CAM presentation Masayuki Nogi R 3 4114 Overview

CAM presentation Masayuki Nogi (R 3) 4/1/14

Overview Introduction Chemical profile Historical & modern usage Mechanism of action Human data Dosage/cost/side effect Conclusion

Taurine Also known as 2 -Aminoethylsulfonic acid Taurina Scientific name 2 -Aminoethane sulfonic acid Latin taurus (a cognate of the Greek ταύρος = ox)

Clinical use (historical) 1827 first isolated from ox bile by German scientists Friedrich Tiedemann and Leopold Gmelin 1993 Worldwide - approximately 5, 000– 6, 000 tons of taurine were produced for commercial purposes 50% for pet food manufacture 50% in pharmaceutical applications. 2009 Japan – approval for therapeutic usage 2010 China - more than 40 manufacturers

Biosynthesis seafood, human breast milk Normally synthesized from cysteine & hypotaurine Distributed highly in brain, retina, heart and platelet Essential amino sulfonic acid found in Cysteine Taurine

In animals… Nutritionally dependent cat (Hayes and Carey 1975; Knopf et al. 1978; Sturman 1986) certain dogs (Gavaghan and Kittleson 1997; Backus et al. 2003; Belanger et al. 2005) Deficiency leads to… retinal and tapetum degeneration (Hayes and Carey 1975; Sturman 1986) cardiac dysfunction (Pion et al. 1987, 1992; Novotny et al. 1991) fox (Moise et al. 1991) immune deficiency (Schuller-Levis some monkeys (Hayes et al. 1980; muscle atrophy (Ito et al. 2008) Stephan et al. 1981; Imaki et al. 1987) anteater (Nofs et al. 2013) et al. 1990) premature aging (Ito et al. 2013 a) impaired reproduction (Hayes et al. 1980; Sturman 1986)

2001 WHO-CARDIAC Study wide multi-center, cross-sectional WHO investigation inverse relationship exists between cardiovascular mortality and dietary taurine intake, as monitored by urinary taurine levels (Yamori et al. 2001) mortality rate from ischemic heart disease (IHD) was lowest in Japanese (Yamori et al. 2009) positively related to total serum cholesterol (TC) inversely related to 24 -U taurine excretion (24 -UT), n-3 fatty acid to total phospholipids ratio of the plasma membrane both biomarkers of seafood intake. Yamori, Y. , Liu, L. , Ikeda, K. , Miura, A. , Mizushima, S. , Miki, T. , et al. (2001). Distribution of twenty-four hour urinary taurine excretion and association with ischemic heart disease mortality in 24 populations of 16 countries: results from the WHO-CARDIAC study. Hypertension Research : Official Journal of the Japanese Society of Hypertension, 24(4), 453– 457.

Clinical use (modern) Clinical base Research base CHF Parkinson dz Hypertension Huntington dz Hepatitis mitochondrial myopathy, encepha- lopathy, lactic acidosis and stroke-like episodes (MELAS) Hyperlipidemia Cystic fibrosis

Mechanism of action Retinal photoreceptor activity Bile acid conjugation Platelet aggregation Cardiac contractility Insulin activity WBC antioxidant activity

In the CV system… Modulator for calcium overload ↓oxidative stress (“anti-oxidant”) Inhibits catecholamine induced peripheral arterial constriction (“vaso-relaxant”) protects the ischemic-reperfused heart against injury (Schaffer et al. 2013) attenuation of neurohumoral-mediated development of cellular hypertrophy and progression of overt heart failure (Ito et al. 2013 b)

In more details… detoxification of hypochlorous acid formation of taurine chloramine anti-inflammatory activity (Schuller. Levis and Park 2003; Marcinkiewicz and Kontny 2013; Kim and Cha 2014) detoxification of xenobiotics and the neutralization of toxic aldehydes (Miyazaki and Matsuzaki 2013) functions as a neuromodulator, interacting and altering the actions of the GABAA receptor and the glycine receptor (Menzie et al. 2013)

MOA in summary Hypo-chlorous acid Ito, T. , Schaffer, S. , & Azuma, J. (2014). The effect of taurine on chronic heart failure: actions of taurine against catecholamine and angiotensin II. Amino Acids, 46(1), 111– 119.

Better LV contractility 14 patients with CHF for a 4 -week period. Taurine significantly improved - NYHA functional class (p <0. 02), - pulmonary crackles (p<O. O 2) - chest film abnormalities (p<O. Ol). LVETI=left ventricular ejection time index; PEPI=pre-ejection period index; QS 2 I =electromechanical systole duration index Azuma, J. , Sawamura, A. , et al. (1985). Therapeutic effect of taurine in congestive heart failure: a double-blind crossover trial. Clinical Cardiology, 8(5), 276– 282.

In the Operation Room… Rapid infusion of 5 g of taurine before bypass surgery provided protection against reperfusion injury (lipoperioxidation) (Milei et al. 1992*) Taurine diminished damage to arrested hearts during cold isotonic storage prior to transplant (Sahin et al. 2011; Oriyanhan et al. 2005) * Reduction of reperfusion injury with preoperative rapid intravenous infusion of taurine during myocardial revascularization. (1992). Reduction of reperfusion injury with preoperative rapid intravenous infusion of taurine during myocardial revascularization. , 123(2), 339– 345.

Under research Parkinson’s disease inhibiting GABAergic substantia nigra cells and attenuating oxidative stress and apoptosis (Menzie et al. 2013) MELAS taurine therapy might partially restore 5 taurinomethyluridine-t. RNALeu(UUR) levels (Santa 2010; Jong et al. 2012) AKI, cisplatin toxicity, renal stones, DM, HTN, ischemic injury and renal transplantation (Han and Chesney 2012)

Dosage For CHF 1 -2 gram BID or TID For Hepatitis 4 gram TID x 6 wks For Steatorrhea in cystic fibrosis children 30 mg/kg daily x 4 mts

Cost 1000 mg tab, 50 tabs $6. 71 i. Herb. com 250 g bottle $12

Side effects No reports in trials! Just one case of encephalopathy in a bodybuilder taking 14 gram with insulin + anabolic steroids. 2003 study by the European Food Safety Authority no adverse effects for up to 1, 000 mg/kg/day of taurine Interaction ↑Lithium level

Conclusion Conditionally essential sulfonic amino acid, found in seafood Used for CHF, hepatitis Old/small trial suggest better CHF parameters and LV contractility Might block the humoral-neural pathway like ACEi/ARB/BB Usage in Neurology under investigation Hardly no side-effects reported Be careful about Energy drinks Also contains high concentrated caffeine!

1. Azuma, J. , Sawamura, A. , et al. (1985). Therapeutic effect of taurine in congestive heart failure: a double-blind crossover trial. Clinical Cardiology, 8(5), 276– 282. 2. Ito, T. , Schaffer, S. , & Azuma, J. (2014). The effect of taurine on chronic heart failure: actions of taurine against catecholamine and angiotensin II. Amino Acids, 46(1), 111– 119. doi: 10. 1007/s 00726 -013 -1507 -z 3. Schaffer, S. W. , Ito, T. , & Azuma, J. (2014). Clinical significance of taurine. Amino Acids, 46(1), 1– 5. doi: 10. 1007/s 00726 -013 -1632 -8 4. Yamori, Y. , Liu, L. , et al. (2001). Distribution of twenty-four hour urinary taurine excretion and association with ischemic heart disease mortality in 24 populations of 16 countries: results from the WHO-CARDIAC study. Hypertension Research : Official Journal of the Japanese Society of Hypertension, 24(4), 453– 457. QUESTIONS?