Q&A with a Longevity Expert, Dr. Terry Grossman

What are this longevity expert’s top 3 tips for living healthier, longer?

Here’s a hint: you can do them at home!

Dr. Terry Grossman – leading medical authority in the world of anti-aging medicine, and our very own Chief Medical Advisor – discusses this and more with AgelessRx Co-founder and Chief Medical Officer, Dr. Sajad Zalzala, in our first ever AgelessRx Ask Me Anything Q&A Series.
Follow along with our experts as they take questions from our subscribers covering everything from recommended supplements and therapies to the ever-expanding body of longevity research.

Video Transcript

Dr. Z: Thank you everyone for joining. My name is Dr. Sajad Zalzala, Chief Medical Officer and Co-founder of AgelessRx. Today is our first Ask Me Anything with our Chief Medical Advisor, Dr. Terry Grossman. Dr. Grossman is a giant in the longevity field. He’s written books on longevity long before…probably long before it was even called longevity. One of his books was actually one of the reasons I became interested in longevity back several years ago. We’re very honored to have him as an advisor and welcome to have him as a guest on our AMA episode today, our very first one. Let me ask Dr. Grossman to take a minute to introduce himself and then the first question specifically he can answer while he’s doing that: how did you get interested in longevity medicine?

Dr. Grossman: Thank you, Dr. Z. I’ve been a doctor for 43 years and I began as a conventional medicine doctor working in the mountains of Denver. I was a GP (general practitioner) and I did things like run an emergency room, setting broken bones; I was in a mountainous area taking care of fish hooks, people who fell off of horses; I set fractures, I delivered babies, and just generally got a wide variety of experience as a general doctor. Then after about 15 years of doing this, I started to become interested in complementary medicine, other ways of treating disease other than simply the drugs and surgery I had learned about in medical school. After about a year of trying some of these natural remedies on patients, I found out a lot of them worked as well if not better than the conventional drugs that I’d been using for years before, so I ended up moving from the mountains of Denver to Oakland Complementary Medicine Clinic.

In the course of a few years, a new specialty of medicine was born called anti-aging medicine. Prior to about 1992, when a seminal paper was published by Daniel Rudman, no one actually thought the aging process could be changed very much. We were all destined to have a certain amount of years, we would get old, then eventually we would pass on. With Daniel Rudman’s study on growth hormone [therapy] in 1992, they found that men who were over 65 years of age who took growth hormones seemed to be aging more slowly.

An organization sprung up around this concept that the aging process could be slowed down, stopped, and maybe even reversed, and that was called A4M, the American Academy of Anti-Aging Medicine, and when I saw a notice about their first annual meeting – back in1993 – I went to Las Vegas and was absolutely fascinated by this idea that we could change the aging process.

I’ve devoted myself since then to anti-aging medicine exclusively. In the year 2000, I published my first book, The Baby Boomers’ Guide to Living Forever, then I became friends with Ray Kurzweil, who’s a well-known inventor, entrepreneur, Chief Science Officer for Google. He’s the man who invented the scanner. He invented any number of inventions that translate: telephone, speech recognition, the list of his accomplishments goes on and on. We decided to write a book together, it was called Fantastic Voyage and came out in 2004. It got translated into a dozen languages, and people started to come to my office from various parts of the country and the world.It changed the nature of my practice, so I really became a longevity physician full time at that point. Then Ray Kurzweil and I wrote another book in 2010, and here we are in 2023 and I continue to practice longevity medicine. That’s kind of a history of my transformation. Now, the answer to your final question, how I got interested, I was in my late 40s at the time, and I was still in the mountains practicing regular medicine, and I found I couldn’t do things as easily as I could do when I was younger. I would go for a run or take a hike in the mountains, and things hurt when they never hurt before. I found that I couldn’t do as much as I could do when I was younger. This was clearly part of the aging process I didn’t like at all and I wondered if there was something I could do. That’s what stimulated me to go to that meeting for anti-aging medicine, so it’s really a personal issue. I’m glad to report that I think it is now possible for us to significantly slow down, stop, and reverse aging.

Dr. Z: Great, thanks for that background, I really appreciate it. The next question to follow up on that, if there were 3 things you could do for longevity in your 50s, what would those be? What are your top 3 longevity hacks? You know, that word “hacks” is a very popular term these days.

Dr. Grossman: Jack LaLanne, the famous weightlifter, I think he lived to 95 or so. He famously said there are two pillars to living longer and living healthy longer: one is diet and one is exercise. He said take diet and exercise, put them together, and you have a kingdom. I think that really diet and exercise are two of the three things that are most important. About diet, it’s really not that complicated. I think a few simple rules: 1) eat less. Intermittent fasting, like going as least 12 hours every day without putting any calories in your body ideally. Several days a week doing 14, 16, or 18 hours without any calories, and that’s actually a lot easier than it seems at first blush. All you have to do is skip breakfast and not eat after supper, and all of a sudden you’re close to 16 or 18 hours the next day. Eating less, doing intermittent fasting, eating more from the plant world as opposed to the animal world, so more plant-based foods. Not necessarily becoming a vegan unless you want to, but more plants, particularly fresh vegetables, things along those lines, fresh fruits are very helpful. Then with respect to exercise, HIIT training (high intensity interval training) does not take a long time. You can complete a HIIT interval in 15-20 minutes, and you get literally, if not all, maybe even more benefits than you do from going on a 45 minute walk or jog. HIIT training can compress the amount of time you need to spend, doing some weight lifting as well, some strength training, doing those two for exercise. So those two cover the two main pillars of diet and exercise. I think a real problem for those of us living in the world today is stress and closely associated with it is sleep. I think that almost everybody that I talk to, one of the first questions I ask is, “What’s your stress level like?” It’s interesting that they almost all answer the same way: “Normally I’m not too stressed, but lately I’ve been under more stress than usual.” I’ll ask them the same question 6 months later and they’ll answer the same way. “Normally I don’t have a lot of stress, but now I’m under more stress than usual.” I think a lot of us are really under a lot of stress. The world’s become a stressful place, COVID has upset the apple cart, so many things have changed, the world is changing at an extremely rapid rate and I think that this is stressful for people. As a result, I think that we’re not sleeping as well, and I think one leads to the other. Stress leads to bad sleep, you’ve got things on your mind, you can’t fall asleep, you’re waking up worried about things, and also bad sleep leads to stress, you don’t feel as well. I think doing something to improve your stress levels, whether that’s meditation, whether that’s exercising more, whatever it is, getting a hobby, getting a pet, doing things to reduce your stress level is very important. Then if you’re not sleeping well and sleep is an issue for you, luckily there are a lot of nutrients and even some prescription drugs that are not sleeping pills that can be used to improve the quality of sleep. I would say that diet, exercise, and stress/sleep are the three things that people not only in their 50s, but adversely every age could begin with as far as their longevity path.

Dr. Z: Absolutely. We emphasize those basic foundations, and what we do at AgelessRx we’re kind of assuming everyone has got the foundations down, and we’re providing value on top of that, kind of extra layers of protection. Now, you mentioned back in 1992 you read that article on human growth hormone. Since then, what is the most impactful evidence you’ve seen in humans that gives you hope that aging can be slowed down or even reversed?

Dr. Grossman: Well I think, a few years after growth hormone was being used not just to help children to grow more quickly so they didn’t end up very very short, that was its original FDA approved purpose, it was being taken by healthy people to avoid aging, they found out that maybe it wasn’t the greatest thing in the world. It might promote, not necessarily cause, cancer, but if people had cancer, it might make it grow faster. So the anti-aging movement moved away from that and began to look at some safer alternatives. Three that come to mind immediately for me: #1 Metformin. Metformin, the most popular diabetes drug in the world, has been found to mimic the effects of intermittent fasting or of calorie reduction. Calorie reduction where the animals in the experiments were given 30 or 40% less than their normal amount of calories were found to live 30-40% longer than the normally fed animals. Some humans decided to try to do that, but it’s extremely difficult to reduce your calories to that extent. The way that calorie restriction works is that it activates an enzyme called AMPK (adenosine monophosphate kinase). Metformin also operates by activating AMPK and they’ve done some studies where they’ve looked at aging genes and also genes that promote anti-aging, youthful genes, and intermittent fasting or calorie reduction will upregulate 200-250 of those genes. Metformin will upregulate 300 or 350, so it’s even more. I think that the best of all possible worlds is to combine the two. Take the Metformin and engage in some kind of calorie reduction, whether it’s time-restricted eating or intermittent fasting, or however you want to do it. I think both of those things are extremely valuable. Another anti-aging strategy that I like a lot is the use of hormone replacement, bioidentical hormones, and in particular one that has anti-aging benefits per se, it makes people feel younger, stronger and better is testosterone. Testosterone is now widely available in multiple formats, it’s available as pellets, it can be implanted under the skin, it lasts for several months, it can be taken as a cream or injections, and I think that has a lot of anti-aging benefits and it’s not a particularly expensive thing. Metformin is not particularly expensive, it’s available easily through AgelessRx. Testosterone would be something you need to see a local doctor about. Then, something I know AgelessRx has been doing a study on is Rapamycin. Rapamycin is a medication that’s been used for a number of years to prevent rejection of organs, like an organ transplant, when a patient gets a kidney from another donor, they need to take something so the body won’t reject it, so this anti-rejection drug would be something like Rapamycin. Interestingly, unlike an anti-rejection use where it needs to be taken every day, maybe taking it every 1-2 weeks, you can get some profound longevity benefits. In every single animal species it’s been tested in, Rapamycin’s been found to extend the longevity of those animals significantly, 20-30% or more. Those are three of the new things that I’ve heard over the years that I think are available to people today.

Dr. Z: To answer the question more directly, it sounds like the impactful evidence is the proof in the pudding so to speak, where you’ve deployed these therapies to your patient population and you’ve actually seen the aging process slow down, you’ve seen patients become healthier and more youthful, is that what you’d say?

Dr. Grossman: Absolutely. In fact with regards to Metformin, it’s been now used by so many people that it’s gotten the attention of the National Institute of Health. They’re currently running a study called TAME, the Trial to Assess Metformin and Aging, and I think it has 2,000-3,000 people. It’s a five year study, it’s funded to the tune of $77,000,000, and it will be unblinded in 2025. In 2025, my strongest guess is we’re going to find out how well Metformin works in changing some of these aging parameters, but there is increasing evidence. If you look up PubMed, The National Library of Medicine, there are any number of studies, literally in the hundreds, where Metformin is being used to prevent cancer, to slow down the aging process, things like that. Similarly, Rapamycin is coming into its own, and a number of studies are being published about that. There’s a lot of studies about testosterone; the overwhelming majority of them show positive benefits. There’ve been a few that suggest perhaps an increase in heart disease, but there are probably many more that suggest it prevents heart disease, and having in fact a lower testosterone level is more harmful than taking testosterone. We’re putting all this data that’s coming out together and finding out more and more all the time.

Dr. Z: That kind of gets me to the next question that was submitted. By the way, for those that are submitting questions by the chat, thank you very much. Some of them we may already be answering and so I may not go back for them, but I see some that I’ll add to the list here. But for another question that was pre-submitted, what are the best ways to measure a person’s longevity potential as well as their progress?

Dr. Grossman: That’s a good question, because just like you go to the doctor and they measure your blood pressure and your blood pressure is a little high, they’re going to do something whether it’s dietary, weight loss, exercise, or blood pressure medicine, and you may come back in a few weeks or months and check your blood pressure again. We need a yardstick and with anti-aging medicine, we need the same kind of yardstick as a blood pressure cuff. Well, luckily, there’s more and more ways of measuring the aging process, and I had mentioned previously that there are genes that are associated with youthfulness and there are genes that are associated with aging. We have the ability to find out which genes are turned on, and which genes are turned off. That’s a specialty of genomics that they refer to as epigenetics – which genes are on and which genes are off. Steve Horvath has been a main researcher in this field of epigenetics and has offered to the public some testing that can be done to see where you are on this aging scale. By looking at the genes that are turned on and looking at the genes that are turned off, we can get an epigenetic age. For instance, if a person is 48 and they’re living a healthy lifestyle and doing things properly, they may find that their biological age is several years younger than that. On the other hand, for any number of reasons including their genetics they were born with, or possibly high levels of stress, or not getting enough exercise, or not following a healthful diet, or God forbid smoking cigarettes, things like that – they might be older than their chronological age. This is the yardstick now (epigenetics) that we’re using by and large to determine how well a person is on the aging scale. Another one that’s being used is the length of the telomeres. The telomeres are the little end caps on the end of chromosomes to keep them from unraveling and every time a cell divides, a little bit of telomere comes off. Unfortunately, in my experience the laboratories that are doing measurements of telomere length don’t provide results that are consistent enough, at least for me, to have a lot of credibility. I find that one year I test somebody and they’re 10 years younger, next year they’ve done some good things and they’re 10 years older. It just seems as though telomere testing is all over the board, but I’m hopeful that in the next few years, more and more companies will enter this field and will have more accurate telomere testing.

Dr. Z: Great, thank you very much. I think you already answered this one, “What is the value of biological age testing?” How about this question, “How are gerotherapeutics aka longevity drugs, different from conventional therapeutics that are prescribed to treat disease?” Maybe to back up for the people that don’t know the term “gerotherapeutics”, can you define gerotherapeutics and talk about how they’re different than conventional therapeutics?

Dr. Grossman: The word gerotherapeutics or just therapeutic drugs, that root “gero” like geriatrics, refers to aging. Gerotherapeutics are drugs that will modify the aging process. I want to make a distinction between aging and getting older. Everybody gets older. We’re all 20, 30 minutes older than when this whole meeting started. But we haven’t necessarily aged over the last 20 or 30 minutes. For instance, if we already exercised this morning, and we didn’t eat breakfast, or we had a healthful breakfast, maybe we turned back the biological clock a little bit. That shows that it’s possible to get older without aging, and that’s what our goal is. That’s what the goal of gerotherapeutics are, to help us get older without aging. Now, what are the drugs that are gerotherapeutic drugs? As of today, there really aren’t any pharmaceutical drugs that have as their FDA-approved purpose, preventing aging or slowing down aging or stopping aging. What we’re doing instead is taking existing drugs and repurposing them. Among the drugs I mentioned previously, namely Metformin, it’s an FDA-approved drug for diabetes, we’re repurposing it to reduce the aging process, slow it down, and prevent cancer. Similarly, with Rapamycin we’re using it instead of its FDA-approved purpose to avoid rejection of organs, to slow down the aging process and also prevent cancer and improve immune function. It has a long list of benefits as well as its memory benefits as well. Testosterone is the same thing. Its FDA-approved purpose is to treat individuals with low, low levels of testosterone, called hypogonadism, but how about if you don’t have a really low level, but it’s low-ish or suboptimal? The idea being maybe being good isn’t good enough. You have a good level of testosterone, but how would you do and how would you feel and how would you age if you had an optimal level? That’s the idea of a little bit of a difference between conventional medicine and anti-aging medicine. In conventional medicine, the idea would be, “Well, we’re just going to treat it if it’s a disease.” If you have a low level, we’re going to give you testosterone for that. But in anti-aging medicine, a lot of doctors would say “Yeah, it’s in the normal range, but it’s on the low side, and I can see from your symptoms you’re not aging as well as you’d like, so why don’t we give it a try.” What we’re doing with gero drugs, gero-protective drugs, is repurposing existing pharmaceuticals for anti-aging purposes. We’re doing the same thing with non-drugs, with some nutrients, for instance fish oil, coenzyme Q10, and NAD+, there are any number of other supplements that people can take that will help with the aging process as well. We talked about diet, exercise, stress management, et cetera. We’ve now talked a little bit about some pharmaceutical drugs, but there are also some supplements that can be of some value as well.

Dr. Z: Okay, great. If I were to summarize, it sounds like conventional therapeutics are targeted to treating a disease, like waiting until you have an A1C above 6.4. Then you put somebody on a drug, like Metformin, in the hope of treating that disease. Where it sounds like with gerotherapeutics, you’re being more proactive with it, where you’re trying to prevent the disease or diseases in general and slow down the aging process, would that be accurate?

Dr. Grossman: That’s exactly right, Dr. Z, perfect.

Dr. Z: Perfect. A question from the audience here, because it fits here pretty well with what we’ve just talked about: a growing body of research suggests that the process of aging accelerates in the early 30s, but it’s steadily chugging along much earlier than that. For example, our skin is never as good as it was when we were a baby. When do you think it’s the right time to safely engage in gerotherapeutics to promote healthy aging? For example, what are some questions a person needs to ask themself when considering a drug like Metformin or Rapamycin or some of the other ones?

Dr. Grossman: That’s a very good question and I think we have some data that can actually give us a fairly precise and specific answer. It’s interesting that you said mid-30s because I think that’s the point. Why do I think that’s the point? A lot of the research into Rapamycin in particular is centered on an enzyme found naturally in the body called mTOR. The enzyme mTOR has been around for hundreds of millions of years, it’s an ancient enzyme in the body, and it has an interesting effect because up until 30-35 years of age, it helps people to grow, to mature, to get stronger, to get healthier. Then around 30-35, it changes and it starts to destroy our health. It makes our lungs get smaller so we can’t run as fast, our hearts get smaller, our vision is not as clear, our hearing isn’t as good. All of these things we associate with the aging process seem to begin for most people in their mid 30s. That I think is the reasonable age for people to start looking at gerotherapeutics. If you’re in your 20s, I think that non-drug therapies are appropriate because you’ve got mTOR working in your favor, your hormones are typically high. Although honestly I’ve found both men and women in their 20s that have low hormone levels and are helped by hormone replacement, by identical hormone replacement, but other than that, just some supplements, diet and exercise, and stress control, good sleep, etc. will take care of things until your 30s. Then by mid 30s, maybe then it’s time to start looking at things like Metformin in particular, and maybe a little bit after that Rapamycin, etc.

Dr. Z: I definitely agree that our stance at AgelessRx is that the age kind of depends on the therapy. Metformin is widely used for PCOS, which is a female fertility issue, so maybe it is appropriate for some patients to start taking it in their 20s or 30s. But Rapamycin for example, you were mentioning mTOR being important early on, but you don’t want it to be as active when you get older so maybe waiting until you’re in your 40s or 50s to take it. I think that’s very much in line with what we’ve been hearing from other experts as well, so thank you for taking the time to explain that. Another question here, going back to testosterone for a minute, I don’t think you’ve covered this one yet – is testosterone supplementation only appropriate for male-sexed individuals as a longevity treatment or does it have value for both?

Dr. Grossman: That’s a great question, and I think the reason that we ask that question is because testosterone is only FDA-approved for use in men. But then again, Metformin is only FDA-approved for use in diabetics. We’re repurposing these drugs for non-FDA approved purposes which is completely legal, completely ethical. A doctor is able to prescribe a drug for a non-FDA approved purpose as long as that patient understands that it’s non-FDA approved and that there’s evidence that it’s safe and effective. In the case of testosterone, even though it’s not FDA-approved for use in women, honestly it’s fantastic for use in women, and when I prescribe testosterone to women, I think they like how they feel better than men do with testosterone replacement. I think that it’s important for women to have their testosterone levels measured, and honestly I see women in their 20s and 30s very commonly with low testosterone levels and they take some form of replacement therapy and they feel better, they just generally feel better. They age more slowly. Testosterone helps prevent osteoporosis in both men and women, but because women are more predisposed to osteoporosis and bone loss, I think testosterone is an important therapy, so no. Testosterone is not just for men, it’s for both men and women.

Dr. Z: Great, thank you. Another question from the audience, specifically about Rapamycin and Metformin, do you have patients taking both at the same time? What are the pros of that? What are the cons of that? How have your patients, for those that you’ve prescribed them together, how have patients responded to that?

Dr. Grossman: I do prescribe them together almost always, if I’m going to use one, I’m going to use the other. I think they work like – Metformin works on AMPK, and Rapamycin works on mTOR, and both of those after the age of 35 in the case of mTOR, harmful towards people as far as living longer and staying young longer. Therefore we want to approach it from different angles. When we go to war, and I regard aging as the enemy, and I want to go to war with that enemy, I’m not going to use just the artillery, I’m going to bring in the tanks and the Navy and the Air Force. We’re going to attack the aging process with every tool that we have. I think that it’s a smart idea to take Rapamycin and Metformin together. Interestingly, I saw a study recently where Rapamycin and Metformin were used together to both prevent and treat pancreatic cancer, which is one of our most serious cancers. Using these I think is both additive and synergistic.

Dr. Z: You don’t see any downside, for example, too much inhibition of mTOR? There’s this thought Metformin might have a slight inhibition of mTOR. Have you ever noticed anyone taking a combination reporting more side effects or any other potential issues you’ve noticed?

Dr. Grossman: No, I really haven’t. I think they get along with one another quite well. While we’re on the mTOR topic, there’s two kinds of mTOR. There’s probably more than two, but there’s two main types. mTOR1, which is our enemy after our mid-30s, and mTOR2 which is our good friend throughout life. We want to inhibit mTOR1 and leave mTOR2 largely alone. Interestingly, Rapamycin does a great job of that–it inhibits mTOR1 but largely leaves mTOR2 alone.

Dr. Z: We kind of touched on this next question a little bit when we talked about adding Metformin to intermittent fasting, but this is kind of more broad. What is the unique value of drugs such as Metformin or Rapamycin compared to lifestyle changes promoting longevity? In other words, can somebody just exercise and diet their way to longevity?

Dr. Grossman: Yes, I mean my grandfather, for instance, lived to be 105. He didn’t take Metformin. He died before we knew that Metformin had any value in anti-aging. It is possible for people to live past the age of 100 just with their lifestyle choices. He ate healthfully, he exercised regularly, he never smoked. Things like that. Now, could he have lived to be 120 if he took Metformin and did some other stuff? Unfortunately, that’s not a question we can answer. My feeling is yes, you can get a lot of longevity benefits from your lifestyle choices, but I think you can get additive benefits from using both supplements and pharmaceuticals. Let’s say for instance someone would prefer not to take pharmaceutical drugs, like they don’t want to take Metformin. We have natural alternatives. For example, there’s one called berberine that also helps regulate AMPK, so that would be a good one to do as well. We have natural alternatives, we have lifestyle alternatives, we have medications and I think they can all work together with one another.

Dr. Z: I don’t want to delve too far down the rabbit hole of berberine versus Metformin, we get that question quite often, but now that you brought it up–yes, berberine does have some overlaps with Metformin. In fact, berberine does some things that Metformin doesn’t, for example, reduce ApoB and LDL levels because it’s thought to be a natural PCSK9, but not as much is known about berberine in term of it AMP kinase and some of the other benefits that you get from Metformin. I know early on when we were starting AgelessRx, people said “Why can’t I just take berberine?” but I think there is some overlap between berberine and Metformin and I don’t think it’s enough overlap. In fact, I take both. For people who it’s appropriate, I recommend taking both as well. It’s not an either or in this case, I think there’s plenty of benefit in taking both. Let’s see, just real quick someone was asking why AgelessRx doesn’t offer testosterone. I’ll answer this one. As Dr. Grossman alluded to earlier, testosterone is a controlled substance and tightly regulated by various different regulatory bodies. As much as we’d like to offer it, it’s not practical, especially with the expiration of some of the COVID easements on controlled substances. We don’t plan to offer any testosterone replacements, it’s just not feasible. We’re looking at other ways to optimize testosterone levels, but not directly, but that’s something we’re actively studying. Unfortunately, sorry, not anytime soon, not as long as testosterone remains a controlled substance. Let’s talk about trade offs. There’s two questions that were posed and are very similar. Have you noticed any downsides from using Metformin as a gerotherapeutic agent? If so, do you think that all longevity therapies have a trade off of some sort? Are there potentially some that have a bigger trade off than others? Can you comment a little bit on that?

Dr. Grossman: Sure. I don’t care what it is, everything has got a downside. I used to believe that there was nothing better to drink than water than green tea. I thought green tea was a wonderful thing to drink, it’s filled with all these antioxidants. Then I found out that green tea is filled with some heavy metal toxins. It’s just the way the leaves take it up. The bottom line is that there’s no free ride in this world. Nothing’s perfect. Metformin is not perfect either. Are the downsides to it about 10-20% of people seem to be intolerant of it largely due to gastrointestinal problems, that can be mitigated by beginning slowly, tapering up slowly, taking the extended release formulations, but even so, maybe 1 in 10 or maybe 1 in 5 just can’t take it because of that. There also seems to be some interference with benefits of exercise. If you take Metformin – I try to personally take Metformin at bedtime so it’s not going to interfere with any of these exercise benefits I’ll get. That applies to everything, I don’t care what it is, whether it’s vitamin C or anything that you take. You take too much vitamin C you get diarrhea. Even though these are good things, they can have downsides.

Dr. Z: The exercise issue with Metformin tends to be a recurring topic that we get. We’ll probably find a similar issue with Rapamycin and maybe other gerotherapeutics. Like you said, there’s no such thing as a free lunch, there might be some tradeoffs. It seems like one of the tradeoffs with Metformin and probably even Rapamycin is the ability to bulk up your muscles. I think the kind of mechanism of action of Metformin and potentially Rapamycin because it has the effect on AMP kinase and it has the effect on mTOR and those are kind of required to bulk up on muscle that’s potentially a trade off. What I tell patients is, if you’re working out for a Mr. Universe or something like that, trying to bulk up for something like a competition, to look good for the beach or something like that, I usually tell people to skip Metformin during that time, or potentially Rapamycin. That’s something that comes up. If you look at the studies, the strength seems to be – even though you don’t bulk up as much, you still seem to have the same amount of strength. It’s not complete – it’s not like it makes muscle weaker, it just doesn’t provide that physical bulking. David Sinclair calls it, or is it Nir Barzilai, talked about vanity things like if vanity’s important to you, if looking bulky is important to you, don’t take Metformin. Let’s move on.

Dr. Z: Let’s talk a little bit about supplements. We talked a lot about Metformin, Rapamycin, and some others – what are some of your favorite supplements and why?

Dr. Grossman: I think that there are a few nutritional supplements that everybody should take. #1 is a multiple vitamin mineral. The reason I think that is maybe our grandparents didn’t need to do that because food was grown locally and it was largely grown organically with manure and compost. Nowadays, they use a lot of agro farming with artificial pesticides and fertilizers. It’s harvested prematurely when it hasn’t really come to its full nutritional value. There are a lot of reasons that food today isn’t as nutritious as food before, which is to say, it doesn’t have the same vitamin and mineral content. For that reason, I think people say, “Well if I eat a healthy diet, do I really need to take a multiple vitamin mineral?” I think that you do unless you’re able to eat all organic and you can source whatever it is that you’re getting, but for most of us that’s difficult to do, and a multiple vitamin is an inexpensive way to do that. What do vitamins and minerals do? Every enzyme in the body, all of the chemical processes that occur in the body, are done by enzymes. Enzymes when they’re made in the body, they come as pre-enzymes ready to work. And they need two keys, like the safety deposit box that you go to, you need the key that you have and the key that the banker has, and you use them together and it unlocks the box. It’s the same way for these enzymes. You need a vitamin and a mineral. Whether it’s vitamin B2 or it’s vitamin B6 or vitamin C as your vitamin, and whether it’s magnesium or cobalt as your mineral, and then the two of those things will unlock the enzymes. By taking that multiple vitamin every day, you make sure that your enzymes are at optimal purpose. Second, vitamin D. Vitamin D is a fat-soluble vitamin and it’s easy to measure the water soluble vitamins like vitamin C and B vitamins, because they’re water soluble, their levels go up and down all the time. Whereas the fat soluble vitamins are more consistent. We measure vitamin D levels, and honestly most people, and most people means 90% of people that I see, they have suboptimal levels of vitamin D. Even the range that’s given by conventional medicine is 30-100. That’s the units that they use for vitamin D. There are a lot of people that are below 30, but then there are a lot of people that are 30, 35, 40 that once again, like testosterone, it’s normal, but suboptimal. I, by the way, regard optimal at 70-80 and many doctors have somewhat different feelings, but a lot of people in the anti-aging field feel 70-80 is a good number to shoot for. Taking some extra vitamin D. How do we get vitamin D? It’s not really available in our diet. You get it when sunlight, UV light hits your skin and then it converts cholesterol into vitamin D for you. The problem is, that people don’t want to get skin cancer, so we use sunscreen and when we use sunscreen, it blocks those UV rays and you don’t form your own vitamin D. For many of us, we need to take supplemental vitamin D and then get your blood checked to make sure you get your level up to 70-80, and I think that’s a really good one. I think that some type of either fish or flax oil – you have omega-3 fats and omega-6 fats. Omega-6 fats are the things that are in vegetable oils, like canola oil and avocado oil. They tend to be inflammatory, by the way. Omega-3s tend to be anti-inflammatory and most of us have an adverse ratio. We have more of the inflammatory than the anti-inflammatory fats in our body, so by taking either flax or fish oil, we increase the anti-inflammatory fats in our body. Then I would say the fourth supplement I would take is coenzyme Q10. CoQ10 is a co-factor in energy production. It helps the body make more ATP, more energy, so I like that one. I could go on and on about NAD+ and many other supplements, but those four that I mentioned, they’re several that are cheap, safe, and I think that most people will find that their health improves by taking them.

Dr. Z: Sorry, I’m chuckling to myself a little bit because I’m like, “Those are boring Dr. Grossman!” People want to hear about AKG and resveratrol–I’m just joking. It goes back to the whole thing about diet and exercise. Yes, sometimes it’s boring to talk about diet and exercise, but you have to master the fundamentals first before adding some of the more exotic supplements like AKG, resveratrol, and pterostilbene, spermidine. Of those more gerotherapeutic-like supplements, do you have any favorites among those?

Dr. Grossman: Yeah, you’ve named them with that list. Resveratrol, which is a red wine extract, is a lot of what David Sinclair has done his research on. NAD+, which I think is one of the most popular supplements in the country right now, is also one that David Sinclair has done a lot of research on. It produces energy, helps the body produce more energy, it improves so many different things. There are several in that ilk that are very good for people to take as well.

Dr. Z: There’s a question about cycling. When taking gerotherapeutics such as Metformin or Rapamycin, what are your thoughts on doing so intermittently or cycling them or do you have a particular regimen that you’ve found more beneficial than others?

Dr. Grossman: I don’t have a hard and fast rule, but I do like the idea of stopping things periodically. Every once in a while, I take a day off from my supplements, I don’t take any of them.

Dr. Z: That’s Sunday for me. I just get sick of taking supplements, so you know what? Sunday’s my day off.

Dr. Grossman: Yeah. Whether it’s you just get sick of taking them, or you just want to give your body a chance to do its own thing I think that that’s okay. I actually think it’s a good thing to do. The same thing applies to testosterone. We have people on testosterone, maybe every six months that take two weeks off, things like that. With most of these things, whether it’s Metformin or Rapamycin or whatever, give your body a break periodically, just to kind of reset the clock. Now, do I have any hard and fast scientific evidence that this is a good thing? No, I don’t. It’s just what I do. I don’t know the answer to that question, it’s just what I’ve always done for the past 45 years. I don’t know, but I don’t think there’s anything wrong with that. Someone had asked previously, and you had mentioned Acarbose, and I think that’s a very interesting medicine to talk about. Would you agree?

Dr. Z: Yeah, absolutely. Can you briefly describe what Acarbose is? It’s an oldie, but coming back in fashion here. What’s your opinion on intermittent use of Acarbose versus using it with every meal?

Dr. Grossman: Just like the other drugs we talked about, Metformin for diabetes, Rapamycin for anti-rejection, Acarbose is another diabetes drug and the way that it works is it’s a starch-blocker. Starch is a collection of sugar/glucose atoms, just glucose, glucose, glucose, glucose. These big bushes and trees of them, and we have enzymes in our body that slice it up and free the glucose. When you eat starch, say a white potato or a piece of bread or some pasta, it’s very easy for the body to slice those glucose molecules off, and you get a rush of glucose in your bloodstream. Your blood sugar goes up, your insulin goes up. Those aren’t necessarily the most healthful things to have happen. Acarbose blocks that from happening. Now that we have these CGMs, people can wear them and find out, “You know, if I have a piece of bread, I’m at an Italian restaurant and they have some wonderful bread, I have some and I ate it, oh my goodness, my blood sugar goes up. If I dip that bread in olive oil, the oil is going to slow down the release and the digestion of the bread, and my blood sugar doesn’t go up as much. When I have a plate of pasta, my blood sugar goes up like crazy.” Well, put some olive oil on it, but also consider taking some Acarbose with these high-starch meals. What we do then is reduce the speed with which the sugars release in the bloodstream, which is called the glycemic index. Should we do it continuously or intermittently? Obviously from my point of view, we should do it intermittently. It doesn’t have any value to take if you’re having a meal that has no starch or carbs in it. If you have a salad for lunch, which really doesn’t have any carbs to speak of, or few but not enough that you want to block their digestion, then I’d say don’t bother. But if you have protein and vegetables, probably not going to be an issue for you. But if you have some of these high-starch foods, whether it’s corn or cereals or rice or bread or pasta, then I would think that Acarbose is a good idea to take. You’ll get more information from one person, one food might make their sugar go up, for another person something else, that’s where the continuous glucose monitors are so valuable to give individuals the data they need about their personal metabolism.

Dr. Z: Great. I think that’s about all the time we have right now. There were a couple more questions about emerging research, about the hallmarks of aging, about LDN, I think we’ll have to keep those for another time. This is just our first one so hopefully we’ll have many more. Any closing thoughts or anything else we didn’t get a chance to talk about that you think people should know about? Any parting words on this Friday afternoon?

Dr. Grossman: Well, when we began I talked about stress and sleep being such an issue, and we didn’t really mention it since then. I think that we should each take away how important it is that we get our stress levels under control by whatever mechanism we can, and with that thought in mind, I want to wish everyone a really relaxing and fun-filled weekend.

Dr. Z: Alright, thank you very much everybody for joining us. At least here in Michigan, it’s nice weather, I hope everyone else enjoys their weekend.