Defective Photoproduction of Cholecalciferol in Normal and Uremic Humans

ALLAN I. JACOB,* AŽALAN SALLMAN,* ZENAIDASANTIZ* ANDBRUCE W. HOLLIS'AŽ'Department of Medicine, University of Miami School ofMedicine, Miami, FL 33101, AŽA/brt/iBeach Dialysis Clinic,North Miami Beach, FL 33169 and iDepartment of Nutrition, Case Western Reserve University, Cleveland, OH 44106ABSTRACT The initial step in cholecalciferol (vitamin D3) metabolism is thephoto-conversion of 7-dehydrocholesterol to previtamin D3. This reaction occurs inthe epidermis and requires ultraviolet light. We measured the circulating concentration of vitamin D (ergocalciferol and cholecalciferol), 25-hydroxyvitamin D and1,25-dihydroxyvitamin D in 14 normal white, 9 normal black subjects, and in 9 whiteand 17 black hemodialysis patients. The mean plasma vitamin D in normal whitesubjects was greater than in normal black subjects, 4.01 ±1.02 ng/ml versus 0.96±0.30 ng/ml, respectively (P < 0.05). Plasma 25-hydroxyvitamin D in normalblacks was also less than in normal whites, 17.7 ±1.5 ng/ml versus 31.3 ±3.0 ng/ml,respectively (P < 0.01). In uremie white subjects, plasma vitamin D, 6.7 ±2.6ng/ml, was similar to normal white subjects. However, vitamin D was not detectablein 12 of 17 uremie black subjects and was depressed in the remainder of the group.Following exposure to a single minimal erythema dose of ultraviolet-B irradiation, themaximal increase in plasma vitamin D was depressed in white dialysis patients ascompared to healthy white subjects, 6.3 ±1.9 ng/ml versus 21.3 ±2.8 ng/ml, respectively (P < 0.02). 7-Dehydrocholesterol content was similar in epidermis from site-matched skin of fresh cadavers and white hemodialysis patients, 131 ±23 ng/mgversus 124 ±14 ng/mg skin, respectively. It is concluded that chronic hemodialysispatients exhibit defective photoproduction of cholecalciferol, despite normal epidermal content of substrate, 7-dehydrocholesterol. J. Nutr. 114: 1313-1319, 1984.INDEXING KEY WORDS uremia •vitamin D •photobiologyMajor advances in understanding the of 25-OH-D then occur in various tissues ofmechanisms and biological regulation of which renal tissue is quantitatively the mostvitamin D synthesis have recently been important (10). The effects of chronicachieved, and sensitive assays for plasma uremia on the photoproduction and circu-vitamin D have been developed (1-4). Dur- lating concentration of vitamin D are theing exposure to ultraviolet-B [UV(B), spec- subject of this investigation,trai range 290-320 nm], 7-dehydrocholesterol (7-DHC) in the epidermis is converted MATERIALSAND METHODSto previtamin D3, which slowly undergoesthermal isomerization to cholecalciferol Sterols. [la,2a-3H]D3 (22 Ci/mmol) and(vitamin D3) (5-8). A carrier protein, vita- 25-OH-[26,27-3H]D3 (20 Ci/mmol) weremin D-binding protein, transports theparent compound to the liver for hydroxyla-tion, giving rise to 25-hydroxyvitamin D 27^^teâ„¢^" Ins"'ute°fNutriM°"'Receivedf°rpublication(25-OH-D) (9). Subsequent hydroxylations 'TOwhomreprintrequestsshouldbeaddressed.1313