Re: Fw: simply water-TAURINE

July 10, 2000

Dehydration leads to depletion of taurine, essential for normal cell

function. Saw this message come in while formating the article below.

Thanks.

Zoe

Therapeutic Applications of Taurine

by C. Birdsall, ND

Abstract

Taurine is a conditionally-essential amino acid which is not utilized in

protein synthesis, but rather is found free or in simple peptides. Taurine

has been shown to be essential in certain aspects of mammalian development,

and in vitro studies in various species have demonstrated that low levels of

taurine are associated with various pathological lesions, including

cardiomyopathy, retinal degeneration, and growth retardation, especially if

deficiency occurs during development. Metabolic actions of taurine include:

bile acid conjugation, detoxification, membrane stabilization,

osmoregulation, and modulation of cellular calcium levels. Clinically,

taurine has been used with varying degrees of success in the treatment of a

wide variety of conditions, including: cardiovascular diseases,

hypercholesterolemia, epilepsy and other seizure disorders, macular

degeneration, Alzheimer's disease, hepatic disorders, alcoholism, and cystic

fibrosis. (Alt Med Rev 1998;3(2):128-136)

Introduction

Taurine (2-aminoethanesulfonic acid, see Figure 1) is a

conditionally-essential amino acid which is not utilized in protein

synthesis, but rather is found free or in simple peptides. First discovered

as a component of ox bile in 1827, it was not until 1975 that the

significance of taurine in human nutrition was identified, when it was

discovered that formula-fed, pre-term infants were not able to sustain

normal plasma or urinary taurine levels.1 Signs of taurine deficiency have

also been detected in children on long-term, total parenteral nutrition,2

and in patients with " blind-loop " syndrome.3 In vivo studies in various

species have shown taurine to be essential in certain aspects of mammalian

development, and have demonstrated that low levels of taurine are associated

with various pathological lesions, including cardiomyopathy, retinal

degeneration, and growth retardation, especially if deficiency occurs during

development.4

Derived from methionine and cysteine metabolism, taurine is known to play an

important role in numerous physiological functions. While conjugation of

bile acids is perhaps its best-known function, this accounts for only a

small proportion of the total body pool of taurine in humans. Other

metabolic actions of taurine include: detoxification, membrane

stabilization, osmoregulation, and modulation of cellular calcium levels.

Clinically, taurine has been used in the treatment of a wide variety of

conditions, including: cardiovascular diseases, epilepsy and other seizure

disorders, macular degeneration, Alzheimer's disease, hepatic disorders, and

cystic fibrosis. An analog of taurine, acamprosate, has been used as a

treatment for alcoholism.

Biochemistry and Metabolism

Although frequently referred to as an amino acid, it should be noted that

the taurine molecule contains a sulfonic acid group, rather than the

carboxylic acid moiety found in other amino acids. Unlike true amino acids,

taurine is not incorporated into proteins, and is one of the most abundant

free amino acids in many tissues, including skeletal and cardiac muscle, and

the brain.5

In the body, taurine is synthesized from the essential amino acid methionine

and its related non-essential amino acid cysteine (see Figure 2). There are

three known pathways for the synthesis of taurine from cysteine. All three

pathways require pyridoxal-5'-phosphate (P5P), the active coenzyme form of

vitamin B6, as a cofactor. A vitamin B6 deficiency has been shown to impair

taurine synthesis.6

The activity of cysteine sulfinic acid decarboxylase (CSAD), the enzyme

which converts both cysteine sulfinic acid into hypotaurine, and cysteic

acid into taurine, is thought to reflect the capacity for taurine

synthesis.7 Compared to other mammals, humans have relatively low CSAD

activity, and therefore possibly lower capacity for taurine synthesis.8 Much

of the published research on taurine has involved studies done on cats,

which do not synthesize taurine, but must consume it in their diet.5

Therefore, since humans have the capacity to synthesize at least some

taurine, it is unclear to what extent feline studies can be extrapolated to

humans.

Cardiovascular Effects

Taurine comprises over 50 percent of the total free amino acid pool of the

heart.9 It has a positive inotropic action on cardiac tissue,10 and has been

shown in some studies to lower blood pressure.11,12 In part, the cardiac

effects of taurine are probably due to its ability to protect the heart from

the adverse effects of either excessive or inadequate calcium ion (Ca2+)

levels.13 The consequence of Ca2+ excess is the accumulation of

intracellular calcium, ultimately leading to cellular death. Taurine may

both directly and indirectly help regulate intracellular Ca2+ ion levels by

modulating the activity of the voltage-dependent Ca2+ channels, and by

regulation of Na+ channels. Taurine also acts on many other ion channels and

transporters. Therefore, its action can be quite non-specific.14 When an

adequate amount of taurine is present, calcium-induced myocardial damage is

significantly reduced, perhaps by interaction between taurine and membrane

proteins.15 At least one study has suggested taurine's ability to function

as a membrane stabilizer is related to its capacity to prevent suppression

of membrane-bound NaK ATPase.16

Other research demonstrates taurine can protect the heart from

neutrophil-induced reperfusion injury and oxidative stress. Because the

respiratory burst activity of neutrophils is also significantly reduced in

the presence of taurine, perhaps taurine's protective effect is mediated by

its antioxidative properties.17

Azuma and associates have observed that taurine alleviates physical signs

and symptoms of congestive heart failure (CHF).18-20 Chazov et al were able

to demonstrate that taurine could reverse EKG abnormalities such as S-T

segment changes, T-wave inversions, and extra systoles in animals with

chemically-induced arrhythmias.21

A double-blind, placebo-controlled crossover study suggested, " taurine is an

effective agent for the treatment of heart failure without any adverse

effects. " 22 Fourteen patients (9 men and 5 women) with CHF were evaluated

initially and baseline data were obtained. Patients were assigned a

" heart-failure score " based on the degree of dyspnea, pulmonary sounds,

signs of right-heart failure, and chest film abnormalities. All patients

were continued on digitalis with diuretics and/or vasodilators throughout

the study period. Patients received 6 grams per day in divided doses of

either taurine or placebo for four weeks, followed by a 2-week " wash-out "

period. Prior to the cross-over period, baseline data were obtained for the

following study period, in which patients received placebo or taurine,

whichever was not taken during the first study period. Heart-failure scores

fell from 5.8 ± 0.7 before taurine administration to 3.7 ± 0.5 after taurine

(p < 0.001); the score did not change significantly during the placebo

period. A " favorable response was observed in 79 percent (11/14 patients)

during the taurine-treated period and in 21 percent (3/14 patients) during

the placebo-treated period; 4 patients worsened during the placebo period,

whereas none did during the taurine period (p less than 0.05). " 22

Research has also been conducted in animals to determine whether oral

taurine increased survivability in CHF which resulted from

surgically-induced aortic regurgitation. Albino rabbits received either

taurine (100 mg/kg) or placebo after surgical damage to the aortic cusps,

which produced aortic regurgitation. " Cumulative mortality at 8 weeks of

non-treated rabbits following aortic regurgitation was 52% (12/23 animals)

compared with 11% (1/9 animals) in taurine-treated group (p less than

0.05)... Taurine prevented the rapid progress of congestive heart failure

induced artificially by aortic regurgitation, and consequently prolonged the

life expectancy. " 23

Bile Acid Conjugation and Cholesterol Excretion

The liver forms a 2-4 gram bile acid pool that has approximately ten

enterohepatic cycles per day, with the terminal ileum serving as the main

absorption site for the enterohepatic recycling of approximately 80 percent

of these acids. Bile acids function as a detergent for emulsification and

absorption of lipids and fat-soluble vitamins. Critical to this function of

bile are the bile salts which, because of their lipophilic and hydrophilic

components, can lower surface tension and form micelles. Two major bile

acids are derived from hepatic cholesterol metabolism: cholic acid and

chenodeoxycholic acid. From these primary bile acids, intestinal bacteria

form the secondary bile acids deoxycholic acid and lithocholic acid,

respectively. For these bile acids to be solubilized at physiological pH, it

is essential they be conjugated through peptide linkages with either glycine

or taurine; these amino acid conjugates are referred to as bile salts.

Taurine conjugation of bile acids has a significant effect on the solubility

of cholesterol, increasing its excretion, and administration of taurine has

been shown to reduce serum cholesterol levels in human subjects. In a

single-blind, placebo-controlled study, 22 healthy male volunteers, aged

18-29 years, were randomly placed in one of two groups and fed a high

fat/high cholesterol diet, designed to raise serum cholesterol levels, for

three weeks. The experimental group received 6 grams of taurine daily. At

the end of the test period, the control group had significantly higher total

cholesterol and LDL-cholesterol levels than the group receiving taurine.24

Cystic Fibrosis

Most cystic fibrosis (CF) patients suffer from nutrient malabsorption, where

much of the insult is in the ileum. Since the terminal ileum serves as the

main absorption site for the enterohepatic recycling of approximately 80

percent of bile acids, they are malabsorbed as well. Taurine supplementation

has been shown to decrease the severity of steatorrhea associated with many

CF cases.25,26 In one double-blind crossover study, 13 CF children with

steatorrhea of at least 13 grams per day were treated with a taurine dose of

30 mg/kg/day. The study continued for two consecutive 4-month durations and

involved both placebo and treatment periods. Ninety-two percent of the CF

children showed decreased fecal fatty acid and sterol excretion while taking

taurine.25 In CF patients with a high degree of steatorrhea, bile acid

absorption was increased with taurine supplementation, suggesting a possible

role for taurine in treating malabsorption.26

Detoxification

Due to its ability to neutralize hypochlorous acid, a potent oxidizing

substance, taurine is able to attenuate DNA damage caused by aromatic amine

compounds in vitro.27 Because of taurine's unique structure, containing a

sulfonic acid moiety rather than carboxylic acid, it does not form an

aldehyde from hypochlorous acid, forming instead a relatively stable

chloroamine compound. Hence, taurine is an antioxidant that specifically

mediates the chloride ion and hypochlorous acid concentration, and protects

the body from potentially toxic effects of aldehyde release.

Taurine has also been reported to protect against carbon

tetrachloride-induced toxicity.28-31 In rats exposed to carbon tetrachloride

(CCl4), hepatic taurine content decreased significantly 12 and 24 hours

after CCl4 administration. However, oral administration of taurine to

CCl4-exposed rats was able to protect these animals from hepatic taurine

depletion, suggesting that hepatic taurine may play a critical role in the

protection of hepatocytes against hepatotoxins such as CCl4.28

Exposure to bacterial endotoxins has been suggested as one factor which can

augment the magnitude of individual responses to xenobiotics.32 Circulating

endotoxins of intestinal origin have been found to create a positive

feedback on endotoxin translocation from the gut, stimulating increases in

serum endo-toxin levels. In experimental animals, taurine was found to

significantly inhibit intestinal translocation and to protect the animals

from endotoxemic injury.33 Therefore, it is possible taurine might be able

to modify factors underlying susceptibility to toxic chemicals.

Hepatic Disorders

Two groups of patients with acute hepatitis, all with serum bilirubin levels

above 3 mg/dl, were studied in a double-blind, randomized protocol. Subjects

in the treatment group received 4 grams of taurine three times daily.

Bilirubin, total bile acids, and biliary glycine:taurine ratio all decreased

significantly in the taurine group within one week as compared to

controls.34

Alcoholism

Twenty-two patients undergoing treatment for alcohol withdrawal were given 1

gram of taurine three times per day orally for seven days. When compared to

retrospective controls, significantly fewer of the taurine-treated patients

had psychotic episodes (14% vs. 45%, p < 0.05). The number of psychotic

cases after admission who had also been psychotic before admission was 1/16

for the taurine group and 11/17 for the controls (p < 0.001).35

Recently, acamprosate, a synthetic taurine analog, has been shown to be

clinically useful in the treatment of alcohol dependence.36-41 Currently

available only in Europe, acamprosate (calcium acetylhomotaurinate) has a

chemical structure similar to that of gamma-aminobutyric acid, and is

thought to act via several mechanisms affecting multiple neurotransmitter

systems, and by modulation of calcium ion fluxes. About 50 percent of

alcoholic patients relapse within three months of treatment. In a pooled

analysis of data from 11 randomized, placebo-controlled trials involving a

total of 3,338 patients with alcohol dependence, those treated with

acamprosate showed higher abstinence rates and durations of abstinence

during 6- to 12-month post-treatment follow-up periods, when compared to

those receiving placebo.36

In a two-year, randomized, double-blind, placebo-controlled study, 272

patients initially were given short-term detoxification treatment, and then

received routine counseling and either acamprosate or placebo for 48 weeks,

after which they were followed for another 48 weeks without medication.

Subjects who received acamprosate showed a significantly higher continuous

abstinence rate at the end of the treatment period compared to those who

were assigned to the placebo group (43% vs 21%, p = .005), and they had a

significantly longer mean abstinence duration of 224 vs 163 days, or 62

percent vs 45 percent days abstinent (p < .001). However, there was no

difference in psychiatric symptoms. At the end of a further 48 weeks without

receiving study medication, 39 percent and 17 percent of the acamprosate-

and placebo-treated patients, respectively, had remained abstinent (p =

..003).37

Two in vitro studies have been published comparing the effects of

acamprosate and calcium acetyltaurinate on ionic membrane transfer.40,41

Ethanol has been shown to reduce ionic transfer through alterations in the

cationic paracellular pathway, the coupling between two adjacent epithelial

cells, the monovalent cation pump, and the antiport system. In both of these

studies, the results indicate two closely related compounds have different

effects on ionic membrane transfer. Therefore, caution should be used in

extrapolating the effects of acamprosate to taurine or other taurine

analogs.

Ocular Disorders

The retina contains one of the highest concentrations of taurine in the

body. In cats, when the retina has been depleted to about one-half its

normal taurine content, changes in the photoreceptor cells begin to appear,

and further depletion can result in permanent retinal degeneration.42 In

some respects, the retinal degeneration seen in the human disease retinitis

pigmentosa (RP) is similar to that observed in taurine-deficient cats.

However, studies of plasma and platelet taurine levels in patients with RP

have yielded very inconsistent results.43-45 A clinical trial of taurine

(1-2 g/day) for one year in patients with RP did not result in any

laboratory or clinical evidence of improvement, although some subjective

benefits were reported.46

Epilepsy

Although several clinical trials involving taurine supplementation in

epileptic patients have been reported, most have major methodological

flaws.47 Depending on the criteria used, the degree of success reported in

various trials using taurine in the treatment of epilepsy has been between

16 and 90 percent.48-56 In these trials, dosages ranged from 375 to 8,000

mg/day. The precise role of taurine in synaptic transmission is uncertain,

and its antiepileptic action, confirmed in several models of experimental

epilepsy and in short-term clinical studies, does not seem to possess major

clinical relevance since trials with a longer follow-up period have

generally produced less satisfactory results. Taurine's limited

diffusibility across the blood-brain barrier may be the main factor

restricting the antiepileptic effect of this compound.

Alzheimer's Disease

Levels of the neurotransmitter acetylcholine have been described as

abnormally low in patients with Alzheimer's disease. These insufficient

levels are presumed to be related to the memory loss which characterizes the

condition, and treatment of Alzheimer's disease based on this premise has

been proposed.57 Taurine administered to experimental animals has been able

to increase the level of acetylcholine in the brain,58 and researchers have

demonstrated that decreased concentrations of taurine are present in the

cerebral spinal fluid of patients with advanced symptoms of Alzheimer's

disease when compared to age-matched controls.59 To date, no clinical trials

on the use of taurine for the treatment of Alzheimer's disease have been

reported in the medical literature.

Diabetes

Both plasma and platelet taurine levels have been found to be depressed in

insulin-dependent diabetic patients; however, these levels were raised to

normal with oral taurine supplementation. In addition, the amount of

arachidonic acid needed to induce platelet aggregation was lower in these

patients than in healthy subjects. Taurine supplementation reversed this

effect as well, reducing platelet aggregation. In vitro experiments

demonstrated that taurine reduced platelet aggregation in diabetic patients

in a dose-dependent manner, while having no effect on the aggregation of

platelets from healthy subjects.

Conclusion

Although it is readily apparent that taurine is important in conjugating

bile acids to form water-soluble bile salts, only a fraction of available

taurine is used for this function. Taurine is also involved in a number of

other crucially important processes, including calcium ion flux, membrane

stabilization, and detoxification. Some areas of investigation into the

clinical uses of taurine have revealed significant applications for this

amino acid: congestive heart failure, cystic fibrosis, toxic exposure, and

hepatic disorders. Other conditions such as epilepsy and diabetes will

require further research before a clear rationale for the use of taurine can

be developed.

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July 11, 2000

EXACTLY, are we hydrated enough. Why do seizure meds lead us to be thirsty

quite often? Makes sense to me

Kathy

Re: [ ] Fw: [ ] simply water-TAURINE

>Dehydration leads to depletion of taurine, essential for normal cell

>function. Saw this message come in while formating the article below.

>Thanks.

>Zoe

>

>Therapeutic Applications of Taurine

>by C. Birdsall, ND

>

>Abstract

>Taurine is a conditionally-essential amino acid which is not utilized in

>protein synthesis, but rather is found free or in simple peptides. Taurine

>has been shown to be essential in certain aspects of mammalian development,

>and in vitro studies in various species have demonstrated that low levels

of

>taurine are associated with various pathological lesions, including

>cardiomyopathy, retinal degeneration, and growth retardation, especially if

>deficiency occurs during development. Metabolic actions of taurine include:

>bile acid conjugation, detoxification, membrane stabilization,

>osmoregulation, and modulation of cellular calcium levels. Clinically,

>taurine has been used with varying degrees of success in the treatment of a

>wide variety of conditions, including: cardiovascular diseases,

>hypercholesterolemia, epilepsy and other seizure disorders, macular

>degeneration, Alzheimer's disease, hepatic disorders, alcoholism, and

cystic

>fibrosis. (Alt Med Rev 1998;3(2):128-136)

>

>Introduction

>Taurine (2-aminoethanesulfonic acid, see Figure 1) is a

>conditionally-essential amino acid which is not utilized in protein

>synthesis, but rather is found free or in simple peptides. First discovered

>as a component of ox bile in 1827, it was not until 1975 that the

>significance of taurine in human nutrition was identified, when it was

>discovered that formula-fed, pre-term infants were not able to sustain

>normal plasma or urinary taurine levels.1 Signs of taurine deficiency have

>also been detected in children on long-term, total parenteral nutrition,2

>and in patients with " blind-loop " syndrome.3 In vivo studies in various

>species have shown taurine to be essential in certain aspects of mammalian

>development, and have demonstrated that low levels of taurine are

associated

>with various pathological lesions, including cardiomyopathy, retinal

>degeneration, and growth retardation, especially if deficiency occurs

during

>development.4

>Derived from methionine and cysteine metabolism, taurine is known to play

an

>important role in numerous physiological functions. While conjugation of

>bile acids is perhaps its best-known function, this accounts for only a

>small proportion of the total body pool of taurine in humans. Other

>metabolic actions of taurine include: detoxification, membrane

>stabilization, osmoregulation, and modulation of cellular calcium levels.

>Clinically, taurine has been used in the treatment of a wide variety of

>conditions, including: cardiovascular diseases, epilepsy and other seizure

>disorders, macular degeneration, Alzheimer's disease, hepatic disorders,

and

>cystic fibrosis. An analog of taurine, acamprosate, has been used as a

>treatment for alcoholism.

>

>Biochemistry and Metabolism

>Although frequently referred to as an amino acid, it should be noted that

>the taurine molecule contains a sulfonic acid group, rather than the

>carboxylic acid moiety found in other amino acids. Unlike true amino acids,

>taurine is not incorporated into proteins, and is one of the most abundant

>free amino acids in many tissues, including skeletal and cardiac muscle,

and

>the brain.5

>In the body, taurine is synthesized from the essential amino acid

methionine

>and its related non-essential amino acid cysteine (see Figure 2). There are

>three known pathways for the synthesis of taurine from cysteine. All three

>pathways require pyridoxal-5'-phosphate (P5P), the active coenzyme form of

>vitamin B6, as a cofactor. A vitamin B6 deficiency has been shown to impair

>taurine synthesis.6

>The activity of cysteine sulfinic acid decarboxylase (CSAD), the enzyme

>which converts both cysteine sulfinic acid into hypotaurine, and cysteic

>acid into taurine, is thought to reflect the capacity for taurine

>synthesis.7 Compared to other mammals, humans have relatively low CSAD

>activity, and therefore possibly lower capacity for taurine synthesis.8

Much

>of the published research on taurine has involved studies done on cats,

>which do not synthesize taurine, but must consume it in their diet.5

>Therefore, since humans have the capacity to synthesize at least some

>taurine, it is unclear to what extent feline studies can be extrapolated to

>humans.

>

>Cardiovascular Effects

>Taurine comprises over 50 percent of the total free amino acid pool of the

>heart.9 It has a positive inotropic action on cardiac tissue,10 and has

been

>shown in some studies to lower blood pressure.11,12 In part, the cardiac

>effects of taurine are probably due to its ability to protect the heart

from

>the adverse effects of either excessive or inadequate calcium ion (Ca2+)

>levels.13 The consequence of Ca2+ excess is the accumulation of

>intracellular calcium, ultimately leading to cellular death. Taurine may

>both directly and indirectly help regulate intracellular Ca2+ ion levels by

>modulating the activity of the voltage-dependent Ca2+ channels, and by

>regulation of Na+ channels. Taurine also acts on many other ion channels

and

>transporters. Therefore, its action can be quite non-specific.14 When an

>adequate amount of taurine is present, calcium-induced myocardial damage is

>significantly reduced, perhaps by interaction between taurine and membrane

>proteins.15 At least one study has suggested taurine's ability to function

>as a membrane stabilizer is related to its capacity to prevent suppression

>of membrane-bound NaK ATPase.16

>Other research demonstrates taurine can protect the heart from

>neutrophil-induced reperfusion injury and oxidative stress. Because the

>respiratory burst activity of neutrophils is also significantly reduced in

>the presence of taurine, perhaps taurine's protective effect is mediated by

>its antioxidative properties.17

>Azuma and associates have observed that taurine alleviates physical signs

>and symptoms of congestive heart failure (CHF).18-20 Chazov et al were able

>to demonstrate that taurine could reverse EKG abnormalities such as S-T

>segment changes, T-wave inversions, and extra systoles in animals with

>chemically-induced arrhythmias.21

>A double-blind, placebo-controlled crossover study suggested, " taurine is

an

>effective agent for the treatment of heart failure without any adverse

>effects. " 22 Fourteen patients (9 men and 5 women) with CHF were evaluated

>initially and baseline data were obtained. Patients were assigned a

> " heart-failure score " based on the degree of dyspnea, pulmonary sounds,

>signs of right-heart failure, and chest film abnormalities. All patients

>were continued on digitalis with diuretics and/or vasodilators throughout

>the study period. Patients received 6 grams per day in divided doses of

>either taurine or placebo for four weeks, followed by a 2-week " wash-out "

>period. Prior to the cross-over period, baseline data were obtained for the

>following study period, in which patients received placebo or taurine,

>whichever was not taken during the first study period. Heart-failure scores

>fell from 5.8 ± 0.7 before taurine administration to 3.7 ± 0.5 after

taurine

>(p < 0.001); the score did not change significantly during the placebo

>period. A " favorable response was observed in 79 percent (11/14 patients)

>during the taurine-treated period and in 21 percent (3/14 patients) during

>the placebo-treated period; 4 patients worsened during the placebo period,

>whereas none did during the taurine period (p less than 0.05). " 22

>Research has also been conducted in animals to determine whether oral

>taurine increased survivability in CHF which resulted from

>surgically-induced aortic regurgitation. Albino rabbits received either

>taurine (100 mg/kg) or placebo after surgical damage to the aortic cusps,

>which produced aortic regurgitation. " Cumulative mortality at 8 weeks of

>non-treated rabbits following aortic regurgitation was 52% (12/23 animals)

>compared with 11% (1/9 animals) in taurine-treated group (p less than

>0.05)... Taurine prevented the rapid progress of congestive heart failure

>induced artificially by aortic regurgitation, and consequently prolonged

the

>life expectancy. " 23

>

>Bile Acid Conjugation and Cholesterol Excretion

>The liver forms a 2-4 gram bile acid pool that has approximately ten

>enterohepatic cycles per day, with the terminal ileum serving as the main

>absorption site for the enterohepatic recycling of approximately 80 percent

>of these acids. Bile acids function as a detergent for emulsification and

>absorption of lipids and fat-soluble vitamins. Critical to this function of

>bile are the bile salts which, because of their lipophilic and hydrophilic

>components, can lower surface tension and form micelles. Two major bile

>acids are derived from hepatic cholesterol metabolism: cholic acid and

>chenodeoxycholic acid. From these primary bile acids, intestinal bacteria

>form the secondary bile acids deoxycholic acid and lithocholic acid,

>respectively. For these bile acids to be solubilized at physiological pH,

it

>is essential they be conjugated through peptide linkages with either

glycine

>or taurine; these amino acid conjugates are referred to as bile salts.

>Taurine conjugation of bile acids has a significant effect on the

solubility

>of cholesterol, increasing its excretion, and administration of taurine has

>been shown to reduce serum cholesterol levels in human subjects. In a

>single-blind, placebo-controlled study, 22 healthy male volunteers, aged

>18-29 years, were randomly placed in one of two groups and fed a high

>fat/high cholesterol diet, designed to raise serum cholesterol levels, for

>three weeks. The experimental group received 6 grams of taurine daily. At

>the end of the test period, the control group had significantly higher

total

>cholesterol and LDL-cholesterol levels than the group receiving taurine.24

>

>Cystic Fibrosis

>Most cystic fibrosis (CF) patients suffer from nutrient malabsorption,

where

>much of the insult is in the ileum. Since the terminal ileum serves as the

>main absorption site for the enterohepatic recycling of approximately 80

>percent of bile acids, they are malabsorbed as well. Taurine

supplementation

>has been shown to decrease the severity of steatorrhea associated with many

>CF cases.25,26 In one double-blind crossover study, 13 CF children with

>steatorrhea of at least 13 grams per day were treated with a taurine dose

of

>30 mg/kg/day. The study continued for two consecutive 4-month durations and

>involved both placebo and treatment periods. Ninety-two percent of the CF

>children showed decreased fecal fatty acid and sterol excretion while

taking

>taurine.25 In CF patients with a high degree of steatorrhea, bile acid

>absorption was increased with taurine supplementation, suggesting a

possible

>role for taurine in treating malabsorption.26

>

>Detoxification

>Due to its ability to neutralize hypochlorous acid, a potent oxidizing

>substance, taurine is able to attenuate DNA damage caused by aromatic amine

>compounds in vitro.27 Because of taurine's unique structure, containing a

>sulfonic acid moiety rather than carboxylic acid, it does not form an

>aldehyde from hypochlorous acid, forming instead a relatively stable

>chloroamine compound. Hence, taurine is an antioxidant that specifically

>mediates the chloride ion and hypochlorous acid concentration, and protects

>the body from potentially toxic effects of aldehyde release.

>Taurine has also been reported to protect against carbon

>tetrachloride-induced toxicity.28-31 In rats exposed to carbon

tetrachloride

>(CCl4), hepatic taurine content decreased significantly 12 and 24 hours

>after CCl4 administration. However, oral administration of taurine to

>CCl4-exposed rats was able to protect these animals from hepatic taurine

>depletion, suggesting that hepatic taurine may play a critical role in the

>protection of hepatocytes against hepatotoxins such as CCl4.28

>Exposure to bacterial endotoxins has been suggested as one factor which can

>augment the magnitude of individual responses to xenobiotics.32 Circulating

>endotoxins of intestinal origin have been found to create a positive

>feedback on endotoxin translocation from the gut, stimulating increases in

>serum endo-toxin levels. In experimental animals, taurine was found to

>significantly inhibit intestinal translocation and to protect the animals

>from endotoxemic injury.33 Therefore, it is possible taurine might be able

>to modify factors underlying susceptibility to toxic chemicals.

>

>Hepatic Disorders

>Two groups of patients with acute hepatitis, all with serum bilirubin

levels

>above 3 mg/dl, were studied in a double-blind, randomized protocol.

Subjects

>in the treatment group received 4 grams of taurine three times daily.

>Bilirubin, total bile acids, and biliary glycine:taurine ratio all

decreased

>significantly in the taurine group within one week as compared to

>controls.34

>

>Alcoholism

>Twenty-two patients undergoing treatment for alcohol withdrawal were given

1

>gram of taurine three times per day orally for seven days. When compared to

>retrospective controls, significantly fewer of the taurine-treated patients

>had psychotic episodes (14% vs. 45%, p < 0.05). The number of psychotic

>cases after admission who had also been psychotic before admission was 1/16

>for the taurine group and 11/17 for the controls (p < 0.001).35

>Recently, acamprosate, a synthetic taurine analog, has been shown to be

>clinically useful in the treatment of alcohol dependence.36-41 Currently

>available only in Europe, acamprosate (calcium acetylhomotaurinate) has a

>chemical structure similar to that of gamma-aminobutyric acid, and is

>thought to act via several mechanisms affecting multiple neurotransmitter

>systems, and by modulation of calcium ion fluxes. About 50 percent of

>alcoholic patients relapse within three months of treatment. In a pooled

>analysis of data from 11 randomized, placebo-controlled trials involving a

>total of 3,338 patients with alcohol dependence, those treated with

>acamprosate showed higher abstinence rates and durations of abstinence

>during 6- to 12-month post-treatment follow-up periods, when compared to

>those receiving placebo.36

>In a two-year, randomized, double-blind, placebo-controlled study, 272

>patients initially were given short-term detoxification treatment, and then

>received routine counseling and either acamprosate or placebo for 48 weeks,

>after which they were followed for another 48 weeks without medication.

>Subjects who received acamprosate showed a significantly higher continuous

>abstinence rate at the end of the treatment period compared to those who

>were assigned to the placebo group (43% vs 21%, p = .005), and they had a

>significantly longer mean abstinence duration of 224 vs 163 days, or 62

>percent vs 45 percent days abstinent (p < .001). However, there was no

>difference in psychiatric symptoms. At the end of a further 48 weeks

without

>receiving study medication, 39 percent and 17 percent of the acamprosate-

>and placebo-treated patients, respectively, had remained abstinent (p =

>.003).37

>Two in vitro studies have been published comparing the effects of

>acamprosate and calcium acetyltaurinate on ionic membrane transfer.40,41

>Ethanol has been shown to reduce ionic transfer through alterations in the

>cationic paracellular pathway, the coupling between two adjacent epithelial

>cells, the monovalent cation pump, and the antiport system. In both of

these

>studies, the results indicate two closely related compounds have different

>effects on ionic membrane transfer. Therefore, caution should be used in

>extrapolating the effects of acamprosate to taurine or other taurine

>analogs.

>

>Ocular Disorders

>The retina contains one of the highest concentrations of taurine in the

>body. In cats, when the retina has been depleted to about one-half its

>normal taurine content, changes in the photoreceptor cells begin to appear,

>and further depletion can result in permanent retinal degeneration.42 In

>some respects, the retinal degeneration seen in the human disease retinitis

>pigmentosa (RP) is similar to that observed in taurine-deficient cats.

>However, studies of plasma and platelet taurine levels in patients with RP

>have yielded very inconsistent results.43-45 A clinical trial of taurine

>(1-2 g/day) for one year in patients with RP did not result in any

>laboratory or clinical evidence of improvement, although some subjective

>benefits were reported.46

>

>Epilepsy

>Although several clinical trials involving taurine supplementation in

>epileptic patients have been reported, most have major methodological

>flaws.47 Depending on the criteria used, the degree of success reported in

>various trials using taurine in the treatment of epilepsy has been between

>16 and 90 percent.48-56 In these trials, dosages ranged from 375 to 8,000

>mg/day. The precise role of taurine in synaptic transmission is uncertain,

>and its antiepileptic action, confirmed in several models of experimental

>epilepsy and in short-term clinical studies, does not seem to possess major

>clinical relevance since trials with a longer follow-up period have

>generally produced less satisfactory results. Taurine's limited

>diffusibility across the blood-brain barrier may be the main factor

>restricting the antiepileptic effect of this compound.

>

>Alzheimer's Disease

>Levels of the neurotransmitter acetylcholine have been described as

>abnormally low in patients with Alzheimer's disease. These insufficient

>levels are presumed to be related to the memory loss which characterizes

the

>condition, and treatment of Alzheimer's disease based on this premise has

>been proposed.57 Taurine administered to experimental animals has been able

>to increase the level of acetylcholine in the brain,58 and researchers have

>demonstrated that decreased concentrations of taurine are present in the

>cerebral spinal fluid of patients with advanced symptoms of Alzheimer's

>disease when compared to age-matched controls.59 To date, no clinical

trials

>on the use of taurine for the treatment of Alzheimer's disease have been

>reported in the medical literature.

>

>Diabetes

>Both plasma and platelet taurine levels have been found to be depressed in

>insulin-dependent diabetic patients; however, these levels were raised to

>normal with oral taurine supplementation. In addition, the amount of

>arachidonic acid needed to induce platelet aggregation was lower in these

>patients than in healthy subjects. Taurine supplementation reversed this

>effect as well, reducing platelet aggregation. In vitro experiments

>demonstrated that taurine reduced platelet aggregation in diabetic patients

>in a dose-dependent manner, while having no effect on the aggregation of

>platelets from healthy subjects.

>

>Conclusion

>Although it is readily apparent that taurine is important in conjugating

>bile acids to form water-soluble bile salts, only a fraction of available

>taurine is used for this function. Taurine is also involved in a number of

>other crucially important processes, including calcium ion flux, membrane

>stabilization, and detoxification. Some areas of investigation into the

>clinical uses of taurine have revealed significant applications for this

>amino acid: congestive heart failure, cystic fibrosis, toxic exposure, and

>hepatic disorders. Other conditions such as epilepsy and diabetes will

>require further research before a clear rationale for the use of taurine

can

>be developed.

>

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>

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July 11, 2000

INterestingly, p5p is mentioned here

www.kirkmanlabs.com s a B vitamin with p5p....I put that one in my

protocol and staved off a cluster of seizures my son was having, along with

TAURINE. I think it was a powerful combo to say the least.