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

The exchange opens by situating the episode as a discussion of science and science-based tools for everyday life. Andrew Huberman introduces Dr. Kyle Gillett as dual board-certified in family medicine and obesity medicine, practicing out of a clinic in Kansas and via telemedicine, and providing full-spectrum medicine that includes hormone health, preventive medicine, obstetrics, and pediatrics. Huberman frames Gillett's distinguishing feature not as any single topic but as an understanding of how nutrition, supplementation, exercise, and hormone therapies interact with one another, and of the safest and most rational ways to approach hormone optimization. The stated scope extends beyond testosterone and estrogen to prolactin and other hormone pathways that impact mood, mental health, and physical health, with the guest also described as an avid educator on zero-cost-to-consumer platforms.

A structural note is made explicit at the outset: the podcast is described as separate from Huberman's teaching and research roles at Stanford, and as part of an effort to bring zero-cost-to-consumer information about science and science-related tools to the general public. A sponsor segment for InsideTracker is included in the material, described as a personalized nutrition platform that analyzes data from blood and DNA, with a personalized dashboard that, where certain values might be too high or too low for a given preference, directs the user to lifestyle factors, nutrition, and supplementation. Huberman also states a long-standing belief in getting regular blood work done, on the grounds that many factors impacting immediate and long-term health can only be analyzed from a quality blood test.

Asked about his training and orientation, Gillett restates his dual board certification and describes a balanced approach to total health that includes body, mind and soul, likening his own trajectory of becoming obsessed with optimal human performance to an account of how a prominent YouTuber became skilled through teenage obsession. He attributes his orientation to the University of Kansas medical school, described as one of the few that still emphasizes full-spectrum care, exercise is medicine, and food is medicine, and to residency work in mindfulness curriculum and Walk with a Doc, where preventive medicine is emphasized. He states that this niche led him to hormone health, that it did not really start as hormone health, and that hormone health is a very important component of health in general that many people do not emphasize.

Huberman sets up a lifespan framing, asking what everybody should be thinking about or doing to optimize hormone health from puberty onward, with the intention of later migrating that snapshot into the 30s and 40s; within this batch the discussion remains in the from-puberty-onward phase. Gillett answers with the law of diminishing returns: doing a little amount of what he calls lifestyle interventions over a long period of time is described as far more helpful or efficacious than doing a lot and then doing nothing. He refers to the big six pillars, of which the two strongest are likely diet and exercise. For hormone health specifically, resistance training is described as particularly helpful, and for diet, caloric restriction is described as particularly helpful given the epidemic of metabolic syndrome that is continuing to ongo in this country and in developed countries in general.

- Diet and exercise are named as the two strongest of the big six pillars, with resistance training particularly helpful for hormone health. - Caloric restriction is described as particularly helpful in the context of the continuing epidemic of metabolic syndrome in this country and developed countries in general. - Stress and stress optimization are tied to cortisol, mental health, societal health, and the collective health of the family. - Sleep optimization is called extremely important, especially for mitochondrial health. - Sunlight encompasses anything outdoors, moving more, cold exposure, and heat exposure. - Spirit is the final pillar, corresponding to body, mind and soul.

The law of diminishing returns applies.

A social dimension is attached to the pillars. Gillett argues that when someone is a member of a family or even a very close friend, trying to achieve optimal health together is very important, and that the same applies to nicotine cessation and to hormone optimization: if done as a household unit, it is far more helpful. Regarding the sixth pillar, he states that if all the other five are dialed in completely but spiritual health is absent, whatever one believes, that is going to profoundly impact the body and the mind as well. Huberman signals that spiritual health will be revisited, noting that for some people it might draw connotations of certain things that may or may not be accurate, and citing academic laboratories, functional medicine clinics, and research clinics and hospitals that he says are achieving some really interesting data not just in people who are quite sick but in healthy people trying to further optimize health.

Huberman raises the combat around vegan, plant-based, and carnivore diets, offers a general view that most people should probably be eating as few highly processed, highly palatable foods as possible, while noting this does not mean eating foods that do not taste good, and poses a tension: he understands that a caloric surplus can support certain hormones like testosterone, so he asks how one combines caloric restriction and still optimizes hormones. Gillett responds that diet should be an individualized approach, using an analogy in which different cars, such as a race car or a diesel truck, require different fuels for different performance outcomes. He states it is pretty well studied that the more intra-workout carbs ultra-long-distance athletes take, in general they do better, and that he thinks this has been studied in cyclists quite often. He adds that it also depends on genetics, since a person can have a genetic polymorphism and metabolize carbs and sugar better, even when they are unopposed by fiber.

Pressed on how one determines whether such a polymorphism is present, Huberman describes himself as an omnivore who eats some high-quality meats, vegetables, and starches, and reports that a very-low-carb diet once gave him a lot of psoriasis and poor sleep, so he backed off, adding that he probably did not do it correctly. Gillett says lower-carb diets may particularly suit those at risk of cancer, because you have less glucose that can be easily uptaken into cells, and people with autoimmune diseases. On how to know, he offers biofeedback, using how one is feeling to guess what one tolerates well, or genetic testing, which can be fairly expensive but, most of all, requires a physician or someone who knows how to interpret the test accurately. On testing cadence, asked whether regular means every three months or every six months against a changing backdrop of stress levels, he says every three to six months for preventative purposes, that at times blood tests are needed at faster frequencies than that, and that one should also get a blood test when fasting and when not fasting.

If you're looking for damage to the beach, you don't just look at low tide.

On the clinical intake, Huberman asks what probe questions Gillett uses when a patient arrives, so that listeners might ask the same of themselves. Gillett distinguishes the history of present illness, if a complaint exists, from cases where the patient maybe does not have a complaint; in that case social history and family history are described as extremely important because they give insight into genetics and into hormone health. He reports asking how a patient is now versus when they were 20, and what has changed, using a hypothetical 50-year-old. On the frequently asked question of how to get a doctor to order a better lab workup or include basic hormones, he says there is no magic answer, but that it helps to report that energy, focus, and athletic performance are not as good as they used to be, and that a pertinent symptom, rather than a pathology, is what makes a lab indicated.

You don't have to have a pathology in order for a lab to be indicated. You just need to have that pertinent symptom.

A gender asymmetry is drawn out. Huberman asks whether the described approach is equally effective for men and women. Gillett replies that it is slightly different: with women there is a lot more objective data, since menstrual irregularities, not having a period, or having too heavy periods are things patients talk about very frequently with their doctor, whereas men are more hesitant. Men really want to know what their testosterone is, but at the same time really do not want to tell their doctor how their libido or energy is, because it is almost like they feel less masculine or less like a guy when they say that, even to their doctor. Huberman calls the whole discussion a bit of a barbed-wire topic, tied to notions of masculinity and femininity, notes that testosterone and estrogen are present in all sexes and all chromosomal backgrounds and just to varying degrees and ratios, and observes that in the general population some of these topics are a little bit taboo, so people seek the information on YouTube and through communities that may or may not be very educated about the actual biology.

On exercise, Huberman states that based on the data he has seen, almost everybody, or everybody, should be getting 150-180 minutes minimum of zone 2 cardio per week, defined as effort one could continue while having a conversation but above which it would be hard to get the words out, for cardiovascular, general brain, and musculoskeletal health, plus resistance exercise. He asks whether that is more or less the contour of what Gillett recommends. Gillett agrees that it is more or less the contour, adding that the more zone 2 cardiovascular exercise one does, the slightly less important a long-duration of caloric restriction is.

The caloric-restriction discussion is introduced with an explicit disclaimer. Huberman names the classic C-I-C-O, calories in, calories out, and says it is not being disputed, observing that somehow that always has to be stated 50 times in any forum, and that he and Gillett agree on calories in, calories out as a fundamental law of thermodynamics. He says it is clear to him, based on what he has read, that when one is in a slight caloric surplus, hormones like testosterone can be optimized, then asks whether that is true for somebody showing up with excessive body fat, noting that body fat is manufacturing enzymes that convert testosterone to estrogen, and asks how someone knows whether to use or avoid caloric restriction.

We are not disputing calories, in calories out.

Gillett says that as a board-certified obesity medicine physician, obviously the laws of thermodynamics apply, and that there is nothing special about intermittent fasting, caloric restriction, or exercise when it pertains to losing body weight in general. He states that when weight is lost, about 33 percent of that is lean body mass, and about 10 percent of fat cells, adipose cells, are actually lean body mass as well, because it has proteins and water and things like that in it too. The reason for exercise and caloric restriction in general, including intermittent fasting, is given as health reasons, as how one increases health span; it is not necessarily going to make the weight on the scale change, but that does not matter as much. He says it has been fairly well studied in both mice and humans, that it is much easier to study in mice, and that if you calorically restrict mice by 40 percent, they can have improved testosterone parameters, but only if they are obese to start, and it appears to be that same way in humans as well.

The apparent contradiction is resolved by stratifying the population. Gillett says the easy way to think about it is that if you are obese or you have metabolic syndrome, caloric restriction will improve your testosterone. He refers to a systematic review from the Mayo Clinic Proceedings, in March of last year, and says they note there is a study in young healthy men in whom caloric restriction caused testosterone to decrease. He concludes that if you are young and healthy and you do not have metabolic syndrome, then caloric restriction will likely decrease your testosterone. The evidence is presented with graded certainty: fairly well studied in mice and humans, much easier to study in mice, it appears to be that same way in humans, and a single study of young healthy men set against a systematic review.

If you're young and healthy and you don't have metabolic syndrome, then caloric restriction will likely decrease your testosterone.

Huberman welcomes the distinction that intermittent fasting is not the only way to achieve caloric restriction. He notes that some healthy or older healthy people use it even when not trying to lose weight, some because they believe it might extend lifespan, which he calls still a bit of an open question and a bit of a hard experiment to do because no one wants to be in the control group; Gillett adds that it does in mice, and Huberman quips about a captive audience. Huberman also points to mental effects, the clarity of mind during fasting and the increased pleasure in eating when one finally does eat, and delimits the practice under discussion to eating windows anywhere from 8 to 12 hours a day, not extended fasts of 24 hours or more. He asks whether, for a healthy, lean-enough, nonobese person getting sufficient calories to maintain weight, oscillating between feast and famine within 24 hours is a problem for hormone health.

I think that's still a bit of an open question.

Gillett answers that if they are in a caloric maintenance, then it is not going to be deleterious and not going to be bad for their hormone health. He says testosterone and DHEA usually go hand in hand, and distinguishes growth hormone as a peptide hormone rather than a steroid hormone, a chain of proteins, amino acids put together instead of a sterol, with sterol hormones described as coming from cholesterol. He states that with intermittent fasting you do get a little spike in growth hormone after you eat, but also a huge, more significant, less negligible spike overnight, and that this is improved if you are intermittent fasting, so it is probably going to help growth hormone and subsequently IGF-1 levels, which will help more in the older age groups than younger age groups. Asked whether avoiding food in the two to three hours before sleep is enough, or whether one has to be very deep into a fast, after describing his own dinner habits and a rare late single meal at 10 o'clock, Huberman is told there is still pretty good growth-hormone output even if you eat two or three hours before you sleep, subject to the law of diminishing returns.

It's just the law of diminishing returns: the longer you go, you get slightly more and slightly more.

Huberman raises a safety concern, that exogenous growth hormone can in some cases be associated with cancers, and asks whether increases from saunas or intermittent fasting could reach levels so high that they cause cancers, stating his impulse is to say no, that it seems like it is not likely to happen, but that he should probably verify that statement. Gillett calls it quite unlikely. He distinguishes endocrine IGF-1, mostly IGF-1 synthesized in the liver and released in the liver, from IGF-1 released classically, giving the example that IGF-1 levels increase after resistance training or exercise in a more paracrine or autocrine fashion with more local action. He notes there is actually an IGF-1 and IGF-2, and that at physiologic levels giving people IGF-1 is not going to improve their body composition, whereas autocrine and paracrine IGF-1 working in local tissues and muscles is likely part of the reason for the improved body-composition response after exercise.

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 an improved body-composition response after exercise.

Asked whether IGF-1 and IGF-2 are simply the active form of growth hormone, the pick ax end of the assembly line, Gillett describes a much longer duration of action. He says he believes the half-life of IGF-1 is several days, almost a week, whereas growth hormone has an extremely fast half-life of only hours, and that growth hormone acts significantly on the liver to produce IGF-1, so it is around in the serum and the blood long enough to be producing an effect pretty much all the time. The hedge I believe is retained for the specific half-life figure.

Huberman asks whether any aspects of hormone optimization can improve sleep, given that sleep can improve hormone optimization, and specifically about the common syndrome of going to sleep and waking at three or four in the morning, which he says can be associated with depression. Gillett says there are three big ones. The first, not super common but a very direct correlation, is a true growth-hormone deficiency, whether adult or child, in which sleep is likely going to be affected; in a child with growth-hormone deficiency, once that is replaced with therapy, sleep is going to get significantly better. The second, a very common scenario, is vasomotor symptoms of menopause or of andropause, which he says are also applicable, tied to progestogenic activity, with the main progestogens named as progesterone, then pregnenolone, then 5-alpha, 3-alpha progesterone.

On where progestogens are manufactured, Gillett says in men, some, in the testes, in the Leydig cells; in women, in the ovaries until menopause, and then also in the adrenal glands. He says that if you are preadrenopausal, where the adrenal glands are still working fairly well, you usually still have a decent amount of progesterone around, and that this can be measured too, and that after menopause women make progesterone from their adrenal glands. He states that if that progesterone crosses the blood-brain barrier, especially if it is 4-alpha and 3-alpha reduced, so modified a little bit, then it is both a GABA agonist, which helps sleep just like GABA does. GABA is identified as gamma-aminobutyric acid, the main inhibitory neurotransmitter, and alcohol, gabapentin, many migraine medicines, benzodiazepines such as Xanax, and nonbenzos such as Ambien are all said to work on GABA. He offers this as why a lot of women in menopause feel like their sleep is much worse, because they have lower activity of those progestogens.

Asked whether low testosterone in so-called andropause is also a cause of poor sleep, Gillett says low testosterone can lead to poor sleep, but identifies his third scenario as a man who begins TRT and then develops poor sleep because of sleep apnea. He says TRT drastically raises the risk that somebody is going to have sleep apnea, and that a lot of people, especially when they first start it, in their first month or two, are put into a hypersympathetic state because they have overactive androgen receptors, especially after a long time of being hypogonadal, so that a physiologic dose of TRT causes the sleep issue itself.