Researchers have uncovered that eating walnuts may improve systemic inflammation and reduce the risk for colorectal cancer, according to a recent study published by Moussa et al in Cancer Prevention Research.
Background
Ellagitannins—plant-derived polyphenol compounds found in walnuts—have been shown to be metabolized exclusively by the gut microbiome into a wide range of anti-inflammatory molecules called urolithins. These urolithins have been associated with anti-inflammatory properties and may inhibit cancer.
“Ellagitannins in the walnut are importantly providing the anti-inflammatory and anticancer properties that we’re seeing in patients in our clinical trial research, particularly the gut’s conversion of ellagitannins to a potent anti-inflammatory agent, urolithin A,” reported senior study author Daniel W. Rosenberg, PhD, the HealthNet Chair in Cancer Biology and an investigator in the Center for Molecular Oncology at the University of Connecticut School of Medicine.
Study Methods and Results
In this study, the researchers screened 39 patients (aged 40 to 65) who were at elevated risk for colorectal cancer and asked them to complete a National Institutes of Health Food Frequency Questionnaire. The participants were further instructed to avoid all ellagitannin-containing foods and beverages for 1 week to set their urolithin levels at or close to zero prior to consuming ellagitannin-rich walnuts as part of their closely monitored diet. At the end of the 3-week study, all participants received a high-definition colonoscopy.
The researchers demonstrated that high levels of urolithin A formation by the gut microbiome from walnut consumption had a positive impact on reducing inflammatory markers across blood, urine, and fecal samples. They indicated that urolithin A may have positively affected the immune cells within colon polyps.
Additionally, elevated urolithin A levels in the urine of patients correlated with the serum levels of peptide YY, a protein associated with the inhibition of colorectal cancer. Reduced levels of several inflammatory markers presented in the blood were also found, especially among patients with obesity, who had the greatest capacity to produce urolithins by their gut microbiomes.
The researchers then used high-dimensional spatial imaging technology to develop a detailed view of the direct cellular interactions present inside colon polyps that were removed during colonoscopy. The imaging technology revealed that high levels of urolithin A formation following walnut consumption were directly associated with the reduction of several proteins often present in the polyps. The researchers also discovered that the protein vimentin, which is correlated with more advanced types of colorectal cancer, was reduced inside polyp tissues obtained from patients who had developed the highest levels of urolithin A by their gut microbiomes.
Conclusions
The findings built upon previous studies demonstrating that walnuts had beneficial and anticancer effects in the colons of cancer-prone mice.
“Urolithin A has a very positive influence on inflammation and maybe even cancer prevention. Our study proves that dietary supplementation with walnuts can boost the general population’s urolithin levels in those … with the right microbiomes, while significantly reducing several inflammatory markers, especially in patients [with obesity],” underscored Dr. Rosenberg. “Our study provides strong rationale for dietary inclusion of walnut ellagitannins for cancer prevention. Nutrients from walnuts can contribute to reduced cancer risk. There are many potential benefits [individuals] can get from eating walnuts, with so little downside risk, that just grabbing a handful every day is really something that [they] can easily do for [their] long-term health benefit,” he concluded.
Disclosure: The research in this study was supported by the American Institute for Cancer Research, the California Walnut Commission, and the National Cancer Institute. For full disclosures of the study authors, visit aacrjournals.org.