The evidences surrounding methionine (and somewhat cysteine or any sulfur amino acid) restriction and the resulting longevity seems to be quite strong. The evidence that we lose methyl group clusters on DNA as we age as a marker of aging and a supplemental methylator such as betaine/TMG or SAMe ameliorating this extends life is also compelling, not to mention the reduction in homocysteine from TMG being a good thing. But it seems the MOA by which betaine does this is to actually recycle homocystiene into methionine:
Effects of betaine supplementation on hepatic metabolism of sulfur-containing amino acids in mice.
We previously reported that acute betaine treatment induced significant changes in the hepatic glutathione and cysteine levels in mice and rats. The present study was aimed to determine the effects of dietary betaine on the metabolism of sulfur-containing amino acids.
METHODS/RESULTS:Male mice were supplemented with betaine (1%) in drinking water for up to 3 weeks. Changes in hepatic levels of major sulfur amino acid metabolites and products were stabilized after 2 weeks of betaine supplementation. Betaine intake increased methionine, S-adenosylmethionine, and S-adenosylhomocysteine levels significantly, but homocysteine and cystathionine were reduced. Methionine adenosyltransferase activity was elevated to three-fold of control. Cysteine catabolism to taurine was inhibited as evidenced by a decrease in cysteine dioxygenase activity and taurine levels in liver and plasma. Despite the significant changes in the transsulfuration reactions, neither hepatic cysteine nor glutathione was altered. Betaine supplementation decreased the hepatotoxicity induced by chloroform (0.5 ml/kg, ip) significantly.
CONCLUSIONS:Betaine supplementation enhances recycling of homocysteine for the generation of methionine and S-adenosylmethionine while reducing its utilization for the synthesis of cystathionine and cysteine. However, the hepatic levels of cysteine or glutathione are not affected, most probably due to the depression of taurine generation from cysteine.
This is alarming. Maybe I'm coming late to the party on this but I was under the impression that many here (myself included) supplement TMG for its marked reduction in homocysteine levels. Does this not run counter to Me restriction and would it not actually shorten life?
And what does this mean for other lipotropics as well such as choline or inositol, or basically any lipotropic that increases sulfur amino acids endogenously?
How do we reconcile the two so that we can lower homocysteine levels via methylators but still observe Me restriction to an appreciable degree?