[00:01] actually slow the clock on your biological aging? Recent data from a landmark vital trial suggests the answer is yes. They saw significant preservation of telomere length equivalent to as much as
[00:14] 3 years of biological aging over a 4-year period. Joining us today is Dr. JoAnn Manson, professor of medicine at Harvard Ben Medical School and the lead investigator of the vital trial.
[00:27] This nationwide study followed over 25,000 participants to examine the long-term effects of vitamin D and omega-3 supplementation. While the primary goals were focused on heart health and cancer, a recent 2025
[00:41] ancillary study has revealed some of the most compelling evidence we've seen regarding vitamin D's role in protecting our cellular integrity. In our discussion, Dr. Manson explains how 2,000 IUs of vitamin D daily
[00:55] resulted in a stunning finding. While the placebo group experienced 4 years of telomere shortening, the vitamin D group saw only one. We also dive into the why, exploring the link between systemic inflammation,
[01:09] autoimmune risk, and why your body mass index might be the gatekeeper to whether these supplements actually work for you. Whether you're interested in longevity science or just looking for the clinical data on your daily supplements,
[01:23] this conversation provides some nuance that the headlines often miss. Let's get into the interview with Dr. JoAnn Manson.
[01:39] professor of medicine at Harvard Medical School and lead investigator of the landmark vital trial, whose latest 2025 research reveals a groundbreaking link between vitamin D supplementation and the preservation of
[01:52] telomere length equivalent to as many as 3 years of biological aging. Span. >> It's great to be here, Richard. >> For people who are not familiar with the VITAL trial,
[02:06] could you introduce it and kind of the main parameters of the of the main trial for which the the telomeres was a subsection? >> The VITAL trial, vitamin D and omega-3 trial, is a large-scale randomized
[02:22] trial, is a large-scale randomized clinical trial done nationwide in the clinical trial done nationwide in the United States. It includes men age 50 United States. It includes men age 50 and older, women age 55 and older, and
[02:36] and older, women age 55 and older, and so midlife and older adults, and we tested both vitamin D 2,000 IUs a day compared both vitamin D 2,000 IUs a day compared to placebo, and the omega-3 fatty acids,
[02:51] um, a gram a day compared to placebo. But, we were able to look separately and independently at the effects of vitamin D, uh, versus placebo. So, that's what I think we're we're focusing on today. It was a primary prevention trial. So, the
[03:09] participants were representative of a generally healthy US midlife and older adult population, but they weren't selected for having, um, specific health selected for having, um, specific health conditions or risk factors.
[03:24] >> And how long did you follow them for? >> The large-scale trial was 5.3 years on average. The primary aims were prevention of cardiovascular disease and
[03:38] prevention of cardiovascular disease and cancer. This was an ancillary study that cancer. This was an ancillary study that was done in a subset of VITAL participants who lived in the greater Boston area and came in for um, um
[03:54] Boston area and came in for um, um blood blood collection and very um blood blood collection and very um you know, optimally processed bloods so you know, optimally processed bloods so that we would be able to measure uh
[04:06] things like telomeres and inflammatory markers and and a number of biomarkers. >> And so the group there was >> Yeah, this subset let let me clarify.
[04:18] >> Um this subset in the greater Boston area was 1,054 participants. We had more than 900 participants who
[04:30] had both a baseline and a two or four-year uh follow-up blood collection. This specific analysis on telomeres was limited to those who had at least one
[04:44] follow-up uh blood collection at two or four years. >> Right. And there was there was a vitamin D and a omega omega-3 group, but there was no vitamin D and omega-3. Is that correct?
[05:00] >> there was there were four treatment groups because the design was what's called a two-by-two factorial design. So we had um we had um vitamin D alone, omega-3s alone, the
[05:13] combination of vitamin D plus omega-3s, and dual placebo. >> Okay. So interestingly in so on in this paper that we're going to talk about, which is the the telomere length,
[05:28] did you see a difference between those on omega-3 and vitamin D and vitamin D on its own? >> It was vitamin D that was the most effective for protecting the telomeres, and there really wasn't a clear additive
[05:46] benefit of the omega-3s, and looking at the omega-3s alone, we didn't see a significant benefit for telomere protection, but it did trend in the
[05:58] direction of some protection. But, the significant findings were for vitamin D. significant findings were for vitamin D. 2,000 IU's a day was the dose we tested.
[06:12] if we go into that in some more detail, which is where I'd like to go. So, this paper came out in this year, right? 2026 2025. this year, right? 2026 2025. >> 2025. So, it came out in May of 2025. It
[06:27] was published in the American Journal of Clinical Nutrition. >> And can you talk about the headline result, which was that the telomere length was will not reduced the
[06:39] the level of reduction was like almost it was only like 12% of the placebo. But, anyway, could you talk about how about the telomere length and how it compares to the placebo?
[06:54] compares to the placebo? >> The vitamin D supplement did protect the >> The vitamin D supplement did protect the telomeres in that over 4 years of telomeres in that over 4 years of treatment, there was only 1 year of
[07:08] treatment, there was only 1 year of telomere shortening in the vitamin D randomized group, the group that received the the vitamin D in comparison received the the vitamin D in comparison to the placebo group that had 4 years of
[07:22] telomere shortening over that 4-year follow-up period. So, there was protection of the telomeres by the vitamin D supplements.
[07:37] >> Could we talk a little bit about how the telomeres were measured? So, which telomeres were measured? So, which telomeres were measured in which cells? >> So, this was a peripheral blood sample measured in leukocytes or white blood
[07:51] measured in leukocytes or white blood cells. And um cells. And um it is a technically complicated measurement. However, we we collaborated with an outstanding lab. And also, I I
[08:07] just want to clarify for the audience. I I know many of them may fully understand what telomeres are. But one way to think about uh the telomeres is that they're
[08:19] the protective caps at the end of the chromosome, similar to the protective caps on shoelaces that keep the shoelace from unraveling and degrading. Um the telomere cap,
[08:37] and degrading. Um the telomere cap, which is a repeated sequence of DNA at which is a repeated sequence of DNA at the end of each telomere. This protects the telomere the um It protects the chromosome from
[08:51] It protects the chromosome from degrading um unraveling, damage uh to the chromosome. So, we we found that the amount of telomere shortening that would
[09:04] normally take place over 4 years, as we saw in the placebo group, had only about saw in the placebo group, had only about 1 year of shortening in the vitamin D randomized group. >> Right. And just for reference,
[09:20] >> Right. And just for reference, what causes the telomeres to to shorten? what causes the telomeres to to shorten? >> It's a biological pathway of aging. The >> It's a biological pathway of aging. The These cells are constantly replicating.
[09:33] These cells are constantly replicating. There's a lot of turnover of cells. Um There's a lot of turnover of cells. Um and it is a marker of biological aging. and it is a marker of biological aging. Over our lifespan, we have a substantial
[09:46] Over our lifespan, we have a substantial shortening of the telomeres in cells. shortening of the telomeres in cells. And it's one of the, um, you know, uh, And it's one of the, um, you know, uh, hopes in trying to extend healthspan and
[10:00] hopes in trying to extend healthspan and and slow biological aging to find ways and slow biological aging to find ways to, um, protect telomeres, prevent the telomere shortening that occurs with biological aging, as well as some of
[10:14] these, uh, affect some of these other biological pathways such as DNA methylation, epigenetic aging. That's a separate biological pathway. But telomere shortening is one of the biological pathways of aging.
[10:31] >> Right. And some years ago, I I mean, 10 years or so, it it was like one of the major markers for aging, and it seems to have not to be to be viewed more nuanced recently, but it's still definitely correlated. Longer telomeres are
[10:45] correlated. Longer telomeres are correlated with younger organisms, I guess. >> Right. And also the, uh, shortening of the telomeres has been linked to some chronic diseases of aging. The The
[11:00] evidence in the literature is not entirely consistent, but there is a pattern of shorter telomeres being predictive of higher risk of
[11:13] cardiovascular disease, of type 2 diabetes, of some cancers, though with diabetes, of some cancers, though with cancer, it's a very complex, uh, relationship where for some cancers, actually shorter telomeres are are are
[11:29] more predictive of of lower, uh, risk. So, it's it's an inconsistent picture with cancer. But, cardiovascular disease, type 2, uh, diabetes, um,
[11:42] osteoporosis, fractures, most aging-related, uh, diseases, there there is an association between shorter telomeres and higher risk of aging-related chronic diseases.
[11:59] whenever I we discuss longer telomeres, uh, the the questions always come up about, well, do longer telomeres don't longer telomeres, uh, correlate with cancer risk? So,
[12:13] if you take vitamin D and you have longer, you have longer telomeres, is there any evidence whatsoever that that increases cancer risk? >> There There are some studies that
[12:28] >> There There are some studies that suggest for certain cancer types that longer telomeres may predict increased risk. It's a mixed picture with cancer. And, um, I think in particular, melanoma has been a particularly surprising kind
[12:47] of relationship. But, for the non-cancer-related chronic diseases, the associations are are much more consistent in the literature. >> Right. Okay, let's leave it there. We
[13:01] could spend all night on that. >> Yeah. the cellular level for these vitamin D
[13:13] that vitamin D does to the white blood cells? >> I think it's all speculation at this point because there really, um, haven't
[13:26] been clear basic science bench research studies explaining the mechanism, but one hypothesis hypothesis is that vitamin D does have some
[13:39] anti-inflammatory uh, benefits and tamps down inflammation. We did see in the vital trial that the 2,000 IUs a day did lower
[13:52] trial that the 2,000 IUs a day did lower the high-sensitivity C-reactive protein levels. Um, that this uh, dose was associated with a lower risk of autoimmune diseases that are related to the
[14:08] inflammatory process. Um, autoimmune diseases like rheumatoid arthritis, um, psoriasis, multiple sclerosis, Um, these are all in the uh,
[14:22] general autoimmune uh, disease endpoint that we we studied. uh, disease endpoint that we we studied. Um, and we we did see a benefit of of vitamin D in reducing risk of a composite autoimmune uh, disease
[14:38] outcome. So, we're we're thinking that the So, we're we're thinking that the benefit for telomeres and the protection benefit for telomeres and the protection of telomeres may relate to telomere
[14:51] of telomeres may relate to telomere shortening being related to chronic systemic inflammation, which does systemic inflammation, which does increase with aging. We we we know that
[15:03] uh, there's a a general association and and systemic um, inflammation is a major and systemic um, inflammation is a major risk factor for diseases of um, aging, risk factor for diseases of um, aging, chronic diseases of aging. So, it may be
[15:18] chronic diseases of aging. So, it may be that the benefit of vitamin D in reducing inflammation, lowering CRP levels, um reducing autoimmune diseases, you having this anti-inflammatory
[15:33] um effect tamping down inflammation may also be protecting the telomeres from also be protecting the telomeres from the effect of inflammation on um which would be part of that biological
[15:48] which would be part of that biological pathway of aging that the long-term pathway of aging that the long-term chronic uh inflammation is shortening telomeres and accelerating the aging process.
[16:03] >> So, maybe my simplified view is that telomeres shorten because the cells divide, right? That's definitely a point where the telomeres divide. So,
[16:15] does shorter telomeres automatically mean that you've you've just had more cell division? Or are there other things that shorten telomeres that are not that shorten telomeres that are not related to cell division?
[16:34] underlying process for telomeres to shorten, but shorten, but what I'm suggesting is that the chronic what I'm suggesting is that the chronic inflammation may make the telomere more
[16:47] likely to shorten with cell division with with this cell replication. So, if the vitamin D is decreasing inflammation, it may be protecting the
[16:59] telomeres from shortening. However, another possibility, which which is supported by the vital trial, is that um trial, is that um vitamin D may play a role in
[17:14] reducing the rate of a cell replication in cancer. And uh we did find that vitamin D was protective against advanced cancers. I
[17:27] don't know in it it totally healthy cell replication that vitamin D is having replication that vitamin D is having that effect, but we did see that vitamin that effect, but we did see that vitamin D it had a borderline benefit for cancer
[17:42] mortality. And when we looked at advanced cancers, metastatic plus fatal advanced cancers, metastatic plus fatal cancer, we did see a significant 17% cancer, we did see a significant 17% reduction in advanced cancers. And it
[17:57] was a signal that wasn't there for overall incident cancers, like the development of a first cancer was not significantly of a first cancer was not significantly reduced, only very modest signal for
[18:12] total incident cancer, but we did see a benefit for cancer death and metastatic cancer, the more advanced cancers. And our thought there is that
[18:24] cancers. And our thought there is that vitamin D may be playing a role in affecting the invasiveness of cancers and the likelihood that they're going to become metastatic and you know, fatal lethal
[18:42] cancers. And there's some bench research to support that, some animal research to support that as well. So, possibly it support that as well. So, possibly it relates to an effect of vitamin D on
[18:57] cell replication and you know, rates of of cell you know, rates of of cell proliferation, but I I think it may be more likely to relate to this inflammatory mechanism, although
[19:11] admittedly this is speculation and we don't know the exact answer to the underlying mechanism. More research is needed.
[19:26] in cell culture and seen that it um activates telomerase? I mean, do we know that it's slowing down the the shortening of telomeres or could it be actually lengthening them in some way?
[19:41] in some way? >> So, we we do know from a study of one of >> So, we we do know from a study of one of our colleagues that vitamin D supplements were affecting uh telomerase activity.
[19:54] And um so, it's probably mediated through so, it's probably mediated through effects on telomerase which may be um affected by inflammation um and the vitamin D by reducing
[20:09] inflammation it is having a favorable effect on uh telomerase and the repair of the uh telomere. Um we don't know that exact mechanism.
[20:22] Let me just clarify. I am and I'm a physician epidemiologist. I'm not a bench researcher. And you know, so And you know, so my role in in the study, we designed the
[20:37] my role in in the study, we designed the vital trial to to look at uh prevention of cancer and cardiovascular disease. Those were the main goals. This was an Those were the main goals. This was an ancillary study uh to look at telomere
[20:50] ancillary study uh to look at telomere um length, but the underlying mechanisms um length, but the underlying mechanisms of the telomere effect, the uh telomere of the telomere effect, the uh telomere benefit is unknown at this point and was
[21:03] not really an original aim of the vital trial. It was it was just an enhancement um with uh collaborations of investigators interested in looking at
[21:17] other outcomes and um other, you know, effects of the vitamin other, you know, effects of the vitamin D or omega-3 supplementation. >> Right. Okay. But, you were ex- you looked for it. So, you were
[21:31] expecting that it might uh reduce the telomere. >> Our collaborator had seen in an earlier smaller trial that there was a benefit smaller trial that there was a benefit of vitamin D on telomerase activity. And
[21:47] of vitamin D on telomerase activity. And they his um research team asked if they they his um research team asked if they could look within vital at the effects of vitamin D um in in vital in the sample that was
[22:00] in in vital in the sample that was having repeated uh blood collections on actual telomere length. >> Right. So, if we think about So, I wanted to think about the dose.
[22:14] So, could you explain uh so, 2,000 IUs was the dose that you used. Um I mean, I have spoken with uh Dr. Michael Holick. And, you know, he he tends to prefer a
[22:27] larger number, like 4,000 was I think what kind of the the general number he what kind of the the general number he he said. So, why why 2,000 IU for the trial? >> So, 2,000 IUs led to an average
[22:44] 25-hydroxy vitamin D level of about 40 ng/mL vitamin D level of about 40 ng/mL or 100 nmol/L. or 100 nmol/L. And, in the epidemiologic research, that
[22:59] And, in the epidemiologic research, that is the blood level at which there tended to be the lowest risk of chronic diseases and then most studies were showing sort of a plateau in the effect after that level. Also,
[23:16] you know, getting into uh higher blood levels of 25-hydroxy levels of 25-hydroxy uh vitamin D, there was no clear benefit in many of the studies in getting to a higher blood level than than that. Also,
[23:32] higher blood level than than that. Also, at the time um VITAL was being designed, it appeared to be a dose that would be the best balance the best balance of efficacy and safety.
[23:46] Um in that the Institute of Medicine, now the National Academy of Medicine, had um released their dietary reference intakes and of course was recommending much lower amounts in order to meet um
[24:04] the dietary allowance, which is defined as meeting the requirements for vitamin D of at least 97.5% of a generally healthy population, and they were recommending 600 to 800 IUs a day
[24:21] and setting the tolerable upper intake level at 4,000 IUs a day. And and the level at 4,000 IUs a day. And and the tolerable upper intake level is the
[24:34] intake at which there is some risk of adverse events. So, um even though it was extremely cautious of the IOM to set that at 4,000
[24:47] IUs a day as opposed to higher, there was a concern about testing a dose um was a concern about testing a dose um um, as high as 4,000 IUs a day because
[24:59] um, as high as 4,000 IUs a day because together with intake from diet and um, some participants wanted to take at least a small supplement in case they were randomized to the placebo group. They wanted to be sure they were getting
[25:12] at least the RDA. So, if you consider adding 4,000 So, if you consider adding 4,000 IUs a day to what might be at least uh,
[25:24] 1,000 that they're getting through diet and uh, supplement, that that gets into a fairly large amount to test in a long-term 5-plus year trial.
[25:37] >> I didn't think that I didn't think about yes, if if you might be in the placebo, then you cuz vitamin D everyone really needs. So, you know, you might want to Did you Did you do a sub-analysis and look at
[25:54] um, the what for whom the vitamin D was most effective? I mean, did you look at maybe people who are low did you look at maybe people who are low at the beginning or or or BMI?
[26:08] >> We have found for several health outcomes in the VITAL trial that the participants who benefit the most from the vitamin D supplements are those in
[26:20] the healthy weight range and those who are in the overweight or obese category are in the overweight or obese category with a a BMI especially above 30 with a a BMI especially above 30 did not derive the same benefits. It was
[26:35] almost like there was some blunting or attenuation attenuation of the vitamin D supplement benefit um, of the vitamin D supplement benefit um, with associated with higher adiposity.
[26:47] with associated with higher adiposity. And even with very high doses of vitamin D such as 4,000 IU's a day, tested in the diabetes prevention, the D2D
[27:00] trial of vitamin D. They found that the benefit was They found that the benefit was concentrated in the participants with a BMI below 30, and there was no clear benefit among the participants with a
[27:14] benefit among the participants with a BMI above 30. So, although this may BMI above 30. So, although this may reflect that people with higher BMI reflect that people with higher BMI just need very very large doses of
[27:27] vitamin D. It may go beyond that, and it may relate to vitamin D receptor activity, activity, um a certain resistance, um or blunting,
[27:40] um a certain resistance, um or blunting, blocking of the effect of vitamin D with blocking of the effect of vitamin D with with higher um adiposity levels. And we're actually exploring this to try to understand if there's a way to bypass
[27:55] um this barrier to the efficacy of vitamin this barrier to the efficacy of vitamin D with higher um BMI. You know, even D with higher um BMI. You know, even even looking at whether uh calcifediol
[28:08] is it it is a potential alternative to cholecalciferol, you know, the vitamin D3, rather than giving the vitamin D3 to
[28:21] uh to give a metabolized form of uh vitamin D, uh which may be of greater benefit or irrespective of a BMI. That still needs
[28:33] to be tested, but that is something that we're interested in understanding. But, um with telomere the telomere study, we with telomere the telomere study, we also saw that body mass index was
[28:47] a modifying the efficacy of vitamin D and that the greatest benefit for and that the greatest benefit for telomere protection was in those who were at a healthy weight. >> Right. And And just to go back to the
[29:01] different forms of vitamin D Uh so the the the form that we normally take has to be it is kind of a pre pre-vitamin D and it has to be processed before it >> Right.
[29:14] were talking about I'm I'm sorry I forgot the name would be >> calcifediol >> calcifediol would be the final form. >> It's not the final form. It's the liver metabolized form. So calcitriol
[29:30] would be the final form that is already metabolized by both the liver and the metabolized by both the liver and the kidneys. It's often given to patients who have kidney failure kidney uh disease um
[29:44] disease um but the intermediate form that is but the intermediate form that is basically the 25 hydroxy vitamin D as opposed to the precursor a form for that it
[29:58] may be of benefit irrespective of body mass index. So we're interested in that question but just to answer your question about whether there were any factors that modified
[30:10] the effect of vitamin D on telomere length um the answer is that um body mass index did modify the um greater response was in uh people who
[30:24] were at healthy weight and also um we did see some role of the baseline we did see some role of the baseline vitamin D blood level uh those who were very low tended to look like they were having a greater benefit but the study
[30:40] having a greater benefit but the study was not large enough, um to look at that with you know, with great statistical power because there were very few people who were profoundly deficient in vitamin D in the vital
[30:56] trial. And that's a good thing because if we found people were were profoundly deficient, we would want to treat them right away and not randomize them in a
[31:09] 5-year trial where they had a 50% chance of getting placebo. >> Right. Yeah, that definitely makes sense. So, one last question on the BMI. Did you Did you look at the serum levels? I mean, did you see that the
[31:22] levels? I mean, did you see that the serum levels of vitamin D were lower in in the people with high BMI? >> We looked at that and there was only a >> We looked at that and there was only a slightly lower blood level at baseline
[31:36] and achieved at 2 years, 4 years. There were only small differences by body mass index, but it's it was the case that those with higher body mass index tended to have less of an increase
[31:53] index tended to have less of an increase in the 25-hydroxy vitamin D blood level, less of an effect of the vitamin D on raising the blood level of 25-hydroxy D,
[32:05] raising the blood level of 25-hydroxy D, which is considered the best marker of vitamin D status. >> Okay. Did Did you do So, the the white blood cells are
[32:19] leukocytes, so they're part of the immune system and they have longer telomeres, so they are perhaps a little bit younger. Did Did you see any bit younger. Did Did you see any improvement in immune system function?
[32:33] Or did you look Were you able to look for that? for that? >> So, we haven't looked yet at immune >> So, we haven't looked yet at immune system function with physiological
[32:46] testing. It requires very specially collected blood samples and immediately collected blood samples and immediately examined. We have looked at markers of
[32:58] inflammation. So, we we've looked at not only the CRP, but also other markers of inflammation panel of
[33:10] markers of inflammation panel of inflammatory markers. And in general, there is an effect of the vitamin D supplements in reducing the CRP, reducing some of the other, but not all of the other
[33:24] all of the other markers of inflammation. 2022 that I also found really interesting was that vitamin D showed
[33:38] a reduction of 22% in autoimmune diseases. >> That was our vital trial. >> Yeah. Could you talk through What were
[33:50] the main parameters? Was that a sub-trial? And And what were the parameters of the kind of the the the subsection? Or Or was it the main trial? >> That was in the overall vital trial, but it wasn't the primary outcome of the
[34:06] vital trial. So, the primary outcomes were cancer and cardiovascular disease. But, we had a a collaboration with a team that was really interested with a team that was really interested in looking at autoimmune outcomes. And
[34:21] in looking at autoimmune outcomes. And it was a composite that was tested within the overall 25,000 plus participants in vital Um, looking plus participants in vital Um, looking at autoimmune diseases including
[34:37] at autoimmune diseases including um, rheumatoid arthritis, psoriasis, uh, multiple sclerosis, lupus, you know, even autoimmune thyroid disease like Hashimoto's. It was and Graves' disease. So, it was looking at overall at a
[34:53] So, it was looking at overall at a composite of autoimmune diseases. And we composite of autoimmune diseases. And we did publish in BMJ in um, about 4 years did publish in BMJ in um, about 4 years ago now that there was a 22%
[35:06] ago now that there was a 22% reduction in the risk of developing um, reduction in the risk of developing um, an autoimmune disease, any one of these uh, disorders that included in this uh, composite. And again, we saw a modifying
[35:21] effect of body mass index. So, the greatest reduction in autoimmune disease, uh, greatest reductions were in those who were at healthy weight. And there were blunted uh, responses in the other
[35:36] were blunted uh, responses in the other body mass index categories. We also saw that with longer treatment and follow-up, there was a uh, greater reduction in the autoimmune disease. So, it took a while which is
[35:51] would be expected. Um, the participants who were in the trial for at least one who were in the trial for at least one to two years had close to a 40% uh, percent reduction in autoimmune disease suggesting there's a latency period
[36:08] um, for the vitamin D to have this benefit. >> Yeah, and that's a really big I mean, 40% is is a really big reduction. So, it
[36:20] So, the these were well-fed healthy people in North America. And yet and they and you said like none of them were them >> Well,
[36:32] some of them were deficient. There were very few who were profoundly deficient. >> Profoundly. But giving them 2,000 IUs extra
[36:44] had this had this effect both on the the telomeres and on the autoimmune disease. Which would seem to imply that you know, people should take extra
[36:57] you know, people should take extra vitamin D. Yeah, we're we're waiting for guideline committees to take a close look at committees to take a close look at whether recommendations for vitamin D
[37:11] should change. As you may know, the Endocrine Society about a year ago did Endocrine Society about a year ago did provide some guidelines saying that the Institute of Medicine guideline 600 to 800 IUs a day still should apply to
[37:28] to 800 IUs a day still should apply to most of the population. However, some groups should consider supplements. They were not very specific about supplements, but they included adults age 75
[37:41] and older should seriously consider a supplement. People with prediabetes supplement. People with prediabetes because of the D2D trial suggestion of some benefit in reducing progression to diabetes once you have
[37:59] um a diagnosis of prediabetes. And they also made some recommendations for also made some recommendations for pregnant women and infants and children. But for the generally healthy adult population, even the the latest
[38:14] Endocrine Society guidelines were not for universal testing or for universal supplementation. However, we do think that
[38:26] based on the vital trial and the benefits that we've seen for reducing inflammation, autoimmune diseases, advanced cancers, and reducing the telomere shortening, this
[38:40] effect on telomere shortening, that taking a 2,000 IU a day supplement, the benefits would be likely to outweigh the risks. It It's a very safe dose.
[38:55] We saw virtually no side effects, so no adverse events with the dose of 2,000 IUs a day. It It increases the blood level
[39:07] It It increases the blood level of vitamin D, the 25-hydroxy D, but not to an excessive level that's been linked to to high blood calcium or urine calcium or
[39:20] or to an increased risk of kidney stones or something like that. So, it's a very safe amount of vitamin D, and it It seemed amount of vitamin D, and it It seemed that it was associated with several
[39:33] benefits, and it would be quite reasonable, especially for older adults. And we do agree with the Endocrine Society that in particular older adults, Society that in particular older adults, people 75 and older should seriously
[39:47] consider a vitamin D supplement. They're less likely to absorb vitamin D from the diet or to synthesize vitamin D in the skin, and it would be a group that would be very likely to benefit. But we think it It is a recommendation that could
[40:04] it It is a recommendation that could apply more broadly to at least the midlife and older adult population. >> Right. Do you recall what the average level blood level was at the beginning? I
[40:17] 40. >> It was It was close to 30. >> It was close to 30. >> But we we had thousands who had a blood level below 20. I mean, that was This was the advantage of the Vital trial.
[40:33] It's such a large trial. You know, we had 25,000 had 25,000 uh participants. So, the vitamin D blood levels at baseline really spanned the spectrum of um vitamin D. But in a
[40:48] general healthy population, you're not going to see a lot of profoundly deficient uh blood levels uh among people who are volunteering to be in a
[41:01] randomized trial. You see um people who have chronic diseases, they people who have chronic diseases, they already have a certain diagnoses that would have been an exclusion. Some of those diagnoses would have been
[41:14] of those diagnoses would have been exclusion for this uh primary prevention randomized trial. Um and you certainly see um you know, undernourished popula- uh populations with lower lower blood
[41:28] levels and and some groups uh with lower blood levels. But we actually had uh 20% of our study population was African American or black uh participants, and
[41:42] their blood levels were slightly lower at baseline than the rest of the population, but they were not um generally deficient or profoundly uh generally deficient or profoundly uh deficient in in vitamin D.
[42:00] They They would be lower because they make less from the sun? >> No, it relates to multiple different pathways. Some of it relates to the pathways. Some of it relates to the vitamin D uh binding globulin,
[42:14] um and gene variants in the vitamin D binding globulin. Some of it relates to binding globulin. Some of it relates to lower intake of um the uh dairy products and and uh vitamin D fortified foods because there is a higher prevalence of
[42:29] because there is a higher prevalence of lactose uh intolerance in certain groups um in the population. And um some of it relates to um less uh skin
[42:41] synthesis of vitamin D because of the melanin, which serves as a a form of a sunblock where with time outdoors when
[42:53] with without as much melanin in the skin, there would be more synthesis of skin, there would be more synthesis of of vitamin D in the skin from exposure to ultraviolet B light, but there's less uh synthesis related to the um melanin
[43:09] Right. >> Are you still following up with any of you know if they continued to take vitamin D? Were they kind of convinced of the benefit? >> We are following up. We continue to
[43:23] >> We are following up. We continue to follow all of our participants. Um so follow all of our participants. Um so we're we're now close to 7 years um 7 to 8 years after the intervention phase ended, and we continue to have regular
[43:38] questionnaires, regular follow-up um with the participants. We have a high uh with the participants. We have a high uh follow-up rate uh in terms of uh response to the surveys, the various questionnaires that we're sending. Um
[43:54] questionnaires that we're sending. Um and there's a substantial percentage uh and there's a substantial percentage uh taking a vitamin D supplement. Um I think this may relate to um the findings of the VITAL which we we have
[44:09] communicated with our participants about all of the findings. You know, we send all of the findings. You know, we send them um updates and newsletters and many of them may have been convinced that it makes sense to um take a supplement.
[44:23] They're particularly likely to take a supplement if they had been originally randomized to the uh vitamin D as opposed to the uh placebo arm. Um but it there's it's still uh close to half of the population not not taking a
[44:39] supplement. >> Right. Uh are are you going to use this >> Right. Uh are are you going to use this data as in as a kind of follow-up study? >> Oh, yes. I mean, we're we're continuing to uh publish from from the VITAL trial.
[44:55] we have hundreds of publications at this point and you know, we're we're very active in try to learn as much as we can um from the study even going beyond the effects of the intervention. We're
[45:12] effects of the intervention. We're really interested in uh the overall topic of prevention of chronic disease and extending health span and staying healthy healthy uh longevity and um we've been looking at a number of
[45:27] biological pathways in addition to the telomere um pathway. We've been looking telomere um pathway. We've been looking at the epigenetic clocks and what is um related to changes in in those clocks and the effects of lifestyle
[45:43] and um we're some of the ancillary studies are also continuing. You know, like the bone health, fractures, autoimmune diseases,
[45:55] you know, continuing to look at other risk factors for those outcomes. >> Yes, it is a bit of a diversion from where we were, but I did see that in the main trial, there was not a significant reduction in bone fractures.
[46:12] >> That's right, and I think that this is further support for the Institute of Medicine's recommended dietary allowance, that we
[46:24] recommended dietary allowance, that we need only small to moderate amounts of need only small to moderate amounts of vitamin D for bone health, which the the RDA, the recommended dietary allowance, was based largely on the
[46:39] allowance, was based largely on the benefits of vitamin D for bone health, and prevention of rickets, osteomalacia, osteoporotic fractures, and the
[46:52] and the conclusion was that you need small conclusion was that you need small amounts, 600-800 IU's a day, in order to amounts, 600-800 IU's a day, in order to maintain good bone health. And in the
[47:04] VITAL trial, we didn't see a clear benefit of an additional 2,000 IU's a day on preventing osteoporotic fractures, total
[47:16] fractures, also did not see clear benefits in terms of bone mineral density. But, the VITAL trial was designed to
[47:28] look at whether vitamin D had benefits beyond bone health. Maybe for bone health, you require only small to moderate amounts of this
[47:40] small to moderate amounts of this 600-800 IU's a day, determined by the Institute of Medicine. However, maybe for cancer prevention or autoimmune for cancer prevention or autoimmune disease prevention or slowing biological
[47:54] disease prevention or slowing biological pathways of aging, you benefit uh from pathways of aging, you benefit uh from 2,000 IUs a day or higher amounts of 2,000 IUs a day or higher amounts of vitamin D. So, that's what we've been
[48:06] testing in VITAL, and certainly for our primary outcomes, it wasn't a clear yes, primary outcomes, it wasn't a clear yes, you definitely benefit from 2,000 IUs a
[48:18] you definitely benefit from 2,000 IUs a day, but for um specific outcomes, it's it's sort of like targeted for specific purposes, um vitamin D supplementations did seem to be a benefit and we benefit. And we
[48:33] also want to understand um the modifying effect of body mass index and other factors because some groups seem to benefit very widely from
[48:47] uh vitamin D supplements, and other groups didn't seem to benefit as much. So, we want to understand is there a way to help all people benefit from vitamin
[48:59] D supplementation? >> Yes. That is interesting, especially the the high and low BMI. Because Because I mean, vitamin D is fat soluble, so it could be just going into the fat, but you said that the the blood
[49:14] >> Yeah, it doesn't seem to be that. So, there's some other >> That's part of it, but it's it doesn't seem to be the full answer because even seem to be the full answer because even with 4,000 IUs a day, there seemed to be
[49:29] this modifying effect um that the benefit was limited to those that the benefit was limited to those with with lower BMI, and also the amount of difference in the vitamin D blood level that's achieved with the
[49:44] supplements is relatively small difference, and it just wouldn't explain the lack of benefit um in the uh high BMI groups.
[49:59] When you measure the blood level of vitamin D, it's called vitamin D, are you measuring the final version or this is the precursor? >> It's the the vitamin D blood level that we
[50:14] measured on nearly everyone in the study was the 25-hydroxyvitamin D. So, it's already metabolized by the liver and it has a longer half-life,
[50:29] several week half-life, so that it's a good stable marker of vitamin D status. good stable marker of vitamin D status. Whereas, the biologically active vitamin Whereas, the biologically active vitamin D, the 125-dihydroxyvitamin
[50:47] kidneys and perhaps some other tissues in the body, that has a very short in the body, that has a very short half-life and it's the measurements are Um it's only a snapshot at that point in
[51:02] it's only a snapshot at that point in time and it may not uh be as reliable. time and it may not uh be as reliable. For example, vitamin D is very um tightly regulated. It's metabolism is very tightly regulated in the body
[51:15] very tightly regulated in the body because it is such a crucial, such a vital um nutrient um marker um nutrient um marker um hormone. And um in order in order to
[51:29] hormone. And um in order in order to ensure that the body does have enough of the biologically active 125-dihydroxyvitamin
[51:43] regulation of metabolism to keep that level normal even if you have relatively level normal even if you have relatively profound deficiency. And so measuring just the biologically active form, the 125 dihydroxy vitamin D, might not alert
[52:02] you to an actual deficiency that's present in terms of the precursor forms of the vitamin. >> Okay. So, Dr. Manson, thank you so much for joining us today. Where can So, there's many more trials going on and
[52:18] you're working on more ancillary papers. Where can people follow the work and what's coming the the papers that are coming out of VITAL of VITAL? >> So, we have a website. It's called
[52:32] >> So, we have a website. It's called vitalstudy.org. investigator section, even to the general public section, you can learn a lot about VITAL. It has a listing of all of our publications. You can access at
[52:47] least the abstract of all of the papers and many of the papers are already in um open access and you can get uh the full the full papers. But, it's got a listing
[53:01] the full papers. But, it's got a listing of um most of the VITAL publications. We're constantly updating it with uh the more recent publications. And it also talks about some of the findings of the VITAL trial that you can find on on the
[53:16] website, vitalstudy.org. >> Okay, thank you. I will definitely link to that. Okay, Dr. Manson, thank you so much for talking with you. >> Yeah, great talking with you, Richard.