Supplementing with free antioxidants in more than RDA amounts is worse than useless

Many illnesses, such as schizophrenia, Alzheimer’s disease, Parkinson’s disease and bipolar disorder are associated with oxidant stress. Yet, increasing levels of free antioxidants by supplementing with more than RDA amounts of vitamin E, beta-carotene and vitamin C does not treat these illnesses.

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.

Insulin resistance and elevated levels of circulating branched-chain amino acids

Elevated circulating levels of branched-chain amino acids have been associated with insulin resistance where decreased degradation of branched-chain amino acids could be what is leading to elevated circulating levels of branched-chain amino acids. Metabolic syndrome is associated with insulin resistance.

Methylcrotonyl CoA carboxylase and propionyl-CoA carboxylase are two biotin-dependent enzymes in the branched-chain amino acid degradation pathway. Dysregulation of the sodium-dependent multivitamin transporter which transports biotin could dysregulate the branched-chain amino acid degradation pathway leading to high levels of circulating branched-chain amino acids and insulin resistance.

Insulin resistance is present in 52% of individuals with bipolar disorder. Insulin resistance develops is brains of individuals with Alzheimer’s disease. In China in individuals with schizophrenia the prevalence of insulin resistance is 37.2% Both disease processes and drugs used to treat these illnesses could increase insulin resistance in theses illnesses. A commonality among these illnesses could be dysregulation of the sodium-dependent multivitamin transporter both by disease processes and drugs used to treat these illnesses.

Biotin supplementation decreases hyperglycemia, normalizing glucose levels, in patients with non-insulin dependent diabetes. There is reduced hyperglycemia is diabetic patients taking biotin.

The sodium-dependent multivitamin transporter transports both biotin and pantothenate. Pantothenate is needed to synthesize coenzyme A which is closely tied to the actions of biotin-dependent enzymes. Biotinylation of the sodium-dependent transporter reduces transport by the sodium-dependent multivitamin transporter. High levels of biotin could decrease transport of pantothenate by the sodium-dependent multivitamin transporter. A combination of pantothenic acid and biotin where 500 mg. of pantothenic acid is taken once a day away from supplemental biotin and 5 mg of biotin is taken three times a day could word work better in controlling hyperglycemia than biotin alone.

Only the abundance of biotinylated 3-methylcrotonyl-CoA carboxylase (holo-MCC) and propionyl-CoA carboxylase (holo-PCC) can distinguish between biotin-deficient and biotin-sufficient individuals. Methylcrotonyl CoA carboxylase and propionyl-CoA carboxylase could be particularly sensitive to biotin deficiencies.

Deficiencies in vitamin D in schizophrenia, bipolar disorder, Alzheimer’s disease and Parkinson’s disease

Low levels of vitamin D are associated with schizophrenia, bipolar disorder Alzheimer’s disease and Parkinson’s disease. Vitamin D is a fat soluble vitamin. Bile acids are required for fat absorption. Taurocholic acid is a bile acid that is a conjugate of cholic acid with taurine. Taurochenodeoxycholic acid is a bile acid formed in the liver by conjugation of chenodeoxycholic acid with taurine. Taurine increases absorption of vitamin D.

There are low levels of vitamin D in schizophrenia, bipolar disorder, Alzheimer’s disease and Parkinson’s disease due to dysregulation of taurine synthesis in these illnesses attendant on dysregulation of the transsulfuration pathway which synthesizes L-cysteine from which taurine is synthesized.

Supplementation with vitamin D in these illnesses heretofore has not helped much as difficulties in fat absorption have not been addressed. Taurine, which regulates calcium homeostasis besides aiding in fat absorption, taurine would be taken with vitamin D, vitamin K and calcium carbonate to address low levels of vitamin D where there are chronic illnesses. Vitamin K is also a fat soluble vitamin whose abosoprtion could be impaired by low levels of taurine.

Difficulties in iron-sulfur cluster formation can lead to iron accumulation in mitochondria

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.

Cholesterol, taurine and Alzheimer’s disease

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.

Iron and Alzheimer’s disease

Iron overload in various regions of the brain has been postulated to be involved in the pathological mechanism of Alzheimer’s disease. Iron overload in the brain may very well be involved in the etiology of Alzheimer’s disease but iron overload in the brain in Alzheimer’s disease would not be due to too much iron in the diet.

A meta-analysis indicates that serum iron levels are significantly lower in Alzheimer’s disease 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.

Loss of control over iron metabolism rather that just ‘too much iron’ could be why iron can have negative effects in Alzheimer’s disease. Treatment in AD would demand that control be regained over iron metabolism. Iron chelators have been proposed as a treatment for Alzheimer’s disease. Iron chelators, however, would not be useful in terms of regaining control over iron metabolism. Iron chelators could have negative effects in AD.

The APOE4 allele is associated with lower levels of selenium in the brain.

Bárbara R Cardoso  1   2 Dominic J Hare  1   3 Monica Lind  1 Catriona A McLean  1   4 Irene Volitakis  1 Simon M Laws  5   6 Colin L Masters  1   6 Ashley I Bush  1   6 Blaine R Roberts  1   6 Affiliations

Abstract

The antioxidant activity of selenium, which is mainly conferred by its incorporation into dedicated selenoproteins, has been suggested as a possible neuroprotective approach for mitigating neuronal loss in Alzheimer’s disease. However, there is inconsistent information with respect to selenium levels in the Alzheimer’s disease brain. We examined the concentration and cellular compartmentalization of selenium in the temporal cortex of Alzheimer’s disease and control brain tissue. We found that Alzheimer’s disease was associated with decreased selenium concentration in both soluble (i.e., cytosolic) and insoluble (i.e., plaques and tangles) fractions of brain homogenates. The presence of the APOE ε4 allele correlated with lower total selenium levels in the temporal cortex and a higher concentration of soluble selenium. Additionally, we found that age significantly contributed to lower selenium concentrations in the peripheral membrane-bound and vesicular fractions. Our findings suggest a relevant interaction between APOE ε4 and selenium delivery into brain, and show changes in cellular selenium distribution in the Alzheimer’s disease brain.

DHA and Alzheimer’s disease

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, taurine and essential fatty acids in schizophrenia, Parkinson’s disease and Alzheimer’s disease

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.