Looking into vitamin C one more time

Linus Pauling brought vitamin C to the world’s attention

Vitamin C has been repeatedly investigated since Linus Pauling focused on vitamin C. TET enzymes and JmjC domain-containing proteins are vitamin C and iron dependent enzymes which demethylate DNA and histones respectively. .Vitamin C is being investigated as a way to reprogram the epigenome..

There are various difficulties with supplementation with vitamin C. First of all vitamin C is poorly absorbed. Secondly vitamin C can affect mineral absorption. The adverse affects on mineral absorption of vitamin C has not been sufficiently stressed as an important limiting factor in vitamin C supplementation. As iron must be available in the gut forming vitamin C-iron complexes in the gut may not be desirable.

Getting vitamin C to work could be as easy as not taking trace minerals such as iron and copper at the same time as vitamin C. What one would be looking for is whether activity of TET enzymes and JmjC domain-containing proteins could be be increased by supplemental vitamin C and carbonyl iron taken at different times of the day. Activity of TET enzymes and JmjC domain-containing proteins in the gut would be investigated. A combination of immediate release vitamin C and liposomal vitamin C where the vitamin C is taken away from trace minerals could be optimal.

Loss of the ability to synthesize vitamin C

Linus Pauling held that loss of the ability to synthesize vitamin C in the forerunners of humans was an evolutionary error that had best be compensated for in humans by mega-dosages of vitamin C. The difficulty with this view is that the forerunners of humans after the loss of the gene required to synthesize vitamin C had much less vitamin C available in tissues than before the loss. Given huge decreases in vitamin C bioavailability were a great disadvantage in terms of evolutionary fitness then the gene would not have been lost or at least would have once again been selected for. The animal forerunners who lost the ability to synthesize vitamin C were eating lots of fruit but were still getting a lot less vitamin C after the loss of the gene. Gulonolactone (L-) oxidase, the lost gene, is widely expressed in rats. Animals who synthesize vitamin C can synthesize huge amounts of vitamin C.

Even with fruit trees all around the loss of the gene to synthesize vitamin C would not have been a neutral mutation given the high levels of vitamin C in tissuses with the gene. The loss of the gene could not come about through genetic drift in a high fruit environment. A high fruit environment could have been permissive which is not to say that the loss of the gene and lessened bioavailability of vitamin C in tissues did not enhance evolutionary fitness.

Loss of the gene to synthesize vitamin C apparently had some evolutionary advantage which argues against supplementing with much more than RDA amounts of vitamin C now.

The weakness of safety testing of supplements

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.