1 european union garlic inflammation study (eugis) history garlic would influence lipid metabolism /...
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European Union Garlic Inflammation Study (EUGIS)
History
• Garlic would influence lipid metabolism / atherosclerosis
• Proposed study:
- 2 x 24 apparently healthy subjects with increased risk (mildly hypercholesterolemic, smoking)
- parallel trial (24 garlic / 24 placebo)
- biochemical measures lipid metabolism / inflammation
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European Union Garlic Inflammation Study (EUGIS)
Current situation:
• No indications that ‘garlic’ influences lipid metabolism
Human intervention study without rationale is unethical; previous proposal not feasible
• New situation requires evaluation; other type of
intervention study
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European Union Garlic Inflammation Study (EUGIS)
Considerations:
• 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 (for example: lipid lowering drugs; statins)
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European Union Garlic Inflammation Study (EUGIS)
Primary endpoint: C-reactive protein
Secondary efficacy parameters:
• fibrinogen, vWF, sensitivity of leukocytes to inflammatory stimulus
• plasma lipids
• blood pressure
• cancer biomarkers (anti-oxidant enzymes, DNA damage, antimutagenic properties)
• metabolites
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European Union Garlic Inflammation Study (EUGIS)
Double dummy placebo-controlled trial; 3 parallel groups (n=30); risk group (40-75 y,BMI 24.5 kg/m2, smoking 10 cig/d, post-menopausal)
1. Spanish Printanor 2001 2.1g/day
2. Statin 40 mg/day
3. Placebo
Power = 0.87- 0.72 for 30 - 25% CRP-reduction
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European Union Garlic Inflammation Study (EUGIS)
1. Garlic powder from EU-sponsored breeding programme, Spanish Printanor year 2001
- all compounds present in fresh garlic / sulphur-rich compounds preserved (allicin content 1.02%)
- compliant with European Pharmacopoeae with respect to microbial impurities
- heavy metals, pesticides, aflatoxin comply
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European Union Garlic Inflammation Study (EUGIS)
• Recruitment: advertisements
• Medical screening + blood sampling
• Randomisation
• Duplicate sampling (10-14 days apart) / measurements at start, after 4 wks and at end treatment period (12 wks)
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European Union Garlic Inflammation Study (EUGIS)
Screening Intervention period
0 4 - 5 11-12 weeks
Blood and urine collection
-2
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European Union Garlic Inflammation Study (EUGIS)
Biomarkers for inflammation
• C-Reactive Protein• Fibrinogen• Cytokines after whole blood stimulation without and with LPS (TNF- or IL-10)• von Willebrand Factor (biomarker for endothelial function)
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European Union Garlic Inflammation Study (EUGIS)
• Clinical measures (ECG, HRV, BP)
• Routine lab (cholesterol, HDL-C, triglycerides, Hb, haematocrit, white cell count, liver/kidney/ muscle function)
• DNA damage in lymphocytes (comet assay)
• Anti-oxidant enzymes (GPX, SOD)
• Antimutagenic properties of urine (Ames test)
• Metabolites of garlic compounds in plasma and urine
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European Union Garlic Inflammation Study (EUGIS)
- Additional biomarkers (suggested (in the EU-proposal))
• s-VCAM / s-ICAM / s-Selectine
• PAI-1
• MCP-1 and other chemokines
• endothelin 1 and 3
• SAA
• ox-LDL (plasma) / isoprostanes (urine)
• soluble CD40L (platelets)
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European Union Garlic Inflammation Study (EUGIS)
Points to discuss
• Positive control (is statin the right control?; preparation placebo; costs)
• Mask taste/smell (DADS in placebo?)
• If bad compliance, reduce dosage to 1.2 g/d
• Costs working up blood/lymphocytes
• Further characterisation of garlic powder
• Additional measurements and financing