Low-Dose of the Sulforaphane Precursor Glucoraphanin as a Dietary Supplement Induces Chemoprotective Enzymes in Humans

Yusuke Ushida,Akinori Yanaka,Hiroyuki Suganuma

doi:10.4236/fns.2015.617165

Abstract

Broccoli sprout (BS) supplements have been marketed for over a decade for the promising health beneficial effects of sulforaphane (SFN), which induces Nrf2 signaling and downstream chemoprotective genes, including phase 2 enzymes. Most commercially available BS supplements encapsulate heat-processed BS containing glucoraphanin (GR), which is hydrolyzed to SFN by the intestinal microbiota. However, the absorption behavior of SFN following the intake of such BS supplements is still unclear. Additionally, the GR dose (around 30 mg) recommended by many manufacturers of BS supplements is relatively lower than the effective dose determined in previous intervention studies. The aims of this study were to assess the effects of a single administration of a typical BS supplement containing lower doses of GR (30 or 60 mg from 3 or 6 capsules, respectively) on SFN absorption, and also to assess the serum activities of phase 2 enzymes as possible surrogate markers of the beneficial effects of SFN. Urinary excreted isothiocyanates and dithiocarbamates showed that the SFN absorption following administration of BS supplement was prolonged and varied among individuals, which conforms to the well-known characteristics of intestinal microbiota-mediated SFN absorption. The amount of SFN absorbed increased dose-dependently but not linear fashion (9.27 μmol and 13.5 μmol for 3 and 6 capsules, respectively). There was no significant difference in SFN bioavailability and the number of capsules consumed. Serum activities of phase 2 enzymes glutathione S-transferase (GST) and NAD(P)H: quinone oxidoreductase 1 (NQO1), which have been reported to display “chemoprotected states” in organs such as the liver, were dose-dependently and synchronously elevated (p < 0.05) following BS supplement intake. This suggests that a low dose of GR (30 mg) exerts chemoprotective effects in humans. In conclusion, our findings will be useful in future clinical studies investigating the chemoprotective effects of SFN, and for the development of BS supplement products.

Highlights

Many epidemiological studies have demonstrated that higher consumption of cruciferous vegetables such as broccoli, kale, and cabbage, is associated with lower risk of various types of cancer and age- and lifestyle-related chronic diseases [1]-[3]
Several studies have shown that SFN can be absorbed into the body due to the intestinal microbiota possessing GR hydrolysis activity, even when cooked or heat-processed Broccoli sprout (BS) containing GR without active myrosinase is consumed [27]-[34]
The present study revealed that the absorption of SFN occurred after the administration of BS supplement, which was confirmed by measuring the excreted amounts of ITCs and dithiocarbamate metabolites (DTC) in urine samples, consistent with many previous studies [27] [29] [30]

Summary

Introduction

Many epidemiological studies have demonstrated that higher consumption of cruciferous vegetables such as broccoli, kale, and cabbage, is associated with lower risk of various types of cancer and age- and lifestyle-related chronic diseases [1]-[3]. SFN has been reported to promote detoxification and elimination of aflatoxin [8], acetaldehyde [9], methylmercury [10], acrolein [11], benzene [12], crotonaldehyde [12] and free radicals [13] through the Nrf2-mediated mechanism. It exerts chemoprotective effects against cancers [14] [15] and chronic diseases such as liver failure [16], type 2 diabetes-induced cardiomyopathy [17], cerebral nerve diseases [18] [19], and macular degeneration [20] in experimental animal models. Some clinical studies have demonstrated that SFN may be effective in the prevention and/or improvement of skin erythema [21], autism [22], insulin resistance [23], Helicobacter pylori-infection [24], and liver abnormality [25]

Objectives

Methods

Conclusion