Bioavailability of Glucoraphanin and Sulforaphane from High-Glucoraphanin Broccoli

Tharsini Sivapalan, Antonietta Melchini, Shikha Saha, Paul W Needs, Maria H Traka, Henri Tapp, Jack R Dainty, Richard F Mithen, Tharsini Sivapalan, Antonietta Melchini, Shikha Saha, Paul W Needs, Maria H Traka, Henri Tapp, Jack R Dainty, Richard F Mithen

Abstract

Scope: Broccoli accumulates 4-methylsulphinylbutyl glucosinolate (glucoraphanin) which is hydrolyzed to the isothiocyanate sulforaphane. Through the introgression of novel alleles of the Myb28 transcription factor from Brassica villosa, broccoli genotypes have been developed that have enhanced levels of glucoraphanin. This study seeks to quantify the exposure of human tissues to glucoraphanin and sulforaphane following consumption of broccoli with contrasting Myb28 genotypes.

Methods and results: Ten participants are recruited into a three-phase, double-blinded, randomized crossover trial (NCT02300324), with each phase comprising consumption of 300 g of a soup made from broccoli of one of three Myb28 genotypes (Myb28B/B , Myb28B/V , Myb28V/V ). Plant myrosinases are intentionally denatured during soup manufacture. Threefold and fivefold higher levels of sulforaphane occur in the circulation following consumption of Myb28V/B and Myb28V/V broccoli soups, respectively. The percentage of sulforaphane excreted in 24 h relative to the amount of glucoraphanin consumed varies among volunteers from 2 to 15%, but does not depend on the broccoli genotype.

Conclusion: This is the first study to report the bioavailability of glucoraphanin and sulforaphane from soups made with novel broccoli varieties. The presence of one or two Myb28V alleles results in enhanced delivery of sulforaphane to the systemic circulation.

Keywords: bioavailability; broccoli; glucoraphanin; pharmacokinetics; sulforaphane.

© 2017 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Figures

Figure 1
Figure 1
Flow diagram for participant recruitment.
Figure 2
Figure 2
Concentration of glucosinolates in the soups with different broccoli genotypes. Glucosinolates measured includes glucoraphanin (4‐MSB, 4‐methylsulphinylbutyl), 3‐methylsulphinylpropyl (3‐MSP), indolylmethyl (IND), 1‐hydroxy‐indolylmethyl (OHIND), 1‐methoxy‐indolylmethyl (1‐MIND), and 4‐methoxy‐indolylmethyl (4‐MIND). Data are represented as mean ± SD (n = 10, Myb28B/B, Myb28B/V soups; n = 4, Myb28V/V soups). Statistical analysis of the data was undertaken by two‐way analysis of variance with Dunnett's multiple comparisons test (**p ˂ 0.01 and ***p˂0.0001 vs Myb28B/B broccoli soup).
Figure 3
Figure 3
Plasma concentrations (μm) of intact glucoraphanin (A) and sulforaphane (B) following consumption of Myb28B/B (84 μmoles glucoraphanin per 300 g soup), Myb28B/V (280 μmoles glucoraphanin per 300 g soup), and Myb28V/V (452 μmoles glucoraphanin per 300 g soup) broccoli soups. The samples were analyzed by UPLC–MS/MS and LC–MS/MS for glucoraphanin and sulforaphane, respectively. Samples were analyzed for sulforaphane metabolites including sulforaphane‐glutathione, sulforaphane‐cysteine, sulforaphane–cysteine‐glycine, and sulforaphane‐NAC. Data (n = 10) are represented as mean ± SD.
Figure 4
Figure 4
Urinary excretion of intact glucoraphanin and glucoerucin (μmoles) in 24 h following consumption of Myb28B/B (84 μmoles glucoraphanin per 300 g soup), Myb28B/V (280 μmoles glucoraphanin per 300 g soup), and Myb28V/V (452 μmoles glucoraphanin per 300 g soup) broccoli soups. Cumulative excretion of glucoraphanin/glucoerucin (A), and the total urinary excretion of glucoraphanin/glucoerucin (B) measured in urine by UPLC–MS/MS. Data (n = 10) are represented as mean ± SD. Total urinary excretion data underwent square root transformation followed by analysis by one‐way analysis of variance with Tukey's honest significance test (***p ˂ 0.0001 vs My28B/B broccoli soup).
Figure 5
Figure 5
Urinary excretion of sulforaphane and metabolites (μmoles) in 24 h following consumption of Myb28B/B (84 μmoles glucoraphanin per 300 g soup), Myb28B/V (280 μmoles glucoraphanin per 300 g soup), and Myb28V/V (452 μmoles glucoraphanin per 300 g soup) broccoli soups. Cumulative excretion (A) and total urinary excretion (B) of sulforaphane and metabolites in urine samples analyzed by LC–MS/MS. Samples were analyzed for sulforaphane metabolites including erucin‐NAC, sulforaphane‐cysteine, sulforaphane–cysteine‐glycine, and sulforaphane‐NAC. Data (n = 10) are represented as mean ± SD. Total urinary excretion data underwent log root transformation followed by analysis by one‐way analysis of variance with Tukey's honest significance test (*p < 0.05 and ***p ˂ 0.001 vs My28B/B broccoli soup).
Figure 6
Figure 6
Percentage of glucoraphanin (A) and sulforaphane (B) excreted in the urine following consumption of the ingested dose of glucoraphanin in the broccoli soups, Myb28B/B (84 μmoles glucoraphanin per 300 g soup), Myb28B/V (280 μmoles glucoraphanin per 300 g soup), and Myb28V/V (452 μmoles glucoraphanin per 300 g soup). Urine samples collected from participants (A–J) were analyzed for glucoraphanin, glucoerucin, sulforaphane, and its metabolites including sulforaphane, erucin‐NAC, sulforaphane‐cysteine, sulforaphane–cysteine‐glycine, and sulforaphane‐NAC.

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