Table II.

Causes of vitamin D deficiency.

Cause	Effect	(Refs.)
Reduced synthesis in the skin Sunscreen: Use of sunscreens to prevent sunburn and skin cancer Skin pigmentation: Melanin reduces the penetration of UV-B rays Time of day: The more oblique the zenith angle, the fewer UV-B photons reach the Earth's surface Aging: Decreased concentration of 7-dehydrocholesterol in the epidermis Other factors: Clothing habits, cloud cover, pollution, season and latitude	May reduce vitamin D3 synthesis under strictly controlled conditions Reduced effectiveness of vitamin D3 synthesis in the skin The production of vitamin D3 in the skin is absent in the early hours or late in the day 50% decrease in vitamin D3 production in old age Decrease or absence of vitamin D3 synthesis in the skin	(145-147,159,160)
Decreased bioavailability Diet: Limited intake of natural and fortified foods with vitamin D, lack of supplementation Malabsorption: Intestinal malabsorption syndromes (cystic fibrosis, celiac disease, inflammatory bowel disease and short bowel syndrome); bile acid sequestrants (colestipol and cholestyramine) and lipase inhibitors (orlistat) Obesity: Volumetric dilution of vitamin D in the compartments that are increased in obesity (serum, muscle, liver and adipose tissue)	Decreased bioavailability of 25(OH)D Decreased ability to absorb vitamin D Decreased bioavailability of 25(OH)D	(58,148,161,162)
Increased catabolism Drugs: Glucocorticoid and antiepileptic treatment	1,25(OH)2D degradation due to increased 24-OHase activity. These drugs may increase the expression of 24-OHase through the activation of the pregnane X receptor	(152-154)
Decreased synthesis of 25(OH)D Liver failure: Chronic liver disease	Decreased hydroxylation of vitamin D resulting in low levels of 25(OH)D	(149)
Increased urinary loss of 25(OH)D Nephrotic syndrome: 25(OH)D bound to DBP is lost in the urine	Significant loss of 25(OH)D in urine due to proteinuria	(150,151)
Decreased synthesis of 1,25(OH)2D Chronic kidney disease: Decreased renal mass limits the amount of CYP27B1; decreased glomerular filtration rate may limit delivery of substrate to the CYP27B1	Progressive decrease in 1,25(OH)2D during the course of kidney disease	(155,156)
Genetic polymorphisms Single nucleotide polymorphisms at DHCR7 (rs7944926), GC (rs2282679), CYP2R1 (rs10741657), CYP27B1 (rs10877012) and VDR (rs2228570)	Low serum 25(OH)D concentrations and less effective transcriptional activation of VDR	(157,158)

Adapted from ref. (62). UV-B, ultraviolet-B; 25(OH)D, 25-hydroxyvitamin D; 1,25(OH)₂D, 1,25-dihydroxyvitamin D; 24-OHase, 25-hydroxyvitamin D-24-hydroxylase; DBP, vitamin D-binding protein; VDR, vitamin D receptor.