Vitamin D for dementia ... but how much?

Back in September, we wrote about research finding that supplementation with vitamin D was shown to reduce the risk of developing dementia.  My own primary care provider had recommended that I take vitamin D, so I had been taking 50mcg a day of vitamin D-3.

So what are these units?  It turns out that supplements and medications are measured in different ways.  "Mcg" stand for microgram, or one millionth of a gram.  And a gram is 1,000th of a kilogram.  But these are also often measured in "international units," or IU.  Fifty mcg turns out to be 2,000 IU.  

As we noted in the earlier post, vitamin D isn't really a vitamin, it's a hormone.  Hormones only signal different parts of the body to do certain things.  The hormone insulin signals cells to take up glucose from the blood.  It does not actually participate in metabolism of glucose.  Vitamin D signals the initiation of a number of processes throughout the body, including the processes associated with bone development.

Vitamin D is normally produced in the body when the skin is exposed to sunlight.  During winter months, and when people otherwise don't get out in the sun enough, we don't have enough vitamin D to prompt the various processes that it controls.  Including, apparently, some processes that defend against dementia.  The concept here is that the supplements will make up for the missing exposure to sunlight.

So there are different kinds of vitamin D with different numbers associated with them.  Kind of like the B vitamins.  But the B vitamins are not hormones, and it makes a big difference if you have B-12 or vitamin B-6.  However, the research we reviewed in September wasn't able to find a big difference between how different D vitamins function.  So it seems which vitamin D you take doesn't matter.  So I get vitamin D-3 at Costco at a reasonable price.

But what's an appropriate dose?  There are warnings about overdosing, and some recommended supplement doses are quite low.  Fortunately, there is some new research leading to a conclusion that 2,000 IU per day is the sweet spot.  And, as it turns out, that's often the dose of commercially available supplements.  Like the Costco gel cap that I take.

The research was published in the journal Nutrients, with the title "Vitamin D Supplementation: A Review of the Evidence Arguing for a Daily Dose of 2000 International Units (50 µg) of Vitamin D for Adults in the General Population."  (Note µg = mcg.)  It claims to have weighed the dose required to produce positive results in a number of bodily process against doses that might be harmful.

While the September article explicitly discussed influence of vitamin D on dementia, the study in Nutrients did not.  It did, however, discuss influence on the development of diabetes, which is difficult to separate from Alzheimer's disease.  Because lifestyle has so much to do with how both Type 2 diabetes and Alzheimer's disease develop, Alzheimer's disease is sometimes called Type 3 diabetes.

Both vitamin D and vitamin K2 contribute to similar functions in the body and my act synergistically.  According to this study (and a few others), the results with respect to health from supplementation with both together is greater than what would be expected as the sum of both.  So you will see vitamin D and vitamin K2 offered together in the one supplement.  Some say they should still be taken separately.  I take them separately, but I haven't seen research demonstrating that as necessary.

Will vitamin D supplements help prevent dementia?

We have been a bit skeptical about many of the claims for various dietary supplements as preventative for Alzheimer's disease and other dementias.  Certainly, if your cognitive issues are caused by a deficiency of vitamin B-12, logic says that taking vitamin B-12 supplements will likely help.  But what about other vitamins?  Evidence has been scant.

About two years ago, I began with a new primary care provider.  He looked at our book and became quite excited.  The story I told and the dementia toolkit were exactly the things he'd been telling his patients.  But he did say he thought I should add vitamin D supplements to my diet.  I followed his plan and then had my vitamin D measured.  The value measured was through the roof, so I significantly backed off.  Nonetheless, I have continued to take 50 mcg of vitamin D3 twice a day since.

Vitamin D is technically not a vitamin, but rather a hormone.  It is manufactured in the bodies of mammals when their skin is exposed to sunlight, and it works to signal the regulation of certain biological processes.  That is what hormones do - signal processes.

So does taking vitamin D supplements affect someone's susceptibility to Alzheimer's disease and dementia?  There is some evidence that it does.  An article published in the March 2023 journal Alzheimer's and Dementia; Diagnosis, assessment, and disease monitoring provides the results of a study of a large population of subjects (12,388) with regard to use of vitamin D supplements and incidence of dementia.  Data on the subjects were found in existing databases from several sources.  The results?  "Across all formulations, vitamin D exposure was associated with significantly longer dementia-free survival and lower dementia incidence rate than no exposure."  In other words, people who took vitamin D supplements had a lower incidence of dementia.

But, as usual, the devil is in the details.  This was a longitudinal study.  Longitudinal studies infer cause and effect relationships by studying behaviors of populations.  They are not "interventional" or "experimental" studies.  The latter will make a change and measure results, often comparing results to a placebo.  Cause and effect relationships can be much more reliably established with experimental studies than with longitudinal studies. Also, variation was found in sex differences, which variant of the APOE gene one carries, and other variables.

Nevertheless, the results were intriguing.  

How might this work?  Vitamin D is involved in many biologic processes.  One suggestion is that it is involved with the clearance of beta amyloid in the brain.  Sort of like those monoclonal antibodies that have been in the news.

I will continue to take vitamin D supplements -- as recommended by my primary care provider.

You can read more about this study here.

More Stories in the News

Back on August 25, we posted about stories in the news regarding Alzheimer’s and brain science that had caught my attention. Since then, a few more stories have popped up. Several involved early detection of AD. Here’s what I’ve seen: 

1. While “neural plasticity,” the ability of the brain to constantly break and reconnect pathways in the brain, is an important feature of how a healthy brain functions, this process may go to excess in persons developing Alzheimer’s. Higher flexibility in the networks involved with vision may turn out to be a new biomarker for diagnosing the disease. Here’s an article about it. 

2. Another one bites the dust: A phase 1 study of another anti-amyloid beta antibody developed by a company named Prothena found an unacceptably high rate of brain swelling. The treatment candidate was named PRX012. Brain swelling is a significant side effect for all of the monoclonal antibody treatments, like Aduhelm and Leqembi. Here’s an article about PRX012. 

3. If you successfully completed 10th grade biology, you know that adenosine triphosphate, or ATP, facilitates the transfer of energy in the cell. (Of course you do.) In so doing, the ATP molecule loses a phosphate group that must be restored. It’s the job of another molecule called creatinine to take care of that. For some time, creatinine supplements have been sold to help facilitate physical exercise by supporting the transfer of energy in muscles. But, if you read Beating the Dementia Monster and this blog, you know that the brain uses a LOT of energy itself, and creatinine plays a role there too. New research found that creatinine supplementation in older adults (like me) appears to support healthy brain functioning. So my wife and I take 5-gram creatinine gummies once a day. Here’s an article about it. 

4. A recent study found that the lower concentrations of omega-3 fatty acids in women may help explain why women are more likely to develop Alzheimer’s. This might be remedied by women consuming more foods and supplements with omega-3s. (For example, by eating more salmon.) While we know that beta amyloid plaques and tau tangles characteristically appear in the brains of people with Alzheimer’s, Alois Alzheimer also identified the presence of lipid (fat) droplets in the brain. Failure to move the fats out of the cells may be a part of AD pathology, and it may be we haven’t been paying enough attention to this. And it may be that a poor balance between LDL and HDL cholesterol is inhibiting the proper metabolism of these fats, causing them to accumulate. (Cholesterol has an important role in fat metabolism.) This appears to be more the case with women, and some believe it might explain why women are more likely to develop Alzheimer’s. Part of the equation is the omega-3 fatty acids found in, for example, some fish oils. The recommendation would be to ensure you are consuming enough omega-3 fatty acids, especially if you are a woman. Here’s an article about it. 

5. Is Alzheimer's an autoimmune disease?  We knew that changes in sense of smell can suggest the onset of Alzheimer’s. But why? In Beating the Dementia Monster, we discussed the microglia, cells that form part of the unique immune system in the brain and how they may play a role in Alzheimer’s. Recent research suggests that a loss of control of the immune process causes the microglia to incorrectly identify olfactory nerves and attack them. This would occur in the context of the development of the disease. Hence to correlation between loss of smell and the appearance of the disease. Here’s an article about it. 

6. As we’ve discussed before, there is ample evidence associating vitamin D supplementation with brain health. It’s not just about strong bones. But why? Some recent research correlates adequate vitamin D with the preservation of telomeres, the caps on the ends of chromosomes. They get shorter with age, which makes us more vulnerable to the diseases of old age – like cancer and Alzheimer’s. Vitamin D consumption, whether in the MIND diet or with supplements, protects the telomeres that protect us. Here’s an article about it. 

7. New research reinforces our understanding of the role that problems in the gut might play in influencing the development of Alzheimer’s. The answer is, of course, a high-fiber diet – which is the answer to a lot of problems in the gut. Apparently, immune cells in an unhealthy gut can travel to the periphery of the brain and contribute to the development of the disease. At least in mice. While this finding reinforces our existing observation that a high-fiber diet is essential to brain health, it opens to door to more possibilities in how to understand and treat the disease. Here’s an article about it. 

8. There’s a new three-minute brain wave test that, so far, appears to be very good at diagnosing Alzheimer’s. It’s called the Fastball EEG. Apparently, it’s more reliable than the hours of testing I was subject to when I was diagnosed. Basically, the subject learns a set of eight pictures. Then, he or she is shown a blast of pictures at a rate of three per second. One in five of these is one of the eight pictures the subject learned previously. The EEG then registers the reaction the brain has to what it sees. This is pretty interesting, but, for ease of administration, it’ll come in second to the new blood tests we’ve discussed previously, and it may be no more accurate. Here’s an article about it.  My sense is that this test might be good at recognizing hippocampus damage caused by Alzheimer's, but it doesn't probe the other parts of the brain which may be failing due to other diseases and disorders.

This isn't all.  More next time.

Vitamins Are Bad for You ... Maybe Kill You?

When I was in high school -- or maybe it was college -- I remember Linus Pauling making news on several fronts.  He had won the Nobel Prize in chemistry and he was a political activist.  But then he was saying that he'd taken supplements with a high vitamin C concentration for an extended period of time and it had kept him from getting a cold.

It was kind of big in the news, and a lot of people started taking vitamin C supplements to keep from getting sick.  But my skepticism antenna went up right away.  As near as I could tell, he was committed to a scientific conclusion based only on his own anecdotal evidence.  As it turns out, the idea that Vitamin C prevents or cures sickness has been scientifically discredited, but the mythology persists to this day.  This has stained Pauling's legacy as a remarkable scientist.    

In the 1970s, the idea that vitamin E had increased fertility in rats generated a lot of consumption of vitamin E supplements on the belief that it might have aphrodisiac properties.  This ended abruptly when a study claimed to have found that people taking vitamin E were more likely to die younger than those not taking them.

Vitamin B-12 deficiency can lead to dementia, although not Alzheimer's dementia.  With the exception of supplements that can be generated from yeast, we normally acquire it from animal products, so vegans must take extra precautions to ensure they get adequate B-12.

Vitamin C and vitamin E are antioxidants that can fight oxidation damage in the brain, and oxidation is part of the Alzheimer's disease process.  This is why foods with antioxidant properties, like blueberries and strawberries, are included in the MIND diet.  (We wrote about this back in June.)  We anticipate the results of a large study of the MIND diet that may confirm its benefit with respect to Alzheimer's disease.

As we discussed in Beating the Dementia Monster, sometimes we extract nutrients and chemical products from beneficial foods and consume them as supplements.  If they benefit our health in the food, then the supplements should convey the same beneficial properties.  But they don't.

The other day, I saw a BBC article about vitamins ("Why Vitamin Pills Don’t Work, and May Be Bad for You") that was saved by Pocket. The article smacked Pauling up side the head and described a lot of research about vitamin supplements.  Several studies suggested premature deaths resulted from consumption of vitamin supplements.  The authors noted that we don't understand all the dynamics of nutrition, and different nutrients and chemicals in the food may act in concert to produce their benefit.  So consuming red wine (moderately) may have a beneficial effect, but consuming the active ingredient (resveratrol) as a supplement does not.

The article was interesting reading, but the bottom line was: skip the supplements and eat your fruits and vegetables. 

New Research on Young Onset Dementia

You may have seen news articles about a study of young onset dementia published in Nature Neurology.  We discussed younger onset (or familial) Alzheimer's disease (AD) in Beating the Dementia Monster.  We said that, while the cause is much more (perhaps entirely) influenced by genetics than older onset (or sporadic) Alzheimer's, it is often very much affected by lifestyle interventions.  But when I began to read the news articles about it, I got the impression the researchers found most young onset dementias were being caused by lifestyle factors -- smoking, alcohol abuse, sedentary lifestyle, etc.

I went to the journal web site where I could read the abstract without having to purchase the whole article.  After reading the abstract, I figured a couple of things out.  First, as we've noted before, "young" refers to under 65 years of age.  (I didn't always think of that as "young," but I sure do now!)  But also, the article was about all causes of dementia, not just Alzheimer's disease.  So the article addressed dementias that included those from vitamin deficiencies, stroke, etc.  Alzheimer's is conceivably a minority of these dementias in the "young."

I was surprised that the researchers found a correlation with the APOE "risk gene" that we discussed in Beating the Dementia Monster.  This gene is normally associated with old onset Alzheimer's.  And they didn't mention the "deterministic genes" we discussed associated with young onset Alzheimer's.  If you have these genes, you almost certainly will get young onset AD.

The research was conducted by scientists from Maastricht University and the University of Exeter.  They studied 350,000 cases in a European database.  The study found 15 factors associated with the development of young onset dementia, including (with my own comments):

Lower formal education (early learning appears to affect how the brain develops)

Lower socioeconomic status (I believe this correlates with other lifestyle habits, such as smoking, alcohol use, diet, and exercise)

Presence of the fourth variant of the APOE gene (I thought this only went with old onset AD)

Excess alcohol use

No alcohol use (a surprise, but alcohol abstinence may be necessitated by other risk factors)

Social isolation (we have discussed this before)

Hearing loss (this promotes social isolation)

Vitamin D deficiency (they don't mention vitamin B12, which we have discussed before)

High levels of C-reactive protein (a symptom of inflammation in the body which promotes AD)

Reduced hand-grip strength (I'm not sure why this is other than a reflection of physical fitness)

Orthostatic hypotension (a likely heart issue)

Stroke (Obviously)

Diabetes (a well-known correlation with Alzheimer's disease)

Heart disease ("What's good for the heart is good for the brain")

Depression (Possible association with social isolation)

So what is modifiable in this list?  There's not much that's inconsistent with the Dementia Toolkit we provided in Beating the Dementia Monster.  But it surprised me that they did not mention diet or exercise.  Of course, these are highly associated with vitamin deficiencies, heart disease, and diabetes. 

The shifting research on vitamin supplements and cognitive decline

Back in 2019 we discussed reports that said not only do vitamins not help with cognitive decline, people who take them have a higher rate of all-cause mortality.  But in 2022 we heard that researchers publishing with the Alzheimer's Association were finding that maybe vitamin supplements help after all.  At least a little.  So that's confusing.

Recently, some of you told me that you'd read about new research supporting the use of multivitamins to fight cognitive decline.  The research was conducted at Massachusetts General Hospital and was published in The American Journal of Clinical Nutrition, January 18, 2024.  In the study, the memory and cognition of 573 individuals were tested at the beginning of the study, although only 492 were still available or willing to be tested at the end of the two-year study period.  The study was placebo controlled, although it wasn't clear to me how many were given the placebo.

The researchers concluded "daily multivitamin supplementation leads to a significantly more favorable two-year change in episodic memory.  [Other research studies] indicate that daily multivitamin use significantly benefits both global cognition and episodic memory.  These findings ... support the benefits of a daily multivitamin in preventing cognitive decline among older adults."  So that's good, although some commentators characterize the effect as "modest."  Some speculate that the multivitamins support the gut microbiome and the gut-brain axis, which we've discussed before.  Other experts believe that the multivitamins are simply making up for vitamin deficiencies that you would not otherwise have if you adhere to the Mediterranean diet.

Of course, the researchers did not believe their findings were sufficiently conclusive; more research needs to be done.

Incidentally, the research did not find a positive effect for executive function or attention, two deficits of brain function associated with Alzheimer's disease.  So I'm inclined to think the context for the benefits of multivitamin supplementation is more associated with slowing the effects of normal aging and less with slowing disease.

More Detail on Dr. Ornish's Sudy of Lifestyle Interventioins for Alzheimer's Disease

We have written often about the distinction between longitudinal studies and randomized controlled trials.  To date, the majority of the research on lifestyle and Alzheimer's has been longitudinal studies.  You look at a population and take surveys on what people eat, what exercise they get, etc.  You assume that they are telling you (and themselves) the truth about what they do (and don't) eat, and how much real exercise they get.  Then you see how many of them develop dementia.  Many longitudinal studies produce disappointing results, but my view is that the quality of their data is very poor.

In a randomized controlled trial, you change peoples' lifestyles and measure the results.  Rather than rely on self-reporting in surveys, you either control the actual food they eat or measure the chemicals in their blood to see what they've been eating.  With respect to exercise, you supervise the exercise and measure it.  You measure the results with intense cognitive tests, MRIs, PET scans, and blood tests.  Oh, and then there's the control group - a set of test subjects who don't change their lifestyles, but are subject to the same results measurements.

Obviously, the randomized controlled trials are MUCH more reliable.  However, they are much more difficult -- and costly -- to actually perform. 

Back in July of 2024, we reported that Dr. Dean Ornish was completing a randomized control trial of lifestyle interventions for Alzheimer's disease.  We were heartened that he not only found improvements in memory and cognition tests, but he also found improvements in biomarker evidence, specifically Alzheimer's biomarkers in cerebrospinal fluid.  That's now one of the two gold standard tests for diagnosing Alzheimer's.  Dr. Ornish's study involved 51 patients between the ages of 45 and 90, all of whom had been diagnosed with MCI or early dementia due to Alzheimer's.  But only about half of these received the interventions.  For the intervention group, Dr. Ornish found positive results after 20 weeks.

The other day I came across another article referencing this research ... except the article called it "new."  Thinking it was newer than what we discussed before, I started to develop a new post on the research ... before realizing I'd already posted about it.  Nevertheless, I think it's worth revisiting, since the research is so compelling.  And it's so consistent with my own experience.

What I think is worth revisiting are specifics about the interventions used in the study.  So here they are:

Diet: 

Whole foods, minimally-processed plant-based (vegan) diet, high in complex carbohydrates (predominantly fruits, vegetables, whole grains, legumes, soy products, seeds and nuts) and especially low in harmful fats, sweeteners and refined carbohydrates.  It was approximately 14-18% of calories as total fat, 16-18% protein, and 63-68% mostly complex carbohydrates. Calories were unrestricted. Those with higher caloric needs were given extra portions.  Twenty-one meals/week and snacks plus the daily supplements listed below were provided throughout the 40 weeks of this intervention to each study participant and his or her spouse or study partner.  Twice/week, three meals plus two snacks per day that met the nutritional guidelines as well as the prescribed nutritional supplements were shipped overnight to participants and partners.  Participants were asked to consume only the food and nutritional supplements sent to them and no other foods.

This is similar to the MIND diet, except the MIND diet restricts cheese, stick margarine, and butter.  It also allows some poultry and fish. 

Group Support:

Each patient and their spouse or study partner met three times/week, four hours/session via Zoom: 

- One hour of supervised exercise (aerobic + strength training) 

- One hour of stress management practices (stretching, breathing, meditation, imagery) 

- One hour of a support group lecture on lifestyle 

- Additional optional exercise and stress management classes were provided. 

Supplements 

- Omega-3 fatty acids with Curcumin (1680 mg omega-3 & 800 mg Curcumin, Nordic Naturals ProOmega CRP, 4 capsules/day). 

- Multivitamin and Minerals (Solgar VM-75 without iron, 1 tablet/day).

- Coenzyme Q10 (200 mg, Nordic Naturals, 2 soft gels/day). 

- Vitamin C (1 gram, Solgar, 1 tablet/day).

- Vitamin B12 (500 mcg, Solgar, 1 tablet/day). 

- Magnesium L-Threonate (Mg) (144 mg, Magtein, 2 tablets/day). 

- Hericium erinaceus (Lion’s Mane, Stamets Host Defense, 2 grams/day). 

- Super Bifido Plus Probiotic (Flora, 1 tablet/day).

The Alzheimer's Association Facts and Figures Report for 2020 Is Now Out

I'm hoping that all of our readers are well, both physically and emotionally.  These are difficult times, but we will persevere.  

Each March I wait for publication of the Alzheimer's Association annual Facts and Figures Report.  (I wrote about last year's report here.)  This is my first go-to resource, and I cite it often in both editions of Beating the Dementia Monster.  So they have now published the 2020 edition, and I have downloaded it.  The report updates the statistics on the disease each year, but it also explains and updates what research is telling us about the disease.  This year adds another increment to our understanding.

We covered most of what's new and (to me, at least) interesting in our regular blog posts since last March.  As the news comes out, I try to write about it promptly.

One thing that struck me was their inclusion of a graphic in this year's report showing the progress of Alzheimer's disease from the pre-clinical stage through the third stage of Alzheimer's dementia.  I made a similar graphic here, and I use it in presentations and in the (still forthcoming) second edition of Beating the Dementia Monster.  In my presentations and in the book's discussion I break down Alzheimer's disease into its five stages (pre-clinical AD, MCI, mild dementia, moderate dementia, and severe dementia), but in my graphic I only show Alzheimer's dementia as a single, final stage of the disease -- so three stages.  Their graphic breaks dementia down into its three stages, so their graphic shows five total stages of the disease (pre-clinical, MCI, and the three individual stages of dementia).  Theirs may be more helpful.

Something that caught my attention was a discussion of the importance of an accurate diagnosis of the cause of a dementia case.  Alzheimer's disease is responsible for 60 to 80 percent of dementia cases, but there are other causes, and their treatments will vary.  This contradicts the too-common practice of diagnosing Alzheimer's disease purely on the basis of a single Mini-Mental Status Exam or a Montreal Cognitive Assessment.  At Harborview in Seattle, they subjected me to a couple of hours of psychometric testing and a brain MRI.  I've also had blood tests looking for vitamin deficiencies and other potential causes of my MCI.  These are required for an accurate diagnosis and an appropriate course of treatment.

Something else they highlighted was a research finding that people who are concerned enough about deteriorating cognition to consult a heath professional often do have Alzheimer's disease or another cause of dementia.  Everyone over about 60 begins to worry if they have Alzheimer's disease, but if they're not worried enough to see a medical professional about it, it's likely they are simply experiencing the result of normal aging.

They continue to promote annual screening for neurodegenerative disease, emphasizing that it's part of Medicare for everyone over 65.  But doctors say they're too busy to do it, and a lot of their patients tell them they don't want to know if they have Alzheimer's disease.  So we continue to not test enough.  On the other hand, they (like us) noted that we are close to a very sensitive blood test for Alzheimer's disease, and I'd bet these tests will become routine soon enough for everyone over 65.

They have re-worded the discussion of the role of lifestyle changes in addressing Alzheimer's disease, but I didn't see anything new.  The role of lifestyle changes is, of course, the thesis of Beating the Dementia Monster.

They simplified their discussion of brain changes over what they had last year, notably the roles of beta amyloid and tau tangles.  I think it's helpful to read both of them -- this year's and last year's.  The two articles overlap a lot, but each seems to have insight missing from the other.

They didn't focus quite so much this year on what to expect in the future, but their discussion is no less bleak than last year's.

If you're nerdy, you'll want to read the first three chapters, but we covered most of the material here our blog over the past 12 months.  If your focus is on caregiving and the consequences of dementia, you'll want to read chapters four through six.