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Int J Cancer. 2019 Apr 15;144(8):1918-1928. doi: 10.1002/ijc.31929. Epub 2018 Dec 7.

Investigating the effects of lycopene and green tea on the metabolome of men at risk of prostate cancer: The ProDiet randomised controlled trial.

Author information

1
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
2
Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom.
3
The National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, Upper Maudlin Street, Bristol, United Kingdom.
4
School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
5
Computational Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland.
6
NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
7
Systems Epidemiology, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
8
Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Victoria, Australia.
9
Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
10
Nightingale Health Ltd., Helsinki, Finland.
11
Bristol Randomised Trials Collaboration, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.

Abstract

Lycopene and green tea consumption have been observationally associated with reduced prostate cancer risk, but the underlying mechanisms have not been fully elucidated. We investigated the effect of factorial randomisation to a 6-month lycopene and green tea dietary advice or supplementation intervention on 159 serum metabolite measures in 128 men with raised PSA levels (but prostate cancer-free), analysed by intention-to-treat. The causal effects of metabolites modified by the intervention on prostate cancer risk were then assessed by Mendelian randomisation, using summary statistics from 44,825 prostate cancer cases and 27,904 controls. The systemic effects of lycopene and green tea supplementation on serum metabolic profile were comparable to the effects of the respective dietary advice interventions (R2 = 0.65 and 0.76 for lycopene and green tea respectively). Metabolites which were altered in response to lycopene supplementation were acetate [β (standard deviation difference vs. placebo): 0.69; 95% CI = 0.24, 1.15; p = 0.003], valine (β: -0.62; -1.03, -0.02; p = 0.004), pyruvate (β: -0.56; -0.95, -0.16; p = 0.006) and docosahexaenoic acid (β: -0.50; -085, -0.14; p = 0.006). Valine and diacylglycerol were lower in the lycopene dietary advice group (β: -0.65; -1.04, -0.26; p = 0.001 and β: -0.59; -1.01, -0.18; p = 0.006). A genetically instrumented SD increase in pyruvate increased the odds of prostate cancer by 1.29 (1.03, 1.62; p = 0.027). An intervention to increase lycopene intake altered the serum metabolome of men at risk of prostate cancer. Lycopene lowered levels of pyruvate, which our Mendelian randomisation analysis suggests may be causally related to reduced prostate cancer risk.

KEYWORDS:

Mendelian randomisation; dietary intervention; green tea; lycopene; prostate cancer

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