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Effect of a Tomato-Based Drink on Markers of Inflammation, Immunomodulation, and Oxidative Stress
Abstract
Regular consumption of tomato and its products is being consistently associated with lower risk of several types of cancer and, to a lesser extent, coronary heart disease. Among the many tomato components credited with healthful properties, carotenoids and particularly lycopene are being actively investigated. Given the recognized role of immune/inflammatory processes in atherogenesis, the effects of a tomato-based drink (Lyc-o-Mato), which was previously shown to afford DNA protection from oxidative stress, on the modulation of immune and inflammatory markers (by enzyme immunoessay), on basal lymphocyte DNA damage (by comet assay), and on F2-isoprostane excretion (by LC-MS/MS), were investigated in 26 healthy young volunteers. In a placebo-controlled, double-blind, crossover study, Lyc-o-Mato (5.7 mg of lycopene, 3.7 mg of phytoene, 2.7 mg of phytofluene, 1 mg of beta-carotene, and 1.8 mg of alpha-tocopherol) or a placebo drink (same taste and flavor, but devoid of active compounds) were given for 26 days, separated by a wash-out period. During the study subjects maintained their habitual, hence unrestricted, diet. TNF-alpha production by whole blood was 34.4% lower after 26 days of drink consumption, whereas the other parameters were not significantly modified by the treatment. In turn, modest effects of the regular intake of a tomato drink, providing small amounts of carotenoids, were found on the production of inflammatory mediators, such as TNF-alpha, in young healthy volunteers. Future intervention trials in subjects with low carotenoid status and/or compromised immune system will resolve the issue of whether carotenoids modulate immune parameters in humans.
... There is also recent evidence suggests that lycopene acts as an anti-inflammatory agent (Kim et al., 2004). It has been demonstrated that lycopene can inhibit the expression of inflammatory cytokines and reverse the loss of antioxidant enzymes induced by inflammation caused by either injecting lipopolysaccharide or exposure to iron (Riso et al., 2006). Accordingly, the present study aimed to evaluate the beneficial effects and chemopreventive potential of lycopene on experimentally induced liver cancer in rats by diethylnitrosamine through evaluation of some serum liver biomarkers and molecular analysis of detoxification enzyme (CYP 2E1), tumor suppressor gene P53 and proinflammatory cytokines TNF-α gene expression in hepatic tissues. ...
... Lycopene is a bioactive compound of tomato exerting antioxidant and anti-inflammatory properties (Reifen et al., 2004). It has been demonstrated that lycopene can inhibit the expression of inflammatory cytokines and reverse the loss of antioxidant enzymes induced by inflammation (Riso et al., 2006). Also, Jamshidzadeh et al. (2008) reported that tomato supplementation ameliorates biochemical indices and oxidative parameters in induced liver injury. ...
... These results are agreement with Bhatia et al. (2015) who reported that, lycopene administration to DEN treated mice modulate the serum levels of these cytokines (TNF-α, IL-1β and IL-6) by inhibiting their production and induction of apoptosis thus showing its antiinflammatory effect. Some literature also supported the amelioration of these inflammatory markers upon administration of lycopene (Riso et al., 2006;Feng et al., 2010). Also, Bahcecioglu et al. (2010) showed that TNF-α level was reduced after lycopene treatment, indicating the anti-inflammatory effect of lycopene. ...
Lycopene was shown to exert anti-inflammatory, antioxidant, hepatoprotective properties, and anticancer activity. This study was done to investigate the protective effects of Lycopene on diethylnitrosamine (DEN)-induced hepatocarcinogensis in rats. Forty-five male albino rats were divided into three groups. Group I (normal control group): rats administered distilled water only. Group II: rats received diethylnitrosamine (200 mg/kg b.wt/i.p), two weeks later rats received (2 ml/kg b. wt) Carbon tetrachloride (CCl4) orally at 1:1 dilution in corn oil as a promoter of carcinogenic effect. DEN and CCl4 injections were repeated once again after 1 month from first DEN injection. Group III: rats received DEN+CCl4 as in group II then treated with lycopene at a dose of (20 mg/kg b.wt/orally) dissolved in tween-80% for 6 weeks. All animals were sacrificed after the end of experiment. DEN induced HCC showed significant increase in hepatic marker enzymes (ALT and ALP), total bilirubin and alpha fetoprotein (AFP) with marked decrease in serum albumin concentration. Also, the results of molecular analysis in liver tissue revealed significant up-regulation in TNF-α gene expression level. Conversely, down-regulation in tumor suppressor gene p53 and Cyp2E1 gene expression compared with control group. Treatment with lycopene to DEN induced HCC protects the liver cells from damage by regulating the biochemical parameters. Lycopene was able to mitigate liver tissue damage induced by DEN through increasing of Cyp2E1 and P53 in addition to decreasing TNF-α gene expression level and ameliorate all serum liver function parameters. These findings suggested, the potential efficacy of lycopene as an additional chemo preventive agent in treatment of hepatocellular carcinoma by modulating the apoptosis, anti-inflammatory and detoxification effects.
... Six studies involved females only (12,39,28,41,53,54), whereas 3 focused on only males (24,31,32). Eleven of the studies were interventions with a placebo-controlled group (13,17,20,21,24,35,42,46,33,31,55), and 16 used a cross-over study design (14,16,22,23,25,35,37,40,49,51,26,38,39,30,29,41). ...
... A study by Colmán Martínez et al. (51) found that 400 mL of tomato juice 4 times/wk for 28 d resulted in significant improvements in intercellular adhesion molecules (ICAMs) and vascular cell adhesion molecule-1 (VCAM-1) (P < 0.001 and P < 0.001, respectively). While a large number of the studies found significant improvements for OS outcomes (12,24,35,37,46,47,44,51,28,29,53,54,27) there were many OS marker studies that showed no improvement (13,14,23,34,40,42,45,49,52,39,38,32,30,41,43). Thus, there is insufficient evidence to determine what the effect of lycopene is with regard to OS markers. ...
... Randomization was used in 30 of the 42 studies, with most of these reporting allocation concealments. Thirteen articles were deemed to be of negative quality (14,25,36,37,40,49,52,39,32,30,43,27), 14 were neutral (12,17,21,22,45,46,51,33,31,38,41,53,54), and 17 were positive (3, 13, 16, 18-20, 23, 24, 34, 35, 42, 47, 50, 26, 28, 29, 48). Studies of negative and neutral quality often lacked information on intervening factors and, in some cases, biases and limitations of the studies. ...
Cardiovascular disease (CVD) is the leading cause of death globally and the presence of ≥1 cardiovascular risk factors elevates total risk. Lycopene, a carotenoid with high antioxidant capacity, may be protective. The aim of this systematic review and meta-analyses is to determine the efficacy of consuming dietary and/or supplemental lycopene on cardiovascular risk factors. Using the PRISMA guidelines, 4 databases were systematically searched from inception: Medline, Cinahl, Proquest, and Scopus. Intervention trials assessing dietary or supplemental lycopene on CVD outcomes were included. The Cochrane Risk-of-Bias tool was used to assess the quality of the included papers. Pooled analysis was conducted using outcomes with available data. Forty-three studies were included. Lycopene interventions were highly variable (supplement with or without food, based as tomato juice/paste/raw product, or combined with olive oil), the dose ranged from 1.44 to 75 mg lycopene/d and was not reported in 11 of 43 included studies. Studies reported conflicting findings for the effect of lycopene on cardiovascular risk factors, This was supported by meta-analyses where there were no significant differences between lycopene intervention and control groups for blood pressure and lipids (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides). This was observed for overall groups and in subgroup analyses for individuals with elevated risk factor concentrations at baseline. Lycopene interventions for cardiovascular risk factors were highly variable across studies in both the dosage provided and the mode of delivery (supplement or food based). As such, there are conflicting findings regarding the efficacy of lycopene to improve cardiovascular risk factors. This systematic review was registered with PROSPERO as CRD42018112174.
... Thus, lycopene has been found to have a beneficial effect in treating chronic illnesses caused by oxidative stress, which have oxidative stress as part of their etiopathogenesis, such as cancer, obesity, cardiovascular diseases, diabetes mellitus, Alzheimer's and inflammatory diseases [12][13][14][15]. Furthermore, studies suggest that lycopene helps to reduce the expression of genes that cause systemic inflammation and the acute phase response through modulation of interleukins and TNF-α synthesis in lymphocytes and macrophages, respectively [16,17]. ...
... Like other natural carotenoids, lycopene possesses low solubility in water, is highly susceptible to light, oxygen and autooxidation, and has low intestinal permeability, challenging its clinical and food applications [26][27][28][29]. In this scenario, nanotechnology applications have emerged as promising solutions [17]. Recently, [30] developed a new LPG-based formu-Pharmaceuticals 2023, 16, 905 3 of 19 lation by self-emulsifying drug delivery (nanoLPG). ...
Lycopene is a carotenoid with potential use in the treatment of chronic illnesses. Here, different formulations of lycopene were studied: lycopene-rich extract from red guava (LEG), purified lycopene from red guava (LPG) and a self-emulsifying drug delivery system loaded with LPG (nanoLPG). The effects of administering orally various doses of LEG to hypercholesterolemic hamsters were evaluated regarding the liver function of the animals. The cytotoxicity of LPG in Vero cells was analyzed by a crystal violet assay and by fluorescence microscopy. In addition, nanoLPG was employed in stability tests. LPG and nanoLPG were tested for their cytotoxic effect on human keratinocytes and antioxidant capacity on cells in an endothelial dysfunction model in an isolated rat aorta. Finally, the effect of different nanoLPG concentrations on the expression of immune-related genes (IL-10, TNF-α, COX-2 and IFN-γ) from peripheral blood mononuclear cells (PBMC) using real-time PCR was also analyzed. Results suggest that LEG, despite not being able to improve blood markers indicative of liver function in hypercholesterolemic hamsters, reduced hepatic degenerative changes. Additionally, LPG did not show cytotoxicity in Vero cells. In relation to nanoLPG, the effects produced by heat stress evaluated by Dynamics Light Scattering (DLS) and visually were loss of color, texture change and phase separation after 15 days without interfering with the droplet size, so the formulation proved to be efficient in stabilizing the encapsulated lycopene. Although LPG and nanoLPG showed moderate toxicity to keratinocytes, which may be related to cell lineage characteristics, both revealed potent antioxidant activity. LPG and nanoLPG showed vasoprotective effects in aortic preparations. The gene expression assay indicates that, although no significant differences were observed in the expression of IL-10 and TNF-α, the PBMCs treated with nanoLPG showed a reduction in transcriptional levels of IFN-γ and an increased expression of COX-2. Thus, the work adds evidence to the safety of the use of lycopene by humans and shows that tested formulations, mainly nanoLPG due to its stability, stand out as promising and biosafe products for the treatment of diseases that have oxidative stress and inflammation in their etiopathology.
... Measurements before and after the intervention showed a significant 24% reduction in DSBs in lymphocytes after ex vivo oxidative challenge [129]. The same group next investigated the bioefficacy of 1 drink per day of a tomato-based drink in a double-blind crossover RCT in young, healthy adults and found no effect on endogenous DSBs in lymphocytes [130]. ...
Background:
Accumulation of deoxyribonucleic acid (DNA) damage diminishes cellular health, increases the risk of developmental and degenerative diseases and accelerates aging. Optimizing nutrient intake can minimize accrual of DNA damage.
Objectives:
To (i) assemble and systematically analyse high-level evidence for the effect of supplementation with micronutrients and phytochemicals on base-line levels of DNA damage in humans and (ii) use this knowledge to identify which of these essential micronutrients or non-essential phytochemicals promote DNA integrity in vivo in humans.
Design:
We conducted systematic literature searches of the PubMed database to identify interventional, prospective, cross-sectional, or in vitro studies that explored the association between nutrients and established biomarkers of DNA damage associated with developmental and degenerative disease risk. Biomarkers included lymphocyte chromosome aberrations, lymphocyte and buccal cell micronuclei, DNA methylation, lymphocyte/leukocyte DNA strand breaks, DNA oxidation, telomere length, telomerase activity, and mitochondrial DNA mutations. Only randomized, controlled interventions and uncontrolled longitudinal intervention studies conducted in humans were selected for evaluation and data extraction. These studies were ranked for the quality of their study design.
Results:
In all, 96 of the 124 articles identified reported studies that achieved a quality assessment score ≥ 5 (from a maximum score of 7) and were included in the final review. Based on these studies, nutrients associated with protective effects included vitamin A and its precursor β-carotene, vitamins C, E, B1, B12, folate, minerals selenium and zinc, and phytochemicals such as curcumin (with piperine), lycopene, and proanthocyanidins. These findings highlight the importance of nutrients involved in (i) DNA metabolism and repair (folate, vitamin B12, and zinc), and (ii) prevention of oxidative stress and inflammation (vitamins A, C, E, lycopene, curcumin, proanthocyanidins, selenium and zinc).
Conclusions:
Supplementation with certain micronutrients and their combinations may reduce DNA damage and promote cellular health by improving maintenance of genome integrity.
... Certain natural antioxidants have been found to be effective in the treatment of periodontitis, as they reduce inflammation and enhance the body's antioxidant defense system; antioxidantrich diets have been shown to have a strong anti-inflammatory capacity (Arora et al., 2013;Belludi et al., 2013). Some studies have found a significant reduction in serum levels of tumor necrosis factor (TNF) and interleukin IL-1 (two critical biomarkers of periodontitis) in people with chronic periodontitis after consuming tomato drinks for a certain time (Riso et al., 2006). Some flavonoids, such as resveratrol, have been shown to be able to slow the progression of periodontal disease (Bhattarai et al., 2016). ...
Periodontal diseases (PD) are common chronic inflammatory oral pathologies that are strongly linked to others not found in the mouth cavity. The immune system mediates the host response, which includes the upregulation of proinflammatory cytokines, metalloproteinases, and reactive oxygen species (ROS); the latter may play an important role in the establishment and progression of inflammatory diseases, particularly periodontal disease, via the development of oxidative stress (OS). Natural antioxidants have powerful anti-inflammatory properties, and some can reduce serum levels of key PD indicators such tumor necrosis factor (TNF) and interleukin IL-1. This review compiles, through a thorough literature analysis, the antioxidant, anti-inflammatory, and antibacterial effects of a variety of natural products, as well as their therapeutic potential in the treatment of PD.
... In addition, consumption of a tomato-based drink for 26 days lowered TNF-α secretion by 34% [45]. In contrast, it is reported that an intake of 2 or 8 servings of fruits and vegetables daily for 4 weeks did not show any impact on TNF-α, IL-12, and CRP; however, consuming more than 8 servings/day declined CRP concentration [46]. ...
Background
The coronavirus disease 2019 (COVID-19) pandemic has been shown to affect nutritional recommendations. Some functional foods have been demonstrated to be useful in the treatment of people with COVID-19. However, little is known about the impact of combining functional foods on disease control. This study aimed to investigate the effects of functional foods mixture on serum levels of inflammatory cytokines and biochemical findings in patients with COVID-19.
Methods
A randomized double-blind controlled trial was conducted in Baqiyatallah Al-Azam hospital in Tehran, Iran. Sixty patients were randomly assigned to receive either a soup containing functional foods (n = 30) or a usual soup (control group) (n = 30). Participants’ sociodemographic information was gathered using a general questionnaire. Blood levels of inflammatory markers and biochemical findings were assessed using standard protocols.
Results
The results showed that soup containing functional foods was more effective in controlling serum levels of D-dimer, blood urea nitrogen, and creatinine than the control group (P < 0.05). Also, more significant improvement was found in the intervention group vs control group in terms of interleukin (IL)-1β, IL-6, IL-17, IL-10, and tumor necrose factor-α (P < 0.05). In contrast, the control intervention more efficiently controlled potassium levels and reduced quantitative C-reactive protein than the intervention group (P < 0.05).
Conclusions
This study indicates a soup containing functional foods could alleviate biomarkers of inflammation in patients with COVID-19. However, its effectiveness on biochemical findings remained inconclusive which warranted further research.
Trial registration
IRCT, IRCT20180201038585N11. Registered 23 August 2021, https://www.irct.ir/trial/57338
... A clinical study on 53 well-nourished, healthy elderly person consumption with 330 mL/day of tomato or 47.1 mg lycopene for 8 weeks also demonstrated that a higher intake of lycopene increased the TNFα, and IL-4 levels, though it also lowered IL-2 levels . However, another clinical study on 26 healthy young volunteers demonstrated that 5.7 mg lycopene intake for 26 days significantly lowered TNFα production (Riso et al., 2006), which could be suggested as the optimum dose for consumption. ...
Aging and aging-related chronic disorders are one of the principal causes of death worldwide. The prevalence of these disorders is increasing gradually and globally. Considering this unwavering acceleration of the global burden, seeking alternatives to traditional medication to prevent the risk of aging disorders is needed. Among them, lycopene, a carotenoid, is abundant in many fruits and vegetables, including tomatoes, grapefruits, and watermelons, and it has a unique chemical structure to be a potent antioxidant compound. This nutraceutical also possesses several anti-aging actions, including combating aging biomarkers and ameliorating several chronic disorders. However, no systematic evaluation has yet been carried out that can comprehensively elucidate the effectiveness of lycopene in halting the course of aging and the emergence of chronic diseases linked to aging. This review, therefore, incorporates previous pre-clinical, clinical, and epidemiological studies on lycopene to
understand its potency in treating aging disorders and its role as a mimic of caloric
restriction. Lycopene-rich foods are found to prevent or attenuate aging disorders in
various research. Based on the evidence, this review suggests the clinical application of lycopene to improve human health and alleviate the prevalence of aging and aging disorders.
... In other words, you will not obtain all the nutrients if you skin the tomatoes (Heber and Lu, 2002). Italian researchers Riso et al. (2006) at the University of Milan reported that a daily glass of a commercial tomato juice could lower one of the primary markers of inflammation by almost 35% in less than one month. In addition, in a recent study at the University of the Negev in Beer Sheva, Israel, Engelhard et al. (2006) evaluated the effect of a tomato extract containing lycopene on systolic and diastolic blood pressure in patients with hypertension, as well as the serum lipoproteins, plasma homocysteine and oxidative stress markers. ...
Tomato belongs to the family, Solanaceae and the genus Lycopersicon, is considered as one of the best healthy foods in the world due to its rich source of vitamin B and phyto-nutrients and abundant in carotenoids and lycopene. There has not been alternative means of preservation asides refrigeration as fast ripening disorder sets in and reduce its shelf life as the level of its calcium and potassium reduces during these processes. Post-harvest waxing has proved to be the alternative means of extending its shelf life. Standard analytical methods were used to test for colour, hardness, ash content, moisture content, total solid, brix, pH and total titrable acidity for two single and eight composite waxing (shea butter and moringa) of tomato fruits from day one to seven respectively. Waxing helps to delay the effect of divalent cations, which played an essential role in pectin metabolism and result to tissue softening in the pericarp of tomato fruit during ripening. The result obtained indicated that single oil waxing at 100%MOT (100% moringa oil) yielded good result up to five days while composite oil waxing at 10:90MST (10%moringa and 90%shea butter) could retard the effect of divalent cations for ripening for four days than the rest of waxing in single and composite oil waxing respectively.
... No evidence for DNA protection was observed in subjects after ingestion of commonly consumed beverages for example with apple and grape juice [71], negative results were also obtained in an older study with tomato juice [72] and wine [73]. Also blood orange juice did not lead to protection against DNA-damage, however reduction of H 2 O 2 induced DNA migration (ROS protection) was observed [74]. ...
The single cell gel electrophoresis technique is based on the measurement of DNA migration in an electric field and enables to investigate via determination of DNA-damage the impact of foods and their constituents on the genetic stability. DNA-damage leads to adverse effects including cancer, neurodegenerative disorders and infertility. In the last 25 years approximately 90 human intervention trials have been published in which DNA-damage, formation of oxidized bases, alterations of the sensitivity towards reactive oxygen species and chemicals and of repair functions were investigated with this technique. In approximately 50% of the studies protective effects were observed. Pronounced protection was found with certain plant foods (spinach, kiwi fruits, onions), coffee, green tea, honey and olive oil. Also diets with increased contents of vegetables caused positive effects. Small amounts of certain phenolics (gallic acid, xanthohumol) prevented oxidative damage of DNA; with antioxidant vitamins and cholecalciferol protective effects were only detected after intake of doses that exceed the recommended daily uptake values. The evaluation of the quality of the studies showed that many have methodological shortcomings (lack of controls, no calibration of repair enzymes, inadequate control of the compliance and statistical analyses) which should be avoided in future investigations.
... The treatment with STE had a greater decrease in the levels of these three cytokines in comparison with SR, therefore, it presented a wide anti-inflammatory effect with respect to Serenoa; it was greater effect on the obese groups. The anti-inflammatory activity of tomato and lycopene has been demonstrated in the reduction of TNF-α, IL-1β, IL-2 and IL-6 concentrations, in the decrease of phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB), as well as in the increase of nuclear factor erythroid 2 (Nrf2) [67][68][69]. The results of this work are consistent with the anti-inflammatory effects of lycopene and/or tomato as previously described. ...
PurposeTomato is an important source of lycopene, a carotenoid that has been emerging as a natural preventive agent for prostate disease. Moreover, tomato contains other components with a wide range of physiological properties, but their potential beneficial effects on prostatic hyperplasia (PH) during obesity have not been completely established. In this study, we compared the effect of a lipidic extract of tomato saladette (STE) with Serenoa repens (SR) on obese rats with PH.Methods
Forty-eight Wistar rats were divided in Control (C) and Obese (Ob) treated without (n = 12) and with (n = 36) testosterone enanthate (TE), once a week for 8 weeks to induce PH. After 4 weeks, SR and STE were administered. Biochemical parameters, oxidative stress markers and inflammatory cytokines production were determined.ResultsTE increased prostate weight and caused prostatic hyperplasia in C group, and these effects were exacerbated by obesity. SR and STE reverted the increase in prostate weight and hyperplasia caused by TE in C and Ob groups. Obesity increased LDL, TGs, NOx and MAD, but decreased HDLc, GSx, SOD and CAT. SR reverted the effects of obesity, but these were significantly reduced and HDLc increased with STE. Obesity and TE increased TNFα, IL-1β and IL-6 levels, but these were partially reverted by STE compared with SR.Conclusions
Excess of fat tissue increases the alterations by PH. STE diminishes these alterations compared with SR, suggesting its beneficial effect to improve prostate function. Whole tomato lipid extract could serve as sole therapy or as an adjunct to pharmacological treatment for PH.
... Lycopene has been given a considerable attention for the management of neuropathologies including AD because of its antioxidant, 62,63 immunomodulatory, 64,65 and antiinflammatory properties. 66,67 Being a lipophilic molecule, it crosses blood-brain barrier. ...
Reports on a significant positive correlation between consumption of carotenoid-rich food and prevention of Alzheimer's disease (AD) led to the investigation of carotenoids for the treatment and prevention of AD. More than 1100 types of carotenoids are found naturally, out of which only around 50 are absorbed and metabolized in human body. Lycopene is one of the most commonly ingested members of fat-soluble carotenoid family that gives vegetables and fruits their red, yellow, or orange color. Lycopene has established itself as a promising therapy for AD owing to its neuroprotective activities, including antioxidant, anti-inflammatory, and antiamyloidogenic properties. In this review, we highlight the various in vitro and preclinical studies demonstrating the neuroprotective effect of lycopene. Also, some epidemiological and interventional studies investigating the protective effect of lycopene in AD have been discussed. Diving deeper, we also discuss various significant mechanisms, through which lycopene exerts its remissive effects in AD. Finally, to overcome the issue of poor chemical stability and bioavailability of lycopene, some of the novel delivery systems developed for lycopene have also been briefly highlighted.
... However, these serum cytokines were significantly decreased (P<0.05) in lycopene treated group compared with the obese one. These results indicated that lycopene has the ability to reduce these serum cytokines in obese individuals, and they are in general accord with a study of Riso et al., 29 that reported moderate efficacy on the released mediators of inflammation, like TNF-á, after the regular administration of lycopene by healthy volunteers. Also, Watzl et al., 30 explained that the highest TNF-á production was accompanied by a low lycopene intake. ...
A chronic low-grade inflammation is one of etiologic conditions closely associated with obesity. The study aims to examine the effect of lycopene on obesity inflammatory conditions in rats. 20 adult male albino rats were divided into four groups (n=5) and for 30-day treatment they were divided into the control group received corn oil as a vehicle, lycopene control group received lycopene extract (10 mg/kg) daily with gavage, obese control group subjected to high fat (HF) diet and received corn oil and obese/lycopene group subjected to HF diet and daily received lycopene extract by the same dose. Bodyweight, weight of thymus and spleen, cytokines [Resistin, Interleukin-1β (IL-1β), Tumor Necrosis Factor α (TNF-α) and Interleukin-6 (IL-6)], lipid profile, and immunohistochemical assay for the Nuclear Factor kappa-B receptors (NF-κB) expression were measured and analyzed. The results revealed that the induced obesity caused a remarkable increase in bodyweight, relative weight of thymus and spleen, levels of serum cytokines, total cholesterol and triglycerides and NF-κB receptors expression, but decreased high-density lipid (HDL) level significantly. Administration of lycopene to obese rats caused a significant depletion in the levels of serum cytokines, total cholesterol (TC) and triglycerides (TG) with a significant increase in HDL level and caused no change in bodyweight, while the relative weight of the spleen and thymus was improved. Also, lycopene caused a marked decline in NF-κB receptors expression in thymus and spleen. These results supported the importance of lycopene as a beneficial carotenoid in combating obesity and companied disturbed fat index and metabolism.
... This theory is based on our finding of a significant reduction in TNF-α-to-IL-10 ratio under in vitro simulated conditions of inflammation with stimulation of leukocytes. These results corroborate findings in humans that whole food diet composition can reduce biomarkers of systemic inflammation including CRP and pro-inflammatory cytokines (e.g., TNF-α, IL-6) (4,11,(20)(21)(22)(23). ...
Whole foods in humans decrease inflammation and risk for various diseases, as well as increase weight loss and immune function. Nutrition has been shown to be an integral component in the management of various diseases in dogs but the immunologic and anti-inflammatory effects of whole food diets have not been explored. Therefore, our objective was to assess the effect of feeding a whole food diet on immune function and inflammatory phenotype in healthy dogs. A prospective, randomized, open-labeled, cross-over clinical trial was performed. Sixteen healthy client-owned dogs were fed either a whole food or an extruded dry diet, and after 67 days, they were fed the alternate diet for an additional 67 days. Blood samples were obtained at the completion of each treatment arm (i.e., days 67 and 134). Serum c-reactive protein (CRP), haptoglobin (Hp), and serum amyloid-A (SAA) were measured with ELISA assays. Whole blood cultures were performed with exposure to a phosphate-buffered solution (PBS), lipopolysaccharide (LPS), and lipoteichoic acid (LTA). A canine specific multiplex bead-based assay was then used to measure tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-2, IL-8, and monocyte chemoattractant protein (MCP)-1 concentrations. Granulocyte/monocyte (GM) phagocytosis and oxidative burst associated with Escherichia coli were evaluated via flow cytometry. Dogs fed a whole food diet had significantly lower TNF-α-to-IL-10 ratios ( P = 0.05) and higher production of IL-8 ( P = 0.03) with LTA-exposed leukocytes compared to dogs fed an extruded dry diet. There were no between-treatment differences in the remaining leukocyte cytokine responses, serum CRP, Hp, SAA concentrations, or GM phagocytic and oxidative burst capacities. Whole food diets could have immunomodulatory effects in dogs. Future studies in non-healthy dogs are warranted.
... Dietary factors play a significant role in the initiation of innate immunity and cytokine secretion. Tomato derived compounds prevent degenerative disease by lessening the production of inflammatory mediators such as TNF-α (Riso et al., 2006) and Cox-2 catalyzes prostaglandin (Shen et al., 2007;Rafi et al., 2007;Liang et al., 1999). Neutrophil gene expression and the response to modulation with polyphenols has been described as a therapeutic approach for the treatment of chronic diseases and Cox-2 is an important target for polyphenolic agents derived from the diet (Plummer et al., 2001). ...
... Supplementation of NDEA mice with LycT modulated the serum levels of these cytokines by inhibiting their production and induction of apoptosis thus showing its anti-inflammatory effect. Literature also supported the amelioration of these inflammatory markers upon administration of lycopene [47][48][49] . ...
Aim: The present study was aimed to determine the modulatory role of lycopene enriched tomato extract (LycT) during initiation of N-nitrosodiethylamine (NDEA) induced hepatocellular carcinoma (HCC).
Methods: Female Balb/c mice were divided into 4 groups: control, NDEA (200 mg NDEA/kg b.wt, cumulative dose), LycT (5 mg/kg b.wt, thrice a week) and LycT + NDEA. LycT administration was commenced 2 weeks prior to NDEA administration in LycT + NDEA group.
Results: NDEA treatment caused histopathological alterations in hepatic tissue and was associated with enhanced serum levels of inflammatory markers, i.e., tumor necrosis factor-alpha, interleukin (IL)-6 and IL-β. NDEA treatment also induced functional alterations in liver as evident by slow 99mTc-mebrofenin hepatic excretion. LycT administration to NDEA mice showed improved hepatic functional status as demonstrated by normal 99mTc-mebrofenin excretion. NDEA treatment also caused alterations in the hematological parameters such as hemoglobin, red blood cells, platelets and total leucocyte counts. A significant increase in plasma lipid peroxidation and decrease in reduced glutathione levels with alterations in various enzymatic antioxidants were observed upon NDEA treatment. LycT pre-treatment aided in boosting the antioxidant defense system and ameliorated the inflammatory and hematological alterations.
Conclusion: As evident by improved functional, hematological and biochemical markers, it may be inferred that LycT has the potential to delay HCC initiation.
... In addition, Kirkil et al. [37] have reported that lycopene supplementation can significantly lower TNF-a levels in patients with chronic obstructive lung disease. Furthermore, RISO et al. [38] have reported the beneficial effects of tomato drink on Values are weighted mean differences with 95% CIs determined with the use of random-effects models. The heterogeneity was assessed by using the I2 statistic, and values > 50% were considered as substantial heterogeneity between studies. ...
Summary
Background and aims
Inflammation is a major cause of chronic diseases. Several studies have investigated the effects of tomato intake on inflammatory biomarkers; however, the results are equivocal. Therefore, the present study aimed to systematically review and analyses randomized clinical trials (RCTs) assessing the effects of tomato intake on inflammatory biomarkers in adults.
Methods
A systematic search was performed in PubMed, Scopus, ISI Web of Science, and Cochrane Library databases to find RCTs related to the effect of tomato intake on inflammatory markers, including C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α), up to November 2021. Meta-analyses were performed using the random-effects model.
Results
A total of 465 subjects sourced from seven eligible RCTs (8 treatment arms) were entered into the analysis. Pooled effect size of articles indicated that tomato intake was not significantly effective on CRP (WMD: 0.13 mg/dL, 95% CI: -0.09 to 0.36; P=0.23, I2: 83.9%) and IL-6 (Hedges’ g= -0.12; 95% CI -0.36, 0.13; P=0.34, I2: 0.0%) levels compared to the control group. But it can significantly reduce TNF-α (Hedges’ g= -0.45; 95% CI -0.76, -0.13; P=0.005, I2: 0.0%) levels.
Conclusion
Generally, the present study showed that tomato intake has no significant effect on serum CRP, and IL-6 concentrations, but can reduce serum TNF-α levels significantly. However, additional well-designed studies that include more diverse populations and longer duration are warranted.
... These results follow others reported with literature, whereas authors attributed the anti-inflammatory activity mainly to lycopene from the tomato juice. Riso et al. [54], exhibited modest effects on the production of TNF-α, due to tomato drink by young, healthy volunteers. Mohri et al. [55] study the anti-inflammatory activity of different compounds extracted from tomatoes on obese people. ...
A nutrient-rich diet is a key to improving the chemical signals, such as antioxidants, which modulate pathogens’ resistance in the gut and prevent diseases. A current industrial problem is the generation of undervalued by-products, such as tomato bagasse, which are rich in bioactive compounds and of commercial interest (carotenoids and phenolic compounds). This work analyzed the effect of gastrointestinal digestion on the bioactivity and bioaccessibility of carotenoids and phenolic compounds from tomato bagasse extracts. Thus, the extraction by ohmic heating (OH) technology was compared with conventional (organic solvents). The results showed that the main phenolic compounds identified by UPLC-qTOF-MS were p-coumaric acid, naringenin, and luteolin. A higher recovery index for total phenolic compounds throughout the gastrointestinal digestion was observed for OH while for carotenoids, a strong reduction after stomach conditions was observed for both extracts. Furthermore, colon-available fraction exhibited a prebiotic effect upon different Bifidobacterium and Lactobacillus, but a strain-dependent and more accentuated effect on OH. Thus, the extraction technology highly influenced bioaccessibility, with OH demonstrating a positive impact on the recovery of bioactive compounds and related health benefits, such as antioxidant, anti-hypertensive, prebiotic, and anti-inflammatory properties. Of these properties, the last is demonstrated here for the first time.
... The amount of tomato products was variable (e.g., from 80 g tomato sauce up to 300 g raw tomatoes; amount of lycopene rarely provided), as was the duration of the interventions (from 7 days up to 16 weeks). The health effects of tomatoes and tomato-based products have been evaluated in numerous dietary intervention studies in our laboratory: we showed their capacity to counteract oxidative stress and inflammation in healthy individuals [37,38], in line with other studies [21,39]. For example, in a metaanalysis of 17 studies, Cheng and colleagues [21] reported that tomato consumption was associated with significant reductions in LDL:cholesterol and inflammatory markers (IL-6), and an improvement in vascular function. ...
Carotenoids have been the object of numerous observational, pre-clinical and interventional studies focused on elucidating their potential impacts on human health. However, the large heterogeneity among the trials, in terms of study duration and characteristics of participants, makes any conclusion difficult to draw. The present study aimed to explore the current carotenoid research trends by analyzing the characteristics of the registered clinical trials. A total of 193 registered trials on ClinicalTrials.gov and ISRCTN were included in the revision. Eighty-three studies were performed with foods, one-hundred-five with food supplements, and five with both. Among the foods tested, tomatoes and tomato-based foods, and eggs were the most studied. Lutein, lycopene, and astaxanthin were the most carotenoids investigated. Regarding the goals, 52 trials were focused on studying carotenoids’ bioavailability, and 140 studies investigated the effects of carotenoids on human health. The main topics included eye and cardiovascular health. Recently, the research has focused also on two new topics: cognitive function and carotenoid–gut microbiota interactions. However, the current research on carotenoids is still mostly focused on the bioavailability and metabolism of carotenoids from foods and food supplements. Within this context, the impacts/contributions of food technologies and the development of new carotenoid formulations are discussed. In addition, the research is still corroborating the previous findings on vision and cardiovascular health. Much attention has also been devoted to new research areas, such as the carotenoid–microbiota interactions, which could contribute to explaining the metabolism and the health effects of carotenoids; and the relation between carotenoids and cognitive function. However, for these topics the research is still only beginning, and further studies are need.
... The immunomodulatory effect of carrot-extracted carotenoid was later confirmed by the Ekam, Udosen, and Chigbu (2006). Reduced risk of various kinds of cancers and, to some extent, coronary heart disease is being consistently associated with the routine intake of tomato and its products (Riso et al., 2006). Though the effect of vitamins and minerals on immune system is well proven, the focus of this review is to draw attention towards the immunomodulatory activities and phytochemicals present in certain vegetables other than the vitamins and minerals for their therapeutic uses. ...
Reorientation of life style becomes necessary for staying healthy, especially during the challenging times as it is prevailing at present. Consumption of ample plant-based foods like vegetables could be an important step towards it. However, certain vegetables hold more significance as they boost immunity. Daily intake of vegetables with immunomodulation properties (modification of the immune response or the functioning of the immune system) seems promising. The immunomodulatory properties of these vegetables are attributed to the presence of certain phytoconstituents like polysachharides (e.g. RG-I in bell pepper; CMDP-4b in pumpkin; MOP-3 in drumstick), lectins (ASA I & ASA II in garlic; BOL in cauliflower), isothiocynates (Sulforaphane in broccoli), unsaturated fatty acids (pumpkin seeds), bryonolic acid (acorn squash), ribosomes inactivating protein (Lagenin in bottle gourd), glycoprotein (Luffaculin in ridge gourd), trypsin inhibitor (MoFTI in drumsticks) etc. The aim of this review is to highlight results of work done on immunomodulatory activity of vegetables. The roles of various vegetables and their phytoconstituents, which are accountable for immunomodulation and reduction in the risk of infectious as well as non-communicable diseases, have been discussed. Such information may be encouraging for researchers to carry out further advanced research on vegetables with potential immunomodulatory properties.
... The use of lycopene can promote the function of endothelial cells, as indicated by preclinical studies. Lycopene has the ability to improve the NO bioavailability, endothelium-regulated vasodilation [170], reduce the damage to proteins, DNA, and lipids, and improve mitochondrial functioning, through its antioxidant activity [171]. Lycopene supplementation boosted mitochondrial gene expression and lowered mitochondrial dysfunction [6,172]. ...
... The use of lycopene can promote the function of endothelial cells, as indicated by preclinical studies. Lycopene has the ability to improve the NO bioavailability, endothelium-regulated vasodilation [170], reduce the damage to proteins, DNA, and lipids, and improve mitochondrial functioning, through its antioxidant activity [171]. Lycopene supplementation boosted mitochondrial gene expression and lowered mitochondrial dysfunction [6,172]. ...
Citation: Bin-Jumah, M.N.; Nadeem, M.S.; Gilani, S.J.; Mubeen, B.; Ullah, I.; Alzarea, S.I.; Ghoneim, M.M.; Alshehri, S.; Al-Abbasi, F.A.; Kazmi, I. Lycopene: A Natural Arsenal in the War against Oxidative Stress and Cardiovascular Diseases.
... The use of lycopene can promote the function of endothelial cells, as indicated by preclinical studies. Lycopene has the ability to improve the NO bioavailability, endothelium-regulated vasodilation [170], reduce the damage to proteins, DNA, and lipids, and improve mitochondrial functioning, through its antioxidant activity [171]. Lycopene supplementation boosted mitochondrial gene expression and lowered mitochondrial dysfunction [6,172]. ...
Citation: Bin-Jumah, M.N.; Nadeem, M.S.; Gilani, S.J.; Mubeen, B.; Ullah, I.; Alzarea, S.I.; Ghoneim, M.M.; Alshehri, S.; Al-Abbasi, F.A.; Kazmi, I. Lycopene: A Natural Arsenal in the War against Oxidative Stress and Cardiovascular Diseases.
... The use of lycopene can promote the function of endothelial cells, as indicated by preclinical studies. Lycopene has the ability to improve the NO bioavailability, endothelium-regulated vasodilation [170], reduce the damage to proteins, DNA, and lipids, and improve mitochondrial functioning, through its antioxidant activity [171]. Lycopene supplementation boosted mitochondrial gene expression and lowered mitochondrial dysfunction [6,172]. ...
Lycopene is a bioactive red pigment found in plants, especially in red fruits and vegetables, including tomato, pink guava, papaya, pink grapefruit, and watermelon. Several research reports have advocated its positive impact on human health and physiology. For humans, lycopene is an essential substance obtained from dietary sources to fulfil the body requirements. The production of reactive oxygen species (ROS) causing oxidative stress and downstream complications include one of the major health concerns worldwide. In recent years, oxidative stress and its counter strategies have attracted biomedical research in order to manage the emerging health issues. Lycopene has been reported to directly interact with ROS, which can help to prevent chronic diseases, including diabetes and neurodegenerative and cardiovascular diseases. In this context, the present review article was written to provide an accumulative account of protective and ameliorative effects of lycopene on coronary artery disease (CAD) and hypertension, which are the leading causes of death worldwide. Lycopene is a potent antioxidant that fights ROS and, subsequently, complications. It reduces blood pressure via inhibiting the angiotensin-converting enzyme and regulating nitrous oxide bioavailability. It plays an important role in lowering of LDL (low-density lipoproteins) and improving HDL (high-density lipoproteins) levels to minimize atherosclerosis, which protects the onset of coronary artery disease and hypertension. Various studies have advocated that lycopene exhibited a combating competence in the treatment of these diseases. Owing to all the antioxidant, anti-diabetic, and anti-hypertensive properties, lycopene provides a potential nutraceutical with a protective and curing ability against coronary artery disease and hypertension.
... On the contrary, lycopene supplementation failed to decrease MDA and hydroxyl nonenal (HNE) levels, as reported by two placebo-controlled RCTs in healthy populations [54,61]. The 8-iso-PGF2α level was also unaltered with supplementation of a lycopenerich tomato-based drink [64]. However, a decreased MDA was evident in postmenopausal females with the lycopene supplementation [65]. ...
Carotenoids are natural pigments generally with a polyene chain consisting of 9–11 double bonds. In recent years, there has been increasing research interest in carotenoids because of their protective roles in cardiovascular diseases (CVDs). While the consumption of carotenoids may have a beneficial effect on CVDs, the literature shows inconsistencies between carotenoid consumption and reductions in the risk of CVDs. Therefore, this review aims to provide a summary of the association between dietary carotenoid intake and the risk of CVDs from published epidemiological studies. Meanwhile, to further elucidate the roles of carotenoid intake in CVD protection, this review outlines the evidence reporting the effects of carotenoids on cardiovascular health from randomized controlled trials by assessing classical CVD risk factors, oxidative stress, inflammatory markers and vascular health-related parameters, respectively. Given the considerable discrepancies among the published results, this review underlines the importance of bioavailability and summarizes the current dietary strategies for improving the bioavailability of carotenoids. In conclusion, this review supports the protective roles of carotenoids against CVDs, possibly by attenuating oxidative stress and mitigating inflammatory response. In addition, this review suggests that the bioavailability of carotenoids should be considered when evaluating the roles of carotenoids in CVD protection.
... The anti-inflammatory activity of tomato and lycopene might also contribute to beneficial effects in cardiovascular health. It was shown to reduce tumor necrosis factor-α concentrations in healthy individuals [145]. Lycopene alleviated chronic prostatitis/chronic pelvic pain syndrome in a rat model, presumably due to its anti-inflammatory properties: cytokines tumor necrosis factor-α, interleukin-1β, interleukin-2, and interleukin-6 were downregulated; phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) decreased, while phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2) increased [146]. ...
Benign prostatic hyperplasia (BPH) is one of the most common urinary diseases affecting men, generally after the age of 50. The prevalence of this multifactorial disease increases with age. With aging, the plasma level of testosterone decreases, as well as the testosterone/estrogen ratio, resulting in increased estrogen activity, which may facilitate the hyperplasia of the prostate cells. Another theory focuses on dihydrotestosterone (DHT) and the activity of the enzyme 5α-reductase, which converts testosterone to DHT. In older men, the activity of this enzyme increases, leading to a decreased testosterone/DHT ratio. DHT may promote prostate cell growth, resulting in hyperplasia. Some medicinal plants and their compounds act by modulating this enzyme, and have the above-mentioned targets. This review focuses on herbal drugs that are most widely used in the treatment of BPH, including pumpkin seed, willow herb, tomato, maritime pine bark, Pygeum africanum bark, rye pollen, saw palmetto fruit, and nettle root, highlighting the latest results of preclinical and clinical studies, as well as safety issues. In addition, the pharmaceutical care and other therapeutic options of BPH, including pharmacotherapy and surgical options, are discussed, summarizing and comparing the advantages and disadvantages of each therapy.
... Higher lycopene concentrations of 35 mg to 75 mg per day could be appropriate for reducing risk of diseases such as cancer and cardiovascular disorders (Heath et al., 2006). Tomato products intake anti-inflammatory properties outweigh the lycopene in a single compound (Hazewindus et al., 2012;Riso et al., 2006). ...
Tomato (Lycopersicum esculentum L.) is an excellent source of many nutrients and secondary metabolites that are important for human health. Its fruits are rich in antioxidant compounds, which are important for human metabolism. Lycopene is one of the abundantly occurring antioxidants found in tomato. Lycopen is beneficial in preventing various chronic diseases such as can- cer, cardiovascular diseases etc. Tomato is an important source of bioactive compounds which have antioxidant, anti-mutagenic, anti-proliferative, anti- inflammatory and anti-atherogenic activities. A group of vitamins (ascorbic acid and vitamin A), phenolic compounds (phenolic acids and flavonoids), carotenoids (lycopene, α, and β carotene), and glycoalkaloids (tomatine) are found in tomato. These compounds can provide protection to our health by neutralizing free radicals which are responsible for the growth of a range of degenerative diseases. The present review provides collective informa- tion on the pharmacological actions and chemistry of bioactive compounds (carotenoids, lycopene, β –carotene, lutein, and vitamins) found in tomato along with discussing possible health benefits.
... The aspects of productivity and sensory quality have attracted most attention, but recently, there has been increasing interest in the nutritional value of fruits and vegetables [14], as consumers demand products with a high content of health-promoting constituents. In this respect, tomato is an important source of carotenoids such as β-carotene, a precursor of vitamin A; lycopene, which has been associate to a reduction in the risk of cancer, cardiovascular disease and macular degeneration [15]; lutein, which plays a fundamental role in the protection of vision [16] and in preventing age-related maculopathy [17]; others that have been less well studied, such as phytoene and phytofluene, which may contribute to inhibiting the progression of atherosclerosis [18]. Furthermore, tomato is also a source of phenolic compounds such as flavonoids and hydroxycinnamic acid derivatives and vitamins such as ascorbic acid. ...
In light of foreseen global climatic changes, we can expect crops to be subjected to several stresses that may occur at the same time, but information concerning the effect of long-term exposure to a combination of stresses on fruit yield and quality is scarce. This work looks at the effect of a long-term combination of salinity and high temperature stresses on tomato yield and fruit quality. Salinity decreased yield but had positive effects on fruit quality, increasing TSS, acidity, glucose, fructose and flavonols. High temperatures increased the vitamin C content but significantly decreased the concentration of some phenolic compounds (hydroxycinnamic acids and flavanones) and some carotenoids (phytoene, phytofluene and violaxanthin). An idiosyncrasy was observed in the effect of a combination of stresses on the content of homovanillic acid O-hexoside, lycopene and lutein, being different than the effect of salinity or high temperature when applied separately. The effect of a combination of stresses may differ from the effects of a single stress, underlining the importance of studying how stress interactions may affect the yield and quality of crops. The results show the viability of exploiting abiotic stresses and their combination to obtain tomatoes with increased levels of health-promoting compounds.
... For example, it has been shown that spiral ganglion cell damage can be induced by the macrophage-mediated immune response [33], while inflammationassociated vascular changes may induce the vasospasm of stria vascularis [19]. Several controlled interventions have demonstrated that inflammatory markers could be decreased by a change in dietary pattern or of single foods [34][35][36]. However, the utility of dietary supplements to preserve hearing remains to be determined. ...
Age-related hearing loss (ARHL) is a major and rapidly growing public health problem thatcauses disability, social isolation, and socioeconomic cost. Nutritional status is known to cause manyaging-related problems, and recent studies have suggested that there are interaction effects betweenARHL and dietary factors. We aimed to investigate the association between ARHL and dietaryassessment using data from the fifth Korean National Health and Nutrition Examination Survey,which is a nationwide cross-sectional survey that included 5201 participants aged≥50 years from2010 to 2012. All participants had normal findings on otoscopic examination and symmetric hearingthresholds of <15 dB between both sides. Nutritional survey data included food consumption andnutrient intake using the 24 h recall method. Data were analyzed using multiple regression modelswith complex sampling adjusted for confounding factors, such as age, sex, educational level, andhistory of diabetes. Higher intake of seeds and nuts, fruits, seaweed, and vitamin A were positivelyassociated with better hearing. Our findings suggest that dietary antioxidants or anti-inflammatoryfood may help reduce ARHL
... Tomatoes are 95% composed of water, essential nutrients and bioactive components (United States Department of Agriculture 2021) such as high amounts of vitamin A, C, fibers, potassium, and various chemoprotective components that can promote the maintenance of redox homeostasis (Burton-Freeman and Sesso 2014), such as polyphenols and carotenoids, among which LYC, phytoene, phytofluene, beta-carotene, naringenin, quercetin, rutin and others (Marti, Rosello, and Cebolla-Cornejo 2016) (Table 1). (Riso et al. 2006). LYC concentrations in human body tissues -particularly in the liver, lungs, prostate gland, colon, and skin -are superior to that of other carotenoids (Srivastava and Srivastava 2015). ...
ABSTRACT
Oxidative stress is a major factor in aging and is implicated in the pathogenesis of tumors, dia- betes mellitus, cardiovascular and neurodegenerative diseases, including Alzheimer Disease (AD). Bioactive constituents of tomato as polyphenols and carotenoids, among which lycopene (LYC) are effective in reducing markers of oxidative stress, and appear to have a protective modulator role on the pathogenetic mechanisms, cognitive symptoms and behavioral manifestations of these diseases in cell cultures and animal models. Epidemiological evidence indicates a consistent associ- ation between the intake of tomatoes and reduced cardiovascular and neoplastic risk. LYC defi- ciency is common in elders and AD patients and it is strongly predictive of mortality and poor cardiovascular (CV) outcomes. Dietary intake of tomatoes seems to be more effective than tomato/LYC supplementation. Limited evidence from human intervention trials suggests that increasing tomato intake, besides improving CV markers, enhances cognitive performances. In this narrative review, we analyze the existing evidence on the beneficial effects of tomatoes on AD- related processes or risk factors. Results support the development of promising nutritional strat- egies to increase the levels of tomato consumption for the prevention or treatment of AD and other dementias. Extensive well-structured research, however, is mandatory to confirm the neuro- protective effects of tomato/LYC in humans.
... Higher lycopene concentrations of 35 mg to 75 mg per day could be appropriate for reducing risk of diseases such as cancer and cardiovascular disorders (Heath et al., 2006). Tomato products intake anti-inflammatory properties outweigh the lycopene in a single compound (Hazewindus et al., 2012;Riso et al., 2006). ...
Tomato (Lycopersicum esculentum) is suitable for the manufacture of drugs, especially for oral delivery; it is a popular vegetable. Lycopene is one of the most strong, naturally and abundantly occurring antioxidants in tomato. It has unique structural and chemical characteristics that contribute to the biological characteristics and pharmacologic actions for lower risk of different chronic diseases, such as cancer and different cardiovascular diseases. Tomato fruit consumption can be associated with various beneficial effects on health. Tomato is an important source of biopsy compounds, having vitamin antioxidants and anticancer substances. A group of vitamins, carotenoids, phenolic acid, and phenolic compounds, are antioxidant metabolites found in tomato that can provide effective protection by neutralizing free radicals and these unstable molecules associated with the growth of a range of degenerative diseases and conditions. This review paper summarizes the pharmacological actions of bioactive compounds (carotenoids, lycopene, β carotene, lutein, and vitamins) and their chemistry. This reviewed information may be valuable source for nutritionist, health workers and tomato growers. [Fundam Appl Agric 2021; 6(2.000): 210-224]
... If we consume tomato in any form like raw tomatoes, tomato sauce or tomato sauce with refined olive oil, it decreases plasma total cholesterol, triglycerides level and several cellular and plasma inflammatory biomarkers, besides it increased plasma HDL cholesterol (Riso et al., 2006). Adding oil to the tomato sauce caused greater changes of plasma and vascular cell adhesion molecules. ...
Red color foods and their impact on human health are always positive and beneficial. Lycopene is a carotenoid while citrulline lowers the hypertension. Strawberries have a photochemical fight against hyperglycemia and dyslipidemia. The outcomes of sweet fruits as wellbeing promoters, especially their antimicr anticancer, hostile to neuro described in this study. Cherries as an antioxidant have blood cancer prevention agent capacity. Cherry "greasy liver product shows antibacterial, mitigating, antiviral, and against cancer activities. Pomegranate counteracts diabetes, dental conditio brokenness, bacterial contaminations, anti brought about by bright. Aftereffects of a creature study demonstrated that both lycopene and tomato powder supplementation given independently were similarl successful and advantageous in lessening provocative and metabolic issues that happen with a high anthocyanin. An investigation on humans show drink of strawberry diminished feast evoked postprand (hs-CRP) and IL Solidified strawberries refreshment seems to have a calming reaction. Beet root contains contingents, a rich c and dyslipidemia. Various constituents in red lessening foundational irritation and fortifying safe status by diminishing diseases.
... Magnolia officinalis [181] o r a n y w h e r e . [165][166][167], anti-cancer and anti-proliferative properties [168]. Lycopene decreased the expression of chemokine (Fig. 3) in macrophages and pro-inflammatory chemokines [169,170]. ...
Alzheimer's disease (AD) is an irrevocable chronic brain disorder featured by neuronal loss, microglial accumulation, and progressive cognitive impairment. The proper pathophysiology of this life-threatening disorder is not completely understood and no exact remedies are found yet. Over the last few decades, research on AD has mainly highlighted in pathomechanisms linked to a couple of the major pathological hallmarks, including extracellular senile plaques, made of amyloid-β (Aβ) peptides, and intracellular neurofibrillary tangles (NFTs), made of tau proteins. Aβ can induce apoptosis, trigger an inflammatory response, and inhibit the synaptic plasticity of the hippocampus, which ultimately contributes to reducing cognitive functions and memory impairment. Recently, a third disease hallmark, the neuroinflammatory reaction that is mediated by cerebral innate immune cells, has become a spotlight in the current research area, assured by pre-clinical, clinical, and genetic investigations. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a cytokine producer, is significantly associated with physiological inflammatory proceedings and thus showing a promising candidate for inflammation-based AD therapy. Recent data reveal that phytochemicals mainly polyphenols compounds exhibit potential neuroprotective functions and it may be considered as a vital resource for discovering several drug candidates against AD. Interestingly, phytochemicals can easily interfere with the signaling pathway of NF-κB. This review represents the anti-neuroinflammatory potential of polyphenols as inhibitors of NF-κB to combat AD pathogenesis.
... Tomatoes are rich in lycopene [242]. Riso et al. stated that lycopene found in tomatoes slows down aging by stopping free radicals from binding with oxygen, a process that slows immune building, cleansing, and repair, and that consumption of tomatoes has been shown to be associated with a lower risk of several types of cancer [243]. Another study found that TNF-a levels were 34.4% lower in the subjects who drank tomato juice in comparison to those who do not [244]. ...
During aging, physiological and physical frailty occur, which is accompanied by a decline in adaptive and innate immunity, termed 'immunosenescence' characterized by marked changes in the composition, function, and competence of the human immune system. Moreover, the capabilities of the immune system to defend the human body against infections, to detect and destruct malignant or autoreactive cells decline, resulting in an increase in the susceptibility to infection, development of cancer, as well as autoimmune disorders. The study of age-related changes in immune function is an important area of investigation. In this review, the function of the immune system during aging, as well as the different ways to rejuvenate the aging immune system, is explored, as medical intervention, balanced nutrition, and a healthy life style will be discussed.
Background and objective:
In recent times, modifying dietary habits to control cardiovascular risk factors has gained significant attention. However, previous studies have yielded inconsistent results regarding the effects of lycopene and tomato consumption on cardiovascular risk factors.
Objective:
The objective of this study was to assess the impact of consuming lycopene and tomatoes on various cardiovascular risks factors such as lipid profile, glycemic control markers, blood pressure, inflammation, oxidative stress, and body weight.
Methods:
A systematic literature search was carried out using electronic databases, including PubMed, Web of Science, and Scopus, up to November 2022 to identify eligible Randomized Control Trials (RCTs) evaluating the effect of lycopene and tomato consumption on cardiovascular risk factors. Heterogeneity tests of the selected trials were performed using the I2 statistic. Random effects models were assessed based on the heterogeneity tests, and pooled data were determined as the weighted mean difference (WMD) with a 95% confidence interval (CI).
Results:
Out of 27,438 records initially identified, a total of 34 studies met the eligibility criteria and were included in this meta-analysis. The results showed that lycopene consumption was associated with a significant reduction in malondialdehyde (MDA) levels, indicating a potential benefit in reducing oxidative stress. However, lycopene and tomato consumption did not have significant effects on other cardiovascular risk factors such as triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), systolic blood pressure (SBP), diastolic blood pressure (DBP), Intercellular Adhesion Molecule 1 (ICAM-1), c-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), body weight, and body mass index (BMI).
Conclusion:
Overall, the findings showed that lycopene and tomato consumption did not affect cardiovascular risk factors. However, lycopene supplementation may result in a significant improvement in MDA levels. With the view to confirming these results, further studies with long-term duration and different doses are needed.
Vegetables are essential part of agriculture production systems and play crucial role in maintaining human life. Sustainable and increasing fruit and vegetable crop production is a critical problem to ensure future food security due to a continual increase in global population and the resulting need for more food. New strategies are needed to further enhance horticulture crop yield, even if conventional breeding techniques have made a considerable contribution to the creation of significant cultivars
Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9 (Cas9), is a new breeding method, has the potential to rapidly and accurately improve a variety of traits, including yield, quality, disease resistance, abiotic stress tolerance, and nutritional qualities in crops. This technique has been used to acquire additional germplasm resources through gene-directed mutation because to its straightforward operation and high mutation efficiency. The capacity to precisely modify essential genes via CRISPR-Cas9 editing can quickly produce new germplasm resources for the development of critical agronomic traits due to the availability of whole-genome sequencing data and knowledge about the role of genes for vital traits
Background
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).Method
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).ResultDuring 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.Conclusion
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.
Bioactive compounds are chemical substances present in small quantities in the food we eat that are known to possess biological activities. Various bioactive compounds have been described and evaluated for their protective effects on human health. They can present with antioxidant, anti-inflammatory, and anticarcinogenic properties with associated physiological and cellular effects that can be protective against various chronic diseases and metabolic disorders, such as diabetes, cardiovascular diseases, and cancer, among others. They are mainly found in fruits and vegetables, and their consumption in diets with pertinent beneficial health effects make them good candidates for development into nutraceuticals and functional foods with potential protective and therapeutic properties. Discussed in this book chapter are numerous bioactive compounds found mainly in plants that have beneficial effects on health and disease, and which are also known to have positive effects on the genome manifested as improvements in the metabolomic and clinical profiles of patients. Although further research is still needed to understand the exact mechanisms of their biological actions, it is beyond a doubt that people should eat more fruits and vegetables so that they get more of these bioactive compounds and benefit from their positive health effects.
Research in the area of diet-associated inflammation is growing at a very rapid rate, with the literature size approximately doubling every 5 years. The wide expanse and general consistency of the literature provide abundant evidence for describing what antiinflammatory diets taste, look, and feel like. Fortunately, naturally colorful foods with the most interesting flavor profiles also are the ones that are most antiinflammatory. The organoleptic, or sensual, properties of natural food, while very rarely a specific focus of epidemiologic study, are consistent with recommendations that we can make—and education we can bestow—regarding consumption of an antiinflammatory diet. As we discuss, the most antiinflammatory diets consist of whole foods, primarily of plant origin. These foods also are the most nutrient-dense and have the lowest concentration of calories per unit weight or volume. By contrast, diets that are proinflammatory tend to be naturally white or colorless and have little natural flavor, even though some may have strong taste (e.g., sucrose or high fructose corn syrup, which tastes sweet). Rather than trying to limit portion sizes of proinflammatory, calorie-dense, nutrient-sparse ultraprocessed foods, including confectioneries and candy, snack items, sugar-sweetened beverages, and meat products, the preferred strategy is to displace consumption of these proinflammatory foods with nutrient-rich, antiinflammatory foods. Because these antiinflammatory foods also are relatively low in calories, they can be eaten in relatively large quantities without undue concern regarding energy balance. Though evidence behind these recommendations is solid, there are structural, societal barriers that must be overcome in order to create environments in which these healthy, antiinflammatory foods are made readily available and consumption is encouraged in societies that are committed to improving population health.
Our inflammatory response and innate immune systems started evolving two billion years ago—long before we humans—and our adaptive immune system—came into being. While the look back in time is useful and productive, epidemiologists and other scientists, who typically follow “lagging indicators,” now must do a better job of anticipating where problems will emerge and, to the extent possible, devising means for preventing them from developing. Unlike the 300,000 years since our emergence as a species and the hundreds of millions of years preceding that, during the Anthropocene epoch, humans have been the primary agents of massive ecological change. Global climate change has resulted in extreme pressure on means of food production. The consequent increase observed in the inflammatory capacity of ultraprocessed foods parallels the rising temperatures globally. With this as background, we make specific recommendations for additional research in areas we believe represent frontiers in the effort to understand and control chronic systemic inflammation including: deep emotional issues related to the chemical senses; amelioration of pain—both physical and mental; discrimination and other psychosocial stress; losses in agricultural productivity and nutrient adequacy in a hotter world; autoimmune diseases and food allergies; how coevolution with microbes can provide additional insight into inflammatory and immune responses; and looking outward and connecting back to global environmental crises to consider the Gaia Hypothesis as a framework for ecological regulation and homeostasis for a more sustainable world with lower overall inflammatory potential. Finally, we discuss the need to engage governmental actors, nongovernment organizations, and commercial entities in order to affect policy changes, marketing decisions, and even methods of conflict resolution in order to optimize making nutrition recommendations regarding both public health and personalized medicine.
Understanding how nutrition has evolved and influenced inflammation over time is essential for placing current knowledge into context and for informing future action. Focusing on the natural history of nutrition and inflammation brings us to the time that life began on our planet—when all the raw ingredients and nutrients necessary for biological functioning were made available and primitive organisms began developing the ability to mount inflammatory, and related innate immune, responses. This review of the ancient history of nutrition and inflammation sets the stage for explaining observations made on the role of nutrition in inflammation during the course of human history. References to the role of nutrition in health extend back into ancient Greek, Indian, and Chinese historical literature. Beginning with classical studies such as the trial conducted by Lind among sailors in the British Royal Navy that established ascorbic-rich foods as a cause of scurvy, we explore the evidence that has accumulated regarding the effect of specific nutrients in relation to inflammation-related diseases. In so doing, we also present evidence for linking deficiencies in other specific nutrients, such as niacin, thiamin, and vitamin D to diseases such as pellagra, beriberi, and rickets that have been important in the history of public health. We then describe evidence implicating combinations of nutrients and dietary patterns that are strongly related to inflammation-related outcomes, including a wide range of chronic diseases. Finally, we discuss the role of nutrition and public health problems that have emerged in the modern era that are linked with overconsumption of energy-dense foods and related macronutrients rather than deficiencies of specific micronutrients. This provides a foundation for subsequent chapters in this book, culminating with the synthesis of where we stand and recommendations for future action, in terms of both research challenges and public health action.
Several authors have pointed out valorization of food wastes and by-products as a solution to improve the economic and environmental sustainability of the food production chain. Numerous valorization schemes have been proposed to explore food wastes and by-products as biomass suppliers to obtain different bio-based products. Among them, integrated value chains have been identified as one of the most promising pathways to achieve the zero-waste goal and accelerate the transition of the food industry to a circular bioeconomy. This chapter applies a mixed-method review methodology to identify the main food waste and by-product streams and to recognize the most promising value-added uses and integrated valorization approaches developed to date for the application of food wastes and by-products. The proposal of new valorization schemes and the indication of the main challenges that need to be addressed to guarantee their implementation in the food industry are also pointed out.
Hypertension and diabetes are two of the leading causes of morbidity and mortality in the current world population, especially in Western societies. These two pathological conditions are key risk factors for the onset and progression of many cardiovascular diseases such as stroke, atherosclerosis, pulmonary hypertension, thrombosis, and heart failure. In general, hypertension and diabetes mellitus coexist in most patients with metabolic disorders. Both pathologies usually develop concomitantly or consecutively in the same individual due to different underlying pathophysiologic mechanisms that are shared between them. Some of these mechanisms include inadequate renin-angiotensin-aldosterone system activation, insulin resistance, dysfunctional immune response, inflammation, oxidative stress, abnormal sodium renal management, exacerbated sympathetic nervous system activation, and endothelial dysfunction, among others.
Diabetes, retinopathy, and cardiovascular diseases are alarmingly increasing day by day due to malnutrition and unhealthy lifestyle. Dietary life style may be the initial step for prevention of diabetes and cardiovascular diseases. Some other factors are also associated with life style like physical exercises, daily intake of vegetable, fruit, cereal, omega-3 fats, and tobacco and alcohol consumption. It is a common quote that eats healthy to stay healthy. Same is suggested by scientific data that carotenoids are important in the prevention of these diseases because of antioxidant and antiinflammatory action. Carotenoids have been proved by epidemiological studies to be protective against cardiovascular disease. All these reports need in vitro and intervention studies in well-controlled conditions so that these results will be more valid. Mixed results have been reported from interventional trials with some positive and many insignificant outcomes. These discoveries also recommended some harm in certain high-risk populations. The objective of this chapter is to summarize the writings accessible about the consumption of carotenoids in the management of cardiovascular disease, retinopathy, and diabetes.
Carotenoids possess strong anti-inflammatory and antioxidant actions in addition to a plethora of other properties. These actions of carotenoids are primarily due to their structure which dictate their functions. Because of their protective potential in disease states, carotenoids are associated with prevention and/or treatment of various neurological diseases. In this chapter, the role(s) of carotenoids in various neurological diseases such as Alzheimer’s disease, vascular dementia, Lewy body dementia, mild cognitive impairment, neurological trauma, brain tumor, schizophrenia, depression, Parkinson’s disease and multiple sclerosis, have been reviewed. A number of studies report associations of low levels of carotenoids with higher likelihood of neurological diseases. Other investigations describe beneficial and protective effects of pharmacological or dietary interventions which lead to enhancement of carotenoids levels in the body. However, further validation of these beneficial actions is required both in clinical and animal studies. Development of good animal models of neurological diseases will help.
Cardiovascular disease alarmingly increases day by day due to malnutrition and unhealthy lifestyle. Dietary intervention may be the initial step for CVD prevention but great importance should be attributed to the life style improvement: increase of physical activity, avoidance of tobacco exposure, limiting alcohol intake and consumption of healthy diet containing monounsaturated fats, vegetables fiber, cereals, essential oils and fruits. It is generally considered that “prevention is better than cure” and recent scientific data suggested the carotenoids as preventing agent for several chronic disorders. Carotenoids are well known for their antioxidant and anti-inflammatory activities. Clinical trials displayed a decrease in inflammatory disease risk after carotenoids supplementation. Oxidative pressure and irritation is major contributor for the development of cardiovascular diseases. Numerous epidemiologic studies reveled that cheap means to prevent and treat cardiac problems is the use of antioxidants. Mixed results have been found from interventional trials which are effective and many are invalid findings. These findings also suggested danger in certain vulnerable populations. The purpose of this section is to review the works existing around the practice of carotenoids in the action of cardiovascular disease.
The vast number of chemicals existing or being added into the environment, have globally aroused great concern regarding their adverse effects in human population. Development and validation of sensitive and better test systems which can assess the adverse effects of chemicals at an early stage for intervention strategies to be implemented in time is currently in progress. This book documents the latest research and showcases the versatile, state-of-the-art technique - the Comet assay - in the field of modern toxicology. The assay is a simple, sensitive rapid and visual technique for the quantitative and qualitative assessment of DNA damage in single cells. The Comet Assay in Toxicology is the first book of its kind to be devoted exclusively to the Comet assay and its applications as an important tool in modern toxicology. This multi-author book will serve as both a reference and a guide to investigations in the biomedical, biochemical and pharmaceutical sciences. Written by investigators from the fields of genetic toxicology and human epidemiology, the authors have first-hand knowledge from their chosen sub-specialities and are active contributors to the peer-reviewed scientific literature. The book is divided into five major sections, reflecting the range of interest in the exploitation of this assay. The book's scope begins with an introduction section reviewing its genesis for those new to the technique and the current knowledge of the various fields in which it finds wide acceptance. This section sets the scene by explaining why the assay has become the most sensitive and sought after assay in modern toxicology. Next is a whole section that considers various procedures being followed to assess different types of DNA damage in various cell types and is contributed by experts in the respective fields. The third section puts together the specific applications of the assay in the diverse fields ranging from genetic toxicity testing to human monitoring, and environmental toxicology. The fourth section consists of the guidelines and recommendations for the conduct of the assay in in vitro and in vivo systems, based on the recommendations of the International Workgroups on genotoxicity test procedures. Finally, the book draws to a close with an assessment of the statistics used for the understanding of the data generated by the assay. This is a unique reference book as it provides the scientific community with the advances in Comet assay as well as its applications. It also incorporates a detailed section with instant and comprehensive information on the procedure of the assay and the latest protocols being used worldwide as well as statistical analyses to be followed. The book is aimed at students as well as scientists in the area of molecular epidemiology and genetic toxicology.
Dietary patterns are changing rapidly all over the world. The body of available local food knowledge, which forms the basis of many local traditions, is decreasing dramatically. In rural areas throughout the Mediterranean, vegetables and salads made from wild plants have been particularly important as local foods since ancient times. However, very little is known about the use of these wild food plants (WFPs) and about their contribution to health, while numerous clinical and pharmacological-biochemical studies have shown beneficial effects for major components of Mediterranean diets. This research project studied WFPs used in the Graecanic area in Calabria, Southern Italy as components of the local diet with potential antioxidant activity. It was embedded in an EU-funded project entitled "Local Food - Nutraceuticals". The research approach adopted for this interdisciplinary research combined ethnobotanical methods with pharmacology and nutritional sciences. The gathering, processing and consumption of these plants were studied using participant observation techniques and semi-structured interviews. Local perceptions about WFPs (beneficial health effects, health risks) and nutritional data were obtained through a socio-nutritional study conducted in Italy, Spain and Greece. More than 40 WFPs are used as condiments, or vegetables, including edible greens, called ta chòrta in the local language. Many are considered to be healthy because of their bitterness (e.g. Reseda alba). Furthermore, the antioxidant activity of WFPs from Italy, Spain and Greece, was evaluated using in vitro assays. Crude extracts were tested for free radical scavenging activity (FRSA), and for the inhibition of xanthine oxidase (XO). Only a small number of plant extracts showed significant antioxidant activity. However, some extracts had promising activity in the XO-system. This interdisciplinary research contributed not only to the understanding of locally used WFPs as a promising source of natural antioxidants, but also to the safeguarding of this rapidly vanishing local knowledge.
Human lymphocytes were either exposed to X-irradiation (25 to 200 rads) or treated with H2O2 (9.1 to 291 μM) at 4 °C and the extent of DNA migration was measured using a single-cell microgel electrophoresis technique under alkaline conditions. Both agents induced a significant increase in DNA migration, beginning at the lowest dose evaluated. Migration patterns were relatively homogeneous among cells exposed to X-rays but heterogeneous among cells treated with H2O2. An analysis of repair kinetics following exposure to 200 rads X-rays was conducted with lymphocytes obtained from three individuals. The bulk of the DNA repair occurred within the first 15 min, while all of the repair was essentially complete by 120 min after exposure. However, some cells demonstrated no repair during this incubation period while other cells demonstrated DNA migration patterns indicative of more damage than that induced by the initial irradiation with X-rays. This technique appears to be sensitive and useful for detecting damage and repair in single cells.
The effects of antioxidants and various other modifying agents on oxygen-radical-generated DNA damage in human lymphocytes have been investigated using the COMET assay. Hydrogen peroxide (H2O2) and bleomycin (BLM) have produced clear dose-related responses. In 38 independent experiments, there was consistency between the two donors used in the study for the negative and positive control data. The endogenous antioxidant catalase abolished effects with H2O2, but only slightly affected the response with BLM. Superoxide dismutase did not alter the response with H2O2 and only slightly affected BLM. The exogenous antioxidant vitamin C produced a clear dose-related response on its own. In combination with H2O2, there were small protective effects at low doses and exacerbating effects at high doses, but these were within the inter-experimental variability range. Vitamin E (trolox) produced no effects with either H2O2 or BLM, or on its own. Silymarin protected against the effect due to H2O2. Other modifying agents such as apo-transferrin and deferoxamine mesylate produced a clear dose-related protection of effects due to BLM. This protection was less due to H2O2. In the presence of ferrous chloride, the effect due to BLM was exacerbated. In a small sample of 6 smokers and 6 non-smokers, responses from smokers approached borderline significance (P = 0.054) by comparison with non-smokers. These observations would suggest that the COMET assay is a useful tool for examining issues related to oxidative stress in human lymphocytes.
The immunomodulatory potential of carotenoids has been investigated thoroughly only for beta-carotene. Data on the immunomodulatory activity of other carotenoids such as lycopene are scarce. The objective of this study was to investigate the effects of prolonged tomato juice consumption on cell-mediated immunity of well-nourished healthy elderly persons. In an intervention study, 33 female and 20 male subjects (aged 63-86 y) consumed 330 mL/d tomato juice (47.1 mg/d lycopene) or mineral water for 8 wk. Immune status was assessed by measuring number and lytic activity of natural killer (NK) cells, secretion of cytokines [interleukin (IL)-2, IL-4, tumor necrosis factor-alpha (TNF-alpha)] by activated peripheral blood mononuclear cells (PBMC), lymphocyte proliferation, and delayed-type hypersensitivity (DTH) skin responses. Tomato juice consumption resulted in significantly increased plasma lycopene and beta-carotene concentrations over time. In both treatment groups, TNF-alpha and IL-4 secretion were increased at the end of the intervention period, whereas IL-2 secretion was decreased. Tomato juice consumption had no effect on lymphocyte proliferation, DTH or the number of NK cells. Lytic activity of NK cells was increased in both groups at the end of the intervention period. In conclusion, these results show that prolonged tomato juice consumption increased plasma lycopene concentrations without significantly affecting cell-mediated immunity in well-nourished elderly subjects.
Epidemiology suggests that Mediterranean diets are associated with reduced risk of cardiovascular disease. Because monocyte adhesion to the endothelium is crucial in early atherogenesis, we evaluated whether typical olive oil and red wine polyphenols affect endothelial-leukocyte adhesion molecule expression and monocyte adhesion.
Phytochemicals in olive oil and red wine, including oleuropein, hydroxytyrosol, tyrosol, elenolic acid, and resveratrol, with or without antioxidant activity, were incubated with human umbilical vein endothelial cells for 30 minutes, followed by co-incubation with bacterial lipopolysaccharide or cytokines to trigger adhesion molecule expression. At nutritionally relevant concentrations, only oleuropein, hydroxytyrosol, and resveratrol, possessing a marked antioxidant activity, reduced monocytoid cell adhesion to stimulated endothelium, as well as vascular cell adhesion molecule-1 (VCAM-1) mRNA and protein by Northern analysis and cell surface enzyme immunoassay. Reporter gene assays with deletional VCAM-1 promoter constructs indicated the relevance of nuclear factor-kappaB, activator protein-1, and possibly GATA binding sites in mediating VCAM-1 transcriptional inhibition. The involvement of nuclear factor-kappaB and activator protein-1 was finally demonstrated at electrophoretic mobility shift assays.
Olive oil and red wine antioxidant polyphenols at nutritionally relevant concentrations transcriptionally inhibit endothelial adhesion molecule expression, thus partially explaining atheroprotection from Mediterranean diets.
Antioxidant properties of carotenoids are thought to be at least partly responsible for the protective effects of fruits and vegetables rich in carotenoids against colon cancer. There are large amounts of in vitro data supporting this hypothesis. But there is little known about the antioxidant effects of carotenoid-rich food in vivo particularly in the gastrointestinal tract. In a randomized, crossover trial, healthy men (n = 22) who were consuming a low-carotenoid diet drank 330 mL/d tomato juice or carrot juice for 2 wk. Antioxidant capacity was assessed by the "lag time" of ex vivo LDL oxidation induced by copper and lipid peroxidation as determined by measurements of malondialdehyde (MDA) in plasma and feces using HPLC with fluorescence detection. Although consumption of both carotenoid-rich juices for 2 wk increased the carotenoid level in plasma and feces (P < 0.001), the antioxidant capacity of LDL tended to be increased by only approximately 4.5% (P = 0.08), and lipid peroxidation in the men's plasma and feces was not affected. Thus, processes other than lipid peroxidation could be responsible for the preventive effects of tomatoes and carrots against colon cancer.
In this overview to a new thematic series on the immune system and atherogenesis, I provide a very brief summary of current conceptions of atherogenesis, of the innate and adaptive immune systems, and of the participation of the latter in atherogenesis, with particular emphasis on studies of the involvement of the immune system in atherosclerosis reported in the last 2 years. This is followed by a short outline of the eight reviews that will make up this thematic series.
The overview is concluded with some caveats that should be considered in the analysis of atherosclerosis in experimental animals.
The salutary characteristics of the tomato are normally related to its content of carotenoids, especially lycopene, and other antioxidants. Our purpose was to verify whether the daily intake of a beverage prototype called Lyc-o-Mato((R)) containing a natural tomato extract (Lyc-o-Mato((R)) oleoresin 6 %) was able to modify plasma and lymphocyte carotenoid concentrations, particularly those of lycopene, phytoene, phytofluene and beta-carotene, and to evaluate whether this intake was sufficient to improve protection against DNA damage in lymphocytes. In a double-blind, cross-over study, twenty-six healthy subjects consumed 250 ml of the drink daily, providing about 6 mg lycopene, 4 mg phytoene, 3 mg phytofluene, 1 mg beta-carotene and 1.8 mg alpha-tocopherol, or a placebo drink. Treatments were separated by a wash-out period. Plasma and lymphocyte carotenoid and alpha-tocopherol concentrations were determined by HPLC, and DNA damage by the comet assay. After 26 d of consumption of the drink, plasma carotenoid levels increased significantly: concentrations of lycopene were 1.7-fold higher (P<0.0001); of phytofluene were 1.6-fold higher (P<0.0001); of phytoene were doubled (P<0.0005); of beta-carotene were 1.3-fold higher (P<0.05). Lymphocyte carotenoid concentrations also increased significantly: that of lycopene doubled (P<0.001); that of phytofluene was 1.8-fold higher (P<0.005); that of phytoene was 2.6-fold higher (P<0.005); that of beta-carotene was 1.5-fold higher (P<0.01). In contrast, the alpha-tocopherol concentration remained nearly constant. The intake of the tomato drink significantly reduced (by about 42 %) DNA damage (P<0.0001) in lymphocytes subjected to oxidative stress. In conclusion, the present study supports the fact that a low intake of carotenoids from tomato products improves cell antioxidant protection.
This review will focus on the role of cytokines in the behavior of macrophages, a prominent cell type of atherosclerotic lesions. Once these macrophages have immigrated into the vessel wall, they propagate the development of atherosclerosis by modifying lipoproteins, accumulating intracellular lipids, remodeling the extracellular environment, and promoting local coagulation. The numerous cytokines that have been detected in atherosclerosis, combined with the expression of large numbers of cytokine receptors on macrophages, are consistent with this axis being an important contributor to lesion development. Given the vast literature on cytokine-macrophage interactions, this review will be selective, with an emphasis on the major cytokines that have been detected in atherosclerotic lesions and their effects on properties that are relevant to lesion formation and maturation. There will be an emphasis on the role of cytokines in regulating lipid metabolism by macrophages.
We will provide an overview of the major findings in cell culture and then put these in the context of in vivo studies.
Atherosclerosis, the leading cause of death in developed countries, is characterized by chronic inflammation in the artery wall. It has been appreciated for decades that this disease is linked to hypercholesterolemia and the accumulation of macrophages in the artery wall, yet the exact mechanisms underlying this inflammatory process remain unclear. The role of innate and adaptive immune responses in the pathogenesis of atherosclerosis has been an area of intense study. It now appears that activation of innate immune signaling pathways designed to protect us from microbes may be responsible for initiating and feeding the chronic inflammatory cascade that characterizes this disease. In this review, we discuss the recent identification of Toll-like receptors and their downstream signaling pathways as critical contributors to atherosclerosis. Unraveling the contribution of individual Toll-like receptors and identifying the ligands that activate these pathways will be a central focus of atherosclerosis research in the next few years. The involvement of these pathways in atherogenesis will not only open up new avenues of investigation, but it also provides new targets for therapeutic manipulation that could ameliorate the atherosclerotic inflammatory response directly.
Early studies demonstrating the ability of dietary carotenes to prevent infections have left open the possibility that the action of these carotenoids may be through their prior conversion to vitamin A. Subsequent studies to demonstrate the specific action of dietary carotenoids have used carotenoids without provitamin A activity such as lutein, canthaxanthin, lycopene and astaxanthin. In fact, these nonprovitamin A carotenoids were as active, and at times more active, than beta-carotene in enhancing cell-mediated and humoral immune response in animals and humans. Another approach to study the possible specific role of dietary carotenoids has used animals that are inefficient converters of carotenoids to vitamin A, for example the domestic cat. Results have similarly shown immuno-enhancement by nonprovitamin A carotenoids, based either on the relative activity or on the type of immune response affected compared to beta-carotene. Certain carotenoids, acting as antioxidants, can potentially reduce the toxic effects of reactive oxygen species (ROS). These ROS, and therefore carotenoids, have been implicated in the etiology of diseases such as cancer, cardiovascular and neurodegenerative diseases and aging. Recent studies on the role of carotenoids in gene regulation, apoptosis and angiogenesis have advanced our knowledge on the possible mechanism by which carotenoids regulate immune function and cancer.
Context Oxidative stress may play a role in the development or exacerbation
of many common diseases. However, results of prospective controlled trials
of the effects of antioxidants such as vitamin E are contradictory.Objective To assess the effects of supplemental vitamin E on lipid peroxidation
in vivo in healthy adults.Design Randomized, double-blind, placebo-controlled trial conducted March 1999
to June 2000.Setting A general clinical research center in a tertiary referral academic medical
center.Participants Thirty healthy men and women aged 18 to 60 years.Interventions Participants were randomly assigned to receive placebo or α-tocopherol
dosages of 200, 400, 800, 1200, or 2000 IU/d for 8 weeks (n = 5 in each group),
followed by an 8-week washout period.Main Outcome Measures Three indices of lipid peroxidation, urinary 4-hydroxynonenal (4-HNE)
and 2 isoprostanes, iPF2α-III and iPF2α-VI,
measured by gas chromatography/mass spectrometry and compared among the 6
groups at baseline, 2, 4, 6, and 8 weeks, and 1, 3, and 8 weeks after discontinuation.Results Circulating vitamin E levels increased in a dose-dependent manner during
the study. No significant effect of vitamin E on levels of urinary 4-HNE or
either isoprostane was observed. Mean (SEM) baseline vs week 8 levels of iPF2α-III were 154 (20.1) vs 168 (22.3) pg/mg of creatinine for subjects
taking placebo; 165 (19.6) vs 234 (30.1) pg/mg for those taking 200 IU/d of
vitamin E; and 195 (26.7) vs 213 (40.6) pg/mg for subjects taking 2000 IU/d.
Corresponding iPF2α-VI levels were 1.43 (0.6) vs 1.62 (0.4)
ng/mg of creatinine for subjects taking placebo; 1.64 (0.3) vs 1.24 (0.8)
ng/mg for those taking 200 IU/d of vitamin E; and 1.83 (0.3) vs 1.94 (0.9)
ng/mg for those taking 2000 IU/d. Baseline vs week 8 levels of 4-HNE were
0.5 (0.04) vs 0.4 (0.05) ng/mg of creatinine for subjects taking placebo;
0.4 (0.06) vs 0.5 (0.02) ng/mg with 200 IU/d of vitamin E; and 0.2 (0.02)
vs 0.2 (0.1) ng/mg with 2000 IU/d.Conclusions Our results question the rationale for vitamin E supplementation in
healthy individuals. Specific quantitative indices of oxidative stress in
vivo should be considered as entry criteria and for dose selection in clinical
trials of antioxidant drugs and vitamins in human disease.
To study the role of carotenoids in the antioxidant defense against oxidative modification of low-density lipoprotein (LDL) particles, human LDL rich in β-carotene and lycopene was prepared from a healthy volunteer following long-term supplementation with tomato juice. This carotenoid-supplemented LDL accumulated cholesteryl ester hydroperoxides (CE-OOH) more slowly than the LDL prepared before supplementation when the suspensions containing these LDL were subjected to a singlet oxygen-generating system. However, there was no significant difference in the rate of CE-OOH accumulation between the two suspensions when they were exposed to a water-soluble radical generator. Therefore, it is strongly suggested that supplementation of LDL with carotenoids mainly improves the antioxidant defense against the attack of singlet oxygen. Keywords: Carotenoids; singlet oxygen; low-density lipoprotein; atherosclerosis
Since cis or trans isomers of carotenoids may have different biological reactivities, the isomeric composition of lycopene and β-carotene was measured in serum and seven human tissues. In addition to all-trans lycopene, at least three cis-isomers (9-, 13-, and 15-cis) were present, accounting for more than 50% of total lycopene. 13-and 15-cis-β-carotene, however, were present at only 5% of the all-trans isomer. In addition, 9-cis-β-carotene was present in tissue samples but not in serum. There were interindividual differences in carotenoid levels of the different tissue types, but liver, adrenal gland, and testes always contained significantly higher amounts of the carotenoids than kidney, ovary, and fat; carotenoids in brain stem tissue were below the detection limit. β-Carotene was the major carotenoid in liver, adrenal gland, kidney, ovary, and fat, whereas lycopene was the predominant carotenoid in testes.
Lycopene, a biologically occurring carotenoid, exhibits the highest physical quenching rate constant with singlet oxygen (kq = 31 X 10(9) M-1 s-1), and its plasma level is slightly higher than that of beta-carotene (kq = 14 X 10(9) M-1 s-1). This is of considerable general interest, since nutritional carotenoids, particularly beta-carotene, and other antioxidants such as alpha-tocopherol (kq = 0.3 X 10(9) M-1 s-1) have been implicated in the defense against prooxidant states; epidemiological evidence reveals that such compounds exert a protective action against certain types of cancer. Also, albumin-bound bilirubin is a known singlet oxygen quencher (kq = 3.2 X 10(9) M-1 s-1). Interestingly, those compounds with low kq values occur at higher plasma levels. When these differences are taken into account, the singlet oxygen quenching capacities of lycopene (0.7 microM in plasma), beta-carotene (0.5 microM in plasma), albumin-bound bilirubin (15 microM in plasma), and alpha-tocopherol (22 microM in plasma) are of comparable magnitude.
Several human studies have observed a direct association between retinol (vitamin A) intake and risk of prostate cancer; other studies have found either an inverse association or no association of intake of beta-carotene (the major provitamin A) with risk of prostate cancer. Data regarding carotenoids other than beta-carotene in relation to prostate cancer risk are sparse.
We concluded a prospective cohort study to examine the relationship between the intake of various carotenoids, retinol, fruits, and vegetables and the risk of prostate cancer.
Using responses to a validated, semiquantitative food-frequency questionnaire mailed to participants in the Health Professionals Follow-up Study in 1986, we assessed dietary intake for a 1-year period for a cohort of 47,894 eligible subjects initially free of diagnosed cancer. Follow-up questionnaires were sent to the entire cohort in 1988, 1990, and 1992. We calculated the relative risk (RR) for each of the upper categories of intake of a specific food or nutrient by dividing the incidence rate of prostate cancer among men in each of these categories by the rate among men in the lowest intake level. All P values resulted from two-sided tests.
Between 1986 and 1992, 812 new cases of prostate cancer, including 773 non-stage A1 cases, were documented. Intakes of the carotenoids beta-carotene, alpha-carotene, lutein, and beta-cryptoxanthin were not associated with risk of non-stage A1 prostate cancer; only lycopene intake was related to lower risk (age- and energy-adjusted RR = 0.79; 95% confidence interval [CI] = 0.64-0.99 for high versus low quintile of intake; P for trend = .04). Of 46 vegetables and fruits or related products, four were significantly associated with lower prostate cancer risk; of the four--tomato sauce (P for trend = .001), tomatoes (P for trend = .03), and pizza (P for trend = .05), but not strawberries--were primary sources of lycopene. Combined intake of tomatoes, tomato sauce, tomato juice, and pizza (which accounted for 82% of lycopene intake) was inversely associated with risk of prostate cancer (multivariate RR = 0.65; 95% CI = 0.44-0.95, for consumption frequency greater than 10 versus less than 1.5 servings per week; P for trend = .01) and advanced (stages C and D) prostate cancers (multivariate RR = 0.47; 95% CI = 0.22-1.00; P for trend = .03). No consistent association was observed for dietary retinol and risk of prostate cancer.
These findings suggest that intake of lycopene or other compounds in tomatoes may reduce prostate cancer risk, but other measured carotenoids are unrelated to risk.
Our findings support recommendations to increase vegetable and fruit consumption to reduce cancer incidence but suggest that tomato-based foods may be especially beneficial regarding prostate cancer risk.
The reproducibility of three questions, related to fullness, satiety and desire to eat, rated on an unmarked triangle was verified. In four sessions 12 volunteers ate pasta with tomato sauce (520 kcal) and were asked to rate the sensations felt. There was no difference in rating scores of the replications so the proposed questionnaire provides a stable measure of sensations related to satiety. Subsequently three satiety conditions were studied. Two foods, one rich in carbohydrate, pasta (baked macaroni) and the other in protein, polpette (meatballs), were used as loads at two calorie levels and as preload before an "ad libitum" meal. All the three questions proved useful in discriminating between the different satiety conditions. The food intake underlines the specificity of satiety: subjects, after eating a preload which previously had satiated them, ate other foods in different amounts depending on the kind of preload eaten. Food intake was significantly higher after the pasta preload, furthermore "fullness" and "satiety" ratings were significantly highest after the meatball preload, suggesting that in our experimental conditions, meatballs were more satiating than pasta. In conclusion, this study highlights the validity of using several quite different questions to study hunger and satiety, together with the actual food intake.
The present study is a biochemical validation of a food-frequency questionnaire (FFQ) with optical reading, i.e. containing food portion photographs to help to assess quantities. Forty-four healthy subjects, non-smokers and not taking vitamin supplements, were recruited for the study. After completion of the questionnaire, subjects were asked to keep a 7 d weighed dietary record (7DR). Three 24 h urine samples were collected on 3 different days over the week of food recording for the analysis of urea-N, P and K. On the 4th day of food recording, blood was collected for determination of alpha-tocopherol, beta-carotene and ascorbic acid. N, P and K determined in urines and from 7DR were significantly correlated (Spearman rank correlation test), r values being 0.77, 0.57 and 0.42 respectively. The correlations with the FFQ were significant only for N (r 0.45) and P (r 0.39). Blood ascorbic acid and beta-carotene concentrations correlated with dietary intake when determined from 7DR (both r 0.44), but not when determined from FFQ. No correlation was found for alpha-tocopherol. The data obtained seem to prove the validity of the FFQ in defining eating patterns in terms of some nutrients, but not vitamins, at least as far as non-supplemented subjects are concerned. The way in which foods were grouped in the questionnaire could account for these results.
An improved semiquantitative self-administered food frequency questionnaire has been designed in order to investigate possible associations between diet and health, to plan nutrition education programmes, and to examine dietary compliance. The questionnaire consists of 16 printed forms and 16 pages with coloured photos of the most common foods and courses from the Italian diet. Instructions and other questions are included. The questionnaire uses optical reading from a scanner connected to a personal computer. The questionnaire was validated by comparing it with the seven-day weighed record method using 46 healthy adult volunteers. Significant correlations were found for all nutrients tested (Spearman rank correlation procedure), r ranging from 0.33 for ascorbic acid to 0.84 for alcohol. The two methods gave comparable results (Wilcoxon matched-pairs signed rank test) for all nutrients except riboflavin and alcohol. Similarity of the two methods in classifying relative intakes was examined by determining the frequency of similar classification into tertiles. Half of the subjects were correctly classified for most nutrients and for frequency of consumption of 18 food groups.
The single cell gel electrophoresis (SCGE) assay is a rapid, simple, visual and sensitive technique for measuring DNA breakage in individual mammalian cells. Here we review the development of the SCGE assay (with particular reference to the alkaline version), existing protocols for the detection and analysis of comets, the relevant underlying principles determining the behaviour of DNA, and the potential applications of the technique.
A physical chemistry technique based on singlet oxygen luminescence at about 1270 nm and a biological cell membrane technique were used to study the quenching of singlet oxygen by four carotenoids bound to the surface of lymphoid cells. All the carotenoids studied showed a beneficial effect in cell protection, but there were subtle differences between them.
In view of the persisting uncertainty concerning possible mechanisms by which high vegetable and fruit intake decreases cancer risk, foods with divergent values for potentially important micronutrients are a priority for investigation. Tomatoes are low in beta-carotene, but high in lycopene, an active antioxidative agent. In order to assess the effect of tomatoes on risk of cancers of the digestive tract, data were analyzed from an integrated series of case-control studies conducted between 1985 and 1991 in northern Italy, where tomato intake is high but, also, heterogeneous. The overall dataset included the following histologically confirmed cancer cases: oral cavity and pharynx, 314; esophagus, 85; stomach, 723; colon, 955; and rectum, 629; and a total of 2,879 controls admitted to hospital for acute non-neoplastic or non-digestive conditions, unrelated to long-term dietary modifications. Multivariate odds ratios (OR) and 95% confidence interval (CI) for subsequent quartiles of intake of raw tomatoes were derived, after allowance for age, sex, study center, education, smoking and drinking level, and tertile of total caloric intake. There was a consistent pattern of protection for all sites (OR in the upper quartile ranging between 0.4 and 0.7), most notably for gastrointestinal neoplasms. All trends in risk were highly significant. The beneficial effect of raw tomatoes in this population may be partly due to the fact that they constitute perhaps the most specific feature of the Mediterranean diet. However, if it is true that tomatoes protect against digestive-tract cancers, this is of interest from both a scientific and a public health viewpoint.
The purpose of this study was to assess the relative antioxidant activities of a range of carotenes and xanthophylls through the extent of their abilities to scavenge the ABTS(.+) radical cation. The results show that the relative abilities of the carotenoids to scavenge the ABTS(.+) radical cation are influenced by the presence of functional groups with increasing polarities, such as carbonyl and hydroxyl groups, in the terminal rings, as well as by the number of conjugated double bonds.
A human intervention study with vegetable products has been performed in twenty three healthy, non smoking males aged 27-40. It was the aim of the study to assess whether consumption of vegetables containing different carotenoids could protect against DNA damage and oxidative DNA damage. The subjects consumed their normal diets, but abstained from vegetables high in carotenoids throughout the study period. After a 2 week depletion period, they received daily 330 ml tomato juice with 40 mg lycopene (weeks 3 and 4), 330 ml carrot juice with 22.3 mg beta-carotene and 15.7 mg alpha-carotene (weeks 5 and 6), and 10 g dried spinach powder (in water or milk) with 11.3 mg lutein (weeks 7 and 8). Blood was collected weekly and DNA damage was detected in peripheral blood lymphocytes with the 'COMET' assay. Oxidised DNA bases were detected by including an incubation step with endonuclease III. The supplementation of the diet with tomato, carrot or spinach products resulted in a significant decrease in endogenous levels of strand breaks in lymphocyte DNA. Oxidative base damage was significantly reduced during the carrot juice intervention. These findings support the hypothesis that carotenoid containing plant products exert a cancer-protective effect via a decrease in oxidative and other damage to DNA in humans.
Elderly persons are more susceptible to bacterial and virus infections and neoplasias than young adults. This is related to an impaired immune response. Lymphocytes of the elderly show a decreased proliferation after induction with mitogens. The decreased proliferation is correlated to a decreased release of interleukin (IL)-2 and soluble IL-2 receptor (sIL-2R). However, IL-2R expression on the cell surface is normal. Interferon (IFN)-gamma as the main T-helper-1 (TH1) cytokine is produced less by lymphocytes of the elderly, whereas the TH2 cytokines IL-4 and IL-10 are produced in higher amounts as compared to stimulated lymphocytes of young donors. The decreased production of IFN-gamma is correlated to a decreased number of CD45RO+/CD8+ T cells. Therefore in the elderly there seems to be a dysregulation in the TH1/TH2-system which is predominated by TH2-functions. Monocyte function seems to be increased in the elderly. Leukocytes of elderly persons produce higher amounts of IL-1, IL-6, IL-8 and tumor necrosis factor (TNF)-alpha after induction with lipopolysaccharide (LPS) than leukocytes from young donors. In contrast, in vitro induction of IFN-alpha by viruses is decreased in the elderly compared to the young. In conclusion, there are cellular defects and dysfunctions in the elderly resulting in an altered immune response.
To study the relationship between lycopene intake and plasma concentration, ten healthy female subjects were given one or more portions of tomato purée or fresh raw tomato containing 16.5 mg total lycopene (all-trans + cis forms). In Expt 1 subjects (n 9) were randomly assigned the single portions of the two tomato products and blood samples were collected to follow the change in plasma carotenoid concentrations within the first 12 h and on each of the following 5 d (104 h). In Expt 2 subjects (n 10) were divided into two groups of five each receiving daily dietary portions of tomato purée or fresh raw tomato containing 16.5 mg total lycopene for 7 d. Fasting blood samples were collected daily. In Expt 1 the plasma total lycopene (all-trans + cis forms) concentration, after the single portions of tomato purée and raw tomato, varied significantly over time, with a first peak reached after 6 h, a further increase after 12 h and a slow decrease until 104 h. In Expt 2, when the tomato products were given daily, there was a day-by-day increase in the plasma total lycopene concentration, and through the following week of a diet without tomato there was a gradual decrease. However, values did not return to basal concentrations. Plasma total lycopene concentration was higher after the tomato purée intake than after the raw tomato in both the first (F(1,8) 7.597; P < 0.025) and the second experiments (F(1,8) 12.193; P < 0.01) demonstrating a significant effect of food matrix on absorption.
Oxidative stress has been implicated as an important etiologic factor in atherosclerosis and vascular dysfunction. Antioxidants may inhibit atherogenesis and improve vascular function by two different mechanisms. First, lipid-soluble antioxidants present in low-density lipoprotein (LDL), including alpha-tocopherol, and water-soluble antioxidants present in the extracellular fluid of the arterial wall, including ascorbic acid (vitamin C), inhibit LDL oxidation through an LDL-specific antioxidant action. Second, antioxidants present in the cells of the vascular wall decrease cellular production and release of reactive oxygen species (ROS), inhibit endothelial activation (i.e., expression of adhesion molecules and monocyte chemoattractants), and improve the biologic activity of endothelium-derived nitric oxide (EDNO) through a cell- or tissue-specific antioxidant action. alpha-Tocopherol and a number of thiol antioxidants have been shown to decrease adhesion molecule expression and monocyte-endothelial interactions. Vitamin C has been demonstrated to potentiate EDNO activity and normalize vascular function in patients with coronary artery disease and associated risk factors, including hypercholesterolemia, hyperhomocysteinemia, hypertension, diabetes, and smoking.
Many epidemiological studies have shown an association between diets rich in carotenoids and a reduced incidence of many forms of cancer, and it has been suggested that the antioxidant properties of these compounds are a causative factor. Attention has focused on the potential role of one specific carotenoid, beta-carotene, in preventing cancer, and numerous publications have described in vitro experiments and animal studies which suggest that not only can this carotenoid protect against the development of cancer, but also several other chronic diseases. Since the immune system plays a major role in cancer prevention, it has been suggested that beta-carotene may enhance immune cell function. Several human trials, using dietary beta-carotene supplementation with a wide range of intakes, have been undertaken to address this hypothesis. The general conclusion of these studies is that this compound can enhance cell-mediated immune responses, particularly in the elderly. The present article will review some of these human studies and, hopefully, complement the reviews of other authors associated with the present symposium, some of whom will also describe work in this area. Potential mechanisms for the effects of carotenoids on immune function will also be reviewed. Finally, possible reasons for the failure of three major prospective studies to demonstrate a beneficial effect of beta-carotene supplementation on lung cancer risk will be discussed.
Oxidative stress may play a role in the development or exacerbation of many common diseases. However, results of prospective controlled trials of the effects of antioxidants such as vitamin E are contradictory.
To assess the effects of supplemental vitamin E on lipid peroxidation in vivo in healthy adults.
Randomized, double-blind, placebo-controlled trial conducted March 1999 to June 2000.
A general clinical research center in a tertiary referral academic medical center.
Thirty healthy men and women aged 18 to 60 years.
Participants were randomly assigned to receive placebo or alpha-tocopherol dosages of 200, 400, 800, 1200, or 2000 IU/d for 8 weeks (n = 5 in each group), followed by an 8-week washout period.
Three indices of lipid peroxidation, urinary 4-hydroxynonenal (4-HNE) and 2 isoprostanes, iPF(2alpha)-III and iPF(2alpha)-VI, measured by gas chromatography/mass spectrometry and compared among the 6 groups at baseline, 2, 4, 6, and 8 weeks, and 1, 3, and 8 weeks after discontinuation.
Circulating vitamin E levels increased in a dose-dependent manner during the study. No significant effect of vitamin E on levels of urinary 4-HNE or either isoprostane was observed. Mean (SEM) baseline vs week 8 levels of iPF(2alpha)-III were 154 (20.1) vs 168 (22.3) pg/mg of creatinine for subjects taking placebo; 165 (19.6) vs 234 (30.1) pg/mg for those taking 200 IU/d of vitamin E; and 195 (26.7) vs 213 (40.6) pg/mg for subjects taking 2000 IU/d. Corresponding iPF(2alpha)-VI levels were 1.43 (0.6) vs 1.62 (0.4) ng/mg of creatinine for subjects taking placebo; 1.64 (0.3) vs 1.24 (0.8) ng/mg for those taking 200 IU/d of vitamin E; and 1.83 (0.3) vs 1.94 (0.9) ng/mg for those taking 2000 IU/d. Baseline vs week 8 levels of 4-HNE were 0.5 (0.04) vs 0.4 (0.05) ng/mg of creatinine for subjects taking placebo; 0.4 (0.06) vs 0.5 (0.02) ng/mg with 200 IU/d of vitamin E; and 0.2 (0.02) vs 0.2 (0.1) ng/mg with 2000 IU/d.
Our results question the rationale for vitamin E supplementation in healthy individuals. Specific quantitative indices of oxidative stress in vivo should be considered as entry criteria and for dose selection in clinical trials of antioxidant drugs and vitamins in human disease.
Antioxidants may prevent atherosclerosis by interfering with endothelial activation, which involves the expression of endothelial adhesion molecules. The aim of this study was to explore the relationship between plasma levels of some lipid-soluble antioxidants (gamma-tocopherol, alpha-tocopherol, lycopene, beta-carotene, and ubiquinone), carotid maximum intima-media thickness (IMTmax), an index of atherosclerotic extension/severity, and soluble adhesion molecules (vascular cell adhesion molecule-1 [VCAM-1], intercellular adhesion molecule-1 [ICAM-1], and E-selectin), which are taken as a reflection of vascular cell expression of adhesion molecules.
We studied 11 healthy control subjects, 11 patients with uncomplicated hypertension (UH), and 11 patients with essential hypertension plus peripheral vascular disease (PVD) who were matched for age, sex, smoking habit, and body mass index.
Patients with PVD had elevated IMTmax (2.7 [1.1-3.1] mm, median [range]) compared with both patients with UH(1.2 [0.8-2.4] mm) and control subjects (1.0 [0.6-2] mm). In patients with PVD, soluble (s)VCAM-1 and sICAM-1 were also significantly higher than in the 2 other categories. Plasma levels of lycopene had a trend toward lower values in patients with PVD compared with other groups (P =.13). A statistically significant correlation was found between lycopene and IMTmax (r = 0.42, P =.014) at univariate analysis, which persisted at multivariate analysis (P <.05) and was independent of low-density lipoprotein cholesterol, creatinine clearance, and plasma insulin. Plasma lycopene did not significantly correlate with any of the soluble adhesion molecules tested.
We conclude that the inverse relationship of plasma lycopene with IMTmax is compatible with a protective role of this natural dietary antioxidant in atherosclerosis, although the mechanism of protection does not apparently involve a decrease in endothelial activation measured through soluble adhesion molecules.
Nuclear factor kappa B (NF-kappaB) is a family of inducible transcription factors found virtually ubiquitously in all cells. Since its discovery by Sen and Baltimore in 1986, much has been discovered about its mechanisms of activation, its target genes, and its function in a variety of human diseases including those related to inflammation, asthma, atherosclerosis, AIDS, septic shock, arthritis, and cancer. Due to its role in a wide variety of diseases, NF-kappaB has become one of the major targets for drug development. Here, we review our current knowledge of NF-kappaB, the possible mechanisms of its activation, its potential role in cancer, and various strategies being employed to target the NF-kappaB signaling pathway for cancer drug development.