Glutathione

//Medical Nutrition:// • -Made from glutamate, Cysteine and Glycine. • -Water soluble amino acids with sulpher (thiol) group (this is antibiotic and is in merthiolate) • -The Greeks used garlic and sulpher to treat RA, Psoriasis, and psychosis. • Glutathione(GSH) is the body’s primary antioxidant, other antioxidants support it. • -It protects proteins, detoxes formaldehyde, acetaminophen, benzpyrene….

• -Se is a cofactor in GSH function • -Glutathione status is measured by 24 hr urine –Dglucaric acid and/or mercapturic acid to evaluate toxic load. • -Glutathione must be in reduced form to detoxify properly (unreduced is often sold with supplements, but it doesn’t work. • -Riboflavin, niacinamide and the enzyme glutathione reductase are co-factors in making reduced glutathione. • -Diabetics have increased excretion of S -amino acids • -Fasting depletes GSH and Cysteine

Functions
• Protects proteins from damage via glycosylation • Liver detoxification – phase one and two – including heavy metalmercury (see p79) • Transports amino acids across cell boundaries • Cysteine has been used for clostridium infections in the gut. • Assists in synthesis of FA • Taurine precursor and bile acid conjugator. • HIV has systemic GSH d l ti GSH t • Maintains cell membrane integrity – including RBCs, mucosal cells and intimal lining • Prevents cancer – induces apoptosis, stimulates immune function depletion. stops cachexia of AIDS • DM – exercise improved GSH status • Decreases detox related illness with weight loss • Neurodegenerative diseases- Alzheimer’s, Parkinson’s, downregulates glutamate NMDA receptors. • Aging decreases with higher levels of GSH, exercise increases • Hepatitis – acetaminophen depletion • COPD and asthma – if low increased lung problems (premies, emphysema, cystic fib) 1-3 gm/d • Crohn’s inflammation Ci l ti MI /ASD • GI irradiation, decreases SE • Hair loss can be improved with Cysteine supplement • Circulation- - improves outcome – via NO pathways • Pancreatitis- NAC

• **N-acetyl Cysteine** • reduces mucous, respiratory incidence, alveolitis, asthma • HIV progression, inhibits HIV replication- 800mg qid reduced CD4 decline (double blind study - Gaby • Reduces incidence of resp illness in general 600mg tid • Inhibits melanoma, prostate cancer, and astrocytoma - initiates apoptosis • Tylenol poisoning – stops hepatic necrosis • Hepatitis C decreases liver enzymes and viral load - • Has been shown to improve the outcome of heart disease and Sjogren’s (Toxicity?) • Precursor GSH • Sjogren’s 200mg 3x/wk ocular symptoms, halitosis, daytime thirst

• NAC - Cancer – chemo reduced N/Vin Lu cancer patients receiving cyclophoaphamide, epirubicin and carboplatinun. NAC stopped Adriamycin cardiotoxicity, neuropathy from oxaliplatin, Bleomycin lung damage, hepatotoxicity from nitrogen mustard compounds, and hemorrhagic cystitis from cyclophosphamide and ifosfamide. (?interference with chemo antica effects.) It enhanced antitumor effects of adriamycin. (Semin Oncol 1983; (Suppl 1) 53-55) • Protects from Renal damage with radigraphic contrast agents and damage during angioplasty. • Chronic posterior blepharitis. 100mg tid x8wk • Polycystic ovaries insulin sensitivity and fertility

**To raise GSH:**
• 1. IV GSH • 2. NAC • 3. A Lipoic acid • 4. Methionine nausea and vomiting, Cysteine – kidney irritant, S-adenosyl methionine (SAMe) tolerated well or Taurine, both increase GSH • 5. exercise/ other antioxidants- C/E/A…

Contraindication – GSH during chemo ? – increased resistance to chemo. • NAC inhibits cytotoxicity of cisplatinum (Adriamycin), and doxyrubicin