Three-day intermittent fasting improves eating behavior and is associated with greater weight loss

Intermittent fasting remains a trend, but what happens not to the numbers on the scale, but to our attitude to food - bouts of overeating, "breakdowns", a sense of control? Nutrients published an analysis of secondary outcomes of the 12-month randomized clinical trial DRIFT (University of Colorado). Scientists compared the classic daily calorie restriction (DCR) with the 4:3 regimen (three "fast" days a week with ~80% deficit and four days without restrictions) and looked at the dynamics of validated scales of eating behavior and the profile of appetite hormones. The conclusion is unexpected: behavior improves precisely with 4:3, but there are no constant differences in leptin / ghrelin / PYY / adiponectin / BDNF between the groups.

Background

Obesity and overweight remain one of the most common causes of chronic diseases, and the key non-drug tool is a sustainable reduction in caloric intake in combination with behavioral support and physical activity. Classic daily restriction (DCR) has proven its effectiveness, but it runs into adhesion: people find it difficult to “stick to the plan” every day, which increases the risk of breakdowns, overeating, and weight rollbacks. Against this background, intermittent fasting (IF) regimens have quickly spread - from daily “windows” of eating (time-restricted eating) to alternating “fasting” and “free” days (alternate-day fasting). The 4:3 option is three “fast” days a week (usually 0-25% of the daily requirement, in clinical protocols it is more often ~20%) and four days without restrictions; in fact, this is a “soft” form of ADF, which many consider psychologically more flexible.

In recent years, RCTs and meta-analyses have shown that if the weekly energy deficit is comparable, then IF on average does not exceed the classic daily restriction in terms of weight loss over a 6-12 month period. At the same time, for some people, IF is easier to maintain due to a smaller number of “food decisions” per week and the ability to plan “hungry” days according to a schedule - and it is precisely adherence that most often predicts the result on the scale. Mechanistically, IF has long been expected to have a “hormonal advantage”, but in people with the same weight loss, the picture is usually typical: leptin falls, ghrelin grows, PYY and other satiety signals change ambiguously; the differences between IF and DCR in endocrine markers are often small and inconsistent. However, eating patterns and psychology are of great importance: the tendency toward uncontrolled and emotional eating, the frequency of overeating episodes, and the level of “cognitive restraint” (the skill of maintaining limits without rigidity) are directly related to weight loss and maintenance.

Therefore, scientific interest has shifted from the question of “who will lose weight easier due to hormones?” to the question of “which regimen is better at correcting eating behavior with the same deficit.” A year-long RCT is exactly about this: to compare 4:3 and daily restriction with the same weekly “hole” of calories, against the background of standardized behavioral support, and to track not only weight, but also trajectories of eating behavior (uncontrolled/emotional eating, episodes of overeating, “craving for rewarding food”) along with appetite hormones. Such a design allows us to understand due to what exactly one regimen can “win” in real life: due to hormonal shifts or due to more stable habits and better commitment.

What did they do?

• A 12-month RCT was conducted: 165 overweight/obese adults (mean age 42±9 years, BMI 34.2; 74% women) were randomized to 4:3-IMF (n=84) or daily calorie restriction DCR (n=81). Both groups received the same target weekly energy gap of ~34%, behavioral group support, and advice to increase cardio to 300 min/week of moderate intensity.
• Eating behavior was assessed using the following scales: BES (binge eating episodes), TFEQ-R18 (uncontrolled/emotional eating and cognitive restraint) and RED-13 (craving for “rewarding” food). Measurements were taken at 0, 3, 6 and 12 months.
• Fasting leptin, ghrelin, PYY, adiponectin, BDNF were measured and the adiponectin/leptin ratio, a sensitive indicator of metabolic homeostasis, was calculated.

In the summary article on primary outcomes, the same protocol showed that 4:3 produced better adherence and greater weight loss for the same target calorie gap. The analysis of secondary outcomes answered the question of “why might this have happened”: perhaps it was the behavioral changes—reduced lapses and increased conscious control—that were driving the results up.

Key Results (12 months)

• Binge eating episodes (BES) and uncontrolled eating (TFEQ-R18) decreased at 4:3, whereas they increased at DCR; the group×time interaction was significant ( p < 0.01).
• Within the 4:3 group, greater weight loss was associated with:
  • reduction in uncontrolled eating (r=−0.27; p =0.03);
  • decreased emotional eating (r=−0.37; p <0.01);
  • an increase in cognitive restraint (r=0.35; p <0.01).
    On the DCR, there was almost no significant relationship between weight and these scales (the exception was a weak relationship with restraint).
• RED-13 (craving for rewarding food) decreased over time in both groups, but an association with weight loss was found only for 4:3 emotional/compulsive eating.
• Appetite hormones: no consistent between-group differences were observed at any time point. General time trends were noted - leptin decreased, ghrelin increased, and adiponectin and the adiponectin/leptin ratio slowly improved (most likely reflecting metabolic adaptation to weight loss); BDNF transiently fell at 6 months by 4:3 with no overall effect over the year.

What could this mean?

• Psychological flexibility versus a "constant diet". The 4:3 regime allows you to choose your own fasting days, unloads the "cognitive counter" of calories and reduces the feeling of deprivation. Against this background, "breakdowns" and emotional overeating are reduced - and people stick to the plan more easily. On the contrary, with the constant restriction of DCR, the load of "control every day" is high, which increases stress and the risk of breakdowns.
• Hormonal “hunger signals” are not the whole story. With equal target energy deficits, the endocrine curves are similar between groups. This means that behavioral shifts (less uncontrolled and emotional eating, more restraint) may be key mediators of 4:3 success in real life.

What the program looked like (important details of the protocol)

• Both groups underwent intensive group sessions: weekly for the first 3 months, then every two weeks until the 12th month; they were led by nutrition coaches, the methodology was cognitive-behavioral skills. At 4:3 they were additionally taught fasting day strategies (distraction, shifting meals to dinner, portion control).
• For objective comparison, we used the same macrosplit (55% carbohydrates, 15% protein, 30% fat) and the same weekly deficit; on DCR we were asked to count calories daily, on 4:3 we were asked to keep records only on “fast” days.

Restrictions

• This is a secondary analysis; power for such outcomes (behavioral scales/hormones) was not initially calculated, multiple comparisons were not adjusted - some of the null results may be a consequence of statistics.
• Hormones were taken only on an empty stomach (0, 6, 12 months) - without tests after meals; the dynamics of "satiety/hunger" according to food intake were not assessed.
• The sample was predominantly middle-aged, female, predominantly non-Latino white; all were from the United States, and all received high levels of behavioral reinforcement. Generalizability to other groups is limited.

What's next in science and practice

• RCTs with behavioral “mechanics”: measure hormones more often (including postprandial), include fMRI/digital behavioral metrics to check whether psycho-behavioral mechanisms are really the main driver of the 4:3 advantage.
• For the clinic: if daily "calorie counting" is oppressive and leads to breakdowns, the 4:3 regime under the supervision of a specialist can be a working alternative with a comparable energy deficit - especially when control over overeating is important. (Contraindications and individual risks, as always, are discussed with a doctor.)

Source: Breit MJ et al. Effects of 4:3 Intermittent Fasting on Eating Behaviors and Appetite Hormones: A Secondary Analysis of a 12-Month Behavioral Weight Loss Intervention, Nutrients, 2025;17:2385. Open access. https://doi.org/10.3390/nu17142385