There was a time when vitamin D prevented rickets and little more was said of it. But as interest in calcium metabolism increased, the role of D expanded to preserving healthy bones and preventing hip fractures. Now, vitamin D is seen as stabilizing the genome and so preventing cancers of colon, breast, prostate and ovary. It’s also credited with modulating immune response and reducing inflammation, with roles in heart disease prevention, diabetes, multiple sclerosis, autoimmune disorders, and seasonal affective disorder. It’s beginning to sound like the new fish oil (which actually contains appreciable quantities of the vitamin).

Many are therefore questioning the new Dietary Reference Intake guidelines of the Institute of Medicine of the National Academies of Science. This joint U.S.-Canada committee recommended 200 IU vitamin D daily for those under 50 years, 400 IU for those 50-70 years and 600 IU for people over 70, whose skin is less able to synthesize it.

Summer sun exposure

Humans appear to get most of their vitamin D requirements from sun exposure. It’s said that the whitening of the skin of peoples who left Africa 70-100 thousand years ago was a response to the need to trap more sunlight for vitamin D synthesis. But exposure to 15 minutes of midday summer sun can generate 10,000 IU of the vitamin, so there’s concern that our total requirement is likely to be far higher than the 200-600 IU currently proposed. In fact, the Canadian Cancer Society now recommends, 1,000 IU daily during fall and winter for the general population, and year-round for the elderly or dark-skinned.

Fracture risk dispute

Currently, there’s general acceptance that supplementation with vitamin D plus calcium reduces the risk of fracture. A recent meta-analysis suggests an overall 12% decrease in relative risk (Tang et al, Lancet 2007; 370:657-66). These data, however, are at odds with the results of the 36,000-plus postmenopausal women in the Women’s Health Initiative (WHI), who took 400 IU vitamin D and 1g calcium a day for 7 years but showed no benefit in terms of fracture rates. This study has been heavily criticized, because many subjects had high Ca++ intakes at entry, were overweight or obese and therefore at less risk for fracture, or were taking HRT or already being treated with bisphosphonates (12.5%). Nevertheless, they represent much of the population found in North America and the lack of benefit is therefore discouraging.

On to cancer

The data look hopeful, together with the latitude or sunshine effect that’s been shown for colon and breast cancers, which are rarer in temperate and equatorial latitudes, presumably due to more vitamin D synthesis. A recent supplementation study (Lappe et al AJCN 2007; 1586-91) showed promising results for all cancers in a group of postmenopausal women followed for 5 years. The best effect was seen with Ca++ plus vitamin D. Calcium alone showed some benefit, while the unsupplemented fared worst. Meta-analyses of cohort studies have shown a particularly consistent effect of vitamin D supplementation on colon cancer, a benefit shown also for calcium. Again, though, this result wasn’t seen in the WHI. With cancer as with fracture, the reasons for a lack of benefit in WHI may be many, but the disappointment remains.

And heart disease?

Case-control studies have indicated a benefit for coronary heart disease (CHD) associated with vitamin D in a 10-year follow-up cohort of middle-aged women. Participants with the lowest level of vitamin D in their plasma had twice the CHD risk as those with the highest concentrations. Again, the WHI failed to show that calcium plus D was protective for CHD and, worse still, a New Zealand study indicated that middle-aged women who took calcium 1,000 mg/day (as in the WHI) — but without vitamin D — had a significantly increased relative risk (RR = 2.12, 95% CI 1.01-4.47). Perhaps, had vitamin D been added, there may have been no adverse effect, and had it been taken alone, even a benefit.

Studies are underway with very high-doses of vitamin D for multiple sclerosis and other major conditions and there’s no doubt that we’ll hear much more about this vitamin and its effects in the next few years. The hope is that vitamin D won’t go the way of vitamin E for cardiovascular disease or beta carotene in lung cancer. We have yet to find a vitamin supplement that brings unqualified benefit. Despite the success of folate for spina bifida prevention and its ability to lower homocysteine levels, its effect on CHD has been disappointing, and the question of timing has been raised in relation to colon cancer, with administration early giving protection, but worsening the outcome when given later in the disease process. There’s no doubt that the old debate between giving nutrients as foods vs supplementation will continue. Our best hope is that sufficient fortified foods will be made available for the randomized trials required to resolve the controversies and uncertainties.