Development and Pragmatic Randomized Controlled Trial of Healthy Ketogenic Diet Versus Energy-Restricted Diet on Weight Loss in Adults with Obesity

Introduction: The ketogenic diet (KD) is widely used for weight management by reducing appetite, enhancing fat oxidation, and facilitating weight loss. However, the high content of total and saturated fats in a conventional KD may elevate low-density lipoprotein (LDL)-cholesterol levels, a known risk factor for cardiovascular diseases, highlighting the need for healthier alternatives. This study aimed to investigate the effect of a newly developed Healthy Ketogenic Diet (HKD) versus an Energy-Restricted Diet (ERD) on weight loss and metabolic outcomes among adults with obesity. Methods: Multi-ethnic Asian adults (n = 80) with body mass index >= 27.5 kg/m2 were randomized either to HKD (n = 41) or ERD (n = 39) for 6 months. Both groups followed an energy-restricted healthy diet, emphasizing on reducing saturated and trans fats. The HKD group additionally limited net carbohydrate intake to no more than 50 g per day. Dietary adherence was supported via the Nutritionist Buddy app with dietitian coaching. The primary outcome was weight change from baseline at 6 months. Secondary outcomes included weight change at 3 months and 1 year, along with changes in metabolic profiles. Data were analyzed using linear regression with an intention-to-treat approach. Results: The HKD group achieved significantly greater mean weight loss at 6 months than the ERD group (-7.8 +/- 5.2 kg vs. -4.2 +/- 5.6 kg, p = 0.01). The mean weight loss percentage at 6 months was 9.3 +/- 5.9% and 4.9 +/- 5.8% for the HKD and ERD groups, respectively (p = 0.004). Improvements in metabolic profiles were also significantly better in the HKD group [glycated hemoglobin (-0.3 +/- 0.3% vs. -0.1 +/- 0.2%, p = 0.008), systolic blood pressure (-7.7 +/- 8.9 mmHg vs. -2.6 +/- 12.2 mmHg, p = 0.005), and aspartate transaminase (-7.6 +/- 15.5 IU/L vs. 0.6 +/- 11.5 IU/L, p = 0.01)], with no increase in LDL-cholesterol (-0.12 +/- 0.60 mmol/L vs. -0.04 +/- 0.56 mmol/L, p = 0.97) observed in either group. Conclusions: The HKD was more effective than the ERD in promoting weight loss and improving cardiometabolic outcomes without elevation in LDL-cholesterol. It can be recommended for therapeutic intervention in patients with obesity.