Abstract

We examined whether gastric acidity would affect the activity of myrosinase, co-delivered with glucoraphanin (GR), to convert GR to sulforaphane (SF). A broccoli seed and sprout extract (BSE) rich in GR and active myrosinase was delivered before and after participants began taking the anti-acid omeprazole, a potent proton pump inhibitor. Gastric acidity appears to attenuate GR bioavailability, as evidenced by more SF and its metabolites being excreted after participants started taking omeprazole. Enteric coating enhanced conversion of GR to SF, perhaps by sparing myrosinase from the acidity of the stomach. There were negligible effects of age, sex, ethnicity, BMI, vegetable consumption, and bowel movement frequency and quality. Greater body mass correlated with reduced conversion efficiency. Changes in the expression of 20 genes in peripheral blood mononuclear cells were evaluated as possible pharmacodynamic indicators. When grouped by their primary functions based on a priori knowledge, expression of genes associated with inflammation decreased non-significantly, and those genes associated with cytoprotection, detoxification and antioxidant functions increased significantly with bioavailability. Using principal components analysis, component loadings of the changes in gene expression confirmed these groupings in a sensitivity analysis.

Highlights

  • broccoli seed and sprout extract (BSE) supplements which contains active myrosinase, in order to verify the rough equivalence of its yield with similar preparations produced at JHU, and we report on that study

  • In addition to monitoring urinary excretion of SF and its DTC metabolites in full 24-h collections, we evaluated a variety of biomarkers thought to be associated with the mode of action of SF, in peripheral blood mononuclear cells (PBMCs) isolated from blood taken from subjects before and after an intervention with an oral GR + myrosinase supplement

  • After validating the fact that the commercial BSE supplement had roughly equivalent SF bioavailability to the laboratory-created food supplements we had for years been creating for clinical studies, we progressed to the “pump inhibitor (PPI) Phase.”

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Summary

Introduction

Consumption of plant-based diets is widely recognized as an important component in reducing the risk of a variety of chronic diseases and in promoting optimal health across the lifespan [1,2].Cruciferous vegetables, including broccoli, cabbage, cauliflower, Brussels sprouts, daikon, watercress, Nutrients 2019, 11, 1489; doi:10.3390/nu11071489 www.mdpi.com/journal/nutrientsNutrients 2019, 11, 1489 mustard, wasabi, and certain tropical vegetable species like Moringa oleifera, are especially protective due to their high contents of glucosinolates as well as flavonoids, carotenoids, and anthocyanins [3,4].Glucosinolates are not protective in native form, but are converted to biologically active isothiocyanates (ITC) by the enzyme, myrosinase [4,5]. Myrosinase is present in cruciferous plant cells and is normally segregated from the glucosinolates until the cells are ruptured by chewing, freeze–thaw, plant pathogens, or other damage. This enzyme is produced by some of the bacteria in our gut—our gastrointestinal microbiome [6,7,8,9]. These ITC are metabolized rapidly by conjugation with glutathione followed by stepwise hydrolysis of those conjugates, leading to N-acetylcysteine derivatives (mercapturic acids). These conjugates are known as dithiocarbamates (DTC) and can be quantified by the cyclocondensation reaction developed in our laboratory in the 1990s, and more recently refined [10]

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