Randomized Clinical Trial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2015; 21(43): 12457-12467
Published online Nov 21, 2015. doi: 10.3748/wjg.v21.i43.12457
Sulforaphane-rich broccoli sprout extract improves hepatic abnormalities in male subjects
Masahiro Kikuchi, Yusuke Ushida, Hirokazu Shiozawa, Rumiko Umeda, Kota Tsuruya, Yudai Aoki, Hiroyuki Suganuma, Yasuhiro Nishizaki
Masahiro Kikuchi, Hirokazu Shiozawa, Rumiko Umeda, Kota Tsuruya, Digestive and Liver Disease Center, Tokai University Tokyo Hospital, Tokyo 153-0065, Japan
Yusuke Ushida, Yudai Aoki, Hiroyuki Suganuma, Research and Development Division, Kagome Co., Ltd., 17 Nishitomiyama, Nasushiobara, Tochigi 329-2762, Japan
Yasuhiro Nishizaki, Department of Clinical Health Science, Tokai University Tokyo Hospital, Tokyo 153-0065, Japan
Author contributions: Kikuchi M, Ushida Y, Shiozawa H, Aoki Y, Suganuma H and Nishizaki Y designed the research; Kikuchi M, Umeda R, Tsuruya K, Shiozawa H and Nishizaki Y performed clinical research; Ushida Y contributed to biological analyses and preformed animal experiments; Kikuchi M and Nishizaki Y interpreted the data; Kikuchi M, Ushida Y and Nishizaki Y wrote the paper.
Institutional review board statement: The clinical trial has been registered with UMIN-CTR (#UMIN000012855); the protocol was approved by the Institutional Review Board for Clinical Research of the Tokai University School of Medicine (#13R-169) and the Ethics Committee of Kagome Co., Ltd (#2013-R05); the study was conducted in accordance with the International Ethical Guidelines and Declaration of Helsinki.
Institutional animal care and use committee statement: The animal experiment was approved by the Animal Care and Use Committee of Kagome Co., Ltd. in accordance with the guidelines established by the Japanese Society of Nutrition and Food Science (Law and Notification 6 of the Japanese Government). The animal experiment was designed to minimize pain or discomfort to the animals.
Conflict-of-interest statement: This study was sponsored by Kagome Co., Ltd. The authors declare no conflict of interest associated with this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Yasuhiro Nishizaki, MD, PhD, Professor, Department of Clinical Health Science, Tokai University Tokyo Hospital, 1-2-5, Yoyogi, Shibuya-ku, Tokyo 153-0065, Japan. dr-yasu@jcom.home.ne.jp
Telephone: +81-3-33702321 Fax: +81-3-5354-5366
Received: June 17, 2015
Peer-review started: June 19, 2015
First decision: July 19, 2015
Revised: August 7, 2015
Accepted: September 13, 2015
Article in press: September 14, 2015
Published online: November 21, 2015

AIM: To evaluate effects of dietary supplementation of sulforaphane (SF)-rich broccoli sprout (BS) extract on hepatic abnormalities in Japanese male participants.

METHODS: In a randomized, placebo-controlled, double blind trial, male participants with fatty liver received either BS capsules containing glucoraphanin [GR; a precursor of SF (n = 24)] or placebo (n = 28) for 2 mo. Liver function markers, serum levels of aspartate and alanine aminotransferases (AST and ALT, respectively) and γ-glutamyl transpeptidase (γ-GTP) and an oxidative stress marker, urinary levels of 8-hydroxydeoxyguanosine (8-OHdG), were measured and compared in participants before and after the trial period. In an animal model, chronic liver failure was induced in Sprague-Dawley rats by successive intraperitoneal injection with N-nitrosodimethylamine (NDMA) for 4 wk. Concomitantly, rats received AIN-76 diets supplemented with or without BS extract. Thereafter, rats were sacrificed, and their sera and livers were collected to measure serum liver function markers and hepatic levels of thiobarbituric acid reactive substances (TBARS) levels and hepatic glutathione S-transferase (GST) activity, a prototypical phase 2 antioxidant enzyme.

RESULTS: Dietary supplementation with BS extract containing SF precursor GR for 2 mo significantly decreased serum levels of liver function markers, ALT [median (interquartile range), before: 54.0 (34.5-79.0) vs after supplementation: 48.5 (33.3-65.3) IU/L, P < 0.05] and γ-GTP [before: 51.5 (40.8-91.3) vs after: 50.0 (37.8-85.3) IU/L, P < 0.05], as well as the alkali phosphatase activity. Placebo showed no significant effects on the markers. The urinary level of 8-OHdG, an established oxidative stress marker, was significantly reduced in participants who had received BS capsules but not the placebo [before: 6.66 (5.51-9.03) vs after: 5.49 (4.89-6.66) ng/mg-creatinine, P < 0.05]. The reduction of urinary 8-OHdG was significantly correlated with decreased levels of both ALT and γ-GTP [∆8-OHdG and ∆ALT: Spearman r (r) 0.514 and P = 0.012, ∆8-OHdG and ∆γ-GTP: r = 0.496 and P = 0.016]. Intake of BS extract prevented NDMA-induced chronic liver failure in rats, which was attributable to the suppression of the increase in TBARS through induction of hepatic phase 2 antioxidant enzymes including hepatic GST (86.6 ± 95.2 vs 107.8 ± 7.7 IU/g, P < 0.01).

CONCLUSION: Dietary supplementation with BS extract containing the SF precursor GR is likely to be highly effective in improving liver function through reduction of oxidative stress.

Keywords: Sulforaphane, Glucoraphanin, Broccoli sprout, Nrf2, Hepatic abnormality, Oxidative stress, Phase 2 enzymes

Core tip: A randomized, placebo-controlled, double blind trial was conducted to assess the efficacy of dietary supplementation with broccoli sprout extract containing glucoraphanin (GR), a sulforaphane (SF) precursor, on hepatic abnormalities in Japanese men without changing their lifestyle or habits. Supplementation for 2 mo significantly decreased serum levels of liver function markers such as alanine aminotransferase and γ-glutamyl transpeptidase. The effect was associated with a reduction of urinary 8-hydroxydeoxyguanosine, an oxidative stress marker. Dietary supplementation with SF precursor GR is effective in improving liver function, and represents a potent method for maintaining good liver condition.