Harvard's JoAnn Manson, M.D. tells which vitamins preserve telomeres & memory, & improve HealthSpan

0:01 Hi, welcome to episode 122 of the Doctor Podcast, Sicard File Show. I'm your host, Doctor Robert Sicard. Please subscribe, follow, repost, like our episodes and share them. We really appreciate that so we can get more great guests like we have today. Our guest today is Doctor Joanne Manson. Doctor Manson is the chief of the Division of Preventive Medicine at Brigham and Women's Hospital, affiliated with Harvard Medical School in Boston, where she drives pioneering research to advance disease prevention and public health.

0:37 She's a Harvard Medical School professor and Women's Health expert. Doctor Manson has significantly shaped research and education with a focus on Women's Health and chronic disease prevention, which is very important, especially these days. She's a global epidemiology authority as well with a doctorate in public health from Harvard. She is a world renowned epidemiologist whose work on landmark studies like the Women's Health Initiative and the Vitamin D and Omega-3 trial, which we'll talk about today, known as VITAL, has influenced clinical guidelines worldwide.

1:14 She's also prolific scholar. She's authored over 1200 that's incredible number peer reviewed articles and she's a trusted voice in medicine, recognized with honors like the Master of American College Physicians for her contributions to patient care and medical science. She's also a nutrition and aging research expert. Her research explores the role of nutrition, including vitamin D and omega-3 fatty acids, which we'll discuss in detail today in preventing age-related diseases, offering insights into healthy aging and cellular health.

1:55 Today's focus, We're going to discuss a very exciting and important topic, and that's her recent study, which was published in the American Journal of Clinical Nutrition, which examines the effects of vitamin D3 and marine omega-3 fatty acids supplementation on telomere length. And we'll talk about what telomeres are and why they're important in the VITAL trial, shedding light on their potential to slow cellular aging and keep people younger and healthier longer. So Joanne, thanks very much for taking time from your busy schedule to join us today and to share your knowledge and and expertise.

2:40 So tell us. Great. To be here, Robert. Yeah, thank you. So, your career has been transformative in preventive medicine. What initially drew you into this field, and how did your experiences shape your focus on epidemiology and Women's Health? My experiences in clinical medicine really motivated me to pursue prevention because so many of the patients I was seeing during my training in internal medicine and a fellowship in endocrinology, a lot of patients with type 2 diabetes, for example, and complications such as heart disease, stroke, kidney disease, It seemed that there were ways to reduce risk of developing type 2 diabetes, developing these complications.

3:37 I became more and more interested in the subject of prevention, and I really wanted to gain the research skills to do minimize clinical trials and epidemiologic research to test different strategies and interventions for reducing A chronic disease risk. I also was concerned about how little research there was on womens''s health and specifically issues that involve women, including diabetes in women where the complications seem to be even more severe, very high risk of cardiovascular disease and other adverse outcomes.

4:22 So I became more and more interested in research and particularly doing randomized clinical trials. Right now, you're the chief of preventive medicine at Brigham and Women's Hospital, and you're also the Michael and Lee Bell Professor of Women's Health. Tell us how your dedication in this area basically triggered A pivotal moment that deepen your focus on addressing Women's Health research gaps. Is there a specific event that occurred or just multiple events and you realize that there was some gaps in research and medical literature?

5:05 I think it was a combination of patients I was seeing during training that really underscored for me that there was a, a major gap in our understanding of health in women. Some of the most pressing issues in in Women's Health really hadn't been well studied. And early in my medical training, my mother died from ovarian cancer. And I realized that there was very little research in that area. There's very little that the doctors could offer her. And I just became more and more interested in research topics that related either specifically to Women's Health or conditions that were predominant in women.

6:01 Right. Many of the older clinical trials didn't even have women participants in right, which made it very difficult to to figure out what's going on. So it's good that you've stress that. And now as people live longer, chronic disease has has become the biggest problem because as people age, they get more conditions that last for a long time. Absolutely. Now I want to get into vitamin D and omega-3 fatty acids specifically and their impact on health as as background, tell us what vitamin D is? How do people get it?

6:38 What? What is its importance to health? Many years ago, like 10 or 15 years ago, you'd hardly hear about vitamin D. It just was in milk and people just kind of ignored it. But in recent years, there's been a greater and greater emphasis on the importance of vitamin D. So tell us all about that. OK, it used to be believed that vitamin D was really only relevant to bone health, and now there are many studies suggesting that there are vitamin D receptors throughout the body. That vitamin D effects really all the tissues, all the organ systems within the body, and there can be effects on a lot of different health outcomes.

7:23 A vitamin D is actually a precursor to a vitamin that stimulates receptors throughout the body just as a hormone would do. Is one of the reasons why I became interested in vitamin D as an endocrinologist and interested in effects of hormones on health. Vitamin D really seemed to be understudied and we just needed to have like large scale randomized trials to understand benefits and risks of supplementation. And so most of the research had been on bone health, but a few what we call observational studies, just health tracking studies looking at people's blood levels of vitamin D or intake of vitamin D through the diet suggested that there might be lower risks of cancer, cardiovascular disease for those with higher vitamin D intake or blood levels.

8:26 And so I and my colleagues became increasingly interested in mounting a large scale randomized trial of vitamin D at a moderate to high dose 2000 I US a day, which is much larger than what the Institute of Medicine was recommending at the time to the only 600 to 800 I us a day of vitamin D, mostly for the purpose of bone health. And we wanted to test vitamin D supplementation for prevention of cancer and cardiovascular disease. Those are the two leading killers. And absolutely. Right. And, and there there was some promising research suggesting there might be benefits of vitamin D in those areas.

9:18 We were also interested in the marine omega-3 fatty acids, the EPA DHA marine sources from fish because there had been large scale randomized trials in people with cardiovascular disease, but there hadn't been any randomized trials in people at usual risk who didn't have a prior history of cardiovascular disease, but might have a few risk factors kind of more typical patient population. So we were interested in testing 1g a day of the marine omega-3 is a combination of EPADHA and we are able to do this in a large scale randomized trial.

10:03 It was funded by the National Institutes of Health and look at the separate effects, the independent effects of vitamin D and of the marine Omega threes as well as their joint effects. By having actually three, I'm sorry, four, I'll start over with that. By having four separate treatment groups, one was taking vitamin D alone in the placebo of through the Omega threes, one taking active Omega threes, placebo for vitamin D1, taking both active, one taking both placebo. Because we had these four different treatment groups, we could look at the independent as well as the combined effect of vitamin D and Omega threes.

10:55 Very interesting, now tell us how people get vitamin D without supplementation. Do do you get it from natural sources and how much do you get from natural sources? Well, vitamin D is interesting in that we can synthesize it in the skin. So actually with ultraviolet B light exposure to unprotected skin, we convert a precursor in the skin to a another precursor of vitamin D, which then gets metabolized in the in the liver and the kidney to active vitamin D that can stimulate the vitamin D receptor.

11:40 And some people may get the majority of their vitamin D from sun exposure, but in many climates, in many parts of the world, especially the higher latitudes for six to nine months of the year, there is very limited UVB exposure. And so we can get it from some natural sources in the diet. It isn't fatty fish just as the Omega threes are. It's also in wild mushrooms, sun dried mushrooms, and it's in many fortified products because the US has a fortified food supply where dairy products such as milk, other other dairy products, some beverages, cereals are fortified with vitamin D. So it's important to read nutrition labels and see you know how much vitamin D you're getting.

12:36 But it's actually not easy to get 800. I use a day. What's recommended for older adults from diet alone? And it usually requires a combination of the fortified foods, the natural foods and some exposure to sunlight, as well as some supplementation, especially in older adults. Right. The other problem is if you get too much sun exposure, then you've got the problem of skin cancer. So you can't say I'm gonna get suntans and sunburns, so I increase my vitamin D, but then you get the skin cancer. So it's an.

13:19 Important point because there are, you know, researchers and people who active in this field who recommend the people go out with unprotected skin for prolonged periods of time and that can increase the risk of skin cancer, skin aging. So we generally wouldn't recommend more than about 15 minutes 2-3 times a week during, you know, the the hours of the day when there's a lot of sunlight with unprotected skin, you know, without any sunscreen. But limited sun exposure while running errands or by while being a physically active outdoors is perfectly fine.

14:05 Right when except when I interviewed dermatologists on this program, they tell me stay out of the skin, put on sunscreen, wear a hat, you know, wear glasses. So. Yeah, yeah. And, and I, you know, I, I tend to agree that skin cancer is a major problem in the US and throughout the world. And really as as far as the benefits of vitamin D, that isn't clear evidence that there are greater benefits getting it from the UVB light exposure as opposed to a supplement. So it's probably best to avoid prolonged sun exposure with unprotected skin.

14:44 Right. It's interesting how things change. When I was in medical school, they kind of taught us that all the vitamin D you need is just enough to prevent rickets, which is a rare right disease. The vitamin deficiency, which is almost impossible to get because if you eat foods here in the USA, you're getting enough to avoid rickets, but you're not getting the benefits of the extra supplementation. So that's, that's pretty interesting. What natural sources of the Omega threes are there? Is it only from marine sources or are there other foods that contain the omega-3 fatty acids?

15:25 Well, the main source is a fish and the seafood products. However, some people are vegetarians or they don't like fish. They don't eat fish. There are plant based sources of alpha linolenic acid and other plant based Omega threes. There's also algae based Omega threes, but the main source in the diet is fish. What about the flaxseed? Does that contain? Flaxseed and the is the alpha linolenic acid, the Ala the plant based of it. Flaxseed is a very good source of the vegetable oil plant based form of the Omega threes.

16:16 OK, so now that we're all experts in that, tell us what telomeres are, what their significance is, why telomere length is important with regard to health, longevity and graceful aging. And for the audience specifically, can you explain why it's a marker of cellular aging and how it's attrition relates to chronic diseases like cancer and various cardiovascular diseases? So telomeres are the protective caps at the end of chromosomes. So you can almost think of it like the plastic caps at the end of shoelaces that the shoelaces from unraveling and fraying and getting tangled up.

17:02 That's a great analogy. I love that. I'm going to use that in the future. It actually is very similar to what the telomeres are doing in protecting the chromosomes from shortening as the cells you know reproduce, you know as they replicate. So the the telomeres tend to shorten over time with cell replication and it's part of the natural aging process. So as we age, we tend to get shorter telomeres and shorter telomeres have been linked to an increased risk of chronic disease, cardiovascular disease, some diabetes, some forms of cancer.

17:49 There are some risk factors for telomere shortening that are particularly relevant to vitamin D and one of the reasons why we wanted to test a vitamin D and telomere shortening. Systemic inflammation is a major risk factor for chronic diseases of aging, including cardiovascular disease, diabetes and cancer. And we know that vitamin D does have the benefit of tamping down inflammation. We found in the VITAL trial that it lowered A biomarker for inflammation, C reactive protein. We found that the vitamin D at 2000 I us a day actually reduced the risk of autoimmune diseases, a composite of autoimmune conditions such as rheumatoid arthritis, psoriasis, lupus, other conditions of that nature, which tied in to the benefit of lowering the CRP and tamp tamping down inflammation.

19:03 We also have found that vitamin D seems to affect tumor biology to make tumors less invasive and less likely to to metastasize. Because we found that in the VITAL trial there was close to a 20% reduction in advanced cancers defined as fatal or metastatic cancer. But we didn't see a clear reduction in total cancer, you know, like a total first cancer, but the more advanced cancers which which can be strongly related to inflammatory processes. So, you know, with the findings in terms of clinical outcomes and the effect on CRP and inflammation, we were really interested in whether vitamin D affected any biological pathway of aging that could be measured.

20:04 And one of them is telomere length. There are other pathways. That's not the only biological pathway of aging. For example, there's DNA methylation and the epidemic. Genetic clocks, which we're currently in the process of looking at with vitamin D, but we started many years ago, you know, being interested in the telomere biology and getting funding, seeking NIH funding to do a study of that. And so we very recently reported those results just a few months ago showing that vitamin D supplementation did slow or protect against telomere shortening.

20:54 And in fact, the results were stronger than we expected because it was over 4 years of testing. You know, we had the baseline telomere length and we looked at two years and at four years. And the participants who were randomized to the vitamin D2000I us a day had very minimal telomere shortening over the four years. They had the equivalent of about one year of telomere shortening over the four years, whereas the group randomized to placebo had the full four years of telomere shortening. So it, it, it was a substantial, you know, three out of four years of telomere shortening that seemed to be prevented.

21:50 However, we do think the findings need replication, think we think they're exciting findings, but we would like to see them replicated, other trials of vitamin D and we would also like to look at other biological pathways of aging again, the DNA methylation and epigenetic markers as well. Is there an approximation for how much telomere length attrition is equivalent to years of longevity? In other words, you you said that there was a significant reduction. Can you approximate how many extra years of life that results in?

22:38 Or is that not really a valid comparison at this point? I, I think that it is not yet to the point where you could really use telomere biology and telomere length to predict lifespan, though I think there's a lot of interest in that question. I mean the, there, there's a a certain number of base pair shortening that tends to occur over time. And you know, again, we saw the expected amount of base pair shortening, base pair loss in the placebo group but not in the active vitamin D group. But we would be reluctant to say this means that people who were randomized to vitamin D wouldn't necessarily live number of years longer or or something like that.

23:38 We are really interested in the question of health span because health, health span and duration of life free of major chronic diseases such as cardiovascular disease, cancer, cognitive decline, loss of mobility. This is really what matters to people. I have had very few patients say to me that they just want a longer lifespan, no matter what their quality of life, no matter what their health. What people want is health span and healthy longevity and that is ultimately the goal. And we we are planning to do an analysis of both the vitamin D and the Mourine Omega threes in terms of the years of life free of chronic diseases.

24:42 I mean, so far we've looked at these individual outcomes like the risk of heart attack and overall cardiovascular disease, cancer, diabetes. But the the concept of health span, we really want to delve into that in terms of whether the the vitamin D or the Omega threes extended health span. Now the Omega threes did not significantly impact telomere shortening. There was a bit of a signal for some protection against telomere shortening, but it was nowhere near statistically significant. So we have to describe that as a a null finding.

25:23 But it was present for vitamin D And with the Omega threes, we did see a significant reduction in heart attack, a 28% reduction in coronary, major coronary events such as heart. But there was no reduction in stroke, which has also been seen in meta analysis. We didn't updated meta analysis to see if the vital findings for Omega threes were kind of consistent with the secondary prevention randomized trials and generally except for the reduce it trial high dose EPA, only the randomized trials of EPA plus DHA have shown some coronary heart disease benefit but not stroke benefit.

26:16 We we had the advantage of being able to assess diet and a fish intake and and dietary intake of Omega threes at baseline. We look to see whether the benefits of the supplements were greater in those who had low fish consumption and we did see a really important role of the baseline fish consumption. So the participants who had less than the median or average intake of fish, about 1 1/2 servings per week of fish, they had an even greater reduction in heart attack. So overall was a 28% reduction.

27:02 But among those with lower fish consumption at baseline, they had a 40 percent reduction in heart attack and almost a 20% reduction in the primary endpoint of major cardiovascular events. But interestingly, with the 1g a day of EPA plus DHA, we didn't see a benefit in those who already had 1 1/2 servings of fish per week or more. It's almost like with that more moderate dose, you know, so small to moderate dose, if you're already getting enough from diet, you're already getting a similar amount from diet, you don't get the benefit from a supplement.

27:49 And then this is consistent with what we generally advise, that dietary supplements will never be a substitute for healthy diet and healthy lifestyle. Which fish specifically are high in the Omega threes? I think it's salmon. Or are there any other one or two fishes? They're they're the darker, the darker fatty fish. Salmon is a great choice. Mackerel, sardines, tuna, herring, those are all really good, good choices. Right. And backing up for a second, we kind of use vitamin D and vitamin D3 interchangeably.

28:31 Are they the same thing or or is there difference? And if you go to a drugstore and buy vitamin D, what are what are you getting there? You're usually getting D3, which is the animal based source of vitamin D, but the D2 in the ergocalciferol that is from plants and it also, you know, has quite similar benefits, but it's not believed to be quite as bioavailable as the vitamin D3. So usually when I've said vitamin D, I've been referring to D3. So we tested 2000. I use a day of vitamin D3. Right now with the omega-3 fatty acids, what what was your source of that?

29:19 Let's say somebody doesn't eat fish, they don't like them or whatever reason. Where can they get a reliable supply of the Omega threes actually? Tested a prescription omega-3 product unlike with the with the vitamin D, which was over the counter a a very high quality over the counter supplement with the Omega threes we we test this prescription product that had excellent quality control. So it's called Omacor. It's also in the US Livasa for triglyceride lowering, but a lower dose than is used for triglyceride lowering.

30:04 What if people want to? Buy it over the counter over the counter over. The counter, it is important to look at the whether there is a seal of quality control testing such as US Pharmacopia, USP Seal, NSF National Science Foundation or it says audited by consumerlab.com, that kind of thing. Because one of the concerns with the omega-3 fatty acids over the counter the fish oil is that some of the products that don't have great quality control can become a little rancid. And also the content may not be what it claims to be.

30:59 And this is true of not just, you know, the fish oil supplements over the counter, but really any dietary supplement because it's important for the public to understand that dietary supplements are not regulated by the FDA the way pharmaceuticals are. This is why we did want to test a pharmaceutical version of the Omega Threes to be sure it was very, very high quality without concerns about the product becoming rancid or anything like that because. Heavy metals. Microbial growth, all of that, but over the counter supplements are fine if you choose really reliable sources and the best way to get an indication of that of the quality controls to look for the seal of like USP and SF, that sort of thing.

32:05 All right, that's great. Now how? Did you pick 2000 units a day? I have to admit that I've been taking 5000 units of vitamin D3 for well over five years now, just because I read some studies back then and I figured that was a good way to do it. I don't think I'm overdosing, but what is the safe dose so we. Started vital back in 2010, two thousand and nine 2010 at the time we just got started in planning the trial the recommended dietary allowance was only 400. I use a day, 600, I use a day, and that's what was called the tolerable upper intake level, which the, you know, National Academy of Medicine, Institute of Medicine considers.

33:02 The intake level at which there may be some risk of adverse events was set at that time at 2000. Very soon after that, the upper limit was set at 4000, and the recommended dietary allowance changed to 600 IUS a day for adults up to age 70 and then 800 IUS a day over age 70. So we wanted to test a dose of vitamin D that would be at least three to four times what the recommended dietary allowance was to have enough separation between the placebo group and the active group. But we wanted to be sure we stayed below what was being set as the tolerable upper intake level considering that people were going to get some vitamin D from diet, fortified foods and etcetera.

34:03 SO2000I us a day seemed a really optimal balance of expected efficacy and safety. It kept us in that range and also the blood level that we expected to achieve which was about 100 to 105 nano moles per liter or close to 40, close to 40 nanograms per mil or a little higher than than that. I that is exactly what we achieved with it. And in the in the observational studies, that was the blood level of vitamin D that seemed to be associated with a substantial reduction in risk. And then it seemed to plateau off without really clear evidence of going that much lower in risk with getting higher blood levels.

35:05 So it seemed it seemed to be a good good balance of efficacy and safety. I think based on more recent evidence, some may may make the case that certainly testing a higher dose should be safe. You know, testing 3000 or 4000 should should be safe. And even 5000, I'm not saying 5000 is associated with risk, but the the problem was that there weren't a lot of data at that time to show that long term use of higher doses was safe and we didn't want to undertake a trial where there could be some risk with the dose being given.

35:56 We thought we would get people to a good blood level associated with very low risk and observational studies and should be virtually free of any risk at that level of intake. And in fact we saw no real adverse events or side effects. We didn't have any significant increase in blood calcium levels in kidney stones, you know, and some of the risks that we were concerned about, right. For people out there who think that Oh well if 2000 good maybe I should take 20,000 a day. What? What's the upper limits where vitamin D can become toxic and cause serious side effects?

36:43 I mean there. There is some concern about long term use of doses of let's say 10,000 I us a day. When you're talking about really long term use there, there are people who have conditions like Sarcoid for example, or Wagoner, you know, where they have granulomatous disease and there is very active synthesis of the, you know, the ACT, the really active form of calcitriol. When they're given the vitamin D precursors, you know, you're given colocalciferol D3 that can get converted very rapidly into the 125 dihydroxy vitamin D in people who have these granulomatous conditions.

37:36 Also, if they have active tuberculosis and it's another condition. So we wanted it, even though these conditions are not that common in your typical clinical trial population. We wanted it to be a dose that would be totally safe for everyone, right? So for the average. Person out there if you're taking 2000 units a day, you're super safe with that. It would be incredibly unlikely that you'd have any side effects from that. Super safe and three. 1000 as well and you know I do recommend avoiding mega dose saying, but I think we're talking about doses that are you know long term consistently above let's say 8009 thousand 10,000 I use a day and that's because there's so little research on long term use of those higher dose supplements.

38:37 What was the? Racial distribution and the gender distribution in in your trial and and does that affect the results? Because people with darker skin have different amounts of vitamin D synthesis from the sun. Is that right? Yeah. No, great question. We were very happy with the the composition of the study population. It's almost exactly 50% women and men. We had 20% African American or Black participants, which we strived to have with 5100 black participants. And the reason we worked really hard to recruit even disproportionately beyond the percentage of population in those age groups, you know, in the older age groups, because this was a study population 50 and older and men 55 and older in women.

39:41 And we really did want to look at the effects of vitamin D supplementation specifically in black Americans and see if there could be greater benefits. And we did see several signals for greater benefit among the African American participants. And this included for cancer we had almost a significant. Risk reduction for total cancer in the African American group. We saw for cognition that there was a benefit of vitamin D that was not seen in the overall cohort or in the, you know, the European white group.

40:28 So there, there were greater benefits of the vitamin D in in the black participants. However, you know, there were many health outcomes that were not benefited or impacted by vitamin D. We didn't see a significant reduction, for example, in cardiovascular events. And this is also true in a meta analysis. We did a meta analysis of more than 80,000 participants, about 18 or more trials, and we did not see a single randomized trial that showed a clear benefit of vitamin D in reducing cardiovascular events.

41:12 So I think 1 lesson that we learned and also no benefit for reducing hip fracture and osteoporotic or or total fracture is that in general, we need only small to moderate amounts of vitamin D for most health outcomes. And more is not necessarily better. Just because you take more vitamin D doesn't mean you know you're suddenly going to get a reduction in bone fractures or cardiovascular disease. Generally you don't have any, you know, change with slightly more where we saw 2000 I us a day being of benefit was with the tamping down inflammation, lowering CRP, lowering autoimmune diseases and advanced cancers.

42:08 And it may be for these specific conditions that are strongly related to inflammation. I mean, really all chronic diseases are related to inflammation. But for these conditions, it seems that a larger amount of vitamin D may be a benefit, but was not a benefit across the board for all outcomes. And we don't interpret that as, oh, vitamin D isn't important. We interpret it more as vitamin D is so essential and so critically important that we need only small to moderate amounts of vitamin D to meet our requirements.

42:52 And the human body has a lot of physiological processes in place to regulate the metabolism of vitamin D to conserve vitamin D. When exposure is low, levels are low, but you know you can get too much of taking very very high doses. So in addition to more isn't necessarily better, it can be worse if it's extremely high intake where there are risks of toxicity. You know another, let me just mention, Robert, that we saw an intriguing interaction with body mass index and adiposity where we found that the participants who were at healthier weights like their body mass index was closer to 25 and below, They seem to have more benefits from the vitamin D than those with the higher body mass index.

44:02 This may be because adiposity and the inflammation associated with adiposity may interfere with bio activity of vitamin D. We know that a higher BMI can interfere with the effect of many medications and many treatments. We saw that in those who had a lower BMI or healthy weight that they did have a significant 24% reduction in total cancers and they had even greater reduction in autoimmune diseases and a number of of other outcomes. So we want to delve more deeply into these findings because if we can find a way to bypass whatever obstacles are in place with higher body mass index in having the full benefit of vitamin D, then that could allow the benefits of vitamin D to become available to all people across all BMI ranges and, and the full spectrum of BMI.

45:16 And actually, you know, reaping the the benefits of vitamin D irrespective active of adiposity level. Interesting was. There any difference in the telomere length attrition between men and women or or was it about the same there was there? Was about the same with men and women, but there was a difference by adiposity. And again, it was those at healthier weights who had a greater benefit. So, you know, we're we're seeing this for a lot of outcomes and we're interested in testing some metabolized forms of vitamin D such as calcidiol, a form of, you know, the 25 hydroxy vitamin D to see if that could bypass whatever is interfering with the efficacy of vitamin D in the setting of a high body mass index or high adiposity levels.

46:20 Now it's easy for. People to get their vitamin D levels, it's a simple blood test or your internist or primary care doctor can do that and get the results in a few days. People watching this are now going to be wondering what's my telomere length? How do people find that out? Is that easy to get that test done? It is not at all. Easy to get done. It is really not commercially available to patients. They probably have to pay a lot out of pocket and some of the sources, you know, labs measuring it may not be reliable.

46:59 So I think it needs to be done in a research setting. There may be other studies going on that are looking at effective acts of interventions on telomere length, but for the time being, I don't think that this is something that everyone needs to run out and get measured. I would, I would say if people, you know, generally try to ensure that you're getting at least what the National Academy of Medicine recommends up to 600 I, US a day up to age 70 and then 800I US a day after age 70. I think it's perfectly fine to take a supplement of 2000 I, US a day.

47:48 It's very, very safe, maybe even a little more than that. Avoid mega dosing, but most importantly focus highest priority on healthy and balanced diet and healthy lifestyle including time outdoors, being physically active because that is really where the long term health benefits will come in. Popping a pill will never be a substitute for that. And I, I think although it's very reasonable to, to take a vitamin D supplement, especially if you, you have osteoporosis, you're on a medication for osteoporosis or you know, if lactose intolerance, you know, you're not having fortified dairy products or you're not spending any time outdoors because of health related reasons or your nursing facility.

48:45 Also, if you have an increased risk of a malabsorption condition such as Crohn's disease, ulcerative colitis, celiac disease, reasonable to take a supplement. But you know the the recommendations of the US Preventive Services Task Force of the American College of Physicians, you know generally the they are not recommending that everyone take a supplement. You know that everyone run out and start taking a supplement or that everyone run out and get tested. Mostly just focus on really healthy diet, healthy lifestyle.

49:28 And if you have concerns for the reason I mentioned that you may be at higher risk of having a vitamin DA, low vitamin D blood level, certainly ask your doctor for the test and I'll talk about taking a supplement and it should be very safe at more moderate levels, right? But. Since a large percentage of the public doesn't have good health habits, there's an obesity epidemic, as you know, a diabetes epidemic. The diets are not great. I don't see any downside and just everybody over age 21, let's say taking 2000 units of vitamin D everyday, it's the risks of side effects are almost zero.

50:15 And there's probably benefits to that since we don't have necessarily a very healthy lifestyle. A lot of people don't exercise. And what what do you say to that? Well. What what I say to that is that the guidelines are are not currently in line with everyone being tested for vitamin D or taking a supplement. So I, I don't want to recommend that people spend their money, you know, across the board on something that may not be necessary for them. And their effort may be better spent and even their money better spent on having a healthier diet, more fruits and vegetables and more fortified foods, whatever.

51:08 And really being physically active, spending time outdoors. I think a strong case can be made during the winter months in areas of the globe, including the US. You know where you're talking about being above the 37th or so parallel. You know where you're going to have very little sun exposure or vitamin D producing exposure in the skin for 6 plus months of the year. Taking a vitamin D supplement 1002 thousand, I used it during those months into the fall through early spring. I I think is quite reasonable during the the summer months.

51:57 I think you can make a case just really encourage people to be active, physically active outdoors. But if people have any concerns and I think you're kind of getting at this issue. If you have any concerns that you may not be getting what you need from diet or physical activity, time outdoors, the sun exposure, then it does make a lot of sense to hedge your bets and take a supplement of 1002 thousand. I use a day. It would be very safe and it's quite affordable, but not completely free but quite affordable and it would be very reasonable to do.

52:44 There are also multi vitamins out there that have 1000 I us a day of vitamin D. So I think taking a supplement is reasonable during winter months, especially in New York and. Boston where we are, but maybe not in Miami exactly. It it will depend on the latitude and also the type of weather and weather, you know, people are wearing a lot of clothing coverage when they're outdoors. I think it in some ways it needs to be an individual decision, but it certainly should be very safe and very reasonable to take in 2000 IUS a day based on a 5.3 year trial.

53:36 The vital trial testing 2000 IUS a day is very, very safe over that period of time. Now going back to your. Trial and the telomere length. Are there other studies that have found similar results to yours? Or how's your study different than what was done before? So there have been. Very few long term trials of vitamin D that had bloods large enough. Sample of bloods at baseline and up to four years of treatment. We didn't see the clear benefit on the telomeres until four years. It takes a duration of treatment to see the benefits, so vital is the first like rigorous randomized trial showing the protection against telomere shortening over the four years.

54:31 Most of the previous trials have not looked at the question or not seen a clear benefit, but they were often smaller and looking at a shorter duration of treatment. So I I think this warrants further study. Would be really nice to have it replicated in another trial and to look at other biological pathways of aging right I think. That primary care doctors, internists should talk to this, talk to this issue with their patients because there's great benefits and and very low risk. So I hope this podcast publicizes that and patients ask their doctors information about this.

55:23 And people who, for example, have a family history of autoimmune diseases or at high risk where we did see those benefits, may want to talk with their doctor about taking the vitamin D. And people with very low fish consumption may want to talk with their healthcare provider about taking an Omega 3A supplement. But again, I, I know I've said this before, but I really want to emphasize that popping a pill, taking a dietary supplement will never be a substitute for the healthy diet, healthy lifestyle and really focus on that because most people will be able to achieve major improvements in their health by improving the quality of their diet.

56:17 You know, having lots of fruits and vegetables, a whole food diet, minimal processed foods, ultra processed foods, and also being physically active, including strength training. So important. And that will really lead to major strides in terms of good health. Absolutely. But. On the other hand, I'm an ophthalmologist. I'm seeing more and more of my patients taking Ozempic and Wigovi and Munjaro and Zetbound because people are always looking for shortcuts, you know, so it's and as an ophthalmologist.

56:55 You know there there is a dietary supplement for slowing progression of age-related macular degeneration. Yeah, I have many patients. On that the A Reds too, right so. I, I think when the supplements are well tested and shown to be a benefit in a given, you know, patient population, people with certain risk factors. I think one of the reasons why there isn't a broad recommendation for vitamin D supplementation and omega-3 supplementation and, you know, applying to the whole population is that most of the randomized trials have not shown the clear benefits.

57:35 We're seeing benefits in certain areas, but it's still limited to just certain outcomes. So you're a great pioneer. Now, after decades of very impactful research like the VITAL Trial, what keeps you motivated to explore nutrition and preventive medicine? And and what big question in this field are you eager to answer next? What studies are you doing now? So. I'm really interested in health span and different interventions that may be able to slow the biological aging, you know, as assessed through the DNA methylation, epigenetic clocks and telomere biology and other approaches.

58:28 I think that the GLP ones, especially if combined with agents that protect against the muscle loss that can so often occur with the GLP ones because there's loss not only of adipose tissue, but also some decrease in muscle and some decrease in bone and and bone density. I think that there could be real promise of these agents in improving cardio metabolic health, lowering risk of cancer and actually extending health span improving quality of life. Another area I have a tremendous interest in is reducing our slowing age-related memory loss and and cognitive decline.

59:21 And we had a surprising finding with the multivitamins in the COSMOS trial that in three separate placebo-controlled studies within Cosmos, the multivitamins actually slowed age-related memory loss and showed clear benefits compared to placebo for cognitive function. And this may be because the micronutrients that are in multivitamins are just so essential for optimal brain health, and that many people may have a deficiency in one or more of these. Vitamins and minerals that are in a comprehensive supplement which contain at least 20 vitamins and minerals.

1:00:12 So we're interested in in further research on nutrition and a slowing cognitive decline and even reversing, you know, some of the mild cognitive impairment, Alzheimer's, a very exciting finding recently on lithium orotate that was just published suggesting in mice a really, really exciting finding in a postmortem brain that there was the deficiency of lithium and lithium orotate having some promising characteristics. So we think there's a need for randomized clinical trial of several interventions, lifestyle as well as nutritional and pharmacologic for slowing age-related memory loss and cognitive decline and maybe even reversing some of the early stages of Alzheimer's disease.

1:01:17 Wow, that's. Great. Looking forward to more studies and trials and research and publications from you. I'd like to thank you very much for taking time and they join us. I learned a lot. I'm sure the audience has learned a lot as well. They're all going to go out there and exercise and eat better and ask their doctors about vitamin D sounds. Great. It was. It was really great talking with you, Robert. Thank you so much. My pleasure. Thanks.