Human Intervention Study

1
Human Intervention Study
From Report of the EU reviewers (Midterm review
14-02-2002, Brussels) The human studies need
careful thought otherwise there is a danger of
the project appearing to have failed simply
because it did not provide the hoped for cure for
heart disease and cancer
2
Human Intervention Study
History - Garlic would influence lipid metabolism
/ atherosclerosis - Proposed study - 2 24
apparently healthy subjects with increased risk
(mildly hypercholesterolemic, smoking) -
parallel trial (24 garlic / 24 placebo) -
biochemical measures lipid metabolism /
inflammation
3
Human Intervention Study

• 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

4
Human Intervention Study
Considerations - Indications that garlic may
influence inflammation - Cardiovascular disease
(atherosclerosis AS) shares common features with
inflammation CRP is primary endpoint - Current
treatment strategies for AS also focus on
inflammation (for example lipid lowering drugs
statins)
5
Human Intervention Study

• Garlic and Inflammation/Atherosclerosis
• parallel design 3 groups (n30) risks groups
  high doses!!
• garlic powder (Kwai / EU??)
• aged garlic extract (Kyolic??)
• control
•  power 0.87- 0.72 for 30 - 25 CRP-reduction

6
Human Intervention Study
- Garlic powder (Kwai / EU??) - all compounds
present in fresh garlic / sulphur-rich compounds
(Alliin) preserved - Aged garlic extract
(Kyolic??) - fermented garlic (S-allyl cystein)
7
Human Intervention Study
- Recruitment advertisements - Medical
screening - 2-week run-in period - Duplicate
sampling (10-14 days apart) / measurements -
Randomisation - Duplicate sampling /
measurements HALF-WAY (6 wks) END treatment
period (12 wks)
8
Garlic and Inflammation

• Biomarkers for inflammation
• C-Reactive Protein (!!)
• Fibrinogen
• Cytokines after whole blood stimulation with LPS
  (TNF-? IL-10)
• Biomarkers for endothelial function
• von Willebrand Factor

9
Additional biomarkers atherosclerosis

• Clinical measures (ECG / HRV / BP)
• Routine lab (chol / HDL-C / triglyc / LDH etc.)
• PAI / s-VCAM / s-ICAM / s-Selectine
• SAA
• ox-LDL (plasma) / isoprostanes (urine)
• soluble CD40L (platelets)

10
Additional biomarkers atherosclerosis

• IL-18 (IL-6)
• mRNA - leukocytes - gene array
• (Metabolites) of garlic compounds in urine (and
  blood?)

11
Additional biomarkers other

• Cancer biomarkers
• phase II enzymes as glutathione S-transferase
  and quinone reductase (plasma and lymphocytes)
• DNA damage (lymphocytes) - comet assay
• Anti-mutagenic properties (urine) - Ames test

12
Points to discuss

• Design
• Positive control? (statin)
• Study group Characteristics
• mildly obese, smokers, postmenopausal women
• Intervention material and supplier
• Lichtwer and Wakanuga? EU-preparation?)
• Dosages
• 6 g/day aged garlic extract / 2-4 g garlic powder

13
Points to discuss

• Questions
• is there a garlic effect?
• - is it dependent on the preparation?
• Are these the questions we want to answer?