L-Carnitine

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 BT) • 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…

5. Food Science and Chemistry - O O • 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 C H C H O C H H H C H + N CH CH 3 3 CH 3 L-Carnitine

6. 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 S-adenosylmethionine • 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.

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

8. 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 Carnitine content of foods (mg/g) adopted Heinz Loster 2003/Rigault 2007

9. 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 Total Carnitine, humans (umol/ml)

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

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

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. Johnny Lopez, PhD Business & Technical Manager 817-995-2484 201-669-3576 johnny.lopez@lonza.com