AMPK is an enzyme that serves as a regulator of metabolism and energy production. AMPK activation increases fatty acid oxidation and glucose transport, releasing additional energy from stored fats and sugars. In essence, activated AMPK promotes energy-releasing processes while suppressing energy-storing processes. AMPK activity declines with aging and obesity, making activation of AMPK a desirable target for weight loss and anti-aging.
A recent study found that supplementing with Folic acid can encourage AMPK activation, suggesting a role for folic acid in weight loss:
Activation of AMPK by folic acid was mediated through an elevation of its allosteric activator AMP and activation of its upstream kinase, namely, liver kinase B1 (LKB1) in the liver. Consistent with in vivo findings, 5-methyltetrahydrofolate (bioactive form of folate) restored phosphorylation (activation) of both AMPK and LKB1 in palmitic acid-treated HepG2 cells. Activation of AMPK by folic acid might be responsible for AMPK-dependent phosphorylation of HMG-CoA reductase, leading to reduced hepatic cholesterol synthesis during high-fat diet feeding. These results suggest that folic acid supplementation may improve cholesterol and glucose metabolism by restoration of AMPK activation in the live (1).
This study compared mice fed a control diet, a high-fat diet, and a high-fat diet supplemented with folic acid. The mice in the high-fat diet group experienced a decline in AMPK activity, however the group that was fed a high-fat diet supplemented with folic acid did not. “Mice fed a high-fat diet exhibited hyperglycemia, hepatic cholesterol accumulation, and reduced hepatic AMPK phosphorylation. Folic acid supplementation restored AMPK phosphorylation (activation) and reduced blood glucose and hepatic cholesterol levels” (1).
Folic acid is a naturally occurring water-soluble B vitamin (B9). While most people get enough folic acid to meet the minimum requirements, studies have found that obesity is often correlated with insufficient levels of folic acid: “In multivariate analysis, women who were overweight had a 12% lower, and obese women had a 22% lower serum folate concentrations compared to normal weight women” (2).
1. Sid, V., Wu, N., Sarna, L. K., Siow, Y. L., House, J. D., & O, K. (2015). Folic acid supplementation during high-fat diet feeding restores AMPK activation via an AMP-LKB1-dependent mechanism. American journal of physiology. Regulatory, integrative and comparative physiology, 309(10), R1215–R1225. doi:10.1152/ajpregu.00260.2015
2. Mahabir, S., Ettinger, S., Johnson, L., Baer, D. J., Clevidence, B. A., Hartman, T. J., & Taylor, P. R. (2008). Measures of adiposity and body fat distribution in relation to serum folate levels in postmenopausal women in a feeding study. European journal of clinical nutrition, 62(5), 644–650. doi:10.1038/sj.ejcn.1602771