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Methylene tetrahydrofolate reductase (MTHFR) single-nucleotide polymorphism (SNPs)


The MTHFR Gene

This is a fascinating topic and one I would love to spread the word on. The methylene-tetrahydrofolate reductase (MTHFR) gene is responsible for the production of the MTHFR enzyme.

The MTHFR enzyme enables the correct metabolism of folate (vitamin B9), it converts 5,10-methylene-tetrahydrofolate to 5-methyl-tetrahydrofoate (5-MTHF).

5-MTHF is the most active form of folate and, together with vitamin B12, it functions as a methyl group donor in a range of metabolic and nervous system processes, making it vital to numerous metabolic pathways in the body.

5-MTHF - The Strongest Type of Dietary Folate

It is the only form naturally found in our circulation, and is therefore the type of folate used for cellular metabolism. Many people are not aware that folic acid is a synthetic form of the vitamin, which means it is only found in fortified foods and supplements.

It must be reduced and methylated to become metabolically active in the body. Within the cell folic acid is reduced to the metabolically active “tetrahydrofolate” form.

5-MTHF Plays an Essential Role in Methylation

  • It enables detoxification of homocysteine, via the conversion to methionine (elevated homocysteine has been linked to heart disease and stroke, pregnancy complications and dementia, and is frequently seen among those with behavioural disorders and autism),
  • The metabolism of dopamine, SAMe, serotonin, and melatonin (to name a few),
  • The formation of red blood cells, white blood cells and platelets, and
  • Is indirectly involved in the synthesis of DNA and RNA.

Therefore, those individuals with a MTHFR SNP are going to have reduced methylation function and the risk of an upstream folate build-up.

Conditions MTHFR Can Affect

Some of the conditions that MTHFR can affect, which are associated with a methylation dysfunction include:

ADD/ADHD, addictive behaviour, allergies, Alzheimer’s disease, anxiety, autism, bipolar disorder, blood clotting, cancer, cardiovascular disease, chemical sensitivities, chronic fatigue syndrome, chronic viral infection, depression, infertility, immune dysfunction, insomnia, migraine, neural tube defects, neuropathy, recurrent miscarriage, thyroid dysfunction… and the list goes on.

MTHFR Gene Mutation

Studies are uncovering that approximately half of the general population may have a mutation in the MTHFR gene. This leads to inactivation, or impaired function of the MTHFR enzyme and therefore significantly lower levels 5-MTHF. This mutation is due to one (or more) single nucleotide polymorphisms (SNPs, pronounced "snips").

SNPs are the variation in a single-nucleotide that occurs at a specific position in the genetic material. Scientists are now working to identify SNPs that may correlate with particular conditions in a patient.

Supplementation with 5-MTHF (particularly over folic acid) in these situations gives the opportunity to deliver the reduced (activated) form of folate that does not need to be converted by the reductase enzyme. Furthermore, it avoids the build-up of free folic acid in the circulation.

Stay Tuned

In my next newsletter I will explain the difference between folic acid, folinic acid, leucovorin calcium and 5-MTHF, and the benefits of using one over another. I am also going to go a little deeper into the types of 5-MTHFR mutations, as well as discussing another key player in these pathways – methionine synthase.

There is so much information out there now on MTHFR gene mutations, I strongly encourage you to continue researching this, especially if you or a patient, family member or a friend, may be affected by MTHFR SNP.

5-MTHF is available at Kingsway Compounding. We can make it up in multiple forms, including capsules and a nasal spray, with or without vitamin B12. Having said that, it is extremely important to remember that 5-MTHF supplementation is only one piece of the puzzle in recovery, cleaning up the diet and healing the gut (among other things) are also vital. So please seek professional guidance to ensure the right treatment protocol is followed. For more details on this topic or anything else I have discussed please feel free to give us a call on 1300 564 799.


Elly Smith



  1. Internet - MTHFR Support Australia.
  2. Internet –MTHFR.Net
  3. Internet – MTHFR.Net
  4. Dean L, MD. Methylenetetrahydrofolate Reductase Deficiency. Medical genetic summaries (internet). 8th March 2012.
  5. Internet – Genetics home reference. What are single nucleotide polymorphisms (SNPs)?
  6. Zetterburg H, Regland B, et al. Increased frequency of combined methylenetetrahydrofolate reductrase C677T and A1298C mutated alleles in spontaneously aborted embryos. European J of human genetics. 2012; 10(2): 113-118.
  7. Internet – American Heart Association, Circulation. Cardiology Patient Page - Homocysteine and MTHFR Mutations Relation to Thrombosis and Coronary Artery Disease.
  8. Leemans L. Does 5-methyltetrahydrofolate offer any advantage over folic acid? J Pharm Belg. 2012; 4:16-22.
  9. Ames BN, Crott JW, Fenech MF, Mashiyama ST. Methylenetetrahydrofolate reductase C677T polymorphism does not alter folic acid deficiency-induced uracil incorporation into primary human lymphocyte DNA in vitro. Carcinogenesis J. 2001; 22(7): 1019-25
  10. Medical Genetics Summaries – Methylenetetrahydrofolate Reductase Deficiency (Laura Dean, MD). (Created: March 2012, visited: September 2013)

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