Treatment

My ideas about the etiology of schizophrenia are presented in Treatment-resistant schizophrenia: focus on the transsulfuration pathway  which was published in Reviews in the Neurosciences.  The treatment section of the paper is out of date.

Treatment

180 milligrams of iron from iron carbonyl is taken four times day. Iron from iron carbonyl is slowly absorbed from the gut which is a large plus. Iron carbonyl is a non-toxic form of iron. Iron carbonyl is taken with the other supplements. Anemia panels must be obtained to insure that iron levels are not high. A dosage of iron would be dropped if iron levels are high. 500 milligrams of vitamin C is taken 4 times a day. 500 micrograms of molybdenum from molybdenum bound to Krebs cycle intermediates is taken twice a day. Xanthine oxidase,  is a molybdenum containing protein. Xanthine oxidase is a powerful ferroxidase and could assist with iron transport.  Whey protein concentrate is taken three times a day. 250 milligrams of pantothenic acid is taken 4 times a day. 10 milligrams of sublingual biotin is taken once a day. Sublingual biotin is taken to decrease the chance of pantothenic acid competitively inhibiting transport of biotin in the gut and also to reduce biotinylation of the SMVT locus in the gut. 200 milligrams of dry coenzyme Q10 is taken 4 times a day. Coenzyme Q10 will support the citric acid cycle. Coenzyme Q10 is a co-factor for succinate dehydrogenase. When taking biotin coenzyme Q10 must be taken. 200 milligrams of sulbutiamine is taken 2 times a day. Sulbutiamine is fat-soluble form of thiamine. Pantothenic acid and sulbutiamine will support the pyruvate dehydrogenase complex and the 2-oxoglutarate complex in the citric acid cycle. 500 milligrams of L-carnitine from L-carnitine tartrate is taken 4 times a day. 200 micrograms of Se-methylselenocysteine is taken once a day. 5000 IUs of dry vitamin D is taken once a day. A EPA and DHA supplement, where EPA is about 65% of the EPA and DHA combination,is taken four times a day. Synthesis of calcitriol requires androdoxin which is an iron-sulfur protein. Dry vitamin D works much better than softgel vitamin D. 3 mg of copper from copper glycinate is taken twice a day. Copper assists with iron transport.   IRP1 can affect copper transport. IRP1 can also affect manganese transport. 10 mg. of manganese glycinate is taken once a day. Anemia panels, thyroid panels, metabolic panels and CBCs should be obtained.  Copper and manganese levels should also be tested. If copper and manganese levels are normal copper then copper and manganese do not have to be supplemented. HealthLabs.com has a panel on sale for $99 that covers a lot. Biotin can affect test results of hormones. Supplemental biotin would be stopped a few days before tests are done. Blood pressure should be checked daily.

All the supplements are taken togther even iron carbonyl. Taking the supplements with whey protein concentrate makes a huge difference. Supplements are synergistic with each other when taken together.

Vitamin E as d-alpha tocopherol and dry beta-carotene are the last supplements added and would be taken with the other supplements. I had all the symptoms of a vitamin E deficiency but I could not tolerate vitamin E. Only when upon almost the complete treatment was I able to tolerate vitamin E. Why was I able to tolerate vitamin E only when I was on almost the complete treatment? Are a complete set of antioxidant supplements required for vitamin E to work? Must the supplements be taken with protein? Would a meal be sufficient or better? Can vitamin E have adverse affects when there are low levels of coenzyme A and/or the TCA cycle is dysregulated? I do not know. However, I do know that poor absorption was not the problem as I was absorbing enough vitamin E to have difficulties. A reminder – N-acetylcysteine, lipoic acid, cysteine, cystine and pantethine must be absolutely avoided as supplements. 400 IUs of vitamin E taken twice a day or 200 IUs of vitamin E taken 4 times a day are dosages that should not be exceeded. I take d-alpha tocopherol. Conceivably only d-alpha tocopherol works. There are lots of different vitamin E’s. I could have been using the wrong vitamin E formulation.

Aconitase is very susceptible to inactivation by free radicals. Vitamin E and beta-carotene by neutralizing free radicals could stop inactivation of aconitase by free radicals.

As it turns out getting rid of positive symptoms is easy and can be quickly done  but positive symptoms are one fifth of the problem. 180 milligrams of iron from iron carbonyl taken four times a day with 500 milligrams of vitamin C each dosage with the iron carbonyl and vitamin C taken with a meal will address positive symptoms. To be avoided supplements would have to be avoided and polyphenol containing drinks would have to be avoided such as coffee, tea and sodas. Two 100 mg caffeine pills taken a day should be okay. Anemia panels should be obtained. Iron, copper and manganese tests should become routine. Iron can affect copper and manganese absorption. DMT1, which transports iron, also transports manganese and copper. Before supplementing with copper and manganese lab tests should be done. Possibly only a small percentage of individuals will have low copper and/or low manganese levels. If copper and manganese tests are normal then copper and manganese are not supplemented. Still copper and manganese levels would be tested periodically.

Selenium has a very low margin of safety. No more than 200 micrograms of selenium is taken a day.

Molybdenum from from molybdenum bound to Krebs cycle intermediates will increase ferroxidase activity in the gut. Molybdenum supplementation significantly increases the activities of xanthine dehydrogenase/oxidase (XDH), sulfite oxidase and superoxide dismutase in the liver, and of XDH in small intestinal mucosa. Xanthine oxidase has 1000 times the ferroxidase activity of ceruloplasmin Molybdenum is a co-factor for sulfite oxidase which metabolizes sulfites which are degradation products of L-cysteine. The ferroxidase activity of xanthine oxidase in the intestines could be slowing down the absorption of iron whereby iron can regulate ACO1 and IRP1 in the gut. Molybdenum glycinate is avoided as molybdenum from molybdenum glycinate may not be available in the gut.

Do individuals with schizophrenia look happy? No. The labeling of schizophrenia as a thought disorder is very askew. Everyone with schizophrenia suffers from depression. Individuals with schizophrenia who do not seem depressed would have very pronounced negative symptoms that mask depressions. Individuals with schizophrenia simply do not like to talk about symptoms though they all know they are ill. Individuals with schizophrenia can learn to manage their illnesses without any exploration at all of delusions but by rather focusing on what is true where a need to take medications is very frequently of what is true.

Tea and coffee are completely avoided. Polyphenols in coffee and tea adversely affect absorption of iron. Caffeine is apparently not the culprit. Coca-Cola has polyphenols and should be avoided. Polyphenols in supplements could be highly available and should be particularly avoided.  Flavonoids are polyphenols. Flavonoid supplements should be avoided.   One might not be psychotic on coffee, but  at very best one will be a bit goofy.

The difficulty with polyphenols is that polyphenols complex with iron making iron unavailable in the gut.

Some bad news. Of drinks all one can drink is water. Both polyphenols that decrease iron absorption and citric acid drinks must be avoided. Why citric acid drinks have such an adverse effect is not clear. Hot drinks with polyphenols and cold drinks with natural favors and/or citric acid may be more liable to decrease iron availablity in the gut than cold drinks with polyphenols but no added natural flavors. Pure fruit juices with no added flavors, beer and wine could be okay but I very much doubt that.

Sodas are avoided. Sodas, for example, Mountain Dew, as this advertisement shows  are frequently associated with goofyness where the goofyneness could be due to  polyphenols in the sodas adversely affecting iron metabolism in the gut.

Coca-Cola is made from kola nuts and kola nuts contain polyphenols. What polyphenols, via natural flavors, are exactly in Coke-Cola, however, is one the most guarded secrets in business. Natural flavors are plant extracts. The switch to plant extracts was in all probability done for greater psychological effects. Calling plant extracts natural flavors was a marketing move of sheer genius. Warren Buffet could have lead Bill Gates far astray in getting Bill Gates on Coca-Cola. Bill Gates apparently had a personality change in midlife which could be due to Bill Gates emulating Warren Buffet in drinking Coca-Cola. The Netflix documentary on Bill Gates shows Bill Gates drinking diet Coke after diet Coke at his lake retreat.  Admittedly Warren Buffet is delightful.   Here is an advertisement  for Cherry Vanilla Coke which must be full of polyphenols. The Coca-Cola Corporation has supported research that pushes that juices are a convenient way to deliver polyphenols into the diet. The interaction of polyphenols with iron is a huge interaction. Drinks with polyphenols could be mainly having an effect in the gut but what happens in the gut is key. One thing can be said about the 19th century. The 19th century was not a goofy century.    Then came the Coca-Cola Corporation. At no time in human history except in the last 100 years have humans ever appeared to humans to be a quite goofy species.  Underdevelopment in Central and South America? Among the very first corporations in Central and South America were Coca-Cola distributors. Coca-Cola is drunk rather than water in Mexico.   Melinda Gates has noted that Coca-Cola is omnipresent in the developing World. The Coca-Cola Corporation could be an integral part of the developing World being the developing World.  Soda drinks with polyphenols combined with iron deficiencies both of which are very wide spread in the developing World could be large double hits against the developing World. Add blood losses from menstruation, which can affect iron status, and there are three strikes against women in the developing World.  Coca-Cola specifically is not the problem. Drinks with polyphenols are the problem. In the soda market Coca-Cola was there first and is still there very, very  big.  Hemoglobin levels and blood iron levels do not provide a complete picture of iron status. Iron-sulfur proteins such as aconitase 1, iron regulated proteins and the citric acid cycle can be dysregulated even though hemoglobin levels are normal and iron blood levels are normal.   Bill Gates could test whether drinks containing polyphenols affect personality.  Bill Gates could stop drinking Coca-Cola and coffee and switch to one or two 100 mg caffeine pills a day. With the reduction of intake of polyphenols from coffee, tea and sodas there will be cravings for polyphenols. Fresh fruits and vegetables can be eaten. On Coca-Colas fresh fruits and vegetables just do not seem like the real thing. Bill Gates now likes diet Coca-Cola and burgers a whole lot. Lots of diet Coca-Cola matches up with lots of burgers and no fresh fruits and vegetables.

Joseph Smith had a revelation which prohibited drinking of hot drinks which practically prohibited the drinking of coffee and tea. The revelation of Joseph Smith against coffee and tea is one of the key factors that contributed to the formation of the LDS character especially in the 19th century. Apparently the revelation does not strictly prohibit cold, caffeinated sodas which can have deleterious effects. Non-caffeinated sodas and juice drinks can also have deleterious effects. Alcoholic beverages, prohibited by a revelation of Joseph Smith, also contain polyphenols though there are lots of grounds on which to prohibit alcohol. Utah is huge on supplements, where many supplements have high polyphenol contents. Somehow or other polyphenol extracts have popped up in LDS diets. For members of the LDS Church drinking soda constantly is almost a fad.

Various studies indicate that coffee and caffeine are protective against depression. First of all caffeine is a positive where the positive effects of caffeine in coffee are felt first and second individuals with mental and neurological illnesses may be particularly affected by polyphenols in drinks. Self reports of coffee inducing depressions would be very unreliable as the first couple of cups of coffee in the morning are a terrific boost. The hypothesis holds that iron-sulfur proteins are dysregulated in schizophrenia and Alzheimer’s disease and in that context polyphenols in drinks can cause various problems. Polyphenols in drinks are a second hit which can worsen the situation. Individuals should feel free to drink coffee, tea and/or sodas but individuals should not say that the treatment does not work for them until the proposed treatment is tried, to be avoided supplements are avoided and polyphenol containing drinks are avoided. A lot of individuals with mental illnesses will stop caffeine containing drinks at one time or another but that does not cure mental illnesses rather individuals only miss the caffeine boost. Adverse affects of coffee may take a long time to develop. Maximal lifetime caffeine intake and caffeine-associated toxicity and dependence are moderately associated with risk for a wide range of psychiatric and substance use disorders. Coffee intake and various benefits of coffee could only be an association rather than be due to causation.

That many individuals with high intakes of polyphenols would absolutely deny having a mental illness does not necessarily imply that polyphenol drinks are not problematical. Take the protestors who are opposite your political position. Those protestors seem delirious and paranoid but the protestors and others hold the protestors clearly grasp political realities. Donald Trump drinks 12 cans of diet Coca-Cola daily. Donald Trump thinks diet Coca-Cola is garbage but drinks diet Coca-Cola anyway. Donald Trump would say he just likes making deals. With aconitase, the TCA cycle and iron regulated proteins dysregulated individuals deny symptoms of mental illness though they know they have serious problems which they all too frequently address inappropriately.

Coffee drinking is very widespread. Here is a coffee advertisement from another planet.

Taking calcium supplements can be problematical as calcium forms complexes with iron Calcium would be taken away from other supplements. Supplemental vitamin D rather than supplemental calcium could be the route to go. Dry vitamin D works better than softgel vitamin D as dry vitamin D, compared to softgel vitamin D, is more bio-available in the gut. When taking a whey protein concentrate taking a whey protein concentrate that is low in calcium such as Now Whey Protein Concentrate is advisable.

The spice trade could have been basically a way to obtain concentrated polyphenol compounds for psychological effects. Spices inhibit iron availability in a dose dependent manner. Spices are now very readily available but individuals are not obsessed with adding spices to foods. Individuals now just drink sodas for the real thing.

William H. McNeil wrote a famous book entitled Plagues and People. McNneil shows that plagues are a little noticed, at least in history books, powerful hidden current in history.

The unnoticed introduction of polypehenol extracts into the diet is a powerful hidden current that could have shaped the history of the Modern Era. The desire for concentrated polyphenols is a desire which explodes in Europe at the start of the modern age and could have shaped the last 500 years.

Iron sulfate is avoided as iron sulfate is quickly absorbed. Iron bisglycinate is avoided as iron from iron bisglycinate may not be available in the gut and where the iron could also be quickly absorbed.   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 at least for now.

Very unfortunately, as the hypothesis posits a basic L-cysteine deficiency, strategies to directly increase L-cysteine levels directly can be disastrous. N-acetyl-l-cysteine and alpha lipoic acid are, for example,totally  disastrous as supplements.  Any supplement that increases L-cysteine by decreasing levels of cystine, as do n-acetyl-l-cysteine  and lipoic acid, must be avoided. Pantethine is also avoided as  pantethine could decrease cystine levels. N-acetyl-l-cysteine and alpha lipoic acid should not be OTC. Alpha lipoic acid should never be used and N-acetyl-l-cysteine should only be used for acetaminophen poisoning if then. L-cysteine taken as supplements can be very toxic. L-methionine taken as a supplement could result in inappropriate DNA methylation. Cystine supplements are not taken. Cystine could be reduced to cysteine by vitamin C.

Ubiquinol is avoided. Ubiquinol is the reduced form of coenzyme Q10. Ubiquinol could increase succinate levels.

That increasing re-methylation of homocysteine to L-methionine, via supplemental folic acid and vitamin B12 is counterproductive, is another surprising rule.

Pantothenic acid,sulbutiamine, sublingual biotin, coenzyme Q10, L-carnitine from L-carnitine tartrate and EPA + DHA can treat negative symptoms of schizophrenia. Biotin can decrease transport of pantothenate by decreasing transcription of the gene for the sodium-dependent multi-vitamin transporter via biotinylation . The gene for SMVT in the could be hypermethylated so biotin is taken sublingually. Taking biotin for hair growth is very ill-advised. Supplemental thiamine is not helpful. Sublingual thiamine cocarboxylase is very unhelpful.

Sulbutiamine 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 must first be increased. The E1 components have thiamine diphosphate as cofactors. Benfotiaimine does not work. There are no genetic mutations so systematic dysregulations of the pyruvate dehydrogenase complex and 2-oxoglutarate complex  do not occur. Transketolase, which is a thiamine-dependent enzyme, is working normally.

Surprisingly biotin can have negative effects if not taken with coenzyme Q10. Apparently biotin has a large effect on the TCA cycle where coenzyme Q10 must be available to support the TCA cycle and oxidative phosphorylation given biotin is taken.Pantothenic acid and biotin are both transported by the sodium-dependent multivitamin transporter.  Biotin is taken sublingually. Pantothenic acid could reduce absorption of biotin as both are transported by the sodium-dependent multivitamin transporter and pantothenic acid is taken in much higher dosages than biotin. High doses of orally taken biotin could reduce transport of pantothenic acid via biotinylation, which is an epigenetic change to histones, that can decrease expression of the sodium-dependent multivitamin transporter. Another factor to consider in taking sublingual biotin is that genes for the SMVT located under the tongue are less likely to be hypermethylated than genes for the SMVT located in the gut.

Sublingual biotin should be taken in tablet formulation where the tablet takes about a minute to dissolve under the tongue. If the biotin tablet dissolves almost immediately whether one is swallowing the biotin or letting the biotin dissolve under the tongue is not clear

Carnitine from l-carnitine tartrate must be supplemented. L-carnitine reverses the inhibition of pantothenic kinase by coenzyme A and acetyl-coenzyme A. Pantothenic kinase is the rate limiting enzyme in coenzyme A synthesis. The supply of pantothenate and the level of expression of pantothenate kinase determine cellular CoA levels. Supplemented L-carnitine must be L-carnitine from L-carnitine tartrate. L-carnitine fumarate is avoided as fumarate can inhibit DNA demethelyases and histone demethylases.

A combination of EPA and DHA is a useful supplement. A way to produce acetyl-coenzyme A is through beta-oxidation of fatty acids. In terms of generating acetyl-coenzyme A via beta-oxidation any fatty acid would in all likelihood work however, EPA and DHA are well studied, are associated with health benefits and research indicates that EPA and DHA are safe to supplement with. Synthesis of fatty acids requires acetyl-coenzyme A. Synthesis of fatty acids could be impaired due to dysregulation of acetyl-coenzyme A synthesis. EPA and DHA by providing acetyl groups for acetyl-coenzyme A synthesis could jump start fatty acid synthesis. EPA and DHA are near the end of the line in terms of fatty acid biosynthesis and would not upset fatty acid biosynthesis pathways. In this view EPA and DHA are beneficial as EPA and DHA increase levels of acetyl-coenzyme A via beta-oxidation and do not upset fatty acid biosynthesis pathways. EPA and DHA levels where EPA levels are greater than 60% are effective against depression. Some DHA is apparently needed. EPA levels should be about around 60% to 65% of the EPA and DHA combination. EPA more rapidly undergoes beta-oxidation compared to DHA which could be why higher levels of EPA are needed compared to DHA. Some DHA is needed as only supplementing with EPA could upset fatty acid biosynthesis pathways. The International Society for Nutritional Psychiatry recommends for depression that a supplement with a total of 1-2 grams of EPA can be taken daily. The supplement would be taken in four divided doses as beta-oxidation of the EPA could have to happen through out the day.

Another very positive point in favor of EPA + DHA is that EPA + DHA are from fish and do not contain polyphenols. Plant oils will contain polyphenols.

Supplemental vitamin B6 is helpful. Alanine transaminase EC 2.6.1.2 alanine-glyoxylate transaminase EC 2.6.1.44 which are are involved in pyruvate, 2-oxoglutarate, and glutamate metabolism as shown in the KEGG  alanine aspartate and glutamate metabolism map are vitamin B6 dependent enzymes.

Supplemental niacin and supplemental niacin derivatives would increase NADH levels inhibiting E1 components of 2-oxogultarate dehydrogenase complex and pyruvate dehydrogenase complex. Riboflavin, niacin and niacin derivatives are not supplemented as such supplements will  negate the effects of pantothenic acid and sulbutiamine on negative symptoms.  NADH is product of the E3 components of the pyruvate dehydrogenase complex and the 2-oxogultarate dehydrogenase complex. Riboflavin via FAD frequently works with NAD+. Riboflavin and niacin undermine the effectiveness of pantothenic acid and sulbutiamine as NADH is a feedback inhibitor of 2-oxogultarate dehydrogenase and pyruvate dehydrogenase.

Lipoic acid and pantethine must not be supplemented as lipoic acid and pantethine  will reduce cystine   to L-cysteine but 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 important. Cysteine is very toxic and is not supplemented. Cystine must not be supplemented either as with antioxidants being supplemented cystine would quickly be reduced to cysteine.

All B-50 vitamin formulations are avoided.

All plant based supplements are highly suspect as plant based supplements very likely contain polyphenols which can inhibit iron absorption. Herbal tea is not a safer alternative to coffee and tea. Mint tea is, for example, very high in polyphenols. Peppermint tea can reduce iron absorption by 84% and lacks the benefits of caffeine. Juice drinks with natural flavors are avoided.   One step parents could take if children are having behavioral difficulties is to cut out drinks with polyphenols such as sodas and fruit juice and any drinks with natural flavors. Natural flavors are plant extracts and plant extracts can have very powerful effects. Children after being weaned for 100’s of thousands of years drank only water.Vegetables and fruits can, of course, be eaten. In terms of a Paleolithic diet only water is drunk by children and adults and mom’s milk by babies.

Whey protein concentrate supplemented should have no whey protein isolates or hydrolyzed whey proteins. Whey protein isolates are highly absorbed but the whey protein must be bioavailable in the the gut whereby only whey protein concentrate with no whey protein isolates or hydrolyzed whey proteins is supplemented. Whey protein concentrate contains calcium but a serving of Now Whey Protein Concentrate only contains 10% of the RDA for calcium.

Sodas contain polyphenols from natural flavors which are highly available in the gut. All  sodas are avoided. All sodas,  either with sugar added or diet, are associated with early death. There were no food extracts in Paleolithic times. The difficulty with modern diets may not be so much with processed foods but rather with plant-based food extracts in food.   Natural flavors are plant extracts. Plant extracts can be very powerful.

Some of the greatest crimes in human history have been committed to obtain, consume and/or sell plant extracts. Slaves were first brought to North America to grow tobacco which, via smoking, is a highly effective way to deliver nicotine. Slavery in the Caribbean and South America was founded on sugar plantations, the British undermined government in China in order to be able to sell opium to the Chinese masses and tea plantations in South East Asia were the basis of European colonies in South East Asia. The trade in spices was ruthless with much harm done to the East Indies by the Dutch. Societies with straightforward access to plant extracts have not been favored by such ready access. For example, the introduction of coffee into the Mid East and Indian subcontinent occurred at about at the same time nations of the Mideast and Indian subcontinent went into decline. With the introduction of coffee and coffee houses into the Netherlands the Dutch Golden Age comes to an end. China, where tea has been drunk for a couple of thousand years, became static. British society as a beacon to the world was irretrievably undermined by the obsession with plant extracts of the British where the British were willing to go to almost any lengths to produce, trade and/or consume plant extracts. Tea, which is a very British drink, is particularly high in polyphenols. British elites had to decide whether the British Empire was about spreading democratic politics and representation in the British parliament or about acquiring and consuming plant extracts with British elites deciding that the British Empire was about acquiring and consuming plant extracts. The ready availability of sodas in the US has not benefited the US. Sodas have pushed the US as a somewhat goofy nation.

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.

Copper from copper glycinate is supplemented as copper from copper gluconate is apparently not well  absorbed. I had low levels of copper on 10 mg of copper gluconate. High levels of IRP1 can decrease copper transport. 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. Manganese glycinate is supplemented as manganese glycinate is well absorbed. On 10 mg. of manganese gluconate my manganese levels were low. Copper and manganese levels should be routinely tested as supplemental iron could decrease absorption of copper and manganese.

At this time the treatment is complementary medicine rather than alternative medicine. Prescribed medications should not be stopped without consultation with MDs.

Appropriate packaging of supplements could reduce numbers of pills that would have to be taken. The complete treatment could only be necessary once full blown illnesses have developed and genes have become hypermethylated.  Avoidance of supplements and drinks that should be avoided along with iron carbonyl supplements could be all that is necessary to prevent illnesses from developing.

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.  Supplementing with L-methionine or S-adenosyl-l-methionine is 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. Iron carbonyl will reside in the gut longer whereby aconitase 1 in the gut can be better regulated by iron carbonyl compared to iron sulfate. Iron carbonyl is also safer that iron sulfate. Pantetheine is not supplemented as pantetheine could decrease cystine levels. Sodium selenite, sodium selenate and any form of L-selenomethionine are not supplemented. Minerals bound to succinate should be avoided. Vitamin E and dry beta-carotene are added only last. Folic acid and vitamin B12 are not supplemented. To produce L-cysteine via homocysteine there must be homocysteine. Increasing re-methylation of homocysteine to L-methionine by taking supplements is counterproductive. Whey protein isolates and hydrolyzed whey proteins are not supplemented.  All B vitamin supplements are avoided except pantothenic acid, sulbutiamine, sublingual biotin and vitamin B6. Riboflavin and niacin supplements must be avoided. Riboflavin and niacin undermine the effectiveness of pantothenic acid and sulbutiamine as NADH is a feedback inhibitor of 2-oxogultarate dehydrogenase and pyruvate dehydrogenase. Riboflavin via FAD frequently works with NAD+ and could increase levels of NADH. Supplementation with iron sulfate and ferrous bisglycinate are avoided.

In terms of supplements that must have extended availability in the gut apparently any supplement that affects the citric acid cycle must have extended availability in the gut whereby supplemental iron must be iron carbonyl, whey protein must be whey protein concentrate with no added whey protein isolates or hydrolyzed whey proteins and molybdenum should be molybdenum bound to Krebs cycle intermediates. Supplemented pantothenic acid will also be available in the gut.

Treatment failure is predicted unless the recommendations as to what not to supplement with are adhered to.