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On Science: Why Vitamin D is suddenly so trendy

This article first appeared in the St. Louis Beacon, Jan. 6, 2010 - My doctor and I have a very simple health plan to keep me going till age 90. It has been in place for more than a decade, and has only five components:

1. Don’t smoke. I had smoked heavily in my 20s, but have not had a cigarette since 1972.

2. Keep my weight down. The hallmark my doctor set is a body-mass index below 26 (that’s your body weight in kilos divided by your height in meters squared; at 5’11” and 185 lbs my BMI is 25). I work out at the gym three days a week to keep it there.

3. Avoid excessive carbs. I am a type 2 diabetic, and so my doctor has me take two pills every morning and evening to keep my blood sugar levels below 120. I also avoid candy, French fries, and other carbohydrate-rich tasties, all of which I love but my health cannot afford.

4. Don’t eat so many steaks. Years ago my cholesterol levels were sky high, as I am by nature a bovine-atarian. For more than a dozen years, my doctor has had me take a daily tablet of lipitor; that and keeping steak to once a week has kept my cholesterol and blood pressure low.

5. Take aspirin. Every morning I take a tiny aspirin tablet. Why has my doctor advised this? Because aspirin thins the blood, making heart problems, should they occur, less severe. It’s a little bit of insurance.

There it is: take six pills, work out, eat sensibly and don’t smoke. Not rocket science, but so far this simple plan seems to be doing the trick. Now, all of a sudden, when I went for my annual checkup last month my doctor added a sixth component!

6. Take vitamin D. Every morning I am to take a small pill, 2,000 units of vitamin D.

As my doctor has never in 25 years suggested I take any extra vitamins, this got my attention. Asking around, I find a lot of my friends have recently received the same advice from their doctors. What is going on? Why has vitamin D suddenly become so trendy?

A Little Background

The world first became familiar with vitamin D in 1919. A British doctor, Sir Edward Mellanby, was treating rickets, a disease of children where softening of bones leads to fractures and deformity. It was, and is, one of the most frequent of childhood diseases in many developing countries.

By 1919 doctors had noticed that the disease was seen mostly among the poor, rickets being strongly associated with malnutrition. Mellanby discovered that what was missing in the diets of rickets children was not calories per se, but rather one specific item – a fat-soluble substance found in cod liver oil and other substances – what we now call vitamin D.

It turns out vitamin D plays a central role in how our bodies manage calcium, and so is essential for the proper development and maintenance of bone. Think of bone as flexible cartilage made stiff and strong by the addition of calcium, and you can see why a deficiency of calcium produced by lack of vitamin D would lead to rickets.

Vitamin D is an unusual vitamin. It is not a metabolite like vitamin C, not a cofactor (part of an enzyme that catalyzes cell activities) like the B vitamins, not a vision pigment like vitamin A, and not an anti-oxidant like vitamin E. Alone among the vitamins, vitamin D is a hormone, with a chemical structure like chickenwire. Synthesized mainly in the kidneys, it has very specific effects elsewhere in the body.

Where and How Vitamin D Works

Just where vitamin D acts in the body is a key element in the story of vitamin D. When the active form of vitamin D was characterized in 1969, the following nifty experiment became possible: by producing radioactive vitamin D (some of the carbon atoms are 14C) and injecting this “labeled” vitamin D into animals, investigators were able to trace the fate of vitamin D in the body. Rather than washing through the body like most vitamins, vitamin D entered cells and there was found to bind to a very specific receptor protein, what came to be called the vitamin D receptor (VDR). This VDR protein had but one function: to bind vitamin D molecules.

Where in the body are cells found that have VDR receptors within them? To find out, investigators prepared antibodies directed against VDR (such “monoclonal” antibodies are proteins with a shape that exactly fits one and only one molecule, in this case VDR) and looked to see where in the body proteins exist that the anti-VDR antibody could fit onto. What did they find out? As expected, bone has VDR receptors, and so do the kidneys where vitamin D is produced. But cells of the immune system also have VDR receptors, as do cells of the nervous system, muscles, intestine, pancreas and a variety of other tissues.

Why should so many other tissues feel the need to recognize vitamin D? The strong hint was that vitamin D is involved in other basic body processes as well as bone formation.

More recent studies, many of them carried out in the Renal Division of the Washington University School of Medicine, shed a great deal of light on this mystery by revealing just how vitamin D works:

  1. Vitamin D enters a cell where it encounters and sticks to the VDR receptor protein, goading it to change its shape and thereby activating it;
  2. The activated VDR protein then is able to cross into the cell nucleus and bind to another receptor protein found there called RXR;
  3. RXR carries VDR to the cell’s chromosomes, where VDR binds to specific base sequences called “vitamin D response elements, or VDREs;
  4. Located at the fronts of specific genes, the VDREs serve as “ON” switches –VDR acts as a transcription factor, its binding to the VDRE unleashing the polymerase enzyme to read the gene.

How Vitamin D Impacts Our Health

Neat. Vitamin D acts as a very specific signal to turn on particular genes. Directly or indirectly, vitamin D controls more than 200 genes. Knowing what these genes are, we can directly assess and understand its importance to our health:

Intestine. One of the most critical roles of vitamin D is to enhance the efficiency of the small intestine to absorb calcium by up to 40 percent. Mice that lack the VDR gene develop vitamin D resistant rickets that can be cured with calcium infusions.

Bone. Vitamin D is essential for the development and maintenance of a mineralized skeleton. It is not essential for the ossification process – mice lacking the VDR gene form bones just fine if you give their bodies enough calcium. Its role is to increase levels of calcium in the blood. Maintaining adequate levels of Vitamin D plays an important role in avoiding osteoporosis. Among elderly women given 800 units of vitamin D daily for three years, the risk of hip fracture was reduced by 43 percent.

The Immune System. Recurrent infections are commonly associated with rickets. The presence of VDR receptors in immune system cells hints at why. It turns out vitamin D interacts with macrophages, enhancing their function and so improving the body’s defense against microbial infection and tumor cell growth. It has been used with success to combat leukemia (the cancerous over-rapid growth and proliferation of white blood cells).

Vitamin D also plays an important role in preventing auto-immune disease. At higher concentrations, vitamin D suppress T and B lymphocytes, limiting the strength of the immune response. It is because of this second function that Vitamin D has a therapeutic role in controlling autoimmune diseases like lupus, rheumatoid arthritis, multiple sclerosis and transplant rejection. Living below 35 degrees latitude (where there is more direct sunlight and thus greater vitamin D production) reduces the risk of multiple sclerosis by approximately 50 percent. Women who take daily vitamin D pills have a 42 percent reduced risk of developing multiple sclerosis, and similar effects are seen for rheumatoid arthritis.

Skin. Sunlight stimulates your body to produce vitamin D. In the mid-1980s, it was first noticed that oral doses of vitamin D dramatically reduced the lesions produced by the skin disease psoriasis, and slowed the development of melanomas (fast-growing skin cancers).

Muscle. In addition to maintaining the levels of calcium needed for proper muscle function in the skeleton and heart, vitamin D appears to have a direct impact on heart and skeleton muscle function, although the mechanisms involved are still unclear.

Nervous System. Recent work indicates vitamin D induces the production of nerve growth factor by injured neurons in particular regions of the brain possessing VDR receptors (cortex, hippocampus, basal forebrain), preventing loss of the injured neurons. As these are just the regions affected in Alzheimer's disease, this suggests that vitamin D may have potential as a therapeutic tool to slow the progress of Alzheimer's brain cell loss.

Cancer. People living at higher latitudes (where less direct exposure to sunlight results in less vitamin D production) are at increased risk of colon, pancreatic, prostate, ovarian, breast and other cancers. Blood levels of vitamin D below 20 nanograms per milliliter are associated with a 30-50 percent increased risk of colon, prostate and breast cancer.

So what do we take away from all this? Said simply, your body uses vitamin D to trigger a lot of important activities, and you don’t want to have too little of it. Vitamin D decreases the risk of many chronic diseases, including common cancers like leukemia and melanoma, autoimmune diseases like lupus and rheumatoid arthritis, and cardiovascular disease like congestive heart failure.

So Why Has Vitamin D Become So Trendy?

So what about our original question? Why have vitamin D supplements suddenly become so trendy? Rickets as a common disease in this country was conquered decades ago when we began to fortify children’s foods with vitamin D, and no one has thought much more about vitamin D deficiency since. It came as an unwelcome surprise when recent studies have shown vitamin D deficiency to be common in American adults!

Humans get almost all of their vitamin D from exposure to sunlight (sunlight’s UVB radiation triggers skin cells to manufacture it from cholesterol), although a little can come from their diet (few foods naturally contain vitamin D, but oily fish are rich in it).

Sensible sun exposure is the normal route to obtaining adequate amounts of vitamin D, which is stored in body fat and released in the winter when sun exposure lessens. Exposure of the arms and legs to 30 minutes in the middle of the day, twice a week, is usually adequate. One hour’s summer exposure in a bathing suit is equivalent to ingesting some 20,000 units of vitamin D. Of course, use of sun screens lowers the exposure.

At what level is someone deficient? Most experts draw the line at 30 nanograms per milliliter. How many people fall below that line? Astonishingly, it is now estimated that 1 billion people worldwide do!

Several recent studies in this country indicate that 40 percent of the elderly living at home (that is, not in nursing homes) are deficient in vitamin D. They don’t get out into sunlight as much as when they were younger, of course, but even more important, their skin cells don’t do as good a job of converting cholesterol into vitamin D. In a 70 year old, vitamin D production in the skin is reduced 70 percent.

And it’s not just the old folks. In recent studies 52 percent of Hispanic and black teens in Boston and 48 percent of preadolescent girls in Maine had vitamin D levels below 20 nanograms per milliliter. Indeed, 42 percent of adult black women throughout the United States have levels below 20 nanograms per milliliter.

Clearly exposure to sunlight is not getting the job done. Some of the deficiency among Americans undoubtedly reflects an aging population. Some more is probably due to absorption of the sun’s rays by melanin in the skin and by widespread sunscreen use. And some of it seems to reflect sequestering of vitamin D in the fat cells of the obese.

In the face of this discouraging news, what do we do? Take vitamin D supplements! Most experts agree that without adequate sun exposure, we need approximately 800 to 1000 units a day. The daily pills my doctor has recommended (available over the counter at any drug store) deliver 2000 units, a little overkill but in the ballpark. The pills don’t cost much, and they prevent a deficiency that could otherwise have an enormous negative impact on my future health. Yours, too.

On Science

George B. Johnson's "On Science" column looks at scientific issues and explains them in an accessible manner. 

Johnson, Ph.D., professor emeritus of Biology at Washington University, has taught biology and genetics to undergraduates for more than 30 years. Also professor of genetics at Washington University’s School of Medicine, Johnson is a student of population genetics and evolution, renowned for his pioneering studies of genetic variability. He has authored more than 50 scientific publications and seven texts.

As the founding director of The Living World, the education center at the St Louis Zoo, from 1987 to 1990, he was responsible for developing innovative high-tech exhibits and new educational programs.

Copyright George Johnson

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