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Stanford’s Low-Fat vs. Low-Carb Comparison Trial Underscores Importance of Robust Study Design

by Lewis Chang, PhD

As the prevalence of obesity continues to increase worldwide, the search for the most effective diet(s) for weight loss continues. Whether one diet is better than another—such as the low-carb vs. low-fat diet approach—is still being hotly debated. Regardless, researchers have noticed substantial inter-individual differences in weight loss success (or failure) in response to the same diet.

It has been speculated that variations in certain genetic makeups or physiological traits in the population may be responsible for the differential response to a diet. For instance, genetic polymorphisms from genes relevant to fat and carbohydrate metabolism can theoretically split individuals into 3 categories: those who are more sensitive to fat, those more sensitive to carb, and those sensitive to neither. Therefore, individuals with the first genotype supposedly may respond better (i.e., lose more weight) to a low-fat diet than a low-carb diet. Another potential factor is individuals’ baseline insulin dynamics. In theory, those who are more insulin resistant may fare better with a diet containing less carbohydrates. However, many of these biologically plausible claims came from exploratory analyses of studies with small sample sizes. The validity and reproducibility of these findings have not been confirmed.

Researchers from Stanford University Medical School (Stanford, CA) thus designed a specific long-term trial (DIETFITS; the Diet Intervention Examining The Factors Interacting with Treatment Success) with sufficient statistical power to test these theories.1 They aimed to (1) compare the effect of a healthy low-fat diet vs. a healthy low-carb diet on weight change and (2) investigate whether genotype pattern or insulin dynamics influence the effect of these diets. More than 600 adult women and men with overweight and obesity were randomized to a 12-month healthy low-fat diet or healthy low-carb diet. Throughout the year, regular sessions were held by health educators to help participants maintain their diet regimen, with emphasis on choosing high-quality whole foods and avoiding processed foods.

The retention rate at 12 months was high for both groups at 79%. Total energy intake was reduced by approximately 500-600 kcal/day in both groups. In the end, both groups experienced a similar range of weight change, from losing 30 kg (66 lb) to gaining 10 kg (22 lb). The average weight change for both groups was similar; 5.3 kg (11.7 lb) reduction for the low-fat diet group and 6.0 kg (13.2 lb) reduction for the low-carb diet group. Neither genotype pattern nor baseline insulin dynamics had clinically meaningful effects on weight loss, which indicates that pairing the diet assignment based on a person’s genotype or baseline insulin secretion does not affect the rate of success in weight loss.

Based on these findings, the study investigators believe that it is more important to focus on the dietary quality of a weight loss diet. However, new investigation is currently under way to determine if other genetic makeups should be considered.

These results, published in JAMA, demonstrate the importance of testing early hypotheses with large and sufficiently-powered trials, especially when the hypotheses are based on exploratory analyses of small studies.

Why is this Clinically Relevant?

  • Both low-fat and low-carb diets, with emphases on high-quality whole foods and avoidance of processed foods, are equally effective in supporting weight management
  • Variations in genes related to fat and carbohydrate metabolism do not decide if one diet is better than another for weight loss
  • Baseline insulin secretion is not associated with the dietary effects on weight loss

View the abstract


  1. Gardner CD, Trepanowski JF, Del Gobbo LC, et al. Effect of low-fat vs low-carbohydrate diet on 12-month weight loss in overweight adults and the association with genotype pattern or insulin secretion: the DIETFITS randomized clinical trial. JAMA. 2018;319(7):667-679.


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