Investigating the effects of dietary and physical activity interventions on the metabolome of men with prostate cancer: The PrEvENT randomised controlled trial


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Meda R. Sandu1,Diana L. Santos Ferreira1,Rebecca Richmond1,Lucy Hackshaw-McGeagh1,Rhona Beynon1,Richard M. Martin2,J Athene Lane1
1University of Bristol,2university of Bristiol

Abstract

Background

Lycopene, plant-based diets (PBD) and physical activity (PA) have been previously associated with reduced risk and slower progression of prostate cancer (PCA), however, the potential mechanisms are not completely understood.

Method

We explored the effects of the PrEvENT randomised controlled trial (RCT) with a 6-month dietary (lycopene supplementation and PBD advice) and brisk walking(BW) intervention on 155 serum metabolites in 74 men with PCA who had undergone prostatectomy, using linear regression and instrumental variable (IV) analysis. One-stage-individual-participant meta-analysis was performed using a subset of data from ProDiet, an RCT of men with raised PSA levels but PCA free who were randomised to lycopene supplements (n=85). The causal effect of the metabolic traits on PCA was assessed by Mendelian Randomization (MR) on 44,825 cancer cases and 27,904 controls in the PRACTICAL consortium.

Results

The effects of lycopene supplementation and PBD advice on the serum metabolic profile were comparable (R2=.64).  There were no strong differences in metabolite levels in either the BW or the dietary intervention.  After adjustment for baseline metabolites, there was evidence for decreases of triglycerides in intermediate-density lipoproteins, large, medium and small low-density lipoproteins and saturated fatty acids (p<0.00385) in the BW arm. When accounting for the effect of the dietary intervention on serum lycopene (IV analysis), pyruvate decreased, and acetate increased (p-value<0.05).  After pooled meta-analysis with ProDiet, there was strong evidence (p-value<0.004) of decreased pyruvate and alanine, and increased acetate levels, in the lycopene arm. Using genetic instruments, the MR analysis showed evidence for a causal effect of pyruvate on PCA (OR 1.29, 95%CI 1.03-1.62).

Conclusion

The interventions to increase lycopene, PBD and PA altered the serum metabolome of men with PCA. BW improved the cardiometabolic profile; lycopene and PBD advice lowered pyruvate, which is known to be involved in cancer mechanisms and may be causally linked to PCA risk.