Low-Carb and Ketogenic Diets Reduce Diabetic Retinopathy in Rats
Nutrients
Summary
This study investigated the protective effects of low-carbohydrate (LCD) and low-carbohydrate ketogenic diets (LCKD) on diabetic retinopathy (DR) in rats with high-fat diet (HFD)-induced diabetes. After 8 weeks of HFD to induce diabetes, rats were transitioned to a normal diet, LCD, or LCKD for another 8 weeks. The researchers measured metabolic markers, oxidative stress levels, inflammation, apoptosis, and retinal structure to evaluate diet impact. Both LCD and LCKD improved key metabolic parameters such as glucose, insulin, HbA1C, and lipid profiles. However, the LCKD consistently outperformed the LCD in reducing retinal damage and associated molecular dysfunction. Mechanistically, the study found that the LCKD was superior at upregulating the Nrf2 antioxidant pathway while suppressing inflammation and apoptosis markers like NF-κB, Bax, and caspase-3. LCKD-fed rats showed improved retinal morphology and preserved neural layers compared to HFD and even LCD-fed groups. Both interventions reduced oxidative stress indicators such as MDA and AGEs while increasing antioxidant enzymes like GSH, SOD, and HO-1. The authors conclude that LCKD is more effective than LCD in preventing DR progression in this model by modulating oxidative stress and inflammatory pathways. The findings suggest dietary composition, not just caloric restriction, plays a critical role in managing diabetes complications.
Study Design
Interventions
Study Type
Outcomes
Duration and Size
Study Population
Age Range
Sex
Geography
Other Criteria
Methodology
The study was conducted using adult male Wistar rats divided into four groups: control, HFD followed by normal diet, HFD followed by LCD, and HFD followed by LCKD. The dietary intervention lasted for 8 weeks after the initial 8-week HFD induction. Blood and retinal samples were collected to evaluate metabolic markers, oxidative stress, inflammation, and apoptosis. Retinal histology was performed to assess structural changes. Biochemical parameters were measured using ELISA kits, and gene expression was analyzed via qPCR. Nuclear and cytoplasmic protein levels were extracted using commercial kits. ANOVA and post hoc tests were employed for statistical analysis.
Interventions
The primary interventions tested were a low-carbohydrate diet (LCD) and a low-carbohydrate ketogenic diet (LCKD) introduced after HFD-induced diabetes. The LCD provided 20% kcal from carbs, 20% protein, and 60% fat, while the LCKD provided nearly 0% carbs, 20% protein, and 80% fat. Both diets were fed ad libitum for 8 weeks. The goal was to compare their protective efficacy on diabetic retinopathy. The interventions were assessed via histological analysis of the retina, molecular measurements of inflammatory and oxidative stress markers, and metabolic indicators such as glucose, insulin, lipids, and β-hydroxybutyrate.
Key Findings
Both the LCD and LCKD significantly improved metabolic profiles and reduced markers of oxidative stress and inflammation in diabetic rats. The LCKD showed stronger effects, with notable increases in antioxidant enzymes and Nrf2 activity, along with decreased Keap1, NF-κB, and pro-apoptotic markers. Histological examination confirmed better retinal layer preservation in LCKD-fed rats compared to LCD. These results suggest that LCKD is more effective than LCD in preventing diabetic retinopathy through mechanisms involving metabolic correction and molecular modulation of antioxidant and anti-inflammatory pathways.
Comparison with other Studies
This study aligns with earlier work demonstrating the benefits of low-carbohydrate and ketogenic diets in managing type 2 diabetes and reducing inflammation. Prior research has shown that ketogenic diets enhance antioxidant defenses and metabolic control more robustly than standard or moderate-carb diets. The current study expands on this by linking these metabolic improvements directly to retinal protection in diabetic models. Unlike previous studies focusing on systemic markers, this study incorporates histological and molecular retinal assessments, making it more comprehensive. Comparatively, the inclusion of retinal Nrf2/Keap1 pathway analysis offers a novel mechanistic insight previously underexplored. The findings also align with earlier work showing that ketone bodies like β-hydroxybutyrate exert anti-inflammatory effects in various tissues, including the retina.
Journal Reference
Jawharji MT, Alshammari GM, Binobead MA, Albanyan NM, Al-Harbi LN, Yahya MA. Comparative Efficacy of Low-Carbohydrate and Ketogenic Diets on Diabetic Retinopathy and Oxidative Stress in High-Fat Diet-Induced Diabetic Rats. Nutrients. 2024;16(18):3074. doi:10.3390/nu16183074
© 2025 deDiabetes. Licensed under CC BY (Attribution)
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