In Friedreich ataxia iron-sulfur clusters are not formed, due to deficiencies in frataxin which results in iron accumulation in mitochondria. The relevant point is that problems in iron-sulfur cluster formation can be associated with iron accumulation in mitochondria and iron toxicity. The point I have been making is that there are difficulties in synthesizing iron-sulfur clusters in many neurological illnesses due to dysregulation of the transsulfuration pathway which synthesizes L-cysteine. L-cysteine supplies sulfur for iron-sulfur cluster formation.
Iron chelators are now being investigated as treatments for Alzheimer’s disease and Parkinson’s disease. If iron is being accumulated in cells in Alzheimer’s disease and Parkinson’s disease due to difficulties in iron-sulfur cluster formation then iron chelators would not be appropriate treatments. Iron-sulfur cluster formation is increased by supplemental iron. Iron chelators by decreasing iron would decrease iron–sulfur cluster formation leading to iron accumulation in mitochondria and iron toxicity.
In Alzheimer’s disease there are high levels of homocysteine which points to the transsulfuration pathway (homocysteine to L-cysteine) being dysregulated in Alzheimer’s disease. Taurine is synthesized from L-cysteine. Taurine lowers LDL cholesterol levels. High LDL cholesterol levels, which increase the risk of Alzheimer’s disease, could be connected to the dysregulation of transsulfuration pathway as with dysregulation of the transsulfuration pathway there will be low levels of taurine which will increase cholesterol levels.
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.
Docosahexaenoic acid (DHA) levels are low in Alzheimer’s disease. DHA is synthesized from alpha-linoelic acid which is an essential fatty acid which must be obtained from the diet. For DHA to be synthesized from alpha-linoelic acid, alpha linoleic acid must first be absorbed.
A meta-analysis indicates that homocysteine levels are significantly high in Alzheimer’s disease. High homocysteine levels in Alzheimer’s disease indicate the transsulfuration pathway is dysregulated in Alzheimer’s disease as homocysteine is not being metabolized to L-cysteine which is what the transsulfuration pathway does.
With low levels of L-cysteine there will be low levels of taurine. Taurine is synthesized from L-cysteine. Taurine is needed for the formation of bile acids which are needed for fat absorption. With alpha-linoelic acid not absorbed in Alzheimer’s disease due to low levels of taurine synthesis of DHA will be impaired in Alzheimer’s disease which is what is seen is Alzheimer’s disease. Effectiveness of supplementation with DHA in Alzheimer’s disease could be limited due to a failure to absorb DHA due to low levels of taurine in Alzheimer’s disease.
Taurine only poorly crosses the blood-brain barrier. However, to assist with essential fatty acid absorption taurine does not have to cross the blood-barrier. Taurine by enhancing fat absorption can enhance brain function.
Homotaurine has has been shown to be a promising therapy for Alzheimer’s disease. In Alzheimer’s disease taurine could be taken with with fatty acid supplements high in alpha linoelic acid, such as lignan free flax seed oil. Lignans are polyphenols so flax seed oil with lignans is avoided.
Inflammation is associated with schizophrenia, Parkinson’s disease and Alzheimer’s disease. A point I have strongly stressed is that the transsulfuration pathway is dysregulated in many neurological illnesses. With the transsulfuration pathway dysregulated there will de decreased levels of L-cysteine which is synthesized via the transsulfuration pathway. Decreased levels of l-cysteine will lead to decreased levels of taurine. Taurine is synthesized from L-cysteine. The bile acid, taurocholate, is synthesized from taurine. With low levels of taurine, essential fatty acids are not absorbed sufficiently. Inflammation in schizophrenia, Parkinson’s disease and Alsheimer’s disease could be due to low levels of taurine which leads to failures to absorb sufficient fatty acids with inflammation resulting.
Taurine chloramine which is synthesized from taurine is also an important immunomodulatory.
Supplemetantion that increases extracellular L-cysteine by decreasing levels of extracellular cystine, as do n-acetyl-l-cysteine and lipoic acid, must be avoided. Cystine, has to be available to enter cells via the cystine/glutamate antiporter so l-glutamate can be transported out. Any supplement that decreases extracellular cystine levels is very dangerous. Blocking the cystine/glutamate antiporter induces ferroptosis which can kill cells.