Exploiting natural diversity the development of BeneforteTM broccoli Maria Traka Food and Health Programme Institute of Food Research UK Wednesday 18th November 2015 A brief summary of…. Plant and crop science What is so special about broccoli then…? IP and industry partners How do you make a better broccoli…? Cell and animal models How do you prove that is better…? Human studies Evidence for health benefit Epidemiological studies show... Reduction in cancer incidence and progression • Prostate • Colon • Lung • Kidney • Breast Richman et al. (2011) Vegetable and Fruit intake after diagnosis and risk of prostate cancer progression. International Journal of Cancer 10.1002/ijc.26348 Kirsh et al. (2007) Prospective study of fruit and vegetable intake and risk of prostate cancer. Journal National Cancer Institute 99, 1200 – 1209 Annema et al. (2011) Fruit and vegetable consumption and the risk of proximal colon, distal colon, and rectal cancers in a case-control study in Western Australia. J Am Diet Assoc. 2011 Oct;111(10):1479-90. Protection from cardiovascular disease Zhang et al (2011) Cruciferous vegetable consumption is associated with reduction in risk of total and cardiovascular disease mortality. AJCN 94, 240-6 Higher levels of consumption! Cruciferous vegetables 1.8 Prostate cancer progression Relative risk 1.6 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0 20 40 60 80 100 g/day Cruciferous vegetables mg/day 1 2 3 4 5 6 7 Portions per week Richman, E.L., P.R. Carroll, and J.M. Chan (2012) Vegetable and fruit intake after diagnosis and risk of prostate cancer progression. International Journal of Cancer 131(1):201-10 Cruciferous vegetables Minerals •Calcium •Potassium •Magnesium •Iron •Manganese •Zinc •Selenium Vitamins Polyphenols Organo-sulphur compounds •C, A, E, K, B1, B2 •Folates •Quercetin glycosides •Kaempferol glycosides •Chlorogenic acid •Sinapic acid •S-methyl cysteine sulphoxide •Glucosinolates 4-methylsylphinylbutyl glucosinolate – Glucoraphanin NOSO3 HO S S OH OH O O OH S N C S O 4-methylsylphinylbutyl isothiocyanate – Sulforaphane Bioactive in cell and animal models: • Inhibition of cancer cell growth • Anti-inflammatory properties • Induction of antioxidant defences Can we develop broccoli with enhanced health benefits? 1983 – collection of wild broccoli ancestors Wild members of the B.oleracea n=9 species complex are found on maritime cliffs of the Mediterranean and western Europe These taxa can be used as a source of novel traits for B.oleracea. Development of BeneforteTM broccoli Three fold increase in glucosinolates through introgression of novel alleles from wild Brassica species NOSO3 S O HO S OH OH O OH Functional food? Plant studies –characterisation and genetics Animal studies – mechanistic understanding Human studies – clinical effects and mechanisms Source of Myb28 Commercial hybrids are heterozygous for Myb28villosa Lines that are homozygous for Myb28villosa have seven fold increase in glucoraphainin Traka et al (2013) Genetic regulation of glucoraphanin accumulation in Beneforte broccoli. New Phytologist 198(4):1085-95 Metabolism & BASH studies – studies with CVD-relevant clinical endpoint • 133 Men and women • 50 – 80 years old • 10 – 30% risk of CVD T12 T0 12 weeks dietary intervention Analyses of plasma lipid metabolites and biomarkers of CVD risk Analyses of plasma lipid metabolites and biomarkers of CVD risk Metabolism & BASH studies – studies with CVD-relevant clinical endpoint serum LDL cholesterol was reduced by 5.8% (P=0.031) Standard broccoli n=67 Beneforte broccoli 2 0 -2 -4 -6 -8 -1 0 n=66 Change in % LDL Armah et al (2015) A diet rich in high glucoraphanin reduces plasma LDL cholesterol: evidence from randomised controlled trials. Molecular Nutrition and Food Research Can we prevent prostate cancer progression by Beneforte broccoli? Thanks to…… Richard Mithen Antonietta Melchini Charlotte Armah Shikha Saha Tharsini Sivapalan Omar Al Kadhi Richard Ball Robert Mills Professor Julie Lovegrove Dr Christos Derdemezis