Life expectancy among persons with schizophrenia or bipolar affective disorder

Life-expectancy was 18.7 years shorter for schizophrenic men compared to men in the general population. Corresponding numbers for schizophrenic women was 16.3 years, for bipolar men 13.6 years, and for bipolar women 12.1 years,.’ With DNA demethylating mechanisms going awry in schizophrenia, due to dysregulation of TET enzymes and JumjC domain-containing proteins, all kinds of illnesses in individuals with schizophrenia can develop shortening life spans.

Dopamine transport, serotonin transport, noradrenaline transport and GABA transport are all sodium dependent

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 the gut

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..

TET enzymes, JMJC domain containing enzymes and the gut

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.

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.