Carotenoids are orange, yellow, and red lipophilic pigments present in many fruit and vegetables, as well as other food groups. Some carotenoids contribute to vitamin A requirements. The consumption and blood concentrations of specific carotenoids have been associated with reduced risks of a number of chronic conditions. However, the interpretation of large, population-based observational and prospective clinical trials is often complicated by the many extrinsic and intrinsic factors that affect the physiologic response to carotenoids. Extrinsic factors affecting carotenoid bioavailability include food-based factors, such as co-consumed lipid, food processing, and molecular structure, as well as environmental factors, such as interactions with prescription drugs, smoking, or alcohol consumption. Intrinsic, physiologic factors associated with blood and tissue carotenoid concentrations include age, body composition, hormonal fluctuations, and variation in genes associated with carotenoid absorption and metabolism. To most effectively investigate carotenoid bioactivity and to utilize blood or tissue carotenoid concentrations as biomarkers of intake, investigators should either experimentally or statistically control for confounding variables affecting the bioavailability, tissue distribution, and metabolism of carotene and xanthophyll species. Although much remains to be investigated, recent advances have highlighted that lipid co-consumption, baseline vitamin A status, smoking, body mass and body fat distribution, and genetics are relevant covariates for interpreting blood serum or plasma carotenoid responses. These and other intrinsic and extrinsic factors are discussed, highlighting remaining gaps in knowledge and opportunities for future research. To provide context, we review the state of knowledge with regard to the prominent health effects of carotenoids.

Background Epidemiologic studies suggests lycopene and tomato intake are inversely associated with human prostate cancer incidence. Genetically-driven murine prostate carcinogenesis (TRAMP model) is inhibited by lycopene- or tomato-feeding, and these effects are modulated by beta-carotene oxygenase 2 (Bco2) genotype. Objectives We seek insight into this interaction through evaluation of prostate gene expression patterns during early TRAMP carcinogenesis. Methods Three-week-old TRAMP/+ or TRAMP/– x Bco2+/+ or Bco2–/– mice were fed a control, lycopene beadlet, or 10% tomato powder-containing semi-purified diet (providing 0, 384 and 462 mg lycopene/kg diet, respectively) for 5 weeks. Gene expression patterns were evaluated by prostate cancer- and cholesterol and lipoprotein metabolism-focused arrays at 8 weeks-of-age. Results TRAMP genotype profoundly alters gene expression patterns, specifically inducing pathways associated with cell survival (z-score = 2.09, –log(P-value) = 29.2), p53 signaling (z-score 1.13, –log(P-value) = 13.5), and PI3K/AKT signaling (z-score = 0.302, –log(P-value) = 12.1), while repressing PTEN signaling (z-score = -0.905, –log(P-value) = 12.3), cholesterol synthesis (z-score = –1.941, –log(P-value) = 26.2), and LXR/RXR pathway activation (z-score = –1.941, –log(P-value) = 23.1). In comparison, lycopene- and tomato-feeding modestly modulate strong procarcinogenic TRAMP signaling. Lycopene decreased gene expression related to carcinogenesis (Nkx3-1), tomato feeding increased expression of a gene involved in circadian regulation (Arntl), and tomato and/or lycopene increased expression of genes involved in lipid metabolism (Fasn, Acaca, Srebf1, Hmgcr, and Ptgs1) (all P < 0.05). The impact of Bco2 genotype was limited to a subset of lycopene-impacted genes (Apc, Mto1, Nfkb1, and Rbm39). Conclusions The TRAMP genotype strongly impacts procarcinogenic gene expression prior to emergence of histopathologic disease. Dietary tomato and lycopene modestly temper these processes, while Bco2 genotype has a limited impact at this early stage. These observed patterns provide insight into the complex interactions between a dietary variable, here tomatoes and lycopene, genes impacting nutrient metabolism, and their modulating influences on oncogene-driven prostate carcinogenesis. These findings provide further mechanistic support, consistent with cancer outcomes in rodents experiments and human epidemiologic studies.

Objectives Dermal carotenoid assessment by portable reflection spectroscopy offers a rapid and non-invasive assessment of carotenoid status. However, feasibility, validity, and reliability has not been assessed in diverse, young infants. We hypothesize that dermal carotenoid measurement of infants’ heels and fingers will be feasible, reliable, and valid. Methods Dermal carotenoid intensity was measured by portable reflection spectroscopy (Veggie Meter) at the index finger and heel of the foot in the first fourteen, 4 month old subjects of the Baylor Infant Biomarker of Nutrition Study. Up to 6 reads were acquired in which the skin was correctly positioned and held still. Infant feeding was assessed by a 7-day infant FFQ. Feasibility was assessed by the time to acquire reads, and reliability was assigned if 3 reads with a 10% CV (conforming reads) could be obtained, per the manufacturer's specifications for adult readings. Internal validity was assessed by correlation between average heel and finger reflection scores. Differences between formula and breastfed infant reflection scores were compared. Results Infants (n = 14, 50% female) were of diverse race-ethnicities (71% White, 21% African American, 7% Asian, and 36% Hispanic), but neither sex nor race-ethnicity predicted reflection score. Three heel reads could be acquired more rapidly than three finger reads (1.1 ± 0.2 min vs. 1.5 ± 0.5 min, P = 0.03), and completion of all finger measurements took longer (4.8 ± 3.2 min) than all from the heel (2.6 ± 1.7 min, N.S.). Acquisition of reliable heel reflection scores was more feasible, with 86% of subjects providing conforming heel reads, but only 36% of subjects providing conforming finger reads. Finger and heel reflection scores were positively correlated (r = 0.73, P = 0.003) within subjects, indicating internal validity. Finger and heel reflection scores were greater in human milk-fed infants (n = 10) compared to breastfed (n = 4) (107 ± 9 vs. 49 ± 14 reflection score, P = 0.005) Conclusions Score differences by feeding method suggest sensitivity to detect differences in dietary carotenoid exposure. Portable reflection spectroscopy of infants’ heels offers a feasible, reliable, and valid measure of dermal carotenoids in infants and should be further validated as a biomarker of infant carotenoid status. Funding Sources Texas Children's Hospital, USDA.

Objectives Epidemiologic evidence suggests consuming tomato and lycopene are associated with a reduced risk of advanced and lethal prostate cancer. Prior studies of prostate cancer prevention in the TRAMP mouse model indicate that lifelong tomato- or lycopene-feeding reduce incidence of early carcinoma by up to 70%, and this effect is dependent on the expression of Bco2 (beta-carotene oxygenase 2, a carotenoid metabolic enzyme). We hypothesize that gene expression patterns will reveal the mechanisms by which these diets act to disrupt early carcinogenesis. Methods To define the early transcriptional responses in the dorsolateral mouse prostate, TRAMP and wild-type littermate mice were crossed with Bco2+/+ or Bco2−/− mice (C57/Bl6 background). All 4 crosses were fed either control, lycopene, or 10% tomato powder diets from weaning at 3 weeks until 8 weeks. Expression of 84 genes was measured by a prostate cancer-focused PCR array (n = 5/group). Protein expression was measured by Western blotting (n = 4/group) and serum carotenoids by HPLC (n = 3–4/group). Statistical effects of TRAMP and Bco2 genotypes and diet treatment on final body mass (n = 6/group), serum lycopene, and gene expression were analyzed by ANOVA (alpha = 0.05). Results Body masses were not influenced by genotypes or diets. Serum lycopene concentrations were subject to a Bco2 genotype effect (P = 0.004), with greater lycopene being present in Bco2−/− mice than Bco2 +/+mice, but did not differ by TRAMP genotype nor between lycopene vs tomato diets. The TRAMP genotype influenced the expression of 49 genes, diet impacted expression of 11 genes, and Bco2 genotype influenced expression of 2 genes. Expression of 4 genes, Apc, Mto1, Nfkb1, and Rbm39, were subject to a significant Bco2 x diet interaction. Expression of 5 genes related to lipid metabolism, Fasn, Acaca, Srebf1, Hmgcr, and Ptgs1, were impacted by a diet effect. Conclusions Semi-targeted analyses suggest tomato and lycopene may affect lipid metabolism in early carcinogenesis. Future studies may elaborate upon specific pathways modulated by tomato and lycopene in early prostate carcinogenesis. Funding Sources NIH/National Cancer Institute, NIH/National Center for Complementary and Integrative Health, USDA/Agricultural Research Service.