Vitamin D and its Major Metabolites: Serum Levels after Graded Oral Dosing in Healthy Men

Abstract

We determined the quantitative relationships between graded oral dosing with vitamin D3, 25(OH)D3, and 1,25(OH)2D3 for short treatment periods and changes in circulating levels of these substances. The subjects were 116 healthy men (mean age, 28 +/- 4 years, with usual milk consumption of < or = 0.47 l/day and mean serum 25(OH)D of 67 +/- 25 nmol/l). They were distributed among nine open-label treatment groups: vitamin D3 (25, 250 or 1250 micrograms/day for 8 weeks), 25(OH)D3 (10, 20 or 50 micrograms/day for 4 weeks) and 1,25(OH)2D3 (0.5, 1.0 or 1.0 microgram/day for 2 weeks). All treatment occurred between January 3 and April 3. We measured fasting serum, calcium, parathyroid hormone, vitamin D3, 25(OH)D and 1,25(OH)2D immediately before and after treatment. In the three groups treated with vitamin D3, mean values for circulating vitamin D3 increased by 13, 137 and 883 nmol/l and serum 25(OH)D increased by 29, 146 and 643 nmol/l for the three dosage groups, respectively. Treatment with 25(OH)D3 increased circulating 25(OH)D by 40, 76 and 206 nmol/l, respectively. Neither compound changed serum 1,25(OH)2D levels. However, treatment with 1,25(OH)2D3 increased circulating 1,25(OH)2D by 10, 46 and 60 pmol/l, respectively. Slopes calculated from these data allow the following estimates of mean treatment effects for typical dosage units in healthy 70-kg adults: an 8-week course of vitamin D3 at 10 micrograms/day (400 IU/day) would raise serum vitamin D by 9 nmol/l and serum 25(OH)D by 11 nmol/l; a 4-week course of 25(OH)D3 at 20 micrograms/day would raise serum 25(OH)D by 94 nmol/l; and a 2-week course of 1,25(OH)2D3 at 0.5 microgram/day would raise serum 1,25(OH)2D by 17 pmol/l.

Oral supplementation with 25(OH)D3 versus vitamin D3: Effects on 25(OH)D levels, lower extremity function, blood pressure, and markers of innate immunity

“…(14,15) In earlier studies, oral intake of HyD resulted in a potent increase in serum 25(OH)D levels and parathyroid hormone suppression. (16)(17)(18)(19)(20)(21) Further, some smaller trials reported a benefit on bone density among groups of cardiac and kidney transplant patients, and elderly hip fracture patients (19,22,23) ; although this was not confirmed in a larger trial among 438 seniors. (18) However, the treatment dose of HyD in the larger trial was low with 15 mg per day.…”

“…The same dose was chosen for HyD, which, based on our review of the literature, offered an optimal balance of efficacy and safety. (16,21) We randomized 15 additional women to onetime bolus groups, which were only included in a pharmacokinetic analysis, while clinical endpoint evaluations for this manuscript are restricted to the daily and weekly treatment groups (n ¼ 20). As the results between daily and weekly HyD and vitamin D 3 supplementation did not differ significantly, the daily and weekly groups for each supplementation were combined for the analysis.…”

Vitamin D intake is low and hypovitaminosis D common in healthy 9− to 15-year-old Finnish girls

“…The effect of vitamin D supplementation on the S-25(OH)D concentration has been demonstrated in several studies on elderly people worldwide (Chapuy et al, 1992;Heikinheimo et al, 1996;Lips et al, 1996). Barger-Lux et al (1998) reported that an 8-week course of vitamin D3 of 10 mgad raised S-25(OH)D by 11 nmolal in healthy adult males. In our study the mean S-25(OH)D concentration was about 25 nmolal among the subjects who had the lowest dietary vitamin D intake (1 mgad) and about 35 nmolal among those with the highest intake (9 mgad); these ®gures agree with the above-mentioned results.…”

Are all steaks created equal?

“…The latter, very high value deserves a special comment later. 25(OH)D 3 has some remarkable properties: in contrast to vitamin D 3 the serum increase of 25(OH)D 3 is directly proportional to oral input (9) and its biological activity, calculated as a function of serum 25(OH)D 3 increase, is between four (9) and nine times higher (10) than that of vitamin D 3 . In food composition tables (2) the vitamin D level of meat is calculated as D 3 plus five times 25(OH)D 3 .…”

“…Given that sunlight exposure is the main determinant for the pro-hormone content of beef, one must conclude that meat from cattle on pasture and slaughtered at the end of summer has a much higher content of the metabolite than meat from cows housed in shelters or slaughtered in winter. If an average meat eater consumes the equivalent of 100 g of fresh beef daily (equivalent to 2.5 mg/g) from pasture-kept cattle (slaughtered late in summer and having the above content of 25(OH)D 3 ), the increase in serum 25(OH)D 3 steady-state levels in nmol/l can be calculated from a formula (9) to be about 10 nmol/l or even more. One cannot exclude that many of the meat eaters analysed by Crowe et al (1) consumed such 'naturally fortified' beef.…”