The carbohydrate–insulin model of obesity posits that high-carbohydrate diets lead to excess insulin secretion, thereby promoting fat accumulation and increasing energy intake. Thus, low-carbohydrate diets are predicted to reduce ad libitum energy intake as compared to low-fat, high-carbohydrate diets. To test this hypothesis, 20 adults aged 29.9 ± 1.4 (mean ± s.e.m.) years with body mass index of 27.8 ± 1.3 kg m⁻² were admitted as inpatients to the National Institutes of Health Clinical Center and randomized to consume ad libitum either a minimally processed, plant-based, low-fat diet (10.3% fat, 75.2% carbohydrate) with high glycemic load (85 g 1,000 kcal⁻¹) or a minimally processed, animal-based, ketogenic, low-carbohydrate diet (75.8% fat, 10.0% carbohydrate) with low glycemic load (6 g 1,000 kcal⁻¹) for 2 weeks followed immediately by the alternate diet for 2 weeks. One participant withdrew due to hypoglycemia during the low-carbohydrate diet. The primary outcomes compared mean daily ad libitum energy intake between each 2-week diet period as well as between the final week of each diet. We found that the low-fat diet led to 689 ± 73 kcal d⁻¹ less energy intake than the low-carbohydrate diet over 2 weeks (P < 0.0001) and 544 ± 68 kcal d⁻¹ less over the final week (P < 0.0001). Therefore, the predictions of the carbohydrate–insulin model were inconsistent with our observations. This study was registered on ClinicalTrials.gov as NCT03878108.

肥胖的碳水化合物-胰岛素模型认为，高碳水化合物饮食会导致胰岛素分泌过多，从而促进脂肪堆积并增加能量摄入。因此，与低脂肪、高碳水化合物饮食相比，低碳水化合物饮食预计会减少随意摄入的能量。为验证这一假设，20 名年龄为 29.9 ± 1.4（平均值 ± 标准误）、体重指数为 27.8 ± 1.3 kg m ^-2的成年人被收治为美国国立卫生研究院临床中心的住院患者，并被随机分配至最低限度的随意进食经过加工的植物性低脂饮食（10.3% 脂肪，75.2% 碳水化合物）和高血糖负荷（85 g 1,000 kcal ⁻¹) 或最低限度加工、动物性、生酮、低碳水化合物饮食（75.8% 脂肪，10.0% 碳水化合物）和低血糖负荷（6 g 1,000 kcal ⁻¹）持续 2 周，然后立即采用替代饮食持续 2 周。一名参与者因低碳水化合物饮食期间的低血糖而退出。主要结果比较了每 2 周饮食期之间以及每种饮食的最后一周之间的平均每日随意摄入的能量。我们发现低脂饮食导致 689 ± 73 kcal d ^-1的能量摄入比低碳水化合物饮食超过 2 周 ( P  < 0.0001) 和 544 ± 68 kcal d ^-1最后一周 ( P < 0.0001）。因此，碳水化合物-胰岛素模型的预测与我们的观察不一致。本研究在 ClinicalTrials.gov 上注册为 NCT03878108。