Discussion

5-MTHF (5-methyltetrahydrofolate)

5-MTHF is the most biologically active form of folate. It is the predominant type of folate present in food and the form in which the body must convert all other forms of folate.[1] Along with vitamin B12, folate serves as a donor of methyl groups.The body utilizes methyl groups in many nervous system and metabolic processes, including the conversion of homocysteine to methionine, the synthesis of monoamine neurotransmitters, the production of melatonin, and the synthesis of DNA. In addition, sufficient folate is necessary for brain and nervous system functions and for a healthy pregnancy outcome.*

5-MTHF—Preferred Over Folic Acid

Folic acid is the synthetic form of folate that is used to fortify foods. It is often found in dietary supplements as well. Despite some research showing that folic acid and 5-MTHF have equivalent bioavailability, 5-MTHF is often the preferred form to replenish folate. This is due, primarily, to the presence of digestive or metabolic variabilities that can affect the conversion of folic acid to 5-MTHF.[2-4] Furthermore, studies have shown that 5-MTHF increased plasma folate more effectively than folic acid irrespective of genetic differences in metabolism.[1,5] A study in women of childbearing age showed that 5-MTHF was more effective than folic acid in improving overall folate status.*[6] Using 5-MTHF instead of folic acid has several important advantages. 5-MTHF provides the biologically active form of folate, reduces the potential for masking hematological symptoms of vitamin B12 deficiency, reduces interactions with drugs that inhibit dihydrofolate reductase, overcomes folate metabolism challenges associated with functioning of methylenetetrahydrofolate reductase (MTHFR), and prevents the potential negative effects of UMFA in the peripheral circulation.*[7]

Quatrefolic®

In Cell FusioNX’s formulas, 5-MTHF is provided as Quatrefolic—the glucosamine salt of 5-MTHF. Quatrefolic is proven to have greater stability, solubility, and bioavailability over the commonly used calcium salt form of 5-MTHF. In a randomized crossover study, subjects received 400 mcg/d of Quatrefolic or 5-MTHF calcium salt. Titer-normalized Cmax and AUC demonstrated a 10% higher bioavailability of Quatrefolic.[8] Quatrefolic has several in vitro and in vivo preclinical and clinical studies to characterize and assure the safety profile of the product.*[9]

Functions of B12

Vitamin B12 supports healthy methylation through its roles in the synthesis of methionine from homocysteine and synthesis of S-adenosylmethionine (SAMe). As an example of its importance in homocysteine metabolism, one study showed that the addition of B12 to a folate regimen had a greater impact (7%) on homocysteine than did folate alone.[13] Like folate, erythroblasts require vitamin B12 for proliferation during their differentiation.[14] B12 is important for neurological health, and chronic insufficiency can affect the spinal cord, peripheral nerves, the optic nerve, and the brain. Research also supports a role for methylcobalamin supplementation in modulating melatonin secretion, enhancing light sensitivity, normalizing circadian rhythms, and improving sleep-wake cycles.