N-acetyl-L-cysteine and vitamin C are frequently taken together, however, the two supplements should never be taken together. One of the selling points of taking the two supplements together was that N-acetyl-L-cysteine would prevent the oxidation of vitamin C to dehyrdroascorbate which N-acetyl-L-cysteine very effectively does. However dehyrdroascorbate is the form of vitamin C absorbed via glucose transporters. Preventing the oxidation of vitamin C with N-acetyl-L-cysteine is a huge error. There are many grounds for not supplementing N-acetyl-L-cysteine. The high effectiveness of N-acetyl-L-cysteine in preventing oxidation of vitamin C is one.
I have been arguing that sodium-dependent transporters are dysregulated in epigenetic illnesses. The sodium-dependent vitamin C transporter (SVCT) could be dysregulated in epigenetic illnesses. Dedydroascorbic acid, which is oxidized vitamin C, is transported by glucose transporters. With the SVCT dysregulated dedydroascorbic acid must be available to be transported by glucose transporters.
Taking antioxidants with vitamin C could reduce any dedydroascorbic acid that is produced to ascorbic acid. Vitamin C must then not be taken with other antioxidants such as selenium, coffee or tea. Vitamin C would also not be taken with carbohydrates or sugar as glucose could competitively inhibit the transport of vitamin C by glucose transporters. Fat soluble antioxidant supplements, such as vitamin E and carotenoids should not be taken in much more than RDA amounts as fat soluble antioxidants could reduce dedydroascorbic acid to ascorbic acid throughout the day. A selling point of vitamin E has been that vitamin E reduces oxidized vitamin C but as it turns out this is a very large negative. With vitamin C inside cells due to transport of dedydroascorbic acid into cells by glucose transporters TET enzymes could start working which would hopefully re-regulate SVCTs.
There is no doubt that high blood levels of manganese can be neurotoxic and can cause movement disorders. Backing out of manganese toxicity can’t really be done as neurons have been killed
Yet manganese is an essential trace element. For animals, such as humans, manganese is required. Manganese is required by a range of enzymes, for example, glutamine synthetase and arginase. Divalent metal transporter 1 (DMT1) transports both iron and manganese and is regulated by iron levels. Dysregulation of iron metabolism could also dysregulate manganese metabolism.
Tea can reduce manganese levels which would suggest that manganese reacts with polyphenols. A main point of this blog is that trace minerals must be available in the gut as well as systematically. The way to take trace minerals so trace minerals are available in the gut as well as systematically is take trace minerals at bedtime away from coffee, tea and other drinks except water, away from food and away from other supplements such as vitamin C.
Supplementation with a non-chelated form of manganese could be required to treat a range of mental illnesses. Tests on manganese bloods are required and not an option if manganese is supplemented. The goal is most definitely not high blood levels of manganese but rather normal blood levels of manganese where manganese is available in the gut and liver as well as systematically.
I think non-chelated forms of iron, manganese and copper have to be supplemented at bedtime in a range of mental illnesses.. I know that if iron, manganese and copper are supplemented that tests on mineral levels are required and not an option Individuals who are heavy coffee, tea and/or soda drinkers should suspect that manganese metabolism is dysregulated.
One group of guinea pigs would be given vitamin C by gavage two times a day, another group of guinea pigs would be given vitamin C and slow release iron sulfate by gavage two times a day with the vitamin C and slow release iron given at the same time and a third group of guinea pigs would be given vitamin C two times a day and and slow release iron once a day with the slow release iron given away from the vitamin C and as the last supplement given each day. . Slow release iron is used where the slow release iron is given last in the day to insure that iron is available or at least has a chance to be available in the gut. A fourth group of guinea pigs would be a control group. Rats synthesize vitamin C, however, guinea pigs do not not so guinea pigs rather than rats are used in the experiment
In six months time the gut epigenomes of the guinea pigs could be investigated. I think there would be large differences in the gut epigenomes of the various groups of guinea pigs. The guinea pigs given vitamin C and iron together and vitamin C alone would show high levels of DNA methylation in the gut as with vitamin C iron is well absorbed and not available in the gut. TET enzymes and JmjC domain-containing proteins require both vitamin C and iron. The guinea pigs given vitamin C and slow release iron at different times would show low levels of DNA methylation in the gut as then both iron and vitamin C would be available in the gut for TET enzymes and JmjC domain-containing proteins
Vitamin C is being investigated as a way to reprogram the gut epigenome in terms of treating cancer. A test of the effects of vitamin C and vitamin C and iron on the gut epigenome could be a preliminary experiment in terms of eventually reprogramming the epigenome in terms of treating cancer with vitamin C. Augmentation of intracellular iron using iron sucrose enhances the toxicity of pharmacological ascorbate in colon cancer cells. This could be due to increased DNA demethylation of colon cancer cells.
The dopamine transporter is sodium dependent. The serotonin transporter is a member of the sodium:neurotransmitter symporter family. The norepinephrine transporter is sodium dependent. GABA transporters are sodium symporters.A symporter is a membrane protein that is involved in the transport of two different molecules across the cell membrane in the same direction.
All classes of psychotropic drugs are either directly or very closely connected to sodium symporters. Yet sodium levels in mental illness are very frequently in the normal range. How could neurotransmitter sodium symporters be dysregulated in mental illness while at the same time sodium levels are normal?
Sodium:neurotransmitter symporters are heavily regulated proteins. When epigenenetic . mechanisms go awry heavily regulated processes can go awry. When epigenetic mechanisms go awry then there is a high probability that sodium:neurotransmitter symporters will go awry.. However, the difficulty can not be fixed by increasing sodium levels. The epigenome must be reprogrammed. When reprogramming the epigenome the gut epigenome must not be overlooked TET and JmjC domain containing proteins demethylate DNA and histones respectively.
TET and JmjC domain containing proteins are vitamin C and iron dependent enzymes. . Carbonyl iron would also be required. Only trace minerals that are available in the gut can be supplemented.There are some extremely well formulated chelated minerals on the market all of which must be avoided.
Vitamin C and iron, however, cannot be taken at the same time. Vitamin C complexes with iron which would make iron unavailable in the gut even though iron absorption can be increased by vitamin C. The great overlooked fact about vitamin C supplementation is that vitamin C supplementation can reduce iron availability in the gut and iron must be available in the gut as well as systematically. Iron from iron carbonyl would be taken at bedtime five or so hours after the last vitamin C dosage of the day. Vitamin C can also interfere with copper absorption so copper from copper gluconate would also be taken at bedtime. Immediate release vitamin C, iron from carbonyl iron and copper from copper gluconate could lessen symptoms in a range of mental illnesses.
Sodium dependent transport in very common with the sodium-dependent multivitamin transporter only one example. Sodium is also required for the transport of vitamin C by sodium-dependent vitamin C transporter 1 and sodium dependent vitamin C transporter 2 .
Why would sodium-dependent transport in the gut be especially prone to dysregulation? Sodium-dependent transport is regulated transport. When the gut epigenome goes awry regulated transport can become dysregulated and a large part of regulated transport in the gut is sodium-dependent. With regulated transport there is an opening for DNA hypermethylation to have a large effect. Transport by passive diffusion may not be so susceptible to dysregulation when the gut epigenome goes awry.
The first order of business would be to re-regulate the gut epigenome. TET enzymes and JmjC domain proteins are vitamin C and iron dependent enzymes. Both iron and vitamin C would be required to re-regulate TET enzymes and JmjC domain proteins in the gut.
Vitamin C and iron, however, cannot be taken at the same time. Vitamin C complexes with iron which would make iron unavailable in the gut even though iron absorption can be increased by vitamin C. Iron from iron carbonyl would be taken at bedtime five or so hours after the last vitamin C dosage of the day. Vitamin C can also interfere with copper absorption so copper from copper gluconate would also be taken at bedtime. Only trace minerals that are available in the gut can be supplemented. There are some excellent chelated minerals on the market all of which must be avoided.
One of the difficulties in any epigenetic approach to illnesses is to select which hypermethylated genes are the relevant hypermethylated genes. In a range of illnesses there could be excess DNA hypermethylation of genes associated with sodium dependent transport. Given this is the case this would clearly be relevant to the etiology such illnesses..
I have repeatedly stressed in this blog what happens in the gut is key. TET2 is highly expressed in the gut. TET3 is also highly expressed in the gut. There are a lot of JMJC domain containing proteins and a lot of them are highly expressed in the gut. For some examples see the Human Protein Atlas.
Reprogramming the gut epigenome via immediate release vitamin vitamin C and iron from iron carbonyl taken at bedtime away from vitamin C could have a large effect on the gut and therefore have large systematic effects. Copper from copper gluceonate would be taken at bedtime too as vitamin C can decrease copper absorption. Even with normal levels of iron iron from iron carbonyl would be supplemented at bedtime. as iron must be available in the gut as well as absorbed.
Unless the epigenome can be reprogrammed one ends up playing whack a mole. Upon addressing one symptom successfully other symptoms become prominent. Address one symptom successfully and one .can still be very ill. Ameliorating .one symptom then does not feel like much of a victory. A minimal program would be vitamin C taken during the day and iron and copper taken at bedtime. Mineral levels would be checked.
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.
Many illnesses, such as schizophrenia, Alzheimer’s disease, Parkinson’s disease and bipolar disorder are associated with oxidant stress. Yet, increasing levels of free antioxidants by supplementing with more than RDA amounts of vitamin E, beta-carotene and vitamin C does not treat these illnesses.
Increasing levels of free antioxidants via supplmentation could be much worse than useless. Before iron can be absorbed iron must be reduced from Fe3+ to Fe2+. Antioxidants like vitamin C, vitamin E , beta-carotene and quercetin could one way or other promote the reduction of Fe3+ to Fe2+ in the gastrointestinal tract which would increase absorption. The goal, however, is to delay iron absorption as long as feasible.
There is oxidant stress in lots of illnesses but this could be due to dysregulation of selenoproteins and dysregulation of iron metabolism which would not be fixed by increasing levels of free antioxidants with supplemental vitamin C, vitamin E , beta-carotene, quercetin etc.
Supplementing with free antioxidants could be associated with very subtle but serious mineral dysregulations which would basically be undiagnosable.
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.