Diet-derived antioxidants and osteoporosis: A Mendelian randomization study

Abstract

Background Antioxidants can prevent osteoporosis, but the association between serum antioxidants and the cause of osteoporosis remains unknown. We aimed to utilize Mendelian randomization (MR) to determine whether genetically predicted serum levels of diet-derived antioxidants can affect the risk of osteoporosis, to determine the effect of dietary supplementation of antioxidants. Methods Genetic variants associated with diet-derived antioxidants were selected from the genome-wide association studies. A total of 12,946 osteoporosis cases and 506,624 healthy controls were obtained from UK Biobank (UKB) and Genetic Factors of Osteoporosis (GEFOS) consortia. We implemented a two-sample MR design and performed several sensitivity analyses to evaluate the causal relationship. Results In UKB, the genetically predicted higher β-carotene (OR = 0.863, p = 7.37 × 10−6, power = 100%) and γ-tocopherol (OR = 0.701, p = 0.021, power = 5%) had an inverse relationship with osteoporosis. However, only the association of serum β-carotene passed FDR correction. In GEFOS, there were no significant diet-derived antioxidants. The direction of the association of β-carotene with osteoporosis (OR = 0.844, p = 0.106, power = 87%) was consistent with that in the UKB dataset. A fixed-effects meta-analysis confirmed that β-carotene (OR = 0.862, p = 2.21 × 10−6) and γ-tocopherol (OR = 0.701, p = 2.31 × 10−2) could decrease the risk of osteoporosis. To reduce exclusion limit bias, we used total body bone mineral density, lumbar spine bone mineral density and femoral neck bone mineral density as surrogates and found that the genetically elevated circulating β-carotene level could increase total body BMD (beta = 0.043, p-value = 8.26 x 10−5, power = 100%), lumbar spine BMD (beta = 0.226, p-value = 0.001, power = 100%) and femoral neck BMD(beta = 0.118, p-value = 0.016, power = 100%). Conclusions We observed that genetically predicted serum β-carotene could elevate BMD and prevent osteoporosis.

Exogenous and endogenous antioxidants in osteoporosis risk: causal associations unveiled by Mendelian Randomization analysis

“…However, the credibility and broad applicability of these outcomes were limited by reliance on just two discrete datasets. Of particular relevance, the extensive osteoporosis-centric research endeavor, the GEFOS database, did not reveal any statistically discernible disparities in OP risk between β-carotene and γ-tocopherol levels (Li et al, 2023).…”

Elucidating causal relationships of diet-derived circulating antioxidants and the risk of osteoporosis: A Mendelian randomization study

“…There is weak evidence that β-carotene levels are associated with increased LS-BMD in the current study. However, the results of a previous MR performed by li et al ( Li et al, 2023 ) showed that serum β-carotene levels significantly reduced OP risk. For the instrumental variables of β-carotene, we used more strict screening criteria ( p < 5 × 10 −8 and r 2 < 0.001), which helped us to make more reliable conclusions.…”

Causal relationship between gut microbiota and ankylosing spondylitis and potential mediating role of inflammatory cytokines: A mendelian randomization study

“…SNPs with linkage disequilibrium (LD) were removed by stringent clumping criteria (kb = 10,000, r 2 = 0.001) to retain mutual independent instrumental SNPs. F-statistic was calculated by the formula (F = β 2 /SE 2 ) to appraise the potency of each SNP [ 35 , 36 ]. β stands for effect size, SE stands for standard error.…”