Protein Intermittent Fasting Is Better Than Calorie Restriction for Gut Health and Weight Loss

In a recent study published in Nature Communications, researchers compared the effects of intermittent fasting with protein (IF-P) versus calorie restriction (CR), which benefits for the heart, on the remodeling of the intestinal microbiota and metabolic profiles.

The gut microbiome plays a key role in weight management and digestive health. Diets that influence both gut microbiota and weight have therapeutic potential for regulating metabolic disorders.

Recent preclinical studies in mice have shown that protein intake may reduce obesity after chronic fatty liver disease. IF-P, for example, is a successful strategy for weight loss and body composition improvement; however, the impact of this approach on the gut microbiome remains unclear.

The current study was conducted in Saratoga Springs, New York. It included people who were either sedentary or moderately active, overweight or obese, maintaining a stable weight, and aged 30 to 65 years. Study participants were randomly assigned to the IF-P or CR groups, which included 21 and 20 people, respectively, over eight weeks.

The caloric intake and expenditure of all study participants were equalized. Individuals using antibiotics, antifungals, or probiotics in the past two months were excluded from the study.

Fecal, microbial and plasma metabolic characteristics of overweight or obese individuals following the IF-P or CR diet were assessed. Changes in food intake, body weight, cardiometabolic parameters, hunger scores, and gut microbiota in each group were also documented. Study participants completed the GI Symptom Rating Scale (GSRS) at baseline and at weeks four and eight.

Fecal samples were collected for deoxyribonucleic acid (DNA) extraction and quantitative polymerase chain reaction (qPCR) analysis to determine total bacterial biomass and fecal microbiota composition. Study participants also provided blood samples for body composition assessment, biochemical assessment, and serum metabolite analysis, which was performed using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-MS for short-chain fatty acid (SCFA) analysis.

The effects of IF-P on gut bacterial colonization, stool parameters, and calorie reduction were determined using 16S ribosomal RNA (rRNA) sequencing and linear mixed effects modeling to identify patterns of covariation and co-occurrence between microbiota and circulating metabolites. Multiomics factor analysis also allowed the researchers to identify patterns of covariation and co-occurrence between the microbiome and circulating metabolites.

Protein nutrition includes four meals containing 25-50 grams of protein each day, while IF-P includes 35% carbohydrates, 30% fat and 35% protein for five to six days a week. The CR regimen contains 41% carbohydrates, 38% fat and 21% protein, meeting US dietary guidelines.

Study participants received supplements and snacks during IF days, while protein days included four to five meals each day, which is based on lifestyle recommendations from the American Heart Association's National Cholesterol Education Program.

IF-P had greater effects on GI symptoms, gut microbiota diversity, and circulating metabolites than CR. In addition, IF-P resulted in increased abundance of Marvinbryantia, Christensenellaceae, and Rikenellaceae, as well as levels of cytokines and amino acid metabolites that promote fatty acid oxidation.

IF-P significantly increased levels of cytokines involved in lipolysis, inflammation, weight loss, and immune response, such as interleukin-4 (IL-4), IL-6, IL-8, and IL-13. While calorie restriction increased the levels of metabolites involved in a metabolic pathway associated with lifespan.

Gut microbiota and metabolic variables influenced weight loss maintenance and body composition. In addition, IF-P had a greater effect on gut microbiota dynamics than caloric restriction.

IF-P also reduced total fat, carbohydrate, salt, sugar, and calorie intake by 40% while increasing protein intake more than CR. Study participants who followed IF-P lost more body weight, total fat, abdominal fat, and visceral fat and had a greater percentage of lean mass. Participants in the IF-P group also showed a significant reduction in visceral fat by 33%.

IF-P was associated with significant improvements in GI symptoms, increased levels of Christensenella, a gut bacteria associated with a lean phenotype, and circulating cytokines regulating overall body weight and fat reduction. Study results highlight the importance of individualized dietary practices for optimal weight control and metabolic health.

However, further research is needed to understand the processes responsible for these observations and the therapeutic implications of establishing individualized methods of obesity control. These findings may also guide future recommendations for gut microbiome-targeted precision diets with larger samples and longer study durations.