Obesity influencing circulating levels of nutrients: Evidence from Mendelian randomization study

Observational studies have established that obesity is associated with nutritional deficiencies, but the exact causality remains uncertain. Thus, this Mendelian randomization (MR) study aimed to identify the causal associations between obesity and circulating levels of nutrients. Single-nucleotide polymorphisms associated with obesity (body mass index and waist-hip ratio), were extracted from a genome-wide association study of 694,649 European ancestry. Summary-level data for minerals (copper, selenium, zinc, calcium, magnesium, and potassium), and vitamins (folate, vitamins A, C, E, B6, and B12), albumin were obtained from the publicly available integrative epidemiology unit OpenGWAS database psychiatric genomics consortium. Inverse-variance weighted method several sensitivity analyses were conducted. Genetically predicted higher body mass index significantly decreased circulating levels of magnesium (β = -0.07, 95% confidence interval [CI]: -0.10 to -0.03, P = 1.47 × 10-4), folate (β = -0.07, 95% CI: -0.10 to -0.04, P = 5.61 × 10-5), vitamin A (β = -0.11, 95% CI: -0.14 to -0.07, P = 3.10 × 10-9), vitamin E (β = -0.10, 95% CI: -0.13 to -0.06, P = 1.84 × 10-8), albumin (β = -0.15, 95% CI: -0.17 to -0.12, P = 9.89 × 10-28); whereas genetically predicted higher waist-hip ratio decreased circulating levels of magnesium (β = -0.07, 95% CI: -0.11 to -0.02, P = 1.87 × 10-3), folate (β = -0.07, 95% CI: -0.11 to -0.03, P = 9.87 × 10-4), vitamin C (β = -0.08, 95% CI: -0.12 to -0.04, P = 2.40 × 10-4), albumin (β = -0.08, 95% CI: -0.11 to -0.04, P = 3.72 × 10-5). The study supports a causal effect of obesity on lower circulating levels of nutrients. Our findings highlight the necessity of adjuvant nutrients in obesity management.