A Pseudo-Ketogenic Sugar-Ghee-Enriched Diet Induces Metabolic and Immune Alterations in Rats: A Model of Flawed Ketogenic Diet Practice

Farah Ismail¹Mohammad Khalifeh^1*Wael Hananeh²Rasha Al-azaizeh¹Batool Khataybeh³Muath Alghadi⁴

• ¹Department of Basic Medical Veterinary Sciences, College of Veterinary Medicine, Jordan University of Science and Technology, Irbid, Jordan
• ²Department of Veterinary Pathology and Public Health, Jordan University of Science and Technology, Irbid, Jordan
• ³Department of Nutrition and Food Technology, Jordan University of Science and Technology, Irbid, Jordan
• ⁴Department of Zoology, College of Science, King Saud University, Riyadh, Riyadh, Saudi Arabia

The ketogenic diet (KD) has gained popularity due to its reported benefits on weight loss and metabolic health. However, in real-world settings, KD is frequently misapplied individuals often continue consuming sugar or fail to calculate macronutrient ratios accurately. These flawed patterns may still result in weight loss but carry unclear long-term effects on metabolism and immune function. The present study aimed to simulate one such misapplication scenario by developing a Sugar-Ghee-Enriched Diet (SGED) rich in animal-derived fat and added sugar. The SGED provided approximately 31.7% of energy from fat and exhibited a ketogenic ratio of 0.21:1, which is far below the threshold required to induce nutritional ketosis. Wistar male rats were divided into control and SGED groups and fed their respective diets for a period of 33 days. Parameters as body weight, visceral fat deposition, serum lipid levels, and selected cytokines (IL-6, TNF-α, IL-10, TGF-β) as well as histological examinations of the liver, kidney, and intestinal tissues, were examined. A reduction in total body weight was presented in SGED-fed rats, but they exhibited a significant increase in visceral fat deposition and a dyslipidemic profile marked by elevated serum triglyceride, cholesterol, vLDL levels, and atherogenic index. Immune modulation was also observed, with increased levels of TNF-α, IL-10, and TGFβ, and a decrease in IL-6. Histopathologically, no major changes were found in the examined organs. To our knowledge, this is the first study to introduce an experimental rat model that represent pseudo-ketogenic dietary (PKD) behavior, characterized by high animal fat intake combined with added sugar leading to superficial weight loss without achieving ketogenic macronutrient thresholds. The SGED model reveals potential risks for adverse immune response and metabolic outcomes, emphasizing the need to address flawed interpretations of ketogenic dieting.