Effects of Dihydrocapsiate on Adaptive and Diet-Induced Thermogenesis with High Protein Very Low Calorie Diet

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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_at_mednet.ucla.edu

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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

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Mechanisms

• Capsaicin
• TRPV1
• Tongue, gut, others
• Peripheral vasodilation
• Sympathetic activity
• Increase thermogenesis

• Capsinoids
• TRPV1
• Doesnt reach the tongue due to structural
  difference
• 1000th x less potent
• Sympathetic activity
• Increase thermogenesis

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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

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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

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Exclusion Criteria

• More than 30 minutes of exercise/ week
• Diabetes, uncontrolled BP (gt160/95), eating
  disorders, chronic infections, malignancy
• Major surgeries in past 12 weeks
• gt 1 alcohol beverage/ day or tobacco
• Antidepressants or weight loss supplement
• Allergy to chili peppers

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Methods

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

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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

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Baseline Characteristics
  Placebo 3 mg 9mg
Subject number      
Age (y) 5011.78 54.589.33 54.2211.872
Females () 70 53 44
Body Mass (kg) 91.814.6 86.319.6 92.916.9
BMI (kg/m2) 31.223.38 30.332.99 31.773.59
Fat Free Mass (kg) 57.611.8 51.114.6 52.515.6
REE (kcal/d) 1431.4276.8 1377.9314.7 1397.6282.2
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Safety

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

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Results
CAPSINOIDs PLACEBO TOTAL
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
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Change of Body Weight
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Resting Metabolic Rate
kcal/day
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Postprandial Energy Expenditure
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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.

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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.

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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

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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.

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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

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Thank you!
Thank you!