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The Role of Vitamin D in Reducing Risk of Alzheimer’s and Dementia - transcript Dr. Grant March 2023


Transcript of Podcast

Patrick Holford: Simple Wisdom for a Healthy Life

In this podcast I’m talking to Dr William Grant, regarding the recent study showing that those who supplement vitamin D have much less risk for Alzheimer’s and dementia.

He knows more about vitamin D and the effects of sunlight than anyone I know. He’s not a medical doctor but a  PhD - in physics with an entire career at NASA. After retiring from NASA, he formed the non-profit organisation, £Sunlight, Nutrition and Health Research Center” in San Francisco to continue his work on the roles of diet and UVB/ vitamin D in reducing risk of chronic and infectious diseases.

He published a review of the role of vitamin D in risk of dementia in 2009 followed by several additional publications on vitamin D and Alzheimer’s disease and dementia. He has 284 publications regarding vitamin D listed at pubmed.gov.

You can read more about Alzheimer's and Dementia on my website.
0:00:02.7 Holford: I'm talking to Dr. William Grant, who knows more about vitamin D and the effects of sunlight than anyone I know. He's not a medical doctor, but a PhD in physics with an entire career at NASA. After retiring from NASA, he formed a nonprofit organization, Sunlight, Nutrition and Health Research Center in San Francisco to continue his work on the role of diet and UVB and Vitamin D in reducing risk of chronic and infectious diseases. He's published a review on vitamin D in relation to dementia in 2009. So really ahead of the curve, followed by several additional publications on vitamin D and Alzheimer's disease and dementia. He has 284 publications regarding vitamin D listed @pubmed.gov, which is where we all look for research. So Bill, and thank you so much for giving me the time. How's the weather in San Francisco?

0:01:00.4 Grant: Well, it's been about 11 or 12 degrees centigrade today. It's... We've had quite a bit of below 10 degrees for the last month or so, fair amount of rain, but today is sunny, clear, and almost warm enough to go out and enjoy a stroll in the parks.

0:01:19.1 Holford: Will you make some vitamin D today?

0:01:22.1 Grant No. No. Sun is too low. If my shadow is longer than I am, I can't make vitamin D and that applies to, in San Francisco for another month or two.

0:01:31.2 Holford: Okay. And then the clouds roll in then you can't make any either.

0:01:35.2 Grant Exactly. In San Francisco, we're known for the fog and clouds this summer.

0:01:39.5 Holford: So what does this study show? The headlines in the newspapers are supplementing Vitamin D helps reduce dementia risk. What does the study actually show?

0:01:50.0 Grant Well, they followed, what was it, 12,000 people for 20... Followed quite a few people in a cohort study. And what they did was they found out which of them were taking prescribed vitamin D. That's either vitamin D3 or vitamin B2, or vitamin D3 plus calcium. They did not find out what their baseline or achieve vitamin D levels were. They didn't find out how much vitamin D they were taking. But the fact that they were taking prescribed vitamin D means a couple things. One is that they probably have low baseline vitamin D levels because the doctors identified that for some reason they needed extra vitamin D. And the other thing is, since it was prescribed, it was probably a reasonably healthy dose, probably at least 1 or 2 thousand if not more international units per day. And that would be enough to raise their vitamin D levels by maybe 10 to 15, just guessing 10 to 15 nanograms per milliliter, or 25 to 35 nanomoles per liter.

0:03:05.7 Holford: What did they actually find from the data?

0:03:08.1 Grant Okay, what they found then was that there was a 40% reduced risk of developing dementia, of which about 80% was Alzheimer's disease. This is over a 10-year period. This is a very important finding. It's a step below a clinical trial, but it's an observational study based on vitamin D supplementation. And that's a good way to do it, that has been shown in the Veterans Administration Hospital to be associated with greatly reduced risk of myocardial infarction and COVID-19. Even though randomized controlled trials have not shown benefits for either of those.

0:03:52.8 Holford: Now, I'm... Of course, we wish, no doubt that we knew the level of the people at baseline when they started the trial in their blood, in their serum. And then again at the end, because that would really help in the exploration of what may be optimal. And I'm so grateful that you can rapidly translate between the American measure, the nanograms per mil, and the UK measure where we measure it in. Is it millimoles or micromoles? Millimoles.

0:04:22.9 Grant Nanomoles per Liter.

0:04:24.5 Holford: Nanomoles. Nanomoles per liter. So here in the UK generally below 50 nanomoles per liter is considered deficient. And I'm not sure what that figure is in nanograms.

0:04:40.1 Grant 20. There's 20 nanograms.

0:04:41.3 Holford: 20 nanograms.

0:04:42.5 Grant Factor 2.5.

0:04:43.6 Holford: Yeah. So probably these people were deficient if they were prescribed that, and we don't know that because the data isn't given. And in your research, what is the level in the blood that equates to optimum in the context of cognitive function, dementia and so on? And is it a straight line? In other words, the more you have, the less your risk. What do we know about optimum?

0:05:12.3 Grant Well, I did a quasi meta-analysis based on four or five observational studies, and it appears that below, say 25 nanomoles per liter it is very high risk for Alzheimer's disease and dementia. Going above 75 nanomoles per liter or 30 nanograms per milliliter, was associated with significant reductions in dementia and Alzheimer's disease. The optimal level may be as high as 40 nanograms per liter or 100 nanomoles per liter. So few people with that high levels were included in these observational studies. We don't have real good evidence on that.

0:06:03.4 Holford: Yeah. This is a really important thing is that the more people we have who we can track in relation to dementia risk or dementia development later in life, and we know their blood vitamin D levels, their serum vitamin D levels, then we can actually start to work out what confers the greatest benefit, the least risk. And you're suggesting in the UK figures it's about a 100 nanomoles per liter. And as you said, very few people have that. What percentage of the population are up at that optimal level? What percentage are at the level that is clearly conferring a much higher risk, like below 50 nanomoles per liter or in the States that would be 20?

0:06:47.7 Grant Well, up to 40 or 50% have below, about 50% have below 50 nanomoles per liter, probably about 5%, have above 100 nanomoles per liter. And maybe above 75 nanomoles per liter, maybe 15, 20 percent. So all those with below 20... 50 nanomoles per liter could certainly benefit from supplementing with vitamin D to try to raise their vitamin D levels.

0:07:18.0 Holford: So we're really saying in effect that at least half of the population have significant risk because their vitamin D level is low and they would clearly benefit from supplementing on a daily basis or a weekly basis. 'cause it stores, doesn't it?

0:07:36.1 Grant Right. Right. Now, of course there's another factor involved too, and that's obesity. Obesity rates are rising because of consumption of ultra-processed foods and obesity is a very important risk factor for Alzheimer's disease. And people who are obese require much more vitamin D a Factor 2 or so, more than those who are not obese. And what's very interesting is that Alzheimer's takes about 20 years to go from start to full-blown Alzheimer's. And they've shown that you've got to look over a 20-year period to find the effect of obesity. If you wanna look at 10 years, you've lost half of the increase.

0:08:19.8 Holford: And this study was a 10-year period, wasn't it?

0:08:23.1 Grant Yeah. But that's okay. They're finding the effects of vitamin D.

0:08:27.2 Holford: Now tell me why would obesity have such a negative effect on vitamin D status?

0:08:34.4 Grant Well, for one obesity is associated with systemic inflammation. In other words, the adipose or fat tissue is producing compounds that increase the inflammation and inflammation is one of the risk factors for Alzheimer's disease. One of the other risk factors for Alzheimer's disease is free radical oxidative stress. And I presume they have more oxidative stress as well. Perhaps in part because due to the diet. See, if you go to a nice optimal plant-based diet with a lot of vitamins and the proper trace minerals, you can reduce the production of free radicals and reduce the amount of inflammation. But it turns out to have the optimal diet to reduce risk of Alzheimer's is much more expensive than having going out and buy hamburgers and chips and that sort of thing.

0:09:44.4 Holford: So those explanations are not sort of direct. I was wondering whether vitamin D is less available if there's more fat tissue...

0:09:54.8 Grant Well, okay, it is stored in the fat tissue. But there's just a larger volume. If you take 1,000 IU per day and you have way small amount, it'll go farther. It raises the blood level much more. The study... The vital study...

0:10:12.4 Holford: Is it good to have a lot of fat tissue storing vitamin D or less 'cause the obesity link would suggest it's not good?

0:10:19.2 Grant Well, it is sort of a sink. However what's very interesting is that in winter vitamin D levels are about 50 to 70 percent of what they were in summer because they are... The body is recirculating stored vitamin D in the muscles and the muscles store vitamin D as 25-hydroxyvitamin D which is the same metabolite of vitamin D that's measured when you get your vitamin D level measured by drawing your blood. And so it's... So having a lot of muscle mass is gonna be better for utilization, storage and utilization and supply of vitamin D than is vitamin D in the fat. Now, if you go on a weight loss program and have a lot of fat, you will raise your vitamin D level as some of the vitamin D stored in the fat tissue is released to the serum. But it's not really very active in the adipose tissue.

0:11:21.9 Holford: So you wanna store it in your muscle not so much fat. Now, how much vitamin D would you need to take to get up to this 100 nanomole level or the equivalent in the US?

0:11:33.6 Grant Okay. So I weigh about 60 kg and by taking 5,000 IU per day, I've gotten up to 72 nanograms per milliliter which is about what, 180 or so nanomoles per liter. So maybe 4,000 IU per day for a smaller person would do.

0:11:58.8 Holford: Okay. So it's certainly sort of 3,000 or above in it.

0:12:04.5 Grant Right.

0:12:06.5 Holford: Now, just out of interest as you are expert on sunlight, how much exposure to sunlight in the months where the angle of the sun is sufficient, or if you live in more equatorial regions, would you need to have to achieve that kind of blood level?

0:12:25.9 Grant Well, it's hard to get up above 100 nanomoles per liter in the sun, in part because the sun not only produces vitamin D, but sunlight also destroys vitamin D. It destroys some of the metabolites. So it's easy to get up around 30 sorry, 75, 80 nanomoles per liter. In fact, in England some people in the summer generally have an average value around 75 to 80 nanomoles per liter. But getting much higher. See, part of the problem is that as you go in the sun every day you start to tan and tanning reduces the amount of UVB hitting the 70 hydro cholesterol level by a Factor 2 to 4, at least in those people who can tan easily. I'm not sure how much people in the UK with Celtic skin tan. But it's...

0:13:24.6 Holford: We tend to get red. laughter

0:13:25.7 Grant Right.

0:13:26.5 Holford: White is red. But the reason I ask you this is, it's sort of interesting because in the research that we've been doing on Omega-3 and particularly DHA, it turns out that the optimal level is maybe 1,000 milligram a day, which is way more than what most people who supplement are even supplementing. So we know that supplementation in the case of omega-3 is associated with reducing risk for dementia by about 10%. So I'm really thinking evolutionarily here because we have to go back to the time when we were hunter-gatherers and Homo Aquaticus and living a lot more time by the water's edge, obviously outdoors. I mean, we're designed to be naked outdoors and living a lot further South than London, for example. So it's kind of interesting that in a sort of... In a large part of our evolutionary history, and certainly, when we came out of Africa rather than being in the Northern climate, it seems that we probably, and I'm asking this as a sub-rhetorical question, may have had blood levels 80 to 100 nanomoles per liter in the UK measure. Is that likely?

0:14:39.0 Grant Yes, yes. Let me explain. There are studies from Eastern Africa showing that pastoral people who stay outdoors all the time, and are unclothed get up around over 100 nanomoles per liter. And I did a study based on data from five Nordic countries on cancer incidents based on occupation. And it turns out that those with outdoor occupations, whether it be gardeners or farmers or fisher-folk or things like that, they had... Cancer rates had about 80% of the average, whereas those with the indoor occupations like waiters and bartenders and office workers and so on, had as much as 10 to 20 percent above average. So even in the Nordic country where they only get sunlight to produce vitamin D in maybe six months of the years, those who had outdoor occupations could get the high levels of 25-Hydroxyvitamin D. Now, as you well know, most people nowadays live indoors, work indoors, live in big cities, do not get much sun. So it is just very, very difficult for most people through casual sun exposure to achieve greater than 100 nanomoles per liter.

0:16:00.8 Holford: So I mean, the essence is if we want to be anywhere near our evolutionary ancestors or 99% of our history so to speak, as Homo Sapiens, really the only way is to supplement probably at least 3000 IU, in the winter maybe a bit less in summer. Is that correct?

0:16:20.5 Grant Yes, more or less. Michael Holick has shown, based on the whole-body radiation of participants in a tanning bed, one can make 10,000 to 20,000 international units of Vitamin D per day with whole body exposure. So if you're exposing a third of the body, that would be maybe 3000-6000 IU per day.

0:16:45.4 Holford: Okay. So with the appropriate sun exposure, maybe 20, 30 minutes a day in the summer, you don't need to supplement so much?

0:16:54.6 Grant Well, it depends on where your targets you're trying to reach.

0:16:57.7 Holford: Indeed. So now there's an interesting finding in this because we are moving now into sort of theory or hypothesis because one of the findings was the APOE4 carriers. So this is a gene that has variations, the APOE gene. And one of them, APOE4, confers a slightly increased risk for dementia. It's 4 to 6 percent overall. And in this study, they found the APOE4 carriers did a bit less well from the vitamin D. And the authors suggest that the APOE4 carriers would be better off because the gene would confer better absorption. And if they're absorbing better, generally speaking, their level would not have been so low, and hence they would have less benefit from the supplements, which is kind of a little bit of a twisted explanation. But what's your take on this possible explanation for why the APOE4 carriers did less well in terms of reducing dementia risk in this study?

0:18:03.7 Grant Yes, yes, that's a good explanation. It's also known that APOE ε4 does increase Vitamin D absorption. But there's an interesting study from England by Crowe, C-R-O-W-E in 2011. The study compared meat-eaters, fish-eaters, vegetarians, and vegans, looked at 25-Hydroxyvitamin D or Vitamin D level, winter, spring, summer, and fall. And they found that for all seasons, the meat-eaters had the highest Vitamin D level, the fish-eaters slightly lower, the vegetarians much lower, and the vegans lowest. And the difference was 20 nanomoles per liter between meat-eaters and vegans. So, yes, diet does provide a lot of Vitamin D, especially if you're eating... Now meat is muscle and muscle, like I said, are good stores of Vitamin D. It has 25-Hydroxyvitamin D and that has not been included in the food frequency tables, but is now being recognized as the explanation.

0:19:07.2 Holford: What's that got to do with the APOE4?

0:19:10.0 Grant Well, so the people with APOE4 are eating the same diet as the people without APOE4 and are just utilizing more of the Vitamin D in their diet than those without the APOE ε4. So the...

0:19:29.3 Holford: Now the thing is, generally we think APOE4 will increase the risk of dementia, but in this case, if APOE4 in fact improves the absorption of Vitamin D, then we're not talking here about a supplement study.

0:19:45.8 Grant Well, but even...

0:19:46.3 Holford: And you would expect that they would've less risk if Vitamin D was the major kind of driver?

0:19:52.0 Grant No, no. APOE ε4 is still a risk factor for Alzheimer's, diet included. But you've gotta look at the differential effect of the supplementation. And since they're starting from a higher base, they... The...

0:20:12.3 Holford: Probably, 'cause we don't know their blood levels, do we?

0:20:14.8 Grant But the relationship between Vitamin D level and vitamin D intake, changes as you go up in vitamin D level. If you have a high vitamin D level, taking more vitamin D is gonna have a less effect than if you have low vitamin D level. It's like if you're thirsty, a glass of water does a lot for your... Hydration of your body. If you're full of water, taking another glass doesn't do anything. Same thing for vitamin D.

0:20:42.7 Holford: So really we would've loved to have seen the blood levels of vitamin D before and after, because then you could look at these differences with APOE4, funny enough what I did recently and it was triggered by a very, very nice study in the British Medical Journal of 30,000 people in relation to their diet. And it didn't change their diet, just looked at their diet and in effect they could be good diet, average diet or bad diet. And what they found was a significant increase in risk of dementia in the bad diet versus the good diet. And slightly less in the average diet versus the good diet. And of course, like so many of these good studies, they measure APOE4, which is present in maybe one in four people, but they found absolutely no difference in APOE4. So I went back to all the other intervention studies with B vitamins, omega-3 and so on. And generally, I could not find any significant difference in the group with APOE4 once they were doing something, eating a better diet, taking B vitamins, having omegas and so on. So this study is slightly different in that respect. But anyway, this is kind of the theoretical explanation for benefits. What do you think are the potential mechanisms that could explain why having enough vitamin D reduces risk for dementia?

0:22:12.6 Grant Well, reduces inflammation, reduces free radical production, oxidative stress, inflammation is a risk factor for neurodegeneration. And...

0:22:29.1 Holford: So should we think of vitamin D like an antioxidant?

0:22:33.0 Grant It has that effect. It reduces... Well, I'm a little hazy on the exact mechanism, but it has been shown to have some antioxidant properties. For one thing, I think it helps increase glutathione levels, and glutathione is an antioxidant as I remember.

0:22:56.4 Holford: And what about mitochondrial function? Does it have any effect on mitochondrial function? They're the energy factories within our cells.

0:23:07.0 Grant Yes. I'm not really up on that yet either.

0:23:09.5 Holford: Yeah. So it's one of the extraordinary things 'cause vitamin D has so many extraordinary effects on so many diseases, cancer, heart disease, obviously bones as we know, immunity, and now dementia. And I'm still myself just struggling, intrigued, interested in what the mechanisms may be. And I'm sure that research in the future may unpack that. One of the things the authors say is that, or suggest, is that vitamin D may lead to less amyloid proteins and P-Tau proteins. I'm a bit suspicious of this, I have to say. And the reason is there have been 30 trials now that have successfully lowered these abnormal amyloid proteins that produce plaques in the gaps between cells and the synapses. So 30 studies that have effectively reduced amyloid by some fairly toxic drugs. And none of them have produced anything that we could call a clinical benefit. So I'm just wondering if this is another myth story. Like we had the story that cholesterol was the cause of heart disease, and now we get the story that amyloid is the cause of Alzheimer's, and yet $50 billion worth of research later and we don't really see any results. What's your take on amyloid and vitamin D? Do you think this is a plausible explanation?

0:24:41.8 Grant Well... Yeah, I tend to agree with you in part that it's like the smoke and it's not the fire. I mean, it's sort of the indication. But I think I'm researching that Alzheimer's now on diet, and I think there is some evidence that I'll try to send you, that amyloid, there is evidence that amyloid plays a role. The... One thing I've found recently is that good sleep helps reduce amyloid buildup. And good sleep is a risk reduction factor for Alzheimer's. If you don't sleep very well, you increase your risk of Alzheimer's. What happens the last hour or so of sleep is when the brain sort of clears a lot of the junk that's in the brain, which includes a lot of the amyloid and I'm actually studying this in my own personal way in that I carefully monitor my number of sleep hours and my functionality during the day with respect to diet. And if I have a just light dinner with fruits and vegetables and maybe some carbohydrates, I sleep very well. If I have a heavy meal with protein and fat and so on, I am often interrupted in the middle of the night and lose an hour or two of sleep, wake up the next morning very groggily. So, and this... I think this, well, helps throw some light on it.

0:26:20.5 Holford: Yeah. I mean the conversation, it's a sort of a, well, not, it's not really quite a chicken or egg thing, but it's a bit like amyloid could be, and I think probably is, just an artifact. In other words, part of a, if you like, inflammatory process. So it's a little bit like if you've got a disease, I mean let's say arthritis or an aching joint, and there is inflammation present, are you saying, A; That inflammation causes this, or B; That inflammation is a response to something that causes the problem. And then if you kill the inflammation, for example, if you take the joint situation with painkillers, it reduces your pain. Does it actually affect or slow down the progression of the disease? And we know in arthritis it doesn't, so long-term studies, it doesn't work. So that's kind of what we're talking about. Is amyloid actually part of the cause or is it just a consequence? And if vitamin D, you know, does many things, it's associated with less inflammation associated with less amyloid and so on. But what's kind of really interesting, and I hope that we will sort of tease out is, and the important finding of course is that having more vitamin D, which for all of us humans who aren't living in the equator and aren't spending as decent amount of time outdoors, it actually means that we all need to be supplementing vitamin D at a level probably in the winter of 3,000-5,000 IUs, in the summer, a bit less. Is that a fair summary? How would you conclude?

0:27:56.8 Grant Yeah. Yeah. Vitamin D is very, very beneficial and should be supplemented. And once you also think about taking vitamin K2 to help put the calcium in the hard tissues, not in the soft tissues.

0:28:11.7 Holford: And how much do you need of K2 in that consequence?

0:28:15.0 Grant I... Whatever the bottle says, I'm not sure.

0:28:17.2 Holford: Yeah, it's usually about 100 microgram, I think. Or a little bit of nattokinase. That'll do it, won't it?

0:28:23.8 Grant Right, right.

0:28:24.6 Holford: Yeah. Great. Well, Bill, thank you so much for sharing your wisdom. It's really good. This is yet another study showing the tremendous benefit of supplementing vitamin D. And thank you very much.

0:28:38.6 Grant You're welcome.


Risk of Dementia and Alzheimer's vs Vitamin D level (Dr. Grant)

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From The role of vitamin D in reducing risk of Alzheimer’s disease - Grant Dec 2022
Corrected March 2023, attached at the bottom of this page


VitaminDWiki - Overview Alzheimer's-Cognition and Vitamin D starts with:

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