NEJM Studies on Vitamin D, Calcium Report Unexpected Results

WASHINGTON--Results of two studies conducted on postmenopausal women and published in the New England Journal of Medicine (NEJM) reported little to no benefit from vitamin D and calcium, contrary to a large volume of scientific evidence and expert theories on the benefits of these nutrients. One study showed the nutrient duo had no effect on hip fractures and only a miniscule benefit to bone density; the other study revealed the tandem had no effect on incidence of colorectal cancer. The studies, part of the Womens Health Initiative (WHI), were funded by the National Institutes of Health (NIH) and the National Heart, Blood and Lung Institute (NHLBI).

The researchers investigating colorectal cancer risk conducted a randomized, double blind, placebo-controlled trial (NEJM 354, 7:684-96, 2006) involving 36,282 postmenopausal women from 40 WHI centers. They gave 18,176 women 500 mg of elemental calcium (as calcium carbonate) with 200 IU of vitamin D3 twice daily, while the other women received a placebo. After seven years of supplementation, the scientists found the incidence of invasive colorectal cancer did not differ significantly between the supplement and placebo groups. While they concluded supplementation with calcium and vitamin D for seven years had no bearing on colorectal cancer, they conceded the long latency associate with development of this cancer, along with the trial length, may have contributed to the disappointing results. They added the longer-term effect of calcium and vitamin D supplementation will be assessed in an ongoing follow-up.

In the hip fracture study (NEJM 354, 7:669-83, 2006), 36,282 postmenopausal women aged 50 to 79 and enrolled in the broader WHI trial were randomly assigned to receive either a placebo or a combination of 1,000 mg calcium carbonate with 400 IU vitamin D3 daily. For an average follow-up of seven years, fractures were charted and bone density was measured at three WHI centers. While hip bone density was 1.06-percent higher in the supplement group, risk of hip fractures was not affected by the nutrient supplements; scientists noted an increased risk of kidney stones among the supplement users. However, the study authors noted the 400 IU vitamin D dose used in the trial contrasts to the 600 IU doses used in previous studies showing hip fracture reduction, suggesting the smaller dose might not have been enough to demonstrate the nutrients expected positive benefits on fracture risk. They also suggested study participants might have been too young to detect a beneficial effect.

These are well-designed, solid studies, and we applaud the researchers, NIH and NHLBI for undertaking this important work of conducting large scale, randomized, double-blind, placebo-controlled trials such as WHI, said John Hathcock, Ph.D., vice president, scientific and international affairs with the Council for Responsible Nutrition (CRN). "As the findings from the various arms of the WHI are presented, were seeing surprising results in a number of areas, including those from these two studies. Without discounting the value or importance of the studies, CRN advised consumers to refrain from over-interpreting the results, as the authors themselves have noted limitations of the studies that may account for the unexpected results.

Hathcock further highlighted the fracture studys conclusion of positive impact by vitamin D and calcium on bone density. He suggested a longer study length might have produced a more significant reduction in hip fracture risk, given the benefit to bone density.

CRN applauded NIHs commitment to continue investigating the effects of supplementation over an extended period of time, given that vitamins and minerals are most appropriately taken consistently over the long term in conjunction with other healthy lifestyle choices.