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Gene in Focus: Part 6 - MTHFR

Posted 598 Days Ago in: Training, Genetics

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The next gene in our series is perhaps one of the more controversial ones; MTHFR. This gene creates an enzyme with an incredibly long name – Methylene tetrahydrofolate reductase. This enzyme is part of a complex chemical pathway known as the methyl cycle, which plays a role in the conversion of a potentially harmful compound called homocysteine, into a safe amino acid, called methionine.

There are two common single nucleotide polymorphisms, or SNPs, found in the MTHFR gene. These have the catchy names of C677T and A1298C. Currently, DNAFit only test for the C677T SNP, because this is the only SNP in MTHFR to meet our scientific criteria for inclusion. The A1298C SNP has been studied extensively, but so far no clear consensus is available as to whether it has a meaningful effect or not – if the evidence becomes clearer in time, then DNAFit will add A1298C to our testing panel, and report on it.

 

With regards to the C677T SNP that we test for, there are two different alleles, C and T, which create three different genotypes, CC, CT, and TT. The research has shown that your genotype for this SNP can impact how well your MTHFR enzyme works. In those with the CC genotype, the enzyme works very well. In the CT and TT genotypes, the enzyme significantly less efficient. And, if the enzyme doesn’t work quite as well, this means that you’re not as good at converting homocysteine to methionine, which means you are more likely to have a build up of homocysteine in your blood. This is potentially problematic, as high levels of homocysteine have been linked to an increased risk of suffering from cardiovascular disease and hypertension.

 

However, the good news is that this risk is very easily reduced by just having slightly more B vitamins on a daily basis. Those with at least one copy of the T allele should focus on consuming more than the RDA of vitamin B6, B9 (folate), and B12.

 

The effects of each MTHFR genotype are summarised in the table below:

 

Genotype

Relative MTHFR Activity

Effect on Homocysteine

Suggested Folate Intake

CC            

100 %

Normal

> 400 ug

CT

80 %

Likely to increase

> 600 ug

TT

35 %

Likely to increase

> 600 ug

 

The evidence is really good that T allele carriers are more likely to have higher levels of homocysteine, but by focusing on consuming more vitamin B9, their homocysteine levels can be significantly reduced.

 

A study from 2002 showed that at least 600ug of vitamin B9 should be consumed by T allele carriers to reduce their homocysteine, compared to the RDA of 400ug. As such, the recommended daily allowance of B9 is insufficient for the needs of T allele carriers, which is why in our report we would recommend a higher amount.

 

So where is the controversy? Some people, particularly in the USA, feel that SNPs in MTHFR are responsible for a host of other illnesses and diseases, which currently the evidence doesn’t really support. There is also a lot of controversy regarding the type of vitamin B9 that should be consumed. Vitamin B9 occurs naturally in foods as folate, and in supplements as folic acid. The vast majority of research into MTHFR shows that folic acid is effective at reducing homocysteine, without reports of side effects. The body of research looking at folic acid in general also supports the notion that low doses of the vitamin are safe. Again, some practitioners believe that folic acid is unsafe for those with the TT genotype of MTHFR, and would recommend a different supplement, called methylated folate (or 5MTHF). The evidence supporting the use of this supplement is limited, particularly when folic acid has repeatedly been shown to be effective in all MTHFR genotypes. We would recommend that everyone attempts to get their vitamin B9 from natural sources, such as green leafy vegetables. Should this evidence change in future, we would also change our recommendations to reflect that.

 

In conclusion, small changes in a persons MTHFR gene can have an impact on their homocysteine levels. The RDA of B6, B9 and B12 is likely sufficient for CC genotypes, but T allele carriers should consume slightly higher amounts for all these vitamins, especially B9, with our recommendation being between 600-800ug per day, compared to the RDA of 400ug. This amount of B9 can be found in a cup each of spinach, asparagus, and broccoli, so all the more reason to load up on your greens!

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Gene In Focus Nutrition MTHFR Genetics Hypertension Vitamin B9

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