Metabolic rhythms involving ketogenic metabolism, intermittent fasting, and chronic dehydration may produce sustained chloride retention relative to bicarbonate, creating a hyperchloremic non–anion gap metabolic acidosis terrain that could contribute to chronic cardiovascular stress before disease onset.
This preprint introduces the regulatory timing architecture underlying the Lantern of Sulfur Concept A series. It proposes the KICO hypothesis, a systems physiology model suggesting that metabolic rhythms involving ketogenic metabolism, intermittent fasting, and chronic dehydration may impose physiologic load on regulatory systems governing electrolyte balance. Within this framework, sustained metabolic rhythms may promote volume-conservation physiology through activation of the renin–angiotensin–aldosterone system (RAAS) and associated shifts in renal ion transport mechanisms including NKCC2 and pendrin activity in the distal nephron. These regulatory responses may favor chloride retention relative to bicarbonate, generating a hyperchloremic non–anion gap metabolic acidosis (NAGMA) terrain. The model integrates circadian regulation, hepatic metabolic signaling, renal electrolyte transport, and neurohormonal control into a vertical systems framework describing how metabolic rhythms may influence electrolyte terrain over extended time horizons. This work extends the electrolyte terrain model introduced in: Reversible HFrEF-The Pattern Five Specialties Missed, Lantern of Sulfur, Concept A, v12.3, March 2026, 10.5281/zenodo.18893393 Where the HFrEF preprint describes downstream cardiovascular expression, the present paper examines upstream metabolic and regulatory mechanisms that may contribute to chloride-dominant electrolyte terrain states. If correct, the framework predicts that longitudinal analysis of routine chemistry panels may reveal reproducible chloride–bicarbonate drift patterns in individuals exposed to sustained metabolic rhythms capable of producing volume contraction and buffering demand. This preprint is part or a triad with Circadian and Metabolic Timing in Electrolyte Regulation: A Coupled Clock Model Linking Metabolic Load, Chloride Terrain Signals, and Cardiovascular Stress, Lantern of Sulfur, Concept A, v12, March 2026, 10.5281/zenodo. 18896061
Beth Ann Martell (Wed,) conducted a other in Individuals undergoing sustained metabolic rhythms including ketogenic metabolism, intermittent fasting, and chronic dehydration potentially leading to electrolyte imbalance and cardiovascular stress. Metabolic rhythms involving ketogenic metabolism, intermittent fasting, and chronic dehydration vs. Normal metabolic rhythms without these sustained metabolic loads was evaluated on Chloride retention relative to bicarbonate levels leading to hyperchloremic non–anion gap metabolic acidosis (NAGMA) terrain. Metabolic rhythms involving ketogenic metabolism, intermittent fasting, and chronic dehydration may produce sustained chloride retention relative to bicarbonate, creating a hyperchloremic non–anion gap metabolic acidosis terrain that could contribute to chronic cardiovascular stress before disease onset.