A theory of supplements

First of all any supplements taken must be safe to take. There should be lots of evidence that the supplements taken are safe to take. Secondly supplements taken must be tied to a hypothesis. I hold that the citric acid cycle is dysregulated in schizophrenia and a lot of other illnesses. Aconitase 1, an enzyme in the citric acid cycle, is dysregulated in schizophrenia. Individuals must also realize that supplements can be very dangerous. So I strongly recommend that individuals take no supplements except the recommended supplements. Also there should be definite and fast results when taking supplements. One should know whether one is going in the correct direction.

What are these very effective treatments for schizophrenia that mental health professionals are pushing? Clozapine, which has five black box warnings and horrendous side-effects, terrible drugs for tardive dyskinesia, depot injections and frequently  multiple antipsychotics. In other words the treatments shown to be totally lacking by the last 50 years are the treatment  that individuals with schizophrenia just have no insight about. I do think very frequently individuals with schizophrenia must take low dosages of antipsychotics.

The supplements suggested on the Treatment page should be safe to take given anemia panels and thyroid panels are obtained.

 

 

 

A couple of perfectly terrible drugs which are a treatment advance for individuals with schizophrenia

Deutetrabenazine and valbenazine are prescribed to stop tardive dyskinesia. Deutetrabenazine and valbenazine  inhibit vesicular monoamine transporter 2 (VMAT2). VMAT2 transports neurotransmitters such as dopamine, norepinephrine,  serotonin, and histamine from the cytosol of cells into synaptic vesicles from which neurotransmitters can then be released into synapses.   VMAT2  is also necessary for the vesicular release of the neurotransmitter, GABA, into synapses. With VMAT2 inhibited a wide range of neurotransmitters needed for mood and cognition cannot be released into synapses so can not be effective. Deutetrabenazine  and valbenazine have the ring of  chemical lobotomies. Deutetrabenazine  and valbenazine would also in probability be taken with antipsychotics.   Mental health professionals now hold deutetrabenazine  and valbenazine are treatment advance for individuals with schizophrenia. Deutetrabenazine  and valbenazine can cause Parkinsonism but there are anti-cholinergics for Parkinsonism  where individuals in all probability would still be on antipsychotics. 

The correct answer in terms of what to do about tardive dyskinesia is to from the start use the very lowest effective dosage of an antipychotic  so individuals with major mental illnesses are safe for themselves and others but still could be strange, use 2nd  generation antipsychotics which are associated with lower incidences of tardive dyskinesia and never take or prescribe more than a single antipsychotic at a time. In Sweden 25% of patients dispensed antipsychotic drugs receive a combination of two or more antipsychotic drugs. In Asia 32% of patients with schizophrenia  get two or more  antipsychotics while in North America 16% get two or more antipsychotics  There are only some many dopamine D2 receptors to fill. Prescribing more than one antipsychotic at a time is ludicrous.

 

A new idea on how antipsychotics work

The notion that anti-psychotics work by basically only adjusting dopamine levels has gone nowhere and will go nowhere. If just adjusting dopamine levels was all that was needed to treat schizophrenia there would be a cure for schizophrenia by now. Just  adjusting dopamine levels as the mode of action of anti-psychotics has as a correlate that individuals with schizophrenia are too full of pleasure causing chemicals and those pleasure causing chemicals must be dialed way, way down in schizophrenia which is ludicrous.

I think the citric acid cycle is dysregulated in schizophrenia due to low activity of aconitase 1 whereby there are various difficulties synthesizing amino acids such as glutamate. With shortages of amino acids such as glutamate the brain has difficulties synthesizing proteins. If individuals can’t synthesize proteins not trying to synthesize proteins could possess  modest  advantages.  Psychostimulants can increase protein synthesis. Dopamine antagonists could basically be turning down protein synthesis. A car with a flat tire had best be driven slowly. If the brain can not synthesize needed glutamate there are modest advantages to not trying to synthesize protein which is where dopamine antagonists come in terms of the  treatment of schizophrenia.

Central dogma of biology not applicable to epigenetics

The Central Dogma of Biology – Information passes from DNA to proteins via RNA, but proteins cannot pass the information back to DNA.

Changes in enzyme activities can result in various epigenetic changes so while DNA sequences are  not altered by enzyme activities and/or enzyme levels transcription and/or translation of genes can be altered by changes in enzyme activities and enzyme levels by genes becoming methylated. Epigenetics is not subject to the Central Dogma whereby enzyme activities and enzyme levels can affect methylation of gametes.  There still has to be a mechanism whereby embryos are not completely stripped of methyl marks for there to be transgenerational epigenetic inheritance. Dysregulation of TET enzymes that demethylate DNA in embryos could leave a path open for transgenerational epigenetic inheritances.

 

Adrenodoxin and systematic epigenetic changes leading to transgenerational epigenetic inheritances

The question arises as to what kinds of epigenetic changes could affect  individuals systematically but also affect gametes whereby transgenerational inheritance  would be feasible.  Adrenodoxin is an iron-sulfur protein that is essential for the synthesis of various steroid hormones. A difficulty in synthesizing iron-sulfur proteins could result in low levels of adrenodoxin. Adrenodoxin is a co-factor for cytochrome P450 enzymes where some P450 enzymes affect the synthesis of estrogen.  Decreases in adrenodoxin levels would decrease activity of P450 enzymes which could increase methylation of P450 genes. With genes not being transcribed due to decreased activity of enzymes transcription factors are not blocking genes from becoming hypermethylated. Decreased activity of enzymes could increase methylation of genes of such enzymes on a use it or loose it principle. As adrenodoxin is demanded  for the synthesis of steroid hormones dysregulation of adrenodoxin could give rise to various phenotypes where epigenetic changes in parents are inherited by children due to concomitant alteration of gametes. Adrenodoxin is highly expressed in male and female tissues.  Various enzymes that demethylate DNA in embryos would also have to be dysregulated. The devil is always in the details and the details are not worked out.

If there is not transgenerational epigenetic inheritances in humans evolution missed a very effective way to maintain cultural advances while at the same time also not locking in the biological basis for such cultural advances leaving room for further cultural advances.  Transgenerational epigenetic inheritances fit all of  human history.  ‘Cultural osmosis’, the leading theory of cultural transmission is a very, very foggy notion of how cultural transmission works and will always be a very, very foggy notion of how cultural transmission works.

Transgenerational epigenetic inheritance

Transgenerational epigenetic inheritance is the transmission of epigenetic marks from parent to child. Transgenerational epigenetic inheritance does not alter DNA of genes. To be at all useful in humans in terms of evolutionary fitness  epigenetic alterations on which transgenerational epigenetic inheritance is founded would have to be systematic    Both the wider organism and sperm cells and egg cells would have to be affected together by a class of epigenetic alterations.  Many illnesses that are classed as brain diseases such as autism, major depression and schizophrenia would have to have systematic effects which in fact these illnesses do have. Parents of children with autism, for example,  very frequently state that their children are systematically ill  and that all physical complaints of their children have to be addressed. Individuals with schizophrenia have much reduced life spans.   The heritability of  Alzheimer’s disease ranges from 49% to 79%. Alzheimer’s is classified as a brain disease but individuals with Alzheimer’s disease are ill in about every way imaginable.

Transgenerational epigenetic inheritance where stuff just happens to gametes and that stuff can be transgenerationally passed along would be totally useless in terms of human evolutionary fitness. Phenotypes are  selected by evolution. There are cultural traits which are very difficult to alter but which can be altered. If such cultural traits had a biological basis inheritance of such cultural traits would be feasible. Holding that there is a biological bases for cultural traits is usually viewed as racist, however, given the biological basis of cultural such traits depends on transgenerational epigenetic inheritances then though there are  biological bases for cultural traits such cultural traits are mutable over the course of generations rather than basically immutable due to such cultural traits being hardwired into DNA.

Any familiarity with history at all would disclose that women in the West are acting much differently than women acted three hundred years ago. Women in the elite classes three hundred years did not all  hold all was oppression and all secretly long to be scientists, head of businesses and heads governments but rather held there were various terrific advantages to being women of the elite classes in 1720.  The biology of women made being women of 1720, at least of the elite classes, very attractive to women in 1720, however, as is also clear cultural traits of women have not been immutable over the last 300 years. With transgenerational epigenetic inheritance various cultural traits of women can be both biologically based and mutable. Women as androgynous men will never work for women wholesale, DNA of women will always be different than the DNA of men, however, women as lawyers, women as doctors, women in business etc can and has worked for women.

What distinguishes  humans from other animal species could be that transgenerational epigenetic inheritances are very prevalent in humans.

 

A new disease class – Epigenetic Disorders

There are infectious diseases subdivided into bacterial and viral diseases, there is cancer where there are many sorts of cancer, there is heart disease, lung disorders  etc. There could be a new disease class. There could  be epigenetic disorders where there is common origin for a wide range of epigenetic disorders. With epigenetic mechanisms  dysregulated many different diseases can arise as there are many different ways genes and histones can become inappropriately methylated.  My idea is that a dysregulation of aconitase 1 can dysregulate iron metabolism and decrease 2-oxogularate synthesis which will in turn dysregulate TET enzymes, which demethylate DNA,  and dysregulate Jumonji domain-containing proteins, which demethylate histones.   Dysregulation of  TET enzymes and dysregulation of Jumonji domain-containing proteins  can play out many different ways in terms of inappropriate DNA methylation and inappropriate histone methylation whereby many different diseases can arise. Though many different diseases can arise from dysregulations of aconitase 1, iron metabolism and 2-oxoglutarate synthesis prevention of a range of illnesses could be achieved by the same treatment. For example, a treatment than prevents schizophrenia could also prevent Alzheimer’s disease and Parkinson’s disease. The Treatment presented in the Treatment section is not ready for home use, however, a Moon shot would not be necessary to get the treatment to a state where family doctors could prescribe a treatment which would prevent a range of chronic illnesses from schizophrenia, to Alzheimer’s disease, to Parkinson’s disease. What is needed is a launch ten weather balloons into the high atmosphere then collect and analyze data kind of effort.