High Dose Folate vs. Broad-Spectrum Nutrition for Methylation Support

The issue of high-dose folate has come up a lot lately, as a number of supplement companies offer folate in excess of 2,000 mcg and sometimes a lot more in products targeted for methylation and homocysteine metabolism. While some references are made to support this, the truth is that the literature is sparse on support of such high doses of folate for any application. Older data has not been validated at all on high-dose folate in certain women's reproductive health concerns, for example.  And, in fact, there appears to be diminishing returns on high-dose folate, as research published in the American Journal of Clinical Nutrition showed that doses of folate of 800 mcg and 2,000 mcg had precisely the same effect on reductions of homocysteine (see my previous post).  

"There are few intervention studies of folic acid or 5-MTHF as a stand-alone treatment." (Altern Med Rev. 2008 Sep;13(3):216-26) And there are no studies at all to my knowledge that show superior results in high dose folate vs. multiple nutrients.  (​If you know of any, please send them my way.)​
   

While the risk of toxicity of high dose folate is low, keep in mind that supplementation with folate can mask a B12 deficiency. 

In the supplement industry, a "more must be better" approach is often promoted among supplement companies and some practitioners, and this, of course, is the mindset of more ​conventional practitioners, as this is more consistent with the traditional medical model.  Providing mega-doses of any one substance is closer to a pharmacological approach rather than a holistic or complementary one.  ​But again, what does the preponderance of literature say?  As far as I can tell, there are no studies showing benefit of high dose folate vs. combining moderate ​folate amounts ​with other supportive nutrients.  

Truly holistic practitioners must resist the temptation to always believe that more is better.  An older study on vitamin E, for example, showed that mega-doses given to smokers actually seemed to increase the risk of lung cancer.  Why?  Because certain compounds given in mega doses in isolation of other supportive nutrients may turn out to be pro-oxidants rather than antioxidants.  

Thus, the most effective approach may be the one that addresses the potential folate deficiency, along with other deficiencies (B12, for example) while offering a comprehensive plan that takes into account a variety of supportive measures.​

Thus, methylation as a whole (and hence effective homocysteine metabolism)​ is less a situation of a singular nutrient and more a breadth of supportive accessory nutrients, such as zinc, B6, B12, betaine, molybdenum, N-acetylcysteine, and others. In other words, the more "natural" and effective approach is likely not high-dose folate but rational folate intake coupled with other methylation support nutrients.