Essentials: Tools for Hormone Optimization in Males | Dr. Kyle Gillett

0:00Andrew 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 with Dr. Kyle Gillett. Dr. Gillett, great to have you back. Great to be back. Thank you. I'd like to begin with a question about what all males ought to do in order to optimize their hormones. What should they be doing? What should they avoid doing if the goal is to have a long arc of healthy hormone optimization throughout the lifespan?

0:38There's many things that you should do. An analogy that I often make is when there's a brand new car that comes off the assembly line, you do a full scope of diagnostic workup, hook it up to the computer. And I think we should do the the same thing with humans as well. During puberty, obviously you're a functioning human, but I would say there's still development. And I think that the human always develops. I don't think development ever ends, but you want to monitor that progress across a person's lifespan.

1:08Andrew Huberman:What do you think are the key things to look for in blood work? I mean, testosterone is always the topic that comes up in the context of male hormone optimization, but certainly there are a lot of other hormones that are important as well. And with testosterone, you want to get either testosterone and SHBG or a free testosterone. Could you define SHBG for our listeners, please? It is sex hormone binding globulin. It is the protein that binds up all androgens and estrogen in the body. So the stronger the androgen, the stronger it binds. During puberty, strong androgens, especially DHT, which is the strongest bioidentical androgen, has a huge role, a prominent role in secondary sexual characteristics.

1:49And if your SHBG is very high, then your DHT can run higher because it's not metabolized, but there's not quite as much free DHT. So you want to balance between a high enough free DHT and a high enough total DHT.

2:04Andrew Huberman:So assuming that there's no major intervention, how often do you recommend that people get their blood work done? Using shared decision-making with their physician, usually a good follow-up is about six months. So on a daily basis, maybe you could just take us through the arc of a day and push out some of the protocols that you use or the things that you'd like to see your male patients use in order to try and optimize their hormone status. I'll briefly touch on some of the lifestyle pillars to start. Diet and exercise are the first two. In puberty, sleep is particularly important, of course. But with diet and exercise, throughout a lifespan, you want to not exclude things that are helping you.

2:48For example, during puberty, if you're consuming dairy and then all of a sudden you cut out all dairy, dairy can help increase IGF-1 and free IGF-1.

2:56Andrew Huberman:And just again for our audience, maybe you just mentioned what having enough IGF-1 can do for us that's beneficial is? It helps you grow. It helps with genital development, secondary sexual characteristics, and long bone growth, skin growth, hair growth, a host of things. So getting an array of nutrients that include dairy, what other sorts of nutrients are important during development? You want to have adequate vitamin D. Vitamin D helps with testosterone production. It helps, again with bone mineralization and stature after an age of about 25 and there's not a strict cutoff but up to about an age of 25 optimizing your growth hormone and igf-1 helps with bone density and bone growth so from the dietary standpoint you want to have enough free estrogen not too much when you're growing but you want to help basically stockpile bone to prevent a risk of osteoporosis or thin bones fractures when you're older.

3:57Andrew Huberman:I realize that some of this relates to ethics and food allergies and things of that sort. But would you say that on balance that most people would benefit from eating a combination of, you know, quality proteins from animal sources and non-animal sources, fruits, vegetables, and starches? I mean, what do you think, for instance, about people following a pure carnivore or a very pure vegan diet in their 20s and 30s? In their late 20s, it might be a reasonable option. In early 20s and certainly teens, it is a horrible idea because it is likely to significantly decrease your free androgens, so you will have less testosterone acting on receptors through the body.

4:37Andrew Huberman:Are there any other micronutrients or macronutrients that people in their 20s and 30s should emphasize? Fiber is going to be paramount in kind of like setting your set point of your gut microbiome the rest of your life. there is prebiotic fiber, which you could think of as fish food for your good gut microbiome. Your gut microbiome is kind of like an aquarium or a fish tank. Any fiber or food that you're putting in your gut, it's either going to, it's going to skew your gut microbiome towards something that is more beneficial or more detrimental. And would you say that the prebiotic fiber and getting essential fatty acids, that would be important to do throughout the lifespan or just for people in their 20s and 30s?

5:18Throughout the lifespan, particularly important in the teenage 20s, 30s, because it helps with brain development. You're certainly more of an expert than me when it comes to brain development, but it does continue to develop really throughout the lifespan, but certainly through the 20s and 30s as well.

5:36Andrew Huberman:In a previous discussion of ours, I asked you about caloric restriction and testosterone. And if I recall correctly, the idea was that if somebody is overweight, they have excess fat adipose tissue, then getting rid of some of that adipose tissue through caloric restriction and exercise, provided it's done not too fast in a healthy way, is going to be beneficial for testosterone in the long run. But that for individuals who are not carrying an excess of body fat, caloric restriction is actually going to lower testosterone. First of all, do I have that correct? And second, are there any addendums to that that you'd like to give us now?

6:13That's correct. If you look at an individual in a caloric deficit, several changes will happen. One is that they'll have less building blocks for hormones. Another is that they will be in a catabolic state more often, so that balance of anabolism and catabolism will be different. They'll likely have less signaling from growth hormone and IGF-1. And they'll also have the high SHBG that we defined earlier as the binding protein, so their free androgens and free estrogens will go down.

6:44Andrew Huberman:Now, what are some of the other pillars of creating the proper environment for hormone optimization? Stress is probably the next one. During both puberty, but also the 20s and 30s, individuals are figuring out how they want to cope with stress and also figuring out what they want to choose to put their effort into. So if someone is overstressed, then it can put all the other lifestyle pillars and then they stop dieting well, they stop exercising, and everything else can go askew. What would be some of the additional things that everybody should do? Another one is finding what your purpose is in life.

7:25So I call this spirit, but it's really just the self-actualization component of Maslow's hierarchy of needs, which is basically your physical needs, your mental needs, and then your purpose in life, what you really like to do.

7:36Andrew Huberman:The idea is not to pick the end goal, it's to pick a goal. And then once you reach that goal to assess and then pick another goal and so on. I think sometimes when people hear about picking a purpose, they're like, oh, goodness, I have to define, sort of like naming oneself, that you actually can change your goals and purpose over time. I'd like to take a quick break and acknowledge one of our sponsors, Element. Element is an electrolyte drink that has everything you need and nothing you don't. That means the electrolytes, sodium, magnesium, and potassium in the correct amounts, but no sugar. Proper hydration is critical for optimal brain and body function.

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9:23Andrew Huberman:Again, that's drinkelement.com slash Huberman to claim a free sample pack. I'd like to return to the key things that people should do, or I should say the key things that men should do to optimize their hormones. What do you think is a healthy, sustainable exercise regimen that anyone can follow that will also support their hormone status? for really vigorous exercise around three to four times a week is very sustainable over a long period of time on top of that you could add in three or four more instances of less vigorous exercise when they study the effect of exercise specifically vigorous exercise one area that's been studied is vigorous exercise episodes lasting longer than an hour and they usually track it by a rating of perceived exertion, which isn't perfect.

10:14And it's not extremely actionable, but it's helpful for clinical science. But the takeaway from that is basically do not, it is not hormonally helpful to train, especially regularly train vigorously for longer than an hour. These days, for better or for worse, I think for worse, younger guys are asking about and using

10:39Andrew Huberman:testosterone replacement therapy, so-called TRT. Why in the world would any male in his teens or twenties or even thirties whose blood levels of testosterone and estrogen are at the appropriate levels, meaning within the normal reference range, why would they take exogenous testosterone given all the negative effects on fertility, some of the challenges that it can present if the dosages aren't quite right, et cetera. Why would they do that? Certainly if they are not being paid for a particular endeavor, like they're not making money. If they are playing a sport, chances are they're not allowed to do that anyway.

11:18Andrew Huberman:It's on the banned substances list. So to me, it just seems like a crazy idea. But then again, I'm of a generation that really hasn't thought about doing that stuff until people were in their forties and fifties, or even never. So is there ever a case for somebody in their 20s or 30s to take testosterone if their blood levels are within the 300 to 900 nanograms per deciliter reference range? You know, everyone has their different reason as far as like, when does the benefit outweigh the detriment? Not very often if you're in your 20s and certainly probably almost hardly never. There's always, you know, rare cases like Kuhlman syndrome and whatnot, but almost never if you're very young.

12:04Andrew Huberman:Okay, so for people in their 20s, 30s and beyond, 40s, et cetera, whose testosterone and estrogen levels are at the appropriate ratios and within the normal reference range, libido, energy, recovery, et cetera, are feeling at least workable for their lifestyle. For those people, what can they do besides get great sleep, train but not too hard or too often etc etc what are some of the things in the realm of supplementation that can help them optimize their testosterone and estrogen without suppressing their own endogenous production of testosterone and estrogen let's mention creatine is the first one creatine is interesting because it has multiple different effects that helps with amino acid synthesis it also helps with oxidative stress it can also serve as the backup fuel tank for your mitochondria, so kind of holding back up ATP.

12:58And it does slightly increase total testosterone, and it also increases the conversion of testosterone to dihydrotestosterone. So potentially it's especially useful in men in their, even their teenage years and their 20s.

13:13Andrew Huberman:You mentioned the conversion of testosterone to dihydrotestosterone, and there is mythology out there that creatine can increase hair loss. I'm guessing because there's at least one study showing that creatine can increase DHT. Dihydrotestosterone and DHT is one of the primary hormones that can promote male pattern baldness. So the question therefore is, does creatine supplementation increase the rate of hair loss? In each individual, preventing hair loss is a very poor reason to take creatine because it's not going to take you to a supra physiologic level. It's not going to, you know, increase your androgens to an unnormal level of binding.

13:58So I feel like this, if that was a reason to not take creatine for hair loss, then that's

14:04Andrew Huberman:sorry. You mean hair loss is not a reason to avoid taking creatine? Correct. Hair loss is not a reason to avoid taking creatine. Think of it as just bringing you to what you are naturally inclined to have. If your conversion of testosterone to DHT is already high, then often creatine does not affect this. It just kind of resets your balance between testosterone being aromatized to estrogen or being 5-alpha reduced to DHT. So it's not going to speed up hair loss more than just naturally BML does. So in some individuals, it will have no effect. In some individuals, for whatever reason, they have almost no 5-alpha reductase activity.

14:47It will return them to natural or normal.

14:49Andrew Huberman:So what other supplement-based tools can people consider? Another one we can loop in with creatine is beta-ene. Some people are non-responders to creatine. So you can increase that to 10 grams, or you can use its cousin beta-ene to help with with amino acid synthesis and shunting of energy. Along with that, I would put L-carnitine. Beta-ene, do you recall what dosage people typically would take if they're a creatine non-responder? One to three grams. In fact, several versions of creatine have beta-ene mixed in because it helps with the processing of methionine and homocysteine. So if somebody is already taking creatine and likes it and responds to it, I'll raise my hand, such as myself, would adding betaine help or is it redundant with creatine?

15:37Only if their homocysteine is persistently elevated. And homocysteine is kind of like an inflammatory marker that can build up if you're not converting enough of it downstream. How would I know? Just a blood test.

15:49Andrew Huberman:So L-carnitine, what are the ways to take L-carnitine? I know that there's an oral form, so capsules, and there's injectables. The injectables, I think you need a prescription, is that right? Correct. You need a prescription for the injectables or you should really get a prescription for the injectables. When you inject it, of course, at the supervision of your doctor, it's usually done intramuscularly. It's an aqueous solution, so it does not have like an oil or a carrier oil in it like testosterone esters do. However, if you inject it too superficially, it's not going to make or break anything.

16:23Often it just burns if you inject it subcutaneously, and it does not disseminate throughout the body as well. L-carnitine potentially has localized effects if you inject it. If you ingest it orally, then it has a very low bioavailability, maybe only 10%.

16:41Andrew Huberman:So what are the dosages of L-carnitine that one needs to ingest then if they want to get a benefit because if only 10 % is being absorbed, it's probably a lot of L-carnitine. How much should people take per day? Usually I recommend for oral L-carnitine between 1 ,000 milligrams and up to 4 ,000 or 5 ,000 milligrams. So one to four, maybe even five grams. Correct, up to five grams a day. If you're on that much, especially if you have a dysregulated gut microbiome, you should be concerned with TMAO, which is a potential carcinogen that both carnitine and choline can convert into. And your gut microbiota determine how much that happens.

17:22Andrew Huberman:Is it true that I can offset any negative effects of alpha-GPC choline, that is, NL carnitine that I take by ingesting garlic. Is that right? There's a compound in garlic called allicin. I believe it's A-L-L-I-C-I-N. It's also part of the scientific name, the genus of types of garlic. And this can help decrease the conversion to TMAO. Berberine actually slightly decreases the conversion to TMAO as well, probably through alteration of the gut microbiome. And then just optimizing your gut microbiome can decrease conversion. So not everyone needs allicin, but it's something that you should certainly consider if you were on a high dose.

18:01Andrew Huberman:I'm going to continue to take the 600 milligrams of garlic every time I take my L-carnitine, but I'm going to skip the berberine because berberine gives me brutal headaches and it makes me crave carbohydrates because it drops my blood sugar. It has many other effects, including the dawn phenomenon where it drops your blood sugar when you're sleeping and you can't even realize it. Okay. And what we did not talk about is what L-carnitine does. It's a shuttle. So I think it's named carnitine, palmitil, coenzyme A. Basically, it just takes nutrients from outside your mitochondria and puts them in.

18:33It also has a unique effect. Well, not too unique because tadalafil actually has this effect as well, is that it increases the density of the androgen receptor in the cytoplasm of your cells. So even if your androgen receptor sensitivity doesn't change, and even if your testosterone does not change, you will have more testosterone binding to that increased number of receptors.

18:55Andrew Huberman:Does one need to cycle L-carnitine, creatine, beta-ene? No reason to cycle any of those. What other supplements can one use to try and improve hormone profiles? And here I realize we're using a very broad brush because when we say improve hormone profiles, what are we really talking about? And for me, at least, I think about the subjective stuff. Do people feel like they are going to have more energy as a consequence of doing these things? Are they going to have the more optimized libido? Are they going to have more optimized recovery from exercise? Because it's not clear to me that taking one's testosterone from 600 to 800 is always going to be a good thing, especially if estrogen is increasing in parallel.

19:36Andrew Huberman:That could cause issues. It could certainly make things better. It could certainly make things worse. Let's briefly mention vitamin D, which is also a hormone. It's actually a sterol hormone. And if you have deficient vitamin D and you replace it, then you will optimize your testosterone. Let's also mention boron. So if you have a very high SHBG, boron can acutely help lower it, usually in a dose of 5 to 12 milligrams per day. It's not really a sustained effect, but boron is depleted in soils. In many countries, I believe it's very high in soils in Greece and Turkey. So eating dates or raisins that are from those areas potentially have more boron.

20:14Boron also might be one of the reasons why the reference range for testosterone is much higher in those countries than other countries.

20:24Andrew Huberman:And just to remind people, the SHBG, sex hormone binding globulin, is attaching to the testosterone molecule and limiting the amount of so-called free testosterone that's available to have its impact on cells. Okay, so vitamin D3, I'm guessing you're talking about vitamin D3 specifically when you say vitamin D, and then boron 5 to 12 milligrams per day, right? And then what are some of the other things to optimize testosterone that are in supplement form. We can talk about things that affect the steroidogenesis cascade. So we could touch on Tonkat Ali. I know we've talked about that a little bit before.

20:54Andrew Huberman:Yeah, but I'm guessing a number of people probably haven't heard that conversation. Also known as Long Jack. And that upregulates several different enzymes in the steroidogenesis cascade. And by that, what you mean if, and this is another good thing to Google. I think anybody interested in hormone optimization should understand where sterol hormones come from. They come usually from cholesterol and they can be shunted off to vitamin D very easily. They can be shunted off to testosterone or estrogens or progestogens quite easily as well. But Tonkat helps with the conversion of multiple key steps where you synthesize testosterone.