Supplement formulations

There are two problems with supplement formulations. First of all sometimes supplements contain adulterants which seems to be a particular problem with herbs and weight loss supplements. I am not going to talk about adulterates in supplements further.

Another difficulty is that supplements very frequently are formulated for high absorption and/or quick absorption. Formulators of supplements assiduously peruse PubMed and then formulate supplements, highly successfully, for high absorption and/or quick absorption. Manufacturing quality is excellent. Individuals manufacturing these supplements are honest and not cutting corners in manufacturing.

The supplements do exactly what is advertised, however, what is advertised, as is often the case, is not what individuals need or is best for individuals. The only difficulty is what is manufactured to high specifications can have adverse effects on health.

The simple fact of the matter is than supplements must first be bioavailable in the gut. Yes, supplements must be bioavailable systematically but only after being bioavailable in the gut. This one small detail about supplements changes everything about supplements.

Serendipity and drug discovery

Frequently scientists talk about the serendipitous finding that leads to important discoveries. In psychiatry serendipitous drug discoveries, however, may not advance understanding of psychiatric illnesses very much. Dopamine antagonists are useful in the treatment of schizophrenia but there has been no revolution in the understanding of schizophrenia resulting from the discovery that dopamine antagonists can partially treat schizophrenia. Lithium has uses but lithium has not revolutionized the understanding of bipolar disorder.

A lot of research seems directed at finding the hidden fact that will be the key to unraveling a disease. Researchers seem to be in search of serendipity which is not how serendipity works. Psychiatric research would better off if there was more emphasis on basic research with translational research then sticking closely to basic research. Succeeding at translational research may require that all the various factors that complicate a hypothesis be considered. The devil is the details. Possessing a sliver of truth is surer route to scientific discovery than searching for serendipity.

The basic idea that the transsulfuration pathway is dysregulated in schizophrenia is a simple idea but treatment is complicated by the fact that downstream pathways from the transsulfuration pathway have to be addressed. Treatment would be so much simpler if only lowering homocysteine levels worked or only increasing l-cysteine levels worked but neither do. There can be effective treatments for schizophrenia that address the fundamental biology of schizophrenia but there can be no simple effective treatments for schizophrenia that address the fundamental biology of schizophrenia.

Muscarinic agonists and schizophrenia

chewing betel nut

Muscarinic agonists are being studied in terms of the treatment of schizophrenia. There is some indication that muscarinic agonists can successfully treat schizophrenia. So far so good.

Nicotine is one of the most addictive substances on Earth. Nicotine agonizes nicotinic acetylcholine receptors which are a different kind of acetylcholine receptor than muscarinic acetylcholine receptors. Muscarinic agonists may have no addictive potential and may in fact be drugs that can treat addictions. However, betel nut which activates muscarinic receptors is very addictive . Before mucarinic agonists are generally prescribed any addiction potential of muscarninic agonists has to be thoroughly addressed.

Phrenology and schizophrenia

All books that address the history of scientific research on the brain have sections on phrenology. The upshot of book sections on phrenology is that phrenology was the dark ages of brain research. A lot of phrenology was nonsense. But is there a kernel of truth to phrenology? I have been claiming that the negative symptoms of schizophrenia are due to brains being compressed due to hidden osteomalacia arising from dysregulation of calcium homeostasis due to deficiencies in taurine.

Wolfgang Pauli once said ‘the idea is so bad it is neither right or wrong‘. My idea could be wrong. I am not quite certain what imagining techniques are used to detect osteomalacia but the evidence may right now be stored in data banks. Currently skulls are stripped from MRI images. A search of PubMed using the search terms “osteomalacia” and “schizophrenia” turned up three articles which were irrelevant. There is apparently a reduction in brain volumes in schizophrenia which could be due to skulls being compressed due to hidden osteomalacias.

So far brain imaging has only discovered that individuals with brain structures that are all in the normal range of sizes can have schizophrenia. Still brain imaging or at least skull imaging could could be a key to treatment of the negative symptoms of schizophrenia which can be devastating.

Cytomegalovirus and schizophrenia

In individuals with schizophrenia 68% of the patients had an increased CSF/serum antibody ratio for cytomegalovirus (CMV) antibody, Cytomegalovirus is associated with anemia. Like toxoplasma gondii the association of cytomegalovirus to schizophrenia could be due to the effect of cytomegalovirus on iron status.

Lots of viruses are associated with anemia. Given that the effect of parasites, bacteria and viruses on incidences of schizophrenia is due to the effect of parasites, bacteria and viruses on iron status then treatments that directly address parasites, bacteria and viruses would not be useful treatments for schizophrenia as individuals can be hit from many different directions while antiparasitics, anti-virals and and antibacterial agents etc would address only a single route. To treat schizophrenia iron status would have to be directly addressed.

Schizophrenia, toxoplasma gondii and iron-responsive protein 1

toxoplasma gondii

The Odd Ratio for schizophrenia for indivduals with IgG antibodies for toxoplasma gondii were 1.81, With toxoplasma gondii infection.there is increased activity of iron-responsive protein 1 (IRP1). Aconitase 1 is a dual fuction protein, When iron levels are low aconitase 1 looses and iron sulfur cluster and becomes IRP1 but when iron levels are increased IRP1 gains an iron-sulfur cluster and becomes aconitase 1. Aconitase 1 is an enzyme in the tricarboxylic acid (TCA) cycle. Increased levels of IRP1 would indicate that the TCA cycle is dysregulated which could set the set the stage for schizophrenia. See my paper Treatment-resistant schizophrenia: focus on the transsulfuration pathway. on how dysregulation of IRP1, aconitase 1 and the TCA cyle could play a part in the development of schizophrenia.

Autism and the transsulfuration pathway

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Dysregulation of the transsulfuration pathway has been implicated in autism with research showing homocysteine and and oxidized glutathione levels were significantly higher in children diagnosed with autism spectrum disorders while cysteine levels, total glutathione and glutathione were remarkably lower in childiren with autism spectrum disorder compared to control subjects. Homocysteine levels levels correlated significantly with increasing Childhood Autism Rating Scale scores.

Taurine is synthesized from l-cysteine. Taurine is involved in calcium homeostasis. Taurine levels in autistic children were lower than than in controls. There may be low taurine levels only in a subset of indivduals with autism. Not all studies show taurine levels are low in autism.

Research points to intracellular calcium homeostasis being dysregulated in autism. Genes for various sub-units of proteins that act as calcium channels are associated with autism. In autism dysregulation of the transsulfuration pathway could dysregulate taurine synthesis which could dysregulate calcium homeostasis.

Whatever the answer is increasing levels of L-cysteine through supplementing with L-cysteine containing amino acids is not the answer. L-cysteine containing amino acids can be very toxic.

Why are all soft drinks carbonated?

Bicarbonate is crucial to the pH buffering system. Enzymes work best at certain pHs. Carbonated drinks could be affecting pH levels in the gut and thereby altering actions of various enzymes in the gut. A small lift could result upon drinking a carbonated drink. That small lift multiplied a billion times could translate into a multi-billion dollar industry.

Seltzer, which is carbonated water, with absolutely no added ingredients may be a safe drink imparting a very small lift. Any added ingredients would ruin the seltzer. 98% of seltzer water has been ruined by added ingredients.

Quercetin is an iron chelator, is bioavailable and crosses the blood-brain barrier

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Quercetin is a very effective iron chelator. Supplemental quercetin is bioavailable increasing blood levels dose-dependently. Quercetin also crosses the blood-brain barrier. Quercetin is being investigated for use in the treatment of Parkinson’s disease.

If iron chelators work in Parkinson’s there should be some positive effect with supplemental quercetin. I very much doubt there will be. See the page on Parkinson’s disease. If quercetin does not work in the treatment of Parkinson’s disease then the narrative that treatment of Parkinson’s disease requires iron chelation has to be re-thought. I would avoid supplementing with quercetin until there are definite clinical studies to the effect that quercetin in the real world ameliorates symptoms of Parkinson’s disease which I think will be never.

Quercetin is found in fruits and vegetables. Querectin found in foods could have benefcial effects. Like other antioxidants, when obtained from food, quercetin could have beneficial effects.

Why lipoic acid should never be supplemented

The sodium-dependent multivitamin transporter transports biotin, pantothenic acid and lipoate (Prasad et al. 1997). The three vitamins competitively inhibit transport of each other. Lipoate inhibits the transport of biotin and pantothenic acid (Prasad et al. 1998). Biotin is taken in microgram quanties while lipoic acid is taken in 600 milligram and higher quantites. What is more lipoate is synthesized on proteins whereby there is no need for free lipoic acid. All supplemental lipoic acid would be doing is blocking the transport of biotin and pantothenic acid.