title: A diet rich in high-glucoraphanin broccoli interacts with genotype to reduce discordance in plasma metabolite profiles by modulating mitochondrial function.
abstract: BACKGROUND
  Observational and experimental studies suggest that diets rich in cruciferous vegetables and glucosinolates may reduce the risk of cancer and cardiovascular disease (CVD).
  
  
  OBJECTIVE
  We tested the hypothesis that a 12-wk dietary intervention with high-glucoraphanin (HG) broccoli would modify biomarkers of CVD risk and plasma metabolite profiles to a greater extent than interventions with standard broccoli or peas.
  
  
  METHODS
  Subjects were randomly assigned to consume 400 g standard broccoli, 400 g HG broccoli, or 400 g peas each week for 12 wk, with no other dietary restrictions. Biomarkers of CVD risk and 347 plasma metabolites were quantified before and after the intervention.
  
  
  RESULTS
  No significant differences in the effects of the diets on biomarkers of CVD risk were found. Multivariate analyses of plasma metabolites identified 2 discrete phenotypic responses to diet in individuals within the HG broccoli arm, differentiated by single nucleotide polymorphisms associated with the PAPOLG gene. Univariate analysis showed effects of sex (P < 0.001), PAPOLG genotype (P < 0.001), and PAPOLG genotype × diet (P < 0.001) on the plasma metabolic profile. In the HG broccoli arm, the consequence of the intervention was to reduce variation in lipid and amino acid metabolites, tricarboxylic acid (TCA) cycle intermediates, and acylcarnitines between the 2 PAPOLG genotypes.
  
  
  CONCLUSIONS
  The metabolic changes observed with the HG broccoli diet are consistent with a rebalancing of anaplerotic and cataplerotic reactions and enhanced integration of fatty acid β-oxidation with TCA cycle activity. These modifications may contribute to the reduction in cancer risk associated with diets that are rich in cruciferous vegetables. This trial was registered at clinicaltrials.gov as NCT01114399.
authors: Food and Health Programme, Institute of Food Research, Norwich Research Park, Norwich, United Kingdom.
authors: Charlotte N
authors: CN
authors: Armah
authors: Maria H
authors: MH
authors: Traka
authors: Jack R
authors: JR
authors: Dainty
authors: Marianne
authors: M
authors: Defernez
authors: Astrid
authors: A
authors: Janssens
authors: Wing
authors: W
authors: Leung
authors: Joanne F
authors: JF
authors: Doleman
authors: John F
authors: JF
authors: Potter
authors: Richard F
authors: RF
authors: Mithen
mesh_terms: D000368:Aged; D000596:Amino Acids / Q000097:blood; D015415:Biomarkers; D001937:Brassica / Q000737:chemistry*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology / Q000235:genetics; D004032:Diet; D005260:Female; D005838:Genotype; D005961:Glucosinolates / Q000494:pharmacology*; D006801:Humans; D007096:Imidoesters / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D015999:Multivariate Analysis; D009713:Nucleotidyltransferases / Q000235:genetics*; D010091:Oximes; D010936:Plant Extracts / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D013454:Sulfoxides
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D005961:Glucosinolates; D007096:Imidoesters; D008055:Lipids; D010091:Oximes; D010936:Plant Extracts; D013454:Sulfoxides; D009713:Nucleotidyltransferases; C119494:glucoraphanin
references: Free Radic Res. 2011 Jan;45(1):29-36
references: 21110783
references: Cancer Sci. 2013 Aug;104(8):1067-73
references: 23679348
references: J Clin Biochem Nutr. 2008 Jul;43(1):1-5
references: 18648653
references: Nat Commun. 2012 Mar 27;3:758
references: 22453831
references: Pharm Res. 2013 Sep;30(9):2248-59
references: 23468051
references: J Nutr Biochem. 2011 May;22(5):426-40
references: 20655719
references: Heart. 2005 Dec;91 Suppl 5:v1-52
references: 16365341
references: Obesity (Silver Spring). 2010 Sep;18(9):1695-700
references: 20111019
references: J Nutr. 2009 Jun;139(6):1073-81
references: 19369366
references: J Natl Cancer Inst. 2007 Aug 1;99(15):1200-9
references: 17652276
references: Free Radic Biol Med. 2005 Jan 1;38(1):70-7
references: 15589373
references: Am J Clin Nutr. 2007 Sep;86(3):752-8
references: 17823442
references: Am J Epidemiol. 2007 Jul 1;166(1):62-70
references: 17456477
references: BMJ. 1995 Jan 21;310(6973):170
references: 7833759
references: Int J Cancer. 2012 Jul 1;131(1):201-10
references: 21823116
references: Lancet. 2000 Aug 26;356(9231):724-9
references: 11085692
references: Carcinogenesis. 2009 Jun;30(6):1024-31
references: 19386581
references: World J Urol. 2013 Feb;31(1):127-33
references: 22391648
references: J Biol Chem. 2001 Sep 7;276(36):33504-11
references: 11431479
references: Cancer Epidemiol Biomarkers Prev. 2003 Dec;12(12):1403-9
references: 14693729
references: Cancer Epidemiol Biomarkers Prev. 2000 Oct;9(10):1017-20
references: 11045782
references: Anal Chem. 2009 Aug 15;81(16):6656-67
references: 19624122
references: Plant Cell. 2011 Jul;23(7):2483-97
references: 21803940
references: Int J Cancer. 2012 Jun 15;130(12):2791-800
references: 21732340
references: Nature. 2005 Sep 15;437(7057):436-9
references: 16079795
references: Bioinformatics. 2010 Jan 15;26(2):242-9
references: 19906825
references: Am J Clin Nutr. 2005 Dec;82(6):1283-91
references: 16332662
references: Cancer Epidemiol Biomarkers Prev. 2010 Oct;19(10):2534-40
references: 20841387
references: BMJ. 1998 Apr 18;316(7139):1236-8
references: 9553006
references: Ann Oncol. 2012 Aug;23(8):2198-2203
references: 22328735
references: Cell Metab. 2008 Jan;7(1):45-56
references: 18177724
references: Am J Clin Nutr. 2011 Jul;94(1):240-6
references: 21593509
references: Cell. 2010 Mar 5;140(5):744-52
references: 20211142
references: Int J Urol. 2012 Feb;19(2):134-41
references: 22121852
references: J Proteome Res. 2012 Nov 2;11(11):5503-14
references: 23046364
references: Free Radic Biol Med. 2004 Nov 15;37(10):1578-90
references: 15477009
references: Metabolomics. 2013 Apr;9(2):506-514
references: 23543136
references: New Phytol. 2013 Jun;198(4):1085-1095
references: 23560984
references: J Dairy Sci. 2005 Jun;88(6):2017-26
references: 15905432
references: Crit Rev Food Sci Nutr. 2011 Apr;51(4):363-73
references: 21432699
references: Cell Mol Life Sci. 2007 May;64(9):1105-27
references: 17396224
references: Proc Natl Acad Sci U S A. 2004 May 4;101(18):7094-9
references: 15103025
references: Biochem Biophys Res Commun. 2012 Oct 5;426(4):492-7
references: 22982310
references: Ann Oncol. 2013 Apr;24(4):1079-87
references: 23211939
references: Biochem Biophys Res Commun. 1995 May 25;210(3):966-73
references: 7763270
references: Cancer Epidemiol Biomarkers Prev. 2001 Oct;10(10):1063-7
references: 11588132
references: Carcinogenesis. 2002 Dec;23(12):2055-61
references: 12507929
references: Biofactors. 2004;22(1-4):271-5
references: 15630296
references: Nutr Res Rev. 2011 Jun;24(1):60-71
references: 24725925
references: Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2399-403
references: 1549603
references: Br J Nutr. 2013 Nov;110(10):1760-70
references: 23657156