Placebo controlled study to investigate the relationship between lowering serum zonulin levels and improved body weight composition using a daily oral dose of phenylcapsaicinAuthor(s): Zeenia Framroze, Lucas Altepost, Erik Lager
Leaky gut syndrome is associated with intestinal dysbiosis. Phenylcapsaicin, a novel analogue of capsaicin, at a low dose of 0.560 mg/day lowered serum zonulin levels from 67.1 (ng/mL) to 58.8 (ng/mL) after 54 days of daily oral supplementation. Lowered serum zonulin levels were correlated to improved body weight composition in the low dose treatment group but not in the high dose treatment group versus placebo in normal healthy subjects. Low dose treatment with phenylcapsaicin may be considered as a potential tool to alleviate the symptoms associated with leaky gut syndrome and commensurate healthy weight loss.
Background: Gastrointestinal disorders are on the rise in the United States, with some studies estimating that around twenty million Americans suffer from chronic digestive disorders. Our gut is made up of over 4,000 square feet of intestinal lining or epithelium. This lining acts as a barrier to limit interaction between luminal contents, such as intestinal microbiota, the immune system, and the rest of the body, while also supporting the transportation of nutrients, water and waste through this lining. When the gut microbiome is unbalanced, the cells in the intestinal wall can become compromised and permeable, allowing the passage of toxins, antigens and bacteria to the enter the bloodstream, causing a ‘leaky gut’. Leaky gut syndrome can dramatically impact an individual’s well being and their quality of life, with disruptions in the gut microbiome affecting an individual’s immunity and increasing the risk factor for infectious disease. Chronic inflammation throughout the body caused by leaky gut syndrome can cause gastrointestinal symptoms such as bloating cramps and constipation, as well as skin problems, like acne rashes and eczema. While certain treatments have shown some promise, such as the administering of pre and probiotics, restrictive diets and dietary supplements, there is no official recommendation regarding treatment or management regimes for the symptoms of leaky gut syndrome.
It might seem incongruous to talk about hot and spicy chili peppers and gut health - after all, natural capsaicin is the major bioactive compound in chili peppers. Recent research has shown a relationship between dietary capsaicin and gut microbiota population. Kang et al. showed that capsaicin may prevent microbial dysbiosis (a reduction in microbial diversity), gut barrier dysfunction and chronic low-grade inflammation, which also resulted in an anti-obesity effect. Though chili peppers have been a part of the human diet for years, and are popular worldwide, the difficult extraction process and variability of capsaicinoids in naturally occurring peppers, has led researchers to focus on finding alternatives that are readily available from chemical synthesis. We herein report the results on obesity and the leaky gut biomarker, zonulin after daily oral treatment with phenylcapsaicin. Phenylcapsaicin is a synthetic analogue of capsaicin, developed by aXichem.
The increased attention in gut health has led to a host of rapidly expanding in vivo, in vitro and ex vivo techniques and methods for investigation of the intestinal barrier.
One such method focuses on zonulin, an endogenous human analogue of the bacterial enterotoxin zonula occludens toxin. By disassembling the tight junctional protein complexes in the intestinal lining, zonulin is believed to modulate intestinal permeability. Research has shown high serum levels of zonulin may point to the presence of increased intestinal permeability, disrupted gut barrier function and an altered immune response. Elevated circulatory levels of zonulin are also directly associated with a number of conditions, such as celiac disease, diabetes, and psychological distress. Unfortunately, few drugs have shown a direct reduction of circulatory zonulin levels, and a potential mitigation of leaky gut symptoms. This paper measures the effect of phenylcapsaicin on serum levels of zonulin at two doses (high and low), and the resultant outcome of reduced body weight and improved body composition in treated subjects.
We aim to evaluate the effect of a novel analogue of capsaicin, phenylcapsaicin, on serum levels of zonulin, weight loss and body composition changes along with diet and lifestyle modifications in healthy adults in a randomized, double-blind, parallel-group clinical trial of male and female subjects. We also aimed to evaluate the anti-obesity effect of phenylcapsaicin on the sample population.