When It Shrinks, Your Immunity Goes With It - Boundless Life Podcast

That's the big concern is that the combined estrogen-progesterone birth control is simulating really pregnancy. The concern is what if this is shrinking the thymus earlier for these ladies and that's maybe contributing to this autoimmune disease risk in ladies? And on top of that, is that contributing to the risk of PCOS and all these other conditions? No one has a good answer, but I'm kind of sounding the alarm bell. I'm like, people should be looking at this because we're putting millions of young girls on these treatments without really telling them that there are some risks.

My guest on today's show is Dr. Abhoud Bakri. He's a board-certified internal medicine doctor, a graduate of the University of Colorado School of Medicine. And, he's an active practicing physician, but he also has a deep knowledge of circadian timing, sleep, peptides, hormones, metabolism. I recently had a chance to get to know him a little better and decided I really wanted to interview him about one of his areas of expertise, the thymus. So, brace yourself, we're going to talk about some stuff we haven't discussed before, some cool stacks, some cool peptides. BenGreenfieldLife.com/ThymusPodcast is where the shownotes reside. Let's go talk with Abud. Abud, dude, we just hung out in Washington, D.C., which is pretty cool.

Yeah. We should have done this in person.

Yeah. Well, actually, yeah, we probably could have. We didn't have better things to do.

Something on my mind.

I usually like my— Ears perk up when I hear somebody who's done podcasts before who kind of knows what they're talking about. But then, I could kind of tell you practice what you preach because you look like you're pre-fit, you maintain some muscles. So, have you kind of been into fitness parallel to getting into medicine or how did the two co-evolve?

I think fitness led me to medicine actually. I was a bodybuilder powerlifter before I was a doctor, competing powerlifting.

Really?

Yeah. I used to have the state deadlift record in In deadlift in Colorado when I was in med school.

Oh, interesting.

Yeah. Wow.

Crazy. So, you were bodybuilding and powerlifting starting when?

16, 17 years old.

Wow. What do you mean when you say that got you into medicine?

Yeah, the physiology, the anatomy of it all, studying the body, trying to optimize both the aesthetic proportions, the physical mass. And then, when I discovered that I had the myostatin mutation, that made me realize that, oh, there's a whole genetic component to this muscle game.

You have the myostatin mutation?

I'm heterozygous for the myostatin knockout.

Interesting.

Okay.

So, for people who don't know what that means, explain.

Yeah. So, myostatin is a protein secreted that limits the amount of muscle you make. So, if you've seen those really muscular cows, you probably have seen them around, They have a double knockout of that gene. So, men in my family on my father's side, there's about 50% of them have this gene where they're very muscular and built despite not really lifting weights. But, when I did start lifting weights, it was like, oh, wow, 3 months in, 500-pound deadlift wasn't a big deal. So, it's an interesting little thing, but it also comes with a higher injury risk when it comes to your ligaments and tendons. Yeah.

I was going to say there's got to be a downside somewhere because you hear about I don't know, there's guys who are big and inspirational like Tony Robbins, for example. I know he has some kind of a pituitary growth hormone gigantism thing going on. And, I interviewed him and he said he gets a lot of joint pain from that. So, it's not all just pure muscle without any side effects. So, for you, it's higher risk of injury?

Yeah, yeah. So, when I did jiu-jitsu, I tore my ACL pretty easily actually unfortunately. So, That was unfortunate. But, cardiometabolic markers, I could eat whatever almost and my A1c is going to be 4.9, my lipids are going to be pretty good. Wow.

Interesting.

Yeah, yeah.

That's super cool. For people listening, the hemoglobin A1c of 4.9 is good. It's kind of like a snapshot of a running multi-month level of your blood glucose values. So, that's super interesting. I did not know that about myostatin knockout. So, Do you still lift?

Yeah, yeah, I still lift. Less aggressively nowadays but more just for maintenance of health and aesthetic goals.

Yeah, yeah. When I met you at that dinner that we were at a couple weeks ago, I had come across your name before, I think on a podcast somewhere where you were kind of positioned as the peptide guy.

Yeah.

And, I kind of assumed that's That was your general area of expertise, but then you started filling me in on thymus and what it does and how important it is and why that's one of your key areas of interest. And, I was like, dude, we should do a podcast about the thymus because I've never really kind of unpacked that in detail before. So, I would love to open that up. So, first of all, is this indeed your area of specialty? Do you work with people who have thymus issues or where did that come into the picture?

Yeah. I'm an internal medicine doctor, so I see patients In the hospital, I admit patients to the floor and to the ICU from the ER. What I started noticing over the last 6, 7 years is that people's lymphocyte counts was lower, people had less immunity. A lot of my colleagues and myself, 21, 22, we started getting sick 7 times a winter, which was not normal by any means. So, I started investigating this. I had the interest in peptides, been in the peptide space for quite some time. And, a lot of the peptides are thymus-derived peptides. But, what is a thymus? We don't really learn about it. No one really hears about it. It's kind of this ignored organ. And, until recently, people kind of considered it a vestigial organ. I don't really buy the vestigial organ. For the audience, vestigial organ means an organ that we no longer need, the appendix and other parts of the body.

Okay.

But, it is an important organ that grows with you until you hit puberty and then starts to shrink. So, it's one of the first organs that actually tends to age. Before your other organs catch up.

So, when you say shrink, that's synonymous with aging?

Yep, yep. So, as soon as you hit puberty, the testosterone, estrogen, progesterone will start to involute or shrink the thymus down. And, it starts out as this giant tissue on top of your heart. And then, within a few years, you start having smaller and smaller and smaller amount. By the time you're 70, 80, you have a couple of specks left in the fat on the chest.

Interesting. So, why is that from a biological standpoint that puberty or hormones would cause a shrinkage of the thymus?

Yeah. No one has a good answer about why it exists evolutionarily, etiologically. There's some thoughts maybe. Number one, for another time period that the thymus shrinks is during pregnancy and that allows the mother's immune system not to attack the growing baby inside of her. So, Theoretically, you can have a poetic look at it and say that we have our actual longevity is through our offspring. And, in order to have offspring, we have to sacrifice some of our own immunity. The other explanations could be that it's such an energy-demanding tissue. It takes a lot of energy to produce those lymphocytes and to train the immune system. And, we can say that after puberty, these lymphocytes that are created in the thymus can last 15, 20 years and biology doesn't seem to optimize for a longer lifespan. Yeah.

Okay, got it. So, it's almost like a resource allocation type of thing where early in life you really need to have training wheels on your immune system and then eventually the thymus shrinks and you still get effects from it for 15 to 20 years afterwards.

Yeah, at least. And then, some people, they'll get into old age and still have larger thymuses. This Nature paper came out this year just. It was kind of a landmark paper and it showed that on CT scans, and you can do this on MRIs, People that had larger thymuses could have less mortality and morbidity across a number of different diseases. And, there's a correlation between chemotherapy and immunotherapy outcomes related to thymus size.

Okay. So, I know a lot of people right now including me would be thinking, well, wouldn't it be good then to figure out ways to avoid shrinkage of the thymus so you get some of the health and longevity benefits that you just described? But then, also my brain asks kind of like the myostatin thing, what could be the downside of that?

Right, right. And, I think that there's no free lunch in biology, let's say.

Yeah.

I think the goal is to preserve thymic size. There are some trials going on about growing thymuses. So far, there isn't a negative signal. I could imagine that there could be thymomas. Those are tumors of the thymus that are associated with certain autoimmune diseases. And then, is there a concern for a T-cell lymphoma because the T-cells are being trained in the thymus? Could there be— you muck around with biology and you get thymic damage. But, I think we have accelerated thymic involution that's happening in modern living because it's really a— let's call it a place where your whole biological systems aggregate together and you can kind of get a readout system of what's going on, your hormones, your lifestyles, circadian rhythms, nutrient status plays a big role. We can kind of unpack all that. But, all these different systems kind of funnel into the thymus.

Well, I know one thing that is rampant is the use of birth control, which I know has an effect on hormones and women are using that at an earlier age. Would that be one of the issues?

Yeah, that's the big concern is that the combined estrogen-progesterone birth control is simulating really pregnancy for these young ladies that are avoiding getting pregnant. But, the concern is what if this is shrinking the thymus earlier for these ladies and that's maybe contributing to this autoimmune disease risk in ladies. The autoimmune diseases are much more common in the females compared to males? And, on top of that, is that contributing to the risk of PCOS and all these other conditions? No one has a good answer, but I'm kind of sounding the alarm bell. People should be looking at this because we're putting millions of young girls on these treatments without really telling them that there are some risks.

Yeah. Has there ever been a study that looked at prevalence of autoimmunity in women specifically who have been on birth control versus those who have not?

I don't think so. I've looked for that. I haven't found that study, but I would love to see that.

Yeah. Yeah. What else besides birth control?

Yeah. So, the thymus shrinks in response to all hormones really. That's the estrogen, progesterone, TRT. So, eunuchs actually have very large thymuses. Those are guys that are castrated before puberty. This was done in pre-modern times for slavery and it was done for singing capacity because eunuchs have— they can keep their voices that they had in—

Hey.

From longer times, right?

The secret to American Idol finally revealed. There you go.

But, the interesting thing is there was a study came out that showed that eunuchs had about a 15-year mortality benefit. So, they lived about 15 years longer than the average man. Now, that's not a worthwhile trade for us. We're not going to snip, snip, snip.

Probably not worth it.

Not worth it, no. Not going to snip, snip for that purpose. But, the question is, is TRT affecting thymuses? Because a lot of men, they have low testosterone. We love testosterone when we treat patients to get them back into action. But, is that decreasing their immunity and having a longevity signal? So far, it doesn't seem to be a negative longevity effect to TRT, but those studies are short and we don't have the 20, 30-year follow-up to see what's actually going on.

Yeah. How would you know, by the way, when you say something like TRT could affect immunity via its effects on the thymus, how would you know? What kind of biomarkers are you looking at? Or, are you literally talking about just MRI to analyze involution?

Yeah. So, you want to look at the thymus from both a functional perspective and an anatomical perspective. So, when we have our patients, we'll pull up their Prenuvos usually and then try to find the thymus on the different MRI slices and see if we can find the size. We're working on trying to get a vibe-coded app to kind of just measure it for us. But, that's one thing. The other thing is looking at what does the thymus do. The thymus creates some hormones. Those are thymosin alpha-1, thymulin, those peptide hormones, but it also trains the lymphocytes. So, when somebody has a low lymphocyte count, there's multiple associations with morbidity and mortality that comes with that, especially when it comes to cancer risk. So, that's an important thing to look at. There's the lymphocyte-to-monocyte ratio. So, everybody's got a CBC before. When you get a differential, they kind of have lymphocytes, monocytes, neutrophils, all these different cell counts. You can almost type up any disease and put lymphocyte-to-monocyte ratio and you'll get a correlation between low lymphocyte-to-monocyte ratio and increased risk of mortality morbidity with that disease, whether that's type 2 diabetes, cancers, dementia even.

Okay. What I'll do in the shownotes for those of you listening in if you didn't track all of that, if you go to BenGreenfieldLife.com/ThymusPodcast, I'll put some of the biomarkers that Abhoud just dropped just in case you want to take a look at your own labs.

And then, the other one to mention too, I think— sorry to cut you off— is the CD4 to CD8 ratio. So, the CD4/CD8 cells are the T cells that are trained by the thymus to last you your whole lifetime. HIV, for example, lowers both of those cell counts. There's an immune health grade. This is like they did a large study of multiple thousands of people and they created 4 immune health grades based on your CD4 to CD8 ratio. So, you have your lymphocytes and amongst your lymphocytes, you have your T cells, your B cells, and your NK cells. So, amongst the T cells, those go down into CD4 and CD8.

Okay.

The CD4 to CD8, if you have a Greater than 800 CD4 and a ratio of CD4 to CD8 above 1, that's considered an immune health grade 1, which is associated with less morbidity and mortality as you age. And, as you get older, those shift down to IHG2, immune health grade 2, 3, and 4. And, the 4 is the worst one there. Hasn't really caught on to modern medicine or even the longevity of the alternative medicine space, but I think that's going to be an interesting biomarker to track, especially Okay.

So, the correlation would be a trending lower CD4 to CD8 ratio.

Yep, yep. And, you want that above 1 and then you want the CD4 count above 800 to be considered the top level there.

Okay. So, we have hormonal issues like birth control and TRT. You had mentioned, I forget if you said nutrient or micronutrient status.

Yep. So, the thymus makes a peptide hormone called thymulin, and that's not to be confused with thymulin, which is Everyone online will confuse those and we can unpack that.

Is it a U and an A? Thymulin and thymolin?

Yes. Thymulin is a 9-amino acid peptide secreted by the thymus. It's only made by the thymus. So, some of these other thymus peptides people might have heard of, thymosin alpha-1, thymosin beta-4, are made in the thymus but also can be made peripherally. But, thymulin is only made by the thymus and requires zinc to be active.

Okay.

Now, what they found in animal models is before blood levels of zinc even get low, if you deprive the animal of zinc, And then check their blood levels, their serum thymulin levels will drop off before the serum zinc levels by 3, 4, 6 months. So, the first marker actually of zinc deficiency would be thymulin levels, but we don't have a clinical assay publicly available to check thymulin levels. That's why zinc sufficiency is a very important part of the immunity. You hear people talk about zinc for immunity and when you have a cold, take zinc. And really, it's about not being deficient in zinc so you have this thymulin— Hormone peptide that trains lymphocytes. It makes NK cells work better. They did an animal study earlier this year where they did immunotherapy for cancers in animals. And, when they gave them thymulin on top of the immunotherapy, they had much better outcomes because it made the immune cells work better.

Okay.

And, there really is no good way to test for thymulin?

Nope, nope. No one's developed that. We're talking to some people to see if that can be developed.

Yeah.

But, it is a very interesting thing because that's an actual functional metric of how much levels you have. And, that thymulin levels also track very closely with your high 15-year-old and then goes down 20, 30, 40, 50, and it goes up again.

Okay, okay, got it. Any other nutrients you can think of beyond zinc?

Yeah, zinc's going to be the critical one. The other nutrients is going to be more indirect. There's a whole arginine link to thymus metabolism, nitric oxide synthase, and the immune cells themselves because they require a lot of arginine. There's some talk about does creatine help out with thymus and immunity in general? That seems to be a trending topic. But, zinc is going to be the key one. The other nutrients that are going to be important are any thyroid nutrients because of its indirect effects on the thymus. Now, there's a paper that showed that there is a positive correlation between T3 and T4 levels and thymulin levels in that because the thymus is such an energetically demanding tissue, if you have sufficient thyroid activity, Okay.

From a semantic standpoint, is there really a link between the reason that they're named thyroid and thymus, that the names are similar?

They come from a similar embryonic development. They come from this embryonic cleft together. So, the thymus is named after the thyme tree because the plant actually, the plant is kind of shaped like a thymus, so they named it that way. The thyroid is not named for that. But, They do have an embryonic similar development but otherwise no kind of link there.

Okay, got it. Now, a couple of times the idea of peptides have come up and people when they hear words like thymus, they might think of thymulin, which is a peptide that you can get. And, I'd love to hear you explain what these are. Thymosin alpha-1 is another one. Those are the two that I can think of.

Thymosin beta-4.

Yeah, thymosin beta-4. Yep.

Yeah.

So, when it comes to peptides, what role do they play potentially in thymus support?

Yeah. So, when it comes to peptides, we'd look at— let's do the thymus peptides and then go zoom out and look at other peptides that might influence the thymus indirectly. The thymus peptides are interesting. Thymulin is too short of a half-life. You'd have to inject a lot of it. Now, this animal model did show that there was positive effects. There's no human models to show that thymulin Injectable would be useful. There are some oral formulations that seem to maybe multiply lymphocytes in the gut tissue because about 70% of your lymphocytes hang out in your gut after they leave the thymus. So, that may be an interesting path to take. Now, thymosin alpha-1 is a 21-amino acid peptide that is immune stimulatory. It stimulates these lymphocytes to kill infections more appropriately. It can be used as a support tool for hepatitis B and hepatitis C. It's not approved as an FDA drug in the U.S. And, has orphan drug status in the U.S., which is another topic. But, in other countries, it's actually used as a treatment for hepatitis B and hepatitis C, also as an adjuvant treatment to certain other infections.

Okay.

But right now, that is a peptide that people would only really get through research-use-only websites?

Yeah. So, some of those compound pharmacies still make it although they're not supposed to be making it.

Okay.

They still will get it. A lot of doctors still prescribe it in these longevity clinics. But, RDO companies is where they're getting thymosin alpha-1.

Okay.

Thymosin beta-4 and then its fragment TB500, which is the 500-daltin fragment of thymosin beta-4, was just voted to be moved, thanks to some of our friends that were in D.C., from Category 2, do not compound list, to Category 1, okay to compound. But, that move hasn't officially happened at the FDA just yet.

Yeah, it hasn't manifested yet. You still can't go to a telemedicine website and get TB500 or the precursor is what, thymosin beta-4?

Yeah, thymosin beta-4 is a big peptide and TB500 is the small one.

Okay.

Alright.

So, we've got those 2. Any others?

Yeah. There's the Russian polypeptide mix that's called Thymulin. So, Thymulin is a— they took young cows like these calves and they took their thymuses when they were still at the peak and they ground up the thymuses and then extracted 30, 40 different peptides from the thymus and then made that into an injection. That's an FDA or whatever the Russian FDA is approved drug in Russia that's used to treat diseases. And, it actually was studied during the pandemic as a treatment for hospitalized patients during the COVID outbreak and had positive effects. That one's an interesting one because it has maybe 30, 40 different peptides that seem to stimulate the immune system, increase lymphocytes, And also, make you more resilient to infections.

And, that one's also— that would be Ruo in the U.S., research use only.

Not even Ruo. So, Ruo sites will list thymulin, but they're actually selling you thymulin because they don't know what they're talking about. Thymulin is a polypeptide mix that has to come from a— there's one in Belarus, one in Ukraine, and one in Russia that actually make this as a pharmaceutical. You have to get cows, you have to take their thymuses out and do this whole extraction process. So, Ruo sites don't have the actual goods. It has to come in a box from Russia in Russian language that has it. So, you'll find vendors online that try to sell it. There's a bunch of oral thymus extracts, kind of similar thing that exist. But, the thymulin actually studied human trial. People complain about peptides, there's no human studies. Thymulin has 40 years of human studies. In fact, probably the longest longevity study ever done was on epitalon, a pineal peptide, and thymulin. Epithalamine technically, not epitalon. Epithalamine is the big pineal gland extract and thymelin is the peptide extract from the thymus. Together, they had a 15-year study for nursing home patients where they had a 2x less mortality risk amongst different diseases with that combination.

Wow. And, was that a Russian study?

Russian study, yeah, Russian nursing home patients.

Interesting. Yeah, it seems like a lot of these longer-term human studies are coming out of Russia.

Yes, yes, if we believe their data, but they seem pretty reliable.

Yeah. Yeah. Okay. So, I mean, this talk about grinding up the gland for producing something like thymolin kind of makes me think of this idea of like supports like, right? So, whatever, Rocky Mountain oysters or bull testicles to increase testosterone or maybe having some liver for liver support. I've even heard, and you might know more about this than I do, about amino acid tracer studies that have actually Proven this might have some legitimacy to it. But, specific to the thymus gland, and feel free to comment on just the whole idea of likes it looks like anyways, would it make sense to eat what's commonly called in the culinary industry sweetbreads but that's basically just thymus glands?

Yeah, yeah. So, the likes it looks like is called organotherapy. It's how do you take organs and use them for therapeutic effects. We use organotherapy for thyroid. People that have thyroid disease, they take desiccated thyroid and there's pharmaceutical preparations of that like Armour Thyroid And, P-thyroid for that. Now, if you asked me 5 years ago, I'd be like, ah, that's kind of crazy. There's no way that eating liver is going to help your liver. But, Vladimir Kavintzin, the doctor in Russia that discovered thymelin and maybe 20 other peptide extracts, he showed that within these extracts, there are specific organ-specific peptides in each of these extracts that seem to have positive effects on each organ system. So, he actually has liver peptides that come out of liver. That seem to actually make the effect. So, it's not necessarily that you take liver and then there's a magical woo-woo that fixes your liver. There's actually peptides within the liver that are 2, 3, 4 amino acids that could be orally bioavailable that would then support liver health or restore whatever it may be. For example, Thymulin, the polypeptide mix, has thylone, thymogen, and chrysogen. Those are 2, 3 amino acid peptides. seems on their own have some clinical effects. They've been sold as supplements in Russia for quite some time. But, for example, Vilon seems to activate IL-2 and kind of prune senescent lymphocytes and then increase healthy lymphocytes.

Yeah.

So, it's an interesting theory of like, hey, like supports like. For example, you mentioned the oysters. There are peptides in oysters to increase the ability to absorb zinc. So, that's why taking oysters and Eating them would be a far better way to get your zinc levels up and increase testosterone. And, we'll dive into why thymus and testosterone are linked from the testicle side. But, the oyster peptides would be better than taking a zinc supplement. Although, if you don't like oysters, then you can still get the supplement.

Yeah, yeah. As my sons say, nature is pretty neat.

Yes.

The idea of these small peptides that go to specific organs kind of Brings to mind for me the idea of peptide bioregulators.

That's it.

Yep. I see these around and they're typically oral capsules that you take that support specific organ groups. Is that kind of a similar idea of what we're talking about?

Yeah. So, Vladimir Khavinson is the originator of the bioregulator peptides. The first ones he made were the thymus and the pineal gland polyextracts. So, in Europe, people for 100 years or so, they were injecting organs into different people. They would take testicles and inject it into people and they would get a virility boost and they'd do all these different things. He kind of took the next step because he kind of studied what are the actual effects of these organ tissues and what's causing this effect. Is it the peptide extracts? And, when he, for example, took the pineal gland and ground it up, he could restore the sleep cycle of submarine guys and pilots and astronauts and all these things. Then, he kind of isolated what is the active ingredient in this peptide extract that's causing that. And then, he found the 4-amino acid peptide epitalon, which is popular in longevity circles nowadays. But, he showed that that was causing the increase in melatonin production and the restoration of the circadian rhythm. So, he's the father of the bioregulators.

That's interesting. And, it agrees with what I've experienced subjectively. And obviously, this is an anecdote, but I'm right now getting some of the best sleep scores of my life, just knocked out 8 hours. And, when I travel, I use higher-dose melatonin and CBN, which is kind of like a cannabinol extract that's pretty good for sleep as an anxiolytic. And, that works really well when I travel, but at home, I've started to do a small dose of epitalon, about 500 micrograms, and a couple capsules of this pineol bioregulator, this pineolone. And, I'm doing that 30 to 60 minutes before bed. I would love to hear your feedback on this if you think it's just in my head or if this really has some legitimacy to it. I am sleeping so well with this stack.

Yeah. No, I'm on the epitalon-pineolone stack too. It's amazing. Epitalon is interesting because it's orally bioavailable, it seems. The injectable seems to be more effective at systemic effects. What we found is the oral epitalon probably doesn't go systemic, but it increases melatonin production in situ locally in the gut.

And, by the way, I'm doing the epitalon as injectable and the pinolenol, I'm doing that as an oral capsule.

Yeah, yeah, yeah. So, the epitalon, what I've noticed is the injectable works really good for circadian issues. Before I travel, I take Some epitalon. When I get back, I want to reset and use epitalon. I share your high-dose melatonin for travel. That's a good protocol. The Pineleon is only 3 amino acids. It's called Pineleon, but it doesn't actually come from the pineal gland. It actually comes from the cortex. There was a Russian drug called Cortexin. It's like the cousin of cerebral lysine, which are ground-up brains of animals.

Okay.

Dr. Cavinson found this bioregulator called Pineleon. I don't know why he named it Pineleon despite not coming from the pineal gland. Their naming conventions are very confusing, as you've seen with the thymulin and the thymulin. But, pinealine is a cerebral cortex bioregulator and it's well-studied for its effects on improving brain function, improving brain function under stress, and brain metabolism. What we've noticed amongst almost 70%, 80% of our patients is anyone put on pinealine, they have a 50% to 60% improvement in their REM sleep. So, I'm seeing guys that are getting 2.5, 3 hours of REM. And very vivid, my friend called it 8K dreams from the pinealon. So, the 1-2 combo of epitalon and pinealon is a pretty effective stack at boosting your sleep because you're getting circadian rhythm effects of the epitalon with the brain performance effects of the pinealon. And, when we talk to a patient, I ask them, do you dream? How vivid are your dreams? Do you have colorful dreams? Because that's kind of my marker of what's your brain doing. Because if your brain's not producing dreams, I know it's not producing the right amount of chemical concoctions during the day to have that cognition that you want.

Yeah. What is it about peptide bioregulators that make them bioavailable when taken orally?

Yeah. So, the next thing Dr. Cavins did is like, hey, I know these are working orally, but let's find out why. And, he identified that they actually get absorbed through LAT and PEP transporters. So, we have amino acid transporters that can get 2 and 3 amino acid peptides if they fit into the transporter. to be orally bioavailable. So, that's how KPV works. It goes through the same kind of transporter because it's 3 amino acids, but he found that certain bioregulators, not all of them, can be used orally for that effect. And, Pinoleone is only 3 amino acids, so it fits in pretty nicely into that transporter. Yeah.

I'm sure people are going to blow up the comments section on sourcing. I have a stash of bioregulators I had ordered from Vasalius. Prior to that, I think I had gotten some at one point from Anti-Aging Systems. It's antiagingssystems.com or something like that. I'll put links in the shownotes. As far as sourcing for those, do you have any tips for people, Abhoud?

Yeah. One of my friend's companies, so biased there, but yourprotocol.co has pretty good oral pineolein at a high enough dose that's interesting.

yourprotocol.co?

Yeah, yeah, yeah. It's a friend's company. He has an encapsulated version, so it kind of survives the stomach acid. A little bit better so you can get more of it bioavailable to the intestinal absorption peptide transporters. So, that's a good one. And then, the injectables, ipitalon is going to be probably moved from Category 2 to Category 1. So, that should be easier to source the injectable here shortly once the FDA moves that. Penileon is not on any Category bulk list. There are a number of compound pharmacies that are still producing it, especially it's popular in nasal spray as well. So, if someone wants a prescriptive nasal spray, those are available through a physician too.

Okay, okay, got it. Now, I know a couple of functional medicine doctors who are doing NK killer cell treatments where they take a patient's blood and they ship it off to freaking Lithuania and then it comes back after the NK cells have been concentrated and they do an infusion or a treatment. That seems like it's When I describe it, I'm sure a lot of people think it sounds like top of the totem pole for immune system support. But, as somebody who understands the thymus, what do you think about that just dumping a bunch of killer cells from your blood back into your body?

Yeah. What seems to happen is as your thymus ages, you get less good at clearing out infections. So, you'll notice you have a fungal infection, you have a little bit of a rash that lasts around longer, things aren't as effective at being And, it seems that post-pandemic, post-whatever happened to our immune systems, we are just far less capable of clearing out infections. And, chronic infections on their own lead to further thymus atrophy. So, when you have these chronic infections hanging around, that inflammation can be negative to the thymus itself. So, what usually happens is when you get sick, your thymus shrinks, you then kind of convalesce, you rest, you recover, and your thymus kind of grows back and you get back to health. Nowadays, you get sick, You board a flight the next day, you go back to work. No one really cares about that recovery process. And, it seems what they're doing is they're taking these NK cells to help clear out any kind of lingering infections that may be in the periphery. And, this should then free up your thymus to rejuvenate and restore itself and then allow you to be more resilient from an immunological perspective. Now, these low-grade infections are associated with Alzheimer's, dementia, and all this low-grade inflammation. So, it seems to be an interesting thing. Now, we'd like to see more trials because you don't want to want With that CAR T-cell therapy, there's autoimmune risks that happens. You get all this immune support, but are you risking autoimmunity? But, it seems to be an interesting concept that I think as we notice that people have low NK cells, they're going to need some kind of exogenous support to help boost that immunity to clear out any kind of lingering infections.

Yeah. Okay, cool. That's helpful. I also increasingly see for organ support claims or uses of red light therapy. Like, on the testicles for stimulating the Leydig cells to produce more testosterone or on the head or intranasally to support mitochondria and neural tissue. When it comes to the thymus, have you come across anything like that, like using red light therapy to somehow stimulate it?

I do red light therapy on the thymus a few times every week. There's a paper that was a postulation like, hey, can photobiomodulation be a positive resource to help rejuvenate immune tissue. The thymus, as we mentioned, is very energetically demanding. It means a lot of mitochondria. Red light therapy is good for the mitochondria. The thymus is pretty shallow right here, right underneath the sternum. So, even red light from the sun should be able to penetrate and go through and get that there.

Right underneath the sternum, like right here where I'm pointing?

Yeah. So, you got your lungs, you got your heart, and then right on top of that is where your thymus is hanging out there.

Okay. So, you could use a panel or even a spot treatment device. You know how they make those little Yeah. If you're laying in bed at night, you could potentially just put that over your sternum.

Yeah, yeah. So, I have a little device, I just put it on there and get some light therapy to the thymus if I feel like I'm getting sick or I'm traveling, kind of a boost. I don't have good data to support that it's good, but it's pretty cost-effective and low risk. So, I'm like, hey, let's try it.

Yeah, yeah. I've heard similar claims about PEMF. Have you come across the use of that for similar reasons?

Yeah. There's an interesting thing about thymus and frequencies and all these things is that there's certain pulsations that should be restored for the thymus. So, I would love to see if there's some kind of EMF negativity to the thymus because when Cavendish noticed that the submarine guys got their thymus, they would shrink actually faster. It was from the radiation that was happening to the chest. So, what if you use some kind of preventative treatments whether that's PEMF or grounding or earthing or whatever it may be to kind of protect against that process?

Okay, yeah. Definitely don't keep your cell phone in your bra.

Yeah.

Exactly.

Or near yours.

I mean, really try to have your cell phone against your skin anywhere preferably, but that's interesting.

Yeah, I noticed you kept it away from your body during that dinner, so kudos to you.

Oh, yeah, yeah. You don't want to know how many times I've been at a restaurant, the waiter picks up my cell phone from the floor and they're like, you dropped this. I'm like, oh, it's intentionally underneath my chair. So, you obviously know, as I alluded to earlier in the show, a lot about other peptides As far as other peptide treatments that might even go beyond thymus, what are some of the things that you're really keen on using in your patient population or in yourself right now?

Yeah. The bioregulators are very interesting. We're exploring that further. We're using penile epitalon. We talked about some of the thymus peptides are very interesting there. Of course, everybody's on IGLP nowadays and figuring out how to get the optimal protocol without the negative side effects from that process. Some of the melanocortins are interesting from a perspective of immune stimulation and also weight loss. I think there's going to be a boom there. Those are the melanotans of the world, the PT-141s. Right now, PT-141 is the sexual peptide, right? But, the company that owns the patent is actually studying it as a combination with tirzepatide for further weight loss. So, that's an interesting—

Well, what would be the link between a melanocyte-stimulating hormone Or melanocyte-stimulating peptide like PT-141 and weight loss or metabolism?

Yeah. When you think about metabolism, the key pathway is the leptin-melanocortin pathway. Leptin is a hormone produced by fat cells. It signals to the brain how much resources we have. So, every night, your brain's doing a calculation of, do we have resources? Do we not have resources? If we have resources, we produce hormones. If we don't, we kind of shut down metabolism, increase appetite. So, leptin binds to these POMC neurons in the brain, which makes Pro-opiomelanocortin, which then gets cleaved into ACTH, which then makes cortisol in the adrenals, and then MSH, melanocyte-stimulating hormone that you mentioned, that then turns on these MC4R neurons. They increase metabolic rate and decrease appetite. So, people that take PT-141, they get a little bit of nausea. That nausea is because you're really decreasing appetite. So, anything in your stomach, your body's like, oh, we don't want to metabolize this right now. So, I think the next pharmaceutical receptor people go after is the MC4R receptor. for obesity. It happens to be that the GLP-1 receptor is on these POMC neurons where the leptin is also binding. So, there's probably going to be a one-two punch that gets produced here pharmaceutically in short order.

Okay. And, from what I understand, there's not any type of melanoma risk for the receptor that PT-141 would target.

Yeah. So far, there isn't. There's a theoretical risk if you have PT-141 despite being an MC4R more specific, it still could activate. There's 5 melanocortins, 1, 2, 3, 4, 5.

It could activate other ones still.

But, it's an FDA-approved drug and so far, there's no phase 4 post-market studies that show that it does increase melanoma risk. There is that concern with melanotan-2, which is the non-FDA-approved peptide that people use for looksmaxxing, but that's still a theoretical risk that no one has really proven.

Yeah, tan masking, tan maxxing.

Yes.

What other peptides do you have up your sleeve as far as ones that you use frequently in your protocol?

Yeah, of course, BPC, but at higher dosages given the myostatin mutation, injuries are more frequent for me than others. But, I found with NMN looking at myself that if you have an acute injury somewhere closer maybe, and not medical advice, but 5 to 10 milligrams seems for me to work a lot better.

5 to 10 milligrams? Oh.

Yeah.

When I inject, I do 250 micrograms.

Yes, yes, which is the kind of baseline dose. I found that if you have an acute infection, that's what really kind of pushes you over the edge. To getting the real blood flow and the healing factors in there. And one, of course, guys, but you're taking up to 40x that amount.

Yes.

Wow. Yeah. And I found that to be like when I had my ACL surgery, I was taking the BPC post-surgically. It was helping out, re-aggravated the injury. It took BPC, took BPC, didn't get effects. And I was like, you know what, last vial. I'm just going to slam the vial and see what happens. Slam the vial. I'm like, whoa, this is interesting. Like woke up the next morning, the meniscus was way Better, less of a glide. The next day, I got another vial. I'm like, okay, let's see what happens now. 10 milligrams again. And, I'm like, okay, this is something.

Yeah.

So, I think the problem is people want BPC studies. We don't even know what the efficacious dose is of BPC for injuries. No one's really kind of explored it properly.

Yeah, yeah. Super interesting. When you're doing high-dose BPC, do you also use higher doses of TB-500?

Yeah. In that instance, I did not. I like TB4 more than TB500. I think there's other effects of TB4 that are interesting.

And, as a reminder to people, TB500 is a smaller fragment kind of broken off from TB4?

Yes, yes.

Okay.

So, yeah, it's the fragment. It seems to have more of the healing effects, but I think there's effects from TB4 that are good. My biggest complaint to the peptide industry is which injury benefits from one or the other and which injury would not benefit from the combination. Because I think there's going to be injuries where like, hey, you only want to use BPC, you wouldn't want to use TB. I don't know the answer there. I think we need to kind of put our heads together instead of just, peptides are great. Let's think critically about when to use which peptide and for what patient. Yeah.

When you say the injury, you mean injury location or do you mean strain versus sprain versus full tear, the actual mechanism of the injury?

Yes, yes. Is it a muscular tear? Is it ligamentous? Is it a blood flow issue? I think we need to think about that more critically. Right, right.

Because if you look at the meniscus, for example, an area of poor blood flow would make sense that BPC-157 would fit well into that protocol. And maybe a tissue with adequate blood flow could benefit from TB4 or TB500 alone.

Yeah, yeah. So, that's at least the theory that we need to kind of flush out. Yeah.

Okay, got it. So, we talked about sleep, muscle recovery, the thymus gland, a little bit about Weight loss. A little while ago, you had mentioned something else about testosterone or the testicles and the thymus. What is it you were referring to? Yeah.

So, the interesting thing there is that not only is the thymus active from an immunological perspective, it's also a very important endocrine gland in that the thymus peptide thymulin is a hormone activator of the pituitary and of the gonads. And, this research was done in the late '80s, '90s and kind of abandoned. But, In animals that they remove their pituitary gland, so they don't make LH and FSH. And, for the audience, LH and FSH is made in the brain that goes to the testicles and that tells the testicles to make sperm and testosterone. And, if you remove that gland, the testicles no longer can respond to that tissue signal. When you inject the animals with hCG alone, they make testosterone again. But, if you inject them with hCG and thymulin, they make more testosterone per unit of hCG. So, that shows that there's an immunological regulatory signal between the thymus-pituitary-gonadal axis, which then now regulates endocrine production. Now, why does this matter? From an evolutionary perspective, from a teleological perspective, if you have low immunity, it makes sense that you shouldn't be making testosterone and sperm because you don't have enough resources to then go take care of that offspring, especially for a female.

Yeah.

But, for us, in practice, if we have a patient that we have low testosterone, they also have really bad immunological markers, so we're assuming they have poor thymus function. When we give them HCG or enclomiphene, they don't respond to it well. And, this is anecdotal from a small patient population, but we're like, hey, there must be some kind of a mechanism that limits their ability to respond to these signals from an immunological perspective. And, it makes sense from that kind of fertility and resources perspective.

Okay. So, would it make sense then that supporting your thymus gland might make you more sensitive to or receptive to something like a hormone replacement therapy protocol?

From HCG and enclomiphene, if you're replacing the LH and FSH signal, that's going to be interesting to see if that plays out because in the animal models, thymulin with HCG makes HCG more effective. So, I postulate that would happen in humans too. Now, interestingly enough, it kind of makes sense because if you think of the thymus as this gland that's shrinking under the influence of testosterone, then your body should have a regulatory mechanism that if your gland is too small, hey, stop making testosterone so we can kind of Right, exactly.

Again, a resource allocation type of thing.

Yep, yep. It seems to be a very resource allocation. On top of that, corticosteroids seem to really shrink thymus mass. And, that might explain why a lot of these people that have these long COVID syndromes, these post-viral infections, they have fatigue always because if your body is not having the immunological resources, it's not going to allow you to make as much corticosteroids from ACTH. So, there's also an ACTH regulation. So, if you look at thymulin, it regulates almost all the hormones that come out of the pituitary: TSH, ACTH, LH, and FSH. And, that's kind of ignored in this modern endocrinology discussion.

Yeah, yeah. Kind of paired with the discussion around hormones, I know so many people ask me constantly about fertility. And, we've talked about a lot of things like keeping the balls cool and not spending a lot of time in a sauna or a hot tub. specific nutrient replenishment protocols, et cetera. But, from a peptide standpoint or anything else that you might commonly use in your practice, do you do anything related to fertility?

Yeah. So, epitalon seems to be interesting on that front. There's some ovarian datasets that aren't that strong but seem to be at least interesting where epitalon seems to be preservative of ovarian health. So, epitalon is going to be interesting. That makes sense because there's a melatonin-pineal kind of access there. So, even high-dose melatonin has seemed to be an interesting avenue to explore for that. The mitochondrial peptides seem to be interesting, especially SS31. These ovarian cells that have the eggs, they've been in existence since the female was in her own mother's uterus. So, that's an older cell that maybe will benefit from some mitochondrial support on that side.

Right. So, you're supporting the mitochondrial membrane with SS31?

Exactly, exactly. That's going to be an interesting target. Yeah, that's right. Dr. Cavinton came up with ovarian bioregulators that I haven't explored yet, but I think it will be interesting to see if those pan out. There's some interesting interest there. In fact, the parent compound of epitalon, epithylamine, got rebranded as PineaMine and it's given in Russia as an approved drug for menopausal symptoms by making the ovaries respond better to the LH and FSH signals that happen after menopause. So, there seems to be an interesting thing where you don't look necessarily at just the ovaries, like what's happening upstream. Is it thymus? Is it pineal? Is it pituitary? Kind of see if those signals can help out. And then, directly in the ovary, there's the thought about the mitochondria there with SS31 and all these other tissues.

Yeah.

I think the key thing is a lot of these ladies that come to us that want more fertility benefits, they're living a very fast-paced life, they're not recovering, they're under high stress. They're usually successful ladies that have big companies or they're lawyers, doctors, and they're not kind of slowing their life down and allow them to become fertile again because those corticosteroids are shrinking thymus tissue, ovarian tissue, all these things.

Yeah, yeah. It's kind of a newer issue humanity has faced, women being in warrior mode and going into like matriarchal mode.

Yep, yep, exactly.

It's a new thing.

Yeah.

I don't think it's conducive to fertility.

Yeah. And then, speaking of stress, the gut is obviously another huge target that a lot of people want to address.

Yeah.

I've talked about KPV, lirazotide, BPC as a few options that people are turning to for inflammation or for permeable gut type of issues. Anything that you particularly focus on in your practice when it comes to the gut?

Yeah. So, the gut is interesting because LPS produced from bacteria that leaks through if someone has a leaky gut, that's a very bad thing for the thymus. LPS really shrinks the thymus. Those signals are not good. So, when someone has the gut problems, they usually have an immunological problem that goes with it downstream from it. So, we like to figure out what's going on, what's the actual cause because you think about it, what actually makes the gut membranes connect together well, you need energy for that. So, is there sufficient thyroid hormone to produce that tissue? But, from a peptide perspective, BPC-KPV is a nice combo especially if you get an enteric coated BPC to get into the lower parts of the digestive tract to kind of support there. We like to use lactoferrin too. Lactoferrin is a very interesting compound that I think will become very popular over the next months to years.

Yeah. Don't you find a lot of that in colostrum?

Yep, yep.

And, I think that's why colostrum is very effective from that perspective. And, it seems that there's maybe some of the thymus peptides or similar peptides in colostrum. They did a study on breast milk from mothers for the first 3 months. There's a high level of thymosin alpha-1 in breast milk. Yeah.

Well, that would make sense based on the need for the immune support that's already highlighted by the delay of the shrinkage of the thymus. So, colostrum would help that also, right?

Yeah, yeah. And, it seems that colostrum has both an effect at the gut itself through lactoferrin and other peptides, but also it seems to have an immunological stimulating effect at the thymus. So, I think colostrum is going to catch on as a thymus-maxing supplement.

Yeah, yeah. Obviously, people are probably scribbling down the names of all these peptides wondering where they're going to get them, et cetera. Are there particular precautionary steps that people should take or red flags when it comes to getting and/or administrating peptides?

Yeah. And, I think you have to think about each peptide itself and then the category in general. Category in general, you want a good source, you want reliable injections, you want to make sure you're not getting— you want sterile technique to make sure or as sterile as possible wiping down the skin, wiping down the bottles so you don't get infection.

If you have weak immunity to start with, that's more likely to have cellulitis.

as a consequence of a faulty injection. When it comes to certain peptides, we have to think about the risk profile of them and dosing properly. So, when it comes to BPC, although we don't have the data that shows that there's a cancer risk, I wouldn't want somebody that has a low-grade colon cancer to be taking oral BPC. Out of abundance of caution, I'm like, hey, stay away from that. If you have a family history of that, probably stay away for an abundance of caution.

For colon cancer specifically?

Yeah, yeah. And then, cancers in general, there's the concern about BPC. I know it's kind of exaggerated but still just don't want to do harm to a patient, so we're more careful to tell them to avoid that. The growth hormone secretagogues are interesting like the Tesamorelin and Sermorelin of the world, they increase growth hormone. But, there's also the same concerns. You have a smoldering cancer and then you increase the gas pedal on that.

Right.

When it comes to ipitalon, for example, if you have poor circadian habits, Epitalon might actually be hurting you more than helping you because you're taking Epitalon. Epitalon seems to have retinal effects on top of its pineal gland effects. And, it's been studied to help rejuvenate retinas in Russia.

Oh, I know where you're going. If your light habits are poor in the evening, then Epitalon is going to concentrate the effects of that.

Yeah. So, our patients, if they don't want to get into the light habits or the blood blockers, do all those things, I'm like, hey, maybe Epitalon is not the best choice. for you at this time. Although, it does seem to help out with shift workers, but for some people, it really makes them sensitive to blue light.

So, that kind of sleep I'm mentioning— Yeah, that's interesting too. You could almost use that for the opposite effect and reverse engineer shifting your sleep clock forward or backwards if you were to, for example, if you're traveling east and you want to stay up for later, basically inject yourself and then get exposed to blue light to shift the clock forward.

Yep, that's my protocol. How'd you find it? That's what I do when I travel. It's like use the apatallon as a circadian maximizer and then use the blue light blocking to make you more sensitive to that signal.

Right, right. And then, high-dose melatonin when it finally is time to knock out.

There you go. And, I think both high-dose melatonin, the one concern there is that it seems to make you more photosensitive also. So, you would want to block blue light and harsh light when you're taking the high-dose melatonin. As to not theoretically create any risk for your revenue.

Right, right. Yeah, super interesting.

Yeah.

And this is fascinating. Do you have like a blog or a website or do you mostly just do podcasts as the way you get content out?

Substack that I'm starting to get more active on. This is a bootbakery. And Twitter is where I post most of the content.

Okay.

That's the fun spot to do it.

You mean X. You're still stuck in the aughts.

I'm still stuck, man.

Sorry.

I don't know if I'm ever going to change the X.

No, I do it too. Alright, cool. Well, I'll link to your stuff in the shownotes. And, for those of you listening, again, it's BenGreenfieldLife.com/ThymusPodcast. It's super interesting. And, if you're listening, if you have questions or comments or feedback, you can also leave them there in the shownotes and I'll check them out. And occasionally, I send comments I can't figure out over to the guests. So, Yeah. So, Abhoud, thank you so much for doing this, dude.

It's awesome. Thanks for having me, bro.

Yeah. Thanks so much for watching, folks. Again, the shownotes are at BenGreenfieldLife.com/ThymusPodcast. Have an incredible week.

Do you want free access to comprehensive shownotes, my weekly roundup newsletter, cutting-edge research and articles, top recommendations from me for everything that you need to hack your life, and a whole A whole lot more, check out BenGreenfieldLife.com. It's all there, BenGreenfieldLife.com.

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