Transcript Effects of Dihydrocapsiate on Adaptive and Diet-Induced
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 [email protected]
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
Mechanisms
Capsaicin – TRPV1 Tongue, gut, others Peripheral vasodilation Sympathetic activity Increase thermogenesis Capsinoids – TRPV1 Doesn’t reach the tongue due to structural difference 1000 th x less potent Sympathetic activity Increase thermogenesis
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
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
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
Methods
VLCD 800 cal/120g protein Capsiate capsules – Placebo, 3mg, 9mg Body composition Indirect calorimetry
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
Baseline Characteristics
Placebo Subject number Age (y) 50 ±11.78
Females (%) Body Mass (kg) 70 91.8
±14.6
BMI (kg/m 2 ) 31.22
±3.38
Fat Free Mass (kg) REE (kcal/d) 57.6
±11.8
1431.4
±276.8
3 mg 9mg 54.58
±9.33
53 86.3
±19.6
30.33
±2.99
51.1
±14.6
1377.9
±314.7
54.22
±11.872
44 92.9
±16.9
31.77
±3.59
52.5
±15.6
1397.6
±282.2
Safety
No severe adverse Events Adverse events from VLCD No significant change of chemistry, liver function tests
Study group (randomized) Screened but never started Had at least one dose Stopped at 1 week Stopped at 2 week Stopped at 3 week Completed 4 weeks
Results
CAPSINOIDs
32 0 0 1 8 0 15
PLACEBO
15 0 0 1 3 0 18 TOTAL 47 3 0 2 13 0 33
Change of Body Weight
Day 0 0 -4 -5 -6 -1 -2 -3 Day 7 Day 14 Day 21 Day 28 Placebo 3 mg DCT 9 mg DCT
Resting Metabolic Rate
1600 1400 1200 1000 800 600 400 200 0 placebo 3 mg DCT 9 mg DCT
Day 0 Day 28
Postprandial Energy Expenditure
8.0
6.0
4.0
2.0
0.0
*
Figure 1 Changes of average of energy expenditure adjusted by fat free mass (EE/FFM) from 1h to 4h during diet induced thermogenesis at Day 28. FFM was determined by BODPOD. Values are shown mean and SE. *; P<0.05 vs placebo.
placebo 3 mg 9 mg
* * 0.06
0.04
0.02
0.00
-0.02
Figure 2 Changes of average of respiratory quotient (RQ) from 1h to 4h during diet induced thermogenesis at Day 28. Values are shown mean and SE. *; P<0.05 vs placebo.
placebo 3 mg 9 mg
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.
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.
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
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.
51 enrolled 33 completed
Drops
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