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Supplement: Significance of Garlic and Its Constituents in Cancer and Cardiovascular Disease

In Vitro Interactions of Water-Soluble Garlic Components with Human Cytochromes P450^1–3,

Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts-New England Medical Center, Boston, MA

⁴ To whom correspondence should be addressed: E-mail: dj.greenblatt{at}tufts.edu.

Eight water-soluble components of aged garlic extract were evaluated to assess their potential to inhibit the activity of human cytochrome-P450 (CYP) enzymes. The in vitro model consisted of human liver microsomes with index reactions chosen to profile the activity of the following six CYP isoforms: CYP1A2, 2B6, 2C9, 2C19, 2D6, and 3A. With only 2 exceptions, none of the 8 garlic components produced >50% inhibition even at high concentrations (100 µmol/L). S-methyl-L-cysteine and S-allyl-L-cysteine at 100 µmol/L produced modest inhibition of CYP3A, reducing activity to 20–40% of control. However available clinical evidence does not indicate CYP3A inhibition in vivo. The findings suggest that drug interactions involving inhibition of CYP3A enzymes by aged garlic extract are very unlikely.

KEY WORDS: • aged garlic extract • Cytochromes P450 • in vitro metabolism • drug interaction

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