An article I wrote on the etiology of schizophrenia, Treatment-resistant schizophrenia: focus on the transsulfuration pathway, was published in Reviews in the Neurosciences. Treatment resistant schizophrenia is not a different kind of schizophrenia rather treatment resistant schizophrenia is a very severe schizophrenia. All schizophrenia is severe. Ahmed Moustafa gave terrific comments and assisted in getting the article into publishable form. The treatment section of the paper is out of date.
Everything should be made as simple as possible, but not simpler. – Albert Einstein.
The proposed treatment has not been tested in clinical trials.
d Most importantly do not take any supplement that could raise L-cysteine levels except taurine which could spare cysteine. Second of all avoid the too be avoided supplements. Third of all cut out sodas, tea including herbal teas. Supplemental iron from carbonyl iron is an antipsychotic. Anemia panels must be obtained. Se-methylselenocysteine will address disorganization. Taurine is taken to assist with absorption of fatty acids, spare cysteine and regulate calcium and sodium metabolism. Taurine is required for calcium homeostasis. Vitamin K and vitamin D are too required for calcium homeostasis. With calcium homeostasis dysregulated by deficiences of taurine, vitamin K and vitamin D there can be hidden osteomalacias that affect bones in the back of the head which result in negative symptoms via cerebellums being compressed. Pantothenic acid and biotin are supplemented. The SMVT, which transports pantothenate and biotin, is dysregulated. See the page on Bipolar Depression. Biotin-dependent enzymes degrade branched-chain amino acids. Free-form branched-chain amino acids are supplementd. L-glutamine is supplemented . 3-methylcrotonyl-CoA carboxylase (holo-MCC) and propionyl-CoA carboxylase which metabolize branched-chain amino acids, which are biotinylated enzymes are particularly affected by biotin deficiencies (Eng et al., 2013). Carbonyl phosphate synthase requires bicarbonate. Due to difficulties in bicarbonate homeostasis carbonyl phosphate synthase is dysregulated. Carbonyl phosphate is synthesized from glutamine. Free form L-glutamine is supplemented. L-glutamine supplementation requires free branched-chain amino acids also be supplemented, .Evening primrose oil is supplemented. Gamma-linolenic acid present in evening primrose oil can decrease inflammation. EPA also can decrease inflammation. For depression a combination of EPA + DHA where EPA is around 65% and the DHA is aroutd 35% is effective. EPA has to approximately balance in milligrams gamma-linolenic oil in evening primrose oil. Taurine will also assist in the absorption evening primrose oil and EPA + DHA. The SMVT also transports iodine. Iodine is supplemented.
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 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. Taurine will assist in the absorption of fatty acids. The SMVT is dysregulated, likely due to dysregulated sodium homeostasis attendant on dysregulation of taurine. Dysregulation of the SMVT calls for supplementation with biotin, pantothenic acid, evening primrose oil, EPA + DHA, and taurine. Biotin-dependent enzymes require bicarbonate. Bicarbonate is synthesized from carbon dioxide and water. Supplements would be taken with a large glass of water to assist with bicarbonate synthesis.
Approximately 600 milligrams of iron from carbonyl iron is taken once a day at bedtime. at least 6-7 hours away from the last cup of coffee of the day given coffee is drunk. There are way too many interactions of iron with drinks, for example, coffee, and supplements for iron to be taken more than once a day. Changes in iron levels in the gastrointestinal tract due to drinks, and/or supplements can be huge difficulties so iron from carbonyl iron must be taken so there are minimal interactions of iron in the gastrointestinal tract with drinks, for and/or supplements. Iron from carbonyl iron is slowly absorbed from the gastrointestinal tract which is highly beneficial. Carbonyl iron is a very safe form of iron. Supplemented carbonyl iron must, of course, be carbonyl iron that is marketed as a supplement. Anemia panels must be obtained to insure that iron levels are not high.
200 micrograms of selenium from Se-methylselenocysteine is taken once a day.
1000 mg. of taurine is taken 3 times a day. Taurine must be taken on an empty stomach for better absorption.
5 milligrams of biotin is taken three times durnig the day away from pantothenic acid. 250 millgrams of pantothenic acid is taken once a day at bedtime away from biotin. Biotin and pantothenic acid are not take at the same time. Pantothenic kinase is the rate limiting step in the synthesis of coenzyme A whereby extra pantothenate can increases synthesis of coenzyme A. Biotin must apparently be available in the gut so sublingual biotin is not taken. See the page on bipolar disorder on how biotin metabolism can be dysregulated. 50 milligrams of thiamine is taken twice a day. The pyruvate dehydogenase complex and alpha keto-glutarate complex require thiamine. Biotin is needed for synthesis of non-essential fatty acids and metabolism of branched-chain amino acids.
Approximately 3 grams of branched-chain amino acids in a 2:1:1 formulation are taken 3-4 times a day. Biotin via methylcrotonyl CoA carboxylase (184.108.40.206) and and propionyl-CoA carboxylase (220.127.116.11) is involved in the degradation of branched-chain amino acids. Apparently degradation of branched-chain amino acids is dysregulated.
Supplemental branched-chain amino acids and L-glutamien reduces fatigue and lifts mood when taken with pantothenic acid and biotin. Pantothenic acid and biotin basically do not work when not taken with branched-chain amino acids and glutamine. Supplemental L-glutamine without branched-chain amino acids to support protein synthesis can have negative effects
Approximately 1000 micrograms of iodine from kelp is taken once a day.
2000 IU’s of vtamin D in capsules or as tablets is taken once a day. Approximately 300 mcg of vitamin K2 MK-7 in capsules is taken 4 times a day. Vitamin K is involved in calcium utlization. Vitamin K MK-7 is much better absorbed than other forms of vitamin vitamin K. Vitamin K MK-7 is the form of vitamin K supplemented. 1000 mg of taurine is taken four times a day. Taurine is involved in calcium homeostasis. 500 milligrams of calcium from calcium hydroxyapatite is is taken twice a day. Taurine is taken on an empty stomach for better absorption.
Around 500 milligrams of EPA and 250 milligrams of DHA is taken four times a day. Evening primrose oli with approximately 500 millgrams of gamma-linolenic oil is taken 4 times a day. Pantothenic kinase is the rate limiting step in the synthesis of coenzyme A whereby extra pantothenate can increases synthesis of coenzyme A. Dosages can be adjusted.
Blood pressure must be monitored. Individuals with low blood pressure must watch their blood pressure carefully as taurine especially when taken on an empty stomach can decrease blood pressure noticebly. Metabolic panels, anemia panels, thyroid tests and CBCs must be obtained.
The treatment could also be effective in Alzheimer’s disease. There are a lot of biological commonalities between schizophrenia and Alzheimer’s disease. See my papers Treatment-resistant schizophrenia: focus on the transsulfuration pathway and A disease-modifying treatment for Alzheimer’s disease: focus on the trans-sulfuration pathway. Indivduals could question whether taking iron from carbonyl iron for Alzheimer’s disease is appropriate. A meta-analysis, however, indicates that serum iron levels are significantly lower in AD patients than in healthy controls. Another meta-analysis also indicates that serum iron is significantly lower in patients with Alzheimer’s disease than in healthy controls. Iron from carbonyl iron is regulating aconitase 1 in the gut, the citric acid cycle in the gut and iron metabolism in the gut. As iron levels are only regulated by absorption and excretion regulating iron levels in the gut can affect iron metabolism systematically.
Iron must be iron from carbonyl iron as carbonyl iron stays in the gut for an extended time. Iron sulfate is avoided as iron sulfate is quickly absorbed. Iron bisglycinate is avoided as iron from iron bisglycinate is apparently not available in the gut. The difficulty with heme iron polypeptide is that the iron in heme iron polypeptide may not have much of an effect on iron metabolism in the gut. Supplementation with heme iron polypeptide is avoided.
Feosol carbonyl iron, 45 milligams of iron per tablet, is a brand of carbonyl iron that is effective.
Supplements should never be formulated for better absorption. Supplements must be bioavailable in the gut as well as systematically for supplements to be effective..
Taurocholic acid, derived from taurine, is a bile acid which aids in fat absorption. Supplemental taurine upregulates cystathionine beta-synthase and cystathionine gamma-lyase which are the two enzymes in the transsulfuraiton pathway (Sun et al., 2016). Supplemental taurine reduces homocysteine levels (Ahn, 2009) likely due to the upregulation of the transsulfuration pathway by taurine. Taurine reduces cholesterol levels in animals (Guo et al., 2017; Chen et al., 2012). Taurine also has an anti-obesity effect. Taurine deficiencies result in premature aging. Taurine is negatively associated with ischemic heart disease. Taurine ameliorates diabetes. The Observed Safe Level for supplementation with L-taurine is 3 grams a day (Shao and Hathcock, 2008). Supplemental taurine can by aiding fat absorption and calcium homeostasis positively affect brain function. 300 micrograms of vitamin K2 (MK-7) is taken twice a day. Vitamin K is fat soluble vitamin whose absorption could be impaired by low levels of taurine. Vitamin D and vitamin K should be taken with food and/or evening primrose oil and EPA + DHA for better absorption.
Decreased levels of biotin would lead to increased beta-oxidation as decreased levels of biotin would decrease levels of malonyl-CoA which inhibits beta-oxidation. Increased beta-oxidation sounds terrific. Rev up metabolism, increase energy, burn fats, loose weight, live to the fullest. However increased beta-oxidation due to decreases in biotin transport would also lead to decreases in fatty acid elongation which requires malonyl-CoA, leading to serious difficulties. See the page on bipolar disorder as to why there could be difficulties in biotin transport.
With deficiencies in taurine fat absorption is impaired and vitamin D and vitamin K are not absorbed from the diet. Supplemental vitamin D and supplemental vitamin K are required. Vitamin D will help with calcium absorption and and vitamin K wils assist with calcium utilization. Supplemental vitamin D and supplemental vitamin K are not helpful without supplemental taurine.
Surprisingly iodine is of assistance. Thyroid tests can be apparesnly be normal but still supplemental iodine is required. There is no need to take thyroid hormones. Supplemental iodine addresses an intense sadness. Iodine works quickly. The sodium-dependent multivitamin transporter (SMVT) transports iodide. Transports of iodide is apparently a very important function of the SMVT. There is another transporter of iodide, the sodium/iodide cotransporter, (SLC5A5) which is largely expressed in the thyroid. The SMVT is expressed in the gastrointestinal tract. The SMVT is apparently not a spare in terms of the transport of iodine. Iodine homeostasis is very important in terms of the actions of the thyroid gland Even with normal levels of thyroid hormones there can be thyroid associated depressions due to upset of iodide homeostasis.
Supranutrional selenium can increase activity of thioredoxin reductase. Thiordoxin reductase is required for activity of ribnucleotide reductase, the rate lmiting enzyme in DNA synthesis. A difficulty with only 200 micrograms of selenium from methylselenocysteine a day is that there is an end of dosage effect apparently due to declines in activity of thioredoxin reductase. On a complete program 200 micrograms of selenium from Se-methylselenocysteine could be taken tvice a day. Se-methylselenocysteineis is an effective anti-cancer agent.
Below are some comments on supplements that could also be helpful and also some comments on what supplements must be avoided.
Free antioxidant supplements must be avoided. A whole lot can go askew given free antioxidant supplements are taken. Iron in the gastrointestinal tract will become dysregulated, With iron dysregulated in the gastrointestinal tract aconitase 1 in the gastrointestinal tract will become dysregulated. With aconitase 1 dysregulated in the gastrointestinal tract the TCA cycle in the gastrointestinal tract will become dysregulated. With the TCA cycle is the gastrointestinal tract dysregulated individuals will not be able to tolerate B vitamins used by the TCA cycle.
EPA and gamma-linolenic oil in each dosage of supplemental fatty acids have to be approximately evenly balanced in terms of milligrams. Gamma-linolenic oil from evening primrose oil and eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) are taken four times a day. Cyclooxygenases and lipoxygenases can act on DGLA, EPA and/or arachidonic acid. DGLA is synthesized from gamma-linolenic acid which is in evening primlrose oil while EPA is in fish oils. With dysregulation of fatty acid absorption more or less second by second supply of DGLA and EPA is dysregulated. Eicosanoid homeostasis is upset when DGLA and EPA, which competitively inhibit production of inflammatory eicosanoids synthesized from arachidonic acid acid, are not available more or less second by second. Supplementation of gamma-linolenic oil from evening primrose oil and EPA + DHA sets up continuous supplies of DGLA and EPA in bodies.
Softgels are highly effective increasing absorption via active ingredients of such softgels not being available in gastrointestinal tracts of individuals. Any softgels taken have to be bitten on though supplementing with softgels is avoided given there are capsule or tablet alternatives. Supplemental vitamin vitamin D3 MK-7 and supplemental vitamn K MK-7 as capsules or tablets are preferred orrather than as softgels. Supplmental coenzyme Q10 in capsules is preferred to supplemental coenzyme Q10 in softgels.
EPA + DHA softgels and evening primrose supplements are bitten on with contents then swallowed with the softgels then thrown away. Softegls can greatly increase absorption howver, fatty acids from fatty acid supplements have to be available in gastrointestinal tracts so softgels are not swallowed. EPA + DHA supplements are very frequently enteric-coated softgels. Enteric coated softgels, given fatty acids are delivered to individuals via such softgels, most definitely have to be bitten on, the contents swallowed and the softgels thrown away.
Enteric coated and/or swallowed EPA + DHA softgels have contributed to very mixed results of supplemental EPA + DHA in clinical trials. Also gamma-linolenic oil in evening primrose oil has to be taken in approximately equal milligrams to EPA each dosage. A point about eicosanoids that has to be taken into account is that eicosanoids have very short half-lives so supplemental EPA + DHA and evening primrose have to be taken three or four times a day. EPA + DHA and gamma-linolenic from supplements oil gets absorbed and have to replaced in the gastrointestinal tract by subsequent dosages of EPA + DHA and gamma-linolenic oil. Another point is that MDs have to take EPA + DHA and evening primrose before clinical trials begin to make sure the balances between EPA + DHA and gamma linoleic oil from evening primrose oil are correct. A balance that is incorrect between EPA + DHA and gamma linoleic oil from evening primrose oil can result in terrific difficulties. MDs will most definitely notice an incorrect balance between EPA + DHA and gamma linoleic oil from evening primrose oil that MDs supplement prior to clinical trials. Of course, balances of EPA + DHA and gamma linoleic oil from evening primrose used in clinical trials have to be based on scientific research, however, given balances selected have adverse effects on MDs who take such EPA + DHA and gamma linoleic oil from evening primrose in planning clinical trials, which could be very adverse effects, such balances are not going to be effective in clinical trials. In all probability reactions to supplemental EPA + DHA and gamma linoleic oil from evening primrose are not illness dependent. EPA + DHA are safer than EPA + DHA and gamma linoleic oil but EPA + DHA have only modest effects in alleviating major depressive disorder. EPA + DHA and gamma linoleic oil from evening primrose oil can have quick effects so MDs who take EPA + DHA and gamma linoleic oil in planning clinical trials could notice adverse effects in 2 or 3 days upon starting such supplements given selected balances are incorrect. A balance of EPA + DHA and gamma linoleic oil from evening primrose oil that has adverse effects short term is not going to be effective long term so keeping with a balance that has adverse effects short term until such a balance is effective is less than pointless. As MDs have suspected inflammation can result in very large difficulties for individuals with mental illnesses, for example, major depressive disorder, bipolar depression and depression associated with schizophrenia.
A difficulty with polyphenols is that polyphenols complex with iron making iron unavailable in the gut. Another difficulty with polyphenols is that polyphenols can increase beta-oxidation which can result in difficulties if there are problems in fat absorption and fatty acid metabolism.
Polyphenols in sodas, coffee and tea including herbal tea can adversely affect absorption of iron. Caffeine is apparently not the culprit. Polyphenols in polyphenol supplements could be highly available and are particularly avoided. Flavonoids are polyphenols. Flavonoid supplements are avoided. Getting off caffeine by switching to non-caffeinated sodas and herbal teas is a disastrous move. Coffee and tea are huge interactions. Iron from carboyl iron can only be taken 6-7 hours after the last cup of coffee for the day
Seltzer water which lists only carbonated water and zip else on the ingredients label could be OK to purchase and drink. Labels must be looked at before Seltzer water is purchased. Seltzer water can not contain any natural flavors, be ‘essenced’ or contain any citric acid. Club Soda is avoided. Club Soda contains sodium citrate.
Getting of caffeine by switching to non-caffeintated sodas with citric acid is a disastrous move. Carbonated waters frequently add added citric acid and these carbonated waters are avoided. Perrier ‘carbonated water’ now frequently contains citric acid and natural flavors and is avoided.
Sodas, for example, Mountain Dew, as this advertisement shows are frequently associated with goofyness where the goofyneness could be due to polyphenols and/or citric acid in the sodas adversely affecting iron metabolism in the gut. Citric acid drinks really do befuddle thinking. Someone might say, ‘Individuals would have to consistently take substances that befuddle thinking. Is that even possible?’ I cite the terrible narcotics problem throughout the world and rest the case.
That citric acid drinks can befuddle individuals can be tested in a very straightforward way. An only citric acid and water drink with 4 grams of food grade citric acid drunk 4 times a day for 5 days would test whether citric acid befuddles individuals.
4 grams of citrate is in a 600 milligram tablet of calcium citrate. Calcium from calcium calcium citrate is avoided. The citrate in the calcium citrate could bind to iron in the gastrointestinal tract making iron unavailable in the gastrointestinal tract with very negative consequences. A point about calcium supplements is that the wrong calcium supplement is worse than no calcium supplement at all. Taurine regulates calcium transport.
Polyphenols increase beta-oxidation. This can be extremely problematical given there are difficulties in fat absorption and fatty acid synthesis. I have been emphasizing how polyphenols decrease iron absorption but increases in beta-oxidation due to polyphenols where those increases are unsupportable due to difficulties in fat absorption and fat metabolism could also lead to serious difficulties.
Clearly no general argument is being made that beta-oxidation is ‘bad’ and fatty acid synthesis is ‘good’. All depends on what illnesses individuals have and metabolic states that individuals are in.
Coffee drinking is very widespread. Here is a coffee advertisement from another planet.
Very surprisingly taking large dosages of vitamin C must be avoided. Vitamin C increases iron absorption at least intially but long term ascorbic acid can downregulate iron absorption by down-regulating iron independent and iron dependent Nramp2 (DMT1) and duodenal cytochrome B (Dcytb) expression. Vitamin C will also decrease copper absorption. Megadosages of vitamin C are definitely to be avoided. Vitamin C can be very surprising. Initially large dosages of vitamin C appear to have very positive effects but long term those postive effects are lost. First impressions of megadosages of vitamin C are incorrect impressions.
Both iron absorption enhancers and iron absorption inhibitors can have very undesirable effects. A goal is for iron to be available both in the gastrointestinal tract and available systematically whereby iron can not be complexed with either iron absorption inhibitors or iron absorption inducers in the gastrointestinal tract.
Sulfur amino acids can be very toxic. Increasing extracellular L-cysteine levels can be disastorous. L-cysteine taken as supplements can be very toxic. N-acetyl-l-cysteine and alpha lipoic acid are, for example, disastrous as supplements. Any supplement that increases extracellular L-cysteine by decreasing levels of extracellular cystine, as do n-acetyl-l-cysteine and lipoic acid, must be avoided. N-acetyl-l-cysteine and alpha lipoic acid are appropriately not OTC. Alpha lipoic acid had best never be used and now N-acetyl-l-cysteine had had best be used only for for acetaminophen poisoning . Lipoic acid could also competitively inhibit biotin and pantothenic acid transport by the SMVT as biotin, pantothenic acid and lipoic acid are all transported by the SMVT. L-methionine taken as a supplement could result in inappropriate DNA methylation. Cystine supplements must not be taken. L-Cystine could be quite toxic as a supplement. L-cystine could result in an large effux of glutamate from cells via the cystine/glutamate antiporter which could be associated with excitoxcity. Absolutely the worst supplement strategy, that has some scientific support, is trying to increases L-cysteine levels via sulfur containing amino acids except via taurine which spares cysteine.
Lipoic acid is also a total disaster as a supplement. Lipoic acid will competitively inhibit biotin and pantothenic acid transport. Lipoic acid and pantethine also must not be supplemented as lipoic acid and pantethine will reduce cystine to L-cysteine, howver, cystine must be available to enter cells via the cystine/glutamate antiporter. Import of L-cystine into cells and export of glutamate out of cells are both key..
Supplemental glycine is avoided. Serine is needed for homocysteine metabolism and serine can be synthesized from glycine but still glycine is not helpful. However, taurine, which can spare cysteine, is of assistance. Attempting to increase synthesis of L-cysteine by supplementing with amino acids except taurine can have very negative effects.
Coenzyme Q10 could be of assistance. Coenzyme Q10 could support activity of succinate dehydrogenase which is an enzyme both in the TCA cycle and the oxidative phosphorylation pathway. Ubiquinol is avoided. Ubiquinol is the reduced form of coenzyme Q10. Ubiquinol could increase succinate levels and could as antioxidant have undesirable effects.
That there is oxidant stress is many illnesses is well established, however, thousands and thousands of oxidation reactions are needed. Greatly increasing levels of free antioxidants, for example, vitamin C or vitamin E is for the most part not of assistance.
Free antioxidants much in excess of amounts obtained from food can have very undesirable effects while increasing activities of antioxidant enzymes via supplements can have desirable effects or even very desirable effects. Supplementation with Se-methylselenocysteine can have very desirable effects.
Manganese and copper levels should be tested. Divalent metal transporter 1 which transports iron also transports manganese and copper.
That increasing re-methylation of homocysteine to L-methionine, via supplemental folic acid and vitamin B12 in more that RDA amounts, is counterproductive, is another surprising rule. Homocysteine must be available to be metabolized to cysteine via the transsulfuration pathway. Supplementation with taurine decreases homocysteine levels. Absent an inactivating mutation in CBS supplemental taurine appears now to to be only helpful way to reduce homocysteine levels via supplement. Folic acid and vitamin B12 supplements do not prevent cognitive decline though the supplements can reduce homocysteine levels.
Thiamine can be of assistance. Thiamine will support activities of pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase which are the E1 components of pyruvate dehydrogenase complex and 2-oxoglutarate dehydrogenase complex respectively. The E1 step in the pyruvate dehydrogenase complex is the rate-limiting step in the whole pyruvate dehydrogenase complex. To increase activities of the E2 components of the pyruvate dehydrogenase complex and 2-oxoglutarate dehydrogenase complex activities of the E1 components have to first be increased. The E1 components have thiamine diphosphate as cofactors.
Supplemental niacin or niacinamide and/or riboflavin in much more than RDA amounts are avoided as supplemental niacin or niacinamide and riboflavin could increase activity of the E3 components of the pyruvate dehydrogenase complex and and alpha-ketoglutarate dehydrogenase complex whose products can inhibit E1 components of the pyruvate dehydrogenase complex and and alpha-ketoglutarate dehydrogenase complex. Supplementing with niacin or niacinamide and/or riboflavin in much more than RDA amounts is a very large misstep.
Supplemental vitamin B6 can be of assistance. Vitamin B6 is required by cystathionine beta-synthase and cystathionine gamma lyase. the two enzymes in the transsulfuration pathwa. Vitamin B6 is also involved in pyruvate metabolism via glutamic–pyruvic transaminase and serine-pyruvate transaminase whereby supplemental vitamin B6 can be of assistance. vitamin B6 is taken daily in divided doses.
All B-50 vitamin formulations are avoided. One Centrum a day could be okay.
Molybdenum from molybdenum bound to Krebs cycle intermediates will increase levels of xanthine oxidase. Xanthine oxidase, is a molybdenum containing protein. Xanthine oxidase is a powerful ferroxidase and could assist with iron transport. Molybdenum from molybdenum bound to Krebs cycle intermediates would be readily available in the gut which could be a strong advantage. Molybdenum chelated to glycine is avoided as xanthine oxidase levels must be increased in the gut. Molybdenum from molybdenum glycinate may not be readily available in the gut. Douglas Laboratories sells a 500 microgram molybdenum supplement where the molybdenum is complexed with Krebs cycle intermediates, which is not ideal, however, the Krebs cycle intermediates must be in such low amounts that the Krebs cycle intermediates would not present difficulties. Douglas Labs also sells a 250 microgram molybdenum supplement, which is an an amino acid chelate, that is not purchased. The 250 microgram supplement of Douglas Laboratories use to to be chelated to glycine. Whether this is still true or not is unclear. The advertising of Albion Minerals which states that glycine is very tightly bound to minerals in glycine chelates is absolutely accurate.
No minerals bound to glycine should should supplemented. Advertising of Albion Minerals is absolutely accurate. Glycine in minerals bound to glycine is tightly bound to minerals which makes the minerals unavailable in the gut, however, minerals to be of assistance must be available in the gut as well as be available systematically. Taking any glycinated minerals is a very large misstep.
At this time the treatment is complementary medicine rather than alternative medicine. Prescribed medications should not be stopped without consultation with MDs.
Supplements are a minefield. Do not start the treatment unless contraindicated supplements are at the same time avoided.
What not to supplement is as important as what to supplement with. Supplementing with L-methionine or S-adenosyl-l-methionine are avoided. Supplementing with N-acetyl-l-cysteine, L-cysteine, cystine, r-lipoic acid and/or alpha lipoic acid supplements is avoided. N-acetyl-l-cysteine and alpha lipoic acid increase L-cysteine levels by decreasing cystine levels which is not of assistance. Supplementing with iron sulfate is avoided. Carbonyl iron will reside in the gut longer whereby aconitase 1 in the gut can be better regulated by carbonyl iron compared to iron sulfate. Carbonyl iron is also safer that iron sulfate. Pantetheine is not supplemented as pantetheine could decrease cystine levels. Sodium selenite and any form of L-selenomethionine are not supplemented. Minerals bound to succinate should be avoided. All supplements bound to TCA cycle intermediates, except in miniscule amounts, are avoided. An Folic acid and vitamin B12 are not supplemented in much more than RDA amounts. To produce L-cysteine via homocysteine there must be homocysteine. Increasing re-methylation of homocysteine to L-methionine by taking more that RDA amounts of folic is counterproductive. Huge doses of B12 are not helpful. Supplementing with more than RDA amounts of niacin, niacinamide and/or riboflavin are avoided. B-50 formulations are avoided. Supplementation with iron sulfate and ferrous bisglycinate are avoided. No minerals bound to glycine should should supplemented. All minerals bound to citrate must be avoided unless amounts are minuscule. Calcium citrate is avoided. All soft drinks and bottled waters with citric acid must be avoided. All minerals bound to succinate must be avoided unless amounts are minuscule. Supplmenting with L-carnitine in any formulation is avoided. . Vitamin C supplements much above RDA amounts are avoided. All citric acid based drinks are avoided. Beta-carotene supplements much above RDA amounts are avoided. Vitamin E supplements much above RDA amounts are avoided. Apparently there are various needed oxidant reactions that free antioxidants adversely affect. Free antioxidants supplements are avoided. Free antioxidants are basically only healthy in amounts found in food. Antioxidant plant extracts are avoided, including natural flavors derived from plants., as such extracts act as free antioxidants. Soft drinks are completely avoided both for added acids, for example, citric acid and phosphoric acid acid that can affect iron absorption, and for the natural flavors derived from plants. Bottled waters and/or canned waters that have added acids that can affect iron absorption, for example, citric acid, and/or plant natural flavors are avoided. Coffee given coffee is drunk must be stopped around 6-7 hours before before iron from iron carbonyl is supplemented. 100% tea could be OK, however, the last cup of tea of the day would have be drunk around 6-7 hours before iron from iron carbonyl is taken. Both coffee and tea have deleterious effects given iron from iron carbonyl is not supplemented around mid evening. Coffee can have beneficial effects.
Treatment failure is predicted unless the recommendations as to what not to supplement with are adhered to.
The treatment is clearly a lot but the treatment treats schizophrenia which is either the worst disease humans face or is in a tie for worst disease humans face. Carbonyl iron, Se-methylselenocysteine, evening primrose oil, EPA + DHA and taurine can treat psychosis and cognitive symptoms of schizophrenia stopping schizophrenia from being treatment resistant. Biotin, pantothenic acid, free-form L-glutaminen and free-form branched-chain amino acids are of assistance. Taurine, vitamin K2 MK-7, calcium hydroxyapatite and vitamin D3 address negative symptoms of schizophrenia. As negative symptoms of schizophrenia are due to hidden osteomalacias that affect bones is the back of heads taurine, vitamin D3 and vitamin K2 MK-7 and calcium hydroxapatite can take a very long while to be completely effective.
Avoid the supplements on the to be avoided list. L-methionine, S-adenosyl-l-methionine, N-acetyl-l-cysteine, L-cysteine, cystine, r-lipoic acid and/or alpha lipoic acid supplements must be absolutely avoided. Do not take glycinated minerals. Get anemia panels, thyroid panels, metabolic panels and CBCs done regularly. Supplements formulated for better absorption are a diaster. Anemia panels, thyroid panels, metabolic panels and CBCs can be ordered online in most states.
Iron from carbonyl iron – must be taken at bedtime away from iron enhancers and iron inhibitors – treats psychosis – very quickly effective – 2 or or 3 days
Se-methylselenocysteine – treats cognitive symptoms – can be toxic in high doses – very quickly effective – 2 or or 3 days
EPA + DHA and evening primrose oil – EPA must be approximately balanced by gamma-linolenic oil found in evening primrose oil – treats depression and neuropathy due to inflammation – taurine will assist in the absorption of EPA + DHA and evening primrose oil – quickly effective – 2 or or 3 days – Softgels cannot be swallowed but rather must bitten, contents swallowed, and softgels thrown away. EPA + DHA can be taken alone but evening primrose can not be taken alone.
Taurine, calcium from calcium hydroxyapatite, vitamin D3 and vitamin K2 MK-7 – treats negative symptoms – vitamin D3 should be dry vitamin D. K2 MK-7 should be in a capsule not a softgel – calcium from calcium hydroxapatite must be supplemented if vitamin D3 is supplemented even if diets should have enough calcium. Do not not take calcium at bedtime with iron from iron carbonyl. Calcium can inhibit iron absorption. Taurine must be taken on empty stomach for better absorption. Takes a long, long while to be fully effective
Biotin, pantothenic acid and thiamine improves mood, stops cycling – Biotin, pantothenic acid and thiamine require free-form branched-chain amino acids and freee form l-glutamine to be effective in lifting mood. Biotin is taken three times durnig the away from pantothenic acid. Pantothenic acid is taken once a day at bedtime away from biotin.
Individuals must stay hydrated.
Branched-chain amino acids and L-glutamine – reduces fatigue — require biotin,. pantothenic acid and thiamine. Branched-chain amino acid supplements and glutamine supplements must be free-form. For fatigue both branched-chain amino acids and L-glutamine must both be taken. L-glutamine taken alone can have negative effects.
A difficulty with the treatment is that with so much askew in schizophrenia successfully addressing one set set of symptoms may not look like much of a success as still a lot is askew. For example, with a psychosis successfully addressed someone could still feel wretched and not count what addressed the psychosis as being very helpful.
The treatment cannot be criticized as being too complex as research has foreclosed there being a simple treatment for schizophrenia that is also effective. Proper packaging of supplements could greatly reduce number of pills taken a day.