Vitamin D3 and Cancer
To easily read about vitamin D and cancer, you need to memorize three words. These three words are cholecalciferol, calcidiol and calcitriol.
- Cholecalciferol is the naturally occurring form of vitamin D. It is sometimes called vitamin D3 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)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-hydroxy-vitamin D.
- Calcitriol [1,25(OH)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 earliest modern connection to cancer and vitamin D was an interesting observation in the 1930s. People who spent years and years in the sun (and subsequently developed a relatively benign form of skin cancer called squamous call skin cancer), were less likely to develop more deadly internal cancers, such as colon, breast 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 non-melanoma skin cancers (which kill about 1,500 Americans a year) but prevent more serious cancers (which kill hundreds of thousands of Americans every year)?
In the late 1980s, the two Garland brothers, now epidemiologists at the University of California at San Diego, discovered the answer. First, they discovered that sunlight reduced your risk of colon cancer. Next, the Garlands 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. 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.
Research scientists in the 1980's 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 anticancer 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.
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 D 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. D3
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 (inside the cell) and the paracrine (around the cell) 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 mouth.
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 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. Again, the scientists didn't seem to know that the best way to raise tissue calcitriol is the raise blood calcidiol. 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 mouth.
The possibility that such analogs may help cancer patients should not be discounted. However, development of the analogs bypassed a crucial medical and ethical question, which is "Does plain vitamin D help cancer patients?" No one knows because the question has never been studied! In spite of the evidence that vitamin D should help cancer patients, no one has ever given simple vitamin D to cancer patients. Instead, the medical industry formed numerous companies to exploit the potential anti-cancer properties of vitamin D analogs.
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 or 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. D3
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 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.
It is increasingly likely that physiological doses of vitamin D would help much more than the analogs. However, as you know, no one knows for sure because that question has never been studied. This year, hundreds of thousands of people around the world will die from cancer and most of them will be vitamin D deficient while they are battling their cancer.
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 calcitriols anticancer activity is paracrine (around the cell), not just autocrine (inside the cell). They also forget 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 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. However, you guessed it; that study has never been done.
The failure to conduct such studies lies both at the feet of the medical industry and at the feet of the National Institutes of Health or NIH. The NIH receives billions of dollars of your tax money to study such questions and is not supposed to be influenced by profit.
However, things are changing and we hope that the proper studies are now being designed. Unfortunately, they will take years to complete and be published. In the meantime, cancer patients continue to die vitamin D deficient.
What can you do? Three things: First, write your congressional representative and demand the NIH conduct studies on vitamin D and cancer. Second, support the Vitamin D Council (contributions are tax deductible). Third, get enough vitamin D.
How much vitamin D should you take to prevent cancer? No one knows. It is a more complicated question than it first appears because most of us get most of our vitamin D from the sun, although we avoid the sun! We get a little in our diet, almost all of it from milk or fish, but none of us get enough from our diet. We also get some in multivitamins, but multivitamins only contain 400 units, about 10 % of the body's daily needs. It appears to us that the best thing to do is be conservative and maintain "natural" vitamin D blood levels year around. In this case, "natural" means calcidiol blood levels similar to humans living in a "natural" relationship with the sun, such as farmers in Puerto Rico or lifeguards in the USA. Both groups have calcidiol levels above 50 ng/ml.
How much vitamin D should you take if you have cancer? We don't know. No one knows. The research is just beginning. The only way to know how much might help is to either consult a knowledgeable professional (hard to find), read the current scientific literature (difficult to understand), or read our summations on this web site. No matter choice you make, in the end, you'll have to decide for yourself.
As we will say repeatedly, although "natural" amounts of vitamin D may help, it should only be taken in addition to standard cancer treatment. It is never the first or only treatment. It is always taken in addition to your regular chemotherapy or surgery. Oncologists and cancer surgeons work miracles every day. D3
Remember, vitamin D may be toxic in overdose although one expert recently said, "worrying about vitamin D toxicity is like worrying about drowning when you are dying of thirst." That said, many people think if a little is good then a lot is better. This is definitely not true about vitamin D. Forewarned is forearmed.
The Vitamin D Council sponsors this web site; we are a non-profit, tax-exempt organization dedicated to educating consumers and professionals about the epidemic of vitamin D deficiency. We are not your doctors and will not make any medical recommendations concerning vitamin D supplementation. We are in the process of writing an e-book discussing supplementation options and hope to be able to soon tell you what we think we would do if we developed cancer.
