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.

Occam’s razor and mood stabilizing drugs for bipolar disorder

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Occam’s razor – the simplest explanation is usually the right one. How do mood stabilizers work to stabilize mood?

Lithium can stabilize sodium-dependent transporters and sodium-dependent G-protein coupled receptors in inactive states. Lithium  reduces activity of various sodium-dependent transporters, for example, Na(+)-coupled inorganic phosphate cotransporters (Andrini et al., 2012), Na+/Cl)/glycine cotransport (Pérez-Siles et al., 2011) and the sodium-myo-inositol co-transporter (Willmroth et al., 2007).

Blocking sodium channels is one of the key mechanisms by which anticonvulsants work (Brodie,  2017). Carbamazepine, valproic acid and lamotrigine are anticonvulsants used to treat bipolar disorder (Bowden and Karren, 2006.). Carbamazepine is a sodium channel blocker (Kennebäck et al., 1995). Valproic acid blocks sodium channels (Zanatta et al., 2019). Lamotrigine also blocks sodium channels (Kuo, 1998).

Occam’s razor applied to mood stabilizers – Mood stabilizers work by affecting sodium-dependent transporters and/or sodium-dependent G-protein coupled receptors.

Autism, intracellular calcium and taurine

Dysregulations of intracellular calcium are thought to play a role in autism. Taurine regulates intracellular calcium in neurons. A subgroup of children with autistic spectrum disorders, 21 out of 66, had low taurine concentrations (<106 μM).

Children with autism spectrum disorders have low bone mineral density. Taurine is involved in bone formation via stimulating bone growth and inhibiting bone loss.

Children with autism had lower serum 25(OH)D (a metabolite of vitamin D) concentrations than did control subjects (19 vs. 33 ng/ml), despite parents of each group reporting the same amount of sun exposure. Taurine conjugated to bile acids assists in the absorption of fat-soluble vitamins. Vitamin D is a fat-soluble vitamin. Vitamin K is fat-soluble vitamin involved in bone formation via osteocalcin. Vitamin K deficiencies could co-occur with vitamin D deficiencies as in both cases there could be a failure to absorb fat-soluble vitamins due to deficiencies in taurine.

Dysregulations of taurine could play a key role in the development of autism. A treatment for autism could look a lot like a treatment for osteoporosis. Taurine, vitamin D3, vitamin K2 MK-7, which is better absorbed than other forms of vitamin K, and calcium from calcium carbonate could be helpful in a subgroup of children with autism who also have low taurine levels. No studies of taurine, vitamin D3, vitamin K (MK-7) and calcium from calcium carbonate in the treatment of autism have yet been done.

CACNA1C (Cav1.2) and psychiatric disease

The calcium channel, voltage-dependent, L type, alpha 1C subunit is a protein that is encoded by the CACNA1C gene. Via calcium channels calcium influxes into cells. Mutations in CACNA1C are associated with bipolar disorder, depression, schizophrenia and autism. Gain of function mutations in CACNA1C are associated with disease, for example, autism.

Taurine regulates intracellular calcium levels by preventing influxes of calcium into cells but not effluxes of calcium out of cells. Via regulating influxes of calcium into cells taurine has a role in the treatment of psychiatric disorders that are in part due to gain of function mutations in CACNA1C.