Serum Lycopene Concentrations Research Articles

Associations of different isomeric forms of serum lycopene with cardiovascular disease and all-cause mortality.

Background: The effect of serum lycopene on the progression of cardiovascular diseases (CVDs) and their longevity remains a controversial topic. The purpose of this study was to evaluate the associations of different isomeric forms of serum lycopene with CVD and all-cause mortality in the American population. Methods: The National Health and Nutrition Examination Survey (NHANES) is a large population survey to investigate public health in the US. We analyzed data from 2003-2006 linked with mortality data obtained in 2015. Cox proportional hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated to assess the risk of CVD and all-cause mortality caused by serum lycopene. Results: Among 7452 participants (aged 20-85 years, 46.7% male), 298 died from CVDs among the total 1213 deaths during a median follow-up of 10.7 years. Serum lycopene is a protective factor for all-cause and CVD mortality. In multivariable-adjusted models, the hazard ratio (with 95% confidence intervals) associated with Q4 compared to Q1 of serum total-lycopene, trans-lycopene and cis-lycopene was 0.49 (0.38,0.63), 0.49 (0.39,0.63) and 0.55 (0.43,0.70) for all-cause mortality (Ptrend<0.05), and was 0.53 (0.32,0.96), 0.48 (0.32,0.72) and 0.63 (0.41,0.97) for CVD mortality (Ptrend<0.05). The subgroup analyses showed that different isomeric forms of lycopene showed varied associations with CVD and all-cause mortality based on age, drinking status, history of hypertension and diabetes. Conclusions: Serum lycopene concentration was significantly associated with the risk of CVD and all-cause mortality. Cis-lycopene had a U-shaped relationship with mortality, while trans-lycopene had an inverse relationship with it.

Association of serum lycopene concentrations with all-cause and cardiovascular mortality among individuals with chronic kidney disease: A cohort study.

Lycopene is one of the hydrocarbon carotenoids which is largely studied for its strong antioxidant and anti-inflammatory properties, as well as improvement of endothelial function and anti-arteriosclerosis effects. The use of lycopene has been shown to reduce mortality in the general population. However, few studies have examined the association between serum lycopene level and all-cause and cardiovascular mortality among participants with chronic kidney disease (CKD). This study included 7,683 adults with CKD from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) and NHANES 2001-2006. Mortality status and cause of death were ascertained by linkage to National Death Index records through 31 December 2018. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% CIs for mortality from all-cause and cardiovascular disease (CVD). During a median follow-up time of 309 months, there were 5,226 total deaths. The median (interquartile range) serum lycopene concentration was 20.0 (12.0, 32.0) μg/dl. After fully adjusted, restricted cubic spline analyses reported that higher serum lycopene concentrations were significantly associated with decreased risk of all-cause and CVD mortality in participants with CKD (P < 0.001, P = 0.001). When extreme quartiles of serum lycopene concentrations were compared, the multivariable-adjusted HR (95% CI) was 0.778 (0.714-0.848) for all-cause mortality (P < 0.001), and 0.791 (0.692-0.905) for CVD mortality (P < 0.001). Specifically, higher serum lycopene decreased the risk of all-cause and CVD mortality at both CKD stage 1-2 and stage 3-5. Further subgroup analyses and sensitivity analyses supported the current results. Higher serum lycopene was independently associated with a decreased risk of all-cause and CVD mortality in patients with CKD. These findings suggested that maintain serum lycopene concentrations could lower mortality risk in CKD patients.

Risk reduction and prevention of cardiovascular diseases: biological mechanisms of lycopene

Background and aims: The conservational effects of dietary interventions as advantageous instruments in the primary and secondary prevention of cardiovascular disease (CVD) have gotten more attention in recent years. Numerous nutritional epidemiological studies have highlighted the ability of diets to decrease costly care and treatments as well as adverse side effects from standard treatments. Lycopene is a non-pro-vitamin A carotenoid that is present in tomatoes, processed tomato products, and different fruits like watermelon, autumn olive, gac, pink grapefruit, pink guava, papaya, sea buckthorn, and wolfberry. As one of the most powerful antioxidants among dietary tetraterpenoids, lycopene can also assist in lowering the risk of early death and extending life in patients with heart disease. By reducing the destructive effects of free radicals along with total and “bad” LDL cholesterol levels while increasing “good” HDL cholesterol, lycopene holds the power to reduce the risk factors of heart disease. Several studies have investigated a reduction of oxidized-LDL (oxLDL) cholesterol levels following lycopene consumption which supports these claims and suggests the conceivable function of lycopene in the blockage of oxidative stress-associated CVD. A negative correlation between serum lycopene concentration and mortality of people with metabolic syndrome was found. Over 10 years, researchers observed a 39% decreased chance of premature death in individuals with the metabolic disease who had the highest blood concentrations of lycopene. Lycopene’s protective impacts are especially beneficial in those with low blood antioxidant levels or high levels of oxidative stress. This includes older adults, smokers, and diabetic individuals or other vascular disorders. Lycopene intake has been thought to reduce the risk of obesity, insulin resistance, and diabetes mellitus.Lycopene acts as an antihypertensive agent by impeding the angiotensin-converting enzyme and improving the production of nitric oxide (NO) in the endothelium. The purpose of this review is to summarize the possible mechanisms of lycopene in the prevention of CVD. Keywords: Lycopene, Risk factors of heart disease, Antioxidants, Carotenoids, Cardio-metabolic, Insulin resistance

Fruit and Vegetable Consumption, Biomarker Score for Fruit and Vegetable Intake and Mortality in the Third National Health and Nutrition Examination Survey (NHANES-III)

ObjectivesFruit and vegetable (FV) are part of a healthy diet as sufficient consumption has been associated with decreased incidence of a range of chronic diseases and mortality through changes in several biomarkers in blood. The present study aimed to examine the association between FV consumption and mortality among US adults, and the extent to which a composite score comprising of six biomarkers of FV intake and a biomarker of inflammation explained this association.MethodsWe used data on 13,892 adults aged ≥20 years enrolled in the NHANES-III between 1988 and 1994 and followed up through Dec 31, 2015. Daily serving of FV was assessed using 24-hour dietary recall and mortality was determined from the National Death Index records. Serum concentrations of lycopene, β-carotene, α-carotene, β-cryptoxanthin, lutein/zeaxanthin, vitamin C, and C-reactive protein (CRP) were measured in blood samples. Multiple regression analyses were performed to evaluate the association between FV intake and mortality while controlling for confounding. We estimated the mediating effects of biomarkers associated with FV intake and inflammation on mortality through causal mediation analyses.ResultsOver the follow-up, 5023 participants died (1503 from cardiovascular diseases, 1110 from malignant neoplasms). Each increase in FV serving/day was associated with reduced risk of mortality from all-cause (HR: 0.97, 95% CI: 0.95–0.99) and cardiovascular (HR: 0.95, 95% CI: 0.91–1.00), but not from malignant diseases (0.95, 95% CI: 0.60–1.23). The causal mediation analysis showed that the biomarker score of FV and CRP mediated approximately 4% and 50%, and 12% and 50% of the association between FV intake and all-cause and cardiovascular mortality, respectively.ConclusionsOur findings confirmed the beneficial effects of FV intake and revealed that the associations were partly mediated by a reduction in circulating inflammatory biomarker.Funding SourcesThe “Fondation de France” The Philippe Foundation.

Associations Between Serum Lycopene and Cancer-Related Fatigue: Findings From the US 2005–2006 National Health and Nutrition Examination Survey (NHANES)

Abstract Objectives Cancer-related fatigue is characterized by an overwhelming sense of tiredness that cannot be relieved by sleep or rest; it often persists for years into survivorship. Maintaining appropriate nutritional status is critical during cancer treatment, though few studies have assessed relationships between diet quality and cancer-related fatigue. Herein, we aimed to investigate the association between serum lycopene, a proxy for diet quality, and fatigue in a large representative sample of the US population. Methods Data were obtained from the 2005–2006 NHANES dataset. Serum total lycopene was quantified from fasting blood samples and used as a continuous variable. Patient-reported fatigue was assessed from a question on the validated Patient Health Questionnaire-9: “Over the last 2 weeks, how often have you been bothered by… feeling tired or having little energy?”; fatigue was categorized as no fatigue (0), low fatigue (1), or moderate-severe fatigue (2–3). Multinomial regression models were applied to assess the association between serum lycopene and fatigue while controlling for age, race/ethnicity, and body mass index. Results are reported as odds ratios (OR) and 95% confidence intervals (CIs) for having low or moderate-severe vs. no fatigue for a 10-μg/dL increase in serum lycopene for all participants and those with a previous cancer diagnosis. Results Participants (n = 4091) were 48.3 ± 18.7 years old, 52% female, and 51.7% non-Hispanic White; 329 had a prior cancer diagnosis. A self-reported cancer diagnosis was associated with a 31.8% greater odds of having moderate-severe vs. no fatigue (OR = 1.32, 95% CI = 1.12–1.55) and a 6.8% greater odds of having low fatigue (OR = 1.07, 95% CI = 0.93–1.22). A 10-μg/dl increase in serum lycopene concentrations was associated with a 5.3% lower odds of moderate-severe vs. no fatigue (OR = 0.95, 95% CI = 0.90–0.99) and a similar odds of low fatigue (OR = 1.01, 95% CI = 0.97–1.04). These associations were similar for patients who had had a cancer diagnosis. Conclusions Higher levels of serum lycopene were associated with lower odds of moderate-severe. Dietary interventions should be further explored for their associations with cancer-related fatigue among patients with cancer and cancer survivors. Funding Sources National Cancer Institute.

Systemic and Adipose Tissue Redox Status in Sprague-Dawley Rats Fed Normal- and High-Fat Diets Supplemented with Lycopene.

Dietary patterns high in fat influence local and systemic oxidative stress through adipose tissue (AT) accrual and increased reactive oxygen species generation. Lycopene, a carotenoid with antioxidant functionality, may mitigate excess oxidative stress, yet the lipophilic nature of this compound may limit its functionality if sequestered by AT. Thus, it is critical to elucidate whether lycopene's efficacy is limited based on adiposity. The purpose of this study was to investigate the influence of lycopene-supplemented normal- and high-fat diets on systemic and AT redox status. Male Sprague-Dawley rats (n = 18) were fed a 30% normal-fat (NFD) or 60% high-fat (HFD) purified diet supplemented with 100 mg of lycopene/day. Body weight and visceral AT mass, as well as serum and AT lycopene, lipid peroxides, and antioxidant capacity (AC), were assessed after 3, 7, and 10 weeks of supplementation. At week 10, AT mass was significantly higher (P = .028) in the HFD group, yet there were no significant differences in serum or AT lycopene concentrations or lipid peroxides between groups. Additionally, AT in the HFD group exhibited significantly greater lipophilic AC (27.6% higher, P = .031). Results suggest that excess adiposity did not negatively influence circulating lycopene, nor did it limit its antioxidant functionality.

Lower serum levels of alpha tocopherol and lycopene are associated with higher pain and physical disability in subjects with primary knee osteoarthritis: A case-control study.

Background: We aimed to determine dietary intake and serum concentration of α-tocopherol and lycopene in subjects with knee osteoarthritis (KOA) in relation to pain intensity and functional status and comparing them with healthy controls. Methods: This case-control study was conducted among 35 patients with primary KOA and 35 matched healthy subjects selected using convenience sampling method. Dietary intakes of alpha-tocopherol and lycopene were estimated from 24-hour dietary records. Visual Analogue Scale (VAS) and Western Ontario and McMaster (WOMAC) index were used to assess the pain and functional status, respectively. Results: Serum concentrations of alpha-tocopherol (0.024±0.005 vs. 0.028±0.007μmol/ml, p-value= 0.021) and lycopene (0.616±0.191 vs. 0.727±0.159μmol/l, p-value=0.011) were significantly lower in OA patients in comparison with healthy controls. Dietary intake of alpha-tocopherol was negatively associated with total WOMAC score (r=-0.401, p-value=0.021) and pain (r=-0.356, p-value=0.042) and physical function (r=-0.355, p-value=0.043) subscales. Dietary intake of lycopene was negatively associated with total WOMAC score (r=-0.616, p-value<0.001) and pain (r=-0.348, p-value=0.047) and physical function (r=-0.606, p-value<0.001) subscales. Additionally, serum concentration of alpha-tocopherol was negatively associated with total WOMAC score (r=-0.574, p-value<0.001) and physical function subscale (r=-0.571, p-value<0.001). Serum concentration of lycopene was negatively associated with total WOMAC score (r=-0.360, p-value=0.040) and physical function subscale (r=-0.350, p-value=0.046) Conclusion: Serum concentrations of α-tocopherol and lycopene were significantly lower in patients with KOA than in healthy controls. Significant negative association was detected between serum concentration and dietary intake of α-tocopherol and lycopene with functional disability in patients with KOA.

Tomato and Lycopene Feeding Impact Expression of Lipid and Cholesterol Metabolism Genes in Early TRAMP Mouse Model Prostate Carcinogenesis (OR05-05-19)

ObjectivesEpidemiologic 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. MethodsTo 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). ResultsBody 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. ConclusionsSemi-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 SourcesNIH/National Cancer Institute, NIH/National Center for Complementary and Integrative Health, USDA/Agricultural Research Service.

The Dose-Response Effect of Lycopene on Cerebral Vessel and Neuron Impairment Induced by Hyperlipidemia.

To study the dose-response effect of lycopene on vessel and neuron damage in the brain against hyperlipidemia, rats were fed with hypercholesterolemic feed and treated with lycopene orally by gavage at the dose of 5, 25, 45, 65, 85, and 105, 125 mg/kg/bw-1/d-1. At the end of the fourth week, lycopene doses and serum lycopene concentration showed an inverse U-shape curve. Serum lycopene concentration was negatively correlated with the levels of serum TC, TG, LDL-C, as well as the cerebral LDL-C, VEGF, and VCAM-1. Serum lycopene concentration was positively correlated with the expression of Claudin-5 and the number of neurons in hippocampal CA1 and CA3. Lycopene could also reduce the pathologic change of these areas. These results suggested an inverse U-shape relation between dose and serum concentration of lycopene, and intermediate doses were most effective to protect cerebral vessels and neurons from being damaged by hyperlipidemia.

Non-Invasive Immunofluorescence Assessment of Lycopene Supplementation Status in Skin Smears

Circulating lycopene level is negatively associated with the prevalence of cardiovascular disease, cancers (prostate and breast), type 2 diabetes mellitus, and aging. Traditionally, lycopene is measured in biological specimens by a combination of high-performance liquid chromatography (HPLC) and mass spectrometry methods. Moreover, as we recently reported, tissue/cell lycopene depositions can be observed by the immunohistochemistry method with a newly developed monoclonal antibody (mAb) against lycopene. A main objective of this study is to evaluate the performance of a new noninvasive immunofluorescence (IF) lycopene quantification skin test with mAbs against lycopene versus HPLC lycopene assay of serum lycopene in volunteers subjected to lycopene supplementation which represents a novel approach to lycopene measurement methodology. For this purpose, 32 healthy volunteers, 30-40 years old, were supplemented with lycopene (n = 15) or placebo (n = 17) for a period of 4 weeks. It was found that lycopene supplementation leads to a significant increase in serum lycopene concentration after 2 and 4 weeks by 2.6- and 3.4-fold over control, respectively. This was accompanied by a concordant step-wise rise in IF staining of skin corneocytes and sebum, quantifiable by arbitrary IF scores. Placebo supplementation did not affect serum lycopene values or intensity of IF staining of the skin samples. There was 86.6% agreement in paired HPLC/IF variants for the intermediate time point and 80.0% agreement at the end of the study in the lycopene group. Intraclass correlation between paired values in this group was +0.49 for the 2-week time point and +0.63 for the end point. These results indicate that the new antibody-based skin assay can be used for rapid detection of lycopene deficiencies. Moreover, the noninvasive nature of the skin swab test would allow using it to monitor, optimize, and personalize lycopene supplementation protocol of risk groups in the general population.

Serum Lycopene Concentrations and Associations with Clinical Outcomes in a Cohort of Maternal-Infant Dyads.

Oxidative stress has been associated with adverse neonatal outcomes, and many carotenoids, including lycopene, potentially have antioxidant properties. The objective of this analysis was to explore the associations between serum lycopene concentrations, including lycopene isomers, and maternal-newborn outcomes. Maternal and cord blood samples were collected in 180 mother-infant pairs. Serum of total lycopene as well as the cis- and trans-isomers concentrations were measured using HPLC (High Performance Liquid Chromatography). Descriptive statistics were calculated; Spearman coefficients were used to assess correlations between maternal and cord concentrations. The relationship between lycopene concentration and outcomes were evaluated with linear and logistic regression models, with adjustment for relevant confounders. A p ≤ 0.05 was considered statistically significant. Maternal and cord serum lycopene concentrations were positively correlated for total lycopene (r = 0.30, p < 0.0001), cis-lycopene (r = 0.29, p = 0.0002); and trans-lycopene (r = 0.32, p < 0.0001). Maternal concentrations of cis-lycopene were significantly lower in mothers whose infants developed respiratory distress syndrome compared to those who did not (0.336 ± 0.171 vs. 0.445 ± 0.238 µmol/L, p = 0.04) and also in mothers whose babies were admitted to the newborn intensive care unit compared to those who were not (0.380 ± 0.202 vs. 0.458 ± 0.244 µmol/L, p = 0.04). Conversely, cord concentrations of trans-lycopene were significantly higher in infants who developed RDS (Respiratory Distress Syndrome) (0.023 ± 0.012 vs. 0.016 ± 0.012, p = 0.007 for RDS vs. no RDS), and a similar pattern was seen NICU admission (0.023 ± 0.016 vs. 0.015 ± 0.009 µmol/L for NICU (Newborn Intensive Care Unit) admission vs. no NICU admission, p = 0.007). Maternal concentrations of total and cis-lycopene were positively associated with infant birth weight, length and head circumference after adjustment for relevant confounders. As serum carotenoids, including lycopene, are modifiable by diet, future research determining the clinical impact of these compounds is warranted.

Lycopene activates antioxidant enzymes and nuclear transcription factor systems in heat-stressed broilers

This study was conducted to evaluate the effects of dietary lycopene supplementation on growth performance, antioxidant status, and muscle nuclear transcription factor [Kelch like-ECH-associated protein 1 (Keap1) and (erythroid-derived 2)-like 2 (Nrf2)] expressions in broiler chickens exposed to heat stress (HS). A total of 180 one-day-old male broiler chicks (Ross 308) were assigned randomly to one of 2 × 3 factorially arranged treatments: two housing temperatures (22°C for 24 h/d; thermoneutral, TN or 34°C for 8 h/d HS) and three dietary lycopene levels (0, 200, or 400 mg/kg). Each treatment consisted of three replicates of 10 birds. Birds were reared to 42 d of age. Heat stress caused reductions in feed intake and weight gain by 12.2 and 20.7% and increased feed efficiency by 10.8% (P < 0.0001 for all). Increasing dietary lycopene level improved performance in both environments. Birds reared under the HS environment had lower serum and muscle lycopene concentration (0.34 vs. 0.50 μg/mL and 2.80 vs. 2.13 μg/g), activities of superoxide dismutase (151 vs. 126 U/mL and 131 vs. 155 U/mg protein), glutathione peroxidase (184 vs. 154 U/mL and 1.39 vs. 1.74 U/mg protein), and higher malondialdehyde (MDA) concentration (0.53 vs. 0.83 μg/mL and 0.78 vs. 0.45 μg/ mg protein) than birds reared under the TN environment. Changes in levels of lycopene and MDA and activities of enzymes in serum and muscle varied by the environmental temperature as dietary lycopene level increased. Moreover, increasing dietary lycopene level suppressed muscle Keap1 expression and enhanced muscle Nrf2 expression, which had increased by 150% and decreased by 40%, respectively in response to HS. In conclusion, lycopene supplementation alleviates adverse effects of HS on performance through modulating expressions of stress-related nuclear transcription factors.

Retinoid and carotenoid status in serum and liver among patients at high-risk for liver cancer.

BackgroundApproximately 2.7 million Americans are chronically infected with hepatitis C virus (HCV). HCV patients with cirrhosis form the largest group of persons at high risk for hepatocellular carcinoma (HCC). Increased oxidative stress is regarded as a major mechanism of HCV-related liver disease progression. Deficiencies in retinoid and carotenoid antioxidants may represent a major modifiable risk factor for disease progression. This study aims to identify key predictors of serum antioxidant levels in patients with HCV, to examine the relationship between retinoid/carotenoid concentrations in serum and hepatic tissue, to quantify the association between systemic measures of oxidative stress and antioxidant status, and to examine the relationship between retinoids and stellate cell activation.MethodsPatients undergoing liver biopsy (n = 69) provided fasting blood, fresh tissue, urine and completed a diet history questionnaire. Serum and questionnaire data from healthy volunteers (n = 11), normal liver tissue from public repositories and patients without liver disease (n = 11) were also collected. Urinary isoprostanes, serum and tissue retinoid concentrations were obtained by UHPLC-MS-MS. Immunohistochemistry for αSMA was performed on FFPE sections and subsequently quantified via digital image analysis. Associations between urinary isoprostanes, αSMA levels, and retinoids were assessed using Spearman correlation coefficients and non-parametric tests were utilized to test differences among disease severity groups.ResultsThere was a significant inverse association between serum retinol, lycopene, and RBP4 concentrations with fibrosis stage. Serum β-carotene and lycopene were strongly associated with their respective tissue concentrations. There was a weak downward trend of tissue retinyl palmitate with increasing fibrosis stage. Tissue retinyl palmitate was inversely and significantly correlated with hepatic αSMA expression, a marker for hepatic stellate cell activation (r = −0.31, P < 0.02). Urinary isoprostanes levels were inversely correlated with serum retinol, β-carotene, and RBP4.ConclusionsA decrease in serum retinol, β-carotene, and RBP4 is associated with early stage HCV. Retinoid and carotenoid levels decline as disease progresses, and our data suggest that this decline occurs early in the disease process, even before fibrosis is apparent. Measures of oxidative stress are associated with fibrosis stage and concurrent antioxidant depletion. Vitamin A loss is accompanied by stellate cell activation in hepatic tissue.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-016-0432-5) contains supplementary material, which is available to authorized users.

A Common Variant in the SETD7 Gene Predicts Serum Lycopene Concentrations.

Dietary intake and higher serum concentrations of lycopene have been associated with lower incidence of prostate cancer and other chronic diseases. Identifying determinants of serum lycopene concentrations may thus have important public health implications. Prior studies have suggested that serum lycopene concentrations are under partial genetic control. The goal of this research was to identify genetic predictors of serum lycopene concentrations using the genome-wide association study (GWAS) approach among a sample of 441 Old Order Amish adults that consumed a controlled diet. Linear regression models were utilized to evaluate associations between genetic variants and serum concentrations of lycopene. Variant rs7680948 on chromosome 4, located in the intron region of the SETD7 gene, was significantly associated with serum lycopene concentrations (p = 3.41 × 10−9). Our findings also provided nominal support for the association previously noted between SCARB1 and serum lycopene concentrations, although with a different SNP (rs11057841) in the region. This study identified a novel locus associated with serum lycopene concentrations and our results raise a number of intriguing possibilities regarding the nature of the relationship between SETD7 and lycopene, both of which have been independently associated with prostate cancer. Further investigation into this relationship might help provide greater mechanistic understanding of these associations.

Higher levels of serum lycopene are associated with reduced mortality in individuals with metabolic syndrome

Metabolic syndrome increases the risk of mortality. Increased oxidative stress and inflammation may play an important role in the high mortality of individuals with metabolic syndrome. Previous studies have suggested that lycopene intake might be related to the reduced oxidative stress and decreased inflammation. Using data from the National Health and Nutrition Examination Survey, we examined the hypothesis that lycopene is associated with mortality among individuals with metabolic syndrome. A total of 2499 participants 20 years and older with metabolic syndrome were divided into 3 groups based on their serum concentration of lycopene using the tertile rank method. The National Health and Nutrition Examination Survey from years 2001 to 2006 was linked to the mortality file for mortality follow-up data through December 31, 2011, to determine the mortality rate and hazard ratios (HR) for the 3 serum lycopene concentration groups. The mean survival time was significantly higher in the group with the highest serum lycopene concentration (120.6 months; 95% confidence interval [CI], 118.8-122.3) and the medium group (116.3 months; 95% CI, 115.2-117.4), compared with the group with lowest serum lycopene concentration (107.4 months; 95% CI, 106.5-108.3). After adjusting for possible confounding factors, participants in the highest (HR, 0.61; P = .0113) and in the second highest (HR, 0.67; P = .0497) serum lycopene concentration groups showed significantly lower HRs of mortality when compared with participants in the lower serum lycopene concentration. The data suggest that higher serum lycopene concentration has a significant association with the reduced risk of mortality among individuals with metabolic syndrome.

Associations of serum carotenoid concentrations and fruit or vegetable consumption with serum insulin-like growth factor (IGF)-1 and IGF binding protein-3 concentrations in the Third National Health and Nutrition Examination Survey (NHANES III).

Dietary intervention may alter the insulin-like growth factor (IGF) system and thereby cancer risk. In a qualitative review, eleven of twenty studies showed a link between one or more carotenoids, vegetable or fruit intake and the IGF system, however, with partly contrary findings, such that no firm conclusion can be drawn. Therefore, we evaluated associations between serum carotenoid concentrations or the intake of fruits and vegetables with IGF-1, IGF binding protein (BP)-3 and their molar ratio (IGF-1:IGFBP-3) within the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). In our analysis, we included 6061 NHANES III participants and used multivariable-adjusted linear regression models. IGF-1 concentrations were significantly positively associated with serum concentrations of lycopene, β-carotene, α-carotene, β-cryptoxanthin and lutein/zeaxanthin in men and women. Statistically significant positive associations were observed for serum concentrations of α-carotene and lutein/zeaxanthin and intake of fruits with serum IGFBP-3 concentrations in women, but not in men. The IGF-1:IGFBP-3 molar ratio was significantly positively associated with serum concentrations of lycopene, β-carotene and α-carotene in men and with β-carotene in women. In conclusion, dietary interventions with carotenoids, fruits and vegetables may affect the IGF system, although the direction of these effects is currently unclear.

Serum lycopene is inversely associated with long-term all-cause mortality in individuals with rheumatoid arthritis: Result from the NHANES III

IntroductionIncreased oxidative stress and/or chronic inflammation may play important roles in the high mortality of individuals with rheumatoid arthritis (RA). As a natural antioxidant, lycopene can alleviate oxidative stress and decrease inflammation. Therefore, we hypothesized that lycopene has a potential to reduce the risk of mortality in individuals with RA. Methods694 RA participants aged 20 years and older from the third National Health and Nutrition Examination Survey were divided into three groups by the tertile rank method according to their serum concentration of lycopene. These participants were followed-up from the date of interviews (1988–1994) to December 31, 2011 for mortality. Mortality, survival functions and hazard ratios of mortality were compared between these three tertile groups. ResultsThe mortality of participants was significantly lower for the third tertile group (46.4%, 95% CI: 40.1–52.7) compared to the first tertile group (66.5%, 95% CI: 60.4–72.6) and the second tertile group (60.0%, 95% CI: 53.6–66.4%) among participants with RA. There was a significant survival difference between the third tertile group and the first tertile group (Logrank p<0.0001). After adjusting for demographic and other risk factors, RA participants in the third tertile group had a significantly reduced hazard ratio for all-cause mortality (HR=0.631, 95% CI: 0.433–0.918) compared to RA participants in the first tertile group. ConclusionsThese findings from a nationally representative sample indicate that serum lycopene has a significant association with long-term all-cause mortality in individuals with RA.

Abstract A33: Pizza and pasta consumption levels in relation to lycopene and other antioxidant nutrients status among a low-income population in Southeast USA

Abstract Purpose: Lycopene is regarded as a promising antioxidant, potentially protective against chronic diseases such as certain cancers. Unlike other antioxidant nutrients, lycopene mostly comes from tomato based processed foods, rather than from fresh vegetables and fruits. Herein we examine whether foods rich in lycopene offer a full spectrum of antioxidant nutrients needed for chronic disease prevention. Methods: Serum levels of lycopene and other antioxidant nutrients were measured in a representative cross-sectional sample of low-income Blacks (n=189) and Whites (n=183) age 40-79 years participating in the Southern Community Cohort Study (SCCS). Dietary intakes of lycopene, other nutrients, and individual foods were ascertained via a food frequency questionnaire (FFQ). Results: Pizza and pasta showed the strongest correlation with dietary lycopene (adjusted for age and total calories, R spearman = 0.54, P&amp;lt;0.0001), and were the only food sources significantly correlated with serum lycopene (adjusted for age and LDL-cholesterol, R spearman = 0.14, P=0.007). Across pizza and pasta consumption tertiles, estimated dietary lycopene intake increased from 4147±305 to 4983±287 to 8208±301 mcg (P&amp;lt;.0001) per day while serum lycopene concentrations were 27.8±1.3, 32.7±1.3 and 32.0±1.2 mcg (P=.01). There were no significant differences in key socio-demographic and lifestyle variables, except for slightly younger age in the highest tertile. Total caloric intake increased substantially with tertiles of consumption of pizza and pasta, rising from 1965±18 to 2294±114 to 3242±114 kcal (P&amp;lt;.0001). Adjusted for age and total calories, the consumption of protein, saturated fat, and trans fat were increased significantly at tertile 3 compared to tertile 1 and tertile 2 (e.g., saturated fat rose from 27.5±0.7 to 27.9±0.7 to 32.1±0.7 g, P&amp;lt;.0001), whereas fiber and sugar intake levels did not differ significantly across the tertiles. For micronutrients, the sodium and sodium to potassium ratio were much higher in tertile 3 than those in tertile 1 and tertile 2 (e.g., sodium tertile levels were 4179±90, 4095±85, 4635±89 mg, P&amp;lt;.0001). The majority of other antioxidant nutrients' intake levels, however, did not vary across tertiles, or even decreased significantly with higher intake of pizza and pasta (e.g., folate declined from 310.3±8.3 to 302.6±7.8 to 270.8±8.2 mcg, P=.003). Similarly, serum concentrations of other major antioxidants either did not change significantly or even decreased across tertiles of pizza and pasta (e.g., serum concentrations of carotene declined from 16.8±1.4 to 12.8±1.4 to 10.3±1.4 µg/dl, P=.0005). Conclusion: In the current study, pizza and pasta were shown to be the main contributors to dietary lycopene and predictive of serum lycopene levels. Pizza and pasta as consumed by the SCCS participants, however, may offer less antioxidation protection than expected based on their lycopene content alone, since such meals provide higher calories, more unhealthy fat and less overall antioxidants. Citation Format: Yuan Eva Zhou, Maciej S. Buchowski, David G. Schlundt, William J. Blot, Margaret K. Hargreaves. Pizza and pasta consumption levels in relation to lycopene and other antioxidant nutrients status among a low-income population in Southeast USA. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A33.

Abstract A59: Dietary tomato and lycopene inhibition of prostate carcinogenesis in the TRAMP Model is β,β-carotene 9',10'-oxygenase (BCO2)-dependent

Abstract Background: Epidemiology and laboratory studies have implicated diets rich in tomatoes and the carotenoid lycopene in prostate cancer risk reduction. However, the specific roles of lycopene, lycopene metabolites, or other tomato phytochemicals are uncertain. The discovery of carotenoid metabolizing enzymes has opened the door to mechanistic studies. The enzyme β,β-carotene 9',10'-oxygenase (BCO2) has been shown to asymmetrically cleave lycopene and other carotenoids, yielding metabolites. We hypothesize that these cleavage products may be more biologically active and convey anti-cancer activity. Therefore, we defined the impact of BCO2 ablation on the efficacy of dietary tomato and lycopene to inhibit cancer progression in the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mouse model of prostate carcinogenesis. Methods: BCO2-/- (B6; 129S6-Bcdo2tm1Dnp) mice were crossed with TRAMP+/- (C57BL/6-Tg(TRAMP)8247Ng/J) transgenic mice leading to the generation of TRAMP+/-:BCO2+/+ and TRAMP+/-:BCO2-/-. Male TRAMP:BCO2+/+ and TRAMP:BCO2-/- mice were randomized to three dietary treatments: AIN-93G control diet, 10% tomato powder diet, or 0.25% lycopene beadlet-containing diet from 3 until 18 weeks of age. Serum was collected for carotenoid analysis by HPLC, and prostate tissues were processed for histopathologic assessment of prostate carcinogenesis. Results: TRAMP:BCO2 +/+ mice fed tomato powder and lycopene attained similar serum lycopene concentrations (0.141μM +/- 0.007μM vs. 0.139μM +/- 0.007μM, respectively). The presence of the tomato carotenoids phytofluene (0.13μM +/- 0.002μM) and phytoene (0.025μM +/- 0.003μM) in serum was only observed with tomato feeding as anticipated. Loss of BCO2 enzyme resulted in significantly increased serum concentrations of total, total cis, 5-cis, and all-trans lycopene in both tomato and lycopene fed mice, and the accumulation of phytoene, phytofluene, and zeta-carotene in the tomato fed mice compared to the BCO2+/+ counterparts. For example, total serum lycopene levels were 0.229μM +/- 0.029μM and 0.223μM +/- 0.030μM in tomato- and lycopene-fed TRAMP:BCO2-/- mice, respectively. Dietary tomato powder and lycopene inhibited cancer progression. Incidence of cancer was 80% in control diet-fed TRAMP:BCO2+/+ mice, while tomato and lycopene feeding decreased incidence to 15% and 11%, respectively. Ablation of BCO2 (TRAMP:BCO2-/-) partially attenuated the anti-cancer efficacy of tomato and lycopene observed in TRAMP:BCO2+/+ mice as the incidence was 24% for tomato-fed and 46% for lycopene-fed mice. Conclusions: Overall, dietary tomato and lycopene inhibited the progression of prostate cancer in TRAMP in a BCO2-dependent manner. Future human studies to examine the role of lycopene metabolism and BCO2 genotype in cancer risk reduction are warranted. Citation Format: Hsueh-Li Tan, Jennifer M. Thomas-Ahner, Nancy E. Moran, Gregory S. Young, John W. Erdman, Jr., Steven K. Clinton. Dietary tomato and lycopene inhibition of prostate carcinogenesis in the TRAMP Model is β,β-carotene 9',10'-oxygenase (BCO2)-dependent. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A59.

Genetic Variation Predicts Serum Lycopene Concentrations in a Multiethnic Population of Postmenopausal Women ,

Background: The consumption and blood concentrations of lycopene are both positively and inversely associated with the risk of several chronic diseases. The inconsistences in lycopene disease association studies may stem from a lack of knowledge about the genetic variation in the synthesis, metabolism, and deposition of transport and binding proteins, which potentially influence serum lycopene concentrations.Objective: We examined the association between variation across the genome and serum concentrations of lycopene in a multiethnic population.Methods: Participants included African (n = 914), Hispanic (n = 464), and European (n = 1203) American postmenopausal women from the Women’s Health Initiative. We analyzed ∼7 million single nucleotide polymorphisms (SNPs). Linear regression models were used to assess associations between each SNP and serum concentrations (log transformed, continuous) of lycopene; we adjusted for age, body mass index, and population substructure. Models were run separately by ethnicity, and results were combined in a transethnic fixed-effects meta-analysis.Results: In the meta-analysis, the scavenger receptor class B, member 1 (SCARB1) gene, which encodes for a cholesterol membrane transporter, was significantly associated with lycopene concentrations (rs1672879; P < 2.68 × 10−9). Each additional G allele resulted in a 12% decrease in lycopene concentrations for African Americans, 20% decrease for Hispanic Americans, and 9% decrease for European Americans. In addition, 2 regions were significantly associated with serum lycopene concentrations in African Americans: the slit homolog 3 gene (SLIT3), which serves as a molecular guidance cue in cellular migration, and the dehydrogenase/reductase (SDR family) member 2 (DHRS2) gene, which codes for an oxidoreductase that mitigates the breakdown of steroids.Conclusions: We found 3 novel loci associated with serum lycopene concentrations, 2 of which were specific to African Americans. Future functional studies looking at these specific genes may provide insight into the metabolism and underlying function of lycopene in humans, which may further elucidate lycopene’s influence on disease risk and health. This trial was registered at clinicaltrials.gov as NCT00000611.