title: Cruciferous vegetables have variable effects on biomarkers of systemic inflammation in a randomized controlled trial in healthy young adults.
abstract: BACKGROUND
  Isothiocyanates in cruciferous vegetables modulate signaling pathways critical to carcinogenesis, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a central regulator of inflammation. Glutathione S-transferase (GST) M1 and GSTT1 metabolize isothiocyanates; genetic variants may result in differences in biologic response.
  
  
  OBJECTIVE
  The objective of this study was to test whether consumption of cruciferous or cruciferous plus apiaceous vegetables altered serum concentrations of interleukin (IL)-6, IL-8, C-reactive protein (CRP), tumor necrosis factor (TNF) α, and soluble TNF receptor (sTNFR) I and II, and whether this response was GSTM1/GSTT1 genotype dependent.
  
  
  METHODS
  In a randomized crossover trial, healthy men (n = 32) and women (n = 31) aged 20-40 y consumed 4 14-d controlled diets: basal (vegetable-free), single-dose cruciferous (1xC) [7 g vegetables/kg body weight (BW)], double-dose cruciferous (2xC) (14 g/kg BW), and cruciferous plus apiaceous (carrot family) (1xC+A) vegetables (7 and 4 g/kg BW, respectively), with a 21-d washout period between each intervention. Urinary isothiocyanate excretion was also evaluated as a marker of systemic isothiocyanate exposure. Fasting morning blood and urine samples were collected on days 0 and 14 and analyzed.
  
  
  RESULTS
  IL-6 concentrations were significantly lower on day 14 of the 2xC and 1xC+A diets than with the basal diet [-19% (95% CI: -30%, -0.1%) and -20% (95% CI: -31%, -0.7%), respectively]. IL-8 concentrations were higher after the 1xC+A diet (+16%; 95% CI: 4.2%, 35.2%) than after the basal diet. There were no effects of diet on CRP, TNF-α, or sTNFRI or II. There were significant differences between GSTM1-null/GSTT1+ individuals for several biomarkers in response to 1xC+A compared with basal diets (CRP: -37.8%; 95% CI: -58.0%, -7.4%; IL-6: -48.6%; 95% CI: -49.6%, -12.0%; IL-8: 16.3%; 95% CI: 6.7%, 57.7%) and with the 2xC diet compared with the basal diet (IL-8: -33.2%; 95% CI: -43.0%, -1.4%; sTNFRI: -7.5%; 95% CI: -12.7%, -2.3%). There were no significant reductions in biomarker concentrations in response to diet among GSTM1+/GSTT1+ or GSTM1-null/GSTT1-null individuals. Twenty-four-hour urinary isothiocyanate excretion was not associated with any of the inflammation markers overall; however, IL-6 was inversely associated with total isothiocyanate excretion in GSTM1-null/GSTT1-null individuals (β = -0.12; 95% CI: -0.19, -0.05).
  
  
  CONCLUSIONS
  In this young, healthy population, consumption of cruciferous and apiaceous vegetables reduced circulating IL-6; however, results for other biomarkers of inflammation were not consistent.
authors.affiliation: Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA; snavarro@fhcrc.org.
authors.forename: Sandi L
authors.initials: SL
authors.lastname: Navarro
authors.affiliation: Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA;
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Schwarz
authors.affiliation: Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA;
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Song
authors.affiliation: Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA;
authors.forename: Ching-Yun
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA;
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN; and.
authors.forename: Sabrina P
authors.initials: SP
authors.lastname: Trudo
authors.affiliation: Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA;
authors.forename: Alan R
authors.initials: AR
authors.lastname: Kristal
authors.affiliation: Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA;
authors.forename: Mario
authors.initials: M
authors.lastname: Kratz
authors.affiliation: Environmental and Occupational Health Sciences, University of Washington, Seattle, WA.
authors.forename: David L
authors.initials: DL
authors.lastname: Eaton
authors.affiliation: Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA;
authors.forename: Johanna W
authors.initials: JW
authors.lastname: Lampe
mesh_terms: D000328:Adult; D015415:Biomarkers; D019607:Brassicaceae; D018592:Cross-Over Studies; D004032:Diet; D005260:Female; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000378:metabolism*; D008297:Male; D014675:Vegetables; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1