Objective: To evaluate the effectiveness of using nicotine metabolite ratio (NMR) as an informed biomarker to optimize acupuncture for smoking cessation. Methods: This was a prospective, two-arm, open-label randomized controlled trial. Participants were recruited and classified as slow or normal metabolizers based on their NMR values, and were randomly assigned to high-frequency or low-frequency acupuncture groups. Acupuncture sessions were held 3 to 5 times per week for 8 weeks. Minimum behavioral support was provided. The primary outcome was the 12-week continuous abstinence rate assessed by urine cotinine levels. Secondary outcomes included point abstinence, treatment adherence, and adverse reactions. Results: Between September 2018 and April 2022, 220 participants were included. Among them, 211 (95.9%) were male, and the mean (SD) age was 48.5 (11.6) years. With 0.31 as the NMR cut-off value, 70 (31.8%) were divided as normal metabolizers and 150 (68.2%) as slow metabolizers. The validated 3-month sustained abstinence was 17.3% (19/110) in the high-frequency acupuncture group, which was significantly higher than 8.2% (9/110) in the low-frequency acupuncture group (OR=3.89, 95% CI: 1.36, 8.11). In slow metabolizers, the validated 3-month sustained abstinence rate was 19.0% (15/79) in the high-frequency acupuncture, which was higher than 7.0% (5/71) in low-frequency acupuncture (OR=3.53, 95% CI: 1.03, 6.13). In normal metabolizers, the validated 3-month sustained abstinence rates were 12.9% (4/31) in the high-frequency acupuncture group and 10.3% (4/39) in the low-frequency acupuncture group, with high-frequency acupuncture non-inferior to low-frequency acupuncture (OR=1.11, 95% CI: 0.24, 5.17). Treatment adherence was high in both groups, and adverse reactions were infrequent. No serious adverse events were recorded. Conclusion: This pioneering study demonstrated that NMR might be used as a biomarker to optimize acupuncture treatments for smoking cessation, particularly among slow metabolizers. This study provides valuable insights into personalized smoking cessation strategies and highlights the potential of integrating acupuncture with other interventions for improved outcomes.

The authors have declared no competing interest.

ChiCTR1800018196

The author(s) received no specific funding for this work.

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The trial was approved by the Chinese Clinical Trial Ethics Review Committee (Grant No.ChiECRCT-20180135) and registered in the Chinese Clinical Trials Registry (Reg. No. ChiCTR1800018196).

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