Driven by the hypothesis that combination of dietary polyphenols, with distinct mechanisms of action, may improve cellular energy and fatty acid metabolism, preventing thereby the development of the metabolic syndrome and diabetes, the following…
ID
Source
Brief title
Condition
- Lipid metabolism disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary study parameter is the difference in postprandial fat oxidation
after the 3 polyphenol conditions
Secondary outcome
As secondary endpoints, differences in the systemic and local tissue lipolysis,
mitochondrial function, oxidative stress, insulin sensitivity and body
composition between the various polyphenol supplements are examined.
Background summary
There is an urgent need for additional preventive strategies against obesity,
diabetes and the metabolic syndrome since the increasing prevalence of these
diseases is one of the major health care problems in both developed as well as
developing countries. Dietary polyphenols may have the potential to improve
lipid oxidation and mitochondrial function and may consequently contribute to
the prevention of diabetes and the metabolic syndrome. So far, no studies have
addressed the additive or possibly synergistic effects of combinations of
specific polyphenols with partly distinct mechanisms of action on fat oxidation
and metabolic profile in overweight subjects.
Study objective
Driven by the hypothesis that combination of dietary polyphenols, with distinct
mechanisms of action, may improve cellular energy and fatty acid metabolism,
preventing thereby the development of the metabolic syndrome and diabetes, the
following objectives will be addressed:
(1) to test short term (3 day) effects of combinations of polyphenols
(supplements of EGCG either in combination with resveratrol or with resveratrol
and soy isoflavones) to affect systemic lipolysis and fat oxidation during
overnight fasted conditions and after ingestion of a high fat meal in
overweight subjects;
(2) to perform a randomized controlled intervention study with the most
promising combination of dietary polyphenols, investigating its effect on fat
oxidation, mitochondrial function and insulin sensitivity in overweight
subjects over a 12 wk period.
Study design
Study 1
A double blind placebo controlled cross over design with 3 treatments will be
used. Treatment duration will be 3 days with a 7 day wash-out period in
between. Treatments will be (1) the combination of of EGCG (282 mg daily) and
resveratrol (200 mg daily), (2) these 2 polyphenols combined with soy
isoflavones (48 mg genistein daily) or (3) placebo. Supplements will be taken
twice a day at breakfast and dinner. At day 3, 13 and 23 circulating metabolite
concentrations, catecholamines, oxidative stress markers and fat oxidation will
be determined in plasma and urine samples during overnight fasted conditions
and after a high fat test load. On the end of the testday an adipose tissue
biopsy will be taken.
Study 2
Duration of the study will be 12 weeks. A double blind parallel design will be
used. Overweight subjects will be randomized to polyphenol supplementation or
placebo with stratification for age and sex. Before and after intervention, at
one day, measurements on fat oxidation during fasting and after a high fat
mixed meal will take place and, at a second day, insulin sensitivity will
determined. Body composition will be determined before and after intervention
by means of DEXA scanning. On a separate day, adipose tissue and muscle
biopsies will be taken and depending on the outcome further molecular
characterization of pathways of lipolysis, fat oxidation, mitochondrial
function and insulin sensitivity will be performed. Faeces will be collected on
the biopsy day. In 10 subjects of each group, local adipose tissue lipolysis
will be determined by microdialysis during the high fat meal.
Intervention
3 different dietary polyphenol conditions:
A. EGCG (282mg daily) + resveratrol (200mg daily)
B. EGCG (282mg daily) + resveratrol (200mg daily) + soy isoflavones (48mg
genistein daily)
C. Placebo
Study burden and risks
Results obtained from the study provide insight on the possible positive
effects of various combinations of polyphenols on postprandial fat oxidation. A
higher postprandial fat oxidation could lead to less accumulation of lipid in
the fat and muscles tissue causing improvement in insulin sensitivity and
metabolic profile on the long-term.
The study carries minor to no risks for the subjects. The only burden comes
from taken blood samples, placement of the microdialysis probes and taking
skeletal muscle and adipose tissue biopsies. These burdens will be kept as
small as possible.
For study 1 the subject visits the university 4 times (screening + 3 long
testdays; total duration of 23 days with a wash-ot of 7 days in between).
During the long testdays a total of 603 ml blood will be taken and the subject
needs to wear the ventilated hood system to measure fat oxidation. At the end
of the testday testday an adipose tissue biopsy will be taken.
For study 2 the subject visits the university 3 times before and 3 times after
the 12 week intervention for. During the testdays a total of 350 ml blood will
be taken and the subject needs to wear the ventilated hood system to measure
fat oxidation, fat and muscle biopsies are taken, faeces be collected and
microdialysis probes are inserted (optional).
PO Box 616
6200 MD Maastricht
NL
PO Box 616
6200 MD Maastricht
NL
Listed location countries
Age
Inclusion criteria
- Overweight men and women (BMI>=25kg/m2- 34.9kg/m2),
- Aged 20-35 and 35-50 years
- Caucasian
- Normal fasting glucose (< 6.1 mmol/L)
- Normal blood pressure (systolic blood pressure 100-140 mmHg, diastolic blood pressure 60-90 mmHg)
- Weight stable in last 3 months (± 2kg).
Exclusion criteria
- Women lactating, pregnant or (post) menopausal
- Regular smokers
- People with intensive fitness training, eg. athletes (>= 3 per week >= 1 hour training)
- Habitual consumption of green tea (more than 1 cup per day) or products containing green tea extract
- Total caffeine consumption > 300 mg/day (1 can of cola or 2 cups of regular coffee or 2 cups of black tea or 1 cup of coffee and 1 cup of black tea or other combinations)
- Alcohol intake >20 g/day (2 glasses of beer or wine)
- Any dietary vitamins or dietary supplements
- Diabetes mellitus (defined as FPG >= 7.0 mmol/l and/or 2hPG >= 11.1 mmol/l)
- Serious pulmonary, cardiovascular, hepatic or renal disease
- History of cardiovascular disease
- All other relevant medical disorders that potentially interfere with this trial (e.g. history of gastro-intestinal, liver or thyroid disorders)
- Current use of medication interfering with study intervention or interfering with study endpoints/hypotheses (e.g. medication containing caffeine like analgesics, anorectics and analeptics)
- Not to be able to understand the study information
- Subjects on a special diet or vegetarian
- Blood donation 2 months prior to the study and during the study
- Participation in other studies
- Drug use
- Use of anti-coagulant medication
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT01302639 |
| CCMO | NL31421.068.10 |