Low-Fat vs. Low-Carb Diet and Weight Loss in Overweight Adults

Study Questions:

What is the effect of a healthy low-fat (HLF) diet compared to a healthy low-carbohydrate (HLC) diet on weight change, and are genotype pattern or insulin secretion related to the dietary effects on weight loss?


The DIETFITS (Diet Intervention Examining The Factors Interacting with Treatment Success) randomized clinical trial included 609 adults aged 18-50 years without diabetes with a body mass index (BMI) between 28 and 40 kg/m2. Participants were randomized to the 12-month HLF or HLC diet. The study also tested whether three single-nucleotide polymorphisms relevant to fat and carbohydrate (carb) metabolism or insulin secretion (INS-30; insulin level 30 minutes after a 75 g glucose challenge) were associated with weight loss. Health educators delivered the behavior modification intervention to equal numbers of HLF and HLC participants via 22 diet-specific small group sessions administered over 12 months. The sessions focused on ways to achieve the lowest fat or carb intake that could be maintained long-term, and emphasized diet quality.


Among 609 participants randomized (mean age 40 [SD 7] years, 57% women; mean BMI 33 [SD 3], 244 [40%] had a low-fat genotype, 180 [30%] had a low-carb genotype, mean baseline INS-30, 93 μIU/ml), 481 (79%) completed the trial. Each group reduced total Kcal intake by about 20%. In the HLF versus HLC diets, respectively, the mean 12-month macronutrient distributions were 48% versus 30% for carbohydrates, 29% versus 45% for fat, and 21% versus 23% for protein. Weight change at 12 months was −5.3 kg for the HLF diet versus −6.0 kg for the HLC diet (mean between-group difference, 0.7 kg; 95% confidence interval, −0.2 to 1.6 kg). There was no significant diet-genotype pattern interaction (p = 0.20) or diet-insulin secretion (INS-30) interaction (p = 0.47) with 12-month weight loss. Eighteen adverse events or serious adverse events were evenly distributed across the two diet groups.


In this 12-month weight loss diet study, there was no significant difference in weight change between a HLF diet versus a HLC diet, and neither genotype pattern nor baseline insulin secretion was associated with the dietary effects on weight loss. In the context of these two common weight loss diet approaches, neither of the two hypothesized predisposing factors was helpful in identifying which diet was better for whom.


The import of the study is related to the inability to predict weight loss by low-carb versus low-fat diets by genes or post-prandial insulin. At 12 months relative to baseline, both diets improved blood pressure, insulin, and glucose levels, but not the low-density lipoprotein cholesterol. The baseline dietary intake in each group was about 35% fat and 11.5% saturated fat. While labeled healthy, the on-trial low-carb diet averaged 15% of kcal from saturated fat.

Clinical Topics: Diabetes and Cardiometabolic Disease, Prevention, Diet

Keywords: Behavior Therapy, Blood Pressure, Body Mass Index, Body Weight, Carbohydrates, Diet, Carbohydrate-Restricted, Diet, Fat-Restricted, Genotype, Glucose, Insulin, Metabolic Syndrome X, Obesity, Overweight, Polymorphism, Single Nucleotide, Primary Prevention, Weight Loss

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