I listened to a podcast by Dr. Ruscio a few weeks ago on this topic. He came down on the side that supplementing with B vitamins can lower your homocysteine levels but that doesn't improve your cardiac risk. Here are all the references - pro and con - to using B vitamins to lower Homocysteine:
PRO ---- Studies showing lowering homocysteine improved cardiovascular outcomes: Review showing B-vitamins lower homocysteine
http://www.ncbi.nlm.nih.gov/pubmed/9659410
Betaine Monograph from Thorne Research 2003
http://www.altmedrev.com/publications/8/2/193.pdf
Meta analysis showing folate and/or B12 lower homocysteine but no mention of cardiovascular disease risk
http://www.ncbi.nlm.nih.gov/pubmed/9569395
Randomized control trial showing folic acid/B6/B12 lowered homo and decrease incidence of cardiovascular event
http://www.ncbi.nlm.nih.gov/pubmed/12190367
Observational trial
http://www.ncbi.nlm.nih.gov/pubmed/11742888
CON ---- Studies showing lowering homocysteine
did not improve cardiovascular outcomes:
Meta analysis of 12 randomized controlled trials
http://www.ncbi.nlm.nih.gov/pubmed/26420127
Meta analysis of 8 randomized controlled trials
http://www.ncbi.nlm.nih.gov/pubmed/20937919
Randomized controlled trial
http://www.ncbi.nlm.nih.gov/pubmed/18460663
Randomized controlled trial
http://www.ncbi.nlm.nih.gov/pubmed/18714059
Cochrane Systemic Review
http://www.ncbi.nlm.nih.gov/pubmed/25590290
Cochrane did 2 earlier Systemic Reviews with same findings:
http://www.ncbi.nlm.nih.gov/pubmed/23440809
http://www.ncbi.nlm.nih.gov/pubmed/19821378
Review
http://www.ncbi.nlm.nih.gov/pubmed/16872232
Review
http://www.ncbi.nlm.nih.gov/pubmed/17622392
Review
http://www.ncbi.nlm.nih.gov/pubmed/20236081
Review
http://www.ncbi.nlm.nih.gov/pubmed/21069462
Review
http://www.ncbi.nlm.nih.gov/pubmed/24863141
Review – homocysteine is a marker rather than a cause
http://www.ncbi.nlm.nih.gov/pubmed/17654449
I don't know if any of those studies included MTHFR mutation status. I am homozygous for A1298C but fine with C677T. I started taking O.N.E multivitamin (from Dr. Rhonda Patrick's podcast) just before my big lab tests that revealed my E4/E4 status. I recently added 200mg of Magnesium, which greatly improved my mood
. The multivitamin is at about 1/2 of the B-vitamin dosage that Julie has been discussing. I did try the Active B12 Lozenge (4,000 mcg Methylcobalamin and 1,000 mcg Adenosylocobalmin) along with the multivitamin but had over-methylation symptoms. The next free weekend I get, I will experiment some by stopping the multivitamin and shifting to half a lozenge (then...) to see where my break-even point is. My one and only Homocysteine measurement was at 13 umol/L while I was on a high animal protein paleo diet (~1.5 pounds red meat a day). I've since cut that down to .3 pounds red meat every other day (want to slowly eat out all that great US Wellness Braunschweiger, head cheese, and liverwurst that is stocked in the freezer - then maybe shift to chicken livers).
If anyone gleans any insights out of those links, please let us know.
Chris