Reduction of inflammation in chronic pancreatitis using a soy bread intervention: A feasibility study

Abstract

Introduction: Chronic pancreatitis is a chronic inflammatory disease, which progresses to fibrosis. Currently there are no interventions to delay or stop the progression to irreversible organ damage. In this study, we assessed the tolerability and feasibility of administering soy bread to reduce circulating inflammatory mediators.

Methods: Subjects with chronic pancreatitis diagnosed using the American Pancreatic Association diagnostic guidelines were enrolled. During the dose escalation (DE) phase, subjects received one week of soy bread based using a 3 + 3 dose-escalation design, which was then followed by a maximally tolerated dose (MTD) phase with four weeks of intervention. Dose-limiting toxicities (DLTs) were monitored. Plasma cytokine levels were measured using a Meso Scale Discovery multiplex assay kit. Isoflavonoid excretion in 24-h urine collection was used to measure soy bread compliance.

Results: Nine subjects completed the DE phase, and one subject completed the MTD phase without any DLTs at a maximum dosage of three slices (99 mg of isoflavones) per day. Reported compliance to soy bread intervention was 98%, and this was confirmed with urinary isoflavones and their metabolites detected in all subjects. There was a significant decline in the TNF-α level during the DE phase (2.667 vs 2.382 pg/mL, p = 0.039); other levels were similar.

Conclusions: In this feasibility study, there was excellent compliance with a short-term intervention using soy bread in chronic pancreatitis. Reduction was seen in at least one pro-inflammatory cytokine with short-term intervention. Larger cohorts and longer interventions with soy are warranted to assess the efficacy of reducing pro-inflammatory mediators of disease.

Keywords: Feasibility study; IL-6; Isoflavones; Soy bread; TNF-Alpha.

Conflict of interest statement

Declaration of competing interest No conflicts of interest exist.

Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Figures

Figure 1.

CONSORT flowchart of study participants.

Figure 2.

Total isoflavones and isoflavone composition quantified in soy bread (A). Total amount of isoflavones excreted across three doses of soy bread (B). Letters represent the mean separation using ANOVA analysis and Tukey’s posthoc test when significant differences (p≤0.05) were observed.

Figure 3.

Pooled cytokine profile changes for all subjects completing the DE phase. A. Absolute differences in the baseline and post-intervention levels of TNF-α. B. Waterfall plot of the mean fold change in plasma cytokine expression.

Figure 4.

Waterfall plot depicting changes in the plasma cytokine profile in a subject exposed to 99mg of soy isoflavones per day for 4 weeks in the MTD phase compared to baseline.