Friday, March 9, 2018

Folate and Homocysteine: Is There Diminishing Returns?

By now it is common knowledge that B-vitamins, particularly folate, B6, and B12, are extremely important to metabolize the amino acid, homocysteine, which is an intermediate in the metabolism of methionine and cysteine, and has been implicated in vascular disease.

Recently I had the opportunity to review a nutritional product that was touted as a supreme homocysteine support product.  It looked good, actually, but something stood out to me that is apparently not common knowledge among practitioners and supplement manufacturers.

The more-is-better idea is a common mindset among holistic pill poppers and those recommending them.  However, the idea that more is better does not apply to many things, and folate's role in homocysteine metabolism is one of them.

The supplement I reviewed has over 2,000 mcg of folate, which impresses many casual observers.  However, it must be noted that according to a study on homocysteine and folate published in The American Journal of Clinical Nutrition, even very low dose folate supplementation of 200 mcg lowers homocysteine significantly, and most notably, there was no difference in high dose folate supplementation and moderate dose supplementation in lowering homocysteine levels. (See chart below.)  Moderate dosing of 800 mcg lowers homocysteine by 23%, but pushing the dose up to 2,000 mcg did not show any additional benefit.  Even very high dosing at 5,000 mcg showed only minimal additional benefit of a mere two percentage points.  

What might make more sense in achieving the perfect formula for homocysteine metabolism is to keep the folate levels moderate in order to keep the cost down and make room for other important nutrients that aid in the methylation cycle and renal clearance of homocysteine -- nutrients such as molybdenum, N-acetylcysteine (NAC), manganese, betaine, etc.

NAC, in particular, is an important antioxidant that serves many roles in the body.  For example, it is an amazingly powerful antioxidant that supports liver detoxification and glutathione levels in the body, but it is also important for renal clearance of homocysteine.  Therefore, significant amounts of NAC (500 mg or more) should be considered to support those with elevated homocysteine or who have had a history of issues along these lines.

Consider supplementation that supports all four levels of homocysteine clearance (see below).