Human Milk Electrolytes as Nutritional Biomarkers of Mammary Gland Integrity: A Study Across Ductal Conditions and Donor Milk

<b>Background/Objectives</b>: Sodium (Na) concentration and the sodium-to-potassium (Na/K) ratio in human milk reflect epithelial tight junction integrity and have been proposed as non-invasive biomarkers of lactational dysfunction, including subclinical mastitis and ductal obstruction. However, their discriminative performance across varied mammary duct conditions, as well as their relevance to milk quality and nutritional integrity, remain underexplored. This study aimed to evaluate the ability of Na, K and the Na/K ratio to discriminate ductal obstruction from non-obstructed lactation-including normal, mixed, and donor milk-and to assess their applicability as nutritional and clinical screening biomarkers. <b>Methods</b>: The study analyzed 635 human milk samples from four groups: obstructed ducts (<i>n</i> = 94), mixed ducts (<i>n</i> = 39), normal ducts (<i>n</i> = 102), and donor milk (<i>n</i> = 400). Na and K concentrations were measured using validated handheld ion-selective electrode analyzers. Statistical analyses included Quade's ANCOVA and receiver operating characteristic curve analysis, adjusting for infant age, gestational age, birth body weight, maternal age and storage duration. <b>Results</b>: Na concentrations were highest in obstructed ducts (Group A: median 810 ppm, IQR 368-1725) compared with normal ducts (Group C: 220 ppm, IQR 140-283) and donor milk (Group D: 98 ppm, IQR 80-130) (<i>p</i> < 0.001). A similar pattern was observed for the Na/K ratio (Group A: 1.5, IQR 0.6-3.1 vs. Group C: 0.3, IQR 0.2-0.5; Group D: 0.3, IQR 0.2-0.3). After adjusting, both Na and the Na/K ratio remained significantly elevated in milk from obstructed ducts compared to non-obstructed samples (<i>p</i> < 0.001). Donor milk exhibited the lowest and most stable electrolyte levels. Na demonstrated excellent discriminative performance (area under the curve = 0.96), slightly outperforming the Na/K ratio (area under the curve = 0.92). <b>Conclusions</b>: Na concentration and the Na/K ratio in human milk are sensitive and practical biomarkers of mammary gland integrity. Given that Na alone can be measured without additional calculations, its simplicity and strong performance support its application as a potential biomarker for ductal obstruction, with implications for both lactation support and nutritional science.