1. L-Carnitine The Science Behind an Important Functional Nutrient for People and Pets Johnny Lopez, PhD

2. Outline Introduction and history Food Science and Chemistry Roles of L-Carnitine in the body Thinking outside the box Summary

3. Introduction and history L-Carnitine first discovered in 1905 – 1927 structure became more defined – 1948 thought to be a B vitamin (Vitamin B T) its role in B oxidation became more understood – 1962 established it to be “L- Carnitine” – Years later much more learned

4. Historical review of progress… ItemTimeframe On Mitochondria1960’s Inflammation and connective tissueLate 60’s-70’s Tumor and cancer cellsEarly 70’s to date Myopathies, cardiac failure90’s thru today infants and feeding formulasMid 90’s Aging, type 2 diabetes, chronic fatigue, Alzheimer's, performance Late 90’s thru today

5. Food Science and Chemistry Synonym: Vitamin B T Reactive properties: Molecular weight 161 Hygroscopic Stability: Thermostable (up to 395°F) Toxicity: Small, LD 50 (rats) >5 g/kg BW Approved: AAFCO and FDA approved L-Carnitine CH 3 3 3 O O N CHH CHH C + CH H O -

6. Naturally synthesized n Manufactured in liver & kidneys but varies by species n In dogs, liver is the only active organ n In cats, both liver and kidney are active n Starts with protein-bound Lysine and S- adenosylmethionine n A 5-step process, typically last step is rate limiting n to manufacture 1 g of LC requires 30 g of muscle protein n requires vitamin C, niacin, vitamin B6 and iron n In humans, 25% of L-carnitine needs met by synthesis. Food Science and Chemistry

7. Metabolic demands for L-Carnitine Can be divided into 3 categories – Primary – Secondary – Functional shortage age dependent condition dependent

8. Carnitine content of foods (mg/g) Muscle (lamb) - 2.03 Muscle (beef) - 0.61 Muscle (pig) - 0.27 Heart (cattle) - 0.23 Muscle (poultry)- 0.09 Milk (cow) - 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

9. Total Carnitine, humans (umol/ml) Infants (3 kg) Skeletal muscle 1.98 Liver 0.55 Heart 0.77 Plasma – males 0.026 – females 0.023 Adults (70 kg) Skeletal muscle 3.96 Liver 2.90 Heart 4.80 Brain 0.30

10. 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

11. Cytosol Cell Mitochondria CoA Fatty acid L-Carnitine ß- Oxidation CoA L-Carnitine CoA + + L-Carnitine CoA + L-Carnitine + Krebs-Cycle Respiration CoA + Energy (ATP) L-Carnitine physiology and its role in energy production

12. L-Carnitine supplementation can influence total metabolism ↓ BCAADH (leucine, iso,) ↑ β-oxidation Pyruvate Acetyl CoA OAA Citrate α-kg Glucose TCA Glycogen Protein Fat + L-Carnitine Amino Acids Pyruvate Carboxylase

13. 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

14. Human usage of L-Carnitine Large number of products entering the market – Examples The amount of publications out per year – Table

15. Thinking outside the box Weight management other applications

16. Thank You! Tel: Fax: Email: Johnny Lopez, PhD Business & Technical Manager 817-995-2484 201-669-3576 johnny.lopez@lonza.com