#102 Why Vitamin D Deficiency Accelerates Brain Aging

Vitamin D Introduction

0:00Dr. Rhonda Patrick here. A new study found that vitamin D supplementation was associated with a 40% lower risk of dementia over a decade. After just five years, 84% of the vitamin D supplement users were dementia-free compared to 68% of the non-users. This was a study of over 12,000 people. And vitamin D reduced dementia risk by around 33% in adults with mild cognitive impairment and also had ApoE4. This is a key genetic risk factor for neurodegenerative diseases.

0:32Up to 25% of the population has one of these alleles, and it can double the risk of Alzheimer's disease if you have one of them. If you have two of these alleles, you can have up to a tenfold higher risk of Alzheimer's disease. Vitamin D is not just a vitamin. Vitamin D gets converted into a steroid hormone that regulates over a thousand genes in our body. It enters the nucleus of our cells, and it regulates, it activates, and turns on, or it suppresses and turns off up to nearly 5%

1:05of the protein-encoding human genome. This is very relevant because up to 70% of Americans fall into a range known as deficient or insufficient. So almost 30% of Americans actually are vitamin D deficient. They have levels of 25-hydroxyvitamin D below 20 nanograms per milliliter. The other 40% or so has levels that's known as insufficient. So these are people that have vitamin D levels above 20 nanograms per milliliter, but they're below 30 nanograms per milliliter. And there's really a

1:37simple solution to avoiding this deficiency and insufficiency, and that is a vitamin D supplement. Usually people that are vitamin D deficient, if they take around 2,000 to 4,000 IUs per day, they can get to a sufficient level. There's a lot of reasons why vitamin D deficiency and insufficiency is so widespread. That is because we actually make vitamin D in our skin upon exposure from UV radiation from the sun. So anything that blocks out UVB radiation is also going to block out

2:13the ability to produce vitamin D3 in our skin. That includes sunscreen. It also includes skin pigmentation. So melanin, this is the darker pigmentation that serves as a natural sunscreen. That also blunts the body's ability to make vitamin D3 from UVB radiation. Age. As you get older, your body is less efficient and effective at producing vitamin D3 from sun exposure. In fact, a 70-year-old makes four times less vitamin D from the sun than a 20-year-old

2:43where you live. So living in a northern latitude, many months of the year, actually, there's no UVB radiation even reaching the atmosphere. So people that are living in more northern latitude areas are not able to make vitamin D3 in their skin from the sun for many, many months out of the year. So that also really affects the ability to make vitamin D. And then also just body fat. So vitamin D is actually a fat-soluble vitamin, and it's stored in fat. And so the more body fat that you have,

3:15that means the less vitamin D3 is bioavailable to be released into the bloodstream where that it undergoes further metabolic conversion to the steroid hormone, which is actually what's

Study on Dementia Risk

3:27regulating all these genes, many of them in the brain. Now, we're going to dive a little bit deeper into this study that showed a 40% lower risk of dementia. But I want to mention first that this is not the first study to show this. I mean, there are many, many, many what are called observational studies that are looking at a correlation between low vitamin D levels and dementia risk. Many different studies have found this same association. And so one might say, well, people that are vitamin D deficient might just be less healthy. They might be going out in the sun less. They're

4:02exercising less. And so vitamin D deficiency might just be biomarking some other health factor. So that is a, I would say, pretty relevant argument. But we also have a whole host of other data to support the link between vitamin D deficiency and dementia risk and Alzheimer's disease risk. So for example, with these observational studies, we can look at what's called Mendelian randomization. This is a way to use genetics to look at how something in the environment can affect an outcome.

4:34In this case, there's many different genes that regulate the ability of your body to produce vitamin D3 and convert it into the steroid hormone. And some people do that less effectively because they have a certain variation in those genes that are not doing it quite as well. And so you can look at genetically low vitamin D levels. In other words, you just look at someone's genes. And if they have a certain variation of that vitamin D converting gene that makes it not as effective, you put them into

5:06the low vitamin D group because we know people with those genes actually do have low vitamin D. And then you compare them to people that have the normal functioning genes that don't make them have low vitamin D levels. They don't have low 125 hydroxy vitamin D, which is the actual steroid hormone. And then you look at the risk for dementia and Alzheimer's disease. And so what's been shown is that genetically low vitamin D levels increase dementia risk by up to 54%. Again, this is really

5:37confirming that observational data, which really can't really show causation. And so it strengthens that data, but then you can go a step further and you can look at other studies that have shown vitamin D deficiency actually accelerates brain aging. So there have been studies that have shown that have looked by fMRI at what's called white matter hyperintensities. So these kind of show up as little white hyper spots, if you're looking at an MRI image of the brain, and it's really a marker of damage to the

6:11white matter in the brain. And the white matter is where it's so important for brain function, for communication. It's how your brain's communicating. So when you have damage to that white matter, it really does affect cognition. It affects communication and memory. For every 10 nanomal per liter increase in vitamin D, there was a small decrease in the volume of these white matter hyperintensities, suggesting that having higher levels of vitamin D can protect against this type

6:43of brain damage. Even a step further, looking at vitamin D supplementation and how that can affect cognition. Now there's a lot of mixed data out there, particularly when it comes to vitamin D supplementation affecting cognition in normal healthy adults. But there have been a few trials that have actually looked at vitamin D supplementation in people with either Alzheimer's disease or people with mild cognitive impairment. So in both those scenarios and people with mild

7:15cognitive impairment, if they took around 800 IUs of vitamin D daily for a year, they had significant improvements in multiple areas of cognition, memory, attention, overall IQ. And the same goes with the Alzheimer's disease study. So people that took, again, 800 IUs a day for over a year, and these people were already diagnosed with Alzheimer's disease, they also had improved scores on memory and attention tests, similar to that first trial I just mentioned. But additionally, there was also a reduction in blood biomarkers of amyloid beta pathology, such as amyloid beta 42, which is associated

7:51with Alzheimer's disease progression. So this data really strengthens the argument that low vitamin D can increase dementia risk and that supplementing with vitamin D can help lower that risk, which brings us back to this recent study where vitamin D supplementation was associated with a 40% lower risk of dementia. So let's dive into that a little bit closer. So the study included 12,388 adults who were divided into two groups. Those who reported using vitamin D supplements in any form, it could be

8:24calcium vitamin D, it could be the active form of vitamin D, it could be vitamin D2. So any form of vitamin D, it didn't matter what form. And then the other group it was divided into is those that did not take any form of vitamin D supplement. There was a 10-year follow-up, and during that period, supplementing with vitamin D was associated with a 40% lower incidence of dementia. Over 2,000 participants who reported never using vitamin D supplements developed dementia compared to just 679 of those participants

8:58who actually did report using vitamin D supplements. Supplementing with vitamin D was also associated with a greater five-year dementia-free survival. So 84% of adults in the vitamin D group were free of dementia during this time period, while only 68% of the non-vitamin D users were dementia-free during that same period. And this was also true regardless of whether or not the participants had baseline mild cognitive decline or normal cognitive function. So vitamin D seemed to provide a benefit in both of

9:31those scenarios. And while dementia prevalence was higher in adults with mild cognitive impairment, it was around 15% lower in this group for adults who supplemented with vitamin D compared to those who didn't. So in other words, even if you already had some sort of mild cognitive impairment, you still had a lower risk of actually transitioning to dementia if you were supplementing with vitamin D. Although vitamin D supplementation reduced dementia risk among all groups, there were several interesting

10:04findings regarding the benefits of vitamin D for certain populations. So for example, women derived the greatest benefit from vitamin D. They actually experienced less dementia compared to men who supplemented. And while vitamin D using men had a 26% lower dementia incidence than non-users, vitamin D using women had almost a 50% lower incidence compared to non-using women. So really, there's a much bigger difference in terms of women having a lower incidence. And I'm wondering if that's because generally speaking, women get dementia and Alzheimer's disease about twice as higher of a

10:41frequency than men do. So there just might be more of a signal here to lower. That's one possibility.

10:48Adults that had normal baseline cognitive function had a 56% lower dementia incidence if they supplemented with vitamin D. But adults that did have mild cognitive impairment only had a 33% lower incidence of dementia if they supplemented. So in other words, if you were already, if you started out dementia-free and healthy, vitamin D had a more robust effect on lowering your dementia incidence, which makes sense. If you're already in a state of mild cognitive impairment, it's much harder to kind of reverse damage that's already been done. And this brings us to APOE4. So I mentioned earlier,

11:23APOE4 is the biggest genetic risk factor for Alzheimer's disease. 25% of the population carries at least one allele. Having one allele can increase the risk of dementia and Alzheimer's disease by twofold. Having two copies of that allele can increase the risk up to tenfold. So it's really important for people to understand that if they have one of these alleles, that they really need to try to do everything they can within their lifestyle to lower their dementia risk. And so people that had APOE4 that supplemented with vitamin D did reduce their incidence of dementia by around 33%.

11:57And among non-carriers, vitamin D reduced the incidence of dementia by 47%, a little bit higher, which is not surprising. And supplementing with vitamin D wasn't enough to outweigh the effects of carrying one or two copies of APOE4. These participants still had a 16% greater risk of dementia than non-carriers, even non-carriers who didn't use vitamin D. The same was true for another risk factor, having mild cognitive impairment, which elevated dementia incidence by nearly 400% compared to

12:28people that had normal cognitive function, even in the presence of vitamin D supplementation. So in other words, if you have an APOE4 allele, or if you had mild cognitive impairment at the baseline, then you had a tremendously higher risk of getting dementia and Alzheimer's disease. However, the vitamin D supplementation did still help. It just didn't help as much as someone that was healthy and had normal cognitive function and was a non-carrier at the start of this study.

Vitamin D Supplementation Benefits

13:00Okay, so let's dig a little bit deeper. Participants with mild cognitive impairment who didn't supplement with vitamin D had more than a 600% increase in dementia risk compared to the adults with normal cognitive function, even those who didn't use vitamin D. So in other words, I just mentioned that people that had mild cognitive impairment had a 400% higher risk of having dementia compared to people that had normal cognitive function at the beginning of the trial, but that was only if they

13:31supplemented with vitamin D. People that didn't supplement with vitamin D had a 600% higher risk of developing dementia if they started with mild cognitive impairment. It also didn't matter what form vitamin D was used. All of them were associated with a lower dementia risk. Specifically, using calcium, vitamin D was associated with a 44% lower risk of dementia. And using vitamin D3 was associated with a 37% lower risk of dementia. And then using vitamin D2, which is the plant version, was actually associated with a 50% lower risk of dementia. Using combined

14:06forms of vitamin D was associated with a 50% lower risk. So I think here in concluding thoughts, overall, not only the findings of this study, but the other studies that I talked about really do give strong support to this idea that everyone should probably be supplementing with at least some vitamin D to make sure they're avoiding deficiency. And I mentioned, as I mentioned earlier, deficiency is a widespread problem in the United States. Up to 70% of people are either deficient or insufficient.

14:39So getting a simple blood test is one of the best things you can do. Measure your 25-hydroxyvitamin D levels. This is the precursor to the active steroid hormone, 125-hydroxyvitamin D. And you want to have your 25-hydroxyvitamin D levels between 30 to 60 nanograms per milliliter is a great, I would say, level to have your vitamin D levels. You don't really want to go above 80 nanograms per milliliter, then you start getting into a pretty high range. Most people can take a supplement in the range of

15:102,000 to 4,000 IUs a day, depending on where your blood levels are at, and keep their vitamin D levels within that, you know, 40 to 60 range. So it's good to kind of do an annual vitamin D blood test just to make sure you're not taking too much or to make sure that you're actually taking enough to raise your levels into that sweet spot. And lastly, I just want to mention how vitamin D can support brain health. So vitamin D can enhance the removal of amyloid beta. This is a protein that's linked to

15:41Alzheimer's disease by promoting its efflux from the brain. Now, I mentioned in that study, it was a randomized controlled trial in people that were giving an 800 IUs of vitamin D a day, people that already had Alzheimer's disease, it lowered their amyloid beta plaque burden. Vitamin D also is an immune modulator. So vitamin D receptors on microglia and astrocytes in the brain help reduce excess neuroinflammation. So it basically helps lower the pro-inflammatory cytokine response in the brain. We know that neuroinflammation plays a major, major role in the cause of dementia and Alzheimer's disease.

16:17Vitamin D also upregulates a variety of neurotrophic factors, including nerve growth factor and also brain drive neurotrophic factors. So this is helping support neurotransmitters, supporting learning and memory. And then lastly, vitamin D also decreases oxidative stress. It's been shown in the mild cognitive impairment trial that I mentioned earlier. This was a randomized controlled trial. Those individuals that took vitamin D also had decreased levels of various markers of oxidative stress compared to people that were given the placebo. And so oxidative stress is an indirect way

16:52that can lead to a variety of inflammatory processes and stuff in the brain as well. So there's several different mechanisms by which vitamin D can support brain health. And again, it's pretty simple to get a vitamin D test and to take a relatively inexpensive vitamin D supplement as well. I'm Dr. Rhonda Patrick, and I'll talk to you soon.