Going beyond MTHFR 677 and 1298

If you are just getting started with researching your MTHFR polymorphisms, you may want to start with some background information.  I have a list of resources on the MTHFR page that you might find helpful.

MTHFR is a key gene in regulating the body’s folate metabolism and, consequently, is involved in the methylation cycle.

Overview of Polymorphisms

MTHFR C677T and A1298C are the two main polymorphisms that you will read about online and in research studies.

Check your 23andMe results for rs1801133 for the MTHFR C677T:

  • GG: common (wildtype)
  • AG: one copy of C677T allele (heterozygous), MTHFR efficiency reduced by 40%
  • AA: two copies of C677T (homozygous), MTHFR efficiency reduced by 70 – 80%

 

Check your 23andMe results for rs1801131 for the MTHFR A1298C:

  • TT: common (wildtype)
  • GT: one copy of A1298C allele (heterozygous), MTHFR efficiency reduced
  • GG: two copies of A1298C (homozygous), MTHFR efficiency reduced

Here are a few of the other mutations of the MTHFR gene.  Not all MTHFR polymorphisms necessarily are a problem.  For example, those with the rs13306560 SNP are found, on average, to have lower diastolic blood pressure in a European study.

Check your 23andMe results for rs2274976, also known as G1793A:

  • TT: associated with cleft lip, OR 3.46 [ref] neural tube defect [ref], higher homocysteine, and folate deficiency [ref]
  • CC: common (wildtype)

 

Check your 23andMe results for rs9651118:

  • TT: somewhat elevated homocysteine, higher risk of T2D [ref],  [ref] – note that this is the more common allele.
  • CC: somewhat protective against lung cancer [ref]

 

Check your 23andMe results for rs13306560:

  • AA: avg 5.2 mmHg lower diastolic blood pressure [ref]
  • AG: avg 2.6 mmHg lower diastolic blood pressure
  • CC: common

 

Check your 23andMe results for rs1476413:

  • TT:higher risk of colon cancer (OR =1.5) [ref]
  • CC: common

 

Check your 23andMe results for rs4846049:

  • TT: higher risk of ADHD[ref]
  • GG: common

 

Folate vs. Folic Acid

A study that came out in The American Journal of Clinical Nutrition in March of 2015 looked at the connection between the consumption of folic acid and MTHFR deficiency.  The study used mice and gave them almost 10 times the normal amount of folic acid to determine the effects of the synthetic folic acid.

Side note on folic acid, which is a synthetic form of folate…. The US RDA for folic acid is 400 mcg/day, but a lot of people, including children, consume more than that amount.   In a 200 calorie serving of cereal, the fortified amount of folic acid ranges from 200 to over 1,000 mcg.  This includes cereals that some may think are healthy such as All Bran (976 mcg / 200 calorie serving) and Kashi Heart to Heart (653 mcg/ 200 calorie serving). Other fortified foods include packaged granola bars, white rice, corn meal, and anything made with white flour such as bread and pasta.[ref]   A 2010 survey showed that 28% of children in the U.S. also take supplements containing folic acid. Try adding up the amount of folic acid that you consume in a day.

Back to the recent mouse study…   The study used mice that were bred to have a mild MTHFR deficiency, similar to MTHFR 677.  The mice on the high folic acid chow ended up with a 2.5x higher level of plasma folate but no decrease in homocysteine.  This result was similar to what is seen in human studies. The mice with the mild MTHFR deficiency and high folic acid diet also had larger spleens and livers.  “Liver histology revealed unusually large, degenerating cells in FASD Mthfr+/− mice, consistent with nonalcoholic fatty liver disease.”  The higher folic acid mice also showed inhibited MTHFR activity with lower 5-MTHF, SAM, and choline levels.  Cholesterol markers were also affected.  So to sum this up, mild MTHFR deficiency plus high folic acid (not folate) caused their serum folate levels to be high, while their active form of folate, 5-MTHF, was low along with MTHFR activity.

My two cents on this…   While the addition of folic acid to flour and rice has cut the rate of neural tube defects in half, it is possibly also causing a lot of long term consequences for about a third of the population who have genetic MTHFR polymorphisms.  Non-alcoholic fatty liver disease is on the rise in the U.S. and is thought to affect up to 25% of the population.[ref]    Read the labels on your supplements and food to figure out how much folic acid you are consuming each day.    Also keep in mind that when you are looking at studies, the serum folate levels may show up as higher for those with MTHFR 677 or 1298 due to unconverted folic acid.

Sources of Folate in the Diet

Leafy green vegetables are, of course, high in folate.  But if you aren’t getting enough spinach, turnip greens and broccoli, beans and pulses are also a good source of folate.  Lentils have 358 mcg of folate per cup, and pinto beans have 294 mcg per cup.  Garbanzo beans have 282 mcg of folate per cup, so go have some hummus for a snack today.  Surprisingly, Kale and Swiss chard don’t have much folate, but they are high in other nutrients.  There is a good chart of folate (excludes folic acid) on the World’s Healthiest Foods website.

 

 


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