The MTHFR C677T defect is easy to understand and even easier to treat, but the consequence of the MTHFR abnormality in kids appears to be profound, such that the parents of Autistic kids add a few more vowels to MTHFR in naming it.
Dietary folic acid, which usually is not in short supply, is readily converted in to one of the active forms of folic acid, known as tetrahydrofolate, or THF. MTHFR converts THF in to 5-methyl THF, more commonly referred to as 5-methyl folate. MTR (methionine synthase) then combines 5-methyl folate with homocysteine to form methionine.
Individuals who are (+/+) for MTHFR C677T (10% of the population, including me) have a great deal of trouble using dietary folic acid to detoxify homocysteine, as we cannot efficiently convert dietary folic acid into its 5-methyl folate form. Elevated homocysteine leads to free radical stress, vascular plaque formation, abnormal clotting, and an increased risk for cardiovascular and neurologic disease yikes!
If you are (+/+) or (+/-) for MTHFR (another 20% of the population), supplementation with folic acid is not the answer it cant help you. However, low dose 5-methyl folate supplementation will bypass this defect with 100% efficacy. If you have a MTHFR C677T defect, we need to provide you with 5-methyl folate.
Sources of 5-methyl folate include Folapro (800 mcg 5-methyl folate), Metanx (5-methyl folate 2.8 mg, P5P 25 mg, and methyl-B12 2 mg), and Cerafolin NAC (5-methyl folate 5.6 mg, NAC 500 mg, and methyl-B12 2 mg). Folapro is available over-the-counter, at the office or on line. Metanx and Cerafolin are available as prescription agents, but your health insurance typically will not cover their cost as they are just vitamins.
Of interest, homocysteine is a known bad actor. An elevated homocysteine level increases your risk for cardiovascular and neurological disease. Many studies have been carried out, utilizing various cocktails of folic acid, B6, and B12, or a placebo agent in large groups of individuals, with or without known disease states.
Average homocysteine levels will fall, but not all subjects will respond with a reduction in homocysteine. Clinical event rates typically fall in response to supplementation, but some studies show no effect, and one study of folic acid supplementation in the elderly showed an increased rate of dementia. Why did this occur? Youve already figured it out.
If we give folic acid to individuals with an elevated homocysteine level and normal MTHFR function, they will respond with a reduction in homocysteine and a reduction in disease risk or event rate, but if we give folic acid to an individual who is MTHFR (+/+) or (+/-), then not much happens.
Actually, if we flood you with folic acid that you cannot use, we can block absorption of the sparse 5-methyl folate present in your diet, so your homocysteine level might even rise. Also, excess folic acid can be converted in to alpha-ketoglutarate, aggravating a co-existent CBS abnormality. Thus we can understand how supplementation inappropriate for ones genotype can have an undesired negative consequence.
I used to think of homocysteine as an individual bad actor, a cause of cardiovascular and neurological disease. Now I look at an elevated homocysteine not as a bad actor, but as a marker of a real bad actor, that being a Methyl Cycle abnormality. To further confuse and befuddle research attempting to link homocysteine with disease states, we must also point out that the sickest patients, or the still healthy but at greatest risk individuals in our society, are those with the lowest homocysteine levels, because their homocysteine levels are low not due to a good diet, but because they harbor the CBS up regulation.
I could go on and try to link homocysteine levels with the story of the three bears, but instead we will cover the SHMT abnormality in THF (dietary folate) processing, and then move on to MTR/MTRR.
