- Email: [email protected]
Does broccoli protect from osteoarthritis?
Joint Bone Spine 81 (2014) 284–286
Available online at www.sciencedirect.com
Editorial
Does broccoli protect from osteoarthritis?
a r t i c l e
i n f o
Keywords: Osteoarthritis Phytotherapy Broccoli Sulforaphane Antioxidants Nrf2 Vegetables Crucifers
1. Introduction “Don’t eat too much fat, sugar, or salt”, “Eat at least five helpings of fruit and vegetables every day”, “Don’t nibble between meals”, and on and on. . . All these messages issued by public health organizations then amplified by the lay media are based on sound evidence that a well-balanced diet is beneficial in various health conditions such as cancer, cardiovascular disease, diabetes, and osteoporosis. However, what we choose to eat also depends on our beliefs, our culture and our environment; and feelings of guilt, anxiety, and confusion may therefore arise when we look at what we have put on our plate. Each new public health nutritional message initially generates a burst of hope in our ability to diminish our risk of disease and/or to increase our life expectancy. Then, when the time for lunch or dinner comes around, we rapidly tend to rebel against the new diktat. The scientific literature can provide enough evidence to support the intake of one food or another with the goal of decreasing the risk or progression of the diseases falling within the purview of each medical specialty. The result may well be a severe case of indigestion. Among rheumatology patients, those with gout will have to stay away from red wine and red meat, those with osteoporosis will be admonished to develop a strong liking for milk and cheese, those with rheumatoid arthritis will force-feed themselves with omega-3-rich fish oils (at the cost of bad breath), and those with osteoarthritis will be expected to know the exact calorie count of each of their meals in the hope of losing the extra weight that at least partially explains their pain and functional impairments. Should we now also recommend broccoli, an undoubtedly lovely vegetable that may nevertheless prove challenging to incorporate into a gourmet meal, based on the very recent publication of a study in a preclinical model of osteoarthritis [1]?
2. Clinical trials A few epidemiological and therapeutic investigations have evaluated the potential benefits from high intakes of broccoli and other cruciferous vegetables (kale, bok choi, cauliflower, Brussels sprouts, chards, spinach, turnips, and, rutabaga). Most of these studies focused on cancer. Eating broccoli at least once a week was reported to decrease the risk of aggressive prostate cancer by 45% [2]. Similarly, a daily intake of at least 25 g of cruciferous vegetables may decrease the risk of stomach cancer by nearly one-fourth [3]. A pilot study in healthy volunteers suggested that eating 14 to 56 g of broccoli twice a day for 7 consecutive days might eradicate Helicobacter pylori from the stomach [4]. The first randomized controlled trial of potential benefits from eating broccoli assessed effects on breastfeeding and found that the application of cabbage leaves to the breasts increased the frequency of successful breastfeeding and diminished perceptions of breast engorgement [5]. The failure of this trial to generate enthusiasm is probably ascribable to the absence of double-blinding and to the failure of cabbage leaf extract to induce similar benefits in another study [6]. The belief in some populations that the roots of certain cruciferous vegetables have aphrodisiac effects prompted a placebo-controlled trial in men with erectile dysfunction, who reported subjective improvements [7]. The ingestion of 10 g/d of broccoli sprouts for 4 weeks decreased insulin resistance and improved lipid parameters in patients with type 2 diabetes mellitus [8,9]. In contrast, broccoli sprouts failed to improve endothelial dysfunction in patients with hypertension [10]. Cruciferous vegetables contain high concentrations of vitamin K, and their ingestion in large amounts may therefore be hazardous in patients on oral vitamin K antagonist therapy [11]. Finally, although adverse effects on thyroid dysfunction have been convincingly demonstrated in cattle but not replicated in humans, keeping the intake of cruciferous vegetables within reasonable bounds is probably advisable in patients with thyroid dysfunction [12]. Of note, 15 or so clinical studies had already been registered on www.clinicaltrials.gov (indexing term, “broccoli sprout”) on February 27, 2014 and are currently at the patient recruitment phase, chiefly in the field of oncology.
3. Potential mechanisms of action of broccoli The mechanisms by which broccoli might exert beneficial health effects include the high concentrations of micronutrients such as folic acid and vitamin C found in cruciferous vegetables. More importantly, cruciferous vegetables generate bioactive compounds
doi:10.1016/j.jbspin.2014.04.001 1297-319X/© 2014 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
Editorial / Joint Bone Spine 81 (2014) 284–286
285
Fig. 1. Chemical components in broccoli. Glucosinolate, a secondary metabolite of cruciferous vegetables (responsible for their well-known bitter taste) is converted to isothiocyanates (including sulforaphane, a biologically active compound) under the effect of the enzyme myrosinase.
belonging to the isothiocyanate family, most notably sulforaphane, which is produced in young sprouts from glucoraphanins under the effect of myrosinases (Fig. 1). Sulforaphane can activate the expression of genes that are dependent on Nrf2, a transcription factor reported to activate cell defence mechanisms and to increase cell longevity by decreasing the deleterious intracellular effects of oxidative stress [13,14]. These mechanisms may explain the anticancer and anti-inflammatory effects ascribed to broccoli. Nrf2 activation by sulforaphane may underlie the improvement in immune defences reported in chronic obstructive pulmonary disease [15]. Sulforaphane dampens certain autoimmunity-related effects, in particular by acting on the Th17 and IL-10 pathways [16]. More broadly, sulforaphane has demonstrated anti-inflammatory effects in preclinical models of inflammation affecting the brain, skin, kidneys, heart, lungs and, as discussed below, joints [17]. Sulforaphane also acts on a number of metabolic pathways involved in obesity [18]. In a rat model, sulforaphane decreased both blood pressure elevation and atherosclerosis by diminishing the degree of endothelial oxidative stress [19]. 4. Broccoli and rheumatoid arthritis (RA) A handful of studies assessed sulforaphane in rheumatoid arthritis (RA). The severity of collagen-induced arthritis in a murine model decreased after the intraperitoneal administration of sulforaphane [20]. In a similar model, the cartilage lesions were more severe in Nrf2-knockout mice than in wild-type mice [21]. Sulforaphane induces the apoptosis of synoviocytes from RA patients by modulating the expression of Bcl-2/Bax, p53, and pAkt [20]. Additional effects are inhibition of T-cell proliferation and decreased IL-17 and TNF␣ production by CD4+ T-cells. Sulforaphane counteracts the proliferative-inducing effects of TNF␣ in a human synoviocyte line [22]. To my knowledge, no published clinical trials have assessed the potential effects of any of the broccoli compounds in RA. 5. Broccoli and osteoarthritis A surprising publication in the British Medical Journal in 2003 suggests that the local application of cabbage leaves can relieve inflammation in any body part (Fig. 2) [23]. The first adequately designed study assessing the potential benefits of sulforaphane in osteoarthritis was published in 2013 [1]. Sulforaphane inhibited the expression of metallo-proteases induced by pro-inflammatory cytokines in articular chondrocytes and human fibroblast-like synovial cells. Furthermore, adding sulforaphane to bovine cartilage explants exposed to pro-inflammatory cytokines lessened the level of cartilage breakdown. Interestingly, these effects seemed independent from Nrf2, being instead mediated by the JNK, p38
Fig. 2. Use in traditional medicine of a cabbage leaf applied locally to relieve knee osteoarthritis.
MAPK, and NFB signaling pathways. In mice with osteoarthritis induced by destabilization of the medial meniscus (DMM model), a sulforaphane-rich diet (3 moles/day) significantly decreased the osteoarthritis score. This innovative preclinical study suggests new avenues for developing treatments based on neutraceuticals. A neutraceutical is any compound isolated or purified from food, commercially available as tablets or other pharmaceutical formulations, and inducing beneficial effects on the body, most notably in the treatment of chronic diseases. Several neutraceuticals are already on the market for osteoarthritis, and debates about their efficacy are steadily gaining momentum [24]. Regarding broccoli, an obvious issue is whether the high sulforaphane concentrations used in published in vitro or ex vivo studies can be achieved by eating broccoli (particularly the young sprouts, whose sulforaphane content is particularly high). The amount that a person might accept to eat seems too small to achieve the necessary local concentrations, despite astute efforts by manufacturers to produce genetically modified super-broccoli containing high levels of glucoraphanins [25,26]. Importantly, the effects obtained in mice required the daily ingestion of sulforaphane, which does not seem feasible in humans in the long term. A more reasonable approach may be to use capsules or powders containing glucoraphanins and the hydrolyzing enzyme myrosinase (as sulforaphane is not sufficiently stable clinically for use as a supplement). However, the large amounts of currently available capsules or powder that would have to be ingested to obtain effective tissue levels seem difficult to accept in everyday practice. New formulations for topical or intra-articular administration are being developed [27,28] and may not only improve bioavailability in the joint, but also minimize potential risks of thyroid dysfunction or of INR destabilization in patients on antivitamin K therapy. In conclusion, although encouragements to eat green vegetables in general and broccoli in particular are obviously beneficial, if only
286
Editorial / Joint Bone Spine 81 (2014) 284–286
by lessening our intake of fries and burgers, there does not seem to be enough evidence to date to support enthusiasm for cruciferous vegetables as a miracle cure for osteoarthritis. On the other hand, following on the traces of other phytotherapy products containing compounds active against rheumatic diseases [29], studies of active molecules contained in broccoli seem warranted in osteoarthritis, and the development of galenic forms for intra-articular administration holds special appeal [27]. Disclosure of interest The author declares that he has no conflicts of interest concerning this article. References [1] Davidson RK, Jupp O, de Ferrars R, et al. Sulforaphane represses matrixdegrading proteases and protects cartilage from destruction in vitro and in vivo. Arthritis Rheum 2013;65:3130–40. [2] Kirsh VA, Peters U, Mayne ST, et al. Prospective study of fruit and vegetable intake and risk of prostate cancer. J Natl Cancer Inst 2007;99:1200–9. [3] Steevens J, Schouten LJ, Goldbohm RA, et al. Vegetables and fruits consumption and risk of oesophageal and gastric cancer subtypes in the Netherlands Cohort Study. Int J Cancer 2011;129:2681–93. [4] Galan MV, Kishan AA, Silverman AL. Oral broccoli sprouts for the treatment of Helicobacter pylori infection: a preliminary report. Dig Dis Sci 2004;49:1088–90. [5] Nikodem VC, Danziger D, Gebka N, et al. Do cabbage leaves prevent breast engorgement? A randomized, controlled study. Birth (Berkeley, Calif) 1993;20:61–4. [6] Roberts KL, Reiter M, Schuster D. Effects of cabbage leaf extract on breast engorgement. J Hum Lact 1998;14:231–6. [7] Zenico T, Cicero AF, Valmorri L, et al. Subjective effects of Lepidium meyenii (Maca) extract on well-being and sexual performances in patients with mild erectile dysfunction: a randomised, double-blind clinical trial. Andrologia 2009;41:95–9. [8] Bahadoran Z, Mirmiran P, Hosseinpanah F, et al. Broccoli sprouts powder could improve serum triglyceride and oxidized LDL/LDL-cholesterol ratio in type 2 diabetic patients: a randomized double-blind placebo-controlled clinical trial. Diabetes Res Clin Pract 2012;96:348–54. [9] Bahadoran Z, Tohidi M, Nazeri P, et al. Effect of broccoli sprouts on insulin resistance in type 2 diabetic patients: a randomized double-blind clinical trial. Int J Food Sci Nutr 2012;63:767–71. [10] Christiansen B, Bellostas Muguerza N, Petersen AM, et al. Ingestion of broccoli sprouts does not improve endothelial function in humans with hypertension. PloS One 2010;5:e12461. [11] Bolton-Smith C, Price RJ, Fenton ST, et al. Compilation of a provisional UK database for the phylloquinone (vitamin K1) content of foods. Br J Nutr 2000;83:389–99. [12] McMillan M, Spinks EA, Fenwick GR. Preliminary observations on the effect of dietary brussels sprouts on thyroid function. Hum Toxicol 1986;5: 15–9. [13] Houghton CA, Fassett RG, Coombes JS. Sulforaphane: translational research from laboratory bench to clinic. Nutr Rev 2013;71:709–26.
[14] Jiang T, Tian F, Zheng H, et al. Nrf2 suppresses lupus nephritis through inhibition of oxidative injury and the NF-kappaB-mediated inflammatory response. Kidney Int 2014;85:333–43. [15] Harvey CJ, Thimmulappa RK, Sethi S, et al. Targeting Nrf2 signaling improves bacterial clearance by alveolar macrophages in patients with COPD and in a mouse model. Sci Transl Med 2011;3:78ra32. [16] Li B, Cui W, Liu J, et al. Sulforaphane ameliorates the development of experimental autoimmune encephalomyelitis by antagonizing oxidative stress and Th17-related inflammation in mice. Exp Neurol 2013. [17] Guerrero-Beltran CE, Calderon-Oliver M, Pedraza-Chaverri J, et al. Protective effect of sulforaphane against oxidative stress: recent advances. Exp Toxicol Pathol 2012;64:503–8. [18] Choi KM, Lee YS, Kim W, et al. Sulforaphane attenuates obesity by inhibiting adipogenesis and activating the AMPK pathway in obese mice. J Nutr Biochem 2014;25:201–7. [19] Wu L, Noyan Ashraf MH, Facci M, et al. Dietary approach to attenuate oxidative stress, hypertension, and inflammation in the cardiovascular system. Proc Nat Acad Sci U S A 2004;101:7094–9. [20] Kong JS, Yoo SA, Kim HS, et al. Inhibition of synovial hyperplasia, rheumatoid Tcell activation, and experimental arthritis in mice by sulforaphane, a naturally occurring isothiocyanate. Arthritis Rheum 2010;62:159–70. [21] Wruck CJ, Fragoulis A, Gurzynski A, et al. Role of oxidative stress in rheumatoid arthritis: insights from the Nrf2-knockout mice. Ann Rheum Dis 2011;70:844–50. [22] Fragoulis A, Laufs J, Muller S, et al. Sulforaphane has opposing effects on TNF-alpha stimulated and unstimulated synoviocytes. Arthritis Res Ther 2012;14:R220. [23] Munns A. Cabbage leaves can help inflammation of any body part. BMJ 2003;327:451. [24] Henrotin Y, Lambert C, Couchourel D, et al. Nutraceuticals: do they represent a new era in the management of osteoarthritis? A narrative review from the lessons taken with five products. Osteoarthritis Cartilage 2011;19:1–21. [25] Traka MH, Saha S, Huseby S, et al. Genetic regulation of glucoraphanin accumulation in Beneforté® broccoli. N Phytologist 2013;198:1085–95. [26] Crop sciences: Super-broccoli secret, solved. Nature 2013;499:9. [27] Ko JY, Choi YJ, Jeong GJ, et al. Sulforaphane-PLGA microspheres for the intraarticular treatment of osteoarthritis. Biomaterials 2013;34:5359–68. [28] Franklin SJ, Dickinson SE, Karlage KL, et al. Stability of sulforaphane for topical formulation. Drug Dev Ind Pharm 2014;40:494–502. [29] Adams M, Berset C, Kessler M, et al. Medicinal herbs for the treatment of rheumatic disorders–a survey of European herbals from the 16th and 17th century. J Ethnopharmacol 2009;121:343–59.
Francis Berenbaum a,b,∗ Sorbonne University, UPMC Université Paris 06, UMR S 938, 75005 Paris, France b DHU i2B, Department of Rheumatology, AP–HP, Saint-Antoine Hospital, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France a
Tel.: +33 149 282 520. E-mail address: [email protected] Accepted 24 March 2014 Available online 20 June 2014
Available online at www.sciencedirect.com
Editorial
Does broccoli protect from osteoarthritis?
a r t i c l e
i n f o
Keywords: Osteoarthritis Phytotherapy Broccoli Sulforaphane Antioxidants Nrf2 Vegetables Crucifers
1. Introduction “Don’t eat too much fat, sugar, or salt”, “Eat at least five helpings of fruit and vegetables every day”, “Don’t nibble between meals”, and on and on. . . All these messages issued by public health organizations then amplified by the lay media are based on sound evidence that a well-balanced diet is beneficial in various health conditions such as cancer, cardiovascular disease, diabetes, and osteoporosis. However, what we choose to eat also depends on our beliefs, our culture and our environment; and feelings of guilt, anxiety, and confusion may therefore arise when we look at what we have put on our plate. Each new public health nutritional message initially generates a burst of hope in our ability to diminish our risk of disease and/or to increase our life expectancy. Then, when the time for lunch or dinner comes around, we rapidly tend to rebel against the new diktat. The scientific literature can provide enough evidence to support the intake of one food or another with the goal of decreasing the risk or progression of the diseases falling within the purview of each medical specialty. The result may well be a severe case of indigestion. Among rheumatology patients, those with gout will have to stay away from red wine and red meat, those with osteoporosis will be admonished to develop a strong liking for milk and cheese, those with rheumatoid arthritis will force-feed themselves with omega-3-rich fish oils (at the cost of bad breath), and those with osteoarthritis will be expected to know the exact calorie count of each of their meals in the hope of losing the extra weight that at least partially explains their pain and functional impairments. Should we now also recommend broccoli, an undoubtedly lovely vegetable that may nevertheless prove challenging to incorporate into a gourmet meal, based on the very recent publication of a study in a preclinical model of osteoarthritis [1]?
2. Clinical trials A few epidemiological and therapeutic investigations have evaluated the potential benefits from high intakes of broccoli and other cruciferous vegetables (kale, bok choi, cauliflower, Brussels sprouts, chards, spinach, turnips, and, rutabaga). Most of these studies focused on cancer. Eating broccoli at least once a week was reported to decrease the risk of aggressive prostate cancer by 45% [2]. Similarly, a daily intake of at least 25 g of cruciferous vegetables may decrease the risk of stomach cancer by nearly one-fourth [3]. A pilot study in healthy volunteers suggested that eating 14 to 56 g of broccoli twice a day for 7 consecutive days might eradicate Helicobacter pylori from the stomach [4]. The first randomized controlled trial of potential benefits from eating broccoli assessed effects on breastfeeding and found that the application of cabbage leaves to the breasts increased the frequency of successful breastfeeding and diminished perceptions of breast engorgement [5]. The failure of this trial to generate enthusiasm is probably ascribable to the absence of double-blinding and to the failure of cabbage leaf extract to induce similar benefits in another study [6]. The belief in some populations that the roots of certain cruciferous vegetables have aphrodisiac effects prompted a placebo-controlled trial in men with erectile dysfunction, who reported subjective improvements [7]. The ingestion of 10 g/d of broccoli sprouts for 4 weeks decreased insulin resistance and improved lipid parameters in patients with type 2 diabetes mellitus [8,9]. In contrast, broccoli sprouts failed to improve endothelial dysfunction in patients with hypertension [10]. Cruciferous vegetables contain high concentrations of vitamin K, and their ingestion in large amounts may therefore be hazardous in patients on oral vitamin K antagonist therapy [11]. Finally, although adverse effects on thyroid dysfunction have been convincingly demonstrated in cattle but not replicated in humans, keeping the intake of cruciferous vegetables within reasonable bounds is probably advisable in patients with thyroid dysfunction [12]. Of note, 15 or so clinical studies had already been registered on www.clinicaltrials.gov (indexing term, “broccoli sprout”) on February 27, 2014 and are currently at the patient recruitment phase, chiefly in the field of oncology.
3. Potential mechanisms of action of broccoli The mechanisms by which broccoli might exert beneficial health effects include the high concentrations of micronutrients such as folic acid and vitamin C found in cruciferous vegetables. More importantly, cruciferous vegetables generate bioactive compounds
doi:10.1016/j.jbspin.2014.04.001 1297-319X/© 2014 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
Editorial / Joint Bone Spine 81 (2014) 284–286
285
Fig. 1. Chemical components in broccoli. Glucosinolate, a secondary metabolite of cruciferous vegetables (responsible for their well-known bitter taste) is converted to isothiocyanates (including sulforaphane, a biologically active compound) under the effect of the enzyme myrosinase.
belonging to the isothiocyanate family, most notably sulforaphane, which is produced in young sprouts from glucoraphanins under the effect of myrosinases (Fig. 1). Sulforaphane can activate the expression of genes that are dependent on Nrf2, a transcription factor reported to activate cell defence mechanisms and to increase cell longevity by decreasing the deleterious intracellular effects of oxidative stress [13,14]. These mechanisms may explain the anticancer and anti-inflammatory effects ascribed to broccoli. Nrf2 activation by sulforaphane may underlie the improvement in immune defences reported in chronic obstructive pulmonary disease [15]. Sulforaphane dampens certain autoimmunity-related effects, in particular by acting on the Th17 and IL-10 pathways [16]. More broadly, sulforaphane has demonstrated anti-inflammatory effects in preclinical models of inflammation affecting the brain, skin, kidneys, heart, lungs and, as discussed below, joints [17]. Sulforaphane also acts on a number of metabolic pathways involved in obesity [18]. In a rat model, sulforaphane decreased both blood pressure elevation and atherosclerosis by diminishing the degree of endothelial oxidative stress [19]. 4. Broccoli and rheumatoid arthritis (RA) A handful of studies assessed sulforaphane in rheumatoid arthritis (RA). The severity of collagen-induced arthritis in a murine model decreased after the intraperitoneal administration of sulforaphane [20]. In a similar model, the cartilage lesions were more severe in Nrf2-knockout mice than in wild-type mice [21]. Sulforaphane induces the apoptosis of synoviocytes from RA patients by modulating the expression of Bcl-2/Bax, p53, and pAkt [20]. Additional effects are inhibition of T-cell proliferation and decreased IL-17 and TNF␣ production by CD4+ T-cells. Sulforaphane counteracts the proliferative-inducing effects of TNF␣ in a human synoviocyte line [22]. To my knowledge, no published clinical trials have assessed the potential effects of any of the broccoli compounds in RA. 5. Broccoli and osteoarthritis A surprising publication in the British Medical Journal in 2003 suggests that the local application of cabbage leaves can relieve inflammation in any body part (Fig. 2) [23]. The first adequately designed study assessing the potential benefits of sulforaphane in osteoarthritis was published in 2013 [1]. Sulforaphane inhibited the expression of metallo-proteases induced by pro-inflammatory cytokines in articular chondrocytes and human fibroblast-like synovial cells. Furthermore, adding sulforaphane to bovine cartilage explants exposed to pro-inflammatory cytokines lessened the level of cartilage breakdown. Interestingly, these effects seemed independent from Nrf2, being instead mediated by the JNK, p38
Fig. 2. Use in traditional medicine of a cabbage leaf applied locally to relieve knee osteoarthritis.
MAPK, and NFB signaling pathways. In mice with osteoarthritis induced by destabilization of the medial meniscus (DMM model), a sulforaphane-rich diet (3 moles/day) significantly decreased the osteoarthritis score. This innovative preclinical study suggests new avenues for developing treatments based on neutraceuticals. A neutraceutical is any compound isolated or purified from food, commercially available as tablets or other pharmaceutical formulations, and inducing beneficial effects on the body, most notably in the treatment of chronic diseases. Several neutraceuticals are already on the market for osteoarthritis, and debates about their efficacy are steadily gaining momentum [24]. Regarding broccoli, an obvious issue is whether the high sulforaphane concentrations used in published in vitro or ex vivo studies can be achieved by eating broccoli (particularly the young sprouts, whose sulforaphane content is particularly high). The amount that a person might accept to eat seems too small to achieve the necessary local concentrations, despite astute efforts by manufacturers to produce genetically modified super-broccoli containing high levels of glucoraphanins [25,26]. Importantly, the effects obtained in mice required the daily ingestion of sulforaphane, which does not seem feasible in humans in the long term. A more reasonable approach may be to use capsules or powders containing glucoraphanins and the hydrolyzing enzyme myrosinase (as sulforaphane is not sufficiently stable clinically for use as a supplement). However, the large amounts of currently available capsules or powder that would have to be ingested to obtain effective tissue levels seem difficult to accept in everyday practice. New formulations for topical or intra-articular administration are being developed [27,28] and may not only improve bioavailability in the joint, but also minimize potential risks of thyroid dysfunction or of INR destabilization in patients on antivitamin K therapy. In conclusion, although encouragements to eat green vegetables in general and broccoli in particular are obviously beneficial, if only
286
Editorial / Joint Bone Spine 81 (2014) 284–286
by lessening our intake of fries and burgers, there does not seem to be enough evidence to date to support enthusiasm for cruciferous vegetables as a miracle cure for osteoarthritis. On the other hand, following on the traces of other phytotherapy products containing compounds active against rheumatic diseases [29], studies of active molecules contained in broccoli seem warranted in osteoarthritis, and the development of galenic forms for intra-articular administration holds special appeal [27]. Disclosure of interest The author declares that he has no conflicts of interest concerning this article. References [1] Davidson RK, Jupp O, de Ferrars R, et al. Sulforaphane represses matrixdegrading proteases and protects cartilage from destruction in vitro and in vivo. Arthritis Rheum 2013;65:3130–40. [2] Kirsh VA, Peters U, Mayne ST, et al. Prospective study of fruit and vegetable intake and risk of prostate cancer. J Natl Cancer Inst 2007;99:1200–9. [3] Steevens J, Schouten LJ, Goldbohm RA, et al. Vegetables and fruits consumption and risk of oesophageal and gastric cancer subtypes in the Netherlands Cohort Study. Int J Cancer 2011;129:2681–93. [4] Galan MV, Kishan AA, Silverman AL. Oral broccoli sprouts for the treatment of Helicobacter pylori infection: a preliminary report. Dig Dis Sci 2004;49:1088–90. [5] Nikodem VC, Danziger D, Gebka N, et al. Do cabbage leaves prevent breast engorgement? A randomized, controlled study. Birth (Berkeley, Calif) 1993;20:61–4. [6] Roberts KL, Reiter M, Schuster D. Effects of cabbage leaf extract on breast engorgement. J Hum Lact 1998;14:231–6. [7] Zenico T, Cicero AF, Valmorri L, et al. Subjective effects of Lepidium meyenii (Maca) extract on well-being and sexual performances in patients with mild erectile dysfunction: a randomised, double-blind clinical trial. Andrologia 2009;41:95–9. [8] Bahadoran Z, Mirmiran P, Hosseinpanah F, et al. Broccoli sprouts powder could improve serum triglyceride and oxidized LDL/LDL-cholesterol ratio in type 2 diabetic patients: a randomized double-blind placebo-controlled clinical trial. Diabetes Res Clin Pract 2012;96:348–54. [9] Bahadoran Z, Tohidi M, Nazeri P, et al. Effect of broccoli sprouts on insulin resistance in type 2 diabetic patients: a randomized double-blind clinical trial. Int J Food Sci Nutr 2012;63:767–71. [10] Christiansen B, Bellostas Muguerza N, Petersen AM, et al. Ingestion of broccoli sprouts does not improve endothelial function in humans with hypertension. PloS One 2010;5:e12461. [11] Bolton-Smith C, Price RJ, Fenton ST, et al. Compilation of a provisional UK database for the phylloquinone (vitamin K1) content of foods. Br J Nutr 2000;83:389–99. [12] McMillan M, Spinks EA, Fenwick GR. Preliminary observations on the effect of dietary brussels sprouts on thyroid function. Hum Toxicol 1986;5: 15–9. [13] Houghton CA, Fassett RG, Coombes JS. Sulforaphane: translational research from laboratory bench to clinic. Nutr Rev 2013;71:709–26.
[14] Jiang T, Tian F, Zheng H, et al. Nrf2 suppresses lupus nephritis through inhibition of oxidative injury and the NF-kappaB-mediated inflammatory response. Kidney Int 2014;85:333–43. [15] Harvey CJ, Thimmulappa RK, Sethi S, et al. Targeting Nrf2 signaling improves bacterial clearance by alveolar macrophages in patients with COPD and in a mouse model. Sci Transl Med 2011;3:78ra32. [16] Li B, Cui W, Liu J, et al. Sulforaphane ameliorates the development of experimental autoimmune encephalomyelitis by antagonizing oxidative stress and Th17-related inflammation in mice. Exp Neurol 2013. [17] Guerrero-Beltran CE, Calderon-Oliver M, Pedraza-Chaverri J, et al. Protective effect of sulforaphane against oxidative stress: recent advances. Exp Toxicol Pathol 2012;64:503–8. [18] Choi KM, Lee YS, Kim W, et al. Sulforaphane attenuates obesity by inhibiting adipogenesis and activating the AMPK pathway in obese mice. J Nutr Biochem 2014;25:201–7. [19] Wu L, Noyan Ashraf MH, Facci M, et al. Dietary approach to attenuate oxidative stress, hypertension, and inflammation in the cardiovascular system. Proc Nat Acad Sci U S A 2004;101:7094–9. [20] Kong JS, Yoo SA, Kim HS, et al. Inhibition of synovial hyperplasia, rheumatoid Tcell activation, and experimental arthritis in mice by sulforaphane, a naturally occurring isothiocyanate. Arthritis Rheum 2010;62:159–70. [21] Wruck CJ, Fragoulis A, Gurzynski A, et al. Role of oxidative stress in rheumatoid arthritis: insights from the Nrf2-knockout mice. Ann Rheum Dis 2011;70:844–50. [22] Fragoulis A, Laufs J, Muller S, et al. Sulforaphane has opposing effects on TNF-alpha stimulated and unstimulated synoviocytes. Arthritis Res Ther 2012;14:R220. [23] Munns A. Cabbage leaves can help inflammation of any body part. BMJ 2003;327:451. [24] Henrotin Y, Lambert C, Couchourel D, et al. Nutraceuticals: do they represent a new era in the management of osteoarthritis? A narrative review from the lessons taken with five products. Osteoarthritis Cartilage 2011;19:1–21. [25] Traka MH, Saha S, Huseby S, et al. Genetic regulation of glucoraphanin accumulation in Beneforté® broccoli. N Phytologist 2013;198:1085–95. [26] Crop sciences: Super-broccoli secret, solved. Nature 2013;499:9. [27] Ko JY, Choi YJ, Jeong GJ, et al. Sulforaphane-PLGA microspheres for the intraarticular treatment of osteoarthritis. Biomaterials 2013;34:5359–68. [28] Franklin SJ, Dickinson SE, Karlage KL, et al. Stability of sulforaphane for topical formulation. Drug Dev Ind Pharm 2014;40:494–502. [29] Adams M, Berset C, Kessler M, et al. Medicinal herbs for the treatment of rheumatic disorders–a survey of European herbals from the 16th and 17th century. J Ethnopharmacol 2009;121:343–59.
Francis Berenbaum a,b,∗ Sorbonne University, UPMC Université Paris 06, UMR S 938, 75005 Paris, France b DHU i2B, Department of Rheumatology, AP–HP, Saint-Antoine Hospital, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France a
Tel.: +33 149 282 520. E-mail address: [email protected] Accepted 24 March 2014 Available online 20 June 2014