Vitamin D and Cardiovascular Disease

Abstract

Vitamin D exists in several forms comprising steroid-like fat-soluble molecules (secosteroids). Cholecalciferol (vitamin D3) is synthesized in the skin in response to ultraviolet irradiation producing photochemical cleavage of a cholesterol precursor (7-dehydro-cholesterol). Irradiation of ergosterol, a membrane sterol found in the Ergot fungus, produces ergocalciferol (vitamin D2). Dietary sources of vitamin D include fish oils (D3), egg yolk (D3), mushrooms (D2), and fortified cereals and dairy products (D2 or D3). Vitamin D derived from all different sources undergoes two successive hydroxylation steps, first in the liver (25-hydroxyvitamin D) and then the kidney (1, 25-hydroxyvitamin D2 / calcitriol). The former form has a longer half-life than the latter (weeks vs. several hours). The biologic effects of vitamin D result largely from its binding to the vitamin D receptor (VDR), a nuclear steroid hormone found in almost every tissue. Calcitriol (D2) appears to have the greatest affinity for the receptor.

 The prevalence of vitamin D deficiency is estimated around 30–50% in the adult population in developed countries, mostly the result of insufficient cutaneous production due to decreased exposure to sunlight, and to a less degree from low dietary intake. Serum levels of 25-hydroxyvitamin D >30 ng/mL are considered adequate, while levels < 20 ng/mL are diagnostic of vitamin D deficiency.

The endocrine functions of vitamin D in relation to bone metabolism and mineral ion homoeostasis are well known. Vitamin D deficiency results in reduced intestinal absorption of calcium, which stimulates the production of parathyroid hormone with an ensuing accelerated bone de-mineralization to maintain serum calcium concentration, with all these alterations leading to the clinical effects of hypocalcemia. These may rarely result in tetany, but due to gradual and insidious development, more commonly produce local, or diffuse musculo-skeletal aches and pains.

Importantly, more recent epidemiological studies have linked vitamin D deficiency with the pathogenesis of cardiovascular disease (CVD) and an attendant increase in cardiovascular morbidity and mortality, but data for a causal relationship are still missing... (excerpt)