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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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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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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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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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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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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• 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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Screening Intervention period

0 4 - 5 11-12 weeks

Blood and urine collection

-2

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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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• 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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- 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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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

1 european union garlic inflammation study (eugis) history garlic would influence lipid metabolism /...

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