Folate and vitamin B12 status is associated with insulin resistance and metabolic syndrome in morbid obesity

Background Low vitamin B12 and high folate during pregnancy are associated with visceral obesity and insulin resistance in offspring. In the general population, high folate exacerbates the increase of methylmalonic acid, a marker of vitamin B12 deficiency. However, the influence of vitamin B12 and folate and their related markers on insulin resistance and metabolic syndrome remains unknown in severe obesity. Aim To evaluate the influence of vitamin B12 and folate on HOMA-IR and components of metabolic syndrome in severe obesity. Methods 278 consecutive obese patients were assessed prospectively for HOMA-IR, red blood cell (RBC) folates, homocysteine and methylmalonic acid. We compared the associations with the components of metabolic syndrome during the preoperative multidisciplinary evaluation (period-1) and before bariatric surgery (period-2). Results The HOMA-IR was higher in patients with highest tertile of RBC and either lowest tertile of plasma B12 or highest tertile of MMA (p < 0.034 and 0.011, respectively). Lg HOMA-IR was negatively correlated with Lg homocysteine (p < 0.0001) and positively correlated with Lg serum folate (p < 0.001). The independent predictors for HOMA-IR at period 2 were either BMI and homocysteine (model 1 without serum folate, p = 0.010 and p = 0.002, respectively) or BMI and MMA (model 2 without homocysteine, p = 0.030 and p = 0.004, respectively). Age and RBC folate remained independently associated with the number of metabolic syndrome components (p = 0.006 and 0.020, respectively). Conclusions RBC folate, homocysteine, and MMA predict HOMA-IR in severe obesity. Our findings challenge the benefit of folate fortified food in severe obesity, in particular in patients with a deficit of vitamin B12. The cohort study was registered at clinicaltrials.gov as NCT02663388.