TY Amy Lee MD Zhaoping Li MD, PhD Alona Zerlin RD Susan Bowerman RD Gail Thames

1. Effects of Dihydrocapsiate on Adaptive and Diet-Induced Thermogenesis with High Protein Very Low Calorie Diet TY Amy Lee MD Zhaoping Li MD, PhD Alona Zerlin RD Susan Bowerman RD Gail Thames David Heber MD, PhD Center for Human Nutrition, David Geffen School of Medicine, University of California Los Angeles, California tszyingl@mednet.ucla.edu

2. Dihydrocapsiate (DCT) • Capsicum annuum L. CH-19 Sweet • Natural • Increases sympathetic nervous system • Acts Transient Receptor Potential Vanilloid 1 (TRPV1) • Good alternative to the pungent chili peppers

3. Capsaicin TRPV1 Tongue, gut, others Peripheral vasodilation Sympathetic activity Increase thermogenesis Capsinoids TRPV1 Doesn’t reach the tongue due to structural difference 1000th x less potent Sympathetic activity Increase thermogenesis Mechanisms

4. Objectives • Examine the effects of DCT on both adaptive thermogenesis as the result of caloric restriction with a high protein, very low calorie diet • Determine whether DCT would increase post-prandial energy (PPEE) in response to 400 calories/ 60 grams protein liquid meal

5. Inclusion Criteria: • Men over age of 30 and postmenopausal women • Nonsmoker or smoke less than 1 cigarette a day • Subject willing to go on a VLCD as meal replacement • Can sign the IRB/ informed consent

6. Exclusion Criteria • More than 30 minutes of exercise/ week • Diabetes, uncontrolled BP (>160/95), eating disorders, chronic infections, malignancy • Major surgeries in past 12 weeks • > 1 alcohol beverage/ day or tobacco • Antidepressants or weight loss supplement • Allergy to chili peppers

7. Methods • VLCD 800 cal/120g protein • Capsiate capsules • Placebo, 3mg, 9mg • Body composition • Indirect calorimetry

8. Method • Week 1 • Safety blood, weigh in, BodPod • Baseline Vmax (1) • 400 calories/ 60 g protein • Vmax (2- 4) • Week 2, 3 • Safety blood, weigh in, BodPod • 800 calories/ 120 g protein • DCT capsules (placebo, 3mg or 9 mg) • Week 4 • Repeat of week one • 400 calories/ 60 g protein • 9 capsules of group

9. Baseline Characteristics

10. Safety • No severe adverse Events • Adverse events from VLCD • No significant change of chemistry, liver function tests

11. Results

12. Change of Body Weight

13. Resting Metabolic Rate kcal/day

14. Postprandial Energy Expenditure

16. Conclusions • We did not see any significant change of the adaptive thermogenesis with the VLCD program. • DCT significantly increased postprandial energy expenditure. • DCT significantly increased fat oxidation.

17. Interpretation • No weight change was detected in this 4 week study. • This may have been due to the effects of the VLCD on weight change in an outpatient setting overwhelming the effects of the DCT. • Increased fat metabolism was observed with an increase of RQ after the 400 cal/ 60 g protein test meal challenge but there was no interference with the adaptive decrease in thermogenesis seen with VLCD.

18. Discussion DCT stimulate thermogenesis in animals, and activate the neuronal TRPV1 receptors on vagal afferent nerves in the intestine leading to increased SNS activity with uncoupling of oxidative phosphorylation leading to heat production. PPEE was also observed in this study after subjects took in 400 calories / 60 g protein

19. Future Research Directions • Need longer term studies with a less intensive diet to detect the effects of 9 mg of dihydrocapsiate per day vs. placebo on weight and obesity-associated co-morbidities.

20. 51 enrolled 33 completed Placebo 3 males, 1 female Noncompliance Feeling weak 3 mg 3 males Noncompliance Uncontrolled BP 9 mg 3 males, 3 females Noncompliance Constipation Feeling weak Low glucose Drops

21. Thank you! Thank you!