DIETFITS Trial

Principal Investigator: Christopher Gardner (Stanford University)

Gardner CD, Trepanowski JF, Del Gobbo LC, Hauser ME, Rigdon J, Ioannidis JPA, Desai M, King AC. 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: 667-679.  Read >>

This trial was prompted by an earlier studyled by Christopher Gardner (“The A to Z Study”), which compared four diets varying in macronutrient (fat and carbohydrate) content and found that participants assigned the diet that resulted in the lowest carbohydrate and highest fat intake lost the most weight.

The Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) trial extended this work by comparing the effects of low-carbohydrate and low-fat diets on body weight when both diets restrict processed foods and sugars. By supplementing a major grant from the National Institutes of Health, NuSI funding for the DIETFITS trial substantially increased the number of study participants and helped support ancillary studies using study participants and secondary analyses based on trial data.

Understanding the role of diet composition in human health and disease over periods of time longer than a few months requires that participants be “free-living;” that they select and eat their own food, live in their own homes, and go about their lives as usual. The longer the study lasts and the greater the number of participants, the more researchers can learn about the health risks and effectiveness of a diet in the “real world,” but the less control they retain over what and how much the participants actually eat.

Participants in the DIETFITS trial were free-living. Consequently, the researchers implemented an intensive program of counseling and monitoring to optimize participant retention and adherence to assigned diets throughout the year-long trial. Nearly 80% of those enrolled completed the 12-month trial, which is notable for a long-term study in free-living participants.

Over a 2-year period, 609 participants in five cohorts were enrolled in the trial and were randomized to one of the two diets2. Participants were given no explicit instructions to reduce calorie intake, but were instructed to eat “healthy” diets, which, among other features, maximized vegetable intake, minimized intake of added sugars and refined flours, and focused on minimally processed foods that were prepared at home. The two groups prescribed the “healthy low-fat“or “healthy low-carbohydrate” diets showed significant differences in their carbohydrate and fat intakes. However, despite these differences, the low-carbohydrate and low-fat diet groups lost similar amounts of body weight during the trial.

This result of the DIETFITS trial differed from that of the A to Z Study in which participants eating the low-carbohydrate diet lost more than twice the weight as those consuming the low-fat diet, a discrepancy that may be attributed to differences in the composition of the diets in the two studies. The differences between total carbohydrate and fat intake were much greater in the A to Z Study than they were in the DIETFITS trial perhaps because in the DIETFITS trial, unlike the A to Z Study, subjects in both groups were counseled to avoid added sugar and refined flour. Participants consuming the low-carbohydrate and low-fat diets in both studies reduced calorie intake to the same extent. Additional research is needed to determine to what extent dietary carbohydrate and fat content need to differ to achieve weight loss greater than would be predicted from a reduction in calorie intake alone.


1Gardner CD, Kiazand A, Alhassan S, Kim S, Stafford RS, Balise RR, Kraemer HC, King AC. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial.  JAMA. 2007; 297: 969-77.  Read >>

2Stanton MV, Robinson JL, Kirkpatrick SM, Farzinkhou S, Avery EC, Rigdon J, Offringa LC, Trepanowski JF, Hauser ME, Hartle JC, Cherin RJ, King AC, Ioannidis JP, Desai M, Gardner CD.  DIETFITS study (diet intervention examining the factors interacting with treatment success) – Study design and methods.  Contemp Clin Trials. 2017; 53: 151-161.  Read >>

Secondary analyses and ancillary studies

Shih CW, Hauser ME, Aronica L, Rigdon J, Gardner CD.  Changes in blood lipid concentrations associated with changes in intake of dietary saturated fat in the context of a healthy low-carbohydrate weight-loss diet: a secondary analysis of the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) trial.  Am J Clin Nutr. 2019; 109: 433–441.  Read >>

Participants in the DIETFITS trial who were instructed to eat a healthy low-carbohydrate diet, and who increased their percentage intake of energy from saturated fat, improved their overall blood lipid profiles provided they decreased both their intake of refined carbohydrates and calories.

Guo J, Robinson JL, Gardner CD, Hall KD.  Objective versus self-reported energy intake changes during low-carbohydrate and low-fat diets.  Obesity. 2019; 27: 420-426.  Read >>

In contrast to estimates of energy intakes of participants in the DIETFITS trial based on self-reported 24-hour dietary recalls, intakes calculated indirectly using a mathematical model based on repeated measures of body weight suggested that energy consumption decreased markedly early in the trial, especially in the low-carbohydrate group, and then gradually returned toward the same pre-diet baseline level in both diet groups.

Fielding‐Singh P, Patel ML, King AC, Gardner CD.  Baseline psychosocial and demographic factors associated with study attrition and 12‐month weight gain in the DIETFITS trial.  Obesity. 2019; 27: 1997-2004.  Read >>

Factors related to sociodemographic (e.g., age, gender, race/ethnicity, marital status) and psychosocial (e.g., self-control, cognitive restraint, food addiction, family encouragement) characteristics of participants collected at baseline correlated with the tendency to drop out of the DIETFITS trial before completion and with weight loss of those that finished the 12-month trial.

Grembi JA, Nguyen LH, Haggerty TD, Gardner CD, Holmes SP, Parsonnet J.  Gut microbiota plasticity is correlated with sustained weight loss on a low-carb or low-fat dietary intervention.  Sci Rep. 2020; 10: 1405-1418.  Read >>

Plasticity of the gut microbiome, as measured by the day-to-day variability of bacterial composition in feces from individual participants in the DIETFITS trial, was correlated with long-term (12-month) weight loss. The relationship was observed with respect to pre-diet microbiota plasticity in participants eating the low-fat diet and with respect to plasticity during the initial 10 weeks of consumption of the low-carbohydrate diet.

Fragiadakis GK, Wastyk HC, Robinson JL, Sonnenburg ED, Sonnenburg JL, Gardner CD.  Long-term dietary intervention reveals resilience of the gut microbiota despite changes in diet and weight.  Am J Clin Nutr. 2020; 111: 1127–1136.  Read >>

Although consumption of the low-fat and low-carbohydrate diets altered the composition of bacterial populations in the gut measured at the 3 month time point compared with that observed prior to introduction of the new diets, the composition of the microbiota returned to baseline thereafter and remained constant through the end of the 12-month DIETFITS trial.

Figarska SM, Rigdon J, Ganna A, Elmståhl S, Lind L, Gardner CD, Ingelsson E.  Proteomic profiles before and during weight loss: Results from randomized trial of dietary intervention. Sci Rep. 2020); 10: 7913-7920.  Read >>

To determine whether there are circulating protein biomarkers that predict weight loss in response to dieting in overweight and obese individuals, 263 proteins were measured in blood plasma from participants in the DIETFITS trial.  More than 100 proteins correlated with BMI prior to assignment to the study diets and tracked weight loss during the diet intervention. Only one protein at baseline, fibroblast growth factor 21, predicted weight loss and did so irrespective of diet.