Vitamin D

Vitamin D is a steroid and a vitamin that "includes both cholecalciferols and ergocalciferols, which have the common effect of preventing or curing rickets in animals. It can also be viewed as a hormone since it can be formed in skin by action of ultraviolet rays upon the precursors, 7-dehydrocholesterol and ergosterol, and acts on vitamin D receptors to regulate calcium in opposition to parathyroid hormone."

Vitamin D serves two classes of functions: (a) an endocrine function, in which a form of vitamin D, calcitriol, produced in the kidneys and secreted into the bloodstream, acts on target organs (gastrointestinal tract, bone, parathyroid glands) in such a way as to regulate aspects of calcium and phosphorus metabolism important to bone health and homeostasis of circulating calcium and phosphorus concentrations; and, (b) an autocrine function, in which the cells of numerous organs and tissues in the body (e.g., parts of the immune system, various epithelial tissues) generate calcitriol that functions in the cells that generate it, in intracellular signaling pathways (e.g., facilitation of the expression of specific genes) important to optimal functioning of those cells. The autocrine mechanisms account for the preponderance of vitamin D utilized by body each day, and therefore tends to set the daily requirement for vitamin D.

Biochemistry

Ergocalciferols (vitamin D₂) is formed in plants. Ergocalciferols are "derivatives of ergosterol formed by ultraviolet rays breaking of the C9-C10 bond. They differ from cholecalciferol in having a double bond between C22 and C23 and a methyl group at C24."

Cholecalciferol (vitamin D₃) is formed in the skin of animals from 7-dehydrocholesterol by sunlight. Cholecalciferol is a "derivative of 7-dehydroxycholesterol formed by ultraviolet rays breaking of the C9-C10 bond. It differs from ergocalciferol in having a single bond between C22 and C23 and lacking a methyl group at C24."

Vitamin D₂ and vitamin D₃ are of equal potency.

Vitamin D₂ and vitamin D₃ are hydroxylated in the liver at the 25 position. This leads to calcitriol (1,25-Dihydroxyvitamin D3). Calcitriol is the "physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (calcifediol). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption."

Genetic variation in the vitamin D–binding protein level can affect the serum levels. "The T allele at rs7041 was associated with decreased levels of total 25-hydroxyvitamin D among blacks. In whites, the A allele at rs4588 was associated with decreased levels of total 25-hydroxyvitamin D."

Administration

The best treatment may be calciferol (ergocalciferol or colecalciferol). For every 100 IU of vitamin D taken, the serum level rises about 1 ng/ml. For 1000 IU daily, a randomized controlled trial found that consuming orange juice fortified with either vitamin D₃ or vitamin D₂ was not significantly different than consuming the corresponding capsules of the vitamins in respect of increasing 25-hydroxyvitamin D blood levels.

In a prior study of healthy adults, Vitamin D₂ and vitamin D₃ are equally effective in maintaining serum 25-hydroxyvitamin D levels.

Clinical uses

Clinical practice guidelines by the Endocrine Society are available.

Clinical practice guidelines by the U.S. Preventive Services Task Force recommend (italics are added):

• "recommends exercise or physical therapy and vitamin D supplementation to prevent falls in community-dwelling adults aged 65 years or older who are at increased risk for falls"
• "recommends against daily supplementation with ≤400 IU of vitamin D3 and 1,000 mg of calcium carbonate for the primary prevention of fractures in noninstitutionalized postmenopausal women" (draft recommendation)
• "the current evidence is insufficient to assess the balance of the benefits and harms of vitamin D supplementation, with or without calcium, for the primary prevention of cancer in adults" (draft recommendation)
• "the current evidence is insufficient to assess the balance of the benefits and harms of combined vitamin D and calcium supplementation for the primary prevention of fractures in premenopausal women or in men" (draft recommendation)
• "the current evidence is insufficient to assess the balance of the benefits and harms of daily supplementation with >400 IU of vitamin D3 and 1,000 mg of calcium for the primary prevention of fractures in noninstitutionalized postmenopausal women" (draft recommendation)

Mortality

"Vitamin D in the form of vitamin D(3) seems to decrease mortality in predominantly elderly women who are mainly in institutions and dependent care" according to the Cochrane Collaboration.

A recent randomized controlled trial found no benefit.

Accidental falls

The American Geriatrics Society recommends regarding vitamin D for prevention of accidental falls in geriatrics:

1. "Vitamin D supplements of at least 800 IU per day should be provided to older persons with proven vitamin D deficiency."
2. "Vitamin D supplements of at least 800 IU per day should be considered for people with suspected vitamin D deficiency or who are otherwise at increased risk for falls."

Meta-analyses supports these recommendations. especially if the level of vitamin D achieved is over 24 ng/ml (60 nmol/l).

Fracture prevention

Vitamin D, if given with or without calcium, may prevent fractures.

Vitamin D levels below 20 ng/ml predicts fractures in anglo women, but not in African-American women.

Cancer prevention

A secondary analysis of a randomized controlled trial originally designed to study fractures suggests that cholecalciferol (vitamin D₃) combined with calcium may reduce risk of cancer. They reported that 1100 IU of vitamin D (cholecalciferol) combined with 1500 mg of calcium per day administered for four years greatly reduced the risk for new cancers compared with placebo controls (p < 0.005). They also noted that the concentrations of serum 25-hydroxy-vitamin D (25[OH]D) levels, both pre-treatment and during treatment independently predicted cancer risk. The treatment group achieved mean concentrations of serum 25-hydroxy-vitamin D (25[OH]D) of 96 nmol/L (38 ng/ml). Natural levels for people who live and work in the sun: ~50-70 ng/ml (~125-175 nmol/L).

A randomized controlled trial found no benefit on colorectal cancer prevention.

An observational analysis of a randomized controlled trial found no benefit for prostate cancer.

A recent randomized controlled trial found no benefit.

Cardiovascular disease

Vitamin D supplementation may reduce cardiovascular disease according to a systematic review although some randomized controlled trials are negative.

A recent randomized controlled trial found no benefit.

Cognition

Vitamin D may help cognition.

Diabetes mellitus type 2

Vitamin D supplementation does not appear to prevent diabetes mellitus type 2.

Chronic pain

Vitamin D supplementation does not seem to reduce chronic pain.

Muscle function

Vitamin D supplementation for individuals with less than 24 ng/mL may improve muscle function according to a randomized controlled trial.

Secondary hyperparathyroidism

Vitamin D can lower levels of parathyroid hormone in patients with secondary hyperparathryoidism from chronic kidney disease.

Vascular disease prevention

Vitamin D may help prevent vascular disease.

Drug toxicity

Vitamin D, when combined with calcium, may increase nephrolithiasis.