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N. Fujioka

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    P1.01 - Poster Session with Presenters Present (ID 453)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Epidemiology/Tobacco Control and Cessation/Prevention
    • Presentations: 1
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      P1.01-012 - Kava Effects on the Metabolism of Tobacco-Specific Carcinogen 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone (NNK) in Humans (ID 6279)

      14:30 - 15:45  |  Author(s): N. Fujioka

      • Abstract

      Kava is extracted from the roots of piper methysticum and is consumed by South Pacific Islanders as a relaxing beverage. Epidemiologic evidence points to a protective effect of kava against tobacco-induced lung cancer. NNK is a potent tobacco-specific carcinogen indisputably linked to lung cancer formation. Kava reduced NNK-induced lung adenoma formation in the A/J mouse model. Data also suggest that enhanced NNAL detoxification may be a potential mechanism by which kava exerts a chemopreventive effect. In humans, urinary NNAL is a validated biomarker of NNK uptake. We conducted a clinical trial in smokers to assess the effect of kava on NNK metabolism. The primary objective was to compare urinary total NNAL before and after kava administration. Secondary objectives included comparing the NNAL-gluc/NNAL-free ratio, determining the safety of kava, and quantifying O[6]-methylguanine adducts. The hypothesis was that kava administration would result in increased levels of NNAL in the urine (and increased NNAL-gluc/NNAL-free ratio), reflecting increased elimination and/or increased detoxification of NNK. Additionally, we hypothesized that kava could reduce O[6]-methylguanine adducts.

      We conducted a single-arm, open-label clinical trial in adult healthy smokers, in which subjects took a commercial kava supplement three times daily for seven days. Twenty-four hour urine collections were collected at baseline, days 4-5, and days 6-7 of the kava intervention for NNAL quantification. Blood samples were collected at baseline, day 4, and day 7 of the kava intervention for safety monitoring and for DNA adduct analysis. Subjects also completed a detailed tobacco questionnaire, food diary, smoking diary, and cigarette evaluation scale (CES) questionnaire. To date, 17 subjects (goal = 18) have completed the study.

      The results and statistics are being finalized. Short-term kava administration was safe with no evidence of hepatotoxicity. Subjects experienced less of the reinforcing effects of smoking after short-term kava administration as determined by the CES scores. The total CES score decreased on average by 4.47, from 45.53 to 41.06 (p=0.053, 95% CI -0.06-9.01). Notably, the smoking “satisfaction” scores decreased by 0.607 (p=0.024, 95% CI 0.09-1.12).

      This is the first study investigating the effect of kava on NNK metabolism in humans and is the first step to gain a more sophisticated mechanistic understanding of kava’s role in potentially modulating tobacco-related lung cancer risk. Short-term kava administration is safe in healthy adult smokers. Kava holds potential as a possible chemopreventive agent for smokers or tobacco cessation aide.