Reza Ghiasvand, Ali Rashidian, Faezeh Abaj, Masoumeh Rafiee
Journal: International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition 2023;93(6):535-558
PMID: 35997204
Vitamin D is important for many functions in the body, including bone health and metabolism. However, not every individual responds to vitamin D supplements in the same way. One possible reason for this is genetic variation in the vitamin D receptor (VDR), which helps the body use vitamin D. This systematic review and meta-analysis was conducted to understand whether differences in VDR genes affect how people respond to vitamin D supplementation.
The results showed that some VDR genetic variations were associated with differences in vitamin D levels after supplementation, although findings were not consistent across all studies. Factors such as ethnicity and baseline vitamin D status also appeared to influence how individuals responded to supplementation. The effects on metabolic traits were less clear and varied between studies.
In conclusion, genetic differences in the vitamin D receptor may partly explain why individuals respond differently to vitamin D supplements. However, the evidence is not fully consistent, and more research is needed. Healthcare professionals may use this information to consider more personalised approaches when recommending vitamin D supplementation.
The authors declare that there are no conflicts of interest.
• No significant differences were reported in serum 25(OH)D or metabolic traits after vitamin D supplementation across the common VDR variants (BsmI, ApaI, TaqI, FokI).
• Subgroup analyses found significant interactions by factors like duration, sex, age, BMI, health status, PCR method, and race (p<0.05).
• High-risk patients may present variable rises in 25(OH)D and this needs to be managed with follow-up testing and dose adjustment.
Introduction=
A systematic review and meta-analysis was conducted to investigate the effect of vitamin D supplementation in four polymorphisms of vitamin D receptor (VDR) and their association with serum 25-hydroxyvitamin-D (25OHD) levels and metabolic traits.
Methods
16 clinical placebo-controlled trials (RCT) involving 2994 participants were included from searches conducted from PubMed, The Cochrane Library, Scopus, Web of Science, ProQuest, Science Direct, and Embase. 12/16 (75%) of the studies were performed on Asian participants. 11/16 (68%) of the studies were performed on women.
The primary outcomes were changes in serum 25-OH Vitamin D and its effect on low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), total cholesterol (TC), triglycerides (TG), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-α) after vitamin D supplementation. The secondary outcomes included subgroup analysis of the study duration, gender, age, BMI, health status, Hardy-Weinberg Equilibrium (HWE), polymerase chain reaction (PCR) type and race.
Results
There was no significant effect of vitamin D supplementation on serum 25-OH vitamin D in the four VDR polymorphism groups compared to the controls in different genotypes - FoKl (ff vs. Ff+FF) (p=0.390),BsmI (BB + Bb vs. bb) (p=0.741), TaqI (TT + Tt vs. tt) (p=0.694)and ApaI (AA + Aa vs. aa) (p=0.350).
Subgroup analysis indicated significant increase of serum 25-OH vitamin D in:
Age < 55 Years
Fokl +10.53 ng/ml (p=0.006), Bsml +5.49 ng/ml (p<0.001), Apal +10.53 ng/ml (p<0.001).
BMI>30
Fokl +16.51 ng/ml (p=0.001), Bsml +5.49 ng/ml (p<0.001), Apal +10.53 ng/ml (p<0.001).
Health Status
Fokl unhealthy +13.19 ng/ml (p=0.007), Bsml healthy +7.05 ng/ml (p<0.001), Apal unhealthy +13.19 ng/ml p<0.001.
Duration Time ≥12 weeks
Fokl +25.40 ng/ml (p=0.002), Bsml +6.28 ng/ml (p<0.001).
Restriction Fragment Length Polymorphism - Polymerase Chain
Reaction(RFLP-PCR)
Fokl +21.04 ng/ml (p<0.001), Bsml +8.26 ng/ml (p<0.001),Apal +21.04 ng/ml (p<0.001).
Females
Fokl +34.52 ng/ml (p=0.001), Bsml +6.16 ng/ml (p=0.001), Apal +34.52 ng/ml(p<0.001).
Taql analysis reported that vitamin D supplementation decreased serum 25-OH vitamin D in younger and obese subjects (p<0.001), while increasing concentration of serum 25-OH vitamin D in women under in tt genotype compared with TT, Tt genotype (p<0.001).
No significant effect of vitamin D supplementation was found in the FoKI (ff vs. Ff+FF), BsmI (BB, Bb) vs. bb) and TaqI (TT, Tt vs. tt) groups on BMI, LDL-C, HDL-C, TC and TG.
Dose-response analysis showed a considerable relationship between a high dosage (30,000 – 50,000 IU/Week) of vitamin D supplementation on increasing serum 25-OH vitamin D in FokI , BsmI, ApaI polymorphisms.
Conclusion:
This meta-analysis showed that four polymorphisms (FokI, BsmI, TaqI and ApaI) had no significant effect on vitamin D supplementation and serum 25-OH vitamin D levels. Subgroup analysis found that subjects with genetic variants (FokI ff, BsmI bb, ApaI aa and TaqI tt) had an effect on the elevation or reduction of serum 25-OH vitamin D and factors such as duration, age, BMI, health status, sex and race with vitamin D supplementation.
Across 16 RCTs, the overall effect of vitamin D supplementation on serum 25(OH)D and metabolic traits was not meaningfully different across common VDR polymorphisms to consider testing for everyday decisions about vitamin D supplementation for cardiometabolic risks.
Subgroup analysis found significant interaction by factors such as duration, age, BMI, health status, sex and race. Practitioners may therefore consider rechecking 25(OH)D at intervals and doses rather than assuming a predictable rise.
This paper reported a dose response at 30 000-50 000 IU/week was associated with increased serum 25(OH)D. However, practitioners should aim to recommend vitamin D primarily to correct deficiency and meet guideline-based indications, while choosing dosing regimens with follow-up testing.
• The results of the clinical studies conducted to date show little consistency based on methodological differences, study design and analysis which may account for discrepancies in the outcomes reported.
• Therefore, additional research is needed to better assess the inflammatory markers and genotypic profiles in a broader population.
• Furthermore, additional research is needed to identify fundamental molecular mechanisms of the interactions between the above-mentioned polymorphisms with vitamin D supplementation.
It is now becoming increasingly recognized that the effects of vitamin D supplementation may vary by several factors including vitamin D deficiency status, ethnicity, and/or the presence of genetic variants, which affect individual responses to supplementation. This study investigates the interaction between metabolic traits and circulating 25-hydroxyvitamin-D (25OHD) concentration with 4 polymorphisms of vitamin D receptor (VDR) including BsmI, ApaI, TaqI, FokI, and vitamin D supplementation. A systematic review and meta-analysis of papers until August 2021 on PubMed, The Cochrane Library, Scopus, Web of Science, Google Scholar, ProQuest, Science Direct, and Embase about the association between functionally relevant VDR variants and vitamin D supplementation on circulating 25OHD and metabolic traits. A total of 2994 cases from 16 randomized controlled trial (RCT) studies were included in meta-analyses. There were no significant changes in the serum concentrations of 25OHD and metabolic traits after vitamin D supplementation in different variants of BsmI, ApaI, TaqI, and FokI polymorphism in the VDR gene in the overall analysis (p>0.05). However, the results showed there is significant interaction between these above VDR polymorphisms and vitamin D supplement on serum 25OHD level after subgroup analyses based on the study duration, gender, age, BMI, health status, Hardy-Weinberg Equilibrium, PCR, and race (p<0.05). The present meta-analysis demonstrates that the effect of vitamin D supplementation on serum 25OHD and metabolic traits is independent of genetic variants of the VDR gene (BsmI, ApaI, TaqI, and FokI). However, future trials should consider inter-individual differences and, in particular, should aim to clarify whether certain subgroups of individuals may benefit from vitamin D supplementation in the context of metabolic health.
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