Why would there be a gut-brain axis?

The gut has the highest exposure to the environment of any organ. The gut-brain axis could assist with appropriate environmental regulation of behavior. Prior to 5000 years ago the environments given individuals lived in were basically stable though those such environment varied across the Earth. What individuals placed into their mouths was an accurate reflection of the environments they lived in whereby the gut-brain axis assisted individuals adapting to environments lived in.

What individuals place into their mouths today has very little connection to the locality such individuals are living in. Now individuals place into their mouths junk food, sodas, chemicals, supplements, coffee and tea from very distant places. A main site of actions of junk food, sodas, chemicals, supplements, coffee and tea would be the gut whereby the brain would be affected.

Williams James held that emotions were cognitive readings of bodily states which is going too far. However, basal states of individuals could be very closely tied to the basal states of the environment where the environment can partly but strongly act on individuals via the gut-brain axis. Junk food, sodas, chemicals, supplements, coffee and tea could be affecting the brain quite directly.

An appropriate diet would demand that there be no attempt to escape the gut. As an example supplements formulated for better absorption would not be supplemented. Pharmacokinetics considerations used with pharmaceuticals could be very misleading when used with nutrients and foods generally. Processing of nutrients in the gut could be a key part of nutrients being nutrients. The adverse affects of refined sugars would be an example of ingested substances not being nutrients via a bypassing of carbohydrate processing in the gut.

A fundamental rule of nutrition

Supplements complexed ith and drinks with citric acid added mush be avoided. 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 tricarboxylic acid cycle in the gut. 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 found all too frequently in 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 all to frequently not taken into account is what supplements are bound to. ‘Better absorption’ is the siren call of supplements. Chelated minerals are also avoided.

What have I said that is straightforwardly testable?

600 milligrams of carbonyl iron taken at bedtime can treat a psychosis quickly. The carbonyl iron must be taken away from food, drinks except water and other supplements.200 micrograms Se-methylselenocysteine can quickly treat disorganization in schizophrenia.

600 milligrams of carbonyl iron taken at bedtime and 200 micrograms Se-methylselenocysteine can end treatment resistant schizophrenia.A huge difficulty is that individuals who are not psychotic can feel wretched.

Chelated minerals are not bioavailable in the gut but supplemented minerals must be bioavailable in the gut. Tests could be done on gut enzymes after chelated mineral supplementation. for example with molybdenum glycinate, compared to sodium molybdate..

Individuals taking lithium and anticonvulsant mood stabilizers will have deficiencies in biotin, pantothenic acid, coenzyme A and protein bound iodide. .

Supplement formulations

There are two problems with supplement formulations. First of all sometimes supplements contain adulterants which seems to be a particular problem with herbs and weight loss supplements. I am not going to talk about adulterates in supplements further.

Another difficulty is that supplements very frequently are formulated for high absorption and/or quick absorption. Formulators of supplements assiduously peruse PubMed and then formulate supplements, highly successfully, for high absorption and/or quick absorption. Manufacturing quality is excellent. Individuals manufacturing these supplements are honest and not cutting corners in manufacturing.

The supplements do exactly what is advertised, however, what is advertised, as is often the case, is not what individuals need or is best for individuals. The only difficulty is these supplements, which are manufactured to stringent specifications, can have adverse effects on health.

The simple fact of the matter is than supplements must first be bioavailable in the gut. Yes, supplements must be bioavailable systematically but only after being bioavailable in the gut. This one small detail about supplements changes everything about supplements.

Parkinson’s disease, alpha-synuclein and iron

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.

I wrote a paper on Parkinson’s disease, which addresses iron dysregulation in Parkinson’s disease, that was published in the International Journal of Neuroscience. The title of the paper is A novel treatment strategy to prevent Parkinson’s disease: focus on iron regulatory protein 1 (IRP1)

Se-methylselenocysteine and cancer

Selenium compounds as establishd by in vitro and in vivo experimental models show than that selenium is an effective anticancer agent. Clinical trials, however, have not shown that selenium supplementation in humans is an effective way to prevent cancer.

The transsulfuration pathway metabolizes L-selenomethionine which is the food form of selenium. L-selenomethionine is stored in the body through replacing L-methionine in proteins. Selenium not exiting L- selenomethionine can explain why selenium supplemenation, heretofore, has not been an effective way to prevent cancer in humans.

Tte transsulfuration pathway metabolizes homocysteine. High homocsyteine levels point to the transsulfurtation pathway being dsyregulated. High homocysteine levels are associated with cancer. High homocysteine levels in cancer would then point to the transsulfuration pathway being dysregulated in cancer. With the transsulfuration pathway dysregulated in cancer L-selenomethionine is not metabolized. As L-selenomethione is not metabolized selenium supplementation in the form of L-selenomethionine is not an effective way to prevent cancer in humans.

Se-methylselenocysteine is a very effective anti-cancer agent. Se-methylselenocysteine is a form of selenium that is not metabolized via the transsulfuration pathway but rather is metabolized by kynurenine aminotransferase, which is not an enzyme in the transsulfuration pathway, so formation of selenoproteins from Se-methylselenocysteine is not stopped by dysregulation of the transsulfuration pathway. Se-methylselenocysteine could be an effective anti-cancer agent in experimental models and also in humans.

Choosing an appropriate dosing scheduls is a key to effective selenium supplementation. Supranutrional selenium can increase activity of thioredoxin reductase. There is an end of dosarge effect with selenium apparently due to declines, during the day, in activity of thioredoxin reductase. For the prevention of cancer 100 micrograms of Se-methylselenocysteine taken twice a day would be a more effective selenium supplmentation schedule than 200 micrograms of of selenium from Se-methylselenocysteine taken once a day.

The cerebellum and schizophrenia

The cerebellum sits at the bottom back of the brain. A meta-analysis indicates there are structural and functional abnormalties in the cerebellum in schizophrenia.

Intraellular calcium homeostasis is regulated by taurine. Taurine is synthesized from L-cysteine wihch is synthesized from homocsysteine via the transsulfuration pathway.

Hidden oosteomalacia due to dysregulation of intracellular calcium homeostasis arising from low levels of taurine stemming from dysregulation of the transsulfuration pathway .could be wide spread. In individuals with schizohpenia there could be hidden osteomalacia that do not show as back pain but could affect necks compressing cerebellums leading to severe psychological effects. Calcium blood levels could be low normal or slightly low.

Some x-ray studies of bones is the neck region are called for in schizophrenia. If cerebellums are being compressed by a hidden osteomalacia treatmens for a range of psychological symptoms in schizophrenia could be much, much different. Taurine, vitamin D, vitamin K and calcium carbonate could treat the hidden osteomalicia addressing structural and functional brain abnormalties in schizophrenia. Bone mineral densities are lower in older indivduals with schizophrenia compared to indivduals without schizophrenia. Early diagnosis would be a key.

With cerebellums compressed there could negative symptoms of schizohrenia. Negative symptoms are are deficit symptoms where such deficits could be due to deficits in the ability of the cerebellum to function due to being compressed from hidden osteomalacia.