**Background:** Preventing nicotine use onset among children and youth is an important public health goal. Caffeine is the most widely consumed psychoactive substance globally, with up to 75% of children and adolescents aged 5–17 consuming it regularly. Both caffeine and nicotine influence dopaminergic function, suggesting a biologically plausible link between the two substances. While studies in older adolescents have shown associations between caffeine and smoking, the prospective association between caffeine use and nicotine onset in young adolescents had not been tested empirically while controlling for well-established covariates such as alcohol use, peer substance use, and perceived access to nicotine.
**Methods:** Data were drawn from the first two waves of the Young Mountaineer Health Study (YMHS) cohort. From October–December 2020, 1,349 sixth-grade students (mean age 11.5 years; response rate 80.7%) from 20 geographically diverse public middle schools in five West Virginia counties completed baseline surveys. A follow-up survey was conducted in April–May 2021 using identical protocols. The analytic sample was limited to 1,187 participants who reported never using any type of nicotine product at baseline. Caffeine consumption was assessed via a validated inventory measuring daily intake of coffee, tea, caffeinated soda, energy drinks, and caffeine shots, weighted for proportional caffeine content and converted into deciles (range 0–3000 mg/day). Nicotine use at follow-up was assessed with three questions covering cigarettes, ENDS/e-cigarettes, and other tobacco products. Two dichotomous outcomes were created: any nicotine use (8.09% of participants) and exclusive ENDS use (4.66%). Covariates included gender, race, family structure, baseline alcohol use (13.19% reported any use), perceived parental reactions to substance use (α = 0.88), peer substance use (α = 0.84), perceived access to nicotine (r = 0.60), and parental tobacco use (36.21% reported daily parental use). Multivariable logistic regression was employed.
**Key Results:** At follow-up, 8.09% (80/989 with available data) of baseline never-nicotine users reported having used nicotine at least once, and 4.66% (46/987) reported exclusive ENDS use. Among the 80 nicotine users, 83.54% had used ENDS, 27.50% had smoked cigarettes, and 20.00% had used other tobacco products. Mean daily caffeine consumption at baseline was 191.81 mg (SD 301.64). The most prevalent caffeine sources were caffeinated soda (69.48%) and tea (50.84%). In Model 1 (any nicotine use), each decile increase in caffeine was associated with a 15% increase in odds of nicotine onset (OR 1.15, 95% CI 1.04–1.27, p = 0.003). Significant covariates included perceived parental reactions to ATOD use (OR 1.19, 95% CI 1.08–1.31, p = 0.0005), peer substance use (OR 1.18, 95% CI 1.08–1.28, p = 0.0001), and perceived access to nicotine (OR 1.38, 95% CI 1.08–1.28, p < 0.0001). In Model 2 (exclusive ENDS use), each decile increase in caffeine was associated with a 13% increase in odds (OR 1.13, 95% CI 1.00–1.28, p = 0.049). Significant covariates were perceived parental reactions (OR 1.18, 95% CI 1.06–1.32, p = 0.002) and any alcohol use at baseline (OR 2.41, 95% CI 1.16–5.03, p = 0.018). Gender, race, and family structure were not significant in either model.
**Clinical Implications:** This study provides the first prospective evidence linking caffeine consumption to nicotine use onset in early adolescents while controlling for a comprehensive set of social and behavioral covariates. The finding that those near the top of the caffeine consumption range were approximately 2.5 times more likely to initiate nicotine use compared to non-caffeine users has significant public health implications given the ubiquity of caffeine in youth diets. The dominance of ENDS as the primary mode of nicotine onset (83.5% of new users) aligns with national trends and Surgeon General concerns about youth ENDS use. The authors note that caffeine withdrawal syndrome can develop after as few as eight hours of abstinence, and that caffeine's effects on adenosine receptors and dopamine pathways may prime biological mechanisms that enhance nicotine's habit-forming potential. Limitations include the predominantly White sample from West Virginia (limiting generalizability), reliance on self-report, inability to distinguish nicotine-bearing from non-nicotine-bearing ENDS use, and lack of data on caffeine from non-beverage sources (e.g., chocolate, candy) or on where participants obtained caffeine products. The authors call for efforts to limit caffeine consumption among youth and for further research into the mechanisms linking early caffeine exposure to subsequent nicotine use.