Taurine chloramine downregulates the production of proinflammatory mediators

Taurine chloramine produced from taurine under inflammation provides anti-inflamnatory and cytoprotective effects

Chaekyun Kim  1 Young-Nam Cha

Abstract

Taurine is one of the most abundant non-essential amino acid in mammals and has many physiological functions in the nervous, cardiovascular, renal, endocrine, and immune systems. Upon inflammation, taurine undergoes halogenation in phagocytes and is converted to taurine chloramine (TauCl) and taurine bromamine. In the activated neutrophils, TauCl is produced by reaction with hypochlorite (HOCl) generated by the halide-dependent myeloperoxidase system. TauCl is released from activated neutrophils following their apoptosis and inhibits the production of inflammatory mediators such as, superoxide anion, nitric oxide, tumor necrosis factor-α, interleukins, and prostaglandins in inflammatory cells at inflammatory tissues. Furthermore, TauCl increases the expressions of antioxidant proteins, such as heme oxygenase 1, peroxiredoxin, thioredoxin, glutathione peroxidase, and catalase in macrophages. Thus, a central role of TauCl produced by activated neutrophils is to trigger the resolution of inflammation and protect macrophages and surrounding tissues from being damaged by cytotoxic reactive oxygen metabolites overproduced during inflammation. This is achieved by attenuating further production of proinflammatory cytokines and reactive oxygen metabolites and also by increasing the levels of antioxidant proteins that are able to scavenge and diminish the production of cytotoxic oxygen metabolites. These findings suggest that TauCl released from activated neutrophils may be involved in the recovery processes of cells affected by inflammatory oxidative stresses and thus TauCl could be used as a potential physiological agent to control pathogenic symptoms of chronic inflammatory diseases.

Taking supplemental taurine lowers blood pressure in humans

Taurine lowers blood pressure in humans by increasing synthesis of hydrogen sulfide, which is a vasodilator, through increasing activities of cystathionine beta-synthase and cystathionine gamma-lyase, the two enzymes in the transsulfuration pathway. Cystathionine beta-synthase and cystathionine gamma-lyase synthesize hydrogen sulfide. A meta-analysis indicates that taurine lowers blood pressure in clinically relevant amounts. Taurine also decreases homocysteine levels in humans. There is also lots of evidence from animals than taurine lowers total cholesterol. Research points to taurine as being the factor for Japanese longevity which could be due to taurine lowering various cardiovascular risk factors. The actions of taurine are more pronounced when taurine is taken on an empty stomach.

Calcium homeostasis in osteoblasts and osteoclasts and bone formation and bone resorption

Osteoblasts are involved in bone formation. Osteoclasts break down bone. Dysregulation of calcium homeostasis in osteoblasts and osteoclasts could lead to bone abnormalities. In the forward mode of the Na/calium exchanger calcium is effluxed from cells while in reverse mode there is an influx of calcium into cells via the Na/calcium exchanger.

Taurine inhibits the reverse mode of the Na/calcium exchanger. The Na/calcium exchanger (NCX) is expressed in osteoblasts. The taurine transporter is expressed in osteoblasts. In osteoblasts inhibting the reverse mode of the Na/calcium exchanger would increase calcium net efflux from osteoblasts which would increase bone formation. Taurine inhibits osteoclastogenesis through the taurine transporter. In osteoclasts inhibiting the reveres mode of the Na/calicum exchanger would inhibit the influx of calcium into osteoclasts from bone which would inhibit bone resorption.

Extracellular calcium levels are very tightly controlled and are very, very frequently tested. However intracellular homeostasis of calcium in osteoblasts and osteoclasts could be very imporant as to whethere there is bone bone growth or bone resorption. Taurine is involved in calcium homeostasis in cells. Taurine both increases bone growth and inhibits bone resorption. The positive effects of taurine on bone fomation could be via the inhibition of the reverse mode of the Na/calcium exchanger in osteoblasts and osteoclasts.

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.

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 conjugate 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, taurine would be taken with vitamin D, vitamin K and calcium carbonate to address low levels of vitamin D where there are chronic illnesses. Vitamin K is also a fat soluble vitamin whose abosoprtion could be impaired by low levels of taurine.

Huge controversies over vitamin D

Over the last few decades there have been huge controversies about whether there are widespread vitamin D deficiencies and whether vitamin D supplementation could prevent many chronic illnesses. Dr. Michael Holick holds there is a vitamin D deficiency pandemic. Dr. Holick points to association of vitamin D deficiency with a myriad of acute and chronic illnesses including preeclampsia, childhood dental caries, periodontitis, autoimmune disorders, infectious diseases, cardiovascular disease, deadly cancers, type 2 diabetes and neurological disorders.

However, a umbrella study that addressed meta-analyses that addressed studies where vitamin D supplements were given did not show much effectiveness in terms of outcomes when vitamin D was supplemented.

The views of Dr. Holick on vitamin D are a lot more correct than incorrect. Taurine, however. is required for calcium homeostasis. See also this paper. See also this paper. With eficiencies in taurine calcium homeostasis is upset. With taurine deficiencies individuals can develop severe bone absormalities even where vitamin D levels are normal.

The umbrella study as to the efficacy of vitamin D supplementation alone is also correct. Supplementation with vitamin D alone is not enough to treat ts dysregulations of calcium homeostasis due to deficiencies in taurine. To treat dysregularities in calcium homeostasis due to deficiencies in taurine, L-taurine must be supplemented with vitamin D3 and vitamin K2 MK-7. Calcium citrate is avoided.

Opioids or taurine, calcium carbonate, vitamin D, and vitamin K for back pain?

Opioids are very frequently prescribed for back pain. Opioid addictions are a horrendous problem in the US and around the World. If a lot of back pain is due to a hidden osteomalicia then there could be a switch away from opioids to treat back pain to taurine, calcium cabonate, vitamin D and vitamin K. Thousands and thousands of lives could be saved by switching to taurine, calcium carbonate, vitamin D3 and vitamin K. Mexico could be brought back from the abyss that drug cartels have brought Mexico to.

A point about a hidden osteomalacia is that in a hidden osteomalacia intracellular calcium homeostasis is dysregulated due to dysregulations of taurine synthesis. Taurine is involved in intracellular calcium homeostasis. Along with a hidden osteomalacia there would be a plethora of very negative psychological effects due to dysregulations in intracellular calcium homeostasis. People with back pain due to a hidden osteomalacia would not only be in physical pain but would also be in very serious psychological pain. Indeed back pain would be an indication that opioids should not be prescribed as individuals with back pain would be very prone to addiction to opioids due to the psychological pain that goes hand in hand with back pain.

The psychological pain associated with a hidden osteomalacia could be the driving force for addictions to opioids where there is back pain as opioids are not all that effective for the physical pain attendant on back aches.

If taurine, calcium carbonate, vitamin D3 and vitamin K (MK-7) could treat back pain this would be infinitely preferable to treatment of back pain with opioids.

A secret of the ages

As it turns out lots of backaches are due to a hidden osteomalacia. With low levels of taurine fine control of intracellular calcium homoestasis is lost. Calcium blood levels can be normal or just slightly low and one can still have a severe case of osteomalicia. Osteomalacia refers to a marked softening of the bones, most often caused by severe vitamin D deficiency. Severe vitamin D deficiencies can result in poor absorption of calcium which can lead to softening of the bones.

Taurine is required for calcium homeostasis. See also this paper. See also this paper. With taurine deficiencies fine control of intracellular calcium homesostasis is lost which can lead to a hidden osteomalicia as calcium levels are normal or very near normal.

The treatment for bach ache would be to take taurine, vitamin D, calcium carbonate. and vitamin K (MK-7). Vitamin K is also a fat soluble whose absorption could be impaired by low levels of taurine. Vitamin K in the form of MK-7 is much better absorbed than other forms of vitamin K. Vitamin D, vitamin K (MK-7) and calcium carbonate would be taken with food for better absorption while taurine would be taken on an empty stomach for better absorption. The right supplements could be very helpful in treating back pain.

Cholesterol, taurine and Alzheimer’s disease

In Alzheimer’s disease there are high levels of homocysteine which points to the transsulfuration pathway (homocysteine to L-cysteine) being dysregulated in Alzheimer’s disease. Taurine is synthesized from L-cysteine. Taurine lowers LDL cholesterol levels. High LDL cholesterol levels, which increase the risk of Alzheimer’s disease, could be connected to the dysregulation of transsulfuration pathway as with dysregulation of the transsulfuration pathway there will be low levels of taurine which will increase cholesterol levels.

Polyphenols, homocysteine, Parkinson’s disease and Alzheimer’s disease

High homocysteine levels indicate the transsulfuration pathway (homocysteine to L-cysteine) is dysregulated. Taurine is synthesized from L-cysteine. Taurine is needed to form various bile acids. Bile acids are needed for fat absorption.

Polyphenols can increase beta-oxidation which can lead to serious difficulties if there are difficulties in fat absorption which are likely if there are high homocysteine levels.

Many illnesses for which polyphenols have been postulated to be treatments are associated with high levels of homocysteine, however, where there are high homocysteine levels there could be difficulties in fatty acid absorption. Increasing levels of polyphenols, which increase beta-oxidation, would be contradicted where there are difficulties in fatty acid absorption and metabolism.

Polyphenol supplements are frequently suggested as treatments for Alzheimer’s disease and Parkinson’s disease, however, both Alzheimer’s disease and Parkinson’s disease are associated with high homocyteine levels whereby there could be difficulties in fatty acid absoption. Polyphenol supplements could worsen Alzheimer’s disease and Parkinson’s disease. In the treatment of Alzheimer’s disease polyphenols have been full of promise but have failed to deliver effective treatments.

Caffeine pills have nowhere near the same effect as coffee. There must be more to the effects of coffee than caffeine and that something more is the polyphenol contents of coffee and the effect of those polyphenols on beta-oxidation.