L-Carnitine The Science Behind an Important Functional Nutrient for People and Pets Johnny Lopez, PhD Outline • • • • • Introduction and history Food Science and Chemistry Roles of L-Carnitine in the body Thinking outside the box Summary Introduction and history • L-Carnitine first discovered in 1905 – 1927 structure became more defined – 1948 thought to be a B vitamin (Vitamin BT) • its role in B oxidation became more understood – 1962 established it to be “L- Carnitine” – Years later much more learned Historical review of progress… Item Timeframe On Mitochondria 1960’s Inflammation and connective tissue Late 60’s-70’s Tumor and cancer cells Early 70’s to date Myopathies, cardiac failure 90’s thru today infants and feeding formulas Mid 90’s Aging, type 2 diabetes, chronic fatigue, Alzheimer's, performance Late 90’s thru today Food Science and Chemistry O- O C H C H H O C H H C H + N CH CH 3 3 CH 3 L-Carnitine Synonym: Vitamin BT Reactive properties: • Molecular weight 161 • Hygroscopic Stability: Thermostable (up to 395°F) Toxicity: Small, LD50 (rats) >5 g/kg BW Approved: AAFCO and FDA approved Food Science and Chemistry Naturally synthesized Manufactured in liver & kidneys but varies by species In dogs, liver is the only active organ In cats, both liver and kidney are active Starts with protein-bound Lysine and Sadenosylmethionine A 5-step process, typically last step is rate limiting to manufacture 1 g of LC requires 30 g of muscle protein requires vitamin C, niacin, vitamin B6 and iron In humans, 25% of L-carnitine needs met by synthesis. Metabolic demands for L-Carnitine • Can be divided into 3 categories – Primary – Secondary – Functional shortage • age dependent • condition dependent Carnitine content of foods (mg/g) • • • • • • Muscle (lamb) Muscle (beef) Muscle (pig) Heart (cattle) Muscle (poultry)Milk (cow) - 2.03 0.61 0.27 0.23 0.09 0.026 • • • • • • Liver (lamb) - 0.022 Salmon 0.0006 Rice 0.018 Eggs and peas - 0.008 Potatoes - 0.0003 Carrots/spinach - 0.000 adopted Heinz Loster 2003/Rigault 2007 Total Carnitine, humans (umol/ml) Infants (3 kg) • Skeletal muscle 1.98 • Liver 0.55 • Heart 0.77 • Plasma – males – females 0.026 0.023 Adults (70 kg) • Skeletal muscle • Liver • Heart • Brain 3.96 2.90 4.80 0.30 L-Carnitine in Pet Food • Varies by type of ingredients – foods of animal origin blended with other ingredients – processing such boiling, soaked, washing – freezing and/or drying • Not understood is bioavailability of natural forms of L-Carnitine • It matters: bound vs free L-Carnitine L-Carnitine physiology and its role in energy production Cell + CoA L-Carnitine L-Carnitine ß- + CoA Oxidation CoA Krebs-Cycle Respiration Fatty acid CoA + Cytosol L-Carnitine L-Carnitine + CoA Mitochondria CoA + Energy (ATP) L-Carnitine supplementation can influence total metabolism Glucose Glycogen Pyruvate Carboxylase Pyruvate ↑ β-oxidation Acetyl CoA OAA TCA Protein Amino Acids α-kg ↓ BCAADH (leucine, iso,) Citrate Fat + L-Carnitine Roles of L-Carnitine in the body • Convert fat into energy. – Helps manage weight loss in dogs and cats • Cardio-vascular system – Heart energy comes mostly from fat and L-Carnitine • Antioxidant support – Serves as an antioxidant • Cognitive function – cerebral absorption of Fat soluble vitamins; protect from oxidative decay • Maintaining muscle integrity – provide blood flow to smooth muscles Human usage of L-Carnitine • Large number of products entering the market – Examples • The amount of publications out per year – Table Thinking outside the box • Weight management • other applications Thank You! Johnny Lopez, PhD Business & Technical Manager Tel: 817-995-2484 Fax: 201-669-3576 Email: johnny.lopez@lonza.com