Intermittent Fasting with Protein Beats Calorie Restriction for Gut Health and Weight Loss

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

The microbiome and nutrition
For gastrointestinal health and weight control, the gut microbiota is essential. Nutritional input has therapeutic promise for metabolic dysregulation since it affects weight and the gut microbiota.

Consuming protein helps lessen obesity after chronic fatty liver disease, according to recent preclinical studies conducted in mice. For instance, IF-P is an effective weight loss and body composition enhancement technique; however, it is still unknown how this strategy would affect the gut microbiota.

Concerning the study
The location of the current study is Saratoga Springs, New York. It comprised individuals who were between the ages of 30 and 65, overweight or obese, with constant weight, and either inactive or very little active. Over the course of eight weeks, study participants were randomized to either IF-P or CR, which included 21 and 20 people, respectively.

The amount of calories consumed and expended by each study participant were equal. Individuals using antibiotics, antifungals, or probiotics during the preceding two months were excluded from the study.

The fecal, microbiological, and plasma metabolomic features of obese or overweight people on an IF-P or CR diet were evaluated. Any variations in the intake of food, weight, gut microbiota, cardiometabolic outcomes, and evaluations of hunger for either group were also recorded. The gastrointestinal symptom rating scale (GSRS), which was completed by study participants at baseline, weeks four and eight, was also administered.

To ascertain the overall bacterial biomass and makeup of the fecal microbiome, fecal samples were collected for quantitative polymerase chain reaction (qPCR) analysis and deoxyribonucleic acid (DNA) extraction. Additionally, blood samples from study participants were given for biochemical analyses, assessments of body composition, and serum metabolomic analysis. These analyses were carried out using gas chromatography-MS for short-chain fatty acid (SCFA) analysis and liquid chromatography-mass spectrometry (LC-MS) for serum metabolomic analysis.

It was established how IF-P affected the colonization of gut bacteria, stool characteristics, and calorie reduction. To this aim, patterns of covariation and co-occurrence between the microbiota and circulating metabolites were found using 16S ribosomal ribonucleic acid (rRNA) sequencing and linear-mixed effects modeling. The researchers were also able to identify patterns of covariance and co-occurrence between the circulating metabolites and the microbiota through the use of a multi-omics factor analysis.

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

On IF days, study participants received supplements and snacks; on protein pacing days, they had four to five meals a day, based on the dietary parameters recommended by the American Heart Association’s National Cholesterol Education Program Therapeutics Lifestyle Changes.

Study results
It was discovered that IF-P had a bigger impact on gut microbial diversity, circulating metabolites, and gastrointestinal symptoms than did CR. Additionally, larger counts of Marvinbryantia, Christensenellaceae, and Rikenellaceae were seen in response to IF-P, as were higher concentrations of cytokines and amino acid metabolites that support fatty acid oxidation.

IF-IP markedly increased cytokines, including interleukin-4 (IL-4), IL-6, IL-8, and IL-13, that are implicated in lipolysis, inflammation, weight loss, and immune response. On the other hand, calorie restriction raised the amounts of metabolites connected to a lifespan-related metabolic pathway.

Body composition and the maintenance of weight loss were impacted by gut microbiota and metabolomic factors. Furthermore, IF-P pacing rather than calorie restriction had a more significant effect on the dynamics of the gut flora.

Along with a 40% reduction in total fat, carbohydrate, salt, sugar, and calorie intake, IF-P increased protein consumption more than CR. Individuals following the IF-IP protocol experienced greater reductions in body weight, visceral, abdominal, and total fat mass, as well as a higher percentage of fat-free mass. The IF-P group of study participants also showed a significant 33% reduction in visceral fat.

In conclusion
Significant reductions in GI symptoms were linked to IF-P, which also increased levels of Christensenella, a gut bacterium linked to a lean phenotype, and circulating cytokines that control body weight and fat loss. The results of the study highlight the importance of customized diet plans for the best results in terms of weight control and metabolic health.

However, more investigation is required to comprehend the mechanisms underlying these findings and the potential therapeutic benefits of developing customized obesity management strategies. These results may help direct future larger sample sizes and longer term precision dietary recommendations focusing on the gut flora.

For more information: Gut microbiome remodeling and metabolomic profile improve in response to protein pacing with intermittent fasting versus continuous caloric restriction, Nature Communications, doi:10.1038/s41467-024-48355-5