Background: Metabolic flexibility is a fundamental marker of health, whereas its disruption underpins metabolic syndrome, type 2 diabetes, and malignancy. Classical paradigms dictate that hepatic ketogenesis occurs exclusively during glucose depletion or lipid overload. This study evaluates the kinetics of physiological ketosis induced by an oral acute L-lysine challenge as a novel, non-invasive indicator of metabolic plasticity and mitochondrial function.

Methods: Two cohorts were evaluated: Group 1 ((N=26) patients with unclassifiable functional gastrointestinal disorders) underwent comprehensive bioimpedance vector analysis (BIA-V), biochemical screening, and liver transient fibroelastometry. Group 2 (N=48) internal medicine physicians with latent functional GI signs) completed a standardized Dietary Inflammatory Index (DII) survey. Both groups underwent an oral L-lysine challenge (2.0 g), with breath acetone tracked via KETONIX® over 180 minutes to calculate the Area Under the Curve (AUC), maximum concentration (Cmax), and time-to-peak (Tmax). Residual ketones were also measured 30 minutes postprandially.

Results: In Group 1, L-lysine induced a highly significant, non-linear wave-like metabolic response (p=0.0012), characterized by a peripheral utilization "dip" at 60 min (p=0.025) and a hepatic production peak near 150 min. Ketone exposure (AUC) and peak concentration (Cmax) strongly correlated with basal metabolic rate (BMR; (r=0.66), (p<0.00) and total cholesterol (r=0.43), (p=0.032), but displayed no relationship with structural liver stiffness or cytolysis enzymes. In Group 2, the cohort split into Responders (56.3%, (Cmax - 5.0ppm) and Non-responders (43.7%), independent of baseline BMI or age. A strong, significant direct correlation was identified between the pro-inflammatory DII and (AUC) (r=0.64), (p=0.00001), with Responders demonstrated higher dietary inflammatory scores (mean DII = 4.4) than Non- responders (mean DII = 0.0). Heavier individuals (BMI (>29) kg/m2) exhibited a delayed peak (Tmax) shifted to 150 min), validating a phenotype of metabolic sluggishness. Furthermore, a profound positive correlation was observed between (AUC) and 30-minute postprandial residual ketone levels (r=0.938), (p<0.0001).

Conclusion: Oral L-lysine administration successfully induces physiological signaling ketosis under eoglycemic conditions without dietary fat loading. The distinct kinetic profiles, responder phenotypes, and high postprandial stability reflect baseline mitochondrial capacity and adaptive inflammatory priming, serving as a safe, practical diagnostic tool for patient populations intolerant to classical ketogenic strategies.