Intermittent fasting with protein pacing trumps calorie restriction in gut health and weight loss

By Pooja Toshniwal PahariaReviewed by Benedette Cuffari, M.Sc.Jun 2 2024

In a recent study published in the journal Nature Communications, researchers compare the effects of intermittent fasting with protein pacing (IF-P) with heart-healthy calorie restriction (CR) on gut microbiota remodeling and metabolomic profiles.

Study: Gut microbiome remodeling and metabolomic profile improve in response to protein pacing with intermittent fasting versus continuous caloric restriction. Image Credit: mentalmind / Shutterstock.com

Nutrition and the microbiome

The gut microbiome is critical for weight management and gastrointestinal health. Nutritional input, which influences both the gut microbiota and weight, has therapeutic potential for metabolic dysregulation.

Recent preclinical research in mice has shown that eating protein can reduce obesity following chronic fatty liver disease. IF-P, for example, is a successful weight reduction and body composition-enhancing strategy; however, the effects of this approach on the gut microbiome remain unclear.

About the study

The current study was conducted in Saratoga Springs, New York. It included people who were either inactive or minimally active, overweight or obese, weight stable, and between 30 and 65 years of age. Study participants were randomized to either IF-P or CR, which comprised 21 and 20 individuals, respectively, over eight weeks.

All study participants' calorie intake and expenditure were matched. Individuals using antibiotics, antifungals, or probiotics during the preceding two months were excluded from the study.

Fecal, microbial, and plasma metabolomic characteristics of overweight or obese individuals who followed an IF-P or CR diet were assessed. Any changes in food consumption, body weight, cardiometabolic outcomes, hunger ratings, and gut flora among either group were also documented. Study participants completed the gastrointestinal symptom rating scale (GSRS) at baseline as well as at weeks four and eight.

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

The effects of IF-P on gut bacteria colonization, stool parameters, and calorie reduction were determined. To this end, 16S ribosomal ribonucleic acid (rRNA) sequencing and linear-mixed effects modeling were used to identify patterns of covariation and co-occurrence between the microbiota and circulating metabolites. A multi-omics factor analysis also allowed the researchers to detect patterns of covariance and co-occurrence between the microbiome and circulating metabolites.

Protein pacing involves four meals containing 25-50 g of protein each day, whereas IF-P involves 35% carbohydrate, 30% fat, and 35% protein intake for five to six days each week. The CR regimen involves 41% carbohydrate, 38% fat, and 21% protein intake, consistent with United States dietary guidelines.

Study participants received supplements and snacks during IF days, whereas protein pacing days involved four to five meals each day, which is based on the American Heart Association's National Cholesterol Education Program Therapeutics Lifestyle Changes dietary guidelines.

Study findings

IF-P was found to influence gastrointestinal symptoms, gut microbial diversity, and circulating metabolites to a greater extent than CR. Moreover, IF-P led to higher Marvinbryantia, Christensenellaceae, and Rikenellaceae counts and increased levels of cytokines and amino acid metabolites that promote fatty acid oxidation.

IF-IP significantly enhanced cytokines involved in lipolysis, inflammation, weight loss, and immunological response, such as interleukin-4 (IL-4), IL-6, IL-8, and IL-13. Conversely, calorie restriction increased the levels of metabolites involved in a metabolic pathway linked to lifespan.

Gut microbiota and metabolomic variables influenced weight loss maintenance and body composition. Moreover, IF-P pacing had a more profound impact on gut microbiota dynamics than calorie restriction.

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

Conclusions

IF-P was associated with significant improvements in GI symptoms while increasing Christensenella levels, which is a gut bacteria associated with a lean phenotype, and circulating cytokines that regulate total body weight and fat reduction. The study findings emphasize the significance of individualized dietary treatments for optimum weight control and metabolic health outcomes.

Nevertheless, further research is needed to understand the processes responsible for these observations and the therapeutic implications of establishing individualized obesity control techniques. These findings may also guide future gut microbiome-focused precision dietary recommendations with larger sample sizes and longer durations.