Supplementation with vitamin D and calcium makes sense as a strategy to reduce risk of type 2 diabetes in people with insulin resistance or other risk factors.
In a thorough metanalysis of published data on the subject, Anastassios Pittas, MD, and colleagues at the Division of Endocrinology, Diabetes and Metabolism, Tufts–New England Medical Center, reviewed all available cross-sectional epidemiologic studies looking at diabetes risk as a function of vitamin D and calcium levels. They also looked at actual clinical trials involving supplementation.
They concluded that, “Vitamin D and calcium insufficiency may negatively influence glycemia, whereas combined supplementation with both nutrients may be beneficial in optimizing glucose metabolism.”
Observational studies have shown a consistent relationship between low vitamin D levels, low calcium intake and increased prevalence of insulin resistance and diabetes. Aggregating the published data, Dr. Pittas calculated that among non-Black people, the odds ratio for type 2 diabetes is 0.36 for those with the highest versus the lowest circulating 25-hydroxyvitamin D levels. Put another way, there is a 64% reduction in prevalence for those with the highest vitamin D levels.
For metabolic syndrome, the odds ratio was 0.71, suggesting a 29% reduction in prevalence among those with the highest vitamin levels. Looking at intake of calcium and vitamin D combined, they found that the inverse associations with diabetes held up; highest versus lowest combined intake was associated with an 18% lower diabetes incidence (Pittas AG, et al. J Clin Endocrinol Metab. 2007; 92(6): 2017–2029).
According to Dr. Pittas, “Evidence from trials with vitamin D and/or calcium supplementation suggests that combined vitamin D and calcium supplementation may have a role in the prevention of type-2 diabetes only in populations at high risk (i.e. glucose intolerance).”
He stressed that observational studies are limited in their utility because most do not control for the myriad confounding variables. Interventional studies up to this point have been small and of short in duration, with considerable variation in the form and dose of vitamin D and calcium from study to study. So it is not possible to draw firm conclusions.
As with many epidemiologic correlations, the relationship between vitamin D, glucose metabolism and heart disease may be more complex than it seems on first glance.
Trevor Marshall, PhD, of the School of Biological Medicine & Biotechnology, Murdoch University, Perth, W. Australia, is among a vanguard of researchers who believe the vitamin D deficiencies observed in association with chronic diseases are actually a result of disease process, not a causative factor.
“We need to discard the notion that vitamin D affects a disease state in a simple way,” Dr. Marshall said in a paper recently published in the journal BioEssays. “Vitamin D affects the expression of over 1,000 genes, so we should not expect a simplistic cause and effect between vitamin D supplementation and disease” (Marshall TG. BioEssays. 2008 Jan 15; 30(2): 173–182).
He contends that many chronic diseases, particularly the so-called Th1-related illnesses, are related to immune system abnormalities brought about by dysregulation of vitamin D receptors, an idea that had roots in his early work with sarcoidosis patients who seemed to get worse with sunshine exposure and the subsequent increase in serum vitamin D levels.
Marshall’s theory holds that abnormal expression of the vitamin D receptors results in chronically low vitamin D levels, but more importantly to a state of immune system compromise that allows over-expression of L-form bacterial pathogens (which lack cell walls), triggering chronic inflammatory reactions.
Moreover, he argues that supplemental vitamin D is actually harmful because it blocks vitamin D receptor activation, and promotes rather than ameliorates the immune system abnormalities.
Dr. Marshall’s controversial hypotheses are far from being definitively proven, and the weight of epidemiological evidence still favors raising vitamin D levels. But they are important to consider because they challenge the tendency to assume that a nutrient deficiency observed in conjunction with one or more disease states is inherently causative, when in fact, it may be a result of disease.
What is very clear is the need for more research into the role of vitamin D in health and disease. As Dr. Pittas points out, most available evidence suggests that two common and inexpensive nutrients could take a big chunk out of diabetes risk.
This makes the vitamin D issue an important public health question, especially in light of the unexpected and disturbing findings from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study showing an increase rather than the expected decrease in cardiovascular death rate following intensive, drug based glucose control regimens (a transcript of the National Heart Lung & Blood Institute’s Feb. 6 press conference about ACCORD is available at www.nhlbi.nih.gov).
Given all the uncertainty triggered by ACCORD, large-scale clinical studies looking at the impact of nutritional supplementation on insulin sensitivity, glucose tolerance, and the progression of insulin resistance to diabetes are clearly warranted.
