Sulforaphane

Sulforaphane is an isothiocyanate occurring in stored form as glucoraphanin in cruciferous vegetables such as cabbage, cauliflower, and kale, and at high levels in broccoli, especially broccoli sprouts. ^[1] Glucoraphanin requires the plant enzyme myrosinase to be converted into sulforaphane, and sulforaphane is metabolized through the mercapturic acid pathway by conjugation with glutathione. ^[1] Sulforaphane is an organosulfur compound categorized as an isothiocyanate, with the molecular formula C6H11NOS2. ^[2]

Sulforaphane activates the antioxidant and anti-inflammatory responses by inducing the Nrf2 pathway and inhibiting NF-kB. ^[3] It also has an epigenetic effect by inhibiting histone deacetylase and DNA methyltransferases and modifies mitochondrial dynamics. ^[3] Sulforaphane preserves proteome homeostasis by activating the proteasome, which has been shown to lead to increased cellular lifespan and prevent neurodegeneration. ^[3]

Since sulforaphane was first isolated from broccoli and shown to have cancer chemoprotective properties in rats in the early 1990s, over 3000 publications have described its efficacy in rodent disease models and over 50 clinical trials have examined its pharmacokinetics, pharmacodynamics, and disease mitigation. ^[4] Preclinical evidence supports an active role of sulforaphane in activating Nrf2 or modulating AMP-activated protein kinase to protect against diabetic complications, with clinical evidence suggesting that sulforaphane-rich foods like broccoli can improve metabolic status in patients with type 2 diabetes. ^[5] In a network meta-analysis of dietary-supplement treatments for autism spectrum disorder, there were indications of improvement by sulforaphane, yet the estimates were imprecise and not robust and confidence in them was very low or low. ^[6] A systematic review of experimental psychopharmacology for autism spectrum disorder concluded that sulforaphane is among a small subset of compounds that may already be considered, with due caution, for clinical use because there is promising evidence of efficacy and a high safety profile. ^[7]

Sulforaphane is described as a promising geroprotector, an agent capable of delaying aging and mitigating age-related diseases through antioxidant and anti-inflammatory properties and induction of autophagy. ^[8] A challenge for sulforaphane application is its weak solubility in water and limited bioavailability, and better integration of animal-model and clinical studies plus validated pharmacodynamic biomarkers in humans is still required. ^{[2] [4]} Sulforaphane activation of the Nrf-2/ARE pathway is an example of a phytochemical inducing an adaptive cellular stress response, or hormesis, at low doses. ^[9]