Vitamin D and Cardiovascular Disease: Can Novel Measures of Vitamin D Status Improve Risk Prediction and Address the Vitamin D Racial Paradox?

Abstract

Purpose of review To provide a state-of-the-art update on some emerging measures of vitamin D status and discuss how assessment of these key vitamin D metabolites might improve prognostication of risk for cardiovascular disease (CVD) outcomes. Recent findings Vitamin D deficiency is a highly prevalent condition and relatively easy to treat with supplementation and/or modest sunlight exposure. A substantial body of experimental and epidemiological evidence suggest that vitamin D deficiency is a risk factor for CVD. Most epidemiologic studies to date have focused on total 25-hydroxyvitamin D [25(OH)D] concentrations, which is the established marker of vitamin D stores. However, there is emerging evidence that other novel markers of vitamin D metabolism may better characterize ‘true’ vitamin D status. Some key novel measures include bioavailable 25(OH)D, free 25(OH)D, 1–25 dihydroxyvitamin D, 24,25-dihydroxyvitamin D3 [24,25(OH)2D3], and ratio of 24,25(OH)2D3 to 25(OH)D [the vitamin D metabolic ratio]. Utilization of these biomarkers may enhance understanding of the association between vitamin D and CVD risk, and may provide explanation for the observation that 25(OH)D is a stronger CVD risk factor in whites than blacks Summary Novel measures of vitamin D status could potentially change clinical practice regarding how patients are currently screened for vitamin D status and defined as vitamin D deficient or not. However, whether measuring any of these alternate markers of vitamin D status can provide further insight regarding CVD risk beyond the traditionally measured 25(OH)D concentrations is uncertain at this time. This is an area where further research is strongly needed.

Effect of Long-term Vitamin D3 Supplementation vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores

“…Large-scale studies would be required to address the effects of high-dose, long-term vitamin D 3 supplementation among those with nutrient deficiency. The use of alternative biochemical vitamin D measures may better address possible racial/ethnic variation . Third, this study may have been underpowered to detect subgroup differences.…”

The Relationship of Falls With Achieved 25-Hydroxyvitamin D Levels From Vitamin D Supplementation: The STURDY Trial

“…Prior meta-analyses have generally focused on comparing doses of vitamin D supplementation with fall risk [ 16 ]. However, there is variable response to an achieved 25(OH)D concentration for a given vitamin D supplementation dose based on age, bioavailability, obesity status, racial factors, and genetic polymorphisms related to vitamin D metabolism [ 44 , 45 ]. Thus, we undertook these analyses because we anticipated the purported benefit of vitamin D supplementation may depend on achieved blood concentration and not the dose per se.…”

Directly measured free and total 25-hydroxyvitamin D levels in relation to metabolic health in multi-ethnic postmenopausal females in Saudi Arabia

“…Data on directly measured free 25(OH)D level and how it relates to lipid parameters is very limited in the literature. Most epidemiological studies relating vitamin D with cardiovascular risk are centered on total 25(OH)D only ( 53 ). Although our results of free 25(OH) relationship with lipid levels are inadequate to draw a definitive conclusion, free 25(OH)D exhibited a different relationship with lipids when compared with total 25(OH)D. However, whether future assessment of free 25(OH)D instead of total 25(OH)D can afford a new vision toward cardiovascular risk is still unclear.…”