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.
Increasing levels of free antioxidants via supplmentation could be much worse than useless. Before iron can be absorbed iron must be reduced from Fe3+ to Fe2+. Antioxidants like vitamin C, vitamin E , beta-carotene and quercetin could one way or other promote the reduction of Fe3+ to Fe2+ in the gastrointestinal tract which would increase absorption. The goal, however, is to delay iron absorption as long as feasible.
There is oxidant stress in lots of illnesses but this could be due to dysregulation of selenoproteins and dysregulation of iron metabolism which would not be fixed by increasing levels of free antioxidants with supplemental vitamin C, vitamin E , beta-carotene, quercetin etc.
Supplementing with free antioxidants could be associated with very subtle but serious mineral dysregulations which would basically be undiagnosable.
Iron deficiency may alter dopaminergic transmission in the brain. This study investigated whether iron metabolism is associated with negative symptoms in patients with first-episode psychosis. The study enrolled 121 patients with first-episode schizophrenia spectrum disorder, whose duration of treatment was 2 months or less. Negative symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) and Clinician-Rated Dimensions of Psychosis Symptom Severity (Dimensional) scale of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Prominent negative symptoms were defined as moderate or severe negative symptoms on the Dimensional scale of the DSM-5. Iron deficiency was defined as a serum ferritin ≤ 20 ng/mL. Patients with iron deficiency were significantly more likely to have prominent negative symptoms (45.2 vs. 22.2%; p = 0.014) and a higher PANSS negative symptoms score (p = 0.046) than those with normal ferritin levels. Patients with prominent negative symptoms had significantly lower ferritin levels (p = 0.025). The significance of these results remained after controlling for the duration of illness and other confounding variables. Our finding of an independent association between iron deficiency and negative symptoms in patients at the very early stage of illness implies that iron dysregulation has an effect on negative symptoms in patients with schizophrenia. The possibility of therapeutic intervention with iron should be further investigated.
I have been argunig in this blog that there are high IRP1 levels in schizophrenia due to difficulties in iron-sulfur cluster formation whereby cytosolic aconitase switches to IRP1. As ferritin mRNA has an iron response element in the 5′ untranslated region high levels of IRP1 will decrease ferritin levels.
High levels of homocysteine are associated with increased risks for a number of illnesses. Hyperhomocysteinemia is a risk factor far osteoporosis, Alzheimer’s disease, Parkinson’s disease, stroke, cardiovascular disease, cancer, aortic aneurysm, hypothyroidism and end renal stage disease among other illnesses. I would add schizophrenia and bipolar disorder.
I have been arguing that high homocysteine levels point to the transsulfuration pathway being dysregulated. That there are so many illnesses associated with high homocysteine combined with the ineffectiveness of folic acid in reducing risk ratios for various illnesses point to high homocysteine levels being a proxy for other dysregulated biological processes. I have been arguing than high homocysteine levels are associated with increased risks for epigenetic dysregulations.
Folic acid supplementation, which reduces homocysteine levels, does not decrease risk ratios for the various illnesses that high homocysteine levels are associated with, for example, cardiovascular illnesses. Folic acid is ineffective as homocysteine must be metabolized through the transsulfuration pathway. Increasing remethylation of homocysteine to L-methionine does not fix the transsulfuration pathway leaving folic acid ineffective in decreasing risk ratios for various illnesses. Very unfortunately increasing levels of L-cysteine through supplementation with N-acetyl-L-cysteine, cysteine, cystine or lipoic acid also does not work where such supplementation can be very dangerous.
Elevated circulating levelsof branched-chain amino acids have been associated with insulin resistance where decreased degradation of branched-chain amino acids could be what is leading to elevated circulating levels of branched-chain amino acids. Metabolic syndrome is associated with insulin resistance.
Insulin resistance is present in 52% of individuals with bipolar disorder. Insulin resistance develops is brains of individuals with Alzheimer’s disease. In China in individuals with schizophrenia the prevalence of insulin resistance is 37.2% Both disease processes and drugs used to treat these illnesses could increase insulin resistance in theses illnesses. A commonality among these illnesses could be dysregulation of the sodium-dependent multivitamin transporter both by disease processes and drugs used to treat these illnesses.
The sodium-dependent multivitamin transporter transports both biotin and pantothenate. Pantothenate is needed to synthesize coenzyme A which is closely tied to the actions of biotin-dependent enzymes. Biotinylationof the sodium-dependent transporter reduces transport by the sodium-dependent multivitamin transporter. High levels of biotin could decrease transport of pantothenate by the sodium-dependent multivitamin transporter. A combination of pantothenic acid and biotin where 500 mg. of pantothenic acid is taken once a day away from supplemental biotin and 5 mg of biotin is taken three times a day could word work better in controlling hyperglycemia than biotin alone.
There are low levels of vitamin D in schizophrenia, bipolar disorder, Alzheimer’s disease and Parkinson’s disease due to dysregulation of taurine synthesis in these illnesses attendant on dysregulation of the transsulfuration pathway which synthesizes L-cysteine from which taurine is synthesized.
Supplementation with vitamin D in these illnesses heretofore has not helped much as difficulties in fat absorption have not been addressed. Taurine, which regulates calcium homeostasis besides aiding in fat absorption, taurine would be taken with vitamin D, vitamin K and calcium carbonate to address low levels of vitamin D where there are chronic illnesses. Vitamin K is also a fat soluble vitamin whose abosoprtion could be impaired by low levels of taurine.
Beta-oxidation is up-regulated in schizophrenia. Malonyl-CoA inhibits beta-oxidation. Malonyl-CoA is synthesized by acetyl-CoA carboxylasewhich is a biotin-dependent enzyme. With deficiencies in biotin due to dysregulation of the SMVT malonyl-CoA will not be synthesized which will lead to low levels of malonyl-CoA and increased beta-oxidation which is what is seen in schizophrenia.
Levels of arachidonic acid (AA), which is synthesized from linoleic acid and docosahexaenoic acid (DHA) which is synthesized from alpha linoelic acid are significantly lower (P < 0.001) in drug-naive patients with schizophrenia compared to controls. See also Reddy et al. Linoleic acid and alpha linoelic are the two essential fatty acids. Essential fatty acids must be obtained from the diet. Essential fatty acids must also be absorbed to be effective.
With difficulties in fat absorption due to low levels of taurine, which is required for synthesis of various taurine conjugated bile acids, absorption of essential fatty acids would be impaired which would lead to low levels of arachidonic acid and low levels of docosahexaenoic acid which is what is seen in schizophrenia.
Taurineis synthesized from L-cysteine. L-cysteine is synthesized by the transsulfuration pathway. With dysregulation of the transsulfuration pathway in schizophrenia there will be low levels of L-cysteine and low levels of taurine which will lead to low levels of various omega-6 and omega-3 fatty acids in schizophrenia.
With a dysregulation of the transsulfuration pathway(homocysteine to L-cysteine) sufficient L-cysteine for iron-sulfur cluster formation is not synthesized. Sulfur for iron-sulfur cluster biogenesis is derived from L-cysteine. Supplemental iron increases levels of iron-sulfur proteins. Supplemental iron can partly compensate for dysregulation of the transsulfuration pathway in schizophrenia. Selenomethionine, the food form of selenium is metabolized by enzymes in the transsulfuration pathway. Metabolism off Se-methylselenocysteine by-passes the transsulfuration pathway whereby Se-methylselenocysteine can provide bioavailable selenium for individuals with schizophrenia. Taurine is synthesized from L-cysteine. With L-cysteine not synthesized appropriately taurine will not be synthesized at appropriate levels. Taurine is needed to form various bile acids, With low levels of taurine there will not be sufficient taurine conjugated bile acids. Fat absorption requires bile acids. With low levels of taurine due to low levels of L-cysteine fat absorption will be impaired. Supplemental taurine and supplemental essential fatty acids will compensate for low levels of taurine due to low levels of L-cysteine which are in turn due to dysregulation of the transsulfuration pathway. Taurine by sparing L-cysteine will also increase levels of L-cysteine.
An Important Warning: No supplements that contain L-cysteine or L-methionine should be supplemented. And no supplements that reduce cystine to L-cysteine, such as lipoic acid, should be supplemented. See the Treatment page for supplements that can be of assistance in the treatment of schizophrenia.