Butyrate effective for treating pediatric obesity

This is part 2 of our 3-part series on pediatric obesity. Check back on Monday, March 27, for part 3. Click here for part 1.

Oral butyrate supplementation might be an effective form of treatment for pediatric patients with obesity, according to a recent study.

As pediatric obesity rapidly grows worldwide, the need for therapeutic strategies has been made known. Gut microbiome (GM) has been considered as a potential factor in obesity. This would make a low intake of dietary substrates for butyrate production contribute to obesity, making butyrate a potential treatment against obesity.

The Butyrate Against Pediatric Obesity (BAPO) trial was conducted to determine the efficacy of butyrate in treating pediatric obesity. Participants included children aged 5 to 17 years with a body mass index (BMI) above the 95th percentile for their sex and age.

Exclusion criteria included having allergies, bariatric surgery, celiac disease, autoimmune diseases, cancer, chronic hematologic diseases, cystic fibrosis, urinary tract diseases, respiratory diseases, gastrointestinal diseases, genetic and metabolic diseases, immunodeficiencies, neurologic or neuropsychiatric disorders, and inflammatory bowel diseases.

Children were also excluded if they had participated in other trials or were being treated with metformin, vitamins, prebiotics, probiotics, or postbiotics. These forms of treatment had the potential to affect GM structure and function within the previous year.

Standard care for pediatric patients with obesity was provided to all patients, with those in the butyrate group also receiving 20 mg/kg body weight sodium butyrate capsules per day, while a placebo group was given standard care plus cornstarch capsules. Children were randomized 1:1 in either the butyrate group or placebo group.

The maximum dosage for butyrate capsules was 800 mg/d, and capsules could be opened, and the content dissolved when children couldn’t swallow pills. As part of standard care, children underwent a balanced Mediterranean diet and at least 60 minutes of aerobic activity per day.

A decrease in BMI SD scores (SDS) of 0.25 or more after 6 months was the primary outcome of the study. Secondary outcomes included changes in waist circumference; serum glucose, insulin, cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, ghrelin, microRNA-221, and interleukin-6 (IL-6) levels.

Study monitoring included onsite visits and telephone interviews with the investigators, monitored by an independent clinical trial monitor. The medical history of patients was collected at enrollment, with a complete physical examination performed monthly. BMI was calculated as weight in kilograms divided by height in meters squared.

Blood samples were collected at enrollment and at 6 months to examine for insulin, glucose, total cholesterol, HDL-C, LDL-C, and triglyceride levels. Stool samples were also collected at enrollment and at 6 months and analyzed.

There were 54 children randomized into the butyrate group or placebo group from November 1, 2020, to December 31, 2021. Four children in the butyrate group and 2 in the placebo group did not participate in the follow-up.

Children in the butyrate group had a median age of 12 years, while those in the placebo group had a median age of 10 years. The butyrate also saw a higher median SDS of the BMI. However, distribution of the BMI SDS was similar between the 2 groups.

A BMI decrease of 0.25 SDS or more at 6 months was observed more often in the butyrate group compared to the placebo group. Decreases in secondary outcomes such as waist circumference, insulin level, ghrelin level, and IL-6 level were more significant in the butyrate group as well.

Adverse reactions to butyrate included mild nausea and headache during the first month of intervention, reported by 2 patients. In both patients, symptoms disappeared throughout the following 4 weeks. Treatment continued in both patients with no issues.

Overall, oral butyrate supplementation showed efficacy in treating pediatric obesity, with beneficial effects consistent with prior data. Investigators recommended further randomized clinical trials with longer follow-ups take place to confirm these findings.

Reference

Coppola S, Nocerino R, Paparo L, Bedogni G, Calignano A, Di Scala C, et al. Therapeutic effects of butyrate on pediatric obesity: A randomized clinical trial. JAMA Netw Open. 2022;5(12):e2244912. doi:10.1001/jamanetworkopen.2022.44912