High vitamin D: Rx for cancer prevention?

High amounts of vitamin D dramatically reduce rates of breast and colorectal cancer, according to a pair of recent studies, but the required levels at least equal the maximum deemed safe by current nutritional guidelines. Reviewing previously published studies, researchers at the University of California, San Diego (UCSD) concluded that 2,000 international units (IU) of vitamin D per day could prevent half of new breast cancer cases and as many as two thirds of new colorectal cancers.

Vitamin D, which maintains normal levels of calcium and phosphorus in the blood and builds strong bones, comes from food—such as fortified milk, fortified cereals, oily fish, and cod liver oil—and sunlight. For most people, 10 to 15 minutes of direct sun at least twice a week on the face, arms, hands, or back is sufficient, according to the NIH.

Most recommendations, including those of the NIH and the HHS's 2005 Dietary Guidelines for Americans, call for daily intakes between 200 and 600 IU, depending on age. They also set the upper limit for safety at 2,000 IU for everyone older than 12 months. These standards were established by the National Academy of Sciences in 1997.

Prolonged intake above the upper limit increases the risk of toxicity, according to the NIH. Side effects can include nausea, vomiting, poor appetite, constipation, weakness, and weight loss. Excess intake can also raise calcium levels in the blood, which can lead to mental confusion.

The UCSD breast cancer team analyzed data from the Harvard Nurses' Study and the St. George's Hospital Study—the only trials done during the past 40 years that reported breast cancer risk by quantiles of serum 25-hydroxyvitamin D (25[OH]D).

This substance is the primary circulating form of vitamin D. Records of 1,760 participants in the two trials were divided into five equal groups, ranked from the lowest blood levels of 25(OH)D to the highest, and the number of breast cancers was then calculated for each quintile.

Findings are “very clear”

Blood levels of 25(OH)D ranged from <13 ng/mL to about 52 ng/mL. The odds ratios for developing breast cancer declined as the level of 25(OH)D increased, going from 1.00, 0.90, 0.70, 0.70 to 0.50. In other words, those with the highest levels of circulating vitamin D had a 50% reduced risk of breast cancer. “The data were very clear,” says co-author Cedric F. Garland, MPH, PhD, “showing that individuals in the group with the lowest blood levels had the highest rates of breast cancer, and the breast cancer rates dropped as the blood levels of 25-hydroxyvitamin D increased.”

The serum level associated with the 50% reduction in risk was 52 ng/mL, which corresponds to a daily vitamin D intake of 4,000 IU. The researchers said that level “is probably impractical to recommend.” But 52 ng/mL “could be maintained by taking 2,000 IU of vitamin D daily, plus, when the weather permits, spending 10 to 15 minutes a day in the sun,” said Garland, in a prepared statement. The study (Vitamin D and prevention of breast cancer: Pooled analysis) is available online from the Journal of Steroid Biochemistry and Molecular Biology.

The colorectal cancer researchers used a similar methodology and found even more dramatic results. Organizing data on 1,448 individuals from five studies into quintiles, they found that the chances of developing colorectal neoplasms went down as the serum levels of vitamin D went up (odds ratios were 1.00, 0.82, 0.66, 0.59 and 0.46). Thus, at the highest level, vitamin D resulted in a 54% risk reduction. And, again, the protective effect was linear, meaning it was dose-related.

“Through this meta-analysis, we found that raising the 25-hydroxyvitamin D to 34 ng/mL would reduce the incidence rates of colorectal cancer by more than half,” coauthor Edward D. Gorham, PhD, said in a prepared statement. “We project a two-thirds reduction in incidence with serum levels of 46 ng/mL, which corresponds to a daily intake of 2,000 IU. This would be best achieved with a combination of diet, supplements, and 10 to 15 minutes per day in the sun.”

Even 40,000 IU may be safe

Published in the American Journal of Preventive Medicine (2007;32:210-216), the study lists 2005 statistics that show 145,300 new cases of colorectal cancer and 56,300 deaths. It directly takes issue with the official 2,000 IU/day upper limit for vitamin D, citing 30 studies of high serum 25(OH)D in adults. “No reproducible toxicity was reported below 100 ng/mL,” the UCSD team found. “The median minimum threshold for toxicity in all studies was 197 ng/mL.” One study found no evidence of vitamin D-induced illness at <3,800 IU per day, and another could find no documented cases of toxicity at doses <40,000 IU per day, they reported.

“An intake of 2,000 IU/day…is well below what would induce even mild hypervitaminosis,” the researchers asserted. “Hypervitaminosis would be a concern with intakes of 5,000-10,000 IU per day and possibly higher, but not with 2,000 IU per day.”

However, investigators stopped short of advising intakes >2,000 IU, noting that the studies they cited were based on Caucasian participants. “Intake of vitamin D should be greater for black people and other individuals with more skin pigmentation than is typical in whites because such individuals have lower rates of photosynthesis of vitamin D3 in the skin,” the researchers said.

Paul Thomas, a scientific consultant to the Office of Dietary Supplements at the NIH, said the new studies “show interesting and provocative findings,” but they do not definitively tie high levels of vitamin D to cancer protection. For that reason, clinicians should not change the way they counsel patients. “These are observational studies,” said Thomas, whose doctorate is in nutrition. “Until we have randomized clinical trials with placebos, where vitamin D intake is the only issue, we can't be sure” whether it actually results in fewer cancer cases. “Policy changes must be based on more rigorous study.”

Linda Massey, a professor of human nutrition at Washington State University at Spokane, agrees. “The literature that says higher vitamin D prevents cancers is largely associational and cannot be viewed as a recommendation to take that much as a supplement,” she said. She recommends “a total deliberate consumption” of 1,000 IU, including 200 IU from two glasses of fortified milk and 800 IU from nutritional supplements. “If there is some synthesis from sun exposure or other fortified foods, then that still keeps intake under 2,000 IU,” she said.

Ms. Dembrow is a senior editor for The Clinical Advisor.

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