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

1. 0:00 – 3:51

   Dr. Sara Gottfried

   1. AHAndrew Huberman0:00

      (instrumental music) Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today my guest is Dr. Sara Gottfried. Dr. Sara Gottfried is an obstetrician-gynecologist who did her undergraduate training in bioengineering at the University of Washington in Seattle. She then completed her medical training at Harvard Medical School, and she currently is a clinical professor of integrative medicine and nutritional sciences at Thomas Jefferson University. She has also been a clinician treating men and women in various aspects of hormone health and longevity for more than 20 years. She is an expert in not just traditional medicine as it relates to hormones and fertility, but also nutritional practices, supplementation, and behavioral practices, and combining all of that expertise in order to help women navigate every aspect and dimension of their hormones, longevity, and vitality, ranging from puberty to young adulthood, adulthood, perimenopause, and menopause. And nowadays she's also treating men across the lifespan in terms of longevity, vitality, and hormone health. During today's discussion, Dr. Gottfried shares an enormous amount of information and tools that women can apply toward their hormone health, fertility, vitality, and longevity. We discuss the gut microbiome, which many people have heard about, but Dr. Gottfried points out the specific needs that women have in terms of managing their gut microbiome and the ways that that influences things like estrogen levels and metabolism, testosterone, thyroid, and growth hormone, and much more. We also discuss nutrition and exercise. We touch on how the omega-3 fatty acids play a particularly important role in managing female hormone health. Dr. Gottfried points out why women have particular needs when it comes to essential fatty acids and how best to obtain those essential fatty acids for hormone health. We also discuss exercise, and she offers some surprising information about the types and ratios of resistance training to cardiovascular training that women ought to use in order to maximize their hormone health. We also talk a lot about the digestive system. This was a surprising aspect of the conversation I did not anticipate. Dr. Gottfried shared with us, for instance, that women suffer from digestive issues at more than 10 times the frequency that do men, and fortunately that there are tools specific to women that they can use in order to overcome those digestive issues, and that in overcoming those digestive issues, they can overcome many of the related hormone issues that so many women face. Dr. Gottfried also shares with you tremendous knowledge about the specific types of tests, not just blood tests but also urine and microbiome tests, that women can use in order to really get a clear understanding of their hormone status, not just of present but also where the trajectory of their hormones is taking them. So, we have an avid discussion about puberty, about young adulthood, adulthood, perimenopause and how best to manage and navigate perimenopause, and menopause, including a discussion about hormone replacement therapy. In addition to her academic and clinical expertise, Dr. Gottfried has authored many important books on nutrition, hormones, and supplementation as it relates to women and to people generally. The two books that I'd like to highlight and that we provided links to in the show note captions are Women, Food, and Hormones and The Hormone Cure. I read The Hormone Cure and found it to be tremendously interesting and informative, not just in terms of teaching me about female hormone health and various treatments for female hormone health, but also as a man trying to understand how the endocrine system interacts with mindset, nutrition, and supplementation more generally. So, I highly recommend The Hormone Cure for anybody interested in hormones and hormone health, and Women, Food, and Hormones in particular for women, although I, again, both books are going to be strongly informative for women wishing to optimize their hormone health, vitality, and longevity. Before

2. 3:51 – 7:50

   ROKA, Thesis, LMNT, Momentous

   1. AHAndrew Huberman3:51

      we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is ROKA. ROKA makes eyeglasses and sunglasses that are of the absolute highest quality. I spent a lifetime working on the biology of the visual system, and I can tell you that your visual system has to contend with an enormous number of challenges in order for you to be able to see clearly. So for instance, when you go from a very brightly lit area to a dimly lit area, your visual system has to make all sorts of adjustments that allow you to still see your environment. ROKA eyeglasses and sunglasses were built with the biology of the visual system in mind, so no matter what environment you're in, you'll be able to see with perfect clarity. And they have terrific aesthetics and enormous number of choices in terms of aesthetics. So, unlike a lot of so-called performance eyeglasses out there that only give you the option to wear the ones that make you look like a cyborg, they have those options, but they also have a lot of options with aesthetics that you would be perfectly comfortable wearing to work or to dinner or anywhere else. If you'd like to try ROKA glasses, you can go to roka.com, that's R-O-K-A dot-com, and enter the code Huberman to save 20% off your first order. Again, that's R-O-K-A dot-com, and enter the code Huberman at checkout. Today's episode is also brought to us by Thesis. Thesis makes custom nootropics, and as many of you know, I am not a fan of the word nootropics because nootropics means smart drugs. And as a neuroscientist, I can tell you there is no neural circuit in the brain for being smart. Thesis understands this and has designed different nootropics in order to bring your brain into specific states for specific types of work, so for instance for creative work or to engage with more focus or to give you more energy for cognitive or physical work. So, with Thesis, they'll design custom nootropics for you that will allow you more focus, better task switching, more creativity, and so on, and they'll be sure to include only the ingredients that you want and not the ingredients that you don't. I've been using Thesis for more than a year now and I can confidently say that their nootropics have been a total game-changer for me. I like the Clarity formula prior to long bouts of cognitive work or the Energy formula prior to physical workouts. If you'd like to try your own personalized nootropic starter kit, go online to takethesis.com/huberman. You'll take a brief three-minute quiz, and Thesis will send you four different formulas to try in your first month. Again, that's takethesis.com/huberman, and use the code Huberman at checkout for 10% off your first box. Today's episode is also brought to us by LMNT. LMNT is an electrolyte drink that has everything you need and nothing you don't. That means the exact ratios of electrolytes are in LMNT, and those are sodium, magnesium, and potassium-... but it has no sugar. I've talked many times before on this podcast about the key role of hydration and electrolytes for nerve cell function, neuron function, as well as the function of all the cells and all the tissues and organ systems of the body. If we have sodium, magnesium, and potassium present in the proper ratios, all of those cells function properly, and all our bodily systems can be optimized. If the electrolytes are not present and if hydration is low, we simply can't think as well as we would otherwise, our mood is off, hormone systems go off, our ability to get into physical action, to engage in endurance and strength and all sorts of other things is diminished. So with LMNT, you can make sure that you're staying on top of your hydration and that you're getting the proper ratios of electrolytes. If you'd like to try LMNT, you can go to DrinkLMNT. That's L-M-N-T.com/huberman, and you'll get a free LMNT sample pack with your purchase. They're all delicious. So again, if you want to try LMNT, you can go to LMNT, L-M-N-T, .com/huberman. The Huberman Lab Podcast is now partnered with Momentous Supplements. To find the supplements we discuss on the Huberman Lab Podcast, you can go to Live Momentous, spelled O-U-S, livemomentous.com/huberman. And I should just mention that the library of those supplements is constantly expanding. Again, that's livemomentous.com/huberman. And now for my discussion with Dr. Sara Gottfried. Dr.

3. 7:50 – 11:00

   Women, Family History, Heredity & Environment

   1. AHAndrew Huberman7:50

      Gottfried, Sara, welcome.

   2. SGSara Gottfried7:52

      Thank you. So happy to be here.

   3. AHAndrew Huberman7:53

      Yeah, I'm delighted and very excited to ask you about an enormous number of topics. You are a expert in so, so many things, so, uh, the challenge for me is going to be to, uh, constrain this walk, as it were.

   4. SGSara Gottfried8:05

      (laughs)

   5. AHAndrew Huberman8:05

      But, uh, I'm hoping that we can touch on a great number of things today, the first of which is really about hormones and female hormones in particular, and I have a question, which is, is it ever informative for a woman, regardless of age, to know something about her mother's, perhaps even her grandmother's, experience vis-á-vis hormones? Not- not just pregnancy, challenges with or, um, ease with pregnancy and child rearing, childbirth, this sort of thing, but, you know, what sorts of conversations should women be having with themselves and with family members to get a window into what their specific needs might be?

   6. SGSara Gottfried8:49

      Love this question. So, my work is really at the interface between genetics and environment, so your question gets to both, and I think it's essential that you understand what your grandmother went through, I'd even say your great-grandmother, depending on longevity in your family. So I grew up with my great-grandmother, I get that. And especially your mother. So, I would probably start first with trauma and intergenerational trauma, because I think that affects the endocrine system so hugely, especially cortisol signaling, but the broader PINE system, psycho, immuno, neuro, endocrine system. And then there's, you know, if I think about the stages, the life cycle that a woman goes through, if you think about puberty, I think... I don't know how genetically determined the age of puberty is. Certainly, there's a lot of environmental influences, like toxins can affect it. But, um, pregnancy, the age at which you start to go through perimenopause, menopause, many of those have a genetic component. So with pregnancy, I mean, you can certainly think, the shape of the pelvis, your ability to have a vaginal birth, some of that is genetically determined. I mean, you do have, you know, the- the sperm donor affecting some of that, but, you know, in my family, for instance, we have no cesarean sections, so everyone goes through this process of a relatively easy vaginal birth. I was a forceps baby, but, you know, for the most part, um, you can find out about that. And then there's certain female conditions that have a very strong component genetically, most of which run in my family, so that includes endometriosis, fibroids. I just had a hysterectomy. I had 50-plus fibroids and, uh, polycystic ovarian syndrome.

   7. AHAndrew Huberman10:57

      And of those three, uh, how frequent are those?

4. 11:00 – 17:26

   Puberty, Stress, Menstrual Cycles, Intrauterine Devices (IUDs)

   1. AHAndrew Huberman11:00

      And, uh, maybe I can constrain the question a little bit by saying, um, today's discussion, I imagine, is gonna be heard by men and women of all sorts of ages, so I, uh, maybe I'll direct the question a little bit toward, you know, at what age should these discussions start? Um, you know, we always imagine that, uh, women in their, um, 30s and 40s and 50s and onward should be getting certain tests and, um, addressing things like, uh, ovarian reserve and- and other sorts of things. But, you know, maybe we could march through and just say, for a woman in her teens who's already hit puberty, what sorts of biomarkers, whether or not they're blood-based or per- or, um, phenotyping, you know, the- the outward appearance of, uh, should those young women be paying attention to? Likewise, for women in their 20s, 30s. Maybe we could take it more or less by- by decade a- starting at puberty-

   2. SGSara Gottfried11:52

      Yeah.

   3. AHAndrew Huberman11:52

      ... assuming that a woman hits puberty sometime, what, between, what is it now? The average I- in the US is somewhere between 12 and 16 years old. Do I have that right?

   4. SGSara Gottfried12:00

      No, you do not.

   5. AHAndrew Huberman12:01

      Oh, great.

   6. SGSara Gottfried12:01

      So that is- (laughs)

   7. AHAndrew Huberman12:02

      I love to be wrong, so... (laughs)

   8. SGSara Gottfried12:04

      So, it used to be 12 to 16, I would say 50 years ago. It's been moving younger, and we think some of that is related to toxin exposure, as I mentioned, but I was 10 when I went through puberty. So, uh, well, I should say menarche, and I started growing breasts much before that. So, I think... Now I'm gonna step away from the science for a moment. I'm gonna do that pretty fluidly, and I'll try to call it out. I think there's also a huge influence from stress.... and, like, the development of the adrenal glands. So going back to the science. The issue in teenage years is that the hypothalamic-pituitary-adrenal axis-- and I like to think of it broader, so stay with me. Hypothalamic-pituitary-adrenal, gonadal, ovaries in women, testes in men, thyroid, gut axis.

   9. AHAndrew Huberman13:08

      Mm-hmm.

   10. SGSara Gottfried13:08

       So that, to me, is the control system, so I'm kind of expressing my bioengineering side here.

   11. AHAndrew Huberman13:14

       Well, I think it's great to include the other organs and tissue systems of the body because, as we both know, that, the narrow definition of just hypothalamic-pituitary-adrenal, it, it can't be just that, right?

   12. SGSara Gottfried13:25

       No.

   13. AHAndrew Huberman13:25

       It can't, right?

   14. SGSara Gottfried13:26

       No.

   15. AHAndrew Huberman13:26

       Yeah.

   16. SGSara Gottfried13:27

       It doesn't tell the whole story. So if you look at the, the main sex hormones in a, a young woman who's in her teenage years, the hypothalamic-pituitary-adrenal-gonadal part of that is not fully mature, so they're more likely to skip periods, especially under stress. They have a lot of influences. It really doesn't get well-established until you're done with adolescence, and I'm told that adolescence now is till, like, age 25 to 26. I heard that, and I was like... I've got two daughters, and I was thinking, "That's a really long time." (laughs)

   17. AHAndrew Huberman14:03

       And not just, uh, uh, psychologically defined or bio, psy- psychosocial?

   18. SGSara Gottfried14:07

       So mostly, mostly psychologically defined. I heard that from a psychologist. So biomarkers, you asked about. In your teenage years, what I think w- is really interesting is to look at cortisol. To look at the dance between estrogen and progesterone in those years is less helpful because I think there's a lot of variability due to the immaturity of the system. If you've got someone who's got really regular periods, it's probably better to do some benchmarking at that age, but generally, I find that benchmarking is best performed in your 20s or 30s.

   19. AHAndrew Huberman14:44

       Are periods not that regular in terms of duration of the menstrual cycle when the menstrual cycle first sets in?

   20. SGSara Gottfried14:52

       It depends. So I was like clockwork every 28 days until I had my hysterectomy in August. Same thing with my daughters. I've got two daughters. One's 17. The other's 23. For a lot of women, they're not regular, and then, there's the whole piece of oral contraceptives and other forms of contraception where you have no idea what the normal cycle is, and I hope we'll have some time to talk a little bit about oral contraceptives because I think it is... This is now opinion again and not science. I think it is the number one endocrinopathy that is iatrogenic for women.

   21. AHAndrew Huberman15:32

       Uh, we will definitely talk about it. I get a lot of questions about oral contraceptives, um, in the social media space and also questions about IUDs quite a lot.

   22. SGSara Gottfried15:43

       Totally.

   23. AHAndrew Huberman15:43

       In particular, copper IUDs, non-

   24. SGSara Gottfried15:45

       Yeah.

   25. AHAndrew Huberman15:45

       ... non-hormonal IUDs, so w- we will definitely touch on that. S-

   26. SGSara Gottfried15:48

       I'm an IUD crusader, so I just want to, you know, give you that warning.

   27. AHAndrew Huberman15:52

       You're, you're a fan? Do I have that right? Or you're anti-IUD-

   28. SGSara Gottfried15:55

       I am a huge fan.

   29. AHAndrew Huberman15:56

       Uh-huh. And whi- which IUDs in particular?

   30. SGSara Gottfried15:59

       So I like copper because it's non-hormonal. It's as effective as getting your tubes tied.
5. 17:26 – 25:11

   Tool: Sex Hormones, Microbiome, Estrobolome & Disease; Biomarker Testing

   1. SGSara Gottfried17:26

      getting back to your original question, which is about biomarkers per decade, in your 20s, that's when you want to do some base casing with estrogen, progesterone, and testosterone. So I think it's really helpful to know about this, this tango. You're from Argentina, or your father is.

   2. AHAndrew Huberman17:46

      I have Argentine lineage.

   3. SGSara Gottfried17:48

      Yes.

   4. AHAndrew Huberman17:48

      Yeah. My grandparents did tango into their late 80s. I-

   5. SGSara Gottfried17:53

      Well-

   6. AHAndrew Huberman17:53

      I am, I'm in my late 40s, and I, I still haven't started, so I suppose there's time.

   7. SGSara Gottfried17:57

      It might be time for you to do that.

   8. AHAndrew Huberman17:59

      (laughs) Okay. Will do.

   9. SGSara Gottfried18:00

      And it might be a factor in their longevity.

   10. AHAndrew Huberman18:03

       Hmm.

   11. SGSara Gottfried18:03

       Did they have good healthspan, not just-

   12. AHAndrew Huberman18:04

       They did, and-

   13. SGSara Gottfried18:05

       ... lifespan?

   14. AHAndrew Huberman18:05

       And my grandfather smoked cigarettes daily, remained mentally sharp until he died in his late 90s, but, um, almost burned down their apartment several times falling asleep with a cigarette in his mouth, so... I don't recommend anyone smoke (laughs) , by the way. Uh, but it was, uh, coffee, latte, uh, red meat, and cigarettes, and they lived into their 90s. So that side of my family has the genetic, uh, advantage. The other side, less so. Um, but in any event, uh, tango, um, will-

   15. SGSara Gottfried18:30

       Tango.

   16. AHAndrew Huberman18:30

       ... is a, is a 2023 goal. It has been every year. Um, the-

   17. SGSara Gottfried18:35

       (laughs)

   18. AHAndrew Huberman18:35

       (laughs) Uh-

   19. SGSara Gottfried18:35

       I'm gonna hold you accountable to that.

   20. AHAndrew Huberman18:37

       Okay. Will do, and there, no, there will be no YouTube video of me doing tango.

   21. SGSara Gottfried18:40

       (laughs) At least not initially.

   22. AHAndrew Huberman18:42

       Tim Ferriss, actually, uh, phenomenal podcaster, as we know, is a, is a-

   23. SGSara Gottfried18:45

       He's a badass tango.

   24. AHAndrew Huberman18:46

       He's a badass tango, t- tango dancer. I, I know this through various sources. Uh-

   25. SGSara Gottfried18:50

       Yes.

   26. AHAndrew Huberman18:51

       Yeah.

   27. SGSara Gottfried18:51

       I've seen. Yeah, so this tango between estrogen and progesterone is incredibly important. You want to have the, the right lead. You want to have the right follow between the two hormones.... again, I'm stepping away from my science hat.

   28. AHAndrew Huberman19:03

       Mm-hmm.

   29. SGSara Gottfried19:04

       But what happens a lot of the time is that estrogen dominates in that tango, and when that happens, it sets you up for greater risk of fibroids, endometriosis, breast pain, probably in association with the microbiome and the estrobolome.

   30. AHAndrew Huberman19:24

       Oh. Can you familiarize me with the estrobolome?
6. 25:11 – 31:13

   Nutritional Testing; Vegetables, Microbiome & Disease

   1. SGSara Gottfried25:11

      A big part of the testing that I do in phenotyping my patients, I practice precision medicine, so I, I like to almost start with nutritional testing. I don't think I've ever had a teenager. I've got some NBA players that are 19, 20, 21, so maybe those count, but, uh, those are men, obviously. But for nutritional testing, that would be potentially a helpful thing to do in your 20s. Becomes less important as you get older and you develop more micronutrient deficiencies, but micronutrients play a huge role in terms of hormone production. Magnesium, you know, the magnesium is hugely involved in the way that you get rid of estrogen, as an example. So micronutrient testing, what I usually do is a combination of blood and urine, and so I'm looking at all of the micronutrients that we can measure that have some clinical scientific basis behind them. If I could do that for a teenager, I think it might be helpful because... I recently gave a lecture on breast cancer risk reduction, another quick sidebar, and I was sad to find that intake of vegetables, polyphenols is such an important predictor of future risk of breast cancer, like when you're 50, 60 plus, and the most important time is when you're a teenager. Now, I have one daughter that eats vegetables. She loves them. And I have another daughter who eats food that's beige, and it's very hard to get her to eat the volume of vegetables, you know, five colors a day, which is what I do. And if you have evidence that you could show a 17-year-old that they've got micronutrient gaps, I think that would be a motivator for them to eat differently at a time when it's so critical, even though it's, you know, 25 years in the future that it's gonna potentially change this arc that they're on.

   2. AHAndrew Huberman27:19

      What do you do for a young woman who doesn't like vegetables?

   3. SGSara Gottfried27:23

      (laughs)

   4. AHAndrew Huberman27:23

      Is... Or is not (laughs) somehow able or willing to, to get those five colors a day of vegetable to help support the microbiome? You know, are supplements a, a useful tool in that case? Um, what other sorts of tools, behavioral or otherwise, are useful?

   5. SGSara Gottfried27:40

      Such a good question. So here, I'm gonna invoke Rob Knight at UCSD. So, I think his, his, uh, his gut project has really been helpful in terms of understanding what kind of modulators are gonna be important. So what I try to get that person to do, and I don't see many teens anymore, other than NBA players. What I try to get them to do is to have a smoothie. Very hard to get them to have a smoothie every day, but if I could get them to have a smoothie three times a week and throw some of these vegetables in, that makes a huge difference.

   6. AHAndrew Huberman28:13

      Mm-hmm.

   7. SGSara Gottfried28:13

      I mean, we know that makes a difference in terms of microbiome change.

   8. AHAndrew Huberman28:17

      So just be blending up broccoli or kale?

   9. SGSara Gottfried28:19

      Cauliflower, so cauliflower is great.

   10. AHAndrew Huberman28:21

       Bell peppers, even. They're putting things into the smoothie, is it?

   11. SGSara Gottfried28:24

       Yeah, I don't know if you can get a teenager to do that-

   12. AHAndrew Huberman28:26

       (laughs)

   13. SGSara Gottfried28:26

       ... but they often will use, like I have them do steamed broccoli that's in the freezer-

   14. AHAndrew Huberman28:30

       Mm-hmm.

   15. SGSara Gottfried28:30

       ... because it's got very little taste. So that, they could do that in a chocolate smoothie. They could add some greens. I like greens. Powders are super convenient. So that with, you know, kind of a, a taste that they like, whether that's chocolate, which is what most of my clients want, or, you know, vanilla with berries and that sort of thing. So that can go a long way if you don't like vegetables. And short of that, I would say some supplements, but I would say that's a distant second to making a smoothie. I've got one patient that I have to mention because, um, he took this to the extreme. So he's a retired physicist professor at UCSD. He found out that his microbiome was a hot mess and, um, developed autoimmune disease, and so he became hellbent, like only a physicist could, on changing his microbiome. And he dramatically shifted it by having a smoothie every day with 57 vegetables and fruits in it. So he would-

   16. AHAndrew Huberman29:35

       57 independent-

   17. SGSara Gottfried29:36

       50, 57 independent. So I mean, this just warms my heart the way that he did this, but he would go to the farmer's market. He would just get a bunch of this, a bunch of that, and he would go home, make the smoothie, and then stick it in the freezer so he'd have a serving every day, and he became a completely different person based on this microbiome change. His, uh, autoimmune disease is in remission. He, um, he dropped a huge amount of weight. He went from being, you know, kind of this phenotype that I know you know well, of a professor, high-performing, traveling around the world, on so many boards, so much innovation, so many great ideas, super computer guy, to being someone who gets up in the morning, gets in his hot tub, exercises for like one to two hours a day, and then does a little work. Like he completely shifted the way that he lives and his microbiome shift, you know, who knows what, what's the chicken and what the, what's the egg there? But he had a huge change in his physiology. Glucose went from being quite high. He had... And he tracks all of this, of course. It's like on a Jupiter-

   18. AHAndrew Huberman30:50

       Scientist after all.

   19. SGSara Gottfried30:51

       Right. He's-

   20. AHAndrew Huberman30:52

       Yeah, and retired, I suppose, might have had something, something to do with it.

   21. SGSara Gottfried30:53

       And he's retired, but he's, he's got the longest time series of anyone I know, and he's tracked his glucose and insulin going back 20 years. So he can show you, "Okay, here's where I started having my smoothie."... and here's how my glucose and insulin changed as a result of that.

   22. AHAndrew Huberman31:12

       I'd

7. 31:13 – 32:22

   AG1 (Athletic Greens)

   1. AHAndrew Huberman31:13

      like to take a quick break and acknowledge one of our sponsors, Athletic Greens. Athletic Greens, now called AG1, is a vitamin mineral probiotic drink that covers all of your foundational nutritional needs. I've been taking Athletic Greens since 2012, so I'm delighted that they're sponsoring the podcast. The reason I started taking Athletic Greens and the reason I still take Athletic Greens once or usually twice a day is that it gets me the probiotics that I need for gut health. Our gut is very important. It's populated by, uh, gut microbiota that communicate with the brain, the immune system, and basically all the biological systems of our body to strongly impact our immediate and long-term health. And those probiotics in Athletic Greens are optimal and vital for microbiotic health. In addition, Athletic Greens contains a number of adaptogens, vitamins, and minerals that make sure that all of my foundational nutritional needs are met, and it tastes great. If you'd like to try Athletic Greens, you can go to athleticgreens.com/huberman, and they'll give you five free travel packs that make it really easy to mix up Athletic Greens while you're on the road, in the car, on the plane, et cetera. And they'll give you a year's supply of vitamin D3 K2. Again, that's athleticgreens.com/huberman

8. 32:22 – 36:08

   Microbiome, Prebiotics & Probiotics, Inflammation

   1. AHAndrew Huberman32:22

      to get the five free travel packs and the year's supply of vitamin D3 K2. Is there a case for, I'll say young women, but young women and men, um, using over-the-counter probiotics as a way to enhance the microbiome? This is something I hear about a lot. I've heard that excessive doses of capsule probiotics can give a brain fog-like condition. Um, I personally don't use capsule probiotics unless, um, I feel like my system is under a significant amount of stress, in which case I might add that in for brief periods of time, or if I've just taken antibiotics for a period of time.

   2. SGSara Gottfried32:53

      Right.

   3. AHAndrew Huberman32:54

      Uh, do you ever recommend that the college student or the high school student, that she or he take capsule probiotics? Assuming that they're getting, let's say, three to five servings of vegetables per day, either in smoothie form or some other form, what are your thoughts on, on supplementing probiotics?

   4. SGSara Gottfried33:14

      It sounds like such a simple question. It is such a complex answer, and I don't think we really have the answer. So I'll tell you the way that I approach it. I look for randomized trials to support my use of probiotics, and frankly, I'm underwhelmed.

   5. AHAndrew Huberman33:29

      Mm-hmm.

   6. SGSara Gottfried33:29

      So I've seen some data, if I invoke my, um, NBA players for a moment, almost every player I've tested has increased intestinal permeability. They just have such a high training load, probably mediated by cortisol, very high glucoses when they train, that they have increased intestinal permeability. So those tight junctions in their intestine become loose. They develop a lot of inflammation as a result of that. And when you're a professional NBA player, and you're making 20 million a year, like, you don't want a lot of inflammation. You want a little bit to, like, help your muscles recover, but you don't want it to be, um, adding to problems when you develop an injury.

   7. AHAndrew Huberman34:11

      So this is leaky gut essentially.

   8. SGSara Gottfried34:12

      Leaky gut.

   9. AHAndrew Huberman34:12

      Yeah.

   10. SGSara Gottfried34:13

       I don't love that term, but-

   11. AHAndrew Huberman34:15

       Yeah.

   12. SGSara Gottfried34:15

       ... yeah, we'll use it here. So there's a, there's a particular probiotic that is helpful in athletes with leaky gut. So that's the kind of specificity and randomized trial that I'm looking for. The rest of it, I think there's support if you find help from it, as you described. If you take a course of antibiotics, I mean, first of all, I would question whether you need them, but there's a time and place.

   13. AHAndrew Huberman34:40

       Yeah, I try and avoid them. There, there have been instances where they've been prescribed, and I took them, mostly in the past. Like, it was in college. They seemed like they kind of gave 'em out for... You had a sinus infection-

   14. SGSara Gottfried34:47

       They totally did.

   15. AHAndrew Huberman34:47

       ... they gave you pro- you know, antibiotics using kind of like, like M&M's.

   16. SGSara Gottfried34:50

       Yeah, the worst treatment ever. Yeah, so if you're coming off of antibiotics, I think that's a good time to do what we call replacement dose probiotics. I think what's far more interesting is prebiotics. I think the data is much better for prebiotics and, um, the selective use of polyphenols.

   17. AHAndrew Huberman35:12

       How would a person in their teens and 20s or any age, for that matter, know what, whether or not they have nutritional deficiencies? What is the best way to analyze if one is getting enough magnesium, um, and for that matter, what is going to be the best way to test the, uh, microbiome? You said stool sample. I- i- and I'll come right back with the same question I asked about a blood test. What time of day, when during the month, um, to establish just a baseline? So this would be prior to embarking on a, you know, 97 vegetables or however many was it per day.

   18. SGSara Gottfried35:46

       (laughs) Oh, it has to be 57.

   19. AHAndrew Huberman35:47

       Um, well, I love the idea that you're telling us, uh, if I'm gathering correctly, is that, yes, there's a case for probiotics, but for the typical person, regardless of age, eating more vegetables, or drinking more vegetables as i- as i- the case may be, is going to be beneficial for the gut microbiome, perhaps without the need to go test whether or not one is making a certain number of estrogen-related metabolites or not. Just that,

9. 36:08 – 42:25

   Microbiome Testing, Magnesium, Constipation & Thyroid

   1. AHAndrew Huberman36:08

      that's a great starting place. Eat or consume more vegetables.

   2. SGSara Gottfried36:11

      Totally.

   3. AHAndrew Huberman36:11

      Um, but if one wants to analyze their gut microbiome, are there good tests available to the general public?

   4. SGSara Gottfried36:17

      Hmm.

   5. AHAndrew Huberman36:17

      This has been... I'm not gonna name companies, but I've h- I've been tracking this over the years, and it's never been clear to me that we know what constituents of the gut microbiome are, are best, yet we-

   6. SGSara Gottfried36:26

      Yeah.

   7. AHAndrew Huberman36:26

      ... know that dysbiosis is bad-

   8. SGSara Gottfried36:28

      Yep.

   9. AHAndrew Huberman36:29

      ... and we know that diversity of the microbiome is good. We hear this.

   10. SGSara Gottfried36:32

       Yeah.

   11. AHAndrew Huberman36:32

       But no one's ever told me that you want a particular ratio of one microbiota to another-

   12. SGSara Gottfried36:38

       Right.

   13. AHAndrew Huberman36:38

       ... in a way that has made any sense to me at least.

   14. SGSara Gottfried36:41

       Totally.

   15. AHAndrew Huberman36:41

       Um, I'm not a microbiologist, but whereas with, you know, with testosterone in men, we hear, "Okay, you want your free testosterone to be about 2% of your total," perhaps.

   16. SGSara Gottfried36:50

       Yeah.

   17. AHAndrew Huberman36:51

       With women you w- women are gonna have more testosterone than estrogen on average, but still less than men when you look at testosterone, et cetera, et cetera, but you can kind of get some, some crude measures. But for the microbiome, it just seems like-

   18. SGSara Gottfried37:02

       (laughs)

   19. AHAndrew Huberman37:02

       ... long lists of microbiota for which, um, I just get dizzy. I just, if you just wrote out a bunch of Is and Ls and Ss, you'd, you can kind of halfway (laughs) -

   20. SGSara Gottfried37:10

       Totally.

   21. AHAndrew Huberman37:10

       You're getting a bit, uh, bit the same information. I'm not trying to poke at that field. It's a beautiful field, but they haven't told me what to, what I, what my microbiota ought to look like. Like, what's a healthy microbiome chart?

   22. SGSara Gottfried37:22

       Well, that's because we don't know.I mean, the best we have is Rob Knight's work, but even that is limited in terms of... You know, can I tell you that a, a woman in her 20s should have this particular pattern with her microbiome? No, I can't. So, um, let me go to your first question 'cause I think you just asked about six. Your first question is about nutritional testing. What I like to do with nutritional testing is run a panel that's looking at antioxidants, so like vitamin A, vitamin C, alpha-lipoic acid, um, plant-based antioxidants, 'cause you can measure that in the blood. I like to look at some of the key vitamins, especially the B vitamin range, because as you probably know, if you've got particular genetic, um, polymorphisms, you might be less likely to be absorbing the right level of vitamin B9, folate, vi- vitamin B12, et cetera. Um, I'm also looking, going back to the antioxidants, at glutathione because I think that's such an important lever when it comes to detoxification, which we haven't talked about yet. And then I'm looking at some of the minerals. Magnesium is really the most important, and we know that somewhere around 70% to 80% of Americans are deficient in magnesium. That's, like, the, the lowest-hanging fruit.

   23. AHAndrew Huberman38:42

       I would be curious, for instance, like with magnesium, if that number of people are deficient, does that mean that that number of people should be targeting their nutrition towards foods that contain magnesium and/or supplementing with magnesium, and if so, what forms of magnesium? Um, we've talked about MAG3+ and 8-

   24. SGSara Gottfried38:57

       Yep.

   25. AHAndrew Huberman38:57

       ... for sleep. There's also mag citrate. There's so many forms, can be a little bit overwhelming to people. So any, any detail, um, in sourcing, I would appreciate it.

   26. SGSara Gottfried39:05

       Great. So first, in terms of testing, what I prefer to do is to mention one, more than one lab and more than one brand. Um, and I can just... I'm speaking mostly from experience. So, uh, for testing, I do a lot of Genova Nutrivals. During the pandemic, they developed an at-home test. Normally with a NutriVal, you have to get your blood drawn, and you have to do a urine sample, so a lot of people can't do that. The great thing about this test is your insurance usually pays for most of it, and so the copay is about $150. So during the pandemic, they developed another test called Metabolomix, which does much of the same testing, but it's a finger prick. So most of my patients prefer that, and in fact, they haven't gone back to the NutriVal. Second lab is SpectraCell. I use SpectraCell occasionally. I find it not quite as easy in terms of fitting into my practice, but I've got friends and mentors, like Mark Houston, who does a lot of, uh, kind of precision, um, cardiometabolic health. He thinks SpectraCell is the best test out there. So you asked about magnesium. You have to measure red blood cell magnesium, like whole blood, and with deficiency, it's interesting with supplementation. For my patients who tend toward constipation, and that's frankly about 80% of the women that I take care of-

   27. AHAndrew Huberman40:38

       Really?

   28. SGSara Gottfried40:38

       Yes.

   29. AHAndrew Huberman40:39

       Wow. I'd be curious as to why that, that is. Um, is it... I, I can guess. Uh, diet, stress, um-

   30. SGSara Gottfried40:47

       Patriarchy, rage-
10. 42:25 – 45:13

    Female Colonoscopy; Network Effect & Modern Medicine, Stress Factors

    1. SGSara Gottfried42:25

       "Yeah, it was really hard to, like, (laughs) get in there and do what we need to do."

    2. AHAndrew Huberman42:28

       As a brief tangent, but I think this is the time to ask, um, w- at what age now do physicians insist their female patients get colonoscopies? Uh, for men, I think the age used to be 50. Now it's getting ratcheted back to 45 or 40. Again, these are recommendations, not requirements, but they're pretty strong recommendations from depending on where you live, et cetera. Um, for women, how early do you think they should get a colonoscopy to, to explore for possible polyps and/or, uh, colon cancer?

    3. SGSara Gottfried42:59

       Yeah, it's a really good question. I don't know the answer. So what I've always operated with is 50. The way that I answer that is to go to the US preventive task force rating to determine, based on their synthesis of the data, what age is the most appropriate. Has it changed, as you just described for men, from 50 to younger? I don't know. So we should fact-check that.

    4. AHAndrew Huberman43:21

       All these, um, additional health hazards for women, um... You mentioned some of the s-... you broadly mention psychological impact, right? And, and, of course, these things are all related, psychology, immunology. I think one of the, I think, wonderful things about neuroscience and science in general and medicine is that there's now an u- an understanding that all the organs are connected to one another. (laughs)

    5. SGSara Gottfried43:44

       It's a network.

    6. AHAndrew Huberman43:45

       It's a network. And that the microbiome sits at, at, um, at a key node within that network. Um, and I think most people accept that now.

    7. SGSara Gottfried43:54

       Yes.

    8. AHAndrew Huberman43:54

       Uh, yeah, uh, that seems to be a theme that, at least in the last 10 years, is really wonderful because, um, certainly for neuroscience, it was thought that, you know, unless it's in the cranial vault, it's not neural, which is ridiculous 'cause there's lots of nervous system outside the, the skull. But in any case, for-

    9. SGSara Gottfried44:10

       Can I interrupt for a second?

    10. AHAndrew Huberman44:10

        Yes, please.

    11. SGSara Gottfried44:11

        So I think you're right that there's an understanding about the network effect, but I think that as much as I love mainstream medicine and I trained in it and I'm so grateful for my education, I still think it is a silo-based way of taking care of patients. So even if there's an understanding of the network effect more at the science level or, as you described, in neuroscience, there's still, you know, if you are a woman who has constipation, fatigue, um, maybe an autoimmune condition, uh, feels stressed out all the time, feel like your hormones are outta whack, you get sent to the gastroenterologist for the constipation. You get sent to the rheumatologist for your autoimmune issues. You maybe get sent to an endocrinologist if you've got thyroid problems, and there's very little collaboration between these groups. So even though there's an understanding of the network effect,

11. 45:13 – 55:35

    Constipation, Stress & Trauma, Autonomic Balance

    1. SGSara Gottfried45:13

       in real life, it's not happening.

    2. AHAndrew Huberman45:16

       W- let's, um, let's go deeper down that path 'cause I, you point out something really important, and th- and you've mentioned constipation a few times. Can we view constipation as a serious enough symptom that it warrants an immediate intervention? That is, does it f- flag or signal problems that are severe enough that that should be the issue that's dealt with, uh, for anybody that's experiencing it? Uh, and I mean, it's sort of an odd topic for many people 'cause they think, "Oh, you know, bowel movements and sort of..." You know, there's that kind of, um, preadolescent humor around this, but I think it's, it's so important. What you're, what I'm hearing you say is that constipation is far more common in women, and it signals a general se- uh, many problems occurring. Does that mean that women should address constipation, and if so, what's the best way (laughs) to address constipation?

    3. SGSara Gottfried46:01

       Yeah, I love this question because you're doing... Can we have a quick little meta conversation? So you're doing something that I knew you would do, which is you're teaching me something, and you're changing... Like, there's a social genomics thing happening where you're changing my thought about this, so I just wanted to acknowledge that. Thank you.

    4. AHAndrew Huberman46:20

       Yeah, thank you. Well, uh, I think for me, you know, when I hear that there's a kinda co- you know, you're talking about a phenotype. Constipation is a phenotype. It's one that people generally don't wear a T-shirt explaining it to people-

    5. SGSara Gottfried46:30

       (laughs)

    6. AHAndrew Huberman46:30

       ... but that I'm guessing anything to do with sexual health, um, bowel health, urology, people just don't talk about.

    7. SGSara Gottfried46:37

       Right.

    8. AHAndrew Huberman46:38

       Um, for all sorts of reasons, and those reasons are probably so obvious that they're not even worth discussing, but (laughs) be- and wh- also because we won't change them except by talking about them.

    9. SGSara Gottfried46:46

       Yep.

    10. AHAndrew Huberman46:47

        So if you say, um, women are far more constipated, and that's signaling a larger set of problems-

    11. SGSara Gottfried46:53

        Yes.

    12. AHAndrew Huberman46:54

        ... then my immediate thought is, "Well, will relieving constipation, um, pun, uh, intended retroactively-"

    13. SGSara Gottfried47:01

        (laughs)

    14. AHAndrew Huberman47:02

        "... um, will that assist in a great number of issues, and/or will it get them down the road of thinking about those other issues more specifically? Like, do I need more magnesium, or should I-"

    15. SGSara Gottfried47:12

        Yeah.

    16. AHAndrew Huberman47:12

        "... be putting vegetables in my smoothie," you know? So I'm curious about constipation as a target-

    17. SGSara Gottfried47:17

        Yeah.

    18. AHAndrew Huberman47:18

        ... for intervention that then opens up a bunch of other discussions 'cause there are these certain nodes in the, in the mental health, physical health space that when someone, you know, like, we talk a lot about deliberate cold exposure. Do I think it's magic? No, but I think that if someone's getting themselves into a cold shower once a day, it opens up a num- a number of questions about themselves and reveals a number of things to themselves. Like, how do I buffer stress?

    19. SGSara Gottfried47:40

        Yeah.

    20. AHAndrew Huberman47:40

        What sorts of levels of control do I actually have? And on and on. So perhaps not the best example, but, um-

    21. SGSara Gottfried47:46

        S- some of us hate cold exposure.

    22. AHAndrew Huberman47:48

        Right, which is prob-

    23. SGSara Gottfried47:48

        And we have, we have, like, a gene that makes us stress out like you wouldn't believe-

    24. AHAndrew Huberman47:52

        Right, which-

    25. SGSara Gottfried47:52

        ... with cold exposure.

    26. AHAndrew Huberman47:53

        Which I would argue makes it, um, very likely that even 10 seconds of cold exposure gets you the effect that you want-

    27. SGSara Gottfried47:59

        (laughs)

    28. AHAndrew Huberman47:59

        ... as opposed to someone who adores cold exposure, like a penguin needs a lot more cold exposure for it to have the, the adaptive response. Anyway, that's my way of-

    29. SGSara Gottfried48:07

        May- maybe.

    30. AHAndrew Huberman48:07

        ... of g- of g- gumbeeing through that, uh, quite, uh, you're, you're, you're quite correct. Um, so-
12. 55:35 – 1:02:58

    Constipation Relief, Stress, Breathwork & Meditation

    1. SGSara Gottfried55:35

       constipation could be pulled out and kind of writ larger as an important signal.

    2. AHAndrew Huberman55:40

       What sorts of tools do you recommend people use to, um, relieve constipation? Um, in- inc- eating more fiber. It sounds like reducing stress is going to be a huge one.

    3. SGSara Gottfried55:52

       Yes.

    4. AHAndrew Huberman55:53

       What are your favorite stress reduction tools? Um, I like to divide these into, um, real-time tools, so big proponent of, like, physiological sighing, real-time, you know, these sorts of things. But, um, things that can really lower the baseline on stress overall to facilitate constipation and other, other, uh, broad indicators of health.

    5. SGSara Gottfried56:17

       So I'm not a fan of lowering stress. I'm a fan of lowering perceived stress, and I think the distinction is really important. I learned when I was in my 30s that I was a massive stress case and I didn't know it. It was just sort of, I think I had, through residency, through working 120 hours a week, I just was so accustomed and sort of, um, trained-

    6. AHAndrew Huberman56:44

       That was 120.

    7. SGSara Gottfried56:46

       Yes.

    8. AHAndrew Huberman56:46

       Not under 20, folks, yeah.

    9. SGSara Gottfried56:47

       Yeah, this is before-

    10. AHAndrew Huberman56:48

        Not unusual in, in medicine that, yeah.

    11. SGSara Gottfried56:50

        Well, they, they've changed training so that you work no more than 80 hours a week now, but that was before my time.

    12. AHAndrew Huberman56:57

        Mm-hmm.

    13. SGSara Gottfried56:57

        So I became accustomed to a massive amount of cortisol, massive, and I would say I've spent the past 20 years really working on perceived stress to find... I think all of us need an a la carte menu of what is most effective. So what works for me now at my age is different than, you know, the, the TM I did as a college student, transcendental meditation. It's different than the... I became a certified yoga teacher when I was in my 30s. That is very effective for a lot of people. It wasn't enough for my matrix. I do holotropic breath work. Um, I didn't read it, but I saw that you just had a paper in Cell on your sighing.

    14. AHAndrew Huberman57:45

        Mm-hmm.

    15. SGSara Gottfried57:45

        And, um, it kinda, it made me think, like, teach me how to sigh. Teach, teach me how to sigh. Like, can you say a little bit about that?

    16. AHAndrew Huberman57:54

        Sure.

    17. SGSara Gottfried57:54

        Like, how do you do it?

    18. AHAndrew Huberman57:55

        Yeah, b- very briefly, that study was we, we wanted to find a minimal effective dose intervention.

    19. SGSara Gottfried58:00

        Yeah, five minutes.

    20. AHAndrew Huberman58:00

        So I just wanted... Yeah.

    21. SGSara Gottfried58:01

        Five minutes.

    22. AHAndrew Huberman58:01

        So five minutes a day. We needed to figure out what people would do every day.

    23. SGSara Gottfried58:04

        Yeah.

    24. AHAndrew Huberman58:04

        And we were monitoring subjective mood, et cetera, but also biometrics remotely, so it was kind of a nice study.

    25. SGSara Gottfried58:10

        Which biometrics? HRV?

    26. AHAndrew Huberman58:12

        Um, HRV, uh, nighttime sleep.

    27. SGSara Gottfried58:14

        Cortisol?

    28. AHAndrew Huberman58:15

        Uh, I wish. Um, so this was done during the pandemic, m- more than 100 subjects. The advantage was that we got data 24 hours a day 'cause they're pinging us and their data, uh, wearing whoop-

    29. SGSara Gottfried58:25

        HRV 24?

    30. AHAndrew Huberman58:26

        Whoop bands. Yeah.
13. 1:02:58 – 1:08:19

    Systemic & Societal Stress Unique to Females

    1. SGSara Gottfried1:02:58

       and loved. Um-

    2. AHAndrew Huberman1:03:00

       Yeah, let's talk about that. You know-

    3. SGSara Gottfried1:03:02

       Yeah.

    4. AHAndrew Huberman1:03:02

       ... you mentioned earlier the, all these stress factors. You, you said patriarchy, right?

    5. SGSara Gottfried1:03:05

       Yeah.

    6. AHAndrew Huberman1:03:05

       But I think what, if I may, um, at risk of, uh, (laughs) of just strengthening that, uh, statement, I, I mean, that, that, to me, is th- is signaling a bunch of other factors around, as you said, like-

    7. SGSara Gottfried1:03:17

       Yes.

    8. AHAndrew Huberman1:03:17

       ... keeping, keeping things in. Um, what do you think explains... L- let's talk about that because I think that that's likely to have raised a certain flag in people's minds. Like, "What exactly is she talking about?" Are you talking about less opportunity? Are you talking about less opportunity to, um, to vocalize? Are you talking about less opportunity to vocalize and be heard? I mean, I realize that there are an infinite number of variables, but given that it sounds like a, a really strong input to the system, uh, what I mean by that is that psychology is influencing biology, and you're saying that, that these, uh, that these powers, power dynamics, structures and dynamics, are impacting it. I'd love to... Let's hear your thoughts on that because, uh, I, I hate to let a flag like that go by-

    9. SGSara Gottfried1:04:04

       (laughs)

    10. AHAndrew Huberman1:04:04

        ... without fleshing it out, and let's, and let's-

    11. SGSara Gottfried1:04:06

        Never waste a good flag, uh-huh.

    12. AHAndrew Huberman1:04:07

        Well, and let's preface it by, by just saying that, like, people will have different opinions on this, and that's, and I think that's healthy, and, and like with the discussion (laughs) about constipation, let's talk about what people aren't willing to talk about when it comes to health.

    13. SGSara Gottfried1:04:17

        Love it. So we might need to talk about patriarchy on part two, but I'll give you some material that I've been working with.

    14. AHAndrew Huberman1:04:25

        Mm-hmm.

    15. SGSara Gottfried1:04:26

        I started... I did not even understand the existence of patriarchy until I was a bioengineering undergraduate, and I-

    16. AHAndrew Huberman1:04:34

        At MIT, I should mention, which has always had a bit of a, of a male, um, a skewed male in terms of-

    17. SGSara Gottfried1:04:41

        You think so?

    18. AHAndrew Huberman1:04:41

        ... faculty numbers. Well, my, my-

    19. SGSara Gottfried1:04:43

        Well, that's true at most universities. (laughs)

    20. AHAndrew Huberman1:04:44

        True. Well, my postdoc advisor was the late Ben Barres, who was a female-to-male transition, transgender-

    21. SGSara Gottfried1:04:51

        Interesting.

    22. AHAndrew Huberman1:04:52

        ... first transgender member of the National Academy of Sciences, one of my closest friends.

    23. SGSara Gottfried1:04:55

        Fantastic.

    24. AHAndrew Huberman1:04:55

        Unfortunately, he died of, of pancreatic cancer.

    25. SGSara Gottfried1:04:57

        Mm-hmm.

    26. AHAndrew Huberman1:04:57

        We were very, very close.

    27. SGSara Gottfried1:04:58

        Yeah.

    28. AHAndrew Huberman1:04:58

        They're actually-

    29. SGSara Gottfried1:04:59

        Mm-hmm.

    30. AHAndrew Huberman1:04:59

        ... making a documentary about Ben. But Ben, this is interesting, Ben went to MIT-
14. 1:08:19 – 1:09:23

    InsideTracker

    1. SGSara Gottfried1:08:19

       umbrella here, but it connects to many other things.

    2. AHAndrew Huberman1:08:24

       I'd like to take a brief break and thank our sponsor, InsideTracker. InsideTracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals. I've long been a believer in getting regular blood work done for the simple reason that many of the factors that impact your immediate and long-term health can only be analyzed from a quality blood test. The problem with a lot of blood and DNA tests out there, however, is that you get data back about metabolic factors, lipids and hormones and so forth, but you don't know what to do with those data. InsideTracker solves that problem and makes it very easy for you to understand what sorts of nutritional, behavioral, maybe even supplementation-based interventions you might want to take on in order to adjust the numbers of those metabolic factors, hormones, lipids, and other things that impact your immediate and long-term health, to bring those numbers into the ranges that are appropriate and indeed optimal for you. If you'd like to try InsideTracker, you can visit insidetracker.com/huberman and get

15. 1:09:23 – 1:11:55

    Testing & Future Behavior

    1. AHAndrew Huberman1:09:23

       20% off any of InsideTracker's plans. That's insidetracker.com/huberman to get 20% off. I want to use this as an opportunity to, A, keep this in mind as we turn to a, a question that I didn't, uh, close the hatch on earlier, and it's my fault, which is, I'm now clear on the fact that a woman in her late teens, early 20s ought to know something about her testosterone, estrogen, thyroid, cortisol levels, should start at least thinking about her microbiome, should be thinking about how, how many bowel movements and the timing of those bowel movements per day, really. And I'm assuming that what I just described is also true for women in their 20s, 30s, 40s, 50s, on up to 100s. Is that correct?

    2. SGSara Gottfried1:10:11

       That's correct, but I would say that there are differential opportunities by decade. So I'm glad you circled it back to teenagers and testosterone because I think if you know, for instance, in your teenage years that you have high androgens and that you've got this potential phenotype way into the future that you may not even notice. I mean, maybe you notice you've got a few extra hairs on your chin or something. If you know that your testosterone is elevated or some other androgen, it might change the arc of how you take care of yourself. So I think that could be very helpful in your teenage years. In your 20s, for people who are a stress case like me, so age 27 on the wards at UCSF, if I had known that I was such a high-cortisol person, I think I would have done things differently. I would have changed my behavior. And I don't know because I didn't base case these, but your testosterone can decline starting in your 20s, kind of depending on how much stress your matrix is under. So for women, that can start as early as 28. Usually, your testosterone declines by about 1% per year.

    3. AHAndrew Huberman1:11:28

       What level of testosterone do you like to see in a woman once she's sort of post- let's say after age 25. What kind of range is healthy? I know what the reference range is only because I know one could look it up.

    4. SGSara Gottfried1:11:39

       Yeah.

    5. AHAndrew Huberman1:11:39

       I don't know it off the top of my head, admittedly.

    6. SGSara Gottfried1:11:42

       Yeah.

    7. AHAndrew Huberman1:11:42

       But w- what i- what's a kind of a nice reference point there?

    8. SGSara Gottfried1:11:47

       So the way I tend to describe this on podcasts is the top half of the normal range.

    9. AHAndrew Huberman1:11:52

       Great.

    10. SGSara Gottfried1:11:53

        So that, I think, is a good benchmark.

16. 1:11:55 – 1:22:57

    Polycystic Ovary Syndrome (PCOS) & Cardiometabolic Disease; Stress

    1. SGSara Gottfried1:11:56

       You know, for PCOS, generally, it's much higher than that. You know, I've seen patients with PCOS where their total testosterone is 100 to 200, but-

    2. AHAndrew Huberman1:12:05

       Do they always have peripheral manifestations of that, a little bit of hair, the, the skin plaques? I've heard about, you know, so darkened skin plaques and lineages.

    3. SGSara Gottfried1:12:11

       Irregular periods.

    4. AHAndrew Huberman1:12:13

       Irregular periods. Is that... Um, you know, I th- I get a lot of questions about PCOS.

    5. SGSara Gottfried1:12:17

       Yeah.

    6. AHAndrew Huberman1:12:17

       Um, and you're the first person we've had on this podcast that's really qualified to talk about PCOS in, in a real way. Um, so here we're talking about too many androgens, cysts on the ovary, irregular ovarian men- sl- uh, oh, excuse me, I keep saying that, ovulatory slash menstrual cycle.

    7. SGSara Gottfried1:12:35

       Right.

    8. AHAndrew Huberman1:12:35

       Um, what are some other indicators? And do you recommend that women start taking androgen blockers?

    9. SGSara Gottfried1:12:43

       Mm-hmm.

    10. AHAndrew Huberman1:12:43

        Or s- or, I mean, how do... There seems to be a lot of PCOS out there. I'm hearing about it a lot.

    11. SGSara Gottfried1:12:49

        So glad you asked about this. So PCOS is one of those really poorly understood conditions that gets... It kind of flows, flies below the radar until a woman wants to get pregnant or she's got some other issue that drives her to a physician. The problem is that it is a syndrome, right? So polycystic ovary syndrome, sometimes polycystic ovarian syndrome. And syndromes don't necessarily fit together into a really clear diagnostic criteria. So in this instance, there are three different c- criteria that we look for. So cysts on the ovaries, having, um-... clinical manifestations of hyperandrogenism. So that could be hirsutism, acne, other things. And then, usually irregular periods. And the way that that's defined, at least by the, uh, latest criteria, is having a period every 35 days or less. So typical cycle length, 28 days, 35 days. You know, you're skipping a period here and there. So those are the, those are the criteria that we use to diagnose PCOS. There are about four different systems out there in the literature for diagnosing PCOS, which is where it starts to get confusing. So there's some women who have no cysts on their ovaries, but they've got hirsutism, and they've got irregular periods.

    12. AHAndrew Huberman1:14:13

        Could you define hirsutism?

    13. SGSara Gottfried1:14:15

        Hirsutism is increased hair growth, usually in places that you don't want it. So for women, it can be, you know, kind of male pattern. They might notice it on their breasts, on their chest. Um, and then there's, of course, a, a familial quality to that. Like I was just looking at a paper last night looking at Israelis and how much hirsutism they have and whether this is related to CAG repeats on the androgen receptor.

    14. AHAndrew Huberman1:14:39

        Mm-hmm. Do they get, um, not Israelis, but, um, do women who, um, who might have PCOS experience, um, androgenic alopecia? So hair loss that's sort of of the m- quote, unquote "male pattern baldness." (laughs) Of course, it's androgen pattern baldness as opposed to male, that we're talking about testosterone, DHT-related.

    15. SGSara Gottfried1:14:57

        Sometimes. You know, this is where I'm gonna invoke clinical experience rather than, uh, what I've seen in the literature. Uh, women definitely can have some androgenic, um, alopecia. I tend to see it later in life. But this is an important point because we think of PCOS as, you know, I was just talking about it in teenage years. Like, wouldn't it be nice to know that you have this phenotype, and you're at risk for all the things that people are at risk for? And we haven't talked about glucose and insulin yet. We should. What we know is that PCOS is not just a problem in terms of irregular periods and then difficulty getting pregnant. So those are mostly problems in your 20s, 30s, early 40s. But it is a massive risk factor for cardiometabolic disease as you get older. So many people tend to pigeonhole PCOS as a problem of reproductive age. We have to be thinking of it over the entire female life cycle, and I would say it's even more important to consider it over the age of 50, you know, average age of menopause is 51 to 52, because we know that that elevated testosterone, the high androgens, are probably the greatest cardiome- metabolic driver of disease for women with PCOS.

    16. AHAndrew Huberman1:16:16

        Wow.

    17. SGSara Gottfried1:16:17

        Now, one other thing I wanna mention, and I still have in my notes that we're gonna talk about microbiome testing-

    18. AHAndrew Huberman1:16:22

        Mm-hmm.

    19. SGSara Gottfried1:16:22

        ...'cause that's such a fun subject. What I was taught to do, again saying this with so much love for the people who have taught me how to do medicine, what I was taught to do is that if you have a woman with PCOS, you make the diagnosis, you measure her testosterone, you see if she has acne, blah, blah, blah. You ask that woman one question, "Do you wanna get pregnant or not?" So then, you have these women with PCOS who get started on a birth control pill if they don't wanna get pregnant. If they wanna get pregnant, then you help them get pregnant by addressing some of these PCOS issues, like maybe you give them Clomid, or you do something to make them ovulate more frequently. That is the way that most conventional medicine approaches this, and it does women a gigantic disservice. So one of the things I'm speaking into is the gender gap that exists. So I th- My feeling is that the research money that goes into women's health is abysmal compared to what goes into men's health.

    20. AHAndrew Huberman1:17:25

        Really?

    21. SGSara Gottfried1:17:25

        And I think that's changing-

    22. AHAndrew Huberman1:17:27

        Huh.

    23. SGSara Gottfried1:17:27

        ... but there's also a huge lack of awareness of sex and gender differences when it comes-

    24. AHAndrew Huberman1:17:31

        Hm.

    25. SGSara Gottfried1:17:31

        ... to the way that we construct clinical trials and other-

    26. AHAndrew Huberman1:17:35

        Oh.

    27. SGSara Gottfried1:17:35

        ... experiments.

    28. AHAndrew Huberman1:17:36

        Well, that's absolutely true. I mean, I sit on, I've sat on NIH review panels for more than a decade now. I'm a regular standing member, which is only to say that I see the research as it's being proposed.

    29. SGSara Gottfried1:17:45

        Yes.

    30. AHAndrew Huberman1:17:46

        And now, it's required, no grant will get funded without sex as a biological variable.
17. 1:22:57 – 1:29:48

    PCOS, Insulin, Glucose Monitoring and Management; Data Access

    1. SGSara Gottfried1:22:57

       And I think that's a really interesting way to look at this, because the thread we haven't talked about with PCOS is the, the role of insulin and glucose. So for some of the phenotypes of PCOS, the problem is hyperinsulinemia, high insulin in the blood is driving those theca cells in the ovaries to overproduce testosterone.

    2. AHAndrew Huberman1:23:23

       These women are insulin insensitive, so more insulin's being cranked out, and the cells in the ovary are therefore making more androgen.

    3. SGSara Gottfried1:23:31

       You don't like to say insulin resistant.

    4. AHAndrew Huberman1:23:33

       Oh, I, I can, uh ... I, I don't have a problem saying insulin resistance.

    5. SGSara Gottfried1:23:36

       Okay. I just, I like the way that you-

    6. AHAndrew Huberman1:23:37

       I'm just, I'm just a little bit outside the lane lines of my expertise, so I, I was trying to use the-

    7. SGSara Gottfried1:23:41

       Sure.

    8. AHAndrew Huberman1:23:41

       ... what, what is the correct nomenclature so that we can make sure everyone hears that?

    9. SGSara Gottfried1:23:44

       Well, what I like about insulin insensitive, the way that you just said it, is that I think that offers people a way in. And I love to do that in terms of messaging. Insulin resistance starts to lose people, 'cause they don't really get what that means-

    10. AHAndrew Huberman1:23:56

        Mm-hmm.

    11. SGSara Gottfried1:23:56

        ... at a receptor level.

    12. AHAndrew Huberman1:23:57

        I think I say insulin insensitive, because when people hear insulin sensitive, it almost sounds like a bad thing, but that's actually what you want.

    13. SGSara Gottfried1:24:05

        Right. It's what you want.

Episode duration: 2:35:04