Precision Cardiology: An Example with the MTHFR Gene

In my preventive cardiology practice, the goal is to identify components of altered lifestyles that can be modified to restore health naturally. The big 4 are better sleep, nutrition, stress management, and movement including standing (which I am doing now as I write this). There are many steps to improved nutrition that I suggest to my patients but optimizing a cycle involving optimal use of the vitamin folate is one of the fundamental ones. One of the best studied examples of nutrition and genetic interactions, called nutrigenomics, is the metabolism of folate. 

Folate is an overall term for both naturally occurring folate in foods and synthetic forms. It shares a root with foliage, or green leafy produce, which is rich in natural folate. Folate refers to a B vitamin, vitamin B9, needed for healthy metabolism. Folic acid is the man-made form of folate that is found in some supplements and added to fortified foods. Folic acid is not the form used by the body and it must be modified to be useful. Folic acid is water-soluble and excess amounts are excreted through the urine, often making it dark yellow. A regular supply of water-soluble vitamins are required for optimal health as they are not stored in the body.

Folate enters a cycle that helps tissues grow and cells work. Folate becomes “methylated” by adding a component that has a methyl (1 carbons and 3 hydrogens) group to it. The active form of folate is methyltetrahydrofolate (MTHF). Taking the right amount of MTHF before and during pregnancy helps prevent spina bifida. Low levels of folate may result in diarrhea, gray hair, mouth ulcers, peptic ulcers, swollen tongue, and anemias. Folate works with foods with vitamin C and sources of vitamin B12 to produce and repair DNA injured from radiation, chemicals and other exposures.

Folate is found naturally in dark green leafy vegetables, legumes like dried beans and peas, and citrus fruits and juices. Many foods are fortified with synthetic folic acid including enriched breads, cereals, flours, cornmeals, pastas, rice, and other grain products. It is uncertain if too much folic acid is harmful as “unmetabolized” folic acid or UMFA can accumulate and may interfere in the normal cycle of folate metabolism.

The genetics of folate metabolism are very well researched and can be tested in your blood easily. I offer this test to my patients. One gene for folate metabolism comes form each parent and dictates the activity of an enzyme called MTHFR or methyl-tetrahydrofolate reductase. If you get two “slow” genes from your parents, something called homozygous MTHFR 677TT, you transform folate to the active form MTHF in reduced amounts. This effects 10% of the population.  Those individuals homozygous for the TT form of the MTHFR677 gene can improve their metabolism by taking supplements with methylfolate or MTHF in them. Up to 40% of the population inherits one MTHFR gene that works slower than normal, called 677CT, and may also benefit from extra methylated folate. If a blood test called the homocysteine level is high I routinely check the MTHFR gene status in an extra blood test.

The best way to get the daily requirement of essential vitamins is to eat a wide variety of foods. There is good evidence that folate of any source can help reduce the risk of certain birth defects such as spina bifida. I see other patients feel better by adding extra folate, the more natural the better, to their diet. It is clear that getting enough folate in your diet on a daily basis, is a foundation to feel better and enjoy your day. Understanding your genetics and SNPs can make your care more personalized and precise. 

Author
Dr. Joel Kahn

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