Taurine and neurotransmitter sodium symporters

Taurine regulates intracellular sodium levels. Long term supplemental taurine decreases levels of intracellular sodium. That taurine can affect intracellular sodium levels is clear. What is not clear is the effect of taurine on various sodium-dependent transporters. I have argued than low taurine levels by affecting sodium levels can dysregulate the sodium-dependent multivitamin transporter.

Neurotransmitter sodium symporters, which co-transport a neurotransmitter and sodium, among other molecules transport taurine, GABA, dopamine, serotonin and noradrenaline. Taurine is clearly involved in calcium homeostasis. Taurine could also be involved in sodium homeostasis.

Dysregulation of sodium homeostasis could dysregulate the transport of dopamine, serotonin, noradrenaline and GABA which play large roles in the regulation of mood. Antidepressants, antipsychotics and anioxylitcs target serotonin, dopamine, noradrenaline and GABA. Antidepressants, antipsychotics and anioxylitcs could be called for now in the treatment of mental illness due to dysregulation of sodium homeostasis which dysregulates dopamine, serotonin, noradrenaline and GABA.

Quite frequently individuals with major mental illnesses will take medications that affect dopamine, serotonin, noradrenaline and GABA. Dysregulation of sodium homeostasis could underlie the need by individuals with major mental illnesses to take medications from all three major classes of drugs used to treat mental illness. Supplemental taurine could help with re-regulation of sodium homeostasis. No argument is being made that only dysregulation of sodium homeostasis is the biological basis of major mental illnesses.

Pyruvate carboxylase and metabolic syndrome

Pyruvate carboxylase is a biotin-dependent enzyme involved in gluconeogenesis and lipogenesis, in the biosynthesis of neurotransmitters, and in glucose-induced insulin secretion by pancreatic islets. Pyruvate carboxylase is a key to beta cell adaptation to insulin resistance where pyruvate carboxylase reduction can lead to beta cell failure. In Agouti-K mice reduction of pyruvate carboxylase in pancreatic islets could play a role in the development of Type 2 diabetes.

Biotin deficiencies both by decreasing metabolism of branched-chain amino acids and decreasing activity of pyruvate carboxylase could lead to the development of metabolic syndrome in humans. Both biotin and pantothenate would have to be taken to treat metabolic syndrome where biotin would be taken three times a day and pantothenic acid taken once a day away from biotin. Both biotin and pantothenate are transported by the the sodium-dependent multivitamin transporter (SMVT). Pantothenic acid taken alone could competitively inhibit transport of biotin by the SMVT while biotin taken alone could decrease transport of pantothenic acid by biotinylation of histones at the SMVT locus.

Insulin resistance and elevated levels of circulating branched-chain amino acids

Elevated circulating levels of branched-chain amino acids have been associated with insulin resistance where decreased degradation of branched-chain amino acids could be what is leading to elevated circulating levels of branched-chain amino acids.

Methylcrotonyl CoA carboxylase and propionyl-CoA carboxylase are two biotin-dependent enzymes in the branched-chain amino acid degradation pathway. Dysregulation of the sodium-dependent multivitamin transporter which transports biotin could dysregulate the branched-chain amino acid degradation pathway leading to high levels of circulating branched-chain amino acids and insulin resistance.

Insulin resistance is present in 52% of individuals with bipolar disorder. Insulin resistance develops is brains of individuals with Alzheimer’s disease. In China in individuals with schizophrenia the prevalence of insulin resistance is 37.2% Both disease processes and drugs used to treat these illnesses could increase insulin resistance in theses illnesses. A commonality among these illnesses could be dysregulation of the sodium-dependent multivitamin transporter both by disease processes and drugs used to treat these illnesses.

Biotin supplementation decreases hyperglycemia, normalizing glucose levels, in patients with non-insulin dependent diabetes. There is reduced hyperglycemia is diabetic patients taking biotin.

The sodium-dependent multivitamin transporter transports both biotin and pantothenate. Pantothenate is needed to synthesize coenzyme A which is closely tied to the actions of biotin-dependent enzymes. Biotinylation of the sodium-dependent transporter reduces transport by the sodium-dependent multivitamin transporter. High levels of biotin could decrease transport of pantothenate by the sodium-dependent multivitamin transporter. A combination of pantothenic acid and biotin where 500 mg. of pantothenic acid is taken once a day away from supplemental biotin and 5 mg of biotin is taken three times a day could word work better in controlling hyperglycemia than biotin alone.

Only the abundance of biotinylated 3-methylcrotonyl-CoA carboxylase (holo-MCC) and propionyl-CoA carboxylase (holo-PCC) can distinguish between biotin-deficient and biotin-sufficient individuals. Methylcrotonyl CoA carboxylase and propionyl-CoA carboxylase could be particularly sensitive to biotin deficiencies.

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 conjugation 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, calcium hydroxyapatite and vitamin D are required to address low levels of vitamin D where there are also chronic illnesses.

The American Heart Association has made a tremendous error in regards to saturated fats

The campaign against saturated fats by the American Heart Association has been a tremendous error. The American Heart Association recommends that intake of saturated fats be severely limited. However, with biotin deficiencies and and underactivity of acetyl-CoA carboxylase fatty acids are not synthesized and saturated fatty acids are the first ‘non-essential’ fatty acids to be synthesized. Where there are long term biotin deficiencies, which I think are very prevalent, saturated fats become essential fatty acids. Profound depressions can result from lack of saturated fats in diets.

The supplemented fats must be animal fats. Butter or ghee works quickly for depression. Ghee appears to work better. Purchased beef tallow is apparently not beef tallow. Purchased beef tallow melts at room temperature which beef tallow should not do. Butter or ghee would be taken with taurine. Taurine assists with the absorption of fats.

I am leaving the question open as to whether saturated fats are bad for the heart, there is evidence that they are not, but many individuals will face the choice of absolutely crippling depressions and heart disease or more butter or ghee in the diet and perhaps statins.

The thyroid and major depression

Thyroid hormones have been extensively investigated in major depression but abnormalities in thyroid hormones have not been found. Still in terms of treating depression thyroid hormones have had attractions. Meta-analyses indicate that augmentation of anti-depressants with triiodothyronine (T3) or thyroxine (T4) and can be helpful in the treatment of refractory depression.

There are definite difficulties with thyroid function in major depression but the problem is too little iodine. With dysregulation of the sodium-dependent multivitamin transporter (SMVT) iodine transport is impaired. The SMVT transports iodine. The role of the SMVT in the transport of iodine has not been emphasized to the same extent as the role of the SMVT in the transport of biotin and pantothenic acid. As it turns out the SMVT plays a key role in iodide homeostasis which if upset can result in major depression despite normal levels of thyroid hormones.

As an augmentation strategy to anti-depressants iodine would be taken three times a day. The Tolerable Upper level Limit for iodine for adults is 1100 micrograms per day. Tests on thyroid function would have to be obtained. Abnormal levels of thyroid hormones as shown by tests on thyroid function must be avoided.

If iodine can augment anti-depressants in the treatment of major depression this would point to the SMVT as playing a key role in psychiatric illnesses.

Blood tests and false negatives

With epigenetic dysregulations dysregulated transcription does not have to be body wide. With hypermethylated genes and histones isolated to only a few organs blood tests may be normal even though there are definite difficulties. MDs in a all probability would agree that blood tests would not pick up a lot epigenetic dysregulations but then MDs would say ‘what can we do about that?’ and continue to draw blood and do tests on blood.

The SMVT and iodide

The sodium-dependent multivitamin transporter (SMVT) also transports iodide. How important the SMVT is for iodide transport is not clear. Supplementing with biotin and pantothenic acid, however, could competitively block the transport of iodide by the SMVT. There is another transporter of of iodide, the sodium/iodide cotransporter, (SLC5A5) which is largely expressed in the thyroid. The SMVT is expressed in the digestive tract.