Demonstration of the Prebiotic-like Effects of Camu-camu Consumption Against Obesity-related Disorders in Humans

Summary

Previous work of the investigators demonstrated the anti-obesity and anti-steatosis potential of the Amazonian fruit camu-camu (CC) in a mouse model of diet-induced obesity \[1\]. It was demonstrated that the prebiotic role of CC was directly linked to higher energy expenditure stimulated by the fruit since fecal transplantation from CC-treated mice to germ-free mice was sufficient to reproduce the effects.

The full protection against hepatic steatosis observed in CC-treated mice is of particular importance since nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease. Thirty percent of adults in developed countries have excess fat accumulation in the liver, and this figure can be as high as 80% in obese subjects. NAFLD is an umbrella term encompassing simple steatosis, as well as non-alcoholic steatohepatitis which can lead to cirrhosis and hepatocellular carcinoma in up to 20% of cases. Up to now, except for lifestyle changes, no effective drug treatment are available. Previous work has suggested that CC possesses anti-inflammatory properties and could acutely reduce blood pressure and glycemia after a single intake. While CC could represent a promising treatment for obesity and fatty liver, no studies have thoroughly tested this potential in humans. Therefore, a robust clinical proof of concept study is needed to provide convincing evidence for a microbiome-based therapeutic strategy to counteract obesity and its associated metabolic disorders.

The mechanism of action of CC could involve bile acid (BA) metabolism. BA are produced in the liver and metabolized in the intestine by the gut microbiota. Conversely, they can modulate gut microbial composition. BA and particularly, primary BA, are powerful regulators of metabolism. Indeed, mice treated orally with the primary BA α, β muricholic (αMCA, βMCA) and cholic acids (CA) were protected from diet-induced obesity and hepatic lipid accumulation. Interestingly, the investigators reported that administration of CC to mice increased the levels of αMCA, βMCA and CA. Primary BA are predominantly secreted conjugated to amino acids and that deconjugation rely on the microbial enzymatic machinery of gut commensals. The increased presence of the deconjugated primary BA in CC-treated mice indicate that a cluster of microbes selected by CC influence the BA pool composition. These data therefore point to an Interplay between BA and gut microbiota mediating the health effects of CC.

Polyphenols and in particular procyanidins and ellagitannins in CC can also be responsible for the modulation of BA that can impact on the gut microbiota. Indeed, it has been reported that ellagitannins containing food like walnuts modulate secondary BA in humans whereas procyanidins can interact with farnesoid X receptors and alter BA recirculation to reduce hypertriglyceridemia. These effects are likely mediated by the remodeling of the microbiota by the polyphenols.

In accordance with the hypothesis that the ultimate effect of CC is directly linked to a modification of the microbiota, fecal transplantation from CC-treated mice to germ-free mice was sufficient to recapitulate the lower weight gain and the higher energy expenditure seen in donor mice.

Conditions

• Overweight
• Microtia
• Endotoxemia
• Metabolic Syndrome
• Insulin Resistance
• Non-Alcoholic Fatty Liver Disease

Interventions

DIETARY_SUPPLEMENT

Camu camu

3 capsules of camu camu powder (500 mg / capsule) daily during 12 weeks

DIETARY_SUPPLEMENT

Placebo

3 capsules of placebo daily during 12 weeks

Sponsors & Collaborators

• Laval University

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2020-10-31

Primary Completion

2022-04-21

Completion

2022-04-21

Countries

• Canada

Study Locations