Commentary: The association between serum vitamin C levels and respiratory infections in children and adolescents

The study's use of cross-sectional serum vitamin C levels provides valuable epidemiological evidence but must be interpreted distinctly from outcomes of supplementation trials. Randomized controlled trials (RCTs) have shown that regular vitamin C supplementation does not consistently prevent common colds in the general population but can shorten illness duration by approximately 14% in children and 8% in adults, particularly under conditions of physical stress such as athletic training or military service (2). These RCTs complement but do not directly equate to serum concentration studies, as circulating vitamin C reflects dietary intake, absorption, and metabolism rather than supplementation alone. Clarifying this distinction avoids overinterpretation of causality and situates Li et al.'s findings appropriately within the continuum from nutritional status to interventional efficacy.micronutrients such as zinc and vitamin D. This multidimensional nutritional perspective is valuable, yet it warrants further nuance. Systematic reviews report that zinc supplementation modestly reduces the duration of common colds but yields inconsistent results depending on formulation and dose(3). Similarly, vitamin D exhibits a protective effect mainly in deficient individuals(4)but more recent evidence (5)suggests attenuated or null associations. Distinguishing between hypothesized and established effects will enhance interpretive precision and scientific balance.Moreover, synergistic micronutrient interactions-while biologically plausible-remain theoretical and require validation through well-controlled factorial trials.To strengthen reproducibility, the commentary should briefly note the NHANES laboratory method (isocratic high-performance liquid chromatography with electrochemical detection) and the commonly applied deficiency threshold of <23 µmol/L for serum vitamin C. Including such technical detail would clarify measurement validity and improve comparability with other population-based studies.Additionally, the reliance on self-reported RIs introduces recall bias; combining questionnaire data with biomarker-confirmed infections (e.g., C-reactive protein or procalcitonin) in future analyses would yield more robust and clinically meaningful outcomes.From a causal standpoint, the cross-sectional nature of NHANES precludes directional inference. Incorporating approaches such as Mendelian randomization-using genetic variants related to vitamin C transporters (e.g., SLC23A1, SLC23A2)-could reduce confounding and reverse causality (6). These methods would strengthen causal plausibility between vitamin C and infection risk.A balanced interpretation benefits from linking population-level associations with mechanistic and interventional evidence. Vitamin C's immunomodulatory effects-through antioxidant activity, leukocyte function enhancement, and epithelial barrier maintenance-provide biological plausibility for its observed associations with RIs (7). Observational studies, such as Li et al.'s, identify population patterns, while RCTs clarify causality under controlled conditions. Integrating both lines of evidence supports a coherent narrative: vitamin C sufficiency contributes to immune resilience, but supplementation benefits may be context-dependent. Future longitudinal or hybrid designs could better capture temporal dynamics and physiological thresholds for protective effects.From a translational perspective, This commentary received no external funding.