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Cruciferous vegetables have variable effects on biomarkers of systemic inflammation in a randomized controlled trial
Sandi L Navarro1, Yvonne Schwarz2, Xiaoling Song2
1Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA; snavarro@fhcrc.org.
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.
Insights
Consumption of cruciferous and apiaceous vegetables lowered interleukin-6 (IL-6) levels in healthy adults. However, effects on other inflammation biomarkers varied, and responses were dependent on glutathione S-transferase (GST) M1 and GSTT1 genetic variations.
Area of Science:
- Nutritional Immunology
- Cancer Prevention Research
- Human Nutrition
Background:
- Isothiocyanates from cruciferous vegetables influence key signaling pathways in carcinogenesis, such as NF-κB, a central inflammation regulator.
- Genetic variations in glutathione S-transferase (GST) enzymes (GSTM1 and GSTT1) affect the metabolism of isothiocyanates, potentially altering biological responses.
Purpose of the Study:
- To investigate if consuming cruciferous and/or apiaceous vegetables impacts serum concentrations of key inflammatory markers: IL-6, IL-8, CRP, TNF-α, and soluble TNF receptors.
- To determine if these dietary effects on inflammation markers are influenced by the individual's GSTM1/GSTT1 genotype.
Main Methods:
- A randomized crossover trial involving 63 healthy adults (20-40 years) consuming four controlled diets over 14-day periods with 21-day washout intervals.
- Diets included: basal (vegetable-free), single-dose cruciferous (1xC), double-dose cruciferous (2xC), and cruciferous plus apiaceous vegetables (1xC+A).
- Measurements included serum inflammatory biomarkers, urinary isothiocyanate excretion, and GSTM1/GSTT1 genotype analysis.
Main Results:
- Consumption of 2xC and 1xC+A diets significantly reduced IL-6 concentrations compared to the basal diet.
- The 1xC+A diet increased IL-8 concentrations, while no significant effects were observed for CRP, TNF-α, or sTNFRs.
- Individuals with GSTM1-null/GSTT1+ genotype showed significant reductions in CRP, IL-6, and IL-8 with the 1xC+A diet, and reductions in IL-8 and sTNFR1 with the 2xC diet, which were not observed in other genotypes.
Conclusions:
- Dietary intake of cruciferous and apiaceous vegetables effectively reduced circulating IL-6 levels in young, healthy individuals.
- The impact of these vegetables on other inflammation biomarkers was inconsistent and appeared to be modulated by GSTM1/GSTT1 genetic polymorphisms.
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