The serum 25-hydroxyvitamin D response to vitamin D supplementation is related to genetic factors, BMI, and baseline levels

Abstract

Objective: The serum 25-hydroxyvitamin D (25(OH)D) level is not only dependent on vitamin D intake and production in the skin but also dependent on genetic factors. Thus, in large genome-wide association studies, it has been shown that single nucleotide polymorphisms (SNPs) in the vitamin D binding protein (DBP), as well as in enzymes related to activation or degradation of vitamin D and its metabolites, are as important for the serum 25(OH)D level as the effect of season. How these SNPs affect the serum 25(OH)D response to vitamin D supplementation is uncertain. Design and methods: Data were pooled from three randomized controlled trials where 40 000 IU vitamin D/week was given for 6 months. Serum 25(OH)D was measured before and at the end of the intervention, and the subjects were genotyped for SNPs related to the serum 25(OH)D level. Results: Baseline 25(OH)D levels were significantly related to SNPs in the DBP and CYP2R1 genes. Those with SNPs associated with the lowest baseline 25(OH)D levels also had the smallest increase (delta) after supplementation. Those with the lowest baseline serum 25(OH)D (without regard to genotypes) had the highest increase (delta) after supplementation. Subjects with high BMI had lowest baseline 25(OH)D levels and also the smallest increase (delta) after supplementation. Conclusions: The serum 25(OH)D response to supplementation depends on genes, baseline level, and BMI. However, whether this is clinically important or not depends on the therapeutic window of vitamin D, an issue that is still not settled.

Anti-inflammatory nutritional intervention in patients with relapsing-remitting and primary-progressive multiple sclerosis: A pilot study

“…This was in disagreement with previous studies showing that six months treatments with cholecalciferol slightly above RDA dosage were sufficient to increase 25(OH)D 3 levels. 55,72,73 The baseline levels of vitamin D 3 in our patients, lower than in other studies, might explain the persistence of low values of vitamin D 3 despite the administration of RDA doses of the vitamin. On the contrary, fish oil supplementation was sufficient to increase the ratio EPA þ DHA/ARA (n-3/n-6 PUFA) to a nearly satisfactory level already after three months (Figure 3), suggesting that a dietary regimen alone, as in the RRTD group, may be sufficient to increase the EPA þ DHA/ARA ratio, thus potentially ameliorating inflammatory status of patients.…”

“…As shown in Figure 6, the metabolic pathway leading to active vitamin D 3 This means that the down-regulation of the CYP2R1 54,55 and/or CYP27B1-the enzymes responsible of the synthesis of 25(OH)D 3 -and/or the up-regulation of gene expression of the CYP24A1 56 -the enzyme responsible for the inactivation of 1a-25(OH) 2 D 3 (calcitriol)-may lead to misbalance of vitamin D 3 . In other words, the levels of active vitamin D 3 depend on the relative rates of its synthesis via CYP27B1 and its modification via CYP24A1.…”

“…61 In fact, genetic factors might be as important as the effect of season, as it has been shown that besides the vitamin D receptor polymorphism, 25(OH)D 3 levels are significantly related also to single nucleotide polymorphisms (SNPs) in the vitamin D binding protein (DBP), RXR, and CYP2R1 genes. 55,62 Finally, the significance of the increased circulating levels of DBP observed in MS patients should be investigated, in regard to vitamin D bioavailability and neuroinflammation. 63 Moreover, the finding that that VDR-D activate the Sirtuin SIRT-1, an anti-inflammatory, and anti-aging enzyme 64,65 suggests that vitamin D can influence also cell metabolism and therefore can indirectly up-regulate oxidative metabolism and down-regulate biosynthetic pathways including those related to the synthesis of pro-inflammatory molecules (Figure 7).…”

Impact of a single oral dose of 100,000 IU vitamin D3 on profiles of serum 25(OH)D3 and its metabolites 24,25(OH)2D3, 3-epi-25(OH)D3, and 1,25(OH)2D3 in adults with vitamin D insufficiency

“…In view of the continuing uncertainty surrounding the clinical utility of different vitamin D metabolites as markers of vitamin D status, and to better understand the vitamin D metabolism pathway in response to supplementation, the present study was performed to investigate the effect of a single high dose (100,000 IU) of vitamin D3 on profiles of circulating 25 …”

Lifestyle and Other Factors Explain One-Half of the Variability in the Serum 25-Hydroxyvitamin D Response to Cholecalciferol Supplementation in Healthy Adults

“…The NAM provides intake recommendations by age and sex, but it is unclear whether supplementation should be varied according to vitamin D status, weight, or other factors (7). In addition, although common genetic variants have been associated with circulating serum 25(OH)D concentrations in genome-wide association studies (29,30), their role in affecting the magnitude of serum response to supplementation is also less clear (31)(32)(33).…”