Transcript The effects of garlic on inflammatory biomarkers of

European Union Garlic Inflammation
Study (EUGIS) in Humans
Martijn van Doorn
Sonia Espirito Santo
TNO-PH
Leiden
The Netherlands
CHDR
Leiden
The Netherlands
Background
• No clear indications that ‘garlic’ influences lipid
metabolism
• Indications from cell and animal studies that ‘garlic’ may
influence inflammation parameters
• Cardiovascular disease (atherosclerosis) shares
common features with inflammation
• Current treatment strategies for atherosclerosis also
focus on inflammation, i.e. lipid lowering drugs like
statins)
Aim
Study the effects of garlic on inflammatory biomarkers of
atherosclerotic disease and on cancer biomarkers in
man
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Primary endpoint: changes in C-reactive protein ( CRP)
Secondary endpoints:
– Indicators of lipid metabolism
– Biochemical markers of inflammation
– Blood pressure / heart rate variability
– Biomarkers for anti-carcinogenic effects
Inclusion criteria
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Able and willing to give informed consent
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90 subjects of either gender
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Power calculation to find a reduction of 30% in
plasma CRP levels with = 0.05 and a power of 80%
about 30 subjects per group are needed.
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Aged between 40-75 years
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Smoking≥ 10 cigarettes/day and BMI≥ 24.5 kg/m2
Exclusion criteria
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Any major clinical significant abnormality detected by a
general health questionnaire or by blood sampling
Chronic drug treatment /use of medication, i.e. aspirin or
hormone replacement therapy, interfering with the study
Participation in prior studie(s) in the last 3 months
Blood donation, including this study, not according to
the guidelines of the blood donation services
Inadequate use of contraceptives
Pregnant or lactating women
History of alcohol or drug abuse
Positive test results for Hepatitis B, Hepatitis C or HIV
Dislike of garlic
Experimental design
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Double dummy placebo-controlled trial
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3 parallel groups (n=30)
I.C. / screening
-2
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Intervention period
4-5
Blood and urine collection
11-12 weeks
Groups design
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EU-sponsored Printanor 2001: 2.1g/day for 12 weeks
= 7 capsules of 300 mg (3 cap at breakfast and 4 cap
at dinner) = one medium-large size fresh garlic clove
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compliant with European Pharmacopoeia with
respect to microbial impurities;
Atorvastatin: 40 mg/day for 12 weeks = 1 tablet of 40
mg at dinner)
Placebo: tablets every day for 12 weeks
Measurements
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Clinical: Blood pressure, ECG 12 lead, Heart rate (HR),
and Heart Rate Variability (HRV).
Biochemical:
– Cholesterol, HDL, and triglycerides;
– CRP, vWF, Fbg, and cytokines after whole blood
stimulation without or with LPS (TNF-α, IL-10);
– Sensitivity of leukocytes to inflammatory stimulus;
– Cancer biomarkers: anti-oxidant enzymes (GPX,
SOD), DNA damage (Comet assay), anti-mutagenic
properties of urine (Ames test);
– Metabolites of garlic compounds in plasma and
urine;
Safety: Parameters of muscle (CPK) and liver function
(ALAT), and haematology (haematocrit, WBC count).
Additional measurements suggested in
the EU proposal
• SAA, and PAI-1
• s-VCAM / s-ICAM / s-Selectine
• MCP-1 and other chemokines
• Endothelin 1 and 3
• Plasma ox-LDL
• Urine isoprostanes
Current study status
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 Informed subjects: 120
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 Screened subjects: 70
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 Included (randomized) subjects: 52
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 Subjects started 1st occasion: 43
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# Subjects planned for info: 20
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# Screenings planned: 10
Ackowledgements
Martijn van Doorn
Koos Burggraaf
Sonia Espirito Santo
Hans Princen