Folate 5,000 Plus provides 5,000 mcg of folate as methyltetrahydrofolate (5-MTHF), the universally metabolized and biologically active form of folate, combined with activated vitamin B₁₂ and B₆. Genetic variations affecting activation and metabolism of supplemental folic acid arecommon. Through bypassing several enzymatic activation steps catalyzed by DHFR (dihydrofolate reductase) and MTHFR (methylenetetrahydrofolate reductase), 5-MTHF is directly usable by the body and provides all of the benefits of folic acid regardless of functional or genetic variations in these enzymes. Activated B vitamins provide methyl groups to support healthy methylation, a key regulator of genetic expression and cellular function. Healthy methylation is vital for cellular health, hormone and neurotransmitter production, and energy metabolism. At the molecular level, the main function of folate is to donate methyl groups in key biochemical reactions occurring in blood cells, neurons, the vasculature and many other tissues. In addition, folate promotes the production of healthy DNA. Research suggests that B vitamins help maintain healthy nervous system function. In a randomized controlled study, a combination of methylfolate, methycobalamin and pyridoxal-5-phosphate promoted healthy epidermal nerve fiber density and nerve comfort. Methyltetrahydrofolate and methylcobalamin may also support psychological health, including positive mood.