Framingham State Food Study

Principal Investigators: David Ludwig and Cara Ebbeling (Boston Children’s Hospital; Harvard Medical School)

Ebbeling CB, Feldman HA, Klein GL, Wong JMW, Bielak L, Steltz SK, Luoto PK, Wolfe RR, Wong WW, Ludwig DS.  Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial.  BMJ. 2018; 363:k4583.

Losing weight is the first challenge in treating obesity. The second challenge is maintaining that loss. Only sustained weight reduction can prevent the negative health consequences associated with obesity. However, maintaining significant weight loss indefinitely is notoriously difficult, making the development of strategies that facilitate maintenance of a reduced body weight critical for the effective long-term treatment of obesity.

An earlier study1 led by Drs. David Ludwig and Cara Ebbeling of 24 subjects suggested that eating a low-carbohydrate, high-fat diet over a 30 day period increased energy expenditure after weight loss more than did eating a high-carbohydrate, low-fat diet. This finding challenged the conventional thinking that obesity is an energy balance disorder in which the amount of calories consumed, independent of the source of those calories (i.e., carbohydrates and fat), is the critical factor in fat accumulation.

NuSI funded the Framingham State Food Study, or (FS)2, a larger, longer, and more robust trial, to more definitively address the question of whether the amount or type of calories eaten is the determining factor for preventing fat accumulation after weight reduction.

(FS)2 was a “feeding study,” meaning that the researchers supplied participants with all of their food throughout the study in order to control the amount and composition of food eaten and monitor the amount consumed. In the first phase of the trial2, the total food intake (carbohydrates, fats, and protein) of these overweight and obese participants was restricted to produce, on average, a 12% loss in body weight. At the start of the second phase of the study, the 164 participants who achieved this weight loss goal were randomly assigned to either a low-, moderate-, or high-carbohydrate diet containing (by calories) 20% protein and, respectively, either 20% carbohydrate and 60% fat, 40% carbohydrate and 40% fat, or 60% carbohydrate and 20% fat. For the next 20 weeks, the number of calories of each diet provided to each participant was adjusted to maintain their reduced body weight.

Total daily energy expenditure, the primary outcome for the trial, was measured before and after participants were randomly assigned to the different diets. If only the amount of calories consumed was important for weight maintenance, then energy expenditure should be the same for all three groups. This was not the case. Instead, energy expenditure increased to a greater extent in participants eating the low- or moderate-carbohydrate diets compared with those consuming the high-carbohydrate diet. Those eating the low-carbohydrate diet showed the largest increase.

Limiting calorie intake and increasing expenditure through physical activity is the standard prescription for both losing weight and preventing weight gain. However, weight loss due to restriction of calorie intake typically results in a decrease in total bodily energy expenditure. This drop in expenditure restrains continuing weight loss and may contribute to weight regain unless calorie intake is even further restricted. Maintaining energy expenditure during weight loss, or increasing it after weight reduction, as observed in the (FS)2 trial in association with the lower-carbohydrate, higher-fat diets, would therefore be expected to facilitate further weight loss and prevent weight regain.

The results also suggest that the type or mix of calories (i.e., carbohydrate or fat) is a critical factor for maintaining a healthy body weight. These findings, while not supportive of an energy balance model of obesity, are consistent with an alternative hypothesis that emphasizes the different effects of carbohydrates and fats on fat accumulation (known as the carbohydrate-insulin model or the hormonal/regulatory model of obesity).


1Ebbeling CB, Swain JF, Feldman HA, Wong WW, Hachey DL, Garcia-Lago E, Ludwig DS.  Effects of dietary composition on energy expenditure during weight-loss maintenance.  JAMA. 2012; 307: 2627-34.

2Ebbeling CB, Klein GL, Luoto PK, Wong JMW, Bielak L, Eddy RG, Steltz SK, Devlin C, Sandman M, Hron B, Shimy K, Heymsfield SB, Wolfe RR, Wong WW, Feldman HA, Ludwig DS. A randomized study of dietary composition during weight-loss maintenance: Rationale, study design, intervention, and assessment.  Contemp Clin Trials. 2018; 65: 76-86.