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After my conversation with Dr. Greg Fahy in August, I realized that I had additional questions that we didn’t have time to address the first time around. Importantly, since here I am studying the effects of dietary and lifestyle interventions on aging, I wanted to know his thoughts on the dietary components of the TRIIM study and beyond. Dr. Fahy shares his thoughts on my question and some others on side effects on different medication and supplement interventions, the mechanism by which he thinks the restoration of hair color occurred in some of his study participants, and how to think about (and feel motivated about!) incorporating safe exercise. This brief bonus podcast episode is just right for squeezing into your holiday schedule. Enjoy! ~DrKF
Missed the first conversation with Dr. Greg Fahy? Catch up on the original episode for key insights and context before diving into the follow-up.
Kara Fitzgerald: Hi everybody. Welcome back to New Frontiers. This is The Podcast After The Podcast. This is the podcast where I still have more questions and I ask my guests if they would be so gracious as to join me again for some of the backup questions. So today I have Dr. Greg Fahy back with me again. You know him as the principal investigator of the TRIIM study. We’ll definitely link to that paper and we’ll link to the podcast I had with him. So what I was going to tell you, Greg, is that this is by far our most popular video on YouTube. We’re releasing on YouTube now.
Dr. Greg Fahy: That’s fantastic.
Dr. Kara Fitzgerald: Yeah. People are extremely interested in what you’re up to with the TRIIM study. Dr. Fahy’s huge claim to fame was the first evidence of biological age reversal in humans using all of the epigenetic clocks. Actually, Steve Horvath, who is just the father of the field of epigenetic biological age measurement was part of the study. And so, our original podcast goes in depth on the 2019 TRIIM and how time sort of stood still when that paper came out and then all your subsequent work. So we talk about all of that over on the baseline podcast and I do encourage you to listen to it because it’s really interesting. But here I am, you know, studying diet and lifestyle interventions, as you know, Greg, and I did not get a chance to ask you about that. So this is the podcast after the podcast so I can ask you a couple of these questions.
Dr. Kara Fitzgerald: First of all, I want to know your thoughts, your guidance to your new cohort of TRIIM participants. What are you thinking about with regard to supplements? I know you’re doing a few of them as the cornerstone TRIIM investigation, but what about additional supplements, especially some of those that are getting PR? And then we’ll talk about exercise and diet, but why don’t we start with supplements?
Dr. Greg Fahy: Yeah. One of the things that we’re learning as a result of doing these trials is that the antidotes to the side effects of growth hormone have their own side effects. But there may be some nutritional approaches that we can use to mitigate those or get rid of those side effects as well. They have to do with things like changing your hormone levels and stuff like that, and we have begun looking at various nutritional interventions to see if we can mitigate some of that. So far, I’d say the jury is kind of out. We’ve had some positive results and we’ve had some non-results, so it’s probably premature for me to go into the details about this because I’m not sure about anything. But there are some possible supplements that might work, at least in theory, to mitigate some of these side effects.
Dr. Kara Fitzgerald: So tell me what the side effects are. Side effects of growth hormone and then the side effects of the interventions you’re using. I’m thinking about metformin primarily, but yeah, talk about the side effects of growth hormone and the side effects of the interventions you’re using for side effects of growth hormone. And if you can tell me any of these supplements, please do.
Dr. Greg Fahy: I want to be a little bit guarded about this, but the side effects of growth hormone, of course, are primarily the insulin elevating effect. And that can sometimes raise glucose as well. And the aging clocks don’t really pick up the insulin side of that. They’re not really geared for that. But at least the plasma PhenoAge aging clock, the one that you can measure using simple, inexpensive blood tests, it ignores insulin. And I understand why it ignores insulin because insulin’s all over the map for all kinds of different people and you can modify it in various ways. So I think as a standard biomarker, it’s difficult to factor in.
Dr. Greg Fahy: But of course we’re [inadvertently] raising insulin as result of the treatment, so it’s very relevant to us. So we use the metformin and the DHEA as we discussed before to lower the insulin and also keep the glucose under control to prevent that from happening. But the DHEA, may reduce kidney function and there may be a remedy for that. And the metformin may lower testosterone, I think, and there may be some remedies for that. These are not-
Dr. Kara Fitzgerald: Without actually prescribing testosterone.
Dr. Greg Fahy: Yes, yeah, exactly. But we don’t know yet. We haven’t really seen very positive effects yet for some of the interventions that we’ve looked at, but it’s still early days. We’re still very early on in this game. We’ve looked in the past at nutrients like chromium, which allegedly increase insulin sensitivity and it just didn’t really seem to work. A lot of things that look good on paper may not actually work when they’re put into practice. Maybe that’s partly because the context is different and the mechanisms are a little bit different.
Dr. Kara Fitzgerald: They are. Yeah.
Dr. Greg Fahy: I think the bottom line for right now, Kara, is just that it’s a work in progress. I really don’t want to mislead people by giving advice that may not work.
Dr. Kara Fitzgerald: Okay, well it’s cool that you’re tussling with that. We’ll just stay tuned. What about diet? What kind of dietary pattern are you suggesting that people eat? Is there variation on that?
Dr. Greg Fahy: Yeah, so there’s a couple things.There’s kind of three answers to that question. The first answer is we want to demonstrate, if we can, that our treatment works for everyone. And people have different diets. People make different choices in their life. And we don’t really want to get into the business, at least not right now, of trying to change people’s lifestyle. I mean, if you’re at Merck and you’re issuing a new drug for treatment of some condition, you don’t only give it to people who are on a Mediterranean diet, you know, and not people who are vegetarians or whatever. So the first answer is we don’t interfere with your dietary choices.
Dr. Greg Fahy: We do restrict you in some ways, like if you’re going to get your blood drawn, we don’t want you to eat a different kind of meal the night before, because that might throw things off. But you’re normally free to eat whatever you want. So that’s one level of answer. Another level of answer would be that if you really want to have a healthy diet and a healthy lifestyle, number one, I’m not a doctor and I’m not authorized to give out health information to people, but just as a personal matter as a private individual, just expressing my opinion, it seems to me the Mediterranean diet is probably the best one that’s out there so far.
Dr. Greg Fahy: And there are pluses and minuses to all these different diets. There’s a million of them out there. None of them have really won the race in the sense that if there was one diet that was super good, most people would already be on that. And that just really hasn’t happened yet. So I think a lot of this is still a matter of opinion and of course, your opinion depends on your level of expertise. So to someone like you, Kara, you know much more than most people and you will have recommendations that are much more informed than most people. But whatever the recommendations are, they haven’t won the day yet in that they haven’t converted the majority of people to one point of view so far.
Dr. Greg Fahy: But nevertheless, on balance, my opinion at the moment would be a Mediterranean type diet. You know, olive oil and fish, broccoli and leafy green vegetables and fruits and vegetables. All that’s really good stuff, I think. And an occasional glass of wine, by the way. People who don’t drink at all don’t live as long as people who do. Obviously there’s a limit to that. You don’t want to overdo that. And sometimes that’s a little difficult, but a little bit is not such a bad idea.
Dr. Kara Fitzgerald: Sure
Dr. Greg Fahy: Now, beyond that, so one of the conundrums that we’ve had to deal with is that we deal with people who are already very health conscious. They want to whatever they can for their health.
Dr. Kara Fitzgerald: Yes, that’s right.
Dr. Greg Fahy: And a lot of them have heard about calorie restriction or intermittent fasting, that sort of thing. And there has been sort of an unknown effect that that might have on the thymus and so we have not known quite how to handle that. So we’ve really requested that people not to be on calorie restriction or not to be on severe calorie restriction. A little goes a long way. I stopped eating lunch in what, 1977 and haven’t looked back and I seem to be doing pretty well and I respond very well to the treatment. So mild calorie restriction like that is fine, but we weren’t sure what would happen if you made it more extreme.
Dr. Greg Fahy: But a study came out recently indicating that calorie restriction might actually improve the immune system and might even improve thymic function so we’re looking at that to see if we want to change our guidelines on that.
Dr. Kara Fitzgerald: Interesting
Dr. Greg Fahy: Yeah. So I think what we’re probably going to end up doing is allowing people to stick on their calorie restriction regimen if they’re on one already. And we will compare them to other people and make sure that they do just as well as everybody else.
Dr. Kara Fitzgerald: Fascinating. All right. We’ll track that paper down and put it in the show notes. Okay, yeah, I was going to say that likely, everybody’s coming to you as a biohacker and you’re just going to have to kind of tease those variables out as best you can. What about exercise?
Dr. Greg Fahy: Well, sure, exercise is great. We’re kind of stuck in the sense that exercise is a lifestyle choice. And if you change your lifestyle in the middle of a trial, then we may not know what’s going on because it might be a lifestyle choice change that we’re looking at the effects of, or it might be that the treatment is even better than we thought it was or something like that. So if you enter with a certain level of exercise, we want you to stick with that at least for the first year. What we’ve noticed is that in some cases the people feel so energetic at the end of the first year, they’ve just got to exercise.
Dr. Greg Fahy: And so I’m willing to open my mind a little bit and say, okay, well that desired exercise, which wasn’t there before, is now a treatment effect. And since it’s a treatment effect, we’ll go ahead and let you do that. But we’re going to make a note of the fact because we don’t want to think it’s just the drugs or whatever, and not the effect on your exercise capacity. So we try to parse that. But in terms of the background question you’re asking, is exercise good? Yes, exercise is good. Within limits, the more the merrier.
Dr. Greg Fahy: Even a little bit is good. If you’re an old person and you just walk as opposed to not walking, even if you don’t walk very fast, even if you don’t walk very far, that is still good for you. Do whatever you possibly can. If you’re weak, but you can lift a dumbbell, a five pounder or one pound or whatever, that’s better than not doing it. So anything you can do is to your benefit. And so we would encourage you to exercise. The only thing that you don’t want to do is get injured.
Dr. Greg Fahy: That’s the main downside of exercise. We had one lady who was on our trial and she was so energetic. She became a fiend on her mountain bike and ended up plowing into a tree and injuring herself.
Dr. Kara Fitzgerald: Wow.
Dr. Greg Fahy: They don’t really want to do that. By the way, the good side of that is that she healed very fast and she even healed her torn meniscus, which doesn’t happen. So we’re pretty excited about that.
Dr. Kara Fitzgerald: Yeah, there’s all sorts of anecdotal reports from your people. You know?
Dr. Greg Fahy: Yeah, yeah. Amazing. We’re not soliciting any of this. It’s just that people tell us these things. So, we note them and an anecdote is just an anecdote, but if you pile up enough of them, then it sort of becomes data.
Dr. Kara Fitzgerald: Right. I published a book early in my career, a collection of case studies and functional medicine. I mean, that’s how you establish questions. It’s the first step, I think. So I have a high regard the so-called anecdotes.
Dr. Greg Fahy: Yeah, I mean, that’s where you start. And people notice things that you wouldn’t have even thought to ask them
Dr. Kara Fitzgerald: That’s right. That’s right.
Dr. Greg Fahy: The guy whose wife would say, hey, honey, your hair’s turning in dark again. He wasn’t expecting that. We weren’t expecting that. But because we got that feedback from him, now we can look for that kind of effect. So you never know what might turn up.
Dr. Kara Fitzgerald: Well, I mean, this kind of brings me to you. I mean, there’s frequently dialogues on how old you are because you don’t look your age at all. I’m not even sure what your age is, but I think that you’re in your 70s. Right?
Dr. Greg Fahy: Yeah, I’m 74.
Dr. Kara Fitzgerald: You’re 74. But I mean, I don’t see any gray hair. This is Zoom, but I think you’re actually one of the people who’s practicing the program, but you’ve benefited from your hair color changing.
Dr. Greg Fahy: Well, I think I I’ve benefited, but with respect to the hair color, there was an old commercial on television when I was a kid—”Does she or doesn’t she? Only your hairdresser knows for sure.”, right? So I mean, I do have to give it a little bit of help. I must tell you that. I can’t take full credit for it.
Dr. Kara Fitzgerald: OK.
Dr. Greg Fahy: Yeah. But I had a handicap in that regard. I started getting some gray hair when I was 35 but I was dating this girl at the time and I couldn’t look like an old guy, so I had to something about that. And so it’s kind of been around for a while.
Dr. Kara Fitzgerald: Well, what’s the mechanism reversing the hair color?
Dr. Greg Fahy: Yeah. It’s actually quite interesting because the mechanism of hair graying in the first place is pretty severe. It’s something that you would not think could be reversed. The hair gets gray because the melanocytes stem cells that give rise to the melanin ultimately in your hair, they die and they’re gone and they’re not there anymore. So for hair color to come back, you have to mobilize your melanocyte stem cells again and they have to come back, migrate into the follicles and remanufacture the melanin generating cells in your hair follicle, which then have to start working and producing hair again.
Dr. Greg Fahy: But it turns out, by happenstance or maybe there’s more to this than that— I tend to think that this is for a biological reason, although we could debate that— but it just turns out that the gene that actually is responsible for reactivating your thymus, which we think we’re turning on with our treatment, is also responsible for hair color. It’s one of the genes responsible for hair color. And so we think that that’s what’s going on: by reactivating FOXN1, we’re also reactivating the production of color in the hair.
Dr. Kara Fitzgerald: In a subset. But it’s a small subset.
Dr. Greg Fahy: It’s a small subset and I think it depends on how far gone your stem cells are. If you have more of them when you start the trial, maybe you have a better chance of multiplying them and bringing them back.
Dr. Kara Fitzgerald: Does it turn around early in the journey or does it take a while before those melanocytes stem cell–-
Dr. Greg Fahy: Our best evidence so far would be the first guy who reported that color change to us, and then one other guy in TRIIM who was pretty enthusiastic about it. Both of them took, I’d say, six to eight months, something like that, before they noticed the change. So somewhere around six months.
Dr. Kara Fitzgerald: Well, I just really thank you for coming on. I just wanted to chat through some of the diet and lifestyle pieces. What about sleep?
Dr. Greg Fahy: Yeah, sleep is really important. There are different schools of thought about that. You were talking about diet recently and one of the guys who studied diet is David Asprey, of course. He wrote a whole book called The Bulletproof Diet. He gave a presentation that I saw recently in which he claimed that we only really need about six and a half hours sleep and that claims to the contrary are just made up, as he put it. No, that’s news to me. I’ve always heard people say you need at least seven, even preferably eight hours of sleep, but he says no. So I guess maybe the jury’s still out on that, but I’m not an expert in that department.
Dr. Greg Fahy: All I can tell you is if you take melatonin when you go to bed, then you don’t necessarily miss sleep. If you lack it, when you wake up in the morning, it’s a bit easier. And that’s why melatonin is used as the jet lag drug. It makes you wake up more easily. I think there’s a school of thought that it makes you fall asleep easily. I’m not sure sure that that’s actually true, but it lets you get the most out of the sleep that you got, apparently.
Dr. Kara Fitzgerald: Well, listen, Greg, thanks for coming on. I’m going to be continuing to pay attention when you release new stuff. You will hear from me until we can jump on and chat it through. Just keep up the great work, and once again, thanks for joining me today.
Dr. Greg Fahy: Thank you so much.
Dr. Greg Fahy received his Ph.D. in Pharmacology and Cryobiology from the Medical College of Georgia in 1977. A world-renowned cryobiologist, Dr. Fahy is the chief science officer and co-founder of Intervene Immune, where he leads groundbreaking research on thymus regeneration and combating age-related immune decline. He designed and led the TRIIM trial, the first to demonstrate both thymus rejuvenation and the reversal of human epigenetic age. His work has been pivotal in advancing aging research, resulting in successful follow-up trials like TRIIM-XA, and further planned studies aimed at refining and expanding these innovative treatments.
Original NFFM Podcast: You Are Only As Young As Your Immune System with Dr. Greg Fahy
Seminal Study: Reversal of epigenetic aging and immunosenescent trends in humans
TRIIM-X Trial: Thymus Regeneration, Immunorestoration, and Insulin Mitigation Extension Trial
The Future of Aging: Pathways to Human Life Extension
Robert (Bobby) Brook, CEO & CTO, Co-founder Intervene Immune
Science: TRIIM trial to target thymus
Nature: First hint that body’s ‘biological age’ can be reversed
Research and Resources from Intervene Immune
Study: Apparent induction of partial thymic regeneration in a normal human subject: a case report
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Better Broths and Healing Tonics book
Interview: Past, Present, and Future of “Biological Aging” with Dr. Fitzgerald
Video Blog: Does Multivitamin Use Increase Mortality Risk?
Podcast: Decoding Aging: The Science Of Cellular Rejuvenation With Dr. Vittorio Sebastiano
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