A colorectal polyp is a fleshy growth occurring on the lining of the colon or rectum. Colon polyps lead to colon cancer if left untreated. One of the reasons that the American Cancer Society recommends a colonoscopy every ten years after the age of 50 is so colon polyps can be identified and removed before they turn cancerous. According to the NIH, colonoscopy every ten years reduces the risk of colon cancer by 50%. Epidemiological data shows that the incidence of colorectal cancer in the USA is decreasing by about 3% per year, probably due to earlier detection.
Most observational studies have found an inverse association between colon cancer/polyps and vitamin D levels. Therefore, it came as a surprise that a well-conducted, multicenter, large, randomized controlled trial of 1,000 IU/day of vitamin D showed it did not prevent colon polyps.
Baron JA, Barry EL, Mott LA, Rees JR, Sandler RS, Snover DC, Bostick RM, Ivanova A, Cole BF, Ahnen DJ, Beck GJ, Bresalier RS, Burke CA, Church TR, Cruz-Correa M, Figueiredo JC, Goodman M, Kim AS, Robertson DJ, Rothstein R, Shaukat A, Seabrook ME, Summers RW. A Trial of Calcium and Vitamin D for the Prevention of Colorectal Adenomas. N Engl J Med. 2015 Oct 15;373(16):1519-30. doi: 10.1056/NEJMoa1500409.
I understand that 1,000 IU/day is not a physiological dose, but at the time the trial was devised, 2003, it was considered a high dose. Also, they excluded all subjects with a 25(OH)D less than 12 ng/ml, so we still don’t know if 1,000 IU/day would prevent colon polyps in subjects who were severely vitamin D deficient. It was no conspiracy that led the researchers to exclude subjects < 12 ng/ml; their ethics committee would not allow them to diagnose but not treat severely deficient subjects.
It was a large trial: 2259 subjects. Twenty-five percent received vitamin D supplementation alone, 25% received vitamin D and calcium (1,200 mg/day), 25% were given calcium alone and 25% only received a placebo. They enrolled subjects who had undergone colonoscopy at baseline and had polyps removed; then they studied these subjects for 3-5 years, repeating the colonoscopy. Neither vitamin D nor calcium had an effect, both in an intention to treat analysis and a per protocol analysis, which simply means if they only studied the subjects that took their vitamin D, they still found no effect on colon polyps. So few subjects developed colon cancer (5 total) that they could make any conclusions regarding these findings.
In the supplemental data obtained by Perry Holeman of the Vitamin D Society, it turns out this study determined what happens with adenomas when the control group’s vitamin D status stays at 25 ng/ml and the treatment group’s improved to 32 ng/ml:
End of treatment serum 25-hydroxyvitaminD level – ng/ml 10/21/15
Interestingly, the researchers found a trend for fewer kidney stones in the vitamin D group (P = 0.18). They also found a trend for fewer cancers of any type in the vitamin D group (P=.17). In the calcium group, they found more hypercalcemia (P = .01) but fewer heart attacks (P = .03), which surprised many.
The mean 25(OH)D level of all subjects was about 23 ng/ml at baseline, but when they excluded all subjects with a 25 (OH)D > 23 ng/ml, they still found no effect. The treatment raised the 25(OH)D only 8 ng/ml, but if there was any robust effect of vitamin D on preventing colon polyps, I think this study would have found it.
That leaves us with no explanation of why observational studies show higher 25(OH)D levels are associated with fewer colon polyps and less colon cancer. One possible explanation is sunshine. Remember serum 25(OH)D is not only a marker for vitamin D status, it is a marker of sun exposure. Maybe sun exposure has a non-vitamin D beneficial effect?