Comparing higher-protein intermittent fasting to a heart-healthy diet for weight loss Original paper

In this randomized controlled trial that compared two hypocaloric diets, a higher-protein intermittent fasting diet reduced body weight more than a heart-healthy diet.

The effects of a heart-healthy diet compared to an intermittent fasting and protein pacing (IF-P) diet on changes in body weight and body composition (the primary outcomes), blood lipids, fasting glucose and insulin, blood pressure, IGF-1, glucagon, ghrelin, and hunger and satiety (assessed via visual analog scales).

39 participants (ages 30–65, 26 women and 13 men) with overweight or obesity who were sedentary or lightly active (<30 minutes of organized physical activity 2 days per week).

The participants were randomized to consume one of two calorie-restricted diets for 8 weeks:

• Heart-healthy (the control): A total daily energy intake of 1,200 for women and 1,500 kcal for men, with a macronutrient distribution of 50%–60% of calories from carbohydrate, less than 35% fat, and the remaining calories allotted to protein; less than 200 milligrams of dietary cholesterol per day, 20–30 grams of fiber per day, and less than 50 grams of sugar per day.
• IF-P: Five to six protein pacing days per week that provided 1,350–1,500 kcal/day for women and 1,700–1,850 kcal/day for men, with a macronutrient distribution of 35% of calories from carbohydrate, 35% protein, and 30% fat, including one to two intermittent fasting days per week that provided 400–500 kcal/day. Beginning at week 5, all participants in IF-P followed a paradigm of 6 protein pacing days per week and 1 intermittent fasting day (36 hours total).

Sample menus

Physical activity was monitored using an accelerometer worn for 2 days at baseline, week 4, and week 8. Dietary intake was monitored through weekly meetings with a registered dietitian, and 2-day food diaries were completed at baseline, week 4, and week 8.

Both groups improved all body composition measures compared to baseline, but improvements were superior in IF-P for body weight (−8.2 vs. −5.0 kg), total body fat (relative reduction of −8.5% vs. −4.3%), visceral fat (relative reduction of −33% vs. −16.8%), and fat-free mass to body weight ratio (relative increase of 5.7% vs. 3%).

Blood pressure and blood lipids improved (decreased) in both groups compared to baseline, with no differences between groups, except for a reduction in high-density lipoprotein cholesterol levels in IF-P compared to the control. The desire to eat decreased in IF-P compared to the control (−40% vs. 2.4%).

Using the average body weights and protein intakes at the midpoint of the study, the participants in IF-P were consuming approximately 1.4 grams of protein per kilogram of body weight per day (g/kg/d), whereas the participants in the control group consumed approximately 0.8 g/kg/d.

This significant difference in protein intake between groups explains a lot of the results. Although the groups had reportedly similar energy intakes (approximately 1,400 kcal/day) and physical activity energy expenditure (about 350 kcal/day), there was a greater energy deficit in IF-P, as evidenced by the greater weight loss.

One reason for this may be the effects of a higher-protein diet on energy metabolism. Protein has a thermogenic advantage over carbohydrate and fat in that the digestion and assimilation of protein uses more calories.^[2][3] Another way that a higher-protein diet can increase energy expenditure relative to lower-protein diets is by preserving fat-free mass (namely, skeletal muscle) during weight loss,^[4] as muscle expends more energy at rest than fat.^[5]

Besides its effects on energy metabolism, a higher-protein diet can enhance weight loss by reducing hunger and increasing satiety, which was supported by the results of the summarized study. Specifically, there was a reduced desire to eat in IF-P.

Protein is considered the most satiating macronutrient.^[6] Higher-protein diets consumed ad libitum have been reported to lead to unintentional weight loss.^[7][8]

Mechanistically, the greater satiety effects of a higher-protein diet may be due to alterations in brain areas involved in reward-driven eating behavior, which is characterized by a loss of control over eating and preoccupation with food,^[9] and gut hormone levels that suppress appetite, like GLP-1, cholecystokinin, and peptide YY.^[10][11]

Considering that self-reported energy intake tends to significantly differ from actual energy intake,^[12][13][14] and the error typically involves underreported energy intake, it’s probable that there was significant underreporting of total daily energy intake in the control group.

Another notable difference between groups was the change in fat-free mass. Specifically, the ratio of fat-free mass to total body weight increased more in IF-P. This ratio is of higher importance than the absolute change in fat-free mass, which did not significantly differ between groups (from 54.8 to 53 kg in IF-P and from 53 to 51.7 in control) because IF-P lost significantly more body weight and fat mass than the control group, and a greater reduction in total body weight tends to coincide with a greater reduction in fat-free mass.^[15]

Higher protein intake attenuates the loss of fat-free mass with caloric restriction.^[16] Previous studies that compared groups with protein intakes similar to that of the summarized study have reported comparable findings. A 2007 study reported a greater preservation of fat-free mass in women with overweight or obesity who consumed a diet containing 1.4 g/kg/d of protein than in women who consumed a diet containing 0.8 g/kg/d.^[17]

In addition, a 2020 study reported a greater preservation of fat-free mass and a greater loss of body fat in men with overweight or obesity who consumed a diet containing 1.4 g/kg/d of protein compared to 0.96 g/kg/d.^[18]

Other studies in people with overweight or obesity that compared two hypocaloric diets differing in protein intake (0.8–1.2 vs. 1.6–2.4 g/kg/d) have also generally reported better preservation of fat-free mass and greater loss of fat mass in the group consuming the higher-protein diet.^[19][20][21]

Considering the well-known effects of a higher-protein diet on satiety and fat-free mass, it’s unclear whether intermittent fasting provided any unique benefit in the summarized study, or whether it just contributed to the weekly energy deficit. In other words, if there was a theoretical third group that consumed the same amount of protein as IF-P and had the same weekly energy deficit, but differed in that they consumed the same number of calories each day as opposed to having one intermittent fasting day per week, would the results have differed between these two groups? Probably not.

A 2022 meta-analysis that examined the effects of intermittent energy restriction (IER) compared to continuous caloric restriction on weight loss found no difference between diets overall. This finding held in subgroup analyses that investigated specific types of IER (i.e., alternate-day fasting, the 5:2 diet).^[22] Another notable finding was similar attrition rates between diets, which suggests that the ability to adhere to an energy deficit is not improved with IER. This is supported by studies that compared IER to continuous caloric restriction and assessed dietary adherence.^{[23][24][25][26]}

Although uncommon, some studies have reported relatively unfavorable feedback in the IER group. For example, in a 1-year trial, hunger levels were higher in the IER group than the continuous caloric restriction group, despite comparable weight loss.^[27] Similarly, a 6-month study that observed comparable weight loss between groups reported that hunger levels tended to be higher in the IER group, particularly during the first 2 weeks of the intervention.^[23] A separate 6-month study reported that 15% of participants in the IER group complained of hunger, whereas none of the participants in the continuous caloric restriction group reported this rate of hunger.^[26] Nonetheless, other studies have reported comparable changes in hunger and satiety between groups.^[28][29]

In conclusion, a higher-protein diet can enhance fat loss by improving appetite regulation and slightly increasing energy expenditure. The inclusion of IER most likely does not augment the effects of a higher-protein diet, on average, but further research is warranted. The inclusion of 1 to 2 intermittent fasting days per week may better suit the preferences and lifestyle of some individuals than continuous caloric restriction and thus improve dietary adherence. However, in other individuals, IER has the potential to impair dietary adherence by increasing hunger levels.

For the first 4 weeks of the intervention, the participants in the IF-P group were subdivided into two groups. The participants followed a paradigm of either 5 protein pacing days per week and 2 intermittent fasting days or 6 protein pacing days per week and 1 intermittent fasting day. The comparison of these two subgroups has been previously published.^[1] In the summarized study, the data from these two subgroups were combined under IF-P.