Essentials: How to Optimize Your Hormones for Health & Vitality | Dr. Kyle Gillett

In this Huberman Lab Essentials episode, my guest is Dr. Kyle Gillett, MD, a dual board-certified physician in family medicine and obesity medicine and an expert in optimizing hormone levels to improve overall health. We explain how to improve hormone levels across the lifespan in both men and women using behavioral, nutritional and exercise-based tools. We also discuss common clinical topics, including hormone testing, PCOS, hair loss, testosterone replacement therapy (TRT) and peptides, focusing on potential benefits, tradeoffs and risks. Read the episode show notes at hubermanlab.com. Thank you to our sponsors AG1: https://drinkag1.com/huberman Maui Nui: https://mauinuivenison.com/huberman Function: https://functionhealth.com/huberman Timestamps (00:00:00) Kyle Gillett (00:00:36) Hormone Health; Women vs Men, Tool: Hormone Testing (00:02:35) Tool: Big 6 Lifestyle Pillars to Optimize Hormone Health (00:04:32) Sponsor: AG1 (00:06:17) Diet, Individualization; Bloodwork & Frequency (00:07:20) Exercise, Zone 2 Cardio; Caloric Restriction (00:08:36) Intermittent Fasting, Growth Hormone, IGF-1 (00:11:05) Hormones & Sleep, Growth Hormone, Menopause, Andropause, TRT (00:13:28) Testosterone & Women, SHGB (00:15:19) Sponsor: Maui Nui (00:16:34) Dihydrotestosterone (DHT), Androgens; Turmeric & Black Pepper; Hair Loss (00:19:47) Polycystic Ovarian Syndrome (PCOS), Symptoms, Metformin, Inositol (00:23:13) Cannabis, Alcohol, Testosterone (00:24:48) Males & Testosterone, TRT, Prostate Cancer (00:26:04) Prolactin, Dopamine "Wave Pool", Tool: Casein & Gluten (00:27:23) Sponsor: Function (00:29:03) Social Relationships & Hormones, Tool: Planning for Crisis (00:31:02) Peptides, Growth Hormone & Risk; BPC 157, Sourcing & LPS (00:36:42) Melanotan, Uses & Risks (00:38:45) Spiritual Health, Interdisciplinary Health Integration (00:41:23) Caffeine & Hormones, Sleep; Acknowledgements Disclaimer & Disclosures Learn more about your ad choices. Visit megaphone.fm/adchoices

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Andrew D. Huberman?

  Welcome to Huberman Lab Essentials, where we revisit past episodes for the most potent and actionable science-based tools for mental health, physical health, and performance. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. And now for my discussion about hormone health and optimization with Dr. Kyle Gillette. Dr. Gillette, welcome.

• 0:23Kyle Gillett?

  Thank you for having me.

• 0:25Andrew D. Huberman?

  Well, I'm super excited to talk to you. You are an encyclopedia of knowledge about hormone health for men and for women across the lifespan. So I have many, many questions. When someone comes to you as a patient, in terms of hormone health, what are the sorts of probe questions that you ask? And what are you looking for? And I ask this because I'd like people to be able to ask some of these very same questions for themselves.

• 0:48Kyle Gillett?

  So when you do a physical exam and a history, you have a lot of different parts. You have your history of present illness. If they have a complaint, maybe the patient doesn't have a complaint. In that case, things like their social history and their family history are extremely important because that gives you an insight into their genetics and an insight into their hormone health. So patients will tell me, I'm doing okay. But it helps to ask them, well, how are you now? Let's say the patient is 50. How are you now versus when you were 20? And what has changed? So I've got the question a lot. How do you get your doctor to order a better lab workup or to even include your basic hormones? And there's no magic answer to that.

• 1:32Kyle Gillett?

  But what really helps is you tell them, you know, my energy is not as good as it used to be. My focus is not as good as it used to be. My athletic performance is not as good as it used to be. So you don't have to have a pathology in order for a lab to be indicated. You just need to have that pertinent symptom.

• 1:48Andrew D. Huberman?

  Would you say that, using the approach you just described, that it's equally effective for men and women? Or do you find that, for one reason or another, that men and women have different challenges and advantages in trying to access their deeper hormone data?

• 2:03Kyle Gillett?

  With women, there's a lot more objective data. So if they're having menstrual irregularities, or if they're not having a period, if they're having too heavy of periods, then those are things that they talk about very frequently with their doctor. Men are more hesitant. Men really want to know what their testosterone is. But they, at the same time, they really don't want to tell their doctor how their libido is or how their energy is because it's almost like they feel less masculine or they feel less like a guy when they say that, even if they're just talking to their doctor about it.

• 2:35Andrew D. Huberman?

  I'd love to just kind of take a snapshot of what you think everybody should be thinking about or doing to optimize their hormone health, male or female, from puberty onward?

• 2:47Kyle Gillett?

  The law of diminishing returns applies. So doing a little amount of what I call lifestyle interventions over a long period of time is going to be far more helpful or efficacious than doing a lot and then doing nothing. So I talk about the big six pillars. The two strongest ones are likely diet and exercise. For hormone health, specifically resistance training is particularly helpful. For diet, caloric restriction can be particularly helpful, especially with the epidemic of metabolic syndrome that is continuing to on go in this country and in developed countries in general. Those are the two most powerful.

• 3:29Kyle Gillett?

  For the last four, I have a little bit of alliteration. So there's stress and stress optimization. That has to do with cortisol, that has to do with your mental health, that has to do with societal health and collective health of your family as well. When you're a member of a family or even a very close friend, trying to achieve optimal health together is very important. It's the same thing with nicotine cessation, it's the same thing with hormone optimization. If you do it as a household unit, it's far more helpful. So after stress, you have sleep optimization. Sleep is extremely important, especially for mitochondrial health as well. And then you have sunlight, which encompasses anything that's outdoors.

• 4:10Kyle Gillett?

  So you move more, you have cold exposure, you have heat exposure. That's sunlight. And then the last one is spirit. So that's kind of the body, mind, and soul. If you have all the other five in, they're dialed in completely, but you don't have your spiritual health, whatever you believe, then that's going to profoundly impact your body and your mind as well.

• 4:32Andrew D. Huberman?

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• 5:16Andrew D. Huberman?

  your metabolic health, your hormone health, and much more. Taking AG1 consistently helps my digestion, keeps my immune system strong, and it ensures that my mood and mental focus are always at their best. AG1 is now available in three new flavors: berry, citrus, and tropical. And while I've always loved the AG1 original flavor, especially with a bit of lemon juice added, I'm really enjoying the new berry flavor in particular. It tastes great, but then again, I do love all the flavors. If you'd like to try AG1 and try these new flavors, you can go to drinkag1.com/huberman to claim a special offer. Right now, AG1 is giving away six free sample packs of AGZ, which is AG1's new sleep formula, which, by the way, is fantastic. It's the only sleep supplement I take. It eliminates the need for all these pills,

• 6:01Andrew D. Huberman?

  and my sleep has never been better. The special offer gives you six free samples of that AGZ, as well as three AG1 travel packs and a bottle of vitamin D3 K2 with your first subscription. Just go to drinkag1.com/huberman to get started. What would you say is a really terrific way to think about and approach diet?

• 6:22Kyle Gillett?

  Yeah, diet should be an individualized approach. So if you have a car, each car is made different and requires a different sort of fuel, whether it's a race car, whether it's a diesel truck. They have different fuels for different performance outcomes. So if you're trying to tow something or you're trying to go fast. It also depends on your genetics. So you can have a genetic polymorphism and you metabolize carbs and sugar better, even when they're unopposed by fiber. Basically, you can use your biofeedback, how you're feeling, to guess what you tolerate well, or you can just get genetic testing, which can be fairly expensive, but most of all, it requires a physician or someone who knows how to interpret the test accurately.

• 7:03Andrew D. Huberman?

  And if someone had the means, or would you say that getting regular blood testing is a good idea? And if so, what is regular blood testing? Is it every three months? Is it every six months?

• 7:13Kyle Gillett?

  Every three to six months for preventative purposes. You should also get a blood test when you're fasting and when you're not fasting.

• 7:19Andrew D. Huberman?

  And in terms of general recommendations around exercise, I'm of the mind, based on the data that I've seen, that almost everybody should, or everybody should be getting 150 to 180 minutes minimum of zone two cardio per week?

• 7:35Kyle Gillett?

  Yeah, that's more or less the contour. The more you're doing your zone two cardiovascular exercise, the slightly less important a long duration of caloric restriction is.

• 7:48Andrew D. Huberman?

  And that brings us to caloric restriction. How does someone know if they should use caloric restriction or avoid caloric restriction?

• 7:54Kyle Gillett?

  The reason for exercise and the reason for caloric restriction in general, including intermittent fasting, is health reasons. That's how you increase your health span. It's not necessarily going to make the weight on the scale change, but that doesn't matter as much. So the easy way to think about it is if you're obese or you have metabolic syndrome, caloric restriction will improve your testosterone. There has been a study, and they talk about all these studies in a systematic review from the Mayo Clinic Proceedings. They note that there is a study in young, healthy men, and they calorically restrict them, and their testosterone does decrease. So if you're young and healthy and you don't have metabolic syndrome, then caloric restriction will likely decrease your testosterone.

• 8:35Andrew D. Huberman?

  For the healthy, lean enough person, right, non-obese person, is intermittent fasting a bad idea in terms of hormone health? Is oscillating between this period of feast and famine within a 24 hours a problem if one is getting sufficient calories to maintain weight?

• 8:54Kyle Gillett?

  So if they're in a caloric maintenance, then it's not going to be...

• 9:00Kyle Gillett?

  It's not going to be deleterious, it's not going to be bad for their hormone health. There's a couple of different hormones that we can talk about. We can talk about testosterone, we can talk about DHEA, which usually go hand in hand. And then we can also talk about growth hormone, which is not a steroid hormone, but it's a peptide hormone. So it's a chain of proteins, amino acids that are put together instead of a sterol. Think of sterol hormones as coming from cholesterol. So you do get a little spike in growth hormone after you eat. But you also get a huge spike in growth hormone, a more significant, less negligible spike overnight. And that is improved if you are intermittent

• 9:42Kyle Gillett?

  fasting. So it's probably going to help your growth hormone and subsequently IGF-1 levels, which will help more in older age groups than younger age groups.

• 9:53Andrew D. Huberman?

  Can I still achieve a high degree of growth hormone output if, let's say I avoid food in the two to three hours before going to sleep? Or does one have to be very deep into a fast in order to achieve this, the increase in growth hormone?

• 10:07Kyle Gillett?

  There's still pretty good growth hormone output, even if you eat two or three hours before you sleep. It's just the law of diminishing returns. The longer you go, you get slightly more and slightly more. But I think about it in terms of endocrine IGF-1, mostly IGF-1 that's synthesized in the liver and released in the liver versus IGF-1 that's released. Classically, an example of this would be your IGF-1 levels increase after resistance training or exercise. And that's more of like paracrin or autocrin, and they have more local action. So that IGF-1, it's pretty well studied that if you just give people IGF-1, it's not going to, at physiologic levels, it's not going to improve their body composition.

• 10:51Kyle Gillett?

  However, that IGF-1 that's autocrine and paracrine just working in those local tissues and muscles is likely part of the reason why you get a improved body composition response after exercise.

• 11:04Andrew D. Huberman?

  Are there any aspects of hormone optimization that can improve sleep? I know sleep can improve hormone optimization, but for people that are suffering from this common syndrome of going to sleep and then waking up at 3 or 4 in the morning, we know that can be associated with depression, but are there any hormonal indications that might lead to that kind of situation?

• 11:25Kyle Gillett?

  There's three big ones. The first one is not super common, but it's a very direct correlation. If you have a growth hormone deficiency, a true deficiency, whether you're an adult or a child, then your sleep is likely going to be affected. And let's say you're a child with growth hormone deficiency. Once that is replaced with therapy, your sleep is going to get significantly better. The second one that's a very common scenario is if you're having what's called vasomotor symptoms of menopause or vasomotor symptoms of andropause, which are also applicable. That's why a lot of women in menopause feel like their sleep is much worse is because they have lower activity of those progestogens.

• 12:07Andrew D. Huberman?

  And for men in so-called andropause, low testosterone, is that also one of the causes of poor sleep?

• 12:15Kyle Gillett?

  Low testosterone can lead to poor sleep, but my third scenario is actually if a man begins TRT, then they develop poor sleep because of sleep apnea. It drastically raises the risk that somebody is going to have sleep apnea. And then a lot of people, especially when they first start it in the first month or two, it puts them into this hyper-sympathetic state because they have overactive androgen receptors, especially after a long time of being hypogonadal. Then they have a physiologic dose of TRT, and that causes the sleep issue itself.

• 12:51Andrew D. Huberman?

  Is that also the case in people that are using TRT who are not hypogonadal? Many people nowadays... Let's be honest, are taking doses of testosterone even though they are in the sort of standard range because the range is so large because of other symptomology. Is that right?

• 13:07Kyle Gillett?

  If you're eugenatal before you start testosterone.

• 13:11Andrew D. Huberman?

  Meaning?

• 13:12Kyle Gillett?

  Meaning you have normal testosterone and then you start TRT or self-administered TRT steroids, however you want to look at it, then your risk of sleep apnea still goes up in a dose-dependent fashion. So the higher the dose, the more risky.

• 13:28Andrew D. Huberman?

  I want to touch on testosterone in women. I'd like to know whether or not knowing a woman's testosterone, for her to know her testosterone is of equal, less than, or more value than knowing, for instance, progesterone and estrogen levels, because I think there are a lot of misconceptions about the roles of testosterone in women.

• 13:46Kyle Gillett?

  For health optimization, testosterone is just as important to know. For pathology prevention, for example, breast cancer, osteoporosis, estrogen and progesterone are more important to know. So when you're thinking about women, women think that they have such a tiny amount of testosterone because you could, you test it. Most people test a free testosterone, so testosterone that's unbound, which is by far the smallest proportion of testosterone. Any androgen is bound by lots of different steroid-binding proteins, but the ones that are most pertinent are called SHBG or sex hormone binding globulin, and that binds the androgenic steroid, for example, DHT or dihydrotestosterone. It's associated with prostate enlargement,

• 14:31Kyle Gillett?

  associated with male pattern baldness. It binds that the most strongly, and then it binds testosterone next most strongly, and then it binds things like androstenidione or DHEA, dehydroepiandrosterone, and then it binds the estrogens, the weakest, like estradiol. So if you look at the total amount of testosterone, women actually have, almost all women, not all women, but almost all of them have significantly more testosterone than estradiol, but it's because it's in different measurements. So estradiol a lot of time is, you know, grams per mill as opposed to nanograms per deciliter. So women have more testosterone than estrogen.

• 15:15Kyle Gillett?

  And significantly more DHEA than either.

• 15:19Andrew D. Huberman?

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• 16:04Andrew D. Huberman?

  I've been adding the summer sausage to my eggs in the morning, to my salads, and to pretty much everything I'm eating these days. It's just so good. Right now, Maui Newey is offering Huberman Lab listeners a free Venison Stick Starter Pack with your first order over $79. These Venison Sticks are also fantastic. Just visit maowinewyvenison.com/huberman to get this free Venison Stick Starter Pack with your first order over $79. Again, that's maowinewyvenison.com/huberman. I'd like to ask about DHT in men. So often, we hear about testosterone in men and free testosterone and being the unbound form, of course, but dihydrotestosterone, but what is it doing?

• 16:47Kyle Gillett?

  DHT is a very androgenic hormone. So whether you're talking about DHEA, which is a mile, a weak androgen, or testosterone, which is a relatively strong androgen, or DHT, which is a very strong androgen, they bind to the androgen receptor in both men and in women. So the effect of all three of those is mediated by the androgen receptor. Intriguingly, it is on the X chromosome. So men get their androgen receptor gene from their mother. So DHT helps a lot for, it's the same reason why testosterone helps. It helps effort feel good, so it can be motivating.

• 17:27Kyle Gillett?

  There's lots of dietary changes and supplementation that you're probably doing right now that's affecting your DHT.

• 17:33Andrew D. Huberman?

  You mean me personally?

• 17:34Kyle Gillett?

  Well, everybody, all of the listeners. Because let's say you have a diet high in plant polyphenols. Many of those inhibit the enzyme that converts testosterone to DHT.

• 17:46Andrew D. Huberman?

  Could you give us an example of one of those, either in supplementation form or in food form?

• 17:53Kyle Gillett?

  Yeah, turmeric, black pepper extract.

• 17:55Andrew D. Huberman?

  Do you recommend that people avoid curcumin and turmeric for that reason?

• 17:58Kyle Gillett?

  If someone's DHT is already low, or if they have somewhat insensitive androgen receptor via genetics or via lifestyle, then I recommend they avoid bioavailable curcuminoids, like bioavailable turmeric, black pepper extract.

• 18:14Andrew D. Huberman?

  I know many people want to avoid the hair loss that can sometimes be associated with DHT levels going too high. If somebody is concerned about or is experiencing hair loss, male or female, what are their options of ways to offset that hair loss that are not going to negatively impact other tissues sensitive to DHT? And what I'm basically saying here is, I could imagine taking a DHT inhibitor, a pill of some sort or an injection of some sort, and offsetting hair loss, maybe even stimulating more hair growth. It's clear that I'm not doing that, but I know people that do. But then experience some of the other negative effects of blunting DHT,

• 18:57Andrew D. Huberman?

  reduced affect, reduced libido, reduced drive, disruptions in prostate function, or even sexual function generally. So what could, can people do if they want to maintain or grow back hair, but they don't want all those other effects? What should they avoid? And what should they perhaps consider talking to their doctor about?

• 19:16Kyle Gillett?

  You want some sort of... Strategy to decrease the activity of that androgen receptor. There's a lot of different things that you can do that are topical. The most promising is called dutasteride mesotherapy. Essentially, what it is, is it's very localized injections in areas that are prone to male pattern baldness, whether they're female or male. And it acts locally only. And you repeat these injections from time to time. It decreases the conversion of testosterone to DHT just in the scalp.

• 19:48Andrew D. Huberman?

  How does a woman know if she has PCOS, polycystic ovarian syndrome? I know you have treated a lot of PCOS. What age women should be thinking about PCOS? What's PCOS? Teach us about PCOS, please.

• 20:02Kyle Gillett?

  Yeah, so PCOS is polycystic ovarian syndrome. And this is one of those conditions which is underdiagnosed. So its prevalence is much higher than we think it is. There's been a lot of studies and some, some studies say prevalence of 10%, some say 20%. It's not completely clinically penetrant. So most people don't know they have PCOS until they have infertility or subfertility.

• 20:29Andrew D. Huberman?

  And is this, is PCOS happening at this frequency in 20-year-old women and 30-year-old women and 40 and onward?

• 20:35Kyle Gillett?

  Most women find out they have PCOS in their 30s. Especially, it's on a spectrum or a continuum like a lot of things where you can have a weaker version or a very severe version.

• 20:45Andrew D. Huberman?

  What are the symptoms?

• 20:47Kyle Gillett?

  There's criteria called the Rotterdam criteria. And in the Rotterdam criteria, there's a couple of different ways that you can diagnose it. You're looking for androgen excess, insulin resistance, and you can also look for polycystic ovaries. You don't actually have to have polycystic ovaries or get an ultrasound of your ovaries to be diagnosed. If you have androgen excess, for example, androgenic acne or hormonal acne, if you have hair growth, like a hair growth on the chin, it's called a hirsutism. Or if you have, you know, like deepening of the voice, any symptom of too much androgen, male pattern baldness, if you're female, that's a symptom of PCOS as well. Then you can also have insulin resistance.

• 21:30Kyle Gillett?

  So this is obesity, it's prediabetes, a high fasting insulin, a HOMA IR over two, a fasting insulin of over six. So if you have significant insulin resistance and also androgen dominance, that's a sign of it. Androgen dominance often leads to what's called oligomenorrhea. So if you're having more than 35 day intervals in between a period, or if you have less than nine per year, then that can be a sign that you have oligo, which means too little, menorrhea, which means menses. So that's a very common sign of PCOS.

• 22:11Kyle Gillett?

  If you have infertility, so if you're under the age of 35 and you've been trying for more than a year, or if you're over the age of 35 and you've been trying for more than six months, then that can also be, it's a very common presenting complaint when somebody presents with PCOS. If they're very strong on the insulin resistance spectrum, then optimizing their body composition, decreasing their body fat, and treating that metabolic syndrome can help. So a lot of people ask, well, does everybody that's on, like, does everybody need to be on metformin that has PCOS? Not necessarily, but metformin is one of the tools that can help with insulin sensitization. Other tools that can help are anostatol. So myoinostatol is an insulin sensitizer.

• 22:56Kyle Gillett?

  It's cousin dekyroanostatol is a weak anti-androgen. A lot of types of anostatol have both of those in it. So depending on if you're a female or a male and you're on anostatol, the type of anostatol does matter.

• 23:13Andrew D. Huberman?

  Marijuana. I've heard that it can decrease testosterone in men and women. I've heard that it can increase testosterone. Alcohol. I think there's general consensus that high alcohol intake, high barbiturate intake does in fact reduce testosterone. I'm not a drinker, so I'm not asking these questions for me. I don't smoke pot, but I just never really liked marijuana or alcohol. They're not my thing. But many people want to know the answers to these. So what about marijuana? Does it reduce testosterone to significant degree or not?

• 23:47Kyle Gillett?

  Cannabinoids itself, whether it's THC or CBD, are not going to reduce testosterone by themselves. If it's smoked marijuana, then it's very likely to increase your aromatase, which increases your estrogen. And, you know, that's gonna, it's aromatizing from testosterone. So that is going to decrease testosterone. When you have an increased estrogen, like estradiol, that's gonna work on your pituitary to make less hormones that cause the release of testosterone. So you're gonna have less LH and less FSH. So it's almost kind of like, you know, opiates are well-known to opiate agonists.

• 24:30Kyle Gillett?

  They're going to decrease LH and FSH and subsequently testosterone. Smoked marijuana will as well. As far as alcohol, high alcohol will decrease testosterone, as will any very potent GABA agonist, whether it's a barbiturate or a benzodiazepine or a non-benzodiazepine or alcohol. They're definitely going to.

• 24:48Andrew D. Huberman?

  So let's talk about testosterone in males. I'm aware that a lot of people are considering increasing their testosterone by taking testosterone. That, a few years ago, that was considered, you know, steroid use and it was really extreme kind of stance. Nowadays, it seems like there's more discussion about it. Does testosterone supplementation, and here I'm talking about prescription from a doctor, does it make one more prone to prostate cancer? That seems to always be the first question that comes out.

• 25:17Kyle Gillett?

  So testosterone is not going to cause a prostate cancer. However, normal aging causes prostate cancer and testosterone will grow your prostate cancer. So if you're an 80-year-old male and you have an autopsy, then there's at least a 50% chance that you have a prostate cancer. If you're 90 or 100 years old, there's at least a 90% chance. So for humans with a prostate, it's only a matter of time until you get a prostate cancer. So that begs the question, do you want to take something that's going to grow it for sure, once you have it? So it's an individual assessment with aging. You know, a fast aging is abnormal. Very slow aging is normal.

• 26:01Kyle Gillett?

  There's a fine line to walk between those two.

• 26:04Andrew D. Huberman?

  What about prolactin? Just as testosterone and estrogen need to be in the proper ratios, dopamine and prolactin need to be in the appropriate ratios. So what, how should we think about and perhaps act on our prolactin systems?

• 26:17Kyle Gillett?

  The way I describe it is the dopamine wave pool. So if you're increasing your dopamine too much, you're going to overflow and then you're going to have that wave crash too much. So you want to have nice even waves that are not going too far above the pool of dopamine and prolactin will follow. So prolactin and estrogen are quite close cousins. Estrogen upregulates a gene called the PRL gene or prolactin gene that directly increases prolactin synthesis. So prolactin is going to also inhibit the release of testosterone from the pituitary. So if you're using a dopamine agonist, then you're going to help decrease the prolactin producing cells.

• 27:01Kyle Gillett?

  So if someone's concerned about dopamine, or maybe they have a slightly higher prolactin, then they eliminate things that could be increasing that prolactin.

• 27:09Andrew D. Huberman?

  Such as?

• 27:10Kyle Gillett?

  So casein or gluten, which are mu opioid receptor agonists, or any mu opioid receptor agonist in the gut.

• 27:18Andrew D. Huberman?

  It's casein, so milk protein?

• 27:20Kyle Gillett?

  Correct.

• 27:21Andrew D. Huberman?

  Can increase prolactin?

• 27:22Kyle Gillett?

  Correct.

• 27:23Andrew D. Huberman?

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• 28:05Andrew D. Huberman?

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• 28:49Andrew D. Huberman?

  Function currently has a waitlist of over 250,000 people, but they're offering early access to Huberman podcast listeners. Again, that's functionhealth.com/huberman to get early access to Function. I'd like to shift gears slightly and talk about social interactions and relational effects on hormones. What would you suggest people do or think about as they enter a relationship, or for people that are in long-term relationships where they feel like something has shifted? And indeed, those shifts may reflect the output of different hormone systems and neurotransmitter systems. It almost certainly has to be the case, right?

• 29:30Kyle Gillett?

  Yeah. So, just like women who spend a lot of time together, whether they're coworkers or whatever, a lot of times their menstrual cycles will align. There is a lot of pheromonal and hormonal crosstalk, including prolactin between men and women. So, spending 100% of the time together, this is why people think it's so hard to work together and live together. They're around each other 24/7. You don't have the reprieve where you let that dopamine settle down, and then you're excited when you see them again. A lot of guys know that they've gone on a trip for a long time, they come back. And they see their partner and it's like a new, not quite like a new relationship, but almost like a new relationship and they have that excitement again.

• 30:12Kyle Gillett?

  And purposely building that into every relationship can help significantly, especially if you choose to have a child or get pregnant or be breastfeeding, because you just plan ahead for both of your prolectins to be high and both of your dopamines to be low and both of your testosterones to be low. So there's a, there's a lot of planning that you can do. Essentially, every relationship goes through a crisis. And that crisis is personal between the two of you and you can plan ahead and figure out a way, maybe it's not supplementation, maybe it's not even the amount of time you

• 30:54Kyle Gillett?

  spend away from each other, but plan ahead to have good times if you know you're about to go into a crisis.

• 31:01Andrew D. Huberman?

  Peptides, lot of discussion these days about peptides. What can we say generally about peptides? Are they safe? Are they not safe? What about sourcing? And are there any peptides that you think could be of particular use for people? And we should probably also touch on peptides that people shouldn't go anywhere near with a 10-foot pole.

• 31:17Kyle Gillett?

  Yeah, definitely. So peptides are very heterogeneous. There's very dangerous ones and very safe ones. My favorite peptide is the original peptide, which is insulin.

• 31:28Andrew D. Huberman?

  And yet insulin can kill you if you take it at the incorrect dose.

• 31:33Kyle Gillett?

  Yeah, so just like insulin should be prescribed by a doctor, there is over the counter insulin, rely on or NPH, but ideally your insulin is prescribed by your doctor for your diabetes as it's life-saving. Peptides should be prescribed by doctors as well. And there's several that are FDA-approved. Growth hormone itself is also a peptide. It's a peptide hormone, not a steroid hormone.

• 31:58Andrew D. Huberman?

  So if somebody wants to increase their growth hormone output, what are the risks and benefits of taking a growth hormone-releasing hormone peptide prescribed by a doctor, of course? What should one be concerned about?

• 32:10Kyle Gillett?

  There's definitely a lot of risk, tumor growth and cancer. So you look at a type 1 diabetic, they have very high incidences of various types of cancer. They have very high growth hormone, but low IGF-1, paradoxically. So they would likely give you a similar cancer risk to a type 1 diabetic that has very high growth hormone. However, there are the benefits of it. You think of lipolysis, decreased body fat, increased lean body mass. A lot of those can, you can use other things to get those benefits. So then, you know, you don't need growth hormone for those benefits.

• 32:51Kyle Gillett?

  It just leaves cosmetic benefit, to which you can usually use topicals to get, you know, your hair and your skin and your nails. There's a lot of other things that you can do other than growth hormone. So a lot of people just don't need these GHRPs.

• 33:07Andrew D. Huberman?

  Yeah, let's talk about BPC 157 and melanotin because I think those are the ones that most people are eyeing, so to speak.

• 33:14Kyle Gillett?

  Yeah, so BPC 157 is body protective compound 157. It's identical or bio-identical to gastric protective compound 157 that's produced in the stomach. So as you age, you get atrophic gastritis very often. That's why you have less intrinsic factor, which is kind of another peptide that binds to vitamin B12. That's why you can get age-related B12 deficiencies. So that's one reason why you have more colitis, more diverticulitis as you age. You don't have that gastric protective compound. It's, it increases VEGF, vascular endothelial growth factor, which basically makes your blood vessels grow more.

• 33:58Kyle Gillett?

  So that's what causes your body to form a blood vessel. So another medication known as Avastin, it's on the WHO's list of essential medications for cancer. So many different types of cancer, including colon cancer, you treat it with Avastin, which is a VEGF inhibitor. So if you have cancer or a high cancer risk, you probably don't want to be taking a medication that's the exact opposite mechanism of action as your essential anti-cancer med.

• 34:27Andrew D. Huberman?

  In other words, if you have cancer or you're at risk of cancer, avoid BPC 157.

• 34:31Kyle Gillett?

  Correct. BPC 157 is not FDA-approved, but it is essentially standard of care at this point. I would say it's, you know, if you're not counting insulin or growth hormone as peptides, it's one of the most commonly used peptides. And anecdotally and in some clinical literature, it's fairly well tolerated for short periods of time. I'm not in the camp that everybody needs to do it two to three times a week or even daily for six weeks, no matter what. The major benefit is when you're going to take it early on because it's going to allow your body to increase blood flow to the injured area. And the less blood flow it has, for example, cartilage ligaments have horrible blood flow,

• 35:13Kyle Gillett?

  especially as people age, it's going to make a significant difference. So I would wager that that Russian gymnast that Achilles healed in one month completely from a full rupture was likely taking BPC157 or something very similar.

• 35:26Andrew D. Huberman?

  Yeah, I'm willing to wager on that as well. A remarkable recovery. And so because it is prescription, there are non-prescription forms. My understanding of the non-prescription forms and the danger of going after non-prescription forms is that oftentimes they will contain what they claim they contain, BPC157 in this case, but they are not adequately cleaning out the LPS, the lipopolysaccharide, which can cause inflammation. In fact, in the laboratory, we use LPS to deliberately induce fever and inflammation to study systemic inflammation. So this is a warning to people, if you're interested in peptides, you absolutely need to work with a physician, in my opinion. Get it from a really good compounding pharmacy who will clean out, that cleans out the LPS.

• 36:08Andrew D. Huberman?

  Because if you're buying it through a source that, you know, a lot of people, I don't want to name sources, but there are these common sources on the internet that everyone knows about, they're buying these sources, they'll ship it to anyone essentially. But then the LPS is really causing inflammation and many people experience a kind of mild fever or tingling from that when they inject it and they're like, oh, I can feel it working. That's probably LPS action, which is not good for the brain. I don't know about the, on other peripheral tissues. I haven't heard of people dropping dead from this stuff yet, but I certainly wouldn't want to be ingesting any LPS unnecessarily. You mentioned melanotan, there are several kinds of melanotan. I first learned about melanotan from reading about peptides and discovering that people

• 36:49Andrew D. Huberman?

  were taking, injecting melanotan to get tan because it's in the melanin synthesis pathway. Are there any clinical usage of melanotan?

• 36:59Kyle Gillett?

  There's actually three FD-approved indications, believe it or not. Not many people know about this, but there's three well-accepted indications. One of them is the hypoactive sexual disorder and more in women. That's for brimelanotide.

• 37:12Andrew D. Huberman?

  So those are, those are women that have essentially no libido whatsoever.

• 37:15Kyle Gillett?

  Yeah.

• 37:16Andrew D. Huberman?

  But other hormones are in check.

• 37:18Kyle Gillett?

  Yeah. Classically, it's before menopause. So those hormonal issues are not contributing. And when you give them this peptide, it's also known as PT141. It helps significantly. A lot of times you use it in nasal spray. It goes straight into the central nervous system and acts centrally. You can also inject it and you can also take it via trokey.

• 37:39Andrew D. Huberman?

  Men and women take it?

• 37:41Kyle Gillett?

  Correct. It's approved for women, but it can also help men. And it's relatively safe. The only relative contraindication that I tell people, and a lot of people say, oh, there's no side effects that I know of. But if you have a family history of melanoma or potentially have a melanoma and don't know about it. That's why I'm a big advocate of dermoscopy as well and regular skin checks. Then theoretically, it's going to increase that alpha melanocyte stimulating hormone. And it can grow that. So that's definitely not a good thing. So be very careful about long-term administration of it. It's also approved for lipodystrophy, which is the same exact thing as tesamoralin, which I believe is also known as Evista or Agrifta.

• 38:25Kyle Gillett?

  And then it's also approved for the rare genetic condition where your receptors or your melanocytes don't proliferate as well. So you usually have hypopigmentation. It's not true albinism, but it's associated with morbid, morbid obesity and very poor outcomes from that in childhood. So it's used in kids, actually.

• 38:44Andrew D. Huberman?

  Interesting. I want to talk about the sixth pillar, spirit. How do you conceptualize the spiritual aspect? And how do you talk to patients about this, given that people walking into your clinic presumably have a bunch of different religious and not a-religious backgrounds? I'm sure some are atheists, some are probably strong believers. How do you? Deal with that and how should people think about this?

• 39:05Kyle Gillett?

  Yeah, it is surprisingly well received. You wouldn't think at first glance that a patient really wants to talk about their spiritual health with their doctor. But the way I think about it and the way that it really is, is it's like a Venn diagram and you have a body and a mind and a soul. And you can't have one healthy without the other healthy. Even if your mental health is phenomenal and even if your physical health is phenomenal, the mental aspect of spirituality, if that piece is not there, then that's going to affect your body physiologically as well. And regardless of someone's an atheist or regardless of regardless of what someone believes as far as religion or the origin of the species, they can know that their

• 39:48Kyle Gillett?

  spirituality is going to have a profound effect on their mental and physical health as well. People like to compartmentalize it. So they like to talk to their doctor only about the physical health because it's comfortable to do that. They only talk to their pastor or a mom or, you know, rekey their for their spiritual health and they just talk to their therapist or psychiatrist about their mental health. But you need to bring all three of those things together. It's well known that interdisciplinary clinics lead to improved patient outcomes and that's just disciplines within medicine. So that's just doctors that are specializing in this or this. So this takes a step back and upper in the upper part of that tree before you reach those dichotomies or the split offs.

• 40:32Kyle Gillett?

  You have your you have your body and your mind and your soul. So your spiritual health and your mental health and your physical health. So if you're in line in all three of those things, that builds the cornerstone for the rest of your health and the rest of your life. So I hope that everybody does find what they truly believe in as far as their own spirituality. But yeah, that's a personal journey.

• 40:57Kyle Gillett?

  From a physician's standpoint, and even if I'm friends with him as well, from a friend's standpoint, I don't like to push anybody in any specific direction. So I don't think that everybody should believe what I believe. And I don't feel like there should be any pressure for them to believe something different. So I think that there can be excellent physician-patient rapport regardless of what we believe and what our backgrounds are.

• 41:23Andrew D. Huberman?

  I have one final question. Is caffeine having an effect one way or the other on testosterone, estrogen, or other hormones that is positive, negative, or neutral?

• 41:35Kyle Gillett?

  Only if it affects your sleep. So it works on adenosine, and it can actually slightly improve allergies as well. But negligible effect otherwise.

• 41:43Andrew D. Huberman?

  Kyle, Dr. Gillette, I should say, thanks so much for your time. I really appreciate it. I know the listeners will too.

• 41:49Kyle Gillett?

  Thank you. My pleasure.

• 41:56Speaker 02

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