Evaluation of Biodistribution of Sulforaphane after Administration of Oral Broccoli Sprout Extract in Melanoma Patients with Multiple Atypical Nevi

Abstract

Broccoli sprout extract containing sulforaphane (BSE-SFN) has been shown to inhibit ultraviolet radiation-induced damage and tumor progression in skin. This study evaluated the toxicity and potential effects of oral BSE-SFN at three dosages. Seventeen patients who each had at least 2 atypical nevi and a prior history of melanoma were randomly allocated to 50, 100, or 200 μmol oral BSE-SFN daily for 28 days. Atypical nevi were photographed on days 1 and 28, and plasma and nevus samples were taken on days 1, 2, and 28. Endpoints assessed were safety, plasma and skin sulforaphane levels, gross and histologic changes, IHC for phospho-STAT3(Y705), Ki-67, Bcl-2, HMOX1, and TUNEL, plasma cytokine levels, and tissue proteomics. All 17 patients completed 28 days with no dose-limiting toxicities. Plasma sulforaphane levels pooled for days 1, 2, and 28 showed median postadministration increases of 120 ng/mL for 50 μmol, 206 ng/mL for 100 μmol, and 655 ng/mL for 200 μmol. Median skin sulforaphane levels on day 28 were 0.0, 3.1, and 34.1 ng/g for 50, 100, and 200 μmol, respectively. Plasma levels of proinflammatory cytokines decreased from day 1 to 28. The tumor suppressor decorin was increased from day 1 to 28. Oral BSE-SFN is well tolerated at daily doses up to 200 μmol and achieves dose-dependent levels in plasma and skin. A larger efficacy evaluation of 200 μmol daily for longer intervals is now reasonable to better characterize clinical and biological effects of BSE-SFN as chemoprevention for melanoma. .

Broccoli sprout supplementation in patients with advanced pancreatic cancer is difficult despite positive effects—results from the POUDER pilot study

“…Additionally, disgust due to the broccoli flavour coming from the stomach after the capsule intake was reported, and this may have increased nausea and emesis; however, no severe impact on patient's self-care and overall abilities were observed, which is highlighted by the Karnofsky performance status, which was comparable between the two groups 3 months after the study began. Our conclusion is in line with the results of former clinical phase I and II studies that demonstrated the safety and tolerance of glucosinolate-and isothiocyanate-rich broccoli sprouts in healthy volunteers and in cancer patients [6,24,27]; however, these studies used lower sulforaphane concentrations.…”

“…The 95% confidence intervals for the treatment (black line) and placebo (grey, dotted line) with censors (+) are shown sprout extract. Unlike our raw broccoli sprout preparation, the broccoli sprout extracts consisted of the aqueous phase of threeday-old, fresh, green broccoli sprouts after boiling and the conversion of glucoraphanin to active sulforaphane by daikon myrosinase after cooling [24,27]. After digestion, the extracts were lyophilized, and 218 mg powder with 50 μmol sulforaphane was packed into capsules-the patients took 4 capsules daily [24,27].…”

“…Unlike our raw broccoli sprout preparation, the broccoli sprout extracts consisted of the aqueous phase of threeday-old, fresh, green broccoli sprouts after boiling and the conversion of glucoraphanin to active sulforaphane by daikon myrosinase after cooling [24,27]. After digestion, the extracts were lyophilized, and 218 mg powder with 50 μmol sulforaphane was packed into capsules-the patients took 4 capsules daily [24,27]. In contrast, our capsules had a higher volume, with approximately 400 mg powder, and had a lower sulforaphane content of 6 mg (34 μmol) but contained approximately 12 mg (27 μmol) glucoraphanin-the patients took 15 capsules throughout the day.…”

“…The sulforaphane-rich extracts were considered safe because no grade 3 adverse events occurred. Prior studies with similar concentrations of broccoli sprout extracts confirmed that these sulforaphane concentrations are safe for patients [25][26][27]. A recent study in 2018 by Tahata et al [27] evaluated comparable broccoli sprout extracts in 17 patients with atypical nevi that received 50, 100 or 200 μmol sulforaphane for 28 days.…”

Chemoprevention agents for melanoma: A path forward into phase 3 clinical trials

“…The study indicated that oral sulforaphane is well tolerated at daily doses up to 200 μmol and achieves dose-dependent levels in plasma and skin. 135…”