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Folinic-Plus - Vitamins B6, B9 & B12

Healthcare Professionals

Folinic-Plus (vitamins B6, B9, & B12) does not require a prescription but is intended for recommendation by healthcare professionals. Taking one Folinic-Plus tablet per day is generally adequate. Healthcare providers interested in receiving free samples of Folinic-Plus should complete the Sample Request Form.

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Once-daily dosing of Folinic-Plus® is generally adequate. Patients should consult with their healthcare professional before using Folinic-Plus® and any non-prescription supplement.

There is a difference between serum half-life (how fast levels in the blood decrease back to baseline) after an oral or IV dose of medication and tissue levels that determine the body’s ability to store and use many substances.


Much is made of the superiority or necessity of 5-methyltetrahydrofolate (5-MTHF) in folate supplementation, especially in persons with genetic mutations of the MTHFR (methylene tetrahydrofolate reductase) gene.


  • Use of 5-MTHF is not necessary for adequate folate supplementation on the basis of MTHFR gene mutation. It has been well demonstrated that persons with adequate folate intake have no problems producing 5-MTHF, even when homozygous for the C677T mutation of the MTHFR gene. 1)
  • Due to reduced folate receptor preference for the l isomer during gastrointestinal uptake of folates, the use of the l isomer for oral folate supplementation offers no practical advantage. 2)
  • Importantly, 5-MTHF facilitates only the methionine synthase mediated homocysteine to methionine cycle.  And the action of the MTHFR gene is a one-way process.  To participate in the single carbon and thymidine synthetase cycles 5-MTHF must pass thru the methionine synthase cycle and be converted to tetrahydrofolate. 3)
  • 5-MTHF is not the predominate folate in the human body.  Much is made of 5-MTHF levels in plasma and erythrocytes.  Red cell folate stores accumulate during erythropoiesis and reflect long term folate intake but not availability. The predominate intracellular stores of folate are as polyglutamates of tetrahydrofolate (THF). Folate concentrations in the liver approach 1000 times those in plasma. 5-MTHF is a poor substrate for folylpolyglutamate synthetase. “…Its retention by cells requires   its metabolism via the methionine synthase reaction to THF, the most effective substrate for folylpolyglutamate synthetase.” 4)
  • It is known that that tissue folate binding proteins are predominately enzymes of one-carbon metabolism, which are not directly supported by 5-MTHF. 4)
  • Uncertain safety - while the saturation of reduced folate binding and transport proteins is not thought to occur at physiologic levels, the question of effects from long-term supra-physiologic doses of 5-MTHF have not been well addressed.


  1. Conversion of 5-Formyltetrahydrofolic Acid to 5-Methyltetrahydrofolic Acid Is Unimpaired in Folate-Adequate Persons Homozygous for the C677T Mutation in the Methylenetetrahydrofolate Reductase Gene
    Lori Lathrop Stern, Pamela J. Bagley, Irwin H. Rosenberg, and Jacob Selhub  J. Nutr. 2000 130: 2238-2242
  2. Clin Pharm. 1993 Apr;12(4):293-9. Bioequivalence of oral and injectable levoleucovorin and leucovorin. DeVito JM1, Kozloski GD, Tonelli AP, Johnson JB.
  3. Folate in Health and Disease  Chapter 3 Folate Biochemical Pathways and Their Regulation  Patrick J Stover 2010 Taylor and Francis Group
  4. Folate in Health and Disease  Chapter 1 Folate Folate Chemistry and Metabolism Berry Shane 2010 Taylor and Francis Group
  5. Am J Clin Nutr. 2008 Mar;87(3):517-33. Is folic acid good for everyone? Smith AD1, Kim YI, Refsum H.
  6. Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials Am J Clin Nutr 2005 82: 806-812

Concerns have been raised about the uncertain risks of folate supplementation even at more conventional doses. 5)   It is suggested that the introduction into the general population of very high dose folates and more specifically a form of folate that does not directly facilitate more generalized metabolic needs should await:

  1. Comparative dosing studies for desired end points.  (The maximal effect of oral folic acid on the lowering of homocysteine levels occurs at approximately 1mg / day.)  6)
  2. Comparative studies with better studied (and less expensive) alternative folates.
  3. Assessment of both the safety of long-term use of very high dose folates and in particular of the long-term use of 5-MTHF.

The Merk KGaA communication to the FDA in 2001 did not address high dosage or use for specific medical indications.


B2; riboflavin, B6, pyridoxal phosphate, B12; cobalamin ,DHF; dihydrofolate, DHFR; dihydrofolate reductase, DMG; dimethylglycine, dTMP; deoxythymidine 5’-phosphate, dUMP; 2’-deoxyuridin-5’-phosphate, MS; methionine synthase, 5-MTHF; 5-methyltetrahydrofolate, MTHFR; methylene tetrahydrofolate reductase, SAM; S-adenosylmethionine, SAH; S-adenosylhomocysteine, SHMT; serine hydroxymethyltransferase, THF; tetrahydrofolate, TS; thymidylate synthetase, UMFA, unmetabolized folic acid.