Any reprogramming of youthful methylation patterns in humans would require that TET enzymes be re-regulated first


Sinclair et al. using the eye as a model CNS tissue, showed that ectopic expression of Oct4, Sox2 and Klf4 genes in mouse retinal ganglion cells restores youthful DNA methylation patterns and transcriptomes, promotes axon regeneration after injury, and reverses vision loss in a mouse model of glaucoma and in aged mice. The beneficial effects of OSK-induced reprogramming in axon regeneration and vision require the DNA demethylases TET1 and TET2.

However, I have been arguing in papers (see Treatment-resistant schizophrenia: focus on the transsulfuration pathway and A disease-modifying treatment for Alzheimer’s disease: focus on the transsulfuration pathway) and on this blog that TET enzymes are the very enzymes that are dysregulated in many chronic illnesses, which results in various chronic illnesses possessing a range of phenotypic expressions. Ectopic expression of OCT4, KLF4 and SOX2 alone would not work in aged humans and/or ill humans as TET enzymes are dysregulated in aged and/or ill humans.

TET enzymes are iron and 2-oxoglutarate dependent dioxyegenases. Fixing TET enzymes could be a key part of the treatment of a range of chronic illness and would be a lot simpler and safer than systematic ectopic expression of OCT4, KLF4 and SOX2 in humans. A lot of methylation changes acquired during aging must be beneficial. Systematically turning back the clock to 18 or so would not be desirable .’Just’ fixing TET enzymes would allow desirable methylations to occur but would allow DNA demethylations of undesirable DNA methyations. Clearly fixing TET enzymes would be a required first step prior to any genetic engineering of humans to restore youthfulness given that such genetic engineering was feasible and desirable.

A fundamental rule of nutrition

Supplements or drinks with tricarboxylic acid cycle intermediates should be avoided though supplements with alpha ketoglutarate could be helpful. TET enzymes are 2-oxoglutarate dependent.enzymes that demethylate DNA. JmjC domain-containing proteins are 2-oxoglutarate dependent.enzymes that demethylate histones .Fumarate and succinate inhibit TET and JmjC domain-containing proteins. This could lead to DNA hypermethylation and histone hypermethylation. Malic acid could inhibit fumarate dehydratase by end product inhibition and lead to a build up of fumarate.

Accumulation of succinate and fumarate are associated with cancer due the inhibition of 2-oxoglutarate-dependent dioxygenases, such as TET and JmjC-domain containing proteins. Citrate is a competitive inhibitor of oxaloacetate for citrate synthase. Citrate synthase also produces coenzyme A which is needed by the 2-oxoglutarate complex. Citric acid from soft drinks could dysregulate the the 2-oxoglutarate complex. There is a lot of circumstantial evidence that citric acid has goofy effects on individuals witness Mountain Dew ads.

A lot of supplements contain tricarboxylic acid cycle intermediates. Calcium citrate contains citrate. Magnesium succinate contains succincate. Carnitine fumarate contains. fumarate. Citruline malate contains malate, TCA intermediates are everywhere is supplements.

But as always the key selling point of supplements is ‘better absorption’ and minerals, for example, minerals bound to citrate, can be well absorbed. A huge and very frequently deleterious factor not usually considered is what supplements are bound to. ‘Better absorption’ is the siren call of supplements. Chelated minerals are also avoided.

Schizophrenia, anosognosia and Se-methylselenocysteine

Lack of insight or lack of awareness of illness in schizophrenia is termed anosognosia with some 30% of individuals with schizophrenia having anosognosia.

What is the cardinal feature of anosognosia? The cardinal feature is not elaborate delusions rather the cardinal feature of anosognosia is confusion and disorganization. Individuals with agonosgnosia are having terrible cognitive difficulties.

Se-methylselenocysteine treats cognitive symptoms of schizophrenia. Supplemental Se-methylselenocysteine could be a treatment for anosognosia. Se-methylselenocysteine would be taken with iodide from kelp. Sadness can pop up in almost any illness and everywhere depression as sadness pops could be due to dysregulation of iodide transporters. Sadness in all depressions could be treated by iodide from kelp, l-tyrosine and Se-methylselenocysteine. L-tyrosine is involved in the synthesis of thyroid hormones. Patients might not be responsive to treatment for anosognosia with Se-methylselenocysteine if they are intensely sad..

Iodide from kelp, L-tyrosine and Se-methylselenocysteine would not treat all states associated with depression only sadness. Kelp and L-tyrosine have to be taken three or four times a day. Thyroid tests must be obtained. The goal is most definitely not high thyroid hormone levels. Iodide from potassium iodide apparently reacts with too many substances. The effect of iodide from potassium iodide is not dependable. Approximately 1000 micrograms of iodide from kelp have to be taken each dosage. Iodide from kelp and L-tyrosine are taken three times a day . L-tyrosine taken without iodide is not helpful. L-tyrosine and kelp are taken away from food.

Se-methylselenocysteine is supplemented. Selenium is also required for thyroid hormone homeostasis. 200 micrograms of Se-methylselenocysteine is taken once a day. More Se-methylselenocysteine is not better. Deiodinases, which are selenoproteins, can both activate and deactivate thyroid hormones. Selenium taken alone could stress the thyroid.

sT4 – active, T3 very active, rT3 not active, ID1 – deiodinase I, ID2 – deiodinase II, IDIII – deiodinase III.

Patients on Se-methylselenocysteine, iodide from kelp and L-tyrosine could have ahedonia but there would be an awareness of illnesses. More organized delusions though with an awareness of illness could be a feature of the treatment. I hold more can be done to treat schizophrenia, however, Se-methylselenocysteine, iodide from kelp and l-tyrosine can readily tested as a treatment for agonosgnosia.

An exclusive focus on absorption of minerals is at odds with the gut being a key to various illnesses

The gut has become a primary focus of a lot of research on various illnesses. The gut has become a focus in research on major depressive disorder, schizophrenia, bipolar disorder, obsessive compulsive disorder, autism, anxiety, Parkinson’s disease, Alzheimer’s disease, osteoporosis, amyotrophic lateral sclerosis etc.

Yet the key selling point of most mineral supplements is increased absorption with increased absorption demanding that the gut be bypassed. Moreover almost all clinical studies done on humans employ inorganic forms of minerals rather than chelated organic forms of minerals. ‘Zinc gluconate human‘ turned up 560 results in Pubmed whereas ‘zinc methionine human, turned up 11 results where there were two human trials with an equivocal result in one of the trials and a positive result on a narrow measure of reduced acne in the other.

Individuals taking organic chelated mineral supplements are venturing into unknown lands and I think dangerous lands. Chelated minerals are highly absorbed but that is a bug not a feature.

The Gene: An Intimate History by Siddhartha Mukherjee


The Gene is a popular introductory book on the gene. This is not a criticism as each new generation has to be introduced to a subject and this an acceptable popular introductory book.. With the field not at all crowded The Gene is a welcome popular introductory book on the gene.

The major criticism I have is that Mukherjee slights epigenetics in terms of behavior, is much too sanguine about genetic engineering to cure what are held to be polygenetic illnesses and is much too sanguine about genetic engineering to instill beneficial polygenetic traits. Geneticists apparently repeatedly assured Mukherjee that geneticists will one day be able treat polygenetic illnesses and moreover will be able to instill beneficial polygenetic traits most likely via some sort of embryo selection. Mukherjee took the geneticists at their word. Genetic determinism is almost a religion among geneticists as determinism is almost a religion in academia.

Medical horrors are apparently inadvertently being planned for the wealthy. Now the wealthy depressed are taking ketamine which can cause a schizophrenia-like psychosis. 10 years from now the wealthy could be selecting embryos on the basis of very abstruse calculations where if something goes wrong the advising geneticist will say ‘the odds slightly favored a favorable outcome. Look at these calculations. You must understand probabilities.’

Biohack mental illness now!

l CRISPR DIY kit not required

A lot of biohacking does not appear to be safe. For example, trying to alter at home one’s genetic makeup via CRISPR seems beyond unsafe.

A lot of biohacking is undertaken to achieve increased longevity. Biohacking for increase longevity requires that one wait around for decades to see the results. One has to wait 30 or 40 years to see whether one selected a right mix of supplements and then in all probability if one lives to a healthy 100 years of age one would not know exactly which supplements were the key supplements. Knowledge as to what increases longevity would still be lacking. One could be interviewed with questions asked as to how longevity was achieved and a laundry list of supplements would then be detailed. Someone listening to the interview could say, ‘I will eat 3 strips of bacon every morning. The other guy eats three strips of bacon every morning and is an alert, healthy 102 year old.’

A lot of specialty nootropics taken for cognitive enhancement have unclear effects and have not been widely tested in clinical trials . Moreover most nootropics are likely manufactured in China which does not have a reputation for tight controls on drug manufacture. What is more there would be a huge mainstream market for nootropics given noontropics worked. Individuals with mental illnesses very frequently could use some cognitive enhancement but nootropics are not being prescribed. After decades of use and study use of nootropics appears to be a very sketchy practice.

The appeal now of becoming part cyborg is 98% aesthetic. Becoming part cyborg now does not result in cognitive enhancements or health enhancements.

Biohacking mental illness

I hold that a lot of mental illness can be biohacked now, this week. 600 milligrams of carbonyl iron taken once a day at bedtime can treat psychosis. 200 micrograms of Se-methylselenocysteine taken once a day in the morning. can treat disorganization. 1,000 micrograms of iodide from kelp taken three times a day with 1000 milligrams of L-tyrosine taken three times a day can treat depression which is presents as sadness. Iron interacts with lots of substances, coffee and tea being two examples. The point of taking the carbonyl iron at bedtime is to take the iron and iodide away from substances that can interfere with iron metabolism in the gut. The last cup of coffee or cup of tea of the day should be drunk at least 6 or 7 hours before carbonyl iron is taken.

300 milligrams of thiamine is taken 4 times a day can decrease fatigue.

No other supplements would be taken.


I hold that iron-sulfur proteins are dysregulated in schizophrenia and that 600 milligrams of carbonyl iron taken once a day at bedtime can address the psychosis of schizophrenia. There is no direct clinical evidence that iron-sulfur proteins are dysregulated in schizophrenia. Given iron-sulfur proteins were dysregulated in schizophrenia this would cause major difficulties where psychosis could be one such difficulty.

There is no clinical evidence Se-methylselenocysteine effectively treats cognitive symptoms of schizophrenia.

Everyone who is treated for depression has had their thyroid hormone levels checked. A search of PubMed using ‘thyroid major depressive disorder’ turns up 999 articles. Thyroid hormones have not proven efficacious in treating major depressive disorder. Yet I hold that major depressive disorder is partly due to thyroid dysregulation. Conceivably doctors when prescribing T3 never asked the correct question. The correct question would be ‘Are you still sad?’ Not ‘Has your depression remitted?’

Why such high dosages of thiamine are needed is not clear. 25 milligrams of vitamin B6 twice a day. could also be helpful.

T4 could work better than iodide and L-tyrosine. T4 is fully iodinated and with T4 one would still be working with natural mechanisms for the production of T3 ,which is the active hormone. T3 could be too much. With T4 the question to ask would be ‘has the sadness passed? not ‘has the depression remitted?’


No other supplements should be taken.

Iodide from kelp and L-tyrosine only treats depression as sadness. Frequently malaise and apathy are associated with major depressive disorder which iodide and L-tyrosine would likely not address. Iodide and L-tyrosine are not going to address all symptoms of major depressive disorder.


Dirt simple and very quick. Very safe for at least a week. If the treatment has not worked at the end of week the treatment would be stopped. If the treatment is effective then safety of the supplements can be studied further and necessary tests obtained.

A lot of research cited on this website points to iron-sulfur cluster formation and selenoprotein metabolism being dysregulated in various neurological illnesses. Dysregulation of thyroid hormones can certainly result in depressive illnesses.

L-glutamate and schizophrenia

NMDA receptor

Dysregulation of glutamatergic neurotransmission has been widely postulated as being involved in the etiology of schizophrenia. In the etiology of schizophrenia I have been stressing the dysregulation tricarboxylic acid (TCA) cycle via dysregulation of aconitase and the 2-oxoglutarate dehydrogenase complex stemming from shortages of coenzyme A.

The TCA cycle produces 2-oxouglutarate. .L-glutamate can be synthesized from 2-oxoglutarate. With dysregulation of the TCA cycle there can be a disruption in the synthesis of L-glutamate which would adversely affect glutamatergic neurotransmission whereby symptoms of schizophrenia could develop. .

Increasing glutamatergic neurotransmission alone via glutamate receptor agonists, however, does not solve the problem. The TCA cycle is still dysregulated.

There is strong focus on NMDA glutamate receptors in research on schizophrenia. Dysregulation of the TCA cycle, however, would dysregulate glutamatergic neurotransmission generally and also dysregulate GABA neurotransmission as GABA is synthesized from L-glutamate . D-serine which is an NMDA receptor agonist has failed in phase II trials where d-serine was being tested for effectiveness against symptoms of schizophrenia though a deuterated (i.e patenable) form of D-serine could still be effective for hair loss.

I hold that only addressing NMDA receptors will always fail in terms of the treatment of schizophrenia. Dysregulation of glutamatergic neurotransmission plays a key role in the etiology of schizophrenia, however, to address dysregulations of glutamatergic neurotransmission in schizophrenia dysregulation of the TCA cycle must be first addressed.

Taurine chloramine inhibits prostaglandin E2


Prostaglandin E2 (PGE2) is highly inflammatory. Inflammation is associated with major depressive disorder. Taurine chloramine inhibits PGE2.

Taurine chloramine inhibits prostaglandin E2 production in activated RAW 264.7 cells by post-transcriptional effects on inducible cyclooxygenase expression.

Quinn MR, Park E, Schuller-Levis G.


Taurine chloramine (Tau-Cl) was recently demonstrated to inhibit production of nitric oxide and tumor necrosis factor-alpha (TNF-alpha) by activated macrophages. Since increased production of prostaglandin E2 (PGE2), a reaction catalyzed by induction of cyclooxygenase-2 (COX-2), is also associated with the inflammatory response, we determined the effects of Tau-Cl on PGE2 production and on expression of COX-2 protein and COX-2 mRNA in activated RAW 264.7 cells, a murine macrophage-like cell line. Tau-Cl inhibited production of PGE2 in a concentration dependent manner with an IC50 of 0.4 mM. The decrease in PGE2 production was largely accounted for by decreased expression of COX-2 protein. Although the kinetics of COX-2 mRNA expression was altered in Tau-Cl treated cells, mRNA expression appeared to be quantitatively unimpaired. These results suggest that Tau-Cl affects the post-transcriptional regulation of COX-2 expression and support the idea that Tau-Cl may function as an inhibitory modulator of the inflammatory response.

See also –

Selective inhibition of cyclooxygenase 2-generated prostaglandin E2 synthesis in rheumatoid arthritis synoviocytes by taurine chloramine.

Kontny E, Rudnicka W, Kowalczewski J, Marcinkiewicz J, Maslinski W.

Objective: To investigate the effects of taurine chloramine (Tau-Cl), a chlorinated derivative of the amino acid taurine, on the expression of cyclooxygenase (COX) isoenzymes and prostaglandin E(2) (PGE(2)) synthesis in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS).

Methods: FLS, isolated from the synovial tissue of RA patients, were treated in vitro with either interleukin-1beta (IL-1beta; 1 ng/ml) alone or together with 200-500 microM Tau-Cl. The expression of COX isoenzymes was evaluated at both the protein (Western blotting) and the messenger RNA (mRNA) (reverse transcriptase-polymerase chain reaction) levels. The concentration of PGE(2) was measured by competitive acetylcholinesterase enzyme immunoassay.

Results: Resting FLS expressed mRNA encoding both COX-1 and COX-2, but only COX-1 was present at the protein level. These cells produced negligible amounts of PGE(2). Upon stimulation with IL-1beta, elevation of COX-2, but not COX-1, mRNA and protein preceded the enhancement of PGE(2) synthesis. In the presence of 300-400 microM Tau-Cl, significant inhibition of IL-1beta-triggered COX-2 mRNA and protein, and a related decrease in PGE(2) production, was observed. In contrast, no significant changes in COX-1 mRNA and protein levels were noted.

Conclusion: Tau-Cl inhibits IL-1beta-triggered elevation of COX-2 and generation of PGE(2) by RA FLS. These results expand the spectrum of known antiinflammatory activities of this compound.

Whey protein and athletics


More than half of high school athletes take protein supplements and percentages could increase in college and in professional sports. The NFL website strongly suggests that protein supplements can be helpful. Whey protein supplements that are quickly absorbed can have very adverse effects. Whey protein isolates are very quickly absorbed and can have very adverse effects. Most whey protein supplements contain at least some whey protein isolates. Whey protein isolate would contain only whey protein isolates but supplements labeled as whey protein usually are partly whey protein isolates.

Head injuries may not be the only problems of athletes are facing in terms of cognitive abilities. Whey protein isolates can negatively affect cognitive abilities. Any supplement formulated for quick absorption can have negative effects with whey protein isolate being one such supplement.

Casein is a much safer protein supplement but I am not recommending that athletes switch to casein from whey protein as taking supplements is full of pitfalls. The calcium phosphate in casein, for example, could decrease absorption of iron. Athletes who hold they need more protein should eat more high protein meals.

Why do individuals have differences in gut microbiota?

Gut microbiota are dependent on the environment of the gut for nutrients. If metabolic processes are dysregulated in the gut this will affect nutrients available in the gut. Some species of microbiota could be favored by various gut metabolic dysregulations while other microbiota could be disfavored. Certain microbiotic ecosystems could have direct effects, for example, causing diarrhea while other microbiotic ecoystems could only be markers for iron dysregulation in the gut which can have systematic effects.

Iron in the gut is a nutrient in the gut that affects the microbiotic ecosystem of the gut. Gut microbiota and iron are held to be crucial actors in health where many species (see Table) of gut microbiota are affected by iron supplementation.

Differences in gut microbiota could largely be a marker for iron dysregulation in the gut. Lots of substances in the diet bind with iron which could be affecting gut microbiota. Probiotics can affect iron metabolism in the gut. Lactobacillus plantarum 299v can increase iron absorption. A meta-analysis indicates that Lactobacillus plantarum 299v increases iron absorption. Lactobacillus plantarum 299v does not require iron which could make iron more available in the gut besides assisting with the absorption of iron via more iron being available to be absorbed. Bifidobacteria,. another beneficial microorganism in the gut, requires iron.

In sum gut microbiota is dysregulated in so many illnesses as iron metabolism in the gut is dysregulated in so many illnesses.