Vitamin D Deficiency and Statin Drugs

dr_duane_graveline_m.d._134By Dr. Duane Graveline, M.D., M.P.H.

In my book, Statin Drugs Side Effects and the Misguided War on Cholesterol, and on this website I have discussed the vital role of cholesterol in the human body. Our most important hormones depend upon adequate reserves of cholesterol for their production and nowhere is this more important than as the precursor substance for the synthesis of vitamin D, known also as calcitriol.

Researchers in this field are sufficiently concerned from the results of their studies to pronounce that we are in the midst of an epidemic of vitamin D deficiency of immense proportion. Study after study of nursing home populations, of nursing mothers, of healthy male and female volunteers and of various children's groups have consistently documented how relatively rare it is to have optimal levels of vitamin D. And predictably vitamin D deficiency is even more severe in dark skinned populations.

Some authorities support more liberal dietary supplementation of vitamin D in food products. Others are urging that practical new approaches for vitamin D repletion are urgently needed. This high prevalence of vitamin D deficiency, even in those taking multivitamins, indicates that a critical review of vitamin D needs is a major priority.

A vitamin D precursor is synthesized in the skin from cholesterol in response to absorbing UVB ( Ultraviolet B ) rays. It then gets converted in the liver to an intermediate form known as calcidiol. In the kidneys it joins with an important enzyme for conversion of the circulating calcidiol into its active hormonal form known as calcitriol but it is in the immune system that calcidiol morphs into its final cytokine state capable of a wide variety of anti-inflammatory and immunomodulatory activities.

Only in the past two years have we been able to glimpse at the true role of vitamin D in overall health. It is far more than just maintaining normal blood levels of calcium and phosphorus and optimizing skeletal health. The extra-skeletal health benefits of vitamin D we now know are numerous, ranging from inhibition of smooth muscle cell migration, suppression of vascular calcification, down-regulation of pro-inflammatory cytokines and up-regulation of anti-inflammatory cytokines. Anti-cancer effects involve multiple immunomodulatory properties.

Only after connecting with the vitamin D receptors (VDRs) of special immune system cells does circulating calcidiol become the cytokine-like calcitriol. Simple vitamin D has now become a biochemical wizard for cytokines are a category of signaling molecules used extensively in intercellular communication.

Each cytokine has a matching cell-surface receptor. Subsequent cascades of intracellular signaling then alter cell functions. This may include the up-regulation and/or down-regulation of several genes. Cytokines are characterized by considerable "redundancy", in that many cytokines appear to share similar functions.

In recent years, the cytokine receptors have come to demand the attention of more investigators than cytokines themselves, partly because of their remarkable characteristics and partly because a deficiency of cytokine receptors has now been directly linked to certain debilitating immunodeficiency states. It is for these reasons that vitamin D has now become a new biochemical. Like the rest of my peers, I thought for fifty years that vitamin D was important only to calcium, the parathyroid gland and our bones. Now, in just two years everything has changed. Giving something a cytokine status can do that!

Many factors potentially interfere with UVB conversion. As noted earlier, people having darker skins are much more likely to have vitamin D deficiency. The aged skin of the elderly impairs cholesterol conversion as does the presence of obesity. The present day emphasis on protecting the skin from the sun, using sun-screens and blockers, also cuts down on the ability of UVB to convert cholesterol to vitamin D. Last but not least, one needs UVB exposure.

Without any sun exposure you need about 4,000 units of vitamin D a day. In the absence of other supplements you would need 40 glasses of milk or ten multi-vitamins capsules daily to supply your vitamin D needs. Most of us make about 20,000 units of vitamin D after 20 minutes of summer sun due to UVB conversion of cholesterol. Numerous studies document that the majority of society falls short of meeting either their dietary or UVB conversion needs for vitamin D.

Now consider the impact of statin drugs on a society already overburdened with an epidemic of vitamin D deficiency. Cholesterol must be available in our bodies in amounts sufficient to allow UVB conversion to vitamin D. We are all genetically blessed with a "natural level" of cholesterol. What is natural for one person may be completely inadequate for another. Into this heterogenous pool we dump statins indiscriminately in a misguided attempt to bring everyone's natural level of cholesterol down to some artificially low level.

I cannot think of anything more likely to aggravate our already immense, vitamin D deficient state. But something strange has happened. Now that we have measured vitamin D levels more extensively we have learned a new truth. Lowering cholesterol does not necessarily lower vitamin D. As a matter of fact, recent studies make it all but certain that statins appear to raise vitamin D levels almost as if each statin user was given 1,000 IU of vitamin D3 at the same time. And we do not as yet know why this is happening.

In time I suspect we will learn it has something to do with the property of statin drugs to inhibit Nuclear factor-kappaB combined with this new cytokine status of calcitriol. When I find out I will let you know. Meanwhile a few researchers have even suggested that the benefits of statins may come from the vitamin D they seem to enhance. So why not just take vitamin D instead? That's still a bit too early for me to say.

Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor

Updated July 2011

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