Jeffrey Bland, PhD, explains the concept of hormesis—small amounts producing large biological effects—and uses vitamin D as a key example. He notes vitamin D is converted to a hormonal form (1,25-dihydroxycholecalciferol) that modulates tens of genes via the vitamin D receptor, affecting insulin sensitivity, immunity, inflammation, neurological and cardiovascular function, and bone. He cites a study in which women taking the aromatase inhibitor Aromadex experienced severe arthralgia/myalgia associated with low 25-hydroxyvitamin D3 levels; raising vitamin D into the normal range with high-dose supplementation reduced or eliminated their pain, illustrating nutrient-based therapeutic effects beyond standard nutriture.
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September 22, 2010
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You know, I've been recently talking about this concept called hormesis, which once again stands for a small amount of substance having a much bigger biological effect than we would have anticipated based upon a traditional dose response relationship. So small means big in this case of hormesis. So can I think of an example other than the essential fatty acid epa, DHA example that I described previously? And yes, the answer is there are many other examples. But one that's certainly been in the news that we've been talking about a lot recently is vitamin D. Vitamin D. If you think about the amount of vitamin D that is required to promote function, it's in the microgram level, very, very small amount. And this amount, you might say, is so trivial and so insignificant relative to the total size of the body that it would have very little if any part positive effect on function. Yet what we find is that vitamin D gets converted by the body through two steps, through the liver and the kidney into a compound that's called125 dihydroxycholecalciferol, which is a sexual hormone. It's a hormonal form of vitamin D which regulates many, many different functions. In fact, tens of different genes are modulated by vitamin D, connecting to the vitamin D receptor through this 125 dihydroxy vitamin D form and then regulating gene expression. Now you might say, well, what's the range of effects that this association could have on human function? It includes things like regulating insulin sensitivity, having a positive effect on immune system, lowering inflammation, improved neurological function, improved cardiovascular function by the effects it has on endothelial cells in the vascular wall, effects that it has on bone, obviously, which we know well about. There are so many different pleiotrophic, meaning multiple effects that this regulatory substance has that we can't say one agent means one outcome. It's a systems biology influence that it has in regulating function. Now, there's a recent report that just appeared in the literature that demonstrates the range of effects that something like this can have. There was a study done in women who had a very serious adverse effect from drug therapy. They were taking the drug called Aromadex, which is an aromatase inhibiting drug that's used in women who have breast cancer. And one of the side effects of this drug, unfortunately is severe arthralgia and myalgia, joint and muscle pain. And this can be so severe in women that are treated with this medication. Often they discontinue the beneficial medication because they're so discomforted. In this particular study, it was found that many of these women have very low levels of the hormonal form of vitamin D. They have low levels of 25 hydroxy vitamin D3 in their blood. And by supplementing these women with very high doses of oral vitamin D, in order to bring their level in the blood up into normal range, that they were able to demonstrate that the pain syndrome that these women were having, their arthralgias and myalgias were basically eliminated or significantly reduced. So you might say, well, how does vitamin D regulate pain? Well, the answer is this inflammatory process associated with this drug and the effect on women who are taking it is modulated through genetic expression patterns that are regulated in part by this vitamin D125 dihydroxy vitamin D hormonal form, through the vitamin D receptor signaling, ultimately into genomic expression. So here's another example of a very small amount of the substance, the right substance at the right place at the right time, having a very large effect on clinical outcome. And in this case, I'm obviously talking about nutritional pharmacology. This is not your normal vitamin D nutriture here. We're using a replacement therapeutic dose in order to get a specific clinical outcome of benefit. So I think these are examples of the emerging frontier of our understanding of how to use nutrients effectively to modulate function throughout the life cycle. And even in those cases where we're getting certain kinds of drug induced adverse side effects.
