The Death D-fying Vitamin

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I n this issue of Mayo Clinic Proceedings, Dudenkov et al 1 report on a retrospective study relating vitamin D status (serum 25-hydroxyvitamin D [25(OH)D]) with the risk of all-cause and cause-specific mortality in their patients registered in the Rochester Epidemiology Project. The article reported that vitamin D deficiency was associated with increased mortality. There was a statistically significant inverse relationship with mortality in both white and nonwhite patients, as well as with their serum 25(OH)D level. For white patients who had 25(OH)D levels of less than 12 and 12 to 19 ng/mL (to convert to nmol/L, multiply by 2.496), their unadjusted all-cause mortality hazard ratios (HRs) were 2.6 and 1.3, respectively , when compared with their reference range of 20 to 50 ng/mL. Equally important was the observation that the HR for those who had a 25(OH)D level greater than 50 ng/mL was 1 and thus not different from the reference range. When race was included in the analysis, there remained an increased mortality risk in nonwhite patients, although to a lesser degree when the HR was adjusted. This editorial begins with a brief summary of the history of the relationship of vitamin D and sunlight with mortality before discussing this meritorious study and offers insights into how pleiotropic effects of vitamin D may improve health and reduce mortality. Vitamin D is the sunshine vitamin. As a result, a multitude of studies have related latitude-associated health outcomes and mortality with vitamin D status. Association studies linking sun exposure with a reduced risk of mortality appeared more than a century ago with the observation that the risk of mortality from cancer increased in those who lived at a higher latitude. In 1941, it was reported that there was an increased risk of cancer mortality in farming communities in northeastern states as compared with those in southern states. 2 In the 1990s, Garland et al 3 observed that colon cancer mortality in the United States inversely correlated with solar radiation, and in a subsequent prospective study, these investigators 3 observed a 3-fold increase in colon cancer risk in people who had a 25(OH)D level less than 20 ng/mL. These studies were advanced by Grant, 4 who reported that premature mortality from various cancers inversely correlated with solar ultraviolet exposure in both men and women. Increases in sun exposure and vitamin D status have been linked to a reduced risk of diverse malignant solid organ tumors. 2 In a Canadian study, the risk of developing breast cancer in women is markedly reduced in those women who were the most sun-exposed in the second decade of life. 5 Observations relating increased sun exposure , living at lower latitudes (thereby making more vitamin D from sun exposure), and having higher 25(OH)D levels have been associated with improvement in cardiovascu-lar health and reduced risk of cardiovascular mortality. 2 There is an inverse association between latitude and elevation in blood pressure. 6 Vitamin D deficiency has been associated with an increased risk of peripheral vascular disease and myocardial infarction, and mortality from myocardial infarction is markedly increased in the setting of vitamin D deficiency. 7 Type 2 diabetes and obesity are dominant risk factors for cardiovascular diseases; in this regard, there is an inverse relationship with a body mass index (calculated as the weight in kilograms divided by the height in meters squared) greater than 30 kg/m 2 and vitamin D status 2,7 ; vitamin D deficiency associates with an increased risk of type 2 diabetes; and the Nurses' Health Study 8 reported a reduced risk of type 2 diabetes in participants with a dietary intake of at least 1200 mg of calcium in conjunction with at least 800 IU of vitamin D per day. Clear evidence also exists in the literature, revealing a substantial association of vitamin D deficiency with hypertension, hyperlipidemia along with peripheral vascular disease, and type 2 diabetes, all of which are risk factors for myocardial infarction, stroke, and mortality. 7 The Ludwigshafen Risk and Cardiovascular Health Study 9 observed that in 1801 patients with metabolic syndrome followed for 7.7 years, marked reduction in all-cause (HR, 0.25; 95% CI, 0.13-0.46) and cardiovascular See also page 721




Holick, M. F. (2018, June 1). The Death D-fying Vitamin. Mayo Clinic Proceedings, 93(6), 679–681.

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