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.
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 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 verysketchy practice.
The appeal now of becoming part cyborgis 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 thiamineis 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.
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-analysisindicates 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.
The Odd Ratio for schizophrenia for indivduals with IgG antibodies for toxoplasma gondii were 1.81, With toxoplasma gondii infection.there is increased activity of iron-responsive protein 1(IRP1). Aconitase 1 is a dual function protein, When iron levels are low aconitase 1 loses an iron sulfur cluster and becomes IRP1 but when iron levels are increased IRP1 gains an iron-sulfur cluster and becomes aconitase 1. Aconitase 1is an enzyme in the tricarboxylic acid (TCA) cycle. Increased levels of IRP1 would indicate that the TCA cycle is dysregulated which could set the set the stage for schizophrenia. See my paper Treatment-resistant schizophrenia: focus on the transsulfuration pathway. on how dysregulation of IRP1, aconitase 1 and the TCA cyle could play a part in the development of schizophrenia.
If iron chelators work in Parkinson’s there should be some positive effect with supplemental quercetin. I very much doubt there will be. See the page on Parkinson’s disease. If quercetin does not work in the treatment of Parkinson’s disease then the narrative that treatment of Parkinson’s disease requires iron chelation has to be re-thought. I would avoid supplementing with quercetin until there are definite clinical studies to the effect that quercetin in the real world ameliorates symptoms of Parkinson’s disease which I think will be never.
Quercetin is found in fruits and vegetables. Querectin found in foods could have benefcial effects. Like other antioxidants, when obtained from food, quercetin could have beneficial effects.
Many studies report coffee as having beneficial effects and a couple of cups of coffee drink only in the morning could have beneficial effects. A meta-analysis indicates that there is at inverse relationshipbetween coffee/caffeine and risk of Parkinson’s disease. A weakness of the forgoing meta-analysis is that the meta-anaylsis focuses on caffeine. Studied indivduals, however, were drinking coffee with is much different than taking caffeine pills. A meta-analysis indicates that moderate coffee intakes is associated with decreased cardiovascular risks. There are, however, increased risks for schizophrenia where there is heavy use of coffee. Where there is heavy use of coffee, coffee most likely is not drunk only in mornings.
Difficulties with coffee can arise given coffee is drunk throughout the day. Coffeeinhibits iron absorption in a concentration-dependent fashion. Polyphenols in coffee inhibit iron absorption. A couple of cups of coffee drunk only in the morning would have minimal effects on iron metabolism. Coffee drunk throughout the day could have very adverse effects on iron metabolism.
A search for “iron chelation” and “Parkinson’s” pulls up 460 cites inPubMed. Given iron chelators worked in Parkinson’s disease that would be outstanding. Iron chelation in Parkinson’s disease, however, always seems to be full of promise but there have been no payoffs in terms of treatment. There are many, many ways available to chelate iron. Quercetin is for example a quite effective iron chelator. Polyphenols are quite effective iron chelators. Deferiprone, which an iron chelator, has been tried in Parkinson’s disease. Deferirone is not significantly effective in the treatment of Parkinson’s disease.
Why haven’t iron chelators worked by now in Parkinson’s disease? Perhaps because iron chelators can’t work in Parkinson’s disease. There could be difficulties with iron in Parkinson’s disease but those difficulties could be due dysregulations of iron metabolism rather than due to iron being toxic per se.
Alpha-synuclein aggregates are present in Parkinson’s disease. mRNAs of alpha-synuclein have iron-responsive elements in 5′ untranslated regions. Iron-responsive elements in mRNAs of iron regulated proteins bind iron regulatory proteins (IRP1 and IRP2) affecting stabililites of transcripts of iron regulated proteins. Iron levels can affect alpha-synuclein levels, however, apparently there is an asymmetry as to how iron affects alpha-synuclein levels. Iron chelators decrease alpha-synuclein levels though added iron does not increase alpha-synuclein levels. With alpha-synuclein homeostasis dysregulated via a dysregulated iron metabolism, rather than via high levels of alpha-synuclein per se, alpha-synuclein aggregates could form.
Friedreich’s ataxia is a genetic disease, where there are expansions of GAA trinucleotide repeats in intron 1 of both frataxin alleles. Gait and limb ataxia, dysarthria and loss of lower limb reflexes are clinical features Friedrich’s ataxia.
Mice models of Friedreich’s ataxia have been developed in which the gene for frataxin in is mutated, where the mice exhibit a progressive Friedreich’s ataxia-like pathology. Frataxin binds ironwhich assists in iron-sulfur cluster biogenesis.
Giving mice, with ataxia due to mutations in genes for frataxin, iron from iron carbonyl by gavage three times a day could be a treatment for such an ataxia as iron carbonyl given by gavage three times a day could tightly regulate iron utilization, making iron constantly available thereby making the frataxin protein less required or even redundant. As the iron chelator, desferal decreases expressiot of frataxin, carbonyl iron given by gavage three times a day to mice could also increase expression of the gene for frataxin.
As deferiprone, an iron chelator, can worsen ataxia in patients with Friedreich’s ataxia iron carbonyl given three times a day to humans could be part of a treatment for Friedreich’s ataxia. Prior to any clinical trials in humans, carbonyl iron, given by gavage three times a day from birth to mice with mutated frataxin genes, would have to stop a Friedreich’s ataxia-like pathology from developing and/or treat in mice, a Friedreich’s ataxia-like pathology after mice with mutated frataxin genes develope a Friedreich’s ataxia-like pathology.
Iron increases glutamate secretion by increasing cytosolic aconitase activity. The synthesis of isocitrate by cytosolic aconitase is the the first step in a three step synthesis of glutamate. Glutamate, arising from increases in cytosolic aconitase due to increases in iron, is secreted via the cystine/glutamate antiporter where at the same time cystine is imported into cells increasing glutathione levels in cells.
With iron supplementation in schizophrenia via iron carbonyl taken three times a day there could be increased glutamatergic neurotransmission via increases is secreted glutamate where at the same time there would be increases in cystine in cells and thereby increases in glutathione levels in cells. Supplementation with iron from iron carbonyl could be part the treatment of schizophrenia.