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
Dihydrocapsiate (DCT)





Capsicum annuum L. CH19 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
 1000th 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
3 mg
9mg
50±11.78
54.58±9.33
54.22±11.872
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
57.6±11.8
51.1±14.6
52.5±15.6
1431.4±276.8
1377.9±314.7
1397.6±282.2
Subject number
Age (y)
Females (%)
Fat Free Mass (kg)
REE (kcal/d)
Safety
No severe adverse Events
Adverse events from VLCD
No significant change of chemistry,
liver function tests
Results
CAPSINOIDs
TOTAL
PLACEBO
Study group (randomized)
32
15
47
Screened but never started
0
0
3
Had at least one dose
0
0
0
Stopped at 1 week
1
1
2
Stopped at 2 week
8
3
13
Stopped at 3 week
0
0
0
Completed 4 weeks
15
18
33
Change of Body Weight
Day 0
0
Day 7
Day 14
Day 21
Day 28
Placebo
Weight (kg)
-1
-2
3 mg
DCT
-3
9 mg
DCT
-4
-5
-6
kcal/day
Resting Metabolic Rate
1600
1400
1200
1000
800
600
400
200
0
Day 0
Day 28
placebo
3 mg DCT
9 mg DCT
Change of EE/FFM
( kcal/day/kg)
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
*
Change of RQ
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 comorbidities.
Drops


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
Thank you!
Thank you!