Rolf Jorde and Guri Grimnes
In addition to its skeletal effects, vitamin D may also be important for health in general. It is uncertain what level of serum 25-hydroxyvitamin D (25(OH)D), marker of vitamin D status, is sufficient for these effects. With decreasing serum 25(OH)D levels there is an increase in serum PTH. The point at which this occurs has been considered as a threshold for vitamin D sufficiency. The thresholds found have varied widely and have mainly been based on observational studies. However, to truly establish a threshold for vitamin D effects, this has to be based on randomized controlled trials (RCTs).
The study included 2803 subjects from a general health survey, the Tromsø study, and pooled individual person data from five vitamin D intervention studies (n = 1544). Serum parathyroid hormone (PTH) and change in PTH after vitamin D supplementation were related to serum 25(OH)D levels in steps of 25 nmol/L (<24, 25–49, 50–74, 75–99, and >99 nmol/L).
In the Tromsø study, in the females there was a gradual decrease in serum PTH with increasing serum 25(OH)D with no apparent plateau, whereas in the males the decrease in PTH in subjects with serum 25(OH)D >74 nmol/l was marginal. In pooled RCTs, there was a significant reduction in serum PTH by vitamin D supplementation regardless of baseline serum 25(OH)D level.
The use of the serum PTH–25(OH)D relation from observational studies to determine a threshold for vitamin D sufficiency is highly questionable.
Julia Kubiak, Per Medbøe Thorsby, Elena Kamycheva and Rolf Jorde
Low serum 25(OH)D levels are associated with cardiovascular disease (CVD) and some of its risk factors. However, in interventional studies, the effects of vitamin D supplementation have been uncertain, possibly due to inclusion of vitamin D-sufficient subjects. Our aim was therefore to examine effects of vitamin D supplementation on CVD risk factors in vitamin D-insufficient subjects.
Double-blinded randomized controlled trial.
A 4-month interventional study with high-dose vitamin D (100,000 IU loading dose, followed by 20,000 IU/week) or placebo with measurements of blood pressure, lipids (total-, LDL- and HDL-cholesterol, triglycerides, apolipoproteins A1 and B), and glucose metabolism parameters (blood glucose, HbA1c, serum human receptors for advanced glycation end products (sRAGE), insulin, C-peptide and HOMA-IR).
A total of 422 subjects with mean serum 25(OH)D level 34 nmol/L were included, with 411 subjects completing the study. Serum 25(OH)D levels increased with 56 nmol/L and decreased with 4 nmol/L in the vitamin D and placebo group, respectively. We found no statistically significant differences between the two groups in any of the measured CVD risk factors, except for a minor increase in sRAGE in the vitamin D group. Stratified analyses of subjects with low baseline serum 25(OH)D levels alone, or combined with blood pressure, lipid and HOMA-IR values above the median for the cohort, did not skew the results in favour of vitamin D supplementation.
Supplementation with vitamin D in subjects with baseline vitamin D insufficiency does not improve CVD risk factor profile.