Intermittent Fasting Combined With Protein Pacing Is Superior To Caloric Restriction

IF is associated with improved body composition (reductions in total and VF mass) that may result in enhanced “metabolic switching” and cardiometabolic health outcomes. This switching is characterized by increased fat oxidation, ketone body synthesis, insulin sensitivity, and autophagy, as well as reduced inflammation, oxidative stress, and enhanced lean body mass.

Most IF regimens focus on the timing and quantity of calories consumed and de‐emphasize the nutritional quality (higher protein and fiber, reduced intake of sugar and highly processed foods) of the overall diet.

Current United States dietary recommendations to improve cardiometabolic health and weight management emphasize a CR heart‐healthy diet of increased intake of fruits, vegetables, whole grains, and liquid plant oils and minimal intakes of processed foods, added sugars, salt, and alcohol (65% carbohydrate intake, 20% fat, and 15% protein).

In comparison, the IF approach used in the study is a modified IF regimen, which allows consumption of 20% to 25% of energy needs on scheduled fasting days (1‐2/wk), combined with a P (IF‐P) meal plan consisting of 35% to 45% carbohydrate, 20% to 30% fat, and 30% to 35% protein for 5 or 6 days weekly.

No previous research has directly compared the effects of extended (≥36 hours) IF‐P versus a heart‐healthy CR meal pattern, matched for total weekly energy intake (EI), meal frequency (4‐5 meals/d), and physical activity energy expenditure (PAEE) on cardiometabolic health, BW and composition, hormones, and hunger responses, in women and men with overweight and obesity.

The purpose of this study was to compare the influence of IF (36‐60 hours) and P (35%; IF‐P) versus a heart‐healthy daily CR (protein, 15%) dietary regimen on total (lean mass and FM) and regional (abdominal/visceral) body composition, cardiometabolic, hormonal, and hunger responses for 8 weeks in women and men with overweight and obesity. The researchers hypothesized that an IF‐P regimen would improve cardiometabolic health, body composition, and satiation compared with a CR regimen.

Participants were matched for BW, BMI, and body fat and randomly assigned in parallel to one of two CR groups: 1) IF‐P or 2) a heart‐healthy daily CR diet for 8 weeks. The IF‐P group was further subdivided into two groups for the first 4 weeks only by randomly assigning participants to one of two groups: 1) IF 1 d/wk (36 hours total) and P regimen for the remaining 6 d/wk (IF1‐P); or 2) IF for two consecutive days (60 hours total) and P for the remaining 5 d/wk (IF2‐P) for 4 weeks. Both groups consumed similar total weekly calories throughout the 4 weeks.

IF1‐P consisted of ~400 kcal/d, in which participants were provided a variety of supplements and snacks. IF2‐P followed an identical meal pattern for both IF days, except for consuming an additional 100 kcal to achieve ~500 kcal/d for each of the two consecutive fasting days during weeks 1 through 4, in order to achieve a similar weekly total EI as IF1‐P. Beginning in week 5, IF2‐P followed the identical meal pattern as IF1‐P, and the combined group is referred to as IF‐P for the week 8 (post) comparisons.

P days for IF1‐P consisted of 4 and 5 meals per day providing 1350 and 1700 kcal/d for women and men, respectively, and a macronutrient distribution targeting 35% protein, 35% carbohydrate, and 30% fat. IF2‐P followed a similar P meal protocol providing 1500 and 1850 kcal/d for women and men, respectively, and similar macronutrient distribution and total weekly calorie intakes (~8500 kcal/wk) as IF1‐1 for weeks 1 through 4. Thereafter, IF1‐P and IF2‐P followed identical meal plans.

Participants assigned to the CR diet followed specific guidelines of the National Cholesterol Education Program Therapeutic Lifestyle Changes (TLC) diet of the American Heart Association. The specific macronutrient distribution was

Compared with baseline, both IF‐P and CR participants improved all body composition measures, with IF‐P producing significantly greater improvements in all outcomes on an absolute and relative basis Specifically, IF‐P lost significantly more total BW (−8.2 kg vs. −5.0 kg; or − 9% vs. −5% of initial BW), total body fat (−8.5% vs. −4.3%), AF (−23% vs. −12.5%), and VF (−33% vs. −15.8%) mass. Most interestingly, whereas absolute FFM decreased in both groups (~1.5 kg), the proportion of FFM to total BW increased significantly following IF‐P compared with CR (5.7% vs. 3%, respectively).

Both nutritional interventions resulted in significant improvements in cardiovascular outcomes. For example, blood pressure, total cholesterol, low‐density lipoprotein cholesterol and triglycerides were reduced significantly in both IF‐P and CR groups at each time during the intervention, with no differences between groups. High‐density lipoprotein cholesterol (HDL‐C) decreased significantly in IF‐P compared with CR; however, the Total Cholesterol:HDL‐C ratio was consistent throughout the intervention for both groups.

The P component of IF‐P played an instrumental role in the favorable body composition outcomes, particularly attenuation of loss of FFM. Interestingly, the increased proportion of FFM in IF‐P compared with CR was associated with significantly lower sugar and increased fiber intakes in IF‐P, despite comparable weekly nutrition counseling by the registered dietitian. Whether the increased sugar and lower fiber intake induced an insulin‐mediated fat deposition or blunting of fat oxidation via the carbohydrate‐insulin model remains to be determined.

Previous research shows that increased dietary protein consumption during calorie‐restricted IF protocols substantially enhances FFM preservation, suggesting enhanced protein synthesis. Given the well‐established greater amount of leucine present in animal protein sources, including whey protein, IF‐P improved FFM retention compared with CR. In some cases, IF protocols induce losses of FFM up to 60% of the total weight lost. However, the current study minimized losses of absolute FFM to 20% and increased relative amounts by more than double in IF‐P compared with CR (6% vs. 3%).

The study’s results provide compelling support for both IF‐P and heart‐healthy daily CR nutritional regimens to enhance all aspects of body composition (BW, waist circumference, total FM, percent FFM), cardiovascular (systolic and diastolic blood pressure, blood lipids), and satiety responses.

IF‐P proved superior on BW, FM, and VF loss and increased proportion of FFM and satiety compared with heart‐healthy CR regimens in women and men with overweight and obesity, despite similar energy intakes and unchanged levels of physical activity energy expenditure.