Almost always clinical trials of supplements are run for short periods of time and moreover only certain side-effects are examined. Supplements programs though very frequently modified are usually started with the intention of being on the supplement for life. I think, for example that acetyl-L-cysteine and lipoic acid can have terrible long term effects though there could be postive effects on some dimensions in the short term. With prescription drugs doctors report side-effects that develop over the long term but that is not the case with supplements as usually doctors do not prescribe supplements.
Carnitine is frequently bound to fumarate in carnitine supplements and mineral supplements are very, very frequently bound to glycine. Fumarate can inhibit enzymes that demethylate DNA and histones. Leiomyomatosis and renal cell cancer can be caused by mutations of fumarate hydratase which metabolizes fumarate. Carnitine fumarate suppplements could be making wild epigenetic changes which could be highly undesirable. My opinion which must now be deeemed a personal opinion is that minerals bound to glycine are not bioavalable in the gastrointestinal tract whereby gylicnated minerals can have many negative effects. On many systematic measures glycinated minerals are very effective though I personally hold there can be higly unforeseen negative effects when supplementing with glycinated minerals.
There is mounting evidence that both sugar sweented and diet drinks have negative effects on cardiovascular health over the long term. What if it is not the artificial sweeteners in diet drinks that raise the difficulties but rather the citric acid and polyphenols and perhaps phosphoric acid are what is raising the difficulties? Many calcium supplements contain citrate. Could calicum citrate have the same adverse effects on cardiovascular health as do diet soft drinks and for the same reasons? I think citric acid based soft drinks can befuddle indivduals. There could be truth in advertising with Mountain Dew. Women under 65 who are on calcium citrate are not going to tell their doctors that they feel befudded and besides increasisng citric intake can lead to lots of fun.
Linus Pauling, who viewed orthormolecular medicine as the practice of delivering ‘the right molecules in the right amounts’, was correct in his view that mental illnesses are orthomolecular in nature and that supplements are required in the treatment of mental illnesses. That is not to say that supplements are not a minefield now.