Vitamin B12 insufficiency in excess folic acid downregulates methylenetetrahydrofolate reductase gene and increases homocysteine, tumor necrosis factor-alpha, and oxidative stress in hepatocytes

Abstract

OBJECTIVE: Folate and Vitamin B12 (B12) are crucial for normal growth, development, and cellular functions. The aim of this study was to determine the effect of required and excess folic acid (FA) concentration and imbalance of FA and B12 caused due to folate fortification on hepatocytes health and function in vitro. MATERIALS AND METHODS: Human hepatocellular carcinoma (HepG2) cells were cultured in FA and B12 deficient media for 15 days and further were supplemented with required FA: (6 μM) and excess FA: (60 μM) individually and in combination with B12: (500 nM). We assessed HepG2 proliferation, viability, tumor necrosis factor-alpha (TNFα) and methylenetetrahydrofolate reductase (MTHFR) mRNA expression, homocysteine, and malondialdehyde levels. RESULTS: Supplementation of B12 with FA increased proliferation as compared to only FA supplemented group. FA and B12 deficient cells and excess FA supplementation resulted in decreased viability. Supplementation of B12 at both FA concentrations increased (P CONCLUSION: These results accord the promoting effect of B12 with FA in developing nations like India where B12 deficiency is common while the concentration of folate is adequate.