Osteoarthritis is a major cause of disability and there is no current pharmaceutical treatment which can prevent the disease or slow its progression. Dietary advice or supplementation is clearly an attractive option since it has low toxicity and ease of implementation on a population level. We have previously demonstrated that sulforaphane, a dietary isothiocyanate derived from its glucosinolate precursor which is found in broccoli, can prevent cartilage destruction in cells, in in vitro and in vivo models of osteoarthritis. As the next phase of this research, we enrolled 40 patients with knee osteoarthritis undergoing total knee replacement into a proof-of-principle trial. Patients were randomised to either a low or high glucosinolate diet for 14 days prior to surgery. We detected ITCs in the synovial fluid of the high glucosinolate group, but not the low glucosinolate group. This was mirrored by an increase in ITCs and specifically sulforaphane in the plasma. Proteomic analysis of synovial fluid showed significantly distinct profiles between groups with 125 differentially expressed proteins. The functional consequence of this diet will now be tested in a clinical trial.Osteoarthritis (OA) of the hip or knee is ranked as 11 th of 291 conditions that contribute to global disability; and the consequent years lived with disability (YLDs) are estimated to have risen by 61% from 1990-2010 1 . There are no disease-modifying OA drugs (DMOADs) currently available, and pharmacological interventions provide symptomatic relief only, which is frequently insufficient 2, 3 .The National Institute for Health and Care Excellence (NICE) and the American College of Rheumatology both recommend OA management strategies based upon activity and exercise, and weight loss if overweight or obese. A third core treatment area recommended by NICE focuses on information to support self-management 4, 5 . Within these core treatment areas, dietary and exercise advice have been identified as cost effective approaches to the treatment of OA 6 .We and others have shown previously that sulforaphane (1-isothiocyanato-4-methylsulfinylbutane, SFN) is a chondroprotective agent in vitro and in vivo [7][8][9][10] . SFN is derived from a precursor, glucoraphanin, gained from eating brassicas, particularly broccoli. Sulforaphane has broad biological activity and its role in joint health was recently reviewed 11 . SFN can repress the expression of key metalloproteinases implicated in OA 7, 10 , regulate NF-κB and Nrf2 signalling, inhibit production of prostaglandin E2 and nitric oxide in chondrocytes 7, 9, 10 and prevent cytokine-induced cartilage destruction in vitro 9,10 . In vivo, SFN reduces cartilage destruction in the 'destabilisation of the medial meniscus' (DMM) murine model of OA 10 and inhibits synovial hyperplasia in collagen-induced arthritis (CIA) 8 . Nrf2 knockout mice also showed increased cartilage lesions and oxidative damage in antibody-induced arthritis (AIA) 12 .The pharmacokinetics of SFN has been studied, with one report measuring t...