Cancer Benefit of Vitamin D May Be Limited to Colon Cancer

BETHESDA, Md., Oct. 30 -- Vitamin D levels do not appear to protect against cancer, with the possible exception of colorectal disease, according to data from a nationwide study.
The analysis failed to show an association between baseline vitamin D status and overall cancer risk in men, women, or in various racial, ethnic or age groups, Michal Freedman, Ph.D., of the National Cancer Institute, and colleagues, reported in the Nov. 7 issue of the Journal of the National Cancer Institute.
However, individuals with baseline serum levels of 25-hydroxyvitamin D of 80 nmol/L or higher did have a 72% (95% confidence interval = 32% to 89%) lower risk of colorectal cancer compared with people who had lower serum levels of vitamin D (lower than 50 nmol/L; P=0.02 for the trend).
The investigators left the door open, though, for continued investigation of associations between the vitamin and cancer risk.
"Additional studies with large numbers of samples of measured 25(OH)D serum levels, preferably at multiple time points, are needed to confirm the total cancer mortality findings of this paper and to obtain more accurate risk estimates for mortality from specific cancers," they concluded.
A variety of preclinical and epidemiologic evidence has suggested that increased intake or endogenous production of vitamin D is associated with reduced cancer risk. In vitro studies have shown that vitamin D reduces cell proliferation, and stimulates apoptosis and cell differentiation, the authors noted.
Ecologic and observational studies have demonstrated an inverse association between residential exposure to ultraviolet radiation (the principal source of naturally occurring vitamin D) and cancer mortality. However, the association between vitamin D and cancer risk and mortality had not been evaluated prospectively.
So Dr. Freedman and colleagues reviewed data from the Third National Health and Nutrition Examination Survey. They focused on 16,818 adult participants who completed the NHANES physical examination from 1988 through 1994 with measurement of serum 25(OH)D. Follow-up from data collection continued until Dec. 31, 2000.
Baseline data showed that men, whites, and better-educated individuals had significantly higher serum levels of 25(OH)D.
Increasing body mass index was associated with decreasing levels of 25(OH)D, but increasing physical activity was associated with higher levels.
Dietary vitamin D and calcium and serum retinol were higher in participants who had higher 25(OH)D levels.
The investigators identified 536 cancer deaths in 146,578 person-years. Analysis of season/latitude subpopulations revealed no association between cancer mortality and winter/lower latitude or summer/higher latitude groups. Extensive subgroup analysis failed to reveal any significant associations between 25(OH)D levels and overall cancer mortality.
Analysis of the relationship between serum 25(OH)D and site-specific cancer mortality revealed no association with lung cancer, non-colorectal digestive cancers, breast cancer, prostate cancer, lymphoma or leukemia, or the category of "other" cancers.
In an editorial that accompanied the article, Johanna T. Dwyer, D.Sc., and Cindy D. Davis, Ph.D., of the National Institutes of Health, emphasized the complicated nature of the relationship between nutritional factors and cancer.
"These findings must be put into the context of total diet and lifestyle," they wrote. "While vitamin D may well have multiple benefits beyond [strengthening] bone, health professionals and the public should not in a rush to judgment assume that vitamin D is a magic bullet and consume high amounts of vitamin D," they continued. "More definitive data on both benefits and potential adverse effects of high doses are urgently needed."
The editorialists noted some limitations with the use of the NHANES III cohort. "NHANES III was a cross-sectional study that identified associations but not causation," they said.
They also pointed out that residual confounding is a particular problem because peculiarities in NHANES sampling may have affected both measures of vitamin D exposure and outcomes. For instance, season and latitude, both related to 25(OH)D levels, were linked in the dataset.
Furthermore, they noted, the fact that 25(OH)D levels were measured only at one point in time means they would not represent long-term levels. "Nor would they reflect the nadir of 25(OH)D reached during the year. There also might be fewer lower 25(OH)D levels in the summer/higher latitude sample than would be the case if all subjects had been examined in the winter. This is a cause of concern because in Norway the maximal level of 25(OH)D is reached between the months of July and September and it is 20% - 120% higher than the corresponding winter value, suggesting that season of diagnosis is a predictor of colon cancer survival."
The authors of the study and editorial had no disclosures. The study was supported by the National Cancer Institute. Primary source: Journal of the National Cancer InstituteSource reference: Freedman DM, et al "Prospective study of serum vitamin D and cancer mortality in the United States" J Natl Cancer Inst 2007; 99: 1594-1602. Additional source: Journal of the National Cancer InstituteSource reference: Davis CD, Dwyer JT, "The 'sunshine vitamin': benefits beyond bone?" J Natl Cancer Inst 2007; 99: 1563-1565.