Overweight adults who followed a low-fat diet did not experience a significant difference in weight loss compared with those on a low-carbohydrate diet for 12 months, and genotype trends and insulin secretion was insignificantly correlated to the weight loss outcomes, according to a study published in JAMA.

Christopher D Gardner, PhD, of the Stanford Prevention Research Center from the Department of Medicine at Stanford University Medical School, and associates conducted The Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) clinical trial to assess the difference between healthy low-fat (HLF) and low carbohydrate (HLC) diets on genotype and insulin secretion trends.

A total of 609 nondiabetic overweight adults (57% women) between ages 18 and 50 years (average age, 40 years) were randomized to either an HLF (n= 305) or a HLC (n=304) diet for 12 months. Additionally, the investigation measured 3 single-nucleotide polymorphisms of multiple loci genotypic responsivity trends and insulin secretion. Body mass indexes ranged from 28 to 40 (average, 33). 

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Of the total cohort, 40% had a low-fat genotype and 30% had a low-carb genotype; 481 participants completed the study. Weight changes among the HLF and HLC participants at the end of the study were -5.3 kg and -6.0 kg, respectively. No significant outcomes were reported for genotype patterns or insulin secretion in either cohort. At the time of investigation, 7 serious and 11 adverse events were reported. Of the events, the authors reported that 2 serious and 9 adverse were possibly correlated with the study.

“The finding of no significant difference in weight loss in genotype-matched vs mismatched groups in the current study highlights the importance of conducting large, appropriately powered trials such as DIETFITS for validating early exploratory analyses,” reported the authors.

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“In the context of these 2 common weight loss diet approaches, neither of the 2 hypothesized predisposing factors was helpful in identifying which diet was better for whom,” the authors continued. “Analyses of all the genomic data obtained are under way to evaluate whether other genetic signatures may demonstrate effect modification.”


  1. Gardner CD, Trepanowski JF, 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. JAMA. 2018 Feb 20. doi: 10.1001/jama.2018.0245