Abstract
Sulforaphane, an isothiocyanate found in cruciferous vegetables such as broccoli, shows promise as an adjuvant therapy for preeclampsia. To inform future clinical trials, we set out to determine the bioavailability of sulforaphane in non-pregnant and preeclamptic women. In six healthy female volunteers, we performed a crossover trial to compare the bioavailability of sulforaphane and metabolites afforded by an activated and non-activated broccoli extract preparation. We then undertook a dose escalation study of the activated broccoli extract in 12 women with pregnancy hypertension. In non-pregnant women, an equivalent dose of activated broccoli extract gave higher levels of sulforaphane and metabolites than a non-activated extract (p < 0.0001) and greater area under the curve (AUC) (3559 nM vs. 2172 nM, p = 0.03). Compared to non-pregnant women, in women with preeclampsia, the same dose of activated extract gave lower levels of total metabolites (p < 0.000) and AUC (3559 nM vs. 1653 nM, p = 0.007). Doubling the dose of the activated extract in women with preeclampsia doubled levels of sulforaphane and metabolites (p = 0.02) and AUC (1653 nM vs. 3333 nM, p = 0.02). In women with preeclampsia, activated broccoli extract was associated with modest decreases in diastolic blood pressure (p = 0.05) and circulating levels of sFlt-1 (p = 0.0002). A myrosinase-activated sulforaphane formulation affords better sulforaphane bioavailability than a non-activated formulation. Higher doses of sulforaphane are required to achieve likely effective doses in pregnant women than in non-pregnant women. Sulforaphane may improve endothelial function and blood pressure in women with pregnancy hypertension.
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Data are available on request from the corresponding author.
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This work is funded by a research grant to SAM and EMW from the Norman Beischer Medical Research Foundation and by an NHMRC Program grant (APP 1113902) to EMW. The funding bodies had no role in trial design or the writing of the manuscript.
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AGC, SM, KP and EMW designed the study protocols and undertook the clinical studies. AGC, DA and DJC performed the LC-MS. AGC wrote the first draft of the manuscript. All authors contributed to manuscript revisions, and read and approved the final manuscript.
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Both studies were approved by the Monash Health Research Ethics Committee: RES17-0000-169A, approved 7 April 2017, and RES18-0000-514A, approved 10 September 2018.
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Langston-Cox, A.G., Anderson, D., Creek, D.J. et al. Sulforaphane Bioavailability and Effects on Blood Pressure in Women with Pregnancy Hypertension. Reprod. Sci. 28, 1489–1497 (2021). https://doi.org/10.1007/s43032-020-00439-5
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DOI: https://doi.org/10.1007/s43032-020-00439-5