Vitamin D Deficiency and Statin Drugs

by Duane Graveline, MD, MPH.

In my books, 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. 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.

There are only a few good natural dietary sources of vitamin D, in particular oily fish like salmon, mackerel and sardines and liver and egg yolks. For many people though, their main dietary sources will come from foods that have been fortified with vitamin D like certain milk, orange juice and breakfast cereal products.

Most of our vitamin D comes from the synthesis of cholesterol in the body by exposure to ultraviolet light from the sun. Predictably, those with dark skin, people in northern latitudes in winter and anyone that routinely avoids sun exposure or uses sunscreen or sunblock, are more likely to be deficient in vitamin D. In addition, the aged skin of the elderly impairs cholesterol conversion as does the presence of obesity.

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. The high prevalence of vitamin D deficiency, even in those taking multivitamins, indicates that a critical review of vitamin D needs is a major priority.

One thing to note is that vitamin D decreases the inflammatory marker C-reactive protein (CRP) so is very beneficial for reducing inflammation. However, according to one study, too much vitamin D has the opposite effect and actually raises CRP.1 So achieving and maintaining the optimal level of vitamin D, without exceeding it, is important.

The body regulates the amount of vitamin D produced from sunlight, so you cannot overdose on vitamin D from prolonged exposure to the sun. It is possible, however, to get too much vitamin D from supplements and because vitamin D is fat soluble, any excess is stored in the body. If you take high dose supplements, it is important to have your vitamin D level checked.

The process by which the body makes vitamin D from sunlight is as follows. 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 decade 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 everything has changed. Giving something a cytokine status can do that.

Without any sun exposure, you need about 4,000 units of vitamin D a day. 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 heterogeneous 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 in everyone.

As a matter of fact, studies make it all but certain that statins appear to raise vitamin D levels in some almost as if each statin user was given 1,000 IU of vitamin D3 at the same time.

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 (NF-κB) combined with this new cytokine status of calcitriol. Meanwhile, be aware that the effect of statins on calcitriol is not fixed, allowing for considerable individual variation.

Ref: 1

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

Updated May 2016

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