Vitamin D3 is made in the skin from 7-dehydrocholesterol under the influence of UV light. Vitamin D2 (ergocalciferol) is derived from the plant sterol ergosterol. Vitamin D is metabolized first to 25 hydroxyvitamin D (25OHD), then to the hormonal form 1,25-dihydroxyvitamin D (1,25(OH)2D)(7). Most foods with the exception of fatty fish contain little vitamin D unless fortified. The vitamin D in fish is D3, whereas that used for fortification is often D2 (ergocalciferol). The differences in D2 from D3 result in faster clearance from the circulation, limit its conversion to 25 hydroxyvitamin D (25OHD), and alter its catabolism by the 24-hydroxyase. Therefore, unless given daily, D2 supplementation does not result in as high a blood level of 25OHD as comparable amounts of D3(7).

The three main steps in vitamin D metabolism are 25-hydroxylation, 1α-hydroxylation, and 24-hydroxylation. The liver is the major if not sole source of 25OHD production from vitamin D. The kidney is the major if not the sole source of circulating levels of 1,25(OH)2D. CYP24A1 controls levels of 1,25(OH)2D within tissues(7).

Your body needs vitamin D to absorb calcium. Calcium keeps your bones and muscles -- including your heart -- healthy and strong. People who do not get enough calcium and vitamin D throughout life have an increased chance of having thin and brittle bones (osteoporosis) in their later years. Your body also uses vitamin D to help your muscles absorb calcium and work well. If your muscles don't get enough calcium, then they can cramp, hurt, or feel weak(1). It has been estimated that 1 billion people worldwide have vitamin D deficiency or insufficiency(2).

Children who don't get enough vitamin D may not grow as much as others their age(1). They also have a chance of getting a rare disease called rickets, which causes weak bones. However, rickets can be considered the tip of the vitamin D–deficiency iceberg. In fact, vitamin D deficiency remains common in children and adults. In utero and during childhood, vitamin D deficiency can cause growth retardation and skeletal deformities and may increase the risk of hip fracture later in life(2).

Few foods naturally contain or are fortified with vitamin D2. Humans get vitamin D from exposure to sunlight, from their diet, and from dietary supplements. While using sunscreen can help prevent skin issues, using an SPF 8 reduces vitamin D3 synthesis by 92.5% and SPF 15 by 99%(2). Vitamin D from the skin and diet is metabolized in the liver then in the kidneys2. Anticonvulsants, glucocorticoids, HAART (AIDS treatment), and antirejection medications can activate the destruction of vitamin D to inactive calcitroic acid(2). Obesity can reduce availability of vitamin D as it is sequestered in body fat(2).

Of great interest is the role it can play in decreasing the risk of many chronic illnesses, including common cancers, autoimmune diseases, infectious diseases, and cardiovascular disease(2). A 2010 assessment by the International Osteoporosis Foundation and a 2011 assessment of the Agency for Healthcare Research and Quality for the U.S. Preventative Services Task Force both identified vitamin D as an effective intervention to prevent falling in older adults(3). Evidence supports an association between vitamin D deficiency and hypertension, peripheral vascular disease, diabetes mellitus, metabolic syndrome, coronary artery disease, and heart failure. Vitamin D supplementation was significantly associated with better survival, specifically in patients with documented deficiency(4). Recent studies have found associations between vitamin D deficiency (VDD), insulin resistance (IR), and nonalcoholic fatty liver disease (NAFLD) among overweight children(5). NAFLD has become the most common form of chronic liver disease in western countries exceeding that of viral hepatitis and alcoholic liver disease(6). Recent studies of VDD in humans and animals indicate that VDD also contributes to increased oxidative stress and increased inflammation(5).