Long-Term Ketogenic Diet Induces Metabolic Acidosis, Anemia, and Oxidative Stress in Healthy Wistar Rats

Abstract

Background. Ketogenic diet has been used as supportive therapy in a range of conditions including epilepsy, diabetes mellitus, and cancer. Objective. This study aimed to investigate the effects of long-term consumption of ketogenic diet on blood gas, hematological profiles, organ functions, and superoxide dismutase level in a rat model. Materials and Methods. Fifteen male Wistar rats were divided into control (n = 8) and ketogenic (n = 7) groups. Controls received standard diet contained 52.20% of carbohydrates, 7.00% fat, and 15.25% protein; meanwhile, the ketogenic group received a high-fat-low-carbohydrate diet which contained 5.66% of carbohydrate, 86.19% fat, and 8.15% protein. All rats were caged individually and received 30g of either standard or high-fat-low-carbohydrate pellets. The experiment was carried out for 60 days before the blood samples were taken and analyzed to obtain blood gas, cell counts, organ biomarkers, and plasma antioxidant superoxide dismutase (SOD) levels. Results. The rats subjected to ketogenic diet experienced a marked decrease in body weight, blood sugar, and increased blood ketones (p<0.05). The average blood pH was 7.36 ± 0.02 and base excess was −5.57 ± 2.39 mOsm/L, which were significantly lower than controls (p<0.05). Hematological analysis showed significantly lower erythrocyte, hemoglobin, and hematocrit levels. No significant changes were found in alanine aminotransferase, aspartate aminotransferase, urea, and creatinine levels, indicating normal liver and kidney functions. Nevertheless, plasma SOD level significantly reduced with ketogenic diet. Conclusion. Long-term ketogenic diet induces metabolic acidosis, anemia, and reduced antioxidant enzyme level in rats following 60 days of consuming high-fat-low-carbohydrate diet.

Increased Beta-Hydroxybutyrate Level Is Not Sufficient for the Neuroprotective Effect of Long-Term Ketogenic Diet in an Animal Model of Early Parkinson’s Disease. Exploration of Brain and Liver Energy Metabolism Markers

“…Previous studies reporting neuroprotection in animal PD models analyzed effects of shorter periods on the diet—2 weeks prior and 2 weeks after lesion [ 22 ], 11 days prior and 2 weeks after lesion [ 24 ], or 1 week prior and 1 week after lesion [ 23 ]. Recently, Arsyad et al [ 65 ] showed that a 60-day, long-term ketogenic diet consisting of 5.66% of carbohydrate, 86.19% fat, and 8.15% protein induced metabolic acidosis, anemia, and reduced antioxidant enzyme level in healthy Wistar rats. In contrast to our study, they observed significantly reduced glucose levels in the blood.…”

Disturbed Cardiac Metabolism Triggers Atrial Arrhythmogenesis in Diabetes Mellitus: Energy Substrate Alternate as a Potential Therapeutic Intervention

“…Ketonemia induced by a 2-week ketogenic diet in rats resulted in lower circulating insulin and myocardial glycogen store, impaired left ventricular function, and increased myocardial injuries following ischemia–reperfusion in the isolated heart [ 146 ]. Long-term ketogenic diets may potentially exert some systemic effects, such as metabolic acidosis [ 147 , 148 , 149 ], leading to arrhythmogenesis or a mechanoelectrical disturbance. Additionally, ketogenic diets are typically high in saturated fat and cholesterol, which may also induce systemic hyperlipidemia and intracellular lipid accumulation, which leads to increased fatty acid oxidation [ 150 ] and atrial arrhythmogenesis [ 87 , 151 ] due to enhanced ROS production [ 152 , 153 , 154 ].…”

Nutrition and Gut–Brain Pathways Impacting the Onset of Parkinson’s Disease

“…The ketogenic diet (KD) is a high-fat low-carbohydrate diet that has been used as a nonpharmacologic approach to improve a range of health markers in metabolic disorders [ 158 , 159 , 160 , 161 ], as well as a treatment for intractable epilepsy [ 158 , 162 , 163 , 164 ]. In recent years, studies have suggested that the KD can be therapeutically useful for adjunctive therapy for PD [ 165 ].…”