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Vitamin D and Your Health Cancer

Vitamin D In Cancer Prevention and Treatment

Before reading about vitamin D and cancer, it would be helpful if one were familiar with the different forms of vitamin D, namely cholecalciferol, calcidiol, and calcitriol.

Cholecalciferol (vitamin D3)

Cholecalciferol is the naturally occurring form of vitamin D. It is the substance made in large quantities in your skin when sunlight strikes your bare skin. It can also be taken as a supplement. Cholecalciferol is vitamin D. All other compounds are either metabolic products or chemical modifications.

Calcidiol (25(OH)D3 or 25D3)

Calcidiol (25-hydroxyvitamin D) is a prehormone in your blood that is directly made from cholecalciferol. When being tested for vitamin D deficiency, calcidiol is the only blood test that should be drawn. When someone refers to vitamin D blood levels, they are usually referring to calcidiol levels. Your doctor can order calcidiol levels but both your doctor and the lab will know the calcidiol blood test as 25-hydroxyvitamin D.

Calcitriol (1,25(OH)2D3 or 1,25D3)

Calcitriol (1,25-dihydroxyvitamin D) is made from calcidiol in the kidneys and in tissues and is the most potent steroid hormone derived from cholecalciferol. In fact, it is the most potent steroid hormone in the human body. It is sometimes referred to as the active form of vitamin D. Calcitriol levels should never be used to determine if you are deficient in vitamin D.

The Vitamin D and Cancer Connection

The earliest modern connection to cancer and vitamin D was due to an interesting observation that was made sometime in the 1930s. The observation was that people who spent years in the sun (and subsequently developed a relatively benign form of skin cancer called squamous cell skin cancer) were less likely to develop deadly internal cancers, such as colon cancer, breast cancer, and prostate cancer. This led to one of the first modern theories of cancer, namely that squamous cell skin cancer conferred immunity against more deadly forms of cancer.

The immunization theory turned out to be false but the observation that associated more skin cancers with less internal cancers held. How could the sun cause nonmelanoma skin cancers (which kill about 1,500 Americans a year) but prevent more serious cancers (which kill hundreds of thousands of Americans every year)?

It wasn't until the late 1980s that the Garland brothers, now epidemiologists at the University of California at San Diego, discovered the answer. First they discovered that sunlight reduced colon cancer risk. Next they discovered that women exposed to sunlight were one-half as likely to die from breast cancer as were women who spent less time in the sun. Then a researcher named Gary Schwartz discovered the same thing about prostate cancer. Both groups of researchers thought vitamin D was the likely explanation.

Then, the Garlands discovered that low calcidiol levels were strongly correlated with developing colon cancer. That would explain the earlier observation that squamous cell skin cancer lowered one's risk of serious internal cancers. Those who developed skin cancer had spent a lot of time in the sun and thus developed both squamous cell skin cancer and high calcidiol blood levels.

The Perfect Anti-cancer Drug

Research scientists in the 1980s had already discovered that calcitriol had profound anti-cancer effects, both in the test tube and in animals. It not only reduced the unregulated growth of cancer cells by promoting normal cell death (apoptosis); vitamin D prevented new cells from becoming cancerous (promoted differentiation). It even helped prevent cancer cells from spreading (metastasis) and inhibited cancer cells from developing new blood supply (angiogenesis). In short, calcitriol seemed like the perfect anti-cancer drug.

However, for many years scientists believed only one form of vitamin D, calcitriol was important in cancer. As calcitriol is the most active form of vitamin D, the scientists just assumed it was the only form to study. They seemed to be unaware that the Garland's discoveries implied that calcidiol, the storage from of vitamin D in the body, was also important in cancer.

Medical Industry Ignores Vitamin D's Promise

Somewhere along the line, the vitamin D and cancer story took a tragic twist. As vitamin D could not be patented, it held little interest for the medical industry. Plain vitamin D3 held no promise for financial gain for drug companies or for the researchers who are often financially involved in such companies. Therefore, the medical industry seemed to ignore the evidence that simple vitamin D helped prevent cancer and that adequate vitamin D nutrition may help retard the growth of cancer.

Nor did the cancer scientists seem realize that vitamin D takes at least two pathways in the body. One path, called the endocrine function, produces calcitriol in the kidney to help maintain blood calcium levels. The second pathway, called the autocrine and the paracrine functions of vitamin D, produces calcitriol in the tissues. The tissue pathway is more important than the endocrine function as far as cancer is concerned. Scientists failed to realize that the easiest way to raise tissue calcitriol levels is to raise blood calcidiol levels. Furthermore, the easiest way to raise blood calcidiol levels is to go into the sun, use a sunlamp, or take the correct amount of vitamin D by supplementation.

Vitamin D Analogs Developed Instead

Instead, the medical industry turned their attention to developing chemical modifications of the most active form of vitamin D, calcitriol. Called vitamin D analogs, these drugs held the promise for a tremendous profit if studies showed they were active against cancer. Although good reasons existed to support clinical trials with plain, natural vitamin D in cancer patients, the medical industry concentrated on developing vitamin D analogs instead. To date, more than 2000 such analogs have been developed and some have been tested on cancer patients. The results have been disappointing because the drugs cause high blood calcium via the endocrine function of vitamin D.

The possibility that such analogs may help cancer patients should not be discounted. However, development of the analogs bypassed a crucial and ethical medical question: Does plain vitamin D3 help cancer patients? The medical industry was not interested in the answer to this question and instead concentrated on forming numerous companies to exploit the potential anti-cancer properties of vitamin D analogs.

Analog Researchers and Ethics in Medicine

Now, let's take a closer look at how the vitamin D analogs are studied because those studies raise important scientific, ethical, and legal questions. Analog researchers, who often own stock in the company developing the analog, select two groups of patients, a control group and a treatment group. However, neither group is tested nor treated for vitamin D deficiency. In fact, the patients are neither informed about the possible anti-cancer effects of simple vitamin D nor informed they will not be tested for vitamin D deficiency. Current research indicates that the vast majority of these cancer patients (both treatment and control groups) are likely to be vitamin D deficient.

The researcher then gives the treatment group the vitamin D analog and the control group gets a sugar pill. Most vitamin D analog studies have not shown any benefit—or they showed only slight improvement—in the treatment groups. However, as both the treatment and control groups are usually advanced cancer patients, both groups usually end up dying without ever being tested or treated for routine vitamin D deficiency.

Some analog researchers point out that some cancer cells lose the ability to activate vitamin D (transform vitamin D into calcitriol) and thus it makes no sense to study plain vitamin D. However, these researchers forget that the majority of cancer cells retain the ability to activate vitamin D and that calcitriol's anti-cancer activity is paracrine as well as autocrine. They also don't realize that the only reasonable, scientific, vitamin D analog question is: Do the vitamin D analogs add anything to the treatment of cancer patients who are vitamin D replete?

The only scientific and ethical way to study the effect of vitamin D analogs in cancer patients is to first treat both the control and the treatment groups with enough vitamin D until their blood tests show they are no longer vitamin D deficient. Then give the analog to the treatment group and the sugar pill to the control group. That way, any additive effect of the analog over simple vitamin D will be clear.

The failure to conduct these studies lied at the feet of the medical industry as well as those of the National Institutes of Health. The NIH receives billions of dollars of taxpayer money to study such questions and is not supposed to be influenced by profit.

Fortunately, numerous studies are now being performed on the anti-cancer properties of both natural vitamin D3 and vitamin D analogs. Vitamin D3 is showing more and more promise with each new study—and not only for cancer, but for numerous other health disorders as well.

John Jacob Cannell MD Executive Director 2006.06.04

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*These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.