I feel like if people, if women went away

02:28:48.740 | with one thing today,

02:28:50.620 | it would be to do a coronary artery calcium score

02:28:54.260 | by age 45 and sooner if you've got premature heart disease.

02:28:57.820 | - How is that taken?

02:28:59.060 | - So it's a CT scan of the chest.

02:29:02.140 | You can self order it.

02:29:03.340 | Like I think at Stanford hospital, you can self order it.

02:29:05.860 | Last time a patient checked, it was $250.

02:29:08.380 | So again, disposable income.

02:29:10.900 | But it tells you, it almost gives you this fork in the road

02:29:15.100 | in terms of how much you need to pay attention

02:29:17.020 | to cardiometabolic health as a woman.

02:29:19.280 | And it's a 45 for men too.

02:29:21.860 | So if you haven't had one, have you had one?

02:29:23.980 | - No. - You need one.

02:29:25.740 | Insulin, cortisol, CAC.

02:29:28.180 | - Great, I'll run all that by you.

02:29:30.260 | - It's really essential and it's,

02:29:35.000 | yeah, it's so fascinating because there's some women

02:29:39.380 | who have a zero, so my score is zero and that's great.

02:29:42.280 | So often you can just keep doing what you're doing.

02:29:44.960 | But if you're 45 and you're starting to be elevated

02:29:48.520 | or you've got, maybe you've got PCOS

02:29:51.620 | or you've got some other biomarkers tending you

02:29:54.240 | in this direction toward the number one killer,

02:29:56.760 | really eight to nine out of the top 10 killers in the US,

02:30:02.580 | that allows you to really start to make changes.

02:30:05.220 | And I think it's essential to know that data.

02:30:08.340 | It's probably not going to be offered by your doctor.

02:30:11.500 | Certainly Peter Attia is going to offer it,

02:30:13.360 | but most conventional doctors are not going to do it.

02:30:15.980 | And then the last thing I want to say.

02:30:17.700 | - Before you mentioned, so if I were to go to my doctor

02:30:19.820 | and I just say, I want a cardiac calcium score,

02:30:22.360 | that's what people should ask.

02:30:23.200 | - Coronary artery calcium score, CAC.

02:30:26.220 | - Okay, so everyone hear that and know that.

02:30:29.260 | If you're 40 or older and maybe if you're-

02:30:30.940 | - 45. - 45 or older, get it.

02:30:33.640 | - So the last thing is, and this is for men and women,

02:30:37.380 | is your ACE score.

02:30:39.380 | So adverse childhood experiences.

02:30:42.380 | Knowing your ACE score is so essential

02:30:44.980 | in terms of a baseline for how much trauma your system,

02:30:49.100 | your PIND system endured when you were a kid.

02:30:52.140 | And we know that childhood trauma,

02:30:55.040 | whether it's abuse or neglect or having an alcoholic parent,

02:31:00.080 | that maps to disease and middle age.

02:31:02.860 | And it can give you so much insight.

02:31:04.540 | I'll give you an example.

02:31:05.380 | I've got a patient who had

02:31:06.880 | an elevated coronary artery calcium score

02:31:08.960 | who does everything right with her food.

02:31:11.300 | I think it was her trauma that elevated her CAC

02:31:14.700 | when she was 45.

02:31:16.480 | So I think an ACE score, knowing your ACE score,

02:31:19.980 | starting as a teenager, like knowing it

02:31:23.760 | and knowing how to work with that is really essential.

02:31:26.720 | - There are certain people, they are exceedingly rare,

02:31:29.220 | but you are one such person that when they speak,

02:31:31.480 | knowledge just comes out of them

02:31:34.240 | and it's incredibly useful and helpful knowledge.

02:31:36.760 | So thank you, I'm going to get both of those things.

02:31:38.880 | - Good.

02:31:39.720 | - And I highly recommend that everyone else

02:31:41.880 | pursue ways that they can get those,

02:31:43.480 | or if they can't get them, that they, you know,

02:31:47.040 | earmark those as things to get at the point

02:31:49.160 | where they can obtain sufficient disposable income.

02:31:53.240 | Sounds like the health, the detriments to health

02:31:57.180 | that those can offset would be well worth the cost.

02:32:00.020 | - Totally, thank you.

02:32:02.500 | - Thank you for joining me for today's discussion,

02:32:04.600 | all about female hormone health, vitality, and longevity

02:32:07.800 | with Dr. Sarah Gottfried.

02:32:09.480 | If you'd like to learn more about Dr. Gottfried's work,

02:32:11.680 | please check out her social media channels.

02:32:13.740 | We've provided links to those in the show note captions.

02:32:16.720 | In addition, please check out one or all

02:32:19.160 | of Dr. Gottfried's excellent books that she's written

02:32:21.780 | about nutrition, supplementation, and various treatments

02:32:24.640 | for hormone health, longevity, and vitality.

02:32:27.380 | We've linked to two of those,

02:32:28.700 | notably "Women, Food, and Hormones" and her book,

02:32:31.080 | "The Hormone Cure" in our show note captions.

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02:33:58.420 | During today's episode,

02:33:59.420 | and on many previous episodes of the Huberman Lab Podcast,

02:34:01.860 | we discuss supplements.

02:34:03.180 | While supplements aren't necessary for everybody,

02:34:05.180 | many people derive tremendous benefit from them

02:34:07.120 | for everything from sleep to focus to hormone regulation.

02:34:10.740 | The Huberman Lab Podcast is happy to announce

02:34:12.740 | that we partnered with Momentous Supplements,

02:34:14.560 | because Momentous Supplements

02:34:15.660 | are of the absolute highest quality.

02:34:17.580 | Also, they include many single ingredient formulations,

02:34:20.700 | which is essential if you wanted to design

02:34:22.300 | a supplement regimen that is both cost-effective

02:34:24.780 | and the most biologically effective supplement regimen.

02:34:27.860 | That's very hard to do with blends of supplements.

02:34:30.180 | It's very straightforward to do

02:34:31.240 | with single ingredient formulations.

02:34:33.280 | Also, Momentous Supplements ship internationally,

02:34:35.780 | which is important because we realize that many of you

02:34:37.660 | reside outside of the United States.

02:34:39.540 | If you'd like to see the supplements discussed

02:34:41.100 | on the Huberman Lab Podcast,

02:34:42.700 | you can go to Live Momentous, spelled O-U-S.

02:34:45.280 | So that's livemomentous.com/huberman.

02:34:48.520 | Thank you once again for joining me for today's discussion,

02:34:51.000 | all about female hormone health, vitality, and longevity

02:34:54.320 | with Dr. Sarah Gottfried.

02:34:56.260 | And last, but certainly not least,

02:34:58.360 | thank you for your interest in science.

02:35:00.160 | [upbeat music]

02:35:02.740 | (upbeat music)

Dr. Sara Gottfried: How to Optimize Female Hormone Health for Vitality & Longevity | Huberman Lab

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