A Dietary Intervention High in Green Leafy Vegetables Reduces Oxidative DNA Damage in Adults at Increased Risk of Colorectal Cancer: Biological Outcomes of the Randomized Controlled Meat and Three Greens (M3G) Feasibility Trial.

Andrew D Frugé,Anna E Arthur,Aaron J Riviere,William J Van Der Pol,Kimberly Braxton-Lloyd,Casey D Morrow,Kristen S Smith,Robert D Arnold,William M Murrah,Rachel Tenpenny-Chigas,Shanese L Jasper,Wendy Demark-Wahnefried

doi:10.3390/nu13041220

Abstract

Green leafy vegetables (GLV) may reduce the risk of red meat (RM)-induced colonic DNA damage and colorectal cancer (CRC). We previously reported the primary outcomes (feasibility) of a 12-week randomized controlled crossover trial in adults with habitual high RM and low GLV intake with body mass index (BMI) > 30 kg/m2 (NCT03582306). Herein, our objective was to report a priori secondary outcomes. Participants were recruited and enrolled in 2018, stratified by gender, and randomized to two arms: immediate intervention group (IG, n = 26) or delayed intervention group (DG, n = 24). During the 4 week intervention period, participants were provided with frozen GLV and counseled to consume 1 cooked cup equivalent daily. Participants consumed their normal diet for the remaining 8 weeks. At each of four study visits, anthropometrics, stool, and blood were taken. Overall, plasma Vitamin K1 (0.50 ± 1.18 ng/mL, p < 0.001) increased, while circulating 8OHdG (−8.52 ± 19.05 ng/mL, p < 0.001), fecal 8OHdG (−6.78 ± 34.86 ng/mL, p < 0.001), and TNFα (−16.95 ± 60.82 pg/mL, p < 0.001) decreased during the GLV intervention compared to control periods. Alpha diversity of fecal microbiota and relative abundance of major taxa did not differ systematically across study periods. Further investigation of the effects of increased GLV intake on CRC risk is warranted.

Highlights

The most recent global estimates of cancer incidence and mortality place colorectal cancer (CRC) as the fourth most prevalent and second deadliest cancer worldwide [1]
A series of preclinical studies indicate that chlorophyll in Green leafy vegetables (GLV) prevents the cytotoxic and carcinogenic effects of heme in red meat (RM) [10,11,12,13], which is mediated by the microbiota residing in the colon [14,15]. 8-hydroxy-20 -deoxyguanosine (8-OHdG) is a marker of DNA damage associated with increased adenoma risk [16], which we aim to use as a proxy for cytotoxicity observed in preclinical models
Between immediate and delayed phyla or across timepoints within phyla. This is the first trial to assess the effects of a dietary intervention high in GLV in adults with elevated body mass index (BMI) and high habitual RM consumption who are at increased risk for CRC

Summary

Introduction

The most recent global estimates of cancer incidence and mortality place colorectal cancer (CRC) as the fourth most prevalent and second deadliest cancer worldwide [1]. 2017 meta-analysis of 111 prospective cohort studies supported the relationships between increased risk of CRC with increased red and processed meat intake, as well as decreased risk of CRC with increased vegetable intake [2]. In 2015, approximately 38.3% of new CRC cases were directly attributed to suboptimal diets in the United States [3]. This high-meat, low-vegetable “Western” dietary pattern is most common in developed and developing countries and is directly associated with CRC risk [4], with a recent meta-analysis of 28 studies indicating a 30% increased risk of CRC for adults consuming this dietary pattern [5]. In a 2018 CUP meta-analysis of 47 cohort studies with

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