Vitamin D and cancer

A variety of studies have suggested that vitamin D protects against cancer. This seemingly intuitive proposition is supported by neither epidemiological nor molecular evidence. In fact, the very opposite is true. This article reviews why this body of research is most likely incorrect – or at the very least, much more complicated than articles in the popular media would have a person believe.

• Latitude studies - The “latitude studies” are observational, as opposed to interventional, studies, which use ambient solar UV radiation as a proxy for latitude and vitamin D status. For these studies, researchers compare rates of certain major cancers - most notably breast, colorectal and prostate cancer - to rates of sunlight exposure. This group of research has the liability of being wildly inconsistent. The choice to publish research on a specific latitude gradient may be a better proxy for a researcher's bias.
• Interventional studies - While some randomized controlled trials have suggested that consuming vitamin D reduces rates of cancer, larger and more carefully controlled studies show no such effect.
• Studies of vitamin D status - Many of the studies examining the relationship between vitamin D status and incidence of cancer argue that low levels of 25-DThe vitamin D metabolite widely (and erroneously) considered best indicator of vitamin D "deficiency." Inactivates the Vitamin D Nuclear Receptor. Produced by hydroxylation of vitamin D3 in the liver. contribute to cancer. This conclusion has been invalidated by larger well-controlled studies. Although the immune system works to downregulate 25-D (25-hydroxyvitamin DThe vitamin D metabolite widely (and erroneously) considered best indicator of vitamin D "deficiency." Inactivates the Vitamin D Nuclear Receptor. Produced by hydroxylation of vitamin D3 in the liver. ) in inflammatory diseases such as cancer, very high levels of 25-D are a clear indication of regular supplementation. These studies suggest that consuming large amounts of vitamin D predispose a person to increased incidence of cancer.
• Observational studies – Some case control studies have found that vitamin D intake seems to increase incidence of certain types of cancer.

While some randomized controlled trials have suggested that consuming vitamin D reduces rates of cancer, larger and more carefully controlled studies show no such effect. Lappe et al published work, conducted over four years, that seemingly showed vitamin D might lower the incidence of colorectal cancer.¹ The study had participants take 1,100 IU’s of vitamin D over the course of four years, a time that corresponds to the period when the short-term immunosuppressive effects of the steroid would be at its strongest.

Lappe opted to discard the data of subjects who developed cancer during the first year of the study. The rationale was that cancers during the first year would have been present but undiagnosed at entry. Of the 50 people who developed cancer during the four-year study, 13 were removed based on this premise, and only 37 cases of cancer were actually analyzed. But the 13 people who developed cancer during the first year were likely to be the study participants with the highest loads of the Th1 pathogens. They would have been the people to suffer the most from the negative impact of elevated 25-D on the immune system. If data from the 13 participants would have been included in the study, the results would have undoubtedly reflected much less of a “benefit” from vitamin D. Even the researchers admit that “their conclusion was strengthened by both the observational, substantial improvement in risk reduction when cancers occurring early in the trial were excluded.”

In a similar study looking at a larger cohort and over a longer period of time, Chlebowski et al. found no such effect.²

In our study we found absolutely no indication of an effect of calcium or vitamin D [on cancer] — zero. And that’s over a seven-year period. It was a much larger study and a much longer study.

Jacques Rossouw, MD, National Institutes of Health ABC News

A second study by the Women’s Health Initiative found no reduction in risk of breast cancer among postmenopausal women supplementing with 1000 mg calcium and 440 IUs of vitamin D.³ Researchers at the American Cancer Society conducted a study on 68,567 postmenopausal women and found that “neither use of supplemental calcium nor vitamin D intake was associated with [breast cancer] risk.”⁴ And researchers at the Northern California Cancer Center found no association between dietary vitamin D intake during adolescence and subsequent breast cancer risk.⁵

Cohort studies are no more likely to show a long-term positive effect of vitamin D intake, The Iowa Women's Health study showed vitamin D intake seemed to protect against breast cancer in the first five years after it was taken. However, the effect began to reverse between years five and ten and was completely lost after year ten, trending towards an opposing effect.⁶

Longitudinal studies (those lasting decades) examining the relationship between long-term intake of vitamin D and incidence of cancer are lacking. Those that have measured incidence of various other diseases, including atopy, allergic rhinitis, and brain lesions, have found that vitamin D intake increases the rate of these diseases. There is no reason to think cancer would be substantially different.

A number of vitamin D studies point to low levels of the inactive metabolite, 25-D, as playing a causative role in the incidence of cancer. Large, well-controlled studies have not been able to verify this claim.

A recent study by the National Cancer Institute - the first study to look at the relationship between measured vitamin D in the blood and subsequent total cancer deaths - failed to show an association between baseline vitamin D status and overall cancer risk in men, women, non-Hispanic whites, non-Hispanic blacks, Mexican Americans, and in persons younger than 70 or 70 years or older.⁷ The study analyzed data from 16,818 subjects.

When asked by a correspondent from CBS News if vitamin D can reduce the risk of cancer, said the following:

I don’t believe vitamin D is the answer. I wish it was as simple as saying ‘If you take vitamin D, cancer will be cured. I don’t think it’s that simple.

David Fishman, M.D, Head of the National Ovarian Cancer Early Detection Program at New York University

An underreported body of research shows that levels of 25-D sufficiently high enough to suggest heavy supplementation are consistent with higher rates of cancer. Stolzenberg-Solomon et al tracked a cohort of men over the course of 16 years for pancreatic cancer.⁸ They found that over this time period, high 25-D levels greater than 26 ng/ml were associated with a three-fold increased risk for the cancer. It is noteworthy that according to molecular modeling research, 26 ng/ml is near the range when 25-D significantly shuts off the Vitamin D ReceptorA nuclear receptor located throughout the body that plays a key role in the innate immune response., particularly when it is already partially blocked by bacterial proteins.

Contrary to expectations, subjects with higher prediagnostic vitamin D status had an increased pancreatic cancer risk compared with those with lower status…. Our results are intriguing and may provide clues that further the understanding of the etiology of this highly fatal cancer.

Rachael Stolzenberg-Solomon, et al. ⁹

Researchers at the Chinese Academy of Medical Sciences in China found a similar association between excessive vitamin D intake and esophageal and gastric cancers in men. Male subjects with levels of 25-D in the range of 48.7 ng/ml (which once again suggests heavy supplementation) were much more likely to develop one of the two forms of cancer.¹⁰

One Norway-based study surveyed over 50,000 participants for their intake of dietary vitamin D and then compared those results to their later risk of cutaneous malignant melanoma. The researchers found that female subjects who consumed cod liver oil, which is high in vitamin D, were significantly more likely to later be diagnosed with melanoma.¹¹