Updated: Sep 7, 2019
With the growing understanding of genetics, we are noticing a trend in a particular genetic variation that affects folate and vitamin B12 levels. This gene is the MTHFR, and its role is to convert the artificial (folic acid) or food-based form (folate) into the form 5-MTHF - the methylated form of folate that our cells need. Specific variations of this gene can affect your body's ability to maintain adequate folate levels without the proper supplementation.
MTHFR Genetic Variation
In the Caucasian population, 1 in 10 people have a homozygous variant (677TT) and 40% of people are heterozygous (677CT). Wondering if you are one of these? You can test for this MTHFR genetic variation with a simple blood test. You can reach out to your physician to have this ordered through insurance, or you can order the lab yourself through Ulta Lab Tests online.
What is the relationship between folate and MTHFR?
MTHFR helps the body to convert both natural folate from foods and folic acid from supplements into the usable form 5-MTHF. The full name is methylenetetrahydrofolate reductase enzyme.
If you have a variation in this gene, you are at risk of low levels of folate being converted into the usable form. For those with homozygous (677TT) the average methylation is decreased by 65%. For those with heterozygous (677CT) the average methylation is decreased by 30%. This means if you are taking 100% of your folate needs, but have a positive homozygous variation for MTHFR your cells are only able to utilize 35% of the total folate in the blood (1).
What is folate and where does it come from?
Folate is one of the B vitamins, also known as B9. Folate is required for DNA replication, amino acid and enzymatic processes. Folate is a significant nutrient for pregnancy because of its role in DNA replication, development, and growth. If folate levels are low in pregnancy it is a risk to both the mother and baby. Low folate levels in the mother can increase the risk of miscarriage and also cause anemia and peripheral neuropathy. In the baby it can cause congenital abnormalities including spina bifida.
Folate can be found naturally in leafy green vegetables, legumes, citrus fruit, egg yolks, and liver. The highest content of folate from an animal source is beef liver, with 3 ounces providing 215 mcg folate. The highest plant source is cooked spinach, with ½ cup boiled spinach providing 131 mcg.
Folic acid can be found in vitamins, fortified foods, and enriched foods. Folic acid is the synthetic form of natural folate. The U.S. made it mandatory that staple foods be fortified with folic acid starting in 1998 to prevent birth defects. You will see folic acid fortified in many processed grain foods such as cereal, bread, pasta, crackers, and baked goods.
Both forms require the liver to convert folate/folic acid into the usable form taken up by the cells (5-MTHF). When I use the word “methylation” I am referring to this conversion of the vitamin in the body.
How much folate do I need?
The National Health and Nutrition Examination Survey found that certain groups, including women of childbearing age and non-Hispanic black women, are at risk of insufficient folate intakes; even when intakes of folic acid from dietary supplements are included (1).
If you are pregnant or conceiving, folate levels should be monitored and supplemented. Folate is necessary for proper neurological growth and overall health of the baby. It is important to know if you are taking the correct form of folate so that your folate levels and the levels the baby receives are sufficient.
Folate needs increase from 400 mcg for an adult female to 600-1000 mcg for prenatal and pregnant women. Needs remain high for breastfeeding women at 500 mcg daily (1). If you’re at high risk of having a child with a neural tube defect (NTD), the National Institutes of Health and the Institute of Medicine recommend increasing your daily dose further. Talk with your doctor to determine the correct supplementation for you.
In a double-blind, randomized, placebo-controlled study involving 144 women, a methylated folate supplement was deemed more effective than folic acid at increasing red blood cell folate concentrations (2).
It is also important to note if you are taking medications, especially oral contraceptives and antidepressants, you can have further depletion of folate levels. Some medications can interfere with folate and have decreased effect. Please check with your doctor before supplementing.
Why is it important to know if you have this variation?
If folate is not being methylated into the active form 5-MTHF, then the cells cannot efficiently uptake folate leading to deficiency. With folate not being taken up into the cell it can also lead to an excess of folate in the blood.
If you have a genetic variation that decreases the activity of this conversion, it can lead to low folate levels, low B12 levels, elevated homocysteine (inflammatory marker). An elevated homocysteine level has been associated with an increased risk of cardiovascular disease (3). Researchers have also found a correlation between low serum folate concentrations and poor cognitive function and higher risk of dementia and Alzheimer’s disease. Most observational studies conducted to date have shown positive associations between elevated homocysteine levels and the incidence of both Alzheimer’s disease and dementia (4, 5).
Another common concern with low folate levels is the link to depression. Low folate has been studied in its correlation with depression and poor response to antidepressants. It is a tough area to study because depression commonly leads to poor nutrition intake and alcohol use which will cause low folate levels (6).
What should you do?
You can know if you have a genetic variation of MTHFR through a simple blood test. You can contact your physician to have the lab ordered through insurance, or you can order yourself using Ulta Lab Tests online. It is also helpful to test for homocysteine at this time to monitor levels and risk of under-methylation.
If you have a positive variation in MTHFR, either homozygous or heterozygous it may be helpful for you to supplement with a methylated-folate multivitamin or prenatal. I always recommend my clients use a B-complex or multivitamin/prenatal for supplementing folate since the B vitamins closely interact with one another. For pregnancy, it is recommend to supplement for at least 3 months before trying to conceive.
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High Quality Multivitamin (with methylated folate and B12)
you can check out my full recommendations for optimal nutrition support, here >>
High Quality Prenatal (with methylated folate, B12, and choline)
you can check out my full prenatal recommendations for support, here >>
You can also continue to eat whole foods rich in folate, including: leafy green vegetables, legumes, citrus fruit, egg yolks, and liver.
Make sure to talk to your health care practitioner before starting a new supplement regimen, especially if you are taking medications, have existing medical conditions, or are already pregnant or breastfeeding.
Stay healthy and happy!
Liz Riesen, RD