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The Link Between Vitamin D and Alzheimer's

Alzheimer’s disease is probably one of the most dreaded diseases of old age and it is often worse on the family than it is on the patient. Many people think that there is no way to prevent Alzheimer’s disease, and that is not quite true.

There is fair evidence that regular physical activity helps stave off dementia, but it is always difficult to be too certain about this association since the people who exercise more tend to be healthier overall. An overall healthy diet of many fruits and vegetables is also felt to be beneficial, although advocating any one food or mineral is more fanciful thinking than hard science. Controlling your cardiovascular risk factors, like high blood pressure, has also been shown to be helpful though the data is not definitive. Of course, walking around with high blood pressure is bad for you for many different reasons. Finally, staying mentally active is also likely beneficial, so reading the paper and doing the daily crossword is probably better for you than you realize.

Despite the caveats and the uncertainty regarding the evidence, most of these things are probably beneficial and hardly a bad idea either way. But it is also hard to maintain long-term lifestyle change of regular exercise and a healthy diet. A simple pill or medication to prevent cognitive decline would be a godsend for many.

Unfortunately, things like anti-oxidants, omega-3s, gingko have been studied without much success. However, the one potential therapy that does keep coming in conversation is Vitamin D.

Interest about Vitamin D and Alzheimer’s disease usually centers on articles like this one from the journal Neurology. This study found an association between low vitamin D levels and Alzheimer’s disease. Unfortunately, when media outlets and people hear this story they make two assumptions. First, that the low Vitamin D levels caused the Alzheimer’s disease and that taking Vitamin D will reverse it.

If it were true, it would be a cheap and easy way to prevent a dreaded disease. Unfortunately there’s another potential explanation: reverse causality.

Reverse causality can be thought of as the statistical equivalent of putting the cart before the horse. All studies investigate associations, meaning that you get a group of people that have X and see how many of them have Y. If people with X are more likely to have Y, you might say to yourself that X causes Y. But, it is equally valid to say that Y causes X. It is usually obvious what causes what. Obviously, smoking causes lung cancer and it is not lung cancer that makes you smoke more. Here timing is everything and since smoking came first, it must be the cause and lung cancer the effect.

But the situation is not always so clear cut. Consider a study published in the New England Journal of Medicine that showed an association between diabetes and pancreatic cancer. The casual reader might conclude that diabetes causes pancreatic cancer. In fact, many websites will claim that it does. But it does not. The trick to unlocking the truth in this study was the realization that subjects had only developed diabetes recently and that the pancreatic cancer predated the diabetes. Then cancer subsequently destroyed the insulin producing islet cells of the pancreas. Therefore this was not a case of diabetes causing pancreatic cancer but of pancreatic cancer causing the diabetes.

Mistaking what came first in the order of causation is a form of protopathic bias. There are numerous examples in the literature. For instance, an assumed association between breast feeding and stunted growth, actually reflected the fact that sicker infants were preferentially breast fed for longer periods. Thus stunted growth led to more breastfeeding, not the other way around.

So let us return to the problem of vitamin D and Alzheimer’s disease. Consider the problem now from the point of view of reverse causality. Does vitamin D lead to Alzheimer’s disease? Or does it happen like this? People with Alzheimer’s disease become less mobile, less independent and more socially isolated. They go out less. When they go out less, they become less exposed to sunshine, and consequently their vitamin D levels fall. Thus, if you took a bunch of people with Alzheimer’s disease they would be more likely to have low vitamin D levels. But vitamin D is not the cause, it is the effect. In fact the authors of the above paper freely acknowledge that reverse causality may explain their findings, it is only the media reporting that seemed to overlook this possibility.

Of course, the question most people really want to ask is “Will taking vitamin D supplements prevent Alzheimer’s disease?” The possibility is doubtful. Firstly, some studies have shown no association between vitamin D and Alzheimer’s. Also, low vitamin D levels have been linked with both heart disease and cancer but large scale trials have shown no benefit to vitamin D supplementation. Most of the research is observational in nature, and there is only one trial about dementia, a post-hoc analysis of the Women’s Health Initiative trial. It showed no benefit.

Finally, even if we accept that the link is true (which it may not be), it is important to note that most Canadians would not benefit from vitamin D supplementation because their levels are NOT low. Despite what many people claim, 68% of Canadians have high vitamin D levels (22% are low and 10% are truly deficient) and taking extra vitamin D would be useless. As Thomas Huxley said, “That is the great tragedy of science: the slaying of a beautiful theory by an ugly fact.”


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