There could be some improvement in Alzheimer’s disease with appropriate treatment

There could be some improvement in Alzheimer’s disease with appropriate treatment. I am making a logical point. I have no biological evidence that this is the case. Various illnesses that present as dementia’s can be treated. Major depressive disorder can appear to be a dementia, however, the dementia of major depressive disorder is treatable. There could be certain aspects of Alzheimer’s disease that arise from biochemical abnormalities which are not strictly related to  death of neurons. With the biochemical abnormalities addressed various aspect of an Alzheimer’s dementia could be reversed. In my paper A disease-modifying treatment for Alzheimer’s disease: focus on the trans-sulfuration pathway  I argue than Alzheimer’s disease can be prevented and stopped with appropriate Treatment, however, from a logical viewpoint  some symptoms of Alzheimer’s disease could even be reversed especially in the early stages of the disease.

One clinical trial to rule them all

Bill Gates in a recent GatesNotes post talks about how expensive and time consuming  clinical trials for Alzheimer’s disease are. What I have been arguing is that a lot of chronic illnesses are due to dysregulations of epigenetic mechanisms. Aconitase 1 is an iron-sulfur enzyme in the  citric acid cycle which is required to produce 2-oxoglutarate and also regulates iron metabolism. Many enzymes are iron dependent and 2-oxoglutarate dependent enzymes. In terms of epigenetic dyregulations dysregulation of TET enzymes, which demethylate DNA and Jumonji domain-containing proteins, which demethylate histones,  are key.  TET enzymes and  Jumonji domain-containing proteins are iron and 2-oxoglutarate dependent enzymes.    With aconitase 1 dysregulated TET enzymes and Jumonji domain-containing proteins will be dysregulated due to lack of availability of 2-oxoglutarate and dysregulation of iron metabolism. With TET enzymes and Jumonji domain-containing proteins dysregulated there will be epigenetic dysregulations. There, however, can be many different kinds of epigenetic dysregulations whereby many different chronic illnesses can develop. A key point is that all these diseases could  respond to the same treatment.   One six week trial of the supplements in schizophrenia could open up a pathway for a new treatment for Alzheimer’s disease.  The evidence for dysregulation of aconitase 1 and dysregulation of epigenetic mechanisms in Alzheimer’s disease is strong. I recently published a paper, A disease-modifying treatment for Alzheimer’s disease: focus on the trans-sulfuration pathway on this subject. The treatment has been modified from what is the paper. Please see the Treatment page.

Supplements as preventive medicine is a fail

Supplements should have some immediate positive effects. Unless supplements have immediate positive effects there is no way to know whether  supplements are taking  individuals in the right direction.  Taking supplements to prevent diseases of aging is a poor strategy for healthy longevity. There are so many ways to go wrong with supplements that stumbling on a longevity supplement regime that really works is very unlikely, however, if supplements have immediate beneficial effects then one knows one is going the right direction. Taking supplements as preventive medicine is a fail as strategy for taking supplements. Balanced meals, watching the weight and exercise are the best preventive medicine all of which have immediate positive benefits.

A simple test

I claim that well-absorbed supplements can have deleterious effects. How could that claim be straightforwardly tested? Whey protein isolates are extremely well-absorbed whereby if my claim is correct supplementing with whey protein isolates should have very negative effects. Individuals taking whey protein isolates will  be overcome by a brain fog. Whey protein concentrate is not formulated for better absorption so whey protein concentrate, which can have no added whey protein isolates or added hydrolyzed whey proteins, can have positive effects. The test will in all probability give clearer results if individuals have some chronic illness. Labels must be looked at carefully. Frequently whey protein isolates are added to what is called whey protein.

Epigenetics changes everything

Each cell has the same DNA.  As this is the case there must be ways for cells to differentiate from other cells while all cells have the same DNA. In different cell types different genes are translated which is achieved by genes in different cell types having different epigenetic marks.  Epigenetic marks on genes can increase or decrease transcription of genes. DNA methylation and histone methylation are two ways genes can be epigenetically marked and thereby transcription of genes affected. There are various other ways that genes can be epigenetically marked. Environment can affect what epigenetic marks are on genes.

With genetic diseases there is systematic evidence of the genetic anomaly. Take any cell from the body and genes in that cell will show the genetic anomaly.  For example, blood tests can be used to detect genetic anomalies   With epigenetic diseases, however, there is no genetic evidence of the disease.

Vitamin D is now suspected to play a part in lots of illnesses and I think this is correct  but with epigenetic anomalies there need not be any genetic anomalies though there is still disease.  The last step in the formation of calcitriol, which is active vitamin D, by CYP27B1 requires an iron-sulfur protein called adrenodoxin. Due to difficulties in forming iron-sulfur clusters there will be low levels of adrenodoxin  whereby there are low levels of calcitriol. Giving calcitriol alone, however, is not sufficient to treat many illnesses where there is evidence of calcitriol deficiencies.  With iron-sulfur proteins dysregulated a lot of processes besides the formation of calcitriol will also be adversely affected.

There not being diseases associated with aberrant epigenetic marks is basically impossible given the large part that epigenetics plays in regulations of cells.   I think schizophrenia is  an illness associated with epigenetic aberrations, an illness in which there are deficiencies of calcitriol but which is basically non-responsive to calcitriol.

Supplementing with whey protein

Whey protein isolate is much better absorbed so whey protein isolate supplements should absolutely be avoided. Lots of whey proteins are mixtures of whey protein concentrate and whey protein isolates. Labels must be looked at carefully. The only whey protein supplements that are safe to take are supplements that are 100% whey protein concentrate with no added whey protein isolates or hydrolyzed whey proteins. Supplement corporations are geniuses at absorption enhancement, however, enhancing absorption of supplements has very deleterious consequences. Nature apparently held that as nutrients are there in the gastrointestinal system the nutrients should be used and the body became dependent on availability  of nutrients in the gastrointestinal system.  Any nutrient to be useful has to be available in the gastrointestinal system.  Supplement formulations that increase absorption of nutrients have been a disaster.

The Gut and Depression

There is a lot of research on connection of the gut to mental disorders. The gut microbiome is being heavily researched in connection with mental illnesses. I think the gut does play a big part in mental orders, however, the problem is that ACO1 is dysregulated in the gut. Taking iron from iron sulfate 4 times a day  with vitamin C and copper from copper sebecate twice  a day can supply continuously the minerals needed to re-regulate ACO1 in the gut.

There are some very effective mineral chelates on the market, however, there is absolutely no need for minerals to be chelated. Chelated minerals bypass the gut and are at best totally useless in terms of treating mental illnesses. The three evilest words in supplements are ‘chelated’ and ‘better absorbed’.

Aconitase 1 and on-off disorders

Aconitase 1 (ACO1) is an enzyme in the citric acid cycle. Aconitase 1 is a dual function protein. Upon loss of an iron-sulfur cluster ACO1  becomes iron regulatory protein 1 (IRP1).  IRP1 affects stability of mRNA transcripts of proteins involved in iron metabolism such as ferritin, DMT1, which is an iron transporter, and ferroportin, which is the only known iron exporter.   Increasing iron levels switches IRP1 to ACO1 as IRP1 gains an iron-sulfur cluster. With a 4Fe-4S iron-sulfur cluster ACO1 can participate in the citric acid cycle and generate ATP.

I think on-off disorders are due to wide swings in ACO1/IRP1. Suddenly the citric acid  cycle is functioning and then the citric acid cycle is not functioning while at the same time there are swings in the regulation of iron regulated proteins. Dietary iron could be associated with swings in on-off symptoms.

ACO1 is regulated  by iron. Increased levels of iron activate ACO1 and deactivate IRP1. What has to be done to stop the on-off effect is to take approximately 33 milligrams of iron from iron sulfate four times a day with 500 milligrams of vitamin C each dosage. Coffee and tea must be avoided and the iron should be taken on an empty stomach. Coffee and tea are big interactions. For coffee addicts I recommend caffeine pills.  Caffeine has less of an interaction with iron than does coffee.

ACO1 is highly expressed in the intestines. All the literature about iron bisglyinate being a very strong chelate is accurate, however, iron must be available in the intestines immediately and throughout the day to stop  on-off symptoms. Iron bisglycinate is avoided even though all the information given out by Albion, which manufactures iron bisgylicnate,  is completely accurate.

An added wrinkle is  that high IRP1 levels adversely affects copper absorption, however, copper is needed for iron metabolism. 4 mg. of copper from copper sebacate is taken twice daily. The Tolerable Upper Intake Level  for copper is 10 mg. a day. Copper as well iron tests must be obtained.

I very much like answers that answer everything. On-off symptoms are prominent in lots and lots of illnesses. There is, of course, bipolar disorder but a lot of depressions cycle rapidly and are some of the most difficult depressions to treat.  Parkinson’s disease has a very prominent on-off symptoms.  In Parkinson’s disease there are  indications that iron metabolism is  dysregulated. There may be a unitary explanation for cycling disorders.

 

Anemia and depression

The symptoms of depression are a lot like the symptoms of anemia except individuals who are depressed have normal hemoglobin levels. As the word ‘hemoglobin’ suggests hemoglobin contains heme. Not all iron proteins are heme proteins. My idea is that there can be difficulties is iron-sulfur proteins though heme proteins, such as hemoglobin, are functioning appropriately.  Would iron supplementation be enough to treat depression? Probably not though iron supplements could be of assistance.   The mechanisms that dysregulate iron-sulfur proteins could also dysregulate other biological processes whereby other supplements would be required.

Iron has to be supplemented with vitamin C and away from food, coffee and tea.    A lot of individuals who are depressed are in very desperate situations. First of all follow medical advice but if someone is still very depressed after following medical advice a treatment trial of the supplements suggested in the Treatment section could be appropriate, however, lab tests must obtained.

Individuals taking iron supplements in more than RDA amounts should have anemias panel done. An anemia panel can be ordered on line for $89. Also a CBC test   (complete blood count) should be done to check that hemoglobin levels are not too high.A metabolic panel should be obtained.  A CBC test costs $28 at Walk-in-Lab. The Treatment could be quickly effective as what is being addressed is iron-sulfur proteins not hemoglobin, which takes weeks to rise to normal levels.

Why are there more women who are depressed than men? Women have monthly blood loss from menstruation whereby more women than men have difficulties with iron metabolism  in terms of both heme proteins and iron-sulfur proteins.

If the proposed Treatment works terrific but do not try to improve on the Treatment. Supplements are a minefield.