An exclusive focus on absorption of minerals is at odds with the gut being a key to various illnesses

The gut has become a primary focus of a lot of research on various illnesses. The gut has become a focus in research on major depressive disorder, schizophrenia, bipolar disorder, obsessive compulsive disorder, autism, anxiety, Parkinson’s disease, Alzheimer’s disease, osteoporosis, amyotrophic lateral sclerosis etc.

Yet the key selling point of most mineral supplements is increased absorption with increased absorption demanding that the gut be bypassed. Moreover almost all clinical studies done on humans employ inorganic forms of minerals rather than chelated organic forms of minerals. ‘Zinc gluconate human‘ turned up 560 results in Pubmed whereas ‘zinc methionine human, turned up 11 results where there were two human trials with an equivocal result in one of the trials and a positive result on a narrow measure of reduced acne in the other.

Individuals taking organic chelated mineral supplements are venturing into unknown lands and I think dangerous lands. Chelated minerals are highly absorbed but that is a bug not a feature.

Alzheimer’s disease and bone mineral density

Alzheimer’s disease patients are also at a higher risk for hip fractures than healthy controls. A meta-analysis indicated that the Odds Ratio for hip fractures in patients with Alzheimer’s disease is 1.80 compared to healthy controls. Low bone mineral density and increased loss rate of bone mineral density were associated with higher risk of Alzheimer’s disease.

There are a lot of illnesses where there are both high homocysteine levels and decreased bone mineral densities, for example, Alzheimer’s diseases. High homocysteine levels and decreased bone mineral densities in range of illnesses can be tied together by dysregulations of the transsulfuration pathway in such illnesses.

Iron, amyloid precursor protein, and Alzheimer’s

amyloid beta plaques

Amyloid precursor protein (APP) mRNA has an iron response element (IRE) in the 5′ untranslated region. Iron regulatory 1 (IRP1) and and iron regulatory protein 2 (IRP2) when bound to the IRE in the 5′ untranslated region destablize transcripts of iron regulated proteins. IRP1 and IPR2 when bound to the IRE in amyloid precursor protein mRNA decrease translation of APP. Iron decreases levels of IRP1 and IRP2. A point of iron chelators in Alzhemeir’s disease is by decreasing iron levels to increase levels of IRP1 and IRP2 thereby decreasing transcripition of APP.

APP is the precusor of amybloid beta protein. Amyloid beta can form plaques which are associated with Alzheimer’s disease. Iron chelators by decreasing APP levels would decrease levels of amyloid beta protein which was thought for decades to be a very good thing. Very effective treatments for Alzheimer’s appeared imminent.

A very serious difficulty arose. Drugs that reduce levels of amyloid beta do not treat or slow the progression of Alzheimer’s disease.

APP can looked at from a different angle. Amyloid precursor protein when ablated increases iron retention in cells by decreasing iron export. Loss of tight control of APP translation not high levels of APP could be what is causing iron retention in neurons.

What I have been arguing is that IRP1 is dysregulated in a range of neurological illnesses, such as Alzheimer’s and that this can lead to iron accumulation in neurons and cell death. Tight control of iron levels, not reducing iron levels via iron chelation, could be part of a treatment for various neurological illnessse such as Alzheimer’s disease.

A meta-analysis indicate that serum iron is significantly lower in Alzheimer’s patients than in controls. Supplmental iron carbonyl given three time a day could be part of a treatment for Alzheimer’s disease. The goal, of course, would not be high iron levels but rather tightly regulated levels of IRP1 and IRP2. Iron homeostasis could be upset in Alzheimer’s disease which is a much different way of loooking at iron than ‘iron is toxic’ in Alzheimer’s disease.

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.

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.

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.

Polyphenols, homocysteine, Parkinson’s disease and Alzheimer’s disease

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.

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.

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.