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Speaker A: 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 doctor Sarah Gottfried. Doctor Sarah 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, Doctor Gottfried shares an enormous amount of information and tools that women can apply toward their hormone health, fertility, vitality, and longevity. We discussed the gut microbiome, which many people have heard about. But Doctor Gottfried points out the specific needs that women have in terms of managing their gut microbiome, 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 three fatty acids play a particularly important role in managing female hormone health. Doctor 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. Doctor Gottfried shared with us, for instance, that women suffer from digestive issues at more than ten 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. Doctor 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, Doctor 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 again, both books are going to be strongly informative for women wishing to optimize their hormone health, vitality and longevity. Before 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 element. Element is an electrolyte drink with everything you need and nothing you don't. That means plenty of salt, magnesium and potassium, the so called electrolytes, and no sugar. Salt, magnesium and potassium are critical to the function of all the cells in your body, in particular to the function of your nerve cells, also called neurons. In fact, in order for your neurons to function properly, all three electrolytes need to be present in the proper ratios, and we now know that even slight reductions in electrolyte concentrations or dehydration of the body can lead to deficits in cognitive and physical performance. Element contains a science backed electrolyte ratio of 1000 milligrams. That's 1 gram of sodium, 200 milligrams of potassium, and 60 milligrams of magnesium. I typically drink element first thing in the morning when I wake up in order to hydrate my body and make sure I have enough electrolytes. And while I do any kind of physical training and after physical training as well, especially if I've been sweating a lot. If you'd like to try element, you can go to drink element. That's lmnt.com huberman. To claim a free element sample pack with your purchase. Again, that's drinkelement. Lmnt.com huberman and now for my discussion with doctor Sarah Gottfried. Doctor Gottfried, Sarah, welcome.

Speaker B: Thank you. So happy to be here.

Speaker A: Yeah, I'm delighted and very excited to ask you about an enormous number of topics. You are expert in so many things. So the challenge for me is going to be to constrain this walk, as it were. But 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 a vis hormones? Not just pregnancy challenges with or ease with pregnancy and child rearing, childbirth, this sort of thing. But 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?

Speaker B: 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 neuroendocrine 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 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 the sperm donor affecting some of that. But 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 for the most part, 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 polycystic ovarian syndrome.

Speaker A: And of those three, how frequent are those? Maybe I can constrain the question a little bit by saying today's discussion, I imagine, is going to be heard by men and women of all sorts of ages. So maybe I'll direct the question a little bit toward at what age should these discussions start? We always imagine that women in their thirties and forties and fifties and onward should be getting certain tests and addressing things like ovarian reserve and other sorts of things. 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 phenotyping, you know, the outward appearance of should those young women be paying attention to. Likewise for women in their twenties, thirties, maybe we could take it more or less by decade, starting at puberty. Assuming that woman hits puberty sometime, what between, what is it now, the average in the US is somewhere between twelve and 16 years old. Do I have that right?

Speaker B: No, you do not.

Speaker A: Oh, great. Love to be wrong.

Speaker B: So it used to be twelve 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 ten when I went through puberty, so. Well, I should say menarche and I started growing breasts much before that. So I think now I'm going to step away from the science for a moment. I'm going to 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. So that, to me, is the control system. So I'm kind of expressing my bioengineering side here.

Speaker A: 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 can't be just that right? No, it can't.

Speaker B: No, it doesn't tell the whole story. So if you look at the main sex hormones in 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.

Speaker A: Not just psychologically defined or bio psychosocial, mostly psychologically defined.

Speaker B: I heard that from a psychologist. So biomarkers you asked about in your teenage years. What I think 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 twenties or thirties.

Speaker A: Are periods not that regular in terms of duration of the menstrual cycle? When the menstrual cycle first sets in?

Speaker B: 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.

Speaker A: We will definitely talk about it. I get a lot of questions about oral contraceptives in the social media space and also questions about IUD's quite a lot, totally. In particular copper IUd's, non hormonal IUd's. So we will definitely touch on that.

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

Speaker A: You're a fan. Do I have that right? Or you're anti.

Speaker B: I am a huge fan.

Speaker A: Uh huh. Which IUd's in particular.

Speaker B: So I like copper because it's non hormonal. It's as effective as getting your tubes dyed.

Speaker A: Who would have thought, right? I mean, it's that toxic to the sperm mobility. Is that how it works? That's my understanding of it. Is that it basically, it's like more or less an electric fence to the sperm cap. And just. That's it.

Speaker B: Electric fence is a bit of a harsh analogy, but I'll work with that. But it's, you know, to have something that can last for ten years so that you really have complete autonomy and sovereignty over your sexual life, that's profound. And to not get all those downstream risks that are associated with the birth control bill. The other thing that's important to know about it, I know this is a sidewar. Women who use the copper IUD have the highest satisfaction rate of anyone on contraceptives. The highest satisfaction rate, and yet it is the least used of all forms of contraception. Now, my favorite is vasectomy. But short of vasectomy, I think the IUD is a really great choice. There are some risks associated with it. I'm not saying it's risk free, but I love the IUD, and I love it for younger women, too, because it used to be that when I went through my training, which was 30 years ago, we were told, don't put it in someone who hasn't had a baby. And that is patriarchal messaging. But getting back to your original question, which is about biomarkers per decade in your twenties, that's when you want to do some base casing with estrogen, progesterone, and testosterone. I think it's really helpful to know about this. This tango. You're from Argentina or your father?

Speaker A: I have argentine lineage, yes. My grandparents did tango into their late eighties. I'm in my late forties and I still haven't started. So I suppose there's time.

Speaker B: It might be time for you to.

Speaker A: Okay.

Speaker B: And it might be a factor in their longevity. Do they have good health span? Not just weight span.

Speaker A: And my grandfather smoked cigarettes daily, remained mentally sharp until he died in his late nineties, but almost burned down their apartment several times, falling asleep with a cigarette in his mouth. So I don't recommend anyone smoke, by the way. But it was coffee, mate, red meat, and cigarettes. And they lived into their nineties. So that side of my family has the genetic advantage, the other side less so. But in any event, tango. Tango is a 2023 goal. It has been every year.

Speaker B: I'm going to hold you accountable to that.

Speaker A: Okay, we'll do. And no, there will be no YouTube.

Speaker B: Video of me doing tango, at least not initially.

Speaker A: Tim Ferriss, actually a phenomenal podcaster, as we know, is he's a badass. He's a badass tango dancer. I know this through various sources.

Speaker B: Yes, I've seen. Yeah. So this tango between estrogen and progesterone is incredibly important. You want to have the right lead. You want to have the right follow between the two hormones. Again, I'm stepping away from my science hat, 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 astrobulome.

Speaker A: Can you familiarize me with the astrobulome? Yeah, I'm delighted to know that. I don't recognize the term.

Speaker B: Yeah. So the astrobulome is the set of microbes and their DNA. Their DNA mostly in the gut microbiome, that set of microbes in their DNA. So it's in the. If you look at the totality, the subset of particular bacteria modulate estrogen levels. So a lot of this work was spearheaded by Martin Blaser and I. What we know is that there are some women who have an astrobulum that makes them have a greater risk of certain estrogen mediated conditions, like breast cancer, endometrial cancer, and in men, prostate cancer. The astrobulum is incredibly important. There's not a lot of attention paid to it. But I always think in terms of my patients, could this be someone who's got a faulty astrobillome? And we need to adjust it with some of the microbiome modulating nutrients, nutraceuticals, that we have so that they're less likely to have that tango that's not working with estrogen and progesterone. So, getting back to the biomarkers, if you gave me an unlimited budget, which I kind of have with some of my clients that I work with now, what I would want to know is estrogen, progesterone, testosterone, and I want the timing right for that. I'd want to know about DHEA and sort of the whole androgen pathway. I'd want to know about the metabolites of estrogen because some of them are protective and very helpful. Others are a bit like Homer Simpson. I mean, they are just like causing all kinds of problems in your body, increasing the risk of quinones like DNA damage and potentially an increased risk of breast cancer, although that data, I think, is mixed. I'd also like to know about their stool. So I want to know about the microbiome. So the best that we have right now is to look. When we do stool testing, I do a lot of stool testing. We can look at things like beta glucuronidase. Are you familiar with BG?

Speaker A: I'm familiar with it as a term. And so for those listening, very often, not always, when you hear an ace ase, you're dealing with an enzyme. So we can take a stab there. And it sounds like it's somehow involved in glucose metabolism of some sort, or is it glucagonidation?

Speaker B: So it's involved in when you produce estrogen in the body. This is like the simplified version, but when you produce estrogen, you are meant to use it, send it to the receptors where it's meant to go, and then lose it. You don't want to keep recirculating estrogen, like bad karma. And that's what happens with people who have high beta glucuronidase. It's this enzyme that's produced by three bacteria in particular in the gut. And I see a lot of men and women who have elevated beta glucuronidase, and then they have semesters and dominance related to that. Is that the total reason? We don't really know, but it's one of the drivers, it's one of the.

Speaker A: Levers, and it can be detected from a microbiome, aka stool sample.

Speaker B: That's right.

Speaker A: And in terms of blood testing or various tests for these other biomarkers getting estrogen, testosterone and other ratios, I realize there are people have different means, financial means, but in general, people wanting to do a blood test, it sounds like they're going to need to do it. Women will need to do it at different stages of their menstrual cycle if they had to pick one, either in the follicular phase or in the luteal stage of their ovarian menstrual cycle. Excuse me, ovulatory menstrual cycle. When would you suggest they do that if they had to pick one?

Speaker B: So if you forced me to pick one, I would say probably day 21 to 22 for someone in her twenties. So we're focused right now in that decade. So for most women, they've got a menstrual cycle date that averages out at 28 days. So this is about a week before they start their period. For women who are more irregular, it's harder to do that as women get older. And we'll talk about this in a moment. Usually the cycle gets a little shorter, so as they start to decline in their progesterone production, their period gets a little closer together. Like mine before August was about every 26 days. So at that point, you want to test sooner, like day 1920. And I'm not talking about blood tests. A blood test is the cheapest thing. It's usually what's covered by insurance. But my preference would be to do dried urine. I like to use saliva for cortisol. I like to use dried urine so that I get metabolomics in addition to the levels of these hormones. And if I'm forced to, I'll use blood testing. And that's certainly the gold standard for all of these hormones that we're talking about, but it's not as comprehensive and as you know, it's a quick little snapshot while the needle's in your vein for 30 seconds.

Speaker A: Yeah, the salivary cortisol makes sense to me because my understanding is that you get free cortisol, which is the active cortisol. You said with urine, you're also getting the metabolites.

Speaker B: That's right.

Speaker A: For blood testing, you're getting sort of a crude window into the averages, a static total level.

Speaker B: So let me go back and say one other thing about biomarkers. A big part of the testing that I do in phenotyping my patients, I practice precision medicine. So 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, 2021. So maybe those count, but those are men, obviously. But for nutritional testing, that would be potentially a helpful thing to do in your twenties 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 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 25 years in the future, that it's going to potentially change this arc that they're on.

Speaker A: What do you do for a young woman who doesn't like vegetables or is not somehow able or willing to get those five colors a day of vegetable to help support the microbiome? Are supplements a useful tool in that case? What other sorts of tools, behavioral or otherwise, are useful?

Speaker B: Such a good question. So here I'm going to invoke Rob Knight at UCSD. So I think his gut project has really been helpful in terms of understanding what kind of modulators are going to 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 to throw some of these vegetables in, that makes a huge difference. I mean, we know that makes a difference in terms of microbiome change.

Speaker A: If you're blending up broccoli or kale, cauliflower.

Speaker B: So cauliflower is great.

Speaker A: They're putting things into the smoothie. Yeah.

Speaker B: I don't know if you can get a teenager to do that, but they often will use, like I have them do steamed broccoli that's in the freezer 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 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 he took this to the extreme. He's a retired physicist professor at UCSD. He found out that his microbiome was a hot mess and developed autoimmune disease. He became hell bent, 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.

Speaker A: 57 Independent.

Speaker B: 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 autoimmune disease is in remission. He dropped a huge amount of weight. He went from being 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, supercomputer guy, to being someone who gets up in the morning, gets in his hot tub, exercises for like one to 2 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's the chicken and 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 scientific after all, right?

Speaker A: And retired, I suppose, might have had.

Speaker B: And he's retired, but 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.

Speaker A: I'd like to take a quick break and acknowledge one of our sponsors, athletic greens. Athletic greens, now called ag one, 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 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 and 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, etcetera. And they'll give you a year's supply of vitamin D. Three k, two. Again, that's athleticgreens.com huberman to get the five free travel packs and the year's supply of vitamin D. Three K, two. Is there a case for I'll say young women, but young women and mendenne, 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 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.

Speaker B: Right.

Speaker A: 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 supplementing probiotics?

Speaker B: It sounds like such a simple question. It is such a complex answer, and I don't think we really have the answer. 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. So I've seen some data. If I invoke my 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 drain 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, you don't want a lot of inflammation. You want a little bit to help your muscles recover, but you don't want it to be adding to problems when you develop an injury.

Speaker A: So this is leaky gut, leaky gut.

Speaker B: I don't love that term, but yeah, we'll use it here. So 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 I.

Speaker A: Try and avoid them. There have been instances where they've been prescribed and I took them mostly in the past, like I was in college. They seemed like they kind of gave them out. You had a sinus infection, they give you antibiotics using.

Speaker B: 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 the selective use of polyphenols.

Speaker A: How would a person in their teens and twenties, or any age for that matter, know whether or not they have nutritional deficiencies? What is the best way to analyze if one is getting enough magnesium? And for that matter, what is going to be the best way to test the microbiome? You said stool sample, and I'll come right back with the same question. I asked about a blood test. What time of day, when during the month to establish a baseline. This would be prior to embarking on a 97 vegetable or per day. Well, I love the idea that you're telling us, 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 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 that's a great starting place. Eat or consume more vegetables. Totally. But if one wants to analyze their gut microbiome, are there good tests available to the general public? I'm not going to name companies, but 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 best. We know that dysbiosis is bad and we know that diversity of the microbiome is good. We hear this, but no one's ever told me that you want a particular ratio of one microbiota to another in a way that has made any sense to me, at least. 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 with women, 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 get some crude measures. But for the microbiome, it just seems like long lists of microbiota for which I just get dizzy. If you just wrote out a bunch of I's and ls and s's, you'd halfway. You're getting a 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 my microbiota ought to look like. What's a healthy microbiome chart?

Speaker B: 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, can I tell you that a woman in her twenties should have this particular pattern with her microbiome? No, I can't. So let me go to your first question, because 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, plant based antioxidants, because 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 polymorphisms, you might be less likely to be absorbing the right level of vitamin b, nine, folate, vitamin b, twelve, et cetera. 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 78% of Americans are deficient in magnesium. That's like the lowest hanging fruit.

Speaker A: I would be curious, for instance, 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? We've talked about three and eight. For sleep, there's a mag citrate. There's so many forms, it can be a little bit of overwhelming to people. So any detail in sourcing, I would appreciate it.

Speaker B: Great. So first, in terms of testing, what I prefer to do is to mention more than one lab and more than one brand. And I can just. I'm speaking mostly from experience. So for testing, I do a lot of Genova neutrals. During the pandemic, they developed an at home test. Normally with a neutral, 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 metabolomics, which does much of the same testing, but it's a finger prick. Most of my patients prefer that. In fact, they haven't gone back to the neutral. Second lab is spectra cell. I use spectra cell 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 precision cardiometabolic health. He thinks spectrosol 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.

Speaker A: Really?

Speaker B: Yes.

Speaker A: Wow. I'd be curious as to why that is. I can guess. Diet, stress, patriarchy, rage.

Speaker B: They may not know.

Speaker A: So, pine.

Speaker B: The pine system.

Speaker A: Right. Psychology, immunology, neural and endocrine factors combined. Is that.

Speaker B: Yes. And then I would say there's another factor, which is being female is a health hazard. So we have twice the rate of depression, insomnia. We've got three to four x, increased risk of multiple sclerosis. We've got five to eight times the risk of thyroid dysfunction. If you just look at that and you look at subtle preclinical thyroid dysfunction, a huge number of the women that I take care of. Well, let me back off. A large number of the women that I take care of have thyroid dysfunction. That's contributing to constipation. And if we go back to that control system, the hypothalamic, pituitary, adrenal, thyroid, gonadal, gut axis, and they have a lot of perceived stress together with this borderline thyroid function that no mainstream medicine doctor has told her is a problem. And then she's got a problem with the tango between estrogen and progesterone, she's going to tend toward constipation. Women have a lot more constipation than men. The gut is about 10ft longer in women compared to men. We should talk about some sex and gender differences and define those.

Speaker A: Sure.

Speaker B: And they are much more likely to have a torturous colon. And the way you know that is you get a colonoscopy and they tell you, yeah, it's really hard to get in there and do what we need to do.

Speaker A: As a brief tangent, but I think this is the time to ask, at what age now do physicians insist their female patients get colonoscopies 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, depending on where you live, etcetera, for women, how early do you think they should get a colonoscopy to, to explore for possible polyps and or colon cancer?

Speaker B: 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.

Speaker A: All these additional health hazards for women, you mentioned some of the, you broadly mentioned psychological impact. And of course, these things are all related. Psychology, immunology. And one of the, I think, wonderful things about neuroscience and science in general and medicine is that there's now an understanding that all the organs are connected to one another.

Speaker B: It's a network.

Speaker A: It's a network and that the microbiome sits at. At a key node within that network. And I think most people accept that now. Yes, that seems to be a theme that, at least in the last ten years, is really wonderful, because certainly for neuroscience, it was thought that unless it's in the cranial vault, it's not neural, which is ridiculous because there's lots of nervous system outside the skull. But in any case.

Speaker B: Can I interrupt for a second?

Speaker A: Yes, please.

Speaker B: 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 am 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, maybe an autoimmune condition, feel stressed out all the time, feel like your hormones are out of 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 in real life, it's not happening.

Speaker A: Let's go deeper down that path, because you point out something really important, 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 flag or signal problems that are severe enough that that should be the issue that's dealt with for anybody that's experiencing it? I mean, it's sort of an odd topic for many people because they think, oh, you know, bowel movements and sort of, you know, there's that kind of pre adolescent humor around this. But I think it's so important. What I'm hearing you say is that constipation is far more common in women, and it signals a general set, many problems occurring. Does that mean that women should address constipation? And if so, what's the best way to address constipation?

Speaker B: Yeah, I love this question, because you're doing, can we have a quick little metaconversation? 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.

Speaker A: Thank you. Well, I think for me, when I hear that there's a kind of. 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, but that, I'm guessing, anything to do with sexual health, bowel health, urology, people just don't talk about for all sorts of reasons, and those reasons are probably so obvious that they're not even worth discussing, and also because we won't change them except by talking about them. So if you say women are far more constipated, and that's signaling a larger set of problems, then my immediate thought is, well, will relieving constipation, pun intended, retroactively, 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 be putting vegetables in my smoothie? So I'm curious about constipation as a target for intervention that then opens up a bunch of other discussions, because there are these certain nodes in the. In the mental health, physical health space that when someone, you know, like, we talk 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 number of questions about themselves and reveals a number of things to themselves. Like, how do I buffer stress?

Speaker B: Yeah.

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

Speaker B: Some of us hate cold exposure, right? Which we have, like, a gene that makes us stress out, like, you wouldn't.

Speaker A: Believe, which cold exposure, which I would argue makes it very likely that even 10 seconds of cold exposure gets you the effect that you want, as opposed to someone who adores cold exposure, like a penguin needs a lot more cold exposure for it to have the adaptive response. Anyway, that's my way of gumbing through that. You're quite correct.

Speaker B: So let's answer this question.

Speaker A: The constipation issue.

Speaker B: Yeah. So this is how you're changing the way I think about this. So you're asking, okay, instead of looking at constipation as a constellation of symptoms of what about if you just used it on its own as sort of a key indicator or signal of dysfunction with PI network or maybe something broader. And I think that's right. So it makes me think of a few things. It makes me. You're also changing this book that I'm writing on autoimmunity and trauma. So thank you for that. Women experience more trauma than men. This is well established. If you look at the AcE studies that were done by the CDC and Kaiser in 1998, we know that men, for the most part, middle aged men, have about 50% of them experience significant trauma, as defined by the AcE questionnaire. Women are at 60%, and that's pretty durable since 1998. So women have more. They have different forms of abuse, much more likely to have sexual abuse. They have a different HPA response than men. Their perceived stress tends to be higher. And I'm generalizing for a population side note, you know, in precision medicine, we don't do that. We do medicine for the individual, not the population, not medicine for the average. And so if you look at the physiology of a female, I think that constipation and that need to control and restrain and hold things in, tighten the anal sphincter, I think that's part of the physiology. So I'm veering away from the science, but I do think that it is a really important signal to pay a lot of attention to. Now, you also asked about microbiome testing. Should we do that or do you?

Speaker A: Yeah. Well, I have a couple more questions about constipation. I never thought I'd ask this many questions about constipation, but now I'm fascinated. By the way, also this morning, I taught medical students at Stanford about the fact that we are basically a series of tubes. So you talked about the anal sphincter. We are a set of sphincters from one end to the other. I mean, we are a set of tubes, our nervous system being one of those tubes. And I think in eastern medicine, they talk about the various locks between those tubes and chambers. It's not without coincidence. There's some real wisdom there, of course.

Speaker B: Wait, did you just talk about energetic anatomy?

Speaker A: More or less. I didn't say the word chakras, but I might in passing. That's the bondas, the bandas. Right. Are the sphincters. Yes, that's right. Thank you for that. So what defines constipation? I mean, in other words, let's think about the healthy rather than think about the unhealthy. Let's. How many bowel movements should a woman or a man have per day? Assuming, and this is where it gets tricky, because some people are doing time restricted feeding, some people are eating more, some people are eating more fiber, more bulk, larger meal at the end of the day, a larger meal at the beginning of the day. We will never be able to sort out all those variables, but on average, how many bowel movements and is timing during the day for bowel movements at all informative?

Speaker B: What works for you?

Speaker A: Well, when I'm asleep, generally, I don't want a bowel movement, so I'm gonna be like most people, right?

Speaker B: Well, sleep is primary for you, right?