Definition:

Vitamin D is a fat-soluble vitamin that regulates calcium homeostasis and is vital for bone health. While it can also be obtained from dietary sources or supplements, vitamin D3 (cholecalciferol) is synthesized in the human skin from 7-dehydrocholesterol upon exposure to ultraviolet-B (UVB) radiation from sunlight. Vitamin D2 (ergocalciferol) is a vitamin D analog photosynthesized in plants, mushrooms, and yeasts; vitamin D2 is also sometimes used in vitamin D food fortification. When vitamin D3 in the skin is inadequate due to insufficient exposure to UVB radiation, oral intake of vitamin D is necessary to meet vitamin D requirements.

• Vitamin D is essential for the maintenance of bone mineralization through the regulation of calcium and phosphorus homeostasis. Vitamin D also exhibits many non-skeletal effects, particularly on the immune, endocrine, and cardiovascular systems.
• Secondary hyperparathyroidism due to vitamin D insufficiency can increase bone breakdown and precipitate osteoporosis. Randomized clinical trials indicate that supplementation with at least 800 IU/day of vitamin D may reduce the risk of falls and fractures in older individuals.
• Vitamin D can regulate cell differentiation and growth by binding to the vitamin D receptor found in most body cells. Observational studies have reported associations between low sun exposure, poor vitamin D status, and increased risk of developing colorectal and breast cancer. Randomized controlled trials are needed to evaluate whether cancer prevention may benefit from vitamin D supplementation.
• Various observational studies have reported inverse associations between vitamin D status and the susceptibility or severity of autoimmune diseases, including type 1 diabetes mellitus, multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus.
• Current evidence from observational studies suggests an inverse relationship between circulating vitamin D concentrations and the risk of type 2 diabetes mellitus. It is not yet known whether correcting vitamin D deficiency in individuals with glucose intolerance can decrease the risk of progression to type 2 diabetes mellitus.
• Randomized clinical trials are currently investigating whether vitamin D supplementation can limit cognitive deterioration and disease progression in subjects with neurodegenerative diseases.
• Vitamin D insufficiency in pregnant women may be associated with several adverse effects for the mother and newborn. The safety and benefits of vitamin D supplementation during pregnancy both need to be evaluated in clinical trials.
• Observational studies have documented an association between vitamin D deficiency and increased incidence and severity of the coronavirus disease, COVID-19.
• Preliminary studies have shown that vitamin D supplementation may offer promising improvements in the management of atopic dermatitis (eczema) and Crohn’s disease.
• Since vitamin D is fat-soluble, it may accumulate in tissues and produce toxic effects after prolonged administration of large doses. Manifestations of vitamin D toxicity may include hypercalcemia, hypercalciuria, fatigue, anorexia, nausea, vomiting, polyuria, polydipsia, and cardiac arrhythmias. Calcification of the kidneys can develop and may progress to renal failure. Death has occurred in some cases of vitamin D intoxication.

Dosage and administration

• The optimal dosage of vitamin D remains a topic of considerable debate. Studies have shown that 800 IU/day is more effective than 400 IU/day in preventing falls and fractures in elderly people. I frequently recommend 800–2000 IU/day of supplemental vitamin D, and sometimes more, depending on age, body mass index, skin color, and amount of sunlight exposure. Larger doses may also be recommended for people who have or are at risk of developing certain diseases.