Olfactory Function, Caffeine Intake, and Mortality in a Nationally Representative Cohort

Olfactory function is closely tied to nutrition, social and emotional well-being, and safety, with its decline reducing quality of life across the lifespan and serving as a marker of frailty, depression, cognitive decline, and mortality risk in older adults [1, 2]. Despite increasing awareness of the importance of olfactory dysfunction (OD), few strategies exist to preserve or restore olfaction in aging populations. Preliminary evidence suggests that caffeine usage is associated with improved olfaction. While it has well documented effects on alertness, mood, and motor performance [3], caffeine's relationship with olfaction remains not fully elucidated. Animal studies suggest that caffeine's antagonistic action on A2a adenosine receptors, abundantly expressed in the olfactory bulb, may enhance olfactory performance [4]. In humans, a cross-sectional study of first-degree relatives of Parkinson's disease patients found improved olfaction among those consuming two to four cups of caffeinated beverages per day [5]. Furthermore, emerging epidemiological evidence suggests coffee consumption may be protective against cellular aging [6]. These findings raise two possible roles for caffeine in olfactory function. First, habitual caffeine consumption may confer long-term benefits for olfactory performance. Second, caffeine may serve as an acute stimulant to temporarily enhance olfactory sensitivity or identification in certain contexts. However, additional prior studies of the impact of caffeine on olfaction report mixed findings. Meusel et al. found no olfactory improvement following 65 mg of caffeine in patients with sinonasal infections [7]. Han et al. reported no effect of 72 mg of caffeine on olfaction in young (mean age of 27.7 ± 2.8 years) normosmic individuals, despite observed improvements in attention [8]. Notably, Stafford et al. observed that 100 mg of caffeine improved olfactory performance, but only in non-habitual caffeine users [9]. These inconsistencies may be due to short-term dosing, small sample sizes, or limited generalizability to aging populations. To address these gaps, the present study investigates the relationship between caffeine intake and olfactory performance in a large, nationally representative sample of US adults. By focusing on both habitual intake and olfactory performance, we aim to clarify whether caffeine could play a protective role against age-related olfactory decline. The data were procured from the 2013-2014 National Health and Nutrition Examination Survey (NHANES), including patients 40 years and older. OD was evaluated using the eight-item Pocket Smell Test. Failing to identify three of eight scents was considered olfactory dysfunction. Caffeine use was categorized into low (≤32.5 mg), moderate (32.6–219.5 mg), and high (≥219.6 mg), with each category representing the 25th, 50th, and 75th percentiles of caffeine intake, respectively. Covariates included age, gender, race, education, income, depression symptom status as per patient health questionnaire-9 (PHQ-9) score, smoking status, or a history of facial trauma or head trauma. Patients missing data on smell function and caffeine intake were excluded from the analysis. A total of 2805 participants met the inclusion criteria. Table 1 compares individuals with normal olfaction and those with OD. Older age, male sex, lower income, and less than a nineth-grade education were significantly associated with OD. Gender, N (%) Race, N (%) Income, N (%) ($) Education, N (%) Smoking, N (%) Head trauma, N (%) Face trauma, N (%) Depression, N (%) In unadjusted logistic regression (Table 2), moderate caffeine intake was associated with 1.28-fold higher odds of normosmia (95% confidence interval [CI]: 1.01–1.61; p = 0.04) and high intake with 1.84-fold higher odds (95% CI: 1.37–2.48; p < 0.001). After adjustment for covariates, moderate (odds ratio [OR]: 1.31, 95% CI: 1.02–1.69; p = 0.036) and high (OR: 1.75, 95% CI: 1.27–2.42; p < 0.001) caffeine intake remained significantly associated with normosmia compared to low intake, with each increase in caffeine quartile linked to 1.32-fold higher odds of normosmia (95% CI: 1.19–1.38; p < 0.001). Caffeine intake and olfactory function were further assessed for mortality risk. Unadjusted models showed that normosmia was strongly protective, associated with 68% lower odds of mortality (OR: 0.32, 95% CI: 0.24–0.42; p < 0.001), whereas caffeine intake was not. In adjusted models, normosmia remained protective against mortality (OR: 0.55, 95% CI: 0.40–0.75; p < 0.001), while higher caffeine intake showed a nonsignificant trend toward reduced mortality (OR: 0.72, 95% CI: 0.48–1.07; p = 0.11). In this population-level analysis, individuals with higher caffeine intake were less likely to have OD. After adjusting for relevant covariates, participants consuming more than 219.5 mg of caffeine per day had 1.32 times higher odds of normosmia. This association remained consistent even after controlling for relevant covariates and suggests a potential protective effect of caffeine on olfactory function in a dose-dependent manner. Interestingly, this dose of caffeine is consistent with the average intake of Americans 55–64 years old (226 ± 2 mg/day) [10]. These findings also help reconcile prior conflicting literature by highlighting the importance of habitual caffeine intake, rather than isolated single doses, in supporting olfactory performance. Earlier studies often administered relatively small amounts of caffeine (e.g., 65–100 mg) in acute settings [7, 9], which may not capture the physiological adaptations associated with long-term consumption. Our results suggest that sustained higher daily caffeine intake, at levels typical of the American diet, may be more relevant to preserving olfactory function, particularly in populations vulnerable to age-related decline. Several limitations should be noted. The cross-sectional design limits causal inference. Furthermore, NHANES dietary intake data rely on participant self-report, introducing potential recall bias and underreporting. Although NHANES urinary caffeine metabolites data could offer objective measures, substantial variability in caffeine metabolism limits their interpretability, whereas dietary intake may better reflect long-term consumption. Neurodegenerative processes are also known to influence olfaction, yet NHANES cognitive testing is limited to a few assessments without formal diagnostic data and is available only for a subset of participants. Longitudinal studies are needed to clarify caffeine's role in olfactory preservation and its underlying mechanisms. This study was accepted as an oral presentation at the American Rhinologic Society 71st Annual Meeting at the American Academy of Otolaryngology. The authors have nothing to report. The authors declare no conflicts of interest.