Butyrate Improves BMI and Other Key Measures in Pediatric Obesity

Supplementation with oral butyrate may be effective as a treatment for pediatric obesity, data indicate.

In a randomized, placebo-controlled Italian study of more than 50 children with obesity, 6 months of daily supplementation with oral butyrate, in addition to standard therapy, was associated with a 10% reduction in body mass index (BMI). Butyrate also had beneficial effects on metabolic measures, dietary measures, and body habitus.

Dr Roberto Berni Canani

“This is the first evidence of the therapeutic activity exerted by a beneficial gut microbiome–derived metabolite against pediatric obesity,” corresponding study author Roberto Berni Canani, MD, PhD, professor of pediatrics at the University of Naples Federico II, in Italy, told Medscape Medical News.

The study was published online December 5 in JAMA Network Open.

Therapeutic Effects

The Butyrate Against Pediatric Obesity (BAPO) trial enrolled 54 children and adolescents aged 5 to 17 years whose BMI was greater than the 95th percentile for sex and age. All study participants received standard-of-care treatment. They were randomly assigned in groups of equal size to receive daily sodium butyrate capsules (20 mg/kg body weight) or placebo for 6 months. Blood sampling was conducted at baseline and at the study conclusion. Six-month data were collected from 25 participants in the placebo group and from 23 in the butyrate group.

Among the butyrate patients who completed the study, BMI had decreased an average of 10% at 6 months. BMI decreased from 29.55 kg/m² at baseline to 26.53 kg/m² in this group. The average BMI decrease for the placebo group was about 2.6%, from 29.47 kg/m² to 28.71 kg/m².

The primary study outcome was decrease of at least 0.25 in BMI standard deviation score (SDS) at 6 months. In the placebo group, BMI SDS decreased from 3.15 at baseline to 2.89 at 6 months. In the butyrate group, that decrease was from 3.15 to 2.58. About 96% of the butyrate group and 56% of control patients achieved the primary outcome.

The butyrate group also showed the following changes, compared with the placebo group:

• Waist circumference, -5.07 cm (P < .001)

• Insulin level, -5.41 μU/mL (P = .03)

• Homeostatic model assessment of insulin resistance, -1.14 (P = .02)

• Ghrelin level, -47.89 μg/mL (P < .001)

• Interleukin-6 level, -4.81 pg/mL (P < .001)

Adherence to standard treatment was similar for both groups, but supplementation adherence was lower with the butyrate group. The study did not report specific supplementation adherence levels for either group, however. Two patients in the butyrate group reported transient mild nausea and headache during the first month of treatment, and four dropped out after their first doses.

The rationale for the study was the fact that normal butyrate production is known to be protective against obesity, Canani said. “Unfortunately, several environmental factors (mainly dietary factors, junk food, and drug exposure, antibiotics) are able to exert detrimental effects on gut microbiome structure and function, reducing the production of butyrate.”

But butyrate supplementation has a serious hurdle to overcome, said Canani. “The taste and smell of the butyrate preparations available on the market are major limiting factors,” said Canani. This study is the first to provide evidence of butyrate’s therapeutic effect against pediatric obesity; additional studies are needed to confirm the findings. “We are planning new multicenter clinical studies using a new and more palatable butyrate formulation,” said Canani.

A Questionable Endpoint?

Commenting on the study for Medscape, Justin Ryder, PhD, associate professor of surgery and pediatrics at Northwestern University Feinberg School of Medicine in Chicago, said, “This was a rigorous placebo-controlled randomized trial.”

But he noted shortcomings with the use of BMI SDS, “which is well established to be a poor metric for outcomes of pediatric obesity trials and a notable limitation of the study.” Ryder, who was not involved with the study, is also vice chair of research for the Department of Surgery at Ann and Robert H. Lurie Children’s Hospital of Chicago and chair of the pediatric obesity section of the Obesity Society.

“That being said,” Ryder added, “when you examine the BMI change, the butyrate group had roughly a 3 kg/m² reduction in 6 months, or about a 10% BMI reduction, which is very impressive.”

Butyrate adherence was probably lower “due to some unpleasant components” of taking the drug, he said. “The long-term sustainability of the supplementation on weight loss needs to be further studied. Evaluation beyond 1 year with a smaller age distribution — 5 to 17 is very wide for these types of studies — would help to determine the reproducibility of these findings.”

The study was supported by the Department of Translational Medical Science of the University of Naples Federico II, which received funding from the National Recovery and Resilience Plan, European Union–NextGenerationEU. Canani reports no relevant financial relationships. Ryder receives funding from the National Institutes of Health and donation of a drug from Boehringer Ingelheim for a clinical trial.

JAMA Netw Open. Published online December 5, 2022. Full text

Richard Mark Kirkner is a medical journalist based in the Philadelphia area.

For more coverage of Italian medical news, visit Univadis Italy.

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