Maternal folic acid supplementation with vitamin B ₁₂ deficiency during pregnancy and lactation affects the metabolic health of adult female offspring but is dependent on offspring diet

Abstract

Epidemiologic studies have reported relationships between maternal high folate and/or low B status during pregnancy and greater adiposity and insulin resistance in children. The goal of this study was to determine the effects of maternal folic acid supplementation (10 mg/kg diet), with (50 μg/kg diet) and without B, on adult female offspring adiposity and glucose homeostasis. Female C57BL/6J mice were fed 1 of 3 diets from weaning and throughout breeding, pregnancy, and lactation: control (2 mg/kg diet folic acid, 50 μg/kg diet B), supplemental folic acid with no B (SFA-B), or supplemental folic acid with adequate B (SFA+B). Female offspring were weaned onto the control diet or a Western diet (45% energy fat, 2 mg/kg diet folic acid, 50 μg/kg diet B) for 35 wk. After weaning, control diet-fed offspring with SFA-B dams had fasting hyperglycemia, glucose intolerance, lower β cell mass, and greater islet hepatocyte nuclear factor 1 homeobox α and nuclear receptor subfamily 1 group H member 3 mRNA than did offspring from control dams. In Western diet-fed offspring, those with SFA-B dams had lower fasting blood glucose and plasma insulin concentrations, and were smaller than control offspring. Our findings suggest that maternal folic acid supplementation with B deficiency during pregnancy/lactation programs the metabolic health of adult female offspring but is dependent on offspring diet.-Henderson, A. M., Tai, D. C., Aleliunas, R. E., Aljaadi, A. M., Glier, M. B., Xu, E. E., Miller, J. W., Verchere, C. B., Green, T. J., Devlin, A. M. Maternal folic acid supplementation with vitamin B deficiency during pregnancy and lactation affects the metabolic health of adult female offspring but is dependent on offspring diet.

Joint effects of folate and vitamin B12 imbalance with maternal characteristics on gestational diabetes mellitus

“…27 More recently, Henderson et al reported that maternal folic acid supplementation with vitamin B 12 deficiency during pregnancy or lactation can affect the metabolic health of adult female offspring, which involves the effects of maternal diet on the β-cells of offspring. 28 Several limitations of this study should be acknowledged. First, this study was a cross-sectional observational study, and it could not prove causation of the relationship between folate and vitamin B 12 imbalance and GDM.…”

Nutritional 1C Imbalance, B12 Tissue Accumulation, and Pregnancy Outcomes: An Experimental Study in Rats

“…Another likely possibility is that the fetal underdevelopment is a result of other components in the 1C imbalanced diet. Excess folate alone has previously been shown to cause placental abnormalities and embryonic defects in mice [ 20 , 21 ]. In addition, low B12 combined with high folate may exacerbate B12 deficiency [ 21 , 22 ].…”

“…Excess folate alone has previously been shown to cause placental abnormalities and embryonic defects in mice [ 20 , 21 ]. In addition, low B12 combined with high folate may exacerbate B12 deficiency [ 21 , 22 ]. The 1C imbalanced diet contained large quantities of methionine (10,635 mg/kg diet), which has been shown to cause in poor physiological and pathological outcomes, both alone and combined with low B12 [ 23 , 24 ].…”

Folic acid supplementation in children with sickle cell disease: study protocol for a double-blind randomized cross-over trial

“…There is growing concern that higher FA intakes may lead to adverse health outcomes, as intakes of 1 mg/d FA have been associated with acceleration of mammary tumors in rats [28], and colorectal [29] and prostate [30] cancer in adults. There is also evidence that excess FA intakes may have adverse effects on metabolic health during development [31,32] suggesting young children undergoing periods of rapid growth and development are especially vulnerable. The association of adverse health outcomes with high FA intake remains controversial, but debate has limited some countries from adopting mandatory nationwide FA fortification programs due to these concerns [33].…”