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 what is manufactured to high 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.
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.
Selenium compoundsas 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-selenomethioninewhich is the food form of selenium. L-selenomethionineis 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 homocysteinelevels 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.
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.
Could there be epigenetics changes to genes when protein pathways become non-fuctional? Say there is decreased activity in a rate limting enzyme in a protein pathway. Do other genes coding for proteins is the pathway keep producing proteins in the pathway even though those proteins now no longer serve any purpose?’
The Central Dogma of Biology according to James Watson – DNA makes RNA makes protein.
The Central Dogma of biology is at the same time a non-sequitur, strictly false and though simple is simpler than possible. What genes are transcribed matters a very great deal and what genes are transcribed is due to epigenetic changes on those genes so the Central Dogma is a non-sequitur is terms of activites of protein pathways and behaviors of organisms. The Central Dogma is strictly false as RNA viruses can change DNA. The Central Dogma is also simpler than possible. Very many genes code for proteins that are splice variants. The production of splice variants of genes is regulated by a system of trans-acting proteins that bind to cis-acting sites on primary transcripts.
Why bring up the the Central Dogma? The Central Dogma of biology is so 1960’s. The genetic determinism of the Central Dogma of biology is still an undercurrent that gets in the way of appreciating the epigenetic basis of many chronic illnesses.
If transcription of genes for proteins in protein pathways in specific organs can fall together this could give rise to unique illnesses where the basis of such illnesses would be due to epigenetic changes, which at first could be isolated to specific organs but which could spread over time worsening such illnesses in relatively predictable ways. With epigenetics, protein pathways falling into disuse can affect only specific organs though over time there could be a spreading effect which fits with how chronic diseases develop.
Another implication of genes becoming hypermethylated when proteins that those genes code for become unused is that optimum nutrition could result in increased numbers of healthy years lived. I would say that as of now there is very, very litttle useful information on what opimum nutrition is in terms of increasing number of healthy years lived. Preventive medicine in terms of nutrition has been one mistep after another. Huge errors have been made. For example, increasing free antioxidants by taking vitamin E, vitamin C and beta-carotene in more than RDA amounts has been a terrible disaster. The only path in terms discovering what optimum nutrition is would be to work back from nutrional strategies than cure diseases rather than are speculations on diet as to how to prevent diseases developing decades and decades later. Pilot studies are very, very frequently misleading. Supplements are now a minefield.
There is lots and lots of research on how to increase absorption of minerals. The supplement industry following up on this has formulated mineral supplements to be better absorbed.
My idea that minerals must be available both in the enteric system and systematically to be useful in treating illnesses does not conflict with any biological findings but it goes against what is held as common sense. Every one just knows that the goal with mineral supplements is to increase and enhance absorption. Minerals that are not formulated for increased abosorption can be absorbed and can effectively treat diseases associated with mineral deficiencies. Most of the clinical trials of minerals do not use amino acid chelates.
The assumption with minerals formulated for increased absorption is that somehow proteins in the enteric system watch minerals pass by unused and hold that is totally acceptable. Proteins in the enteric system are willing to go the end of the line and wait for minerals to get back to them. The common sense idea is that the gastrointestinal tract is like a busy 4 way intersection.
Metal proteins in the enteric system could set the stage for metal proteins throughout the body. Systematically metal proteins might not work effectively unless the stage is set by metal proteins in the enteric system working.
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.
In terms of alternative and complimentary medicine 5-MTHF, alpha lipoic acid, folate and N acetyl cysteine are mainline treatments for depression.
There are lots of grounds to think these supplements could be very unsafe. Lipoic acid shares the same transporterwith biotin and pantothentic acid. Lipoate inhibits the transport of pantothenic acid and biotin. The body uses miniscule quantities of biotin. 300 milligrams of lipoic acid twice a day could have a large negative affect on biotin transport. Lipoic acid does not work in bipolar depressionwhich is not suprising, See the page on Bipolar Depression.
N-acetyl cysteine is associated with musculoskeletal adverse side effects. These musculoskeletal adverse side effects are almost totally impossible to get rid of and can be horrendous. Clincal trials are usually about 6 weeks long but musculoskeletal effects accumulate over time and can persist long after N-acetyl cysteine is stopped.
There are no grounds whatsover to hold than S-adenosyl methionine taken long term would not affect DNA methylation and histone methylation. Abberrant DNA methylation is associated with cancer, aging and mental illnesses. Minimally an explantion as to why greatly increasing S-adenosyl-l-methionine levels does not affect DNA and histone methylation long term has to be given but no explanatiton is provided.
5-methyltetrahydrofolateinhibts glycine-N-methyltransferase which degrades S-adenosyl methionine. With 5-methyltetrahydrofolate supplementation S-adenosyl methionine levels would again be expected to greatly increase with again unknown consequences to DNA methylation and histone methylation. No consequences would be very surprising. Despite great early enthusiasm folic acid supplementation has been a bust in the prevention of a range of illnesses associated with high homocysteine levels.
What is it about these supplements that makes them so attractive? One very definitely notices these supplements when one takes them.