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Vitamin D and prevention of cardiovascular disease and diabetes: the potential sunny vitamin d effects are clouded by unclear evidence.

What are the recommended intakes for vitamin D? What concentration of 25-hydoxyvitamin D delineates "normal" from vitamin D deficient? These recurring questions have received considerable attention and debate. The Institute of Medicine (IOM) used a systematic, evidence-based review approach to make its recommended dietary allowances for vitamin D, including a critical evaluation of the plethora of evidence relevant to the role of vitamin D in human health and disease. According to the 2011 IOM report (1), despite a large body of scientific evidence supporting the potential role of vitamin D in preventing cardiovascular disease and type 2 diabetes, these data were deemed insufficient to inform nutritional requirements. How could such substantial evidence have had minimal influence on the IOM recommended intakes for vitamin D?

In a recent commentary in the Journal of the American Medical Association (2), 2 members of the IOM committee, Drs. Sue Shapses and JoAnn Manson, discussed the committee's assessment of available evidence and subsequent conclusions that led to the IOM recommended intakes for vitamin D. The principle that association does not prove causation was highlighted as a key criterion, which contended that a cause-and-effect relationship between a nutrient and a health outcome is essential. The IOM committee reviewed several observational studies and uncovered both uncertainty and inconsistency among the studies that associated 25-hydroxyvitamin D concentrations with subsequent cardiovascular events. Select studies further suggested a nonlinear association with potential increased risk of cardiovascular disease or total-mortality outcomes, not only at lower 25-hydroxyvitamin D concentrations but at higher concentrations as well. Additionally, disparate results were noted from a limited number of randomized controlled trials with respect to vitamin D and cardiovascular disease events, as well as was the absence of any completed trials with cardiovascular disease as the primary prespecified outcome. Taking these findings together and consistent with previous systematic reviews, the IOM committee concluded that the evidence for a role for vitamin D in the prevention of cardiovascular disease was conflicting and not sufficient to prove a cause-and-effect relationship.

Numerous studies have hypothesized a role for vitamin D in the prevention of type 2 diabetes. A systematic review and metaanalysis of observational and intervention studies with vitamin D supplementation demonstrated a lack of consensus, which was likely precipitated by confounding factors such as small study sizes and short durations of intervention, with few studies demonstrating an inverse relationship between a higher vitamin D intake or 25-hydroxyvitamin D concentrations and the risk of type 2 diabetes. Randomized trials of vitamin D supplementation and the risk of type 2 diabetes also demonstrated inconsistent findings. Thus, the collective evidence for vitamin D in prevention of type 2 diabetes could not support causality.

The possibility of an enhanced role for vitamin D in human health beyond maintaining healthy bones has sparked renewed interest in the sunshine vitamin, although the potential sunny vitamin D effects are clouded by unclear evidence. Despite the large body of scientific findings supporting potential roles for vitamin D in prevention of cardiovascular disease and type 2 diabetes, the IOM committee concluded that the collective evidence was not sufficient to inform nutritional requirements. Ongoing randomized trials assessing the role of vitamin D supplementation in cardiovascular disease and prevention of type 2 diabetes will likely provide invaluable insight; however, until future findings support a clear benefit of vitamin D supplementation in reducing cardiovascular disease, diabetes, or other extraskeletal health risks, the "bare bones" remain the basis for the IOM recommended intakes for vitamin D.

Author Contributions: All authors confirmed they have contributed to the intellectual content of this paperandhave met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and(c) final approval of the published article.

Authors' Disclosures or Potential Conflicts of Interest: No authors declared any potential conflicts of interest.

References

(1.) Ross AC, Taylor CL, Yaktine AL, Del Valle HB, eds., Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. DRI (dietary reference intakes): calcium and vitamin D. Washington (DC): National Academies Press; 2011. 1116 p. http://books.nap.edu/openbook.php?record_id=13050 (Accessed January 2012).

(2.) Shapses SA, Manson JE. Vitamin D and prevention of cardiovascular disease and diabetes. JAMA 2011;305:2565-6.

Nichole L. Korpi-Steiner *

Department of Hospital Laboratories, UMass Memorial Medical Center, Worcester, MA.

* Address correspondence to this author at: Department of Hospital Laboratories, UMass Memorial Medical Center, 365 Plantation St., Worcester, MA 01605. Fax 774-442-9604; e-mail nichole.korpi-steiner@umassmemorial.org.

Received February 21, 2012; accepted February 22, 2012.

DOI: 10.1373/clinchem.2012.183012
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Title Annotation:News & Views
Author:Korpi-Steiner, Nichole L.
Publication:Clinical Chemistry
Geographic Code:1USA
Date:May 1, 2012
Words:767
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