Variation of Serum Lycopene in Response to 100% Watermelon Juice: An Exploratory Analysis of Genetic Variants in a Randomized Controlled Crossover Study

Abstract

Background Watermelon, a rich source of lycopene, has garnered attention for cardioprotective effects including cholesterol reduction and promotion of redox balance. It is unknown whether 100% watermelon juice may represent a food-first approach to confer cardioprotective benefits of lycopene. Objectives This study examined influences of 100% watermelon juice on serum lycopene, lipids, and antioxidant capacity. Secondly, the study explored genetic influences on lycopene metabolism and bioavailability. Methods A placebo-controlled, randomized, double-blind, crossover trial with postmenopausal women (n = 16, mean ± SD age: 60 ± 4.1 y) assessed effects of 100% watermelon juice on mechanistic and clinical outcomes influencing vascular function. Participants maintained low-lycopene diets for a 1-wk run-in period and throughout the study. Morning and evening consumption of 100% watermelon juice provided a daily dose of 14.4 ± 0.34 mg lycopene. Study arms of 4 wk were separated by a 2-wk washout period. Saliva was collected for genetic analysis of single nucleotide polymorphisms, and fasting blood samples were taken pre– and post–study arms. Statistical analyses included mixed models, linear regression, and nonparametric tests. Results Serum lycopene exhibited a significant treatment effect (P = 0.002) along with notable interindividual responses; however, significant improvements in serum lipids or antioxidant capacity were not observed. Genetic variant rs6564851 in the β-carotene 15,15’-oxygenase-1 (BCO1) gene was associated with changes in lycopene such that TT homozygotes exhibited a significantly greater increase (β ± SE: 13.4 ± 1.6, P = 1.4 × 10−06). Conclusions Watermelon juice supplementation did not result in improvements in serum lipids or antioxidant capacity; however, results support findings in which watermelon juice significantly, yet differentially, increased circulating lycopene. Genetics appears to explain some of the variability. Given that dose has been shown to overcome individual responsiveness to lycopene interventions, future investigations with varying doses of lycopene-rich foods would be strengthened by genotyping so as to establish personalized nutrition recommendations. This trial was registered at clinicaltrials.gov as NCT03626168.

The Anticancer Potential of Plant-Derived Nutraceuticals via the Modulation of Gene Expression

“…Furthermore, there are several factors related to the characteristics of human subjects ingesting lycopene that have been reported to influence the bioavailability of this bioactive compound. Gender, adiposity, body mass index, and smoking habits appear to contribute to about 25% of the variation in serum lycopene concentrations [ 256 ]. In addition, there are studies to suggest that certain genetic variants linked to carotenoid metabolism may have an impact on lycopene bioavailability [ 256 , 257 , 258 ].…”

“…Gender, adiposity, body mass index, and smoking habits appear to contribute to about 25% of the variation in serum lycopene concentrations [ 256 ]. In addition, there are studies to suggest that certain genetic variants linked to carotenoid metabolism may have an impact on lycopene bioavailability [ 256 , 257 , 258 ]. For example, the single nucleotide polymorphism rs6564851 in the β-carotene 15,15′-oxygenase-1 (BCO1) gene, which encodes for the BCO1 enzyme responsible for carotenoid cleavage in mammals, has been reported as being significantly associated with changes in lycopene circulating levels [ 256 ].…”

Targeted capture sequencing identifies genetic variations of GRK4 and RDH8 in Han Chinese with essential hypertension in Xinjiang

“…RDH8 may participate in two biological processes, vitamin A metabolism and hypertension. Another interaction protein of RDH8, BCO1 (Beta-carotene 15,15'-dioxygenase), was related to lycopene [39], and thus hypertension [40].…”