PMC

A Schematic Representation of the Major Causes for Vitamin D Deficiency and Potential Health Consequences. Holick copyright 2010. Reproduced with permission.

Comparison of serum vitamin D₃ levels after a whole-body exposure (in a bathing suit; bikini for women) to 1 MED (minimal erythemal dose) of simulated sunlight compared with a single oral dose of either 10,000 or 25,000 IU of vitamin D₂. Reproduced with permission from Holick copyright 2004

Photosynthesis of previtamin D₃ after exposure of 7-dehydrocholesterol (7-DHC) to sunlight. Measurements were as follows: in Boston (42°N) after 1 hr (□) and 3 hr (◻) and total photoproducts (previtamin D₃, lumisterol, and tachysterol) after 3 h in Boston (●); in Edmonton, Canada (52°N), after 1 hr (■); in Los Angeles (34°N) (▲) and Puerto Rico (18°N) in January (○). Reprinted with permission from Webb et al. [6].

The serum 25-hydroxyvitamin D levels in healthy adults with skin types II, III, and IV exposed to 0.75 MEDs of simulated sunlight in a bathing suit 3 times a week for 12 weeks compared to healthy adults receiving a daily dose of 1000 IU of vitamin D₃ daily for 12 weeks *p < 0.01. Copyright Holick 2010; reproduced with permission.

Mean (± SEM) serum 25-hydroxyvitamin D levels after oral administration of vitamin D₂ and/or vitamin D₃. Healthy adults recruited at the end of the winter received either placebo [(n = 14; 1,000 IU of vitamin D₃ [D₃, n = 20; (-■-)], 1,000 IU of vitamin D₂ [D₂, n = 16; (-▲-)] or 500 IU of vitamin D₂ and 500 IU of vitamin D₃ [D₂ and D₃, n = 18; (-□-)] daily for 11 weeks. The total 25-hydroxyvitamin D levels are demonstrated over time. *P = 0.027 comparing 25(OH)D over time between vitamin D₃ and placebo. **P=0.041 comparing 25(OH)D over time between 500 IU vitamin D₃ + 500 IU vitamin D₂ and placebo. ***P=0.023 comparing 25(OH)D over time between vitamin D₂ and placebo. Reproduced with permission ()

A. Mean serum 25-hydroxyvitamin D [25(OH)D] levels in all patients: Includes patients treated with 50,000 IU vitamin D₂ every 2 weeks (maintenance therapy, N=81), including those patients with vitamin D insufficiency who were initially treated with 8 weeks of 50,000 IU vitamin D₂ weekly prior to maintenance therapy (N=39). Error bars represent standard error of the mean, mean result over 5 years shown. Time 0 is initiation of treatment, results shown as mean values averaged for 6 month intervals. When mean 25(OH)D in each 6 month group was compared to mean initial 25(OH)D, p < 0.001 up until month 43; p < 0.001 when all remaining values after month 43 were compared to mean initial 25(OH)D. Pietras et al; reproduced with permission.()

Schematic representation of the synthesis and metabolism of vitamin D for regulating calcium, phosphorus and bone metabolism. During exposure to sunlight 7-dehydrocholesterol in the skin is converted to previtamin D₃. PreD₃ immediately converts by a heat dependent process to vitamin D₃. Excessive exposure to sunlight degrades previtamin D₃ and vitamin D₃ into inactive photoproducts. Vitamin D₂ and vitamin D₃ from dietary sources is incorporated into chylomicrons, transported by the lymphatic system into the venus circulation. Vitamin D (D represents D₂ or D₃) made in the skin or ingested in the diet can be stored in and then released from fat cells. Vitamin D in the circulation is bound to the vitamin D binding protein which transports it to the liver where vitamin D is converted by the vitamin D-25-hydroxylase to 25-hydroxyvitamin D [25(OH)D]. This is the major circulating form of vitamin D that is used by clinicians to measure vitamin D status (although most reference laboratories report the normal range to be 20-100 ng/ml, the preferred healthful range is 30-60 ng/ml). It is biologically inactive and must be converted in the kidneys by the 25-hydroxyvitamin D-1α-hydroxylase (1-OHase) to its biologically active form 1,25-dihydroxyvitamin D [1,25(OH)₂D]. Serum phosphorus, calcium fibroblast growth factors (FGF-23) and other factors can either increase (+) or decrease (-) the renal production of 1,25(OH)₂D. 1,25(OH)₂D feedback regulates its own synthesis and decreases the synthesis and secretion of parathyroid hormone (PTH) in the parathyroid glands. 1,25(OH)₂D increases the expression of the 25-hydroxyvitamin D-24-hydroxylase (24-OHase) to catabolize 1,25(OH)₂D to the water soluble biologically inactive calcitroic acid which is excreted in the bile. 1,25(OH)₂D enhances intestinal calcium absorption in the small intestine by stimulating the expression of the epithelial calcium channel (ECaC) and the calbindin 9K (calcium binding protein; CaBP). 1,25(OH)₂D is recognized by its receptor in osteoblasts causing an increase in the expression of receptor activator of NFκB ligand (RANKL). Its receptor RANK on the preosteoclast binds RANKL which induces the preosteoclast to become a mature osteoclast. The mature osteoclast removes calcium and phosphorus from the bone to maintain blood calcium and phosphorus levels. Adequate calcium and phosphorus levels promote the mineralization of the skeleton. Holick copyright 2007. Reproduced with permission.