While cigarette smoking has declined, e-cigarette use among young adults has increased in the USA. This cross-sectional study compared complete blood counts, C-reactive protein, and select blood metals (lead, cadmium, mercury, selenium, manganese) among exclusive combustible tobacco users, exclusive e-cigarette users, and non-users using NHANES data from 2013–2023 in the USA. The goal of this study was to compare biomarker data from e-cigarette users and combustible tobacco users to that of non-users. Among 756 participants aged 18–30, 229 reported no tobacco use, 74 used only e-cigarettes, and 453 smoked only combustible tobacco. Survey-weighted analyses adjusted for age, sex, race/ethnicity, and body mass index revealed that exclusive combustible use was associated with significantly elevated white blood cell counts, hemoglobin, hematocrit, mean corpuscular volume, lymphocytes, monocytes, neutrophils, and higher blood lead and cadmium. E-cigarette-only use showed fewer deviations overall but included higher mean corpuscular hemoglobin concentration and lower cadmium, selenium, and methyl mercury relative to non-users. Neither group differed significantly in red blood cell count or C-reactive protein, and inorganic/ethyl mercury and manganese levels were largely unchanged. These findings underscore pronounced hematologic and metal-related alterations in combustible tobacco users and fewer, but not negligible, changes among e-cigarette users. Further research is needed to determine the long-term health implications of exclusive e-cigarette use, including potential impacts on antioxidant micronutrient levels.

Summary: In modern healthcare, decision-making favours neatly delineated, categorical imperatives. We prefer to say: ‘This practice is good’ and ‘That one is bad’, believing that each decision has a straightforward yes-or-no resolution. However, medicine thrives in uncertainty, partial improvements and small steps that can lead to life-altering gains. Harm reduction, whether for tobacco use, opioid dependence or beyond, embodies the acceptance of imperfect solutions. It is precisely in these areas that black-or-white thinking can be most destructive. Insisting on total cessation or complete eradication of risk, rather than supporting incremental progress, alienates many patients and perpetuates preventable morbidity and mortality. Recognising this pattern and transcending ‘all-or-nothing’ mindsets is crucial for compassionate, evidence-based care. Accordingly, we ask: ‘How does binary thinking in medical decision-making impact the effectiveness of harm reduction strategies?’ Such an inquiry addresses how well we can truly meet patient needs in real-world practice, especially amid complexity.