1. Los Angeles, California
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

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. Mechanisms Capsaicin Capsinoids TRPV1 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

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 Body composition
Placebo, 3mg, 9mg
Body composition
Indirect calorimetry

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

9. Baseline Characteristics
Placebo
3 mg
9mg
Subject number
Age (y)
50±11.78
54.58±9.33
54.22±11.872
Females (%) 70 53 44
Body Mass (kg)
91.8±14.6
86.3±19.6
92.9±16.9
BMI (kg/m2)
31.22±3.38
30.33±2.99
31.77±3.59
Fat Free Mass (kg)
57.6±11.8
51.1±14.6
52.5±15.6
REE (kcal/d)
1431.4±276.8
1377.9±314.7
1397.6±282.2
This should be all the 51 subjects not just the completers.

10. Safety No severe adverse Events Adverse events from VLCD
No significant change of chemistry, liver function tests
Divide into 3 groups

11. Results TOTAL CAPSINOIDs PLACEBO Study group (randomized) 32 15 47
Screened but never started 3
Had at least one dose
Stopped at 1 week 1 2
Stopped at 2 week 8 13
Stopped at 3 week
Completed 4 weeks 18 33
Divide into 3 groups with reason to drop

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

21. Thank you!
Thank you!