Abstract
There is robust epidemiological evidence for the beneficial effects of broccoli consumption on health, many of them clearly mediated by the isothiocyanate sulforaphane. Present in the plant as its precursor, glucoraphanin, sulforaphane is formed through the actions of myrosinase, a β-thioglucosidase present in either the plant tissue or the mammalian microbiome. Since first isolated from broccoli and demonstrated to have cancer chemoprotective properties in rats in the early 1990s, over 3000 publications have described its efficacy in rodent disease models, underlying mechanisms of action or, to date, over 50 clinical trials examining pharmacokinetics, pharmacodynamics and disease mitigation. This review evaluates the current state of knowledge regarding the relationships between formulation (e.g., plants, sprouts, beverages, supplements), bioavailability and efficacy, and the doses of glucoraphanin and/or sulforaphane that have been used in pre-clinical and clinical studies. We pay special attention to the challenges for better integration of animal model and clinical studies, particularly with regard to selection of dose and route of administration. More effort is required to elucidate underlying mechanisms of action and to develop and validate biomarkers of pharmacodynamic action in humans. A sobering lesson is that changes in approach will be required to implement a public health paradigm for dispensing benefit across all spectrums of the global population.
Highlights
In addition to their role in plant defense, high levels of isothiocyanates have been shown to reduce the biomass of the plant, and interestingly, mutants deficient in glutathione biosynthesis are more susceptible than their wild-type counterparts to the growth-inhibitory effect sulforaphane [33], suggesting similarities in sulforaphane metabolism in plants and mammals
Glucoraphanin occurs in all tissues of broccoli plants, though it is most abundant in the aerial portions and the developing florets and the seeds, are richest in this compound (Figure 1)
12-week placebo-controlled, randomized clinical trial involving 291 participants from the same area using broccoli sprout beverages containing a combination of 40 μmol sulforaphane and 600 μmol glucoraphanin confirmed and extended these findings by showing that the excretion levels of the glutathione-derived conjugates of benzene and acrolein were significantly increased, by 61% and 23%, respectively in the volunteers who received the broccoli sprout beverage compared with placebo [78]
Summary
The collective retrospective (observational), prospective, and interventional evidence for the beneficial effects of broccoli on health is robust. The former two categories will be briefly summarized and the latter make up the bulk of this review. Since there have been impressive demonstrations of risk reduction associated with cruciferous vegetables and/or broccoli for bladder cancer [3] and prostate cancer [4] just to name a few. We and others have recently reviewed the growing body of epidemiologic and mechanistic work implicating cruciferous vegetables in general, broccoli and sulforaphane, with respect to its association with neurologic, neoplastic, dermatologic, and other conditions (e.g., [5,6,7,8,9]). All evidence points to broccoli and to sulforaphane from broccoli, and its biogenic precursor glucoraphanin, as being protective against a variety of chronic, and even infectious (e.g., Helicobacter pylori) conditions [11]
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