S819 Walnut Consumption Decreases Cytokine Secretion in Obese Subjects at Increased Risk of Colorectal Cancer

Introduction: Walnuts contain an array of anti-inflammatory properties that have been shown in preclinical models to reduce risk of colorectal cancer (CRC) development. The following study evaluates the impact of obesity, associated with the chronic production of inflammatory cytokines, on the potential benefits of walnuts in a clinical study. We evaluated the effects of walnuts on inflammation in 28 subjects with increased risk of CRC and assessed whether obesity status impacted these changes. Methods: Twenty-eight subjects were enrolled with elevated risk of CRC, defined as: 1) significant family history of CRC, 2) positive fecal immunochemical test/Cologuard test, or 3) personal history of advanced colorectal polyps. After consent, subjects underwent a 7-day wash-out period followed by a 21-day intervention, during which subjects consumed shelled, raw walnuts (56 gm/day). Peripheral blood mononuclear cells (PBMCs) were isolated from 28 subjects before and after walnut consumption. The percentage of lymphocytes, monocytes, T cells, T helper cells, cytotoxic T cells, B cells, and NK cells was determined by flow cytometry. For a subset of 8 obese (body mass index [BMI] ≥30 kg/m2) and 8 non-obese (BMI <30 kg/m2) subjects, PBMCs were stimulated in culture for 24 hours with PMA (10 ng/mL) and ionomycin (1 µg/mL), and multiplex ELISA was used to determine the changes in secretion of 17 inflammatory cytokines, before and after walnut consumption. The Wilcoxon signed-rank test was conducted to determine whether there was a statistically significant change between paired samples before and after walnut consumption. Results: Obesity status had a significant effect on cytokine secretion in PBMCs. Obese subjects showed significantly impaired mean capacity to secrete IL-17A (-58.9 pg/mL vs 13.3 pg/mL, P = 0.03) and IL-21 (-5.4 pg/mL vs -0.7 pg/mL, P = 0.05), as well as a borderline statistically significant decreased mean capacity to secrete GM-CSF (-348.9 pg/mL vs 55.2 pg/mL, P = 0.06), compared to non-obese subjects. No statistically significant differences in immune cell populations were found in obese vs non-obese subjects following walnut consumption, although CD64+ monocytes were trending towards a decline in obese subjects. Conclusion: Our study provides support for the role of walnut consumption in decreasing systemic inflammation in a subset of patients with increased risk of CRC with high BMI. Further research is needed to determine the mechanisms by which walnuts affect immune cell composition and function, especially among the obese population.