Tomato Phytonutrients Balance UV Response: Results from a Double-Blind, Randomized, Placebo-Controlled Study

Abstract

Background: Our previous double-blinded, placebo-controlled cross-over study indicated that a nutritional supplement named lycopene-rich tomato nutrient complex (TNC) can protect from UVA1-induced (340-400 nm) and UVA- (320-400 nm)/UVB-induced (280-320 nm) upregulation of molecular markers associated with oxidative stress, inflammation, and ageing.

Objectives: in the current double-blind, randomized, placebo-controlled multicenter study, we analyze whether a similar, synergistic carotenoid-rich TNC can protect from broadband UVB-induced threshold erythema formation assessed as increase in minimal erythemal dose (MED) reading, the intensity of erythema formation, and the upregulation of molecular markers associated with inflammation and immunosuppression, and whether this correlates with carotenoid blood levels.

Methods: One hundred and forty-nine healthy volunteers were randomized to two groups and subjected to a 5-week washout phase, followed by a 12-week treatment phase receiving either 15 mg lycopene, 5.8 mg phytoene and phytofluene, 0.8 mg β-carotene, 5.6 mg tocopherols from tomato extract, and 4 mg carnosic acid from rosemary extract per day or placebo made from medium-chain triglycerides. At the end of each phase, MED determination, UVB irradiation, chromametry, biopsies, and blood samples were undertaken.

Results: The active supplement was well tolerated. Interestingly, no significant difference was seen in the MED between the active-supplement and placebo groups, as determined by visual grading by expert assessors. Of note, the carotenoid-containing supplement significantly protected against UVB-induced erythema formation measured as Δa* after the intervention minus Δa* after the washout phase as compared to the placebo. Moreover, intake of the active supplement significantly protected against UVB-induced upregulation of IL6 and TNFα as compared with the intake of placebo. Lastly, carotenoid plasma levels were significantly increased.

Conclusion: This well-tolerated carotenoid-containing supplement significantly protected against UVB-induced erythema formation and upregulation of proinflammatory cytokines in healthy volunteers.

Keywords: Carotenoids; Double-blind, randomized, placebo-controlled study; Erythema formation; Oral photoprotection; UVB.

© 2019 The Author(s) Published by S. Karger AG, Basel.

Figures

Fig. 1

Design of the study. a Overall trial design giving the number of volunteers per protocol and the corresponding dropouts. AEs, adverse events. b Details for both arms of the double-blind, randomized, placebo-controlled, multicenter study as performed in each of the centers. Shown are only those visits at which data were collected.

Fig. 2

Compliance reflected by carotenoid blood levels. Lycopene (a) phytofluene (b), and phytoene (c) content in blood samples taken at the indicated time points was determined as described in Materials and Methods. Given are medians, 75th and 25th percentiles from n = 71 volunteers taking carotenoid-rich TNC and n = 74 volunteers taking placebo. Significance was determined by Kruskal-Wallis one-way ANOVA on ranks (Dunn's) for each time point compared to the starting level at week 5, * p < 0.05 versus week 5 (beginning of supplementation).

Fig. 3

Effect of carotenoid-rich TNC on erythema formation and gene expression. a Change of erythema (Δa*) formation was determined by chromametry, as described in Materials and Methods, from n = 71 volunteers taking carotenoid-rich TNC and n = 74 volunteers taking placebo. Δa* is defined as the difference between erythema development levels at 24 h following UV irradiation after supplementation (visit 8) and erythema development levels at 24 h following UV irradiation before supplementation (visit 4). Given are the differences by box plots with medians (solid line) and means (dashed line), dots represent outliers, and error bars represent the 95th and 5th percentiles. Significance between the treatment groups was determined by the t test; p < 0.05 and as indicated. b Gene expression analysis presented as quotient of gene induction after 12 weeks of supplementation with carotenoid-rich TNC or placebo (visit 8) divided by gene induction before supplementation (visit 4) from n = 46 volunteers taking carotenoid-rich TNC and n = 48 volunteers taking placebo. Given are the quotients as box plots with medians; dots represent outliers, and error bars represent the 95th and 5th percentiles. Significance between the treatment groups was determined by the Mann-Whitney rank sum test; p < 0.05 and as indicated. ns, not significant.