Methionine synthase reductase (MTRR) is a vital enzyme of homocysteine/methionine metabolic pathway and is required for the conversion of inactive form of methionine synthase (MTR) to its active form. MTRR helps recycle B12.

The MTRR enzyme places a methyl group on B12 so it can be used by MTR to convert homocysteine into methionine and requires B2. Variants here may hamper this function. When combined with other variants that impact the absorption and transport of B12, and if the MTR variant exists (which is trying to make it go faster), this function may be impaired.

Lithium plays a role in B12 transport

Foods that contain lithium and Trace Minerals Research Concentrace drops for reverse osmosis water or Gerolsteiner Water are good sources. According to Dr. Amy Yasko, 83% of people are lithium deficient. High B12 supplementation or injections, iodine supplementation and thyroid medication may increase the need for lithium.

MTRR is inhibited by Alcohol and Sugar/Candida overgrowth

Sugar and yeast (produces acetylaldeyde) shuts down methionine synthase. Too much methylfolate can lead to high NO, which can shut down methionine synthase and transsulfuration pathways. NO levels tend to be higher in those with immune dysfunction, chemical sensitivity, Lyme’s disease and fibromyalgia, so methylfolate supplementation can make these individuals worse.

With MTRR/MTR inhibition, the compensation pathway is BHMT (betaine-homocystine methyltransferase (betaine to dimethylglycine). Betaine and choline needs go up. B12 and folate may be normal to high in blood work. In time, SAM production goes down. Methyltransferases slow and lead to low creatine, phosphatidylcholine, glycine, sarcosine, carnitine, CoQ10 along with cell membrane damage and ROS (inflammation) levels going up.

Folate Methylation Chart