In terms of alternative and complimentary medicine 5-MTHF, alpha lipoic acid, folate and N acetyl cysteine are mainline treatments for depression.
There are lots of grounds to think these supplements could be very unsafe. Lipoic acid shares the same transporter with biotin and pantothentic acid. Lipoate inhibits the transport of pantothenic acid and biotin. The body uses miniscule quantities of biotin. 300 milligrams of lipoic acid twice a day could have a large negative affect on biotin transport. Lipoic acid does not work in bipolar depression which is not suprising, See the page on Bipolar Depression.
N-acetyl cysteine is associated with musculoskeletal adverse side effects. These musculoskeletal adverse side effects are almost totally impossible to get rid of and can be horrendous. Clincal trials are usually about 6 weeks long but musculoskeletal effects accumulate over time and can persist long after N-acetyl cysteine is stopped.
There are no grounds whatsover to hold than S-adenosyl methionine taken long term would not affect DNA methylation and histone methylation. Abberrant DNA methylation is associated with cancer, aging and mental illnesses. Minimally an explantion as to why greatly increasing S-adenosyl-l-methionine levels does not affect DNA and histone methylation long term has to be given but no explanatiton is provided.
5-methyltetrahydrofolate inhibts glycine-N-methyltransferase which degrades S-adenosyl methionine. With 5-methyltetrahydrofolate supplementation S-adenosyl methionine levels would again be expected to greatly increase with again unknown consequences to DNA methylation and histone methylation. No consequences would be very surprising. Despite great early enthusiasm folic acid supplementation has been a bust in the prevention of a range of illnesses associated with high homocysteine levels.
What is it about these supplements that makes them so attractive? One very definitely notices these supplements when one takes them.