5-MTHF is the most biologically active form of folate and is the molecule to which folic acid must be converted in the body to be utilized.

As a dietary requirement, folic acid cannot synthesize in human body. Dietary folate is a complex and variable mixture of folate compounds, including polyglutamate conjugate compounds, reduced folates, and tetrahydrofolates, but cooking or processing always destroys these compounds.Therefore, supplementing of 5-MTHF is the most biologically active and effective way to gaining adequate folate.

Human pharmacokinetic studies indicate folic acid has high bioavailability, with large oral doses of folic acid substantially raising plasma levels in healthy subjects in a time- and dose-dependent manner. A number of drugs can interfere with the pharmacokinetics of folic acid:

1.     Anticonvulsants, antituberculosis drugs, alcohol, and oral contraceptives produce low serum and tissue concentrations of folate. The anticonvulsant drugs phenytoin and valproic acid appear to interfere with folate absorption. Supplementation may be helpful to prevent deficiency if taken at a time of day other than when taking an anticonvulsant.

2.     Continuous long-term use of acetaminophen and aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs appears to increase the folate need of human body.

3.     Folic acid can reduce elevated liver enzymes induced by methotrexate therapy in rheumatoid arthritis; however, it had no effect on the incidence, severity, and duration of other adverse events.

4.     There is evidence folic acid might inhibit the activity of anti-folate cancer chemotherapy medications, although in some cases it may increase activity. The folic acid metabolite folinic acid is often used to rescue normal tissue after anti-folate cancer chemotherapy medications therapy. Folic acid, folinic acid, or 5-MTHF supplementation does not appear to interfere with methotrexate’s anti-arthritic or anti-inflammatory activity. However, since they might interfere with cancer chemotherapy, their indiscriminate use during chemotherapy is not recommended.

5.     Some literatures report that supplementation with high doses of folic acid could mask a vitamin B12 deficiency, resulting in neurological injury secondary to undiagnosed pernicious anemia, but supplementation with 5-MTHF appears to sidestep this potential problem. As 5-MTHF is not active in DNA synthesis without the help of B12, it will not mask a B12 deficiency.

These drug and nutrient Interactions of folate can make us better understand how to using 5-MTHF and  how to make a reasonable formulation including 5-MTHF.

References

1. Lambie DG, Johnson RH. Drugs and folate metabolism. Drugs 1985; 30: 145-155.

2. Pironi L, Cornia GL, Ursitti MA, et al. Evaluation of oral administration of folic and folinic acid to prevent folate deficiency in patients with inflammatory bowel disease treated with salicylazosulfapyridine. Int J Clin Pharmacol Res 1988; 8: 143-148.

3. Backman N, Holm AK, Hanstrom L, et al. Folate treatment of diphenylhydantoin-induced gingival hyperplasia. Scand J Dent Res 1989; 97: 222-232.

4. van Ede AE, Laan RF, Rood MJ, et al. Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty-eight week, multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum 2001; 44: 1515-1524.

5. Gori T, Burstein JM, Ahmed S, et al. Folic acid prevents nitroglycerin-induced nitric oxide synthase dysfunction and nitrate tolerance: a human in vivo study. Circulation 2001; 104: 1119-1123.

6. Butterworth CE Jr, Tamura T. Folic acid safety and toxicity: a brief review. Am J Clin Nutr 1989; 50:353-358.

7. Goggin T, Gough H, Bissessar A, et al. A comparative study of the relative effects of anticonvulsant drugs and dietary folate on the red cell folate status of patients with epilepsy. Q J Med 1987; 65: 911-919

8. Pentieva K, McNulty H, Reichert R, et al. The short-term bioavailabilities of [6S]-5-methyltetrahydrofolate and folic acid are equivalent in men. J Nutr 2004; 134: 580-585.

9. Houghton LA, Sherwood KL, Pawlosky R, et al. [6S]-5-methyltetrahydrofolate is at least as effective as folic acid in preventing a decline in blood folate conc