Vitamin D, Calcium, and Cardiovascular Disease: A“D”vantageous or “D”etrimental? An Era of Uncertainty

Abstract

While the function of vitamin D in regulating calcium homeostasis is well established, there has been growing interest in its role in the prevention of numerous chronic diseases, including cardiovascular disease (CVD). There is mounting epidemiological evidence suggesting that vitamin D deficiency is linked to increased CVD risk. However, the results of previous vitamin D supplementation trials have yielded mixed results in regards to cardiovascular health, and the results of on-going large-scale randomized controlled trials are not yet available. Further complicating the issue, calcium supplementation, which is often prescribed concurrently with vitamin D, has been associated with increased CVD risk in some (but not all) studies. Thus, it is currently unclear whether vitamin D supplements, particularly for those that are deficient, can help prevent the development of CVD. In addition, there has not been uniform consensus regarding the threshold of 25-hydroxyvitamin D levels that constitutes “sufficiency” across organizational guidelines. This review will provide an update on the most recent evidence regarding the effects of vitamin D and calcium supplements on CVD clinical outcomes, summarize ongoing vitamin D trials, and discuss the current but remarkably disparate recommendations regarding vitamin D deficiency screening and supplementation.

Markers of vitamin D metabolism and incidence of clinically diagnosed abdominal aortic aneurysm: The Atherosclerosis Risk in Communities Study

“…If suboptimal 25(OH)D or elevated serum calcium or PTH influence AAA risk, they likely do so by elevating established cardiovascular risk factors, namely hypertension, 5–11 inflammation 12,13 and vascular calcification. 14,15 Our analysis did not provide convincing evidence that either 25(OH)D or PTH [which is downstream from 25(OH)D], are associated with AAA development. This is in contrast to the existing, albeit limited, literature.…”

“…Briefly, suboptimal 25(OH)D, PTH, and calcium concentrations have been linked to several AAA risk factors such as hypertension, 5–11 inflammation, 12,13 and vascular calcification. 14,15 Elevated FGF23 has been related to aneurysmal development in both in vitro studies of human and rat aorta cells 16 and in rat experimental models. 17 High phosphate concentrations precede elevated FGF23 and have been associated with vascular calcification 18–20 and myocardial fibrosis.…”

Relation of Serum Vitamin D to Risk of Mitral Annular and Aortic Valve Calcium (from the Multi-Ethnic Study of Atherosclerosis)

“…7,26,27 However whether vitamin D supplementation, a widely available and low cost remedy, can reduce CVD risk remains uncertain at this time. 27 The recent Vitamin D Assessment Study failed to show that high-dose vitamin D supplementation prevented CVD events.…”

“…7,26,27 However whether vitamin D supplementation, a widely available and low cost remedy, can reduce CVD risk remains uncertain at this time. 27 The recent Vitamin D Assessment Study failed to show that high-dose vitamin D supplementation prevented CVD events. 28 However, confirmatory results from other large randomized clinical trials [such as the ongoing Vitamin D and Omega-3 Trial (VITAL) study 29 ] that include more diverse populations and include individuals with 25(OH)D deficiency are needed to definitively determine the benefit of vitamin D supplementation on CVD outcomes.…”

Have We Been Measuring the Wrong Form of Vitamin D?

“…In summary, despite the evidence linking CAD and vitamin D deficiency, Vitamin D supplementation trials have not yielded convincing clinical benefits 13, 14 . Ultimately, we must ask ourselves, first, are we correctly defining what normal vitamin D levels are in different patient populations, and second, are we chasing after simply discerning a biomarker for increased CAD risk or is vitamin D actually a crucial part in the pathogenesis?…”