I delete all place holder followers. I am not making recommendations on what supplements to take. A sensible reaction to this blog would not be to start a supplement program. There are too many unknowns, there could be surprising toxicities and a lot more research is required. What I would like is that at some future point researchers focus on the differential effect of different mineral formulations on the gut. Then some of these posts could be helpful. I also can imagine levels of TET enzymes being tested in a variety of mental illnesses where then again some of what I have posted could click.

Ahmed A. Moustafa was kindly willing to listen to my views allowing me to write the papers and publish my views.

I published an article on the etiology of schizophrenia in Reviews in the Neurosciences. The title of the paper is Treatment-resistant schizophrenia: focus on the transsulfuration pathway.  The abstract is below.   The treatment for schizophrenia has been updated with the updated treatment presented on the Treatment Page.


Treatment-resistant schizophrenia (TRS) is a severe form of schizophrenia. The severity of illness is positively related to homocysteine levels, with high homocysteine levels due to the low activity of the transsulfuration pathway, which metabolizes homocysteine in synthesizing L-cysteine. Glutathione levels are low in schizophrenia, which indicates shortages of L-cysteine and low activity of the transsulfuration pathway. Hydrogen sulfide (H2S) levels are low in schizophrenia. H2S is synthesized by cystathionine β-synthase and cystathionine γ-lyase, which are the two enzymes in the transsulfuration pathway. Iron-sulfur proteins obtain sulfur from L-cysteine. The oxidative phosphorylation (OXPHOS) pathway has various iron-sulfur proteins. With low levels of L-cysteine, iron-sulfur cluster formation will be dysregulated leading to deficits in OXPHOS in schizophrenia. Molybdenum cofactor (MoCo) synthesis requires sulfur, which is obtained from L-cysteine. With low levels of MoCo synthesis, molybdenum-dependent sulfite oxidase (SUOX) will not be synthesized at appropriate levels. SUOX detoxifies sulfite from sulfur-containing amino acids. If sulfites are not detoxified, there can be sulfite toxicity. The transsulfuration pathway metabolizes selenomethionine, whereby selenium from selenomethionine can be used for selenoprotein synthesis. The low activity of the transsulfuration pathway decreases selenoprotein synthesis. Glutathione peroxidase (GPX), with various GPXs being selenoprotein, is low in schizophrenia. The dysregulations of selenoproteins would lead to oxidant stress, which would increase the methylation of genes and histones leading to epigenetic changes in TRS. An add-on treatment to mainline antipsychotics is proposed for TRS that targets the dysregulations of the transsulfuration pathway and the dysregulations of other pathways stemming from the transsulfuration pathway being dysregulated.

The transsulfuration pathway could be dysregulated is other illnesses, for example, Alzheimer’s disease. I published an article on Alzheimer’s disease that focuses on the transsulfuration pathway. The abstract is given below.   The article was published in Reviews in Neuroscience as A disease-modifying treatment for Alzheimer’s disease: focus on the trans-sulfuration pathway.  The treatment for Alzheimer’s disease and schizophrenia would be basically the same is surprising but both diseases arise from dysregulations of the transsulfuration pathway though there are different epigenetic changes in the two diseases.


High homocysteine levels in Alzheimer’s disease (AD) result from low activity of the trans-sulfuration pathway. Glutathione levels are also low in AD. L-cysteine is required for the synthesis of glutathione. The synthesis of coenzyme A (CoA) requires L-cysteine, which is synthesized via the trans-sulfuration pathway. CoA is required for the synthesis of acetylcholine and appropriate cholinergic neurotransmission. L-cysteine is required for the synthesis of molybdenum-containing proteins. Sulfite oxidase (SUOX), which is a molybdenum-containing protein, could be dysregulated in AD. SUOX detoxifies the sulfites. Glutaminergic neurotransmission could be dysregulated in AD due to low levels of SUOX and high levels of sulfites. L-cysteine provides sulfur for iron-sulfur clusters. Oxidative phosphorylation (OXPHOS) is heavily dependent on iron-sulfur proteins. The decrease in OXPHOS seen in AD could be due to dysregulations of the trans-sulfuration pathway. There is a decrease in aconitase 1 (ACO1) in AD. ACO1 is an iron-sulfur enzyme in the citric acid cycle that upon loss of an iron-sulfur cluster converts to iron regulatory protein 1 (IRP1). With the dysregulation of iron-sulfur cluster formation ACO1 will convert to IRP1 which will decrease the 2-oxglutarate synthesis dysregulating the citric acid cycle and also dysregulating iron metabolism. Selenomethionine is also metabolized by the trans-sulfuration pathway. With the low activity of the trans-sulfuration pathway in AD selenoproteins will be dysregulated in AD. Dysregulation of selenoproteins could lead to oxidant stress in AD. In this article, we propose a novel treatment for AD that addresses dysregulations resulting from low activity of the trans-sulfuration pathway and low L-cysteine.

I published an article on the prevention of Parkinson’s disease, which focuses on iron regulatory protein 1 (IRP1), where an experiment is proposed that has to be tested in rats. Clinical trials could show that the treatment proposed to prevent Parkinson’s disease could also be effective as part of a treatment for Parkinson’s disease. The paper was published in the International Journal of Neuroscience as A novel treatment strategy to prevent Parkinson’s disease: focus on iron regulatory protein 1 (IRP1). IRP1 is also involved in schizophrenia and Alzheimer’s disease.


We propose that neural damage in Parkinson’s disease (PD) is due to dysregulation of iron utilization rather than to high iron levels per se. Iron deposits are associated with neuronal cell death in substantia nigra (SN) resulting in PD where high levels of iron in SNs are due to dysregulation of iron utilization. Cytosolic aconitase (ACO1) upon losing an iron-sulfur cluster becomes iron regulatory protein 1 (IRP1). Rotenone increases levels of IRP1and induces PD in rats. An increase in iron leads to inactivation of IRP1. We propose a novel treatment strategy to prevent PD. Specifically in rats given rotenone by subcutaneous injections, iron, from iron carbonyl from which iron is slowly absorbed, given three times a day by gavage will keep iron levels constant in the gut whereby iron levels and iron utilization systematically can be tightly regulated. Rotenone adversely affects complex 1 iron-sulfur proteins. Iron supplementation will increase iron-sulfur cluster formation switching IRP1 to ACO1. With IRP1 levels kept constantly low, iron utilization will systematically be tightly regulated stopping dysregulation of complex 1 and the neural damage done by rotenone preventing PD.

I also published a paper on the prevention on osteoporosis which focuses on the transsulfuration pathway and taurine. The paper was published in Clinical Nutrition ESPEN as Osteoporosis and the effect of dysregulation of the transsulfuration pathway via taurine on intracellular calcium homeostasis, vitamin D absorption and vitamin K absorption.

Background & Aims

In this article we connect the dysregulation of the transsulfuration pathway to bone dysregulations and propose a novel treatment for osteoporosis. Current treatments for osteoporosis are very frequently inadequate. In osteoporosis, the risk of fractures increases with increased homocysteine (Hcy).


Here, we conduct a review on the relationship between osteoporosis and the dysregulation of the transsulfuration pathway.


We show that the transsulfuration pathway metabolizes Hcy to L-cysteine. Increased Hcy levels point to the transsulfuration pathway being dysregulated. With the transsulfuration pathway dysregulated, there will be decreased levels of L-cysteine and decreased levels of taurine, which is synthesized from L-cysteine. Taurine levels are decreased in patients with osteoporosis. Taurine regulates intracellular calcium homeostasis. Taurine, also, when conjugated with bile acids assists with absorption of fats and fat-soluble vitamins such as vitamin D and vitamin K. Dysregulated calcium homeostasis, decreased calcium absorption and decreased absorption of vitamin D and vitamin K due to low levels of taurine negatively affect bone mineral density (BMD) leading to osteoporosis and fractures.


In this article, we propose that a combination of taurine, calcium, vitamin D and vitamin K, could increase BMD reducing number of years spent in disability and reducing deaths due to fractures in patients with osteoporosis.

The graphic at the top of the website pages shows methylation marks (shiny stars )  on DNA. Methylation marks placed on genes control transcription of genes. Epigenetic changes can lead to the development various neurological illnesses, for example, schizophrenia and Alzheimer’s disease.