Almost always clinical trials of supplements are run for short periods of time and moreover only certain side-effects are examined. Supplements programs though very frequently modified are usually started with the intention of being on the supplement for life. I think, for example that acetyl-L-cysteine and lipoic acid can have terrible long term effects though there could be postive effects on some dimensions in the short term. With prescription drugs doctors report side-effects that develop over the long term but that is not the case with supplements as usually doctors do not prescribe supplements.
Carnitine is frequently bound to fumarate in carnitine supplements and mineral supplements are very, very frequently bound to glycine. Fumarate can inhibit enzymes that demethylate DNA and histones. Leiomyomatosis and renal cell cancer can be caused by mutations of fumarate hydratase which metabolizes fumarate. Carnitine fumarate suppplements could be making wild epigenetic changes which could be highly undesirable. My opinion which must now be deeemed a personal opinion is that minerals bound to glycine are not bioavalable in the gastrointestinal tract whereby gylicnated minerals can have many negative effects. On many systematic measures glycinated minerals are very effective though I personally hold there can be higly unforeseen negative effects when supplementing with glycinated minerals.
There is mounting evidence that both sugar sweented and diet drinks have negative effects on cardiovascular health over the long term. What if it is not the artificial sweeteners in diet drinks that raise the difficulties but rather the citric acid and polyphenols and perhaps phosphoric acid are what is raising the difficulties? Many calcium supplements contain citrate. Could calicum citrate have the same adverse effects on cardiovascular health as do diet soft drinks and for the same reasons? I think citric acid based soft drinks can befuddle indivduals. There could be truth in advertising with Mountain Dew. Women under 65 who are on calcium citrate are not going to tell their doctors that they feel befudded and besides increasisng citric intake can lead to lots of fun.
Linus Pauling, who viewed orthormolecular medicine as the practice of delivering ‘the right molecules in the right amounts’, was correct in his view that mental illnesses are orthomolecular in nature and that supplements are required in the treatment of mental illnesses. That is not to say that supplements are not a minefield now.
Acetyl-CoA carboxylase is a biotin-dependent enzyme that catalyzes the irreversible carboxylation of acetyl-CoA to produce malonyl-CoA. Malonyl-CoA inhibits the rate-limiting step in beta-oxidation of fatty acids. Malonyl-CoA inhibits fatty acids from associating with carnitine by regulating the enzyme carnitine acyltransferase.
Malonyl-CoA also plays a key role in chain elongation in fatty acid biosynthesis
Biotin supplementation would then both inhibit beta-oxidation and assist with chain elongation in fatty acid biosynthesis.
I have been arguing that increases is beta-oxidation that result from increased intakes of polyphenols can lead to difficulties in schizophrenia. Given the dual functions of malonyl-CoA in inhibiting beta-oxidation and assisting with fatty acid elongation if there is excessive beta-oxidation there could be difficulties in fatty acid elongation. Supplemental biotin would decrease beta-oxidation and increase fatty acid elongation which would be headed in the right direction. Biotin would not be supplemented at the same time as pantothenic acid as pantothenic acid is a competitive inhibitor of biotin transport.
High homocysteine levels indicate the transsulfuration pathway (homocysteine to L-cysteine) is dysregulated. Taurine is synthesized from L-cysteine. Taurine is needed to form various bile acids. Bile acids are needed for fat absorption.
Polyphenols can increase beta-oxidation which can lead to serious difficulties if there are difficulties in fat absorption which are likely if there are high homocysteine levels.
Many illnesses for which polyphenols have been postulated to be treatments are associated with high levels of homocysteine, however, where there are high homocysteine levels there could be difficulties in fatty acid absorption. Increasing levels of polyphenols, which increase beta-oxidation, would be contradicted where there are difficulties in fatty acid absorption and metabolism.
Polyphenol supplements are frequently suggested as treatments for Alzheimer’s disease and Parkinson’s disease, however, both Alzheimer’s disease and Parkinson’s disease are associated with high homocyteine levels whereby there could be difficulties in fatty acid absoption. Polyphenol supplements could worsen Alzheimer’s disease and Parkinson’s disease. In the treatment of Alzheimer’s disease polyphenols have been full of promise but have failed to deliver effective treatments.
Caffeine pills have nowhere near the same effect as coffee. There must be more to the effects of coffee than caffeine and that something more is the polyphenol contents of coffee and the effect of those polyphenols on beta-oxidation.
Polyphenol extracts are everywhere. Natural flavors are polyphenol extracts. Sodas contain polyphenols from natural flavors. Various plant oils contain concentrated polyphenols. Various supplements are marketed on the very basis that such supplements contain polyphenols, for example quercetin, pycnogenol and resveratrol. Coffee and tea contain polyphenols. Almost all frozen foods will contain natural flavors. Polyphenol extracts are a major difficulty.
This is starting to sound about as bad as ‘electromagnetic hypersensitivity’ in terms of being able to escape the difficulty. Cases of ‘electromagnetic hypersensitivity’ could in fact be adverse reactions to polyphenol extracts and concentrated polyphenols.
Adverse reactions to polyphenols are not immune responses. A difficulty with polyphenols is that polyphenols bind to iron. Polyphenols binding to iron in the gut could lead to inactivation of aconitase 1 in the gut which could have systematic effects.
I have been very strongly stressing the effect of polyphenols on iron absorption, however, there are likely other difficulties with polyphenols for individuals. Polyphenols increase beta-oxidation. If the there are difficulties in fatty acid absorption and fatty acid metabolism increases in beta-oxidation due to polyphenols can not be sustained with difficulties then arising. Even with no difficulties in fatty acid absorption and fatty acid metabolism polyphenol laden drinks should not be drunk throughout the day. Limiting coffee to two cups of coffee drunk in the morning away from iron supplements could be a safe way to drink coffee.
Different polyphenols have different binding affinities to iron apparently due to different levels of iron-binding galloyl groups in different polyphenols. The polyphenols in foods with high levels of polyphenols would also bind iron at higher levels than polyphenols of foods with low levels of polyphenols. The point is that different foods with different kinds of polyphenols and different levels of polyphenols can have different affects on iron. However, if all iron is basically complexed with polyphenols due to coffee, tea and/or sodas then foods with different polyphenols and different levels of polyphenols might not make a difference. Fruits and vegetables would seem not to be delivering the real thing as well as Coca-Cola.
A direct connection between the gut and brain and mood is widely accepted now. How signals are sent from the gut to brain and how those signals affect mood has not been clearly established. Levels of aconitase 1 in the gut, activity of the TCA cycle in the gut and regulation of iron regulated proteins in the gut could play a large role in that connection.
Polyphenols besides inhibiting non-heme iron absorption in a dose dependent manner can also inhibit heme iron absorption in a dose dependent manner.
There is lots of controversy about flavorings for e-cigarettes. Here are some of the plant extract flavorings for e-cigarettes. Lung damage has been associated with vaping with e-cigarettes with flavorings found to be particularly harmful. Polyphenols bind iron. Polyphenols binding iron, which is needed for hemoglobin, in the lungs could adversely affect the ability to breathe. Mint flavorings are getting a pass in the FDA regulations on e-cigarette flavorings, however, mint has very high polyphenol contents.