Metabolic and Hormonal Adaptations to Ketogenic Diet in Central Indian Adults: A Case-Control Study

Background: The ketogenic diet (KD) induces nutritional ketosis through drastic carbohydrate restriction, profoundly altering gastrointestinal hormone secretion and metabolic signaling. This study systematically examines KD's effects on key gastric hormones (ghrelin, gastrin, cholecystokinin, glucagon-like peptide-1, motilin) and systemic ketone levels (β-hydroxybutyrate) in Central Indian adults, representing a population gap in ketogenic research. Material and Methods: In this prospective case-control study conducted January 2023–December 2024 at Index Medical College (n=264; 132 KD group, 132 controls), healthy adults aged 18-50 years (BMI 18.5-29.9 kg/m²) followed either monitored KD (10% carbohydrates, 70% fats, 20% proteins; <50g carbs/day) or standard Indian diet for 8 weeks. Fasting and postprandial gastric hormones plus plasma β-hydroxybutyrate (BHB) were quantified via ELISA and enzymatic assays at baseline and 8 weeks. Dietary compliance was verified through weekly ketone strips and food diaries. Data analysis used SPSS v28 (paired/independent t-tests, Pearson correlations; p<0.05). Results: The KD group achieved nutritional ketosis (BHB: 0.3±0.1 to 1.8±0.4 mmol/L, p<0.001). Significant hormonal adaptations included fasting ghrelin suppression (-28.4%, 856±142 to 613±118 pg/mL, p<0.001), gastrin elevation (+18.2%, 42.3±8.2 to 50.0±9.1 pg/mL, p=0.002), postprandial CCK increase (+42.1%, 18.5±4.2 to 26.3±5.1 pg/mL, p<0.001), GLP-1 reduction (-22.7%, 24.8±5.6 to 19.2±4.8 pg/mL, p=0.001), and motilin elevation (+31.5%, 156±28 to 205±34 pg/mL, p<0.001). Strong BHB-hormone correlations emerged (ghrelin: r=-0.62, p<0.001; CCK: r=0.59, p<0.001). Controls showed minimal changes (all p>0.05). Conclusion: KD induces a characteristic enteroendocrine signature in Central Indian adults—ghrelin suppression with gastrin/CCK/motilin elevation and GLP-1 reduction—directly correlated with ketosis depth. These adaptations optimize high-fat digestion, enhance satiety signaling, and accelerate gastric motility, offering mechanistic insights for metabolic and gastrointestinal applications in non-Western populations.

Keywords: Ketogenic diet, ghrelin, gastrin, cholecystokinin, glucagon-like peptide-1, motilin, β-hydroxybutyrate, nutritional ketosis, gastric hormones.