Cracking the Longevity Code with Dr. Michael Roizen: Rational Wellness Podcast 296

Dr. Michael Roizen discusses Cracking the Longevity Code with Dr. Ben Weitz.

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Podcast Highlights

3:55  The reason Dr. Roizen decided to write this The Great Age Reboot book is that the science related to longevity since he wrote his first book on longevity, Realage: Are You As Young As You Can Be?  has changed enough that the potential to not only slow aging but to reverse it is close.  Dr. Roizen describes 14 different areas of research that are looking at different mechanisms for reversing aging.

8:55  Yamanaka Factors.  Six labs have now shown that using all 4 or 3 of the 4 Yamanaka factors are able to reverse aging in mice or other animals.  The most recent study was conducted and published in Cell by Dr. David Sinclair’s Lab at Harvard University: Loss of epigenetic information as a cause of mammalian aging. 

18:48  Yamanaka moved to the Gladstone in San Francisco and they are using a quantum computer to look at the 1,363 drugs that were already approved by the FDA that are generic, meaning $4 per month or less, and they looked at which ones might block the attachment of amyloid and tau to neurons and they found that a diuretic, Bumetadine, blocked the attachment by 70% in cell culture.  We might be able to prevent dementia for $4 per month.

23:33  Brown fat. Mike West was one of the people who worked on the epigenetics of using the Yamanaka factors found that we could regress white fat to pluripotent fat and then turn it into brown fat.  Brown fat is around our organs and it generates heat to keep us warm and it uses a lot of calories.  11 minutes a week of cold exposure will stimulate this metabolically active brown fat.

26:48  Stem Cells.  Stem cells hold out hope in the future but you need to have between 30 and 50 million stem cells plus growth factors plus exosomes.  You need to take a bone marrow sample from your iliac crest and grow it in culture till you get to 20-50 million and then inject it back in along with the growth factors. Japan is now testing mass produced stem cells for use in heart failure patients. 

29:20  Regenerative Plasma Exchange. You go in and donate blood and you get your red cells back after they are washed along with some fresh albumin and this reversed dementia as we have seen in the AMBAR studies (Alzheimer’s Management by Albumin Replacement): Therapeutic plasma exchange with albumin: a new approach to treat Alzheimer’s disease

37:18  TMAO.  TMAO is a biomarker for inflammation that is found in the blood that is correlated with heart disease risk.  If you consume the combination of carnitine, lecithin, choline and saturated fat, you change the genome and turn on the genes in the bacteria inside your gut to produce a compound, trimethylamine. If you take L-carnitine pills without saturated fat, then that is not a problem.  If you regularly consume saturated fat, it will change your microbiome, so that the bacteria in your gut produce trimethylamine oxide out of the trimethylamine and this is very inflammatory.  Having some TMAO in your blood from fresh fish is not a problem, since this is a short term situation, as compared to your gut bacteria regularly producing TMAO.



Dr. Michael Roizen is the Emeritus Chief Wellness Officer at the Cleveland Clinic, a professor at the Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, and author of four #1 New York Times best-selling books and 9 top 10 books.  Several of these books he cowrote with Dr. Oz.  He has written more than 190 peer-reviewed scientific articles and has been recognized with an Elle, an Emmy, and the Paul G. Rogers Award from the National Library of Medicine for Best Medical Communicator.  And now we will be talking about his newest book, The Great Age Reboot: Cracking the Longevity Code for a Younger Tomorrow.  Dr. Roizen’s website is GreatAgeReboot.com.

Dr. Ben Weitz is available for Functional Nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss and also athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.



Podcast Transcript

Dr. Weitz:            This is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting edge health information. Subscribe to the Rational Wellness Podcast for weekly updates, and to learn more, check out my website, drweitz.com. Thanks for joining me and let’s jump into the podcast. Hello, Rational Wellness Podcasters, thank you so much for joining me again today. Today we’re here with Dr. Michael Roizen about his new book, The Great Age Reboot. Dr. Michael Roizen is the Emeritus Chief Wellness Officer at the Cleveland Clinic, a professor at the Cleveland Clinic Lerner College of Medicine and author of five number one bestselling books and a total of like 22 books.  I understand several of these books he co-wrote with Dr. Oz. He’s written close to 200 peer review scientific articles. And today we’re going to be talking about his newest book, which is The Great Age Reboot: Cracking the Longevity Code for a Younger Tomorrow. In this book, Dr. Roizen, who co-wrote it with economist Peter Linneman and demographer Albert Ratner, he discusses all this new scientific and medical breakthroughs like stem cells, gene editing, and being able to 3D print new organs that will not only enable us to live longer, so that living to be 120 years old will become increasingly common, but also to reduce our rate of biological aging so that we live younger. Dr. Roizen writes that 90 will be the next 40. Dr. Roizen, thanks so much for joining us.

Dr. Roizen:          Thank you, Ben, for letting me come on. It’s a privilege.

Dr. Weitz:            Absolutely. So before we get into the book, since the focus of my podcast is on functional medicine, I’d be curious to get an update on where the Cleveland Functional Medicine Clinic is. I recall being at a Jeffrey Bland seminar maybe like 10 years ago when Mark Hyman announced that he was going to be opening the first functional medicine clinic within a major medical center.

Dr. Roizen:          It’s thriving. It’s actually in four locations now. The main campus it’s doing well. Mark has returned, he’s basically a part-time consultant here now, and so he’s returned back to his Lennox Hill roots. It’s Lennox, Massachusetts that is, Hill roots. It runs very well and is still thriving.

Dr. Weitz:            That’s great.

Dr. Roizen:          I share some space with other people there on Thursdays in our wellness and integrated medicine center, which I showed you a picture of the snow here, winter setting, but it is in Cleveland, and so it showed you the picture of the beautiful, it’s gorgeous here today, but it has a white background in the gorgeousness. But the wellness center is out in Lindhurst, which is about seven miles from our main downtown campus.

Dr. Weitz:            So Doc, given your long career and accomplishments and all the books and papers you’ve written, why did you feel compelled to write this book? I just wanted to say, I guess it’s easier than trying to run for the Senate. Just kidding.

Dr. Roizen:          Much easier than that. But the only reason you write a book, at least in my case, the only reason I write a book is because the science has changed enough that you want to help people plan for and motivate them to plan for the future. In this case, what has happened is when we wrote the first book, Realage: Are You As Young As You Can Be? We predicted that 60 would be the new 40, because of the slowing you could do in your rate of aging. That’s come true. Nurses health study, our own data at the Cleveland Clinic for our own employees by motivating them to get healthier, that’s come true. But now it is likely not that we’re going to just be able to slow aging, but reverse it. That is there are 14 mechanisms that we go over in the book that look at the research into the basic mechanism of aging.  Research, there are 14 areas that have rebooted at least two animal species, and by rebooted I mean turned back the clock, not just slowed the clock. That is likely to happen. We think with 14 shots on goal, they’re at least an 80% chance that we humans get rebooted. That changes everything. In other words, if you heard in the last couple days, China’s population had decreased, the Japan prime minister said they could no longer function as a society because of the dearth of births. The France individuals protested the increase in the century retirement age from 62 to 64. And the point is the age of 65 in the US as a retirement age was really motivated by a German general in 1858 who said, I want to motivate my employees. Their morale is low. I want to give them a retirement age. What’s the oldest person lived to?   And the oldest soldier who had lived at that time in his regimen to 64. So he said, let’s make 65 the retirement age, to increase morale. And it’s stuck since 1858. We’ve had the same retirement age essentially.

Dr. Weitz:            Interesting.

Dr. Roizen:          But now we’re going to be, if you’re going to live to 115, which is what the prediction is with one reboot, and it’s going to be as a younger person. It takes a real emotional change. That’s really why we wrote the book, to help people understand the emotional change and plan for it. If you’re going to live to 115, you’re not going to want to retire at 65 and do nothing for 50 years. We expect that people will work, they’re going to live an extra 30 years, they’re going to work an extra 20 years, they’ll still have plenty of time for retirement. But that takes an emotional and a thought process and a planning for it both fiscally and physically to plan for it. And so we go through, and that’s why there’s an economist as a co-author, what happens to the economy and it actually is wonderful if we do this right and what happens, in other words, human capital is the ultimate wealth of nations, the ultimate wealth of ourselves as individuals.  If we live, if we’re going to work instead of 40 years, 60 years, we increase our GDP and the amount each of us has as disposable income by about 50%, that gives us an enormous range of extra experiences, extra things that we can use and do and benefit from. To give you the example, if you put 3% of a minimum wage, $15 per hour income away, starting at age 25 and you work to 65, you have about $250,000, assuming it aggregates at about 4% in increase per year. But if you work to 95, it’s 1.4 million. And if your employer matches it, it’s 2.8 million. So the point is this is a tremendous ability to improve society and to improve the quality of every one of our lives if we plan for it.

Dr. Weitz:            If we plan for it. There’s a number of scientific, medical, technological developments that you mentioned in the book. Stem cells, senolytics, autophagy, gene editing. One of the ones that’s been in the news recently was the Yamanaka factors, which were utilized by David Sinclair’s lab where they just recently published a study in cell that they were able to reverse the aging in mice. Maybe you can comment on that concept.

Dr. Roizen:          Actually they’re the sixth lab that is able to do this.

Dr. Weitz:            Is that right?

Dr. Roizen:          We shouldn’t say, that’s the sixth different lab.

Dr. Weitz:            Oh wow. Okay.

Dr. Roizen:          So there’s a private company outside of Davis that did it.

Dr. Weitz:            Okay.

Dr. Roizen:          A group at MIT in Harvard, independent of David Sinclair did it as well about four years ago. George Church’s lab. A group in Switzerland has done it. A group at Hopkins repeated that. And a group at Calico, which is the moonshot group of Google, published a paper I think in February of last year on it using three of the four Yamanaka factors. In other words, there are four factors in-

Dr. Weitz:            Can you explain what those are?

Dr. Roizen:          Yeah. Yamanaka was a Japanese scientist. He’s now at the Gladstone in San Francisco, but was a Japanese scientist who did 12 million elimination and comparisons with gene editing, turning on and off different genes. So part of this started with the human genome project. We expected to find 300,000 genes. Only 22,000 were found. Only 1500 are on at any one time. The rest of the DNA, initially called junk DNA led to be epigenes or switches. And by turning on those switches to the three of the four, the one that didn’t, I’ll code as c-myc, MYC, but therefore are genes. If you turn on those three and not the c-myc of the Yamanaka factors, the mouse or rat or dog, in the case of George Church’s lab at Harvard becomes younger without losing mental facilities, the organs become younger and they live in the mice’s case someplace between 30 and 80% longer.

Dr. Weitz:            Wow. That’s amazing.

Dr. Roizen:          They live as a younger mouse, and if you don’t turn on the c-myc, if you don’t turn on only the three, they don’t develop cancer at any greater rate than the normal mice would develop cancer. So the point is, by turning on all four, the problem was when Yamanaka did this, not only he got the animals to be younger, but they developed cancer and didn’t live any longer. In fact they lived shorter. But by turning on only three of them, you reboot your epigenes. These are genes that correct the DNA abnormalities that we have acquired from the environment and from the sun and from our own choices as we’ve gone along. So you’re rebooting to your original factory settings. And by doing that, and again, David Sinclair’s lab was the sixth as far as I can tell, with the Yamanaka factors of being able to reboot mice or other animals species to a younger age.

Dr. Weitz:            That’s interesting. How long do you think they are before they start experimenting with humans?

Dr. Roizen:          I understand they’ve already started.

Dr. Weitz:            Interesting.

Dr. Roizen:          Not in the United States because the regulations are a little too tough. But remember, other countries, as I said, Japan already has a declining population. They’ve gone from I think 128 million in 2017 to 125 million last year due to deaths greater than births. And so that’s why their prime minister came out and said this past week that if they don’t change this, if they don’t have more workers, their society won’t function. China reported a decline in population and the whole world has not enough young children so that we need living longer to be able to survive as societies. So we understand this has already started in some other countries.

Dr. Weitz:            It’s interesting all these developed countries have lower birth rates, that they have less kids as they get more developed. This is a problem in many countries.

Dr. Roizen:          Well, it’s in every developed country. You can’t find, in other words replacement is 2.1, and without immigration every one of the developed countries, that is the G7, the G20, whatever you want to go to on the limits and until you get to Africa and India, those are the only two societal areas where in fact the replacement rate is now still greater than 2.1. In the US we’re at 1.4, which is the lowest we’ve been including lower than the Great Depression. And without immigration we’d be declining too. We still have a society where people want to come here. But every one of the Koreas at 1.4. Japan I saw. In China are at 1.2. Russia is at 1.1.

Dr. Weitz:            It’s interesting. You’re making a really good point. I think a lot of people don’t realize that without a growing population, your GDP is going to shrink, your economy’s going to shrink. So it’s an argument for people who are in favor of more immigration, more sensible immigration. And I noticed-

Dr. Roizen:          And just to make the point, GDP equals population times productivity. It’s a very simple formula. If our population, which has been increasing at around 10% per decade until this last decade, this last decade we were at 7.2%, which is the lowest since the Great Depression, which was 7.4. The congressional budget office predicts even with immigration, we’re going to be at 3%. But they don’t take into account the increased longevity. Longevity, living longer and younger is the solution to the problem, not the cause of the problem. So I want to get people, if we do it, this is going to help America and help the world greatly.

Dr. Weitz:            Which is great because I think the common sense thought is we’re going to have more people collecting social security and Medicare for longer and therefore it’s going to drain the system.

Dr. Roizen:          Right. I’m 77 now. I’ve been paying into social security since age about 22 I think. If you will, we need to extend the years when you can collect it slowly, but there’ll be enough money in it. So because I keep paying in, right? The trust fund keeps getting more money from me. That’s the whole point, is if we do this right, if we have a rational plan, Simpson-Bowles had it, but it didn’t get out of, if you will, didn’t get a vote out of the Senate. And that was a bipartisan plan to gradually increase this concurrent with about half of the medical gain in life expectancy. So you’ve heard life expectancy is decreasing in the United States, that’s what we call the war. That’s period life expectancy is if you were born. But life expectancy at any age, what we say cohort. So if you’re 65, your life expectancy was about 15 years, about 20 years ago.  It’s now 18 years. Our cohort life expectancy has continued to increase so that the average 65 year old actually, who’s a male, is expected to live to 84. So now and female about 87. We keep extending that cohort life expectancy. That’s a great thing because it also means we have less disability. The key will be to do what we have in the last part of the book, which is how you can slow your rate of aging while you’re waiting for this. This is going to happen. As I said, each one of these 14 areas is moving into human testing. I’ll give you one of my favorites in a second. But each one of these is moving into human testing, which means sometime in the next 10 years we’re likely to have that breakthrough and it’s going to be probably be inexpensive enough. And I’ll give you that example, for us to do it for all of us.

                                And let me give you the example. I told you Yamanaka had moved to the Gladstone in San Francisco. Well, they’ve done a lot of excellent research on aging. Now they used to be focused on cardiovascular disease, but they’ve figured out how and said, we can postpone that cardiovascular disease essentially if people do what’s right in lifestyle changes. And so it’s nonexistent. It kills 40% of the people, but it doesn’t have to kill anyone is what they’ve said. Because we’ve got things that lower blood pressure, that reduce your LDL cholesterol, that reduce inflammation. We’ve got treatments, if you will, or lifestyle choices you can make. So it shouldn’t be the cardiovascular disease. So they went to the basic mechanism of aging, and that’s why Yamanaka is there now.  And they actually, using a quantum computer, looked at all 1,363 drugs that had been at that time last year approved by the FDA and were generic, meaning $4 a month or less. And they said, which ones block the attachment of amyloid and tau to neurons?  So that is there any that do that, so that we can block dementia? And they found that a $4 a month water pill, a pill that’s a diuretic. It’s largely been replaced by Lasix or Furosemide now, Bumetanide or Bumex blocked the attachment by at least 70% in cell culture. They did it computer first. They then did it and showed it did in cell culture. They went into a mouse model of Alzheimer’s and it blocked the development of Alzheimer’s by more than 70%.  They then went and used two databases, large databases, one from UC San Francisco, had 1.3 million people in it. One with the help of the Cleveland Clinic that had 3.8 million people in it. And they found that those people taking that water pill had a 70 and a 72% reduced rate of dementia compared to those people who were taking other water pills like Hydrochlorothiazide or Lasix. So now they’re doing a randomized study. How expensive would it be to prevent dementia if this really works? $4 a month.

Dr. Weitz:            I don’t know. I’m kind of skeptical that a water pill is actually going to prevent dementia. I think making life style changes-

Dr. Roizen:          Remember it isn’t because it’s a water pill, it’s because it has a side effect of its quaternary structure and blocks the attachment of amyloid or tau to neurons. So it’s the side effect that they found, not the main effect.

Dr. Weitz:            Of course once we get to the root cause, which is inflammation, which is related to diet and lifestyle, that’s really where I think the biggest gains are going to be. Because we have drugs that will remove amyloid and they don’t really reverse it-

Dr. Roizen:          The reason, remember what amyloid does when amyloid and tau attach their waste products of the neurons, and when they attach that’s what stimulates the inflammation that destroys the neurons.

Dr. Weitz:            Well, they’re also-

Dr. Roizen:          They are blocking the attachment, they’re preventing, they’re doing one step before the inflammation.

Dr. Weitz:            Right. But aren’t they protecting the neurons from damage from the inflammation or the infections that occur?

Dr. Roizen:          Well, they’re preventing the initial cause of the inflammation. That’s right. The thing that would instigate the inflammation is what they’re stopping with this. Now, we don’t know that it’s going to work perspectively, but if you will, just to give you the example, the example is for $4 a month you would get something on a 26 greater effect, 26 fold greater effect at blocking amyloid and tau than you would by this, I think it’s a $28,000 pill that’s just been I think approved by the FDA, Biogen. It’s a much more potent and much less expensive way of treating you without the side effects that that monoclonal has.

Dr. Weitz:            Now you mentioned that that group found that we could prevent heart disease if we made the proper diet and lifestyle changes. The problem is, as a country we’re not doing a very good job of that and we’ve seen obesity rates go up, not down.

Dr. Roizen:          That’s exactly right. But one of the other things that, in fact Mike West who was one of the people who worked on the epigenetics of using the Yamanaka factors, Dr. West did, was he said, could we regress white fat to potent fat, mother fat and then turn it into brown fat? So we have brown fat when we’re born. Brown fat is around our vital organs. It generates heat, it’s brown because it’s got many more mitochondria, which generates the heat to keep us warm. But it uses calories as opposed to, and it comes from mother fat. But as we get older, we lose our brown fat and our fat becomes white fat. So Mike West said, could we regress white fat into mother fat and then turn it into brown fat. And he’s done that as have three other groups. You can do it now by just being exposed to the cold. So the group is-

Dr. Weitz:            All you need to do is go out in the snow in Cleveland.

Dr. Roizen:          The group had said 11 minutes of essentially shivering, a week, will activate your brown fat, go back to and use calories. But in fact, West did it by doing an epigenetic change by giving two treatments, if you will. One, to regress it to mother fat, one to turn it into brown fat. And in three species, mice, guinea pigs and sheep, it’s been done at various. Now you say, why did Clemson do it in sheep? Because sheep won’t stop eating either. They developed non-alcoholic fatty liver disease just like humans do in metabolic syndrome and stop producing wool or the quality of beef they normally produce. So from an economic standpoint they didn’t want the sheep to develop it, and they’ve been able to at least experimentally do this in sheep as well. So eliminated obesity may be on the table-

Dr. Weitz:            Well, it’d be nice to have more brown fat, but I don’t know how much good it’s going to be to have a bunch of brown fat if you’re shoveling in cheeseburgers and fries.

Dr. Roizen:          Well, no, that’s right. The new drugs, the Mounjaro and semaglutide seem to take away craving and maybe we may be able to get much less expensive versions of those to help people control craving. The side effect of those, I don’t know, I’ve got a couple patients who not only were obese, but were prior opioid addicts and they’ve said it’s taken away the cravings for opioids as well as alcohol for them too. We don’t know whether that’ll prove to be a real benefit, but if that’s true, we can solve a lot of problems with those.

Dr. Weitz:            You talk about stem cells in your book, and these have been a promising concept for a while, but so far the results haven’t really been there from what I’ve seen.

Dr. Roizen:          No, that’s exactly right. And that’s because the stem cell research patterns have been, what I would say is inappropriate, not done well. In order to replace an injury in for example, the heart or the brain or a cartilage, you need between 30 and 50 million stem cells plus growth factors. What’s typically been done in experiments is using an extract of blood platelet-rich plasma and growth factors. That gives you between five and 800 stem cells, not 20 to 50 million. And in order to get that much, you have to take out a bone marrow sample from your iliac crest, your bone near your thigh, and grow it in culture till you get 20 to 50 million and then inject it back with the growth factors.  Now, the growth factors in platelet-rich plasma and the exosomes, it may be the exosomes that are beneficial because they call for your natural stem cells. But to see the replacement, you’d need to grow this and to do it economically. For me to put it in my own in a culture and grow it is very expensive. But if I could give stem cells, knock out their immunogenicity and grow sheets of them so that I can take my stem cells and inject it to 100 people or someone else’s stem cells and inject it to 1,000 people because I mass produced these stem cells in culture, that makes it much more economic. That started in Japan last year and they’re now testing it with heart failure patients in Japan to inject 20 to 50 million on the heart where there’s no immunogenicity in these stem cells grown in these huge sheets in vats. That’s coming, but we’re not there yet.

Dr. Weitz:            Okay, that’s interesting. You also mentioned regenerative plasma exchange, and that’s where you donate plasma and then you get some younger plasma put in that was heated, to purify it, and that gets you fresh albumin. I did a podcast where I spoke to Dr David Hussey, who’s been using this on his patients.

Dr. Roizen:          The AMBAR studies are the real, very good study on this. Six centers, two in Spain, two in Chile, two in the US, University of Pittsburgh and Cleveland Clinic, where they dementia by nine donations of plasma. Literally you donate nine units of blood with the plasma, you get the red cells back after they’re washed. It’s not a very expensive process. People do it. We pay graduate students often to do it to get the albumin, and then they throw away, they actually in this case did four different groups. One group of which they threw away their plasma and gave them saline salt water, very inexpensive again. The group that got had no different results than the group that got the albumin or the albumin and the immunogenicity components.  And what they found was just these nine replacements reversed early dementia in every Alzheimer’s patient and has continued to, they published the data in 15 months. I’ve talked to them, they say it’s still improving cognitive function after 24 months, presumably because we take away old signaling proteins. This was nine donations. It wasn’t one, it was nine over a five month period, one per week from five weeks, and then one per month for the next four months. And then they followed them out to 15 months and they’ve now continued to follow them. Well, they’re now starting, that’s a phase 3A at the FDA. It’s got breakthrough designation because it reverses early dementia. And so they’re now doing a 3000 person hundred site center.  They’ve started, I think they’re about halfway through an enrollment of the 3000 patients. So in two or three years we’ll know whether that is the breakthrough. Again, not very expensive. We actually pay people to do this. The saline you get back, not very expensive. That is salt water you get back. This would be doable if the Bumex or Bumetanide treatment doesn’t pan out either. But that’s, one is prevention and the other is treatment of early dementia. But that’s AMBAR, A-M-B-A-R, if you want to look at it. And you can donate plasma now if you want.

Dr. Weitz:            We also have Dale Bredesen’s work showing that using a functional medicine approach that you can reverse Alzheimer’s in a number of patients as well.

Dr. Roizen:          The data on Bredesen’s work isn’t as convincing, hasn’t been published in a randomized controlled trial like it has for AMBAR. And so I want to see more data before, don’t get me wrong, I think a functional medicine approach is appropriate, that is getting at the cost. And I do think lifestyle changes make a difference. I don’t know that they can reverse it once it started, the way there was early 10 patients that he published-

Dr. Weitz:            Well, he did publish a study on 25 patients. It wasn’t randomized, but he does have a randomized trial underway right now.

Dr. Roizen:          In other words I think we’re going to see a lot of these breakthroughs over time. And I think whatever, with all these shots on goal, we’re likely to be able to live when we’re calendar age 90 as if we’re 40 again. So old age won’t be old. That’s the emotional change we have to get over to get more people, I believe, to do things to avoid disability, avoid obesity, avoid osteoarthritis, avoid heart disease and stroke, to do the basic things of getting their blood pressure, et cetera, under control. I think what, if you will, talking about is incredibly important so that we can prepare for it and take advantage of it.

Dr. Weitz:            You talk a lot about biological aging. What do you think about the new DNA methylation tests to measure biological aging?

Dr. Roizen:          We need a better test to measure aging. The problem with the methylation test is they’re not consistent and they change too quickly. What do I mean by that? By eating a McDonald’s meal today, you can be on methylation clock 28 years older than you were yesterday. Well, that’s not physiologic. You’re really not 20 years older or 28 years older by one meal. I think the methylation clocks, we need to refine them. We need a biomarker. This has been a good instigation for a biomarker. As of now we came up with real age based on your choices, your lifestyle choices and your biomarkers in 1993 to eight, that’s when we said that 60 was likely to be the new 40. And it’s come to pass.  It has a better receiver operating curve for disability and death. Independently verified that UC San Diego than anything, any other test, by a substantial amount. I think it’s going to end up being something like the choices combined with biomarkers. And we don’t know quite the right ratio to get the right formula. But I think, you pray that the epigenetic clocks, the methylation clocks would be better or that some combination of them would work. We haven’t seen the data that they’re accurate yet, a prediction of disability or death. [inaudible 00:36:17].

Dr. Weitz:            What about the telomere length, which has been around for a bit?

Dr. Roizen:          It’s the same problem. The first person, we were excited about that. We did it on a whole bunch of patients in our executive health practice. And the problem was the telomere on white cells versus some other cells or on different white cells or on cells from the spinal cord versus cells from the blood were so different as we didn’t know what to do with the data. And there’s not then there. But there is the fervent to get a biomarker is exactly what we need. Because you’d like it to be able to say to someone, this is what it is now, and you can change that and let them follow it, because that would be very motivating. We hope there will be something or some combination of these that works.

Dr. Weitz:            Right. Since you’re mentioning biomarkers, I did want to ask you, I was listening to another podcast you did, and I know you mentioned various serum tests. TMAO is a marker for heart disease risk that was pioneered by Cleveland Clinic. And I’ve always had a problem seeing that that is really a good marker, even though I know there’s some data on it. For those who don’t know, you can measure TMAO levels in the blood. And this has been shown to correlate with heart disease risk. And this is correlated with-

Dr. Roizen:          It’s an inflammatory marker. So let me tell you how it develops and then what you do when you take it, because it’s much more accurate if you take it when you don’t eat fish the night before. And I’ll come back for-

Dr. Weitz:            That was one of the issues I have with that marker. Because fish is the highest dietary source of TMAO.

Dr. Roizen:          No, no, but let me go and explain it to you so that it’s clear, Ben. If you have red meat, egg yolks or some cheeses. So the combination of carnitine, lecithin, choline and saturated fat, if you have carnitine pills without saturated fat, no problem. But you change the genome, which genes are on in the bacteria inside your gut. They produce a compound called trimethylamine. And that continually, not once, but continually gets converted to trimethylamine oxide, which is very inflammatory. It’s more inflammatory than, for example, C-reactive protein by a factor of about six. The problem, and it’s been reproduced in 13 different centers now, Mayo, Cedars of Sinai, not just Cleveland Clinic, European centers as well. The key, when you have fish, you get a little TMAO in your food, that shows up as it in your blood, but isn’t a continual production by your bacteria of it.

                                The difference, the fish have it because it’s what that fish smell is. So if you eat old fish, you are getting TMAO, not the precursors of it, you’re getting the metabolic products. It’s the difference of do you have something that manufactures it or do you have just a little. So you don’t want to eat fish the night before, especially old fish. So frozen fish is the best kind. It turns out fresh, frozen right at the source is what you want for fish. And if you have that, doesn’t raise your TMAO at all. If you have fish that’s been aging in a fish market on ice for a few days, you’re going to have a pretty high level of TMAO. But it’s a fake out compared to your bacteria in your gut producing.

Dr. Weitz:            You made two really interesting points is that even though fish raises TMAO, it doesn’t increase your risk of heart disease. In fact it lowers it, because the TMAO is only there for a short period of time and it’s not being continually produced by U bacteria. And the other thing you mentioned, which was the other problem I had with this TMAO marker, which is that we know that choline, for example, is really beneficial for the brain, for liver health. And we know that L-carnitine is beneficial for fat burning and for heart health, that how could taking an L-carnitine supplement actually increase your risk for heart disease? And you’re saying only if you are consuming something like red meat that has a combination of those along with what you say saturated fat.

Dr. Roizen:          Right. You need saturated fat plus any one of those three amino acids gets converted. If you don’t have saturated fat, it doesn’t get converted at the same time. So taking L-carnitine pills doesn’t do it. L-carnitine pills plus butter does do it.

Dr. Weitz:            I see. Interesting.

Dr. Roizen:          So it’s the two of those together. We don’t know why that changes the gene functioning of your, if you will, the bacteria inside you, but it does. It’s like an epigenetic change that you’re causing in the bacteria. We know that our habits change our epigenes. Well it turns out, one, our habit of red meat changes the epigenes of the bacteria inside us. So when you eat, you’re not only affecting your genes but you’re affecting the bacteria which affect your genes. It’s one of the reasons we think that over the long run we’re going to find out that a lot of the food we eat will affect our mental status, not directly, but through the bacteria with the bacteria produced inside us from our food.

Dr. Weitz:            That’s interesting because there’s been a big controversy in the dietary world about, how can saturated fat actually increase our risk of heart disease? And there’s looking back at the studies, we really haven’t had that many really good studies and that really correlated that. And there’s really no mechanism by which saturated fat actually increases cholesterol levels. Saturated fat doesn’t turn into cholesterol in the body.

Dr. Roizen:          You’re exactly right. And in fact in the studies, saturated fat by itself without carnitine lesser than choline doesn’t do it. Just like carnitine lesser than choline don’t do it.

Dr. Weitz:            Interesting. Interesting.

Dr. Roizen:          Who would’ve guessed that it works through the bacteria inside us? It’s crazy, right?

Dr. Weitz:            Well, once again, we got the connection between the gut and the brain. We got the gut and the heart, and this is important gut heart connection. And another reason why it’s so important to have a healthy gastrointestinal tract and microbiome.

Dr. Roizen:          Right. And you’re into exercise obviously just like I am. But it turns out if you exercise, you actually change, this is crazy and I don’t know the mechanism of this at all, but you again change which genes are on in the bacteria in your gut. There must be a two-way communication system that’s occurring that’s much more sophisticated than any of us thought 20 years ago or 40 years ago.

Dr. Weitz:            Right. Probably through the vagal nerve. I’m sure we’re going to learn a lot more about that. In terms of diet, what do you think is the healthiest long-term diet for promoting longevity?

Dr. Roizen:          We know that five food or five food groups are bad. Everything else we think is neutral or good. So the five foods are simple sugars, added syrup, simple carbs, anything that raises your blood sugar level in a glucose version or fructose version quickly. There’s some weirdness, in that trehalose and allulose seem to block the absorption of other sugars. But with those exceptions, simple sugars, added syrup, simple carbs that raise your blood sugar level quickly are bad for you. So are foods that combine carnitine lesser than choline and saturated fat. And that’s basically red meat, processed red meat, egg yolks, and a few hard cheeses. Everything else is fine. So we don’t know the difference between salmon and the same amino acids if you can get them from beans and quinoa. And we think you need, the data look like as you get older, you need more protein to keep your muscles up.

                                I just underwent the rotator cuff surgery because when doing a chest press, I tore muscles, horrible sound. I was amazed that in six weeks being, I’m just now two days out of the cast, out the swing, in six weeks of being in a swing, my muscle, my right arm went down by a third in size. Who would’ve thought that much that quickly? But we need to continue to do resistance activity and get protein as we get older. But basically, so I think you need to make sure you’re getting enough protein and enough of the micronutrients that we know are healthy. But other than that, you want to eat food you love and that loves you back. I love avocados, they love me back. I love salmon, it loves me back. Most of my diet based on the data in the literature is high fiber plant-based with salmon and a rare other fish thrown in.

Dr. Weitz:            Let’s go through a couple of recommended nutritional supplements as probably our last thing we talk about that might potentially move the needle as far as longevity goes.

Dr. Roizen:          We have a scientific advisory board and we’ve been presented with 53 of them. That is people have sent into our greatagereboot.com website. What’s the data on this? 53 different ones. And it turns out about 18 of them are beneficial, have substantial benefits greater than risks for those over the age of 45 men and 55 women. I can go through whatever you want, but if people want to ask questions, tell them they can send it or have a different supplement to ask about, they can send it to greatagereboot.com.

Dr. Weitz:            Let me ask you about one of them that’s one I hadn’t really heard of and I’m pretty familiar with all the supplements. Is this avocado-soybean unsaponifiables.

Dr. Roizen:          Right. ASU. It’s used in Europe, very prolifically. There’s good data published in the British Medical Journal on lack of side effects and benefit. It is the only disease modifying agent is a supplement we know of for joint health. So for preventing, and by disease modifying I mean it prevents progression. So just like I’ve talked about lifestyle, essentially getting your blood pressure below 120 and below 80 for preventing the progression of cardiovascular disease, for preventing osteoarthritis, ASU seems to do it. Now, you can get it from France or Canada has it as well by ordering ASU, going on the internet and ordering it. The one site and I have no financial relationship at all to it, the one site in the United States that has it is drtheos.com. It’s Dr. Theodosakis, that’s his website.  He imports it and has a very good supplier, he believes that has quality ASU from France. He is out of it right now. I speak about it enough that he says I’ve caused a run. In any case, ASU is, I wouldn’t give it to my wife unless it was really good or use it myself. It’s that good, that it is disease modifying.

Dr. Weitz:            I know we have glucosamine sulfate, which has not only been shown to be helpful potentially for joint pain, but actually I think there’s like a 30% reduced risk of cardiovascular mortality from glucosamine sulfate.

Dr. Roizen:          Right. It’s an anti-inflammatory, but the ASU complete has ASU plus glucosamine and chondroitin sulfate.

Dr. Weitz:            Okay. There you go.

Dr. Roizen:          So you can get ASU complete is what Dr. Theo’s website is sells.

Dr. Weitz:            Let’s just touch on one more. How about the NAD precursors? You mentioned NR, there’s also NMN and some people take NAD intravenous.

Dr. Roizen:          I’m going to talk about not intravenous because we don’t have really any outcome data on that as far as I can tell. But the precursors, we know in animal models, they are both safe and reverse a number of neurodegenerative conditions. In humans we also know they are safe with one exception, I’ll come back to that exception in a second. We know they are safe, but we don’t have outcome data showing benefit. That may be due to the fact that they become racemic or something happens in the pill form that doesn’t happen in the intravenous form that we give to animals. It may be that intravenous is different, but as of now we know they’re safe but we don’t have benefit. So you could probably take it. Now, there’s a study from UT Austin of one gentleman, one scientist who looked at it at about 10,000 times the amount you would give to humans in mice, in a mouse model of glioblastoma.

Dr. Weitz:            I saw that one.

Dr. Roizen:          He did this because I think it was his wife, it may be his daughter died of glioblastoma and she was taking NAD. But he gave it 10,000 times as much to these mice and it caused the cancer to grow faster. When given in a hundred times as much it didn’t do anything. I think this is an abnormality by, if you will, a dose craziness in that one study. I still think it’s probably safe, we just don’t know whether it’s beneficial or not in the form we take it in. I have at one point in, I guess three or four years ago, I was routinely taking it. About a year ago I stopped taking it routinely as I expected the studies on efficaciousness to come out and none of them have. Although I probably didn’t do any harm, I probably didn’t do any major benefit until at least I wait to be shown the data and efficacy. The efficacy studies are undergoing, but we don’t have the data yet.

Dr. Weitz:            I guess I’m a bit more of a risk-taker. I’m currently consuming NR and NMN to hedge my bets there on NAD production.

Dr. Roizen:          I don’t think they’re harmful and they may, you expect them to be beneficial like they were in the animals because multiple animal models, but we just don’t have the data.

Dr. Weitz:            That’s great doc. So you also have an app and a website that people can go to to monitor their risk factors or get more information, I understand.

Dr. Roizen:          Right. The website is greatagereboot.com, and you can ask us questions and there’s a free newsletter that we try and get the article of the week. I wrote last week about, I can’t remember, I think it was, one of the ones was compounding a benefit for health. Another one was on red dye. Red food dye has been shown to be harmful to gut performance. I know next week I’ve written that already. Canada came out with a advisory to avoid all alcohol and I go over the benefits and risks of alcohol. And the data that Canada didn’t have is how it improves socialization, improves posse and stress relief. And so I think it has a substantial benefit in getting us to socialize as long as you stay under two drinks a night and only three nights a week.

                                I know that that’s one of the newsletter. But the app is a subscription app. It’s free now, but sometime in the future we’re going to start charging for it. And it’s a rebootyourage.com app. That’s how we expect to be able to pay for the scientific advisory board and the technology that’s in it. But in any case, Reboot Your Age is the app that you can get through the greatagereboot.com site.

Dr. Weitz:            That’s great. Thank you Dr. Roizen.

Dr. Roizen:          Ben, thank you. And thank you for all you do. Obviously listeners to this website get a huge benefit from all that you do. So thank you for letting me also, because my passion is helping people live younger. You’ve helped me stay young myself by having the passion.

Dr. Weitz:            Thank you. And you’ve helped me with the same passion, being able to help others.

Dr. Roizen:          Thank you.



Dr. Weitz:            Thank you. And thank you for making it all the way through this episode of the Rational Wellness Podcast. And for those of you who enjoy listening to the Rational Wellness Podcast, I would certainly appreciate it if you could go to Apple Podcasts or Spotify and give us a five star ratings and review. That way more people will be able to discover the Rational Wellness Podcast. I wanted to say thank you to all the patients that we’ve been working with at our Weitz Sports Chiropractic and Nutrition clinic, most of whom we’ve been able to help with a range of various health conditions from various types of gut disorders to thyroid and hormonal issues, autoimmune diseases and various other cardiometabolic conditions.  And so I very much appreciate you and I’m excited about going forwards, helping you to do improve your health on your journey towards optimal health. I wanted to let everybody know that I do have a few openings now for new clients and you can take advantage of that by calling my Weitz Sports Chiropractic and Nutrition, Santa Monica office at +1 310-395-3111, and we could set you up for a new consultation for functional medicine nutrition, and we can get that going as early as the new year. So give us a call and I’ll talk to you next week.


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