Oxidative stress has been implicated in the pathogenesis of chronic diseases related to aging such as cancer and cardiovascular disease. Carotenoids could be a part of a protective strategy to minimize oxidative damage in vulnerable populations, such as the elderly.
Our aim was to determine the protective effect of carotenoids against DNA damage.
A randomized, double-blind, placebo-controlled intervention study was conducted. Thirty-seven healthy, nonsmoking postmenopausal women aged 50-70 y were randomly assigned to 1 of 5 groups and were instructed to consume a daily dose of mixed carotenoids (beta-carotene, lutein, and lycopene; 4 mg each), 12 mg of a single carotenoid (beta-carotene, lutein, or lycopene), or placebo for 56 d. Plasma carotenoid concentrations were analyzed by using HPLC, and lymphocyte DNA damage was measured by using a single-cell gel electrophoresis (comet) assay.
At day 57, all carotenoid-supplemented groups showed significantly lower endogenous DNA damage than at baseline (P < 0.01), whereas the placebo group did not show any significant change. Significantly less (P < 0.05) endogenous DNA damage was found as early as day 15 in the mixed carotenoid (P < 0.01) and beta-carotene (P < 0.05) groups.
The results indicate that carotenoid supplementation decreases DNA damage and that a combination of carotenoids (4 mg each of lutein, beta-carotene, and lycopene), an intake that can be achieved by diet, or a larger dose (12 mg) of individual carotenoids exerts protection against DNA damage.
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... Two previous RCTs from Zhao et al. [74] and Torbergsen and Collins [75] assessed three types of carotenoids, namely lutein, β-carotene and lycopene, and these two studies reported consistent findings. Zhao et al. [74] conducted a relatively longer intervention whereby subjects consumed lutein, β-carotene, lycopene or a mixture of these three carotenoids for 56 days. ...
... Two previous RCTs from Zhao et al. [74] and Torbergsen and Collins [75] assessed three types of carotenoids, namely lutein, β-carotene and lycopene, and these two studies reported consistent findings. Zhao et al. [74] conducted a relatively longer intervention whereby subjects consumed lutein, β-carotene, lycopene or a mixture of these three carotenoids for 56 days. The authors revealed that all types of carotenoid supplementation significantly decreased DNA damage, as evidenced by a shorter DNA tail length. ...
... It is plausible that lutein may require a longer period to exert a substantial favorable effect on DNA damage. Moreover, a combination of carotenoids (lutein, β-carotene and lycopene) was also reported to lower DNA damage, as evidenced by decreased DNA degradation products (as assessed by the 8-OHdG/creatinine ratio in urine) [56] and a reduced DNA tail length [74]. ...
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.
... Lycopene can protect human lymphoid cells against singlet oxygen by binding to the outer membrane of these cells [97]. Although the consumption of tomato products has been proven to safeguard lymphocytes against DNA damage, it does not result in a decrease in the level of malondialdehyde (MDA) for lipid oxidation [98]. However, Rios et al. [99] discovered no significant differences in the levels of natural lymphocyte DNA damage and 8iso-prostaglandin F2α between a group that consumed a tomato-based beverage and a control group that received a placebo. ...
Food processing by-products constitute a rich reservoir of bioactive compounds and natural pigments, offering significant potential for applications in functional food development, nutraceuticals, food additives, and cosmeceuticals. Lycopene, a naturally occurring carotenoid, exhibits potent antioxidative and bioactive properties and is primarily responsible for the red pigmentation in various plant sources. Industrial by-products of plant origin represent a valuable and sustainable source for lycopene extraction. The growing scientific interest in lycopene is driven by accumulating evidence from in vitro, in vivo, and ex vivo studies, which consistently correlate lycopene-rich dietary intake with a reduced incidence of various pathophysiological conditions, including carcinogenesis, cardiovascular disorders, and metabolic diseases such as diabetes. This review provides a comprehensive analysis of the physicochemical characteristics, absorption kinetics, metabolic pathways, and biodistribution of lycopene and its derivatives within the human body. Additionally, the molecular interactions of lycopene with other bioactive constituents are explored to elucidate its mechanistic roles in disease prevention. Furthermore, the influence of food processing techniques on the structural integrity, stability, and bioavailability of lycopene is critically examined, with the objective of optimizing its functional applications in health and disease management.
... They also performed 3 separate RCTs to test the effect of daily supplementation with either 15 mg β-carotene, 15 mg lutein, or 15 mg lycopene and again found no effect of carotenoid supplementation on DNA strand breaks [110]. However, Zhao et al. [111] reported a significant reduction of DSBs in each of 4 carotenoid intervention arms: -33% for lutein, -35% for β-carotene, -43% for lutein, -36% for the combination, and no change in the placebo after 57 d of intervention. Devaraj et al. [112], who did a dose-response RCT of lycopene supplementation (0, 6.5, 15, or 30 mg/d), found a significant 8.9% reduction in DSBs only with the highest dose. ...
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.
... A similar result was also found in a study of HgCL 2induced Wister rats (Yang et al., 2011) and cisplatin-induced Wistar rats (Sahin et al., 2010), as summarized in Table 2. Sahin et al. (2010) also demonstrated that lycopene could improve antioxidant levels by inducing Nrf2 accumulation and HO-1 expressions. Likewise, Dai et al. (2015) observed that a 7-day oral treatment of lycopene restored antioxidation levels in colistin-induced Kunming mice by (Visioli et al., 2003;Zhao et al., 2006) and chronic diseases (T2D and prostate cancer) patients (Chen et al., 2001;Upritchard et al., 2000) reported that lycopene prevented lipid oxidation as well as downregulating oxidative DNA damage (Table 2). In addition, a study proved that the lycopene mycelium powder protected Drosophila melanogaster from oxidative stress, delayed longevity, increased reproductivity, and sexual capacity by increasing SOD and decreasing MDA levels (Hu et al., 2013). ...
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.
... While only a moderate decrease of oxidized purines was detected in the first group, a more pronounced effect was found in the patient group (reduction of comet formation under standard conditions and reduction of formation of oxidized purines and pyrimidines). We did not find studies concerning the effects of vitamin A, which is one of the most important dietary antioxidants, but an older investigation with beta-carotene (pro-vitamin A), lycopene, lutein or the mix of all three carotenoids was published by Zhao et al. in 2006 [115]. The participants consumed daily 12 mg/person over a period of 56 days. ...
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.
... Supplementation of lycopene at a daily dose of 12 mg for 56 days showed markedly lower endogenous DNA damage at 57th day (6.8 ± 0.6; data represented as % DNA in the tail of a comet assay) than at baseline (11.9 ± 0.9), whereas the placebo group did not show any significant change (8.7 ± 0.8 at Day 1 and 9.9 ± 1.5 at Day 57), indicating protective effect of lycopene against oxidative DNA damage (NCT00356252). 116 Recently, an eight-week study to evaluate the effect of antioxidant mixture (lycopene, bacopa, astaxanthin, and vitamin B 12 ) on cognitive performance was conducted in subjects in the age group of more than 60 years in which no evidence of cognitive dysfunction was reported. Analysis of score of neuropsychological tests, and changes of metabolic markers like glucose, insulin, triglycerides, uric acid, cholesterol in terms of total, LDL, and HDL, and plasma markers of oxidative stress (8-iso-prostaglandin F2alpha, plasma malondialdehyde) indicated the improvement in cognitive functions by supplementation of antioxidant mixture (NCT03825042). ...
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.
... An inverse association of plasma lycopene levels with oxidative stress is revealed [87]. In lymphocytes, it was found that lycopene-rich foods, supplements and juices showed protective effects against oxidative stress [88]. Lycopene consumption in the form of oleoresin capsules and ketchup in humans showed a decrease in lipid and protein oxidation [89]. ...
Foods rich in antioxidants such as lycopene have a major role in maintaining cardiac health. Lycopene, 80% of which can be obtained by consuming a common vegetable such as tomato, can prevent the disturbances that contribute to cardiovascular disease (CVD). The present work begins with a brief introduction to CVD and lycopene and its various properties such as bioavailability, pharmacokinetics, etc. In this review, the potential cardio-protective effects of lycopene that reduce the progression of CVD and thrombotic complications are detailed. Further, the protective effects of lycopene including in vitro, in vivo and clinical trials conducted on lycopene for CVD protective effects are explained. Finally, the controversial aspect of lycopene as a protective agent against CVD and toxicity are also mentioned.
Sunlight, despite its benefits, can pose a threat to the skin, which is a natural protective barrier. Phototoxicity caused by overexposure, especially to ultraviolet radiation (UVR), results in burns, accelerates photoaging, and causes skin cancer formation. Natural substances of plant origin, i.e., polyphenols, flavonoids, and photosynthetic pigments, can protect the skin against the effects of radiation, acting not only as photoprotectors like natural filters but as antioxidant and anti-inflammatory remedies, alleviating the effects of photodamage to the skin. Plant-based formulations are gaining popularity as an attractive alternative to synthetic filters. Over the past 20 years, a large number of studies have been published to assess the photoprotective effects of natural plant products, primarily through their antioxidant, antimutagenic, and anti-immunosuppressive activities. This review selects the most important data on skin photodamage and photoprotective efficacy of selected plant carotenoid representatives from in vivo studies on animal models and humans, as well as in vitro experiments performed on fibroblast and keratinocyte cell lines. Recent research on carotenoids associated with lipid nanoparticles, nanoemulsions, liposomes, and micelles is reviewed. The focus was on collecting those nanomaterials that serve to improve the bioavailability and stability of carotenoids as natural antioxidants with photoprotective activity.
The bioactive red-colored carotenoid grabs attention due to its antioxidant properties, though it has no provitamin A activity. It has the highest singlet oxygen quenching ability among all carotenoids. Lycopene is responsible for the red to pink colors observed in many fruits and vegetables. The unique structure of lycopene for its ruby red color enhances its usage as a natural food colorant. Several promising data from in vivo and in vitro studies suggest that lycopene intake is inversely associated with chronic diseases like cancers, cardiovascular disease, diabetes, and many more. Lycopene in fresh fruits and vegetables is found in all-trans configuration. Due to isomerization and oxidation, the degradation (trans to cis) of lycopene takes place. The absorption of cis-isomers in food is higher than all trans-isomers. The food-processing technique improves lycopene absorption or bioavailability by loosening the bonds between lycopene and tissue matrix and induces cis-isomerization. The health properties of lycopene encourage itself to develop as enriched food with functional properties. Various eco-friendly lycopene extraction techniques with a slight loss of bioactivities are highly acceptable in the food and pharmaceutical industries. More advanced research works on absorption, biochemistry, and various physiological pathways to expose the mechanism of lycopene extraction and fortification, which can further improve various existing operations. This review paper summarizes various ongoing researches on lycopene fortification and extraction methods and their chemopreventive roles.
The initiation and progression of cancerous lesions causes changes to DNA structure.
Carcinogenesis can occur because of non-modifiable (genetic) and modifiable risk factors. Evidence revealed that of all the types of cancer, 5-10% are caused by nonmodifiable risk factors. Many are caused by modifiable risk factors which revealed that it is preventable. The prevention of cancer is feasible because of the distinctive features of phytochemical agents. This chapter sheds more light on the agents that cause DNA damage which can in turn lead to cancer. In this chapter, the authors also shed more light on the molecular mechanism through which phytochemical agents can prevent cancer. The antioxidant activities, detoxification processes, mechanism of DNA repair, and demethylation activities of phytochemical agents were discussed in this chapter. The clinical evidence of the genoprotective nature of natural substances was also explained.
Changes in plasma carotenoids were determined in 36 healthy men and women before and after being fed controlled diets of moderate fat (26% of total calories) and high carotenoid content (=16 mg/day) for two 15 day periods. In addition, broccoli (205 g/d) was provided either during the first or the second 15-day residency period in a cross-over design. Plasma was digested with lipase, and plasma carotenoids were extracted and measured using HPLC. Three oxygenated carotenoids (lutein, zeaxanthin, cryptoxanthin), three hydrocarbon carotenoids (a-carotene, alltrans -carotene, 13-e -carotene) and 4 lycopene geometric isomers (15-cu, 13-c/s, 9-ci's and all rrans-lycopene) were separated using a C30 carotenoid column. A small unidentified peak coeluted with standard 9cis -carotene and was identified as Ç-carotene (Xmax = 400 nm). The concentrations of plasma lutein, cryptoxanthin, a-carotene, 13-cis carotene, all-rraw -carotene, and ci'i and trans lycopenes were all significantly increased (p<0.05) by day 6-16 by the high fruit and vegetable diets. The provision of additional broccoli for 5 days to the basic high carotenoid diet resulted in a further significant increase in the serum concentration of lutein as compared to the feeding of the basic high carotenoid diet alone. Most of the carotenoids of human plasma can be increased by moderate alterations in human diets within a short period of time, although the plasma response may be related to the baseline carotenoid concentrations.
Carotenoids are thought to act as antioxidants in vivo, decreasing oxidative damage to biomolecules and thus protecting against coronary heart disease and cancer. However, human intervention studies with b-carotene have given equivocal results in terms of cancer incidence. In an alternative molecular epidemiological approach, we have employed the ‘comet assay’ (single cell alkaline gel electrophoresis) to measure strand breaks, oxidized pyrimidines and altered purines in the DNA of lymphocytes from volunteers supplemented with a/b-carotene, lutein, lycopene or placebo. In addition, we measured concentrations of the main serum carotenoids, and vitamins E and C, by HPLC. We report a significant negative correlation between basal concentrations of total serum carotenoids and oxidized pyrimidines. A similar correlation was seen between individual carotenoids (notably lutein and b-carotene) and oxidized pyrimidines. However, carotenoid supplementation did not have a significant effect on endogenous oxidative damage. This suggests that there are some factors in the basal diet, probably found in fruit and vegetables, that decrease oxidative damage to DNA. In this case, basal serum carotenoids may simply be markers of consumption of fruit and vegetables, they themselves having little or no protective value.
Lymphocytes are routinely used in human biomonitoring to assess the potential toxic and cytoprotective effects of diet on both DNA damage and repair and, by implication, health. Logistically, samples may require to be cryopreserved and stored. How this affects cells used in human biomonitoring is often not considered. In this study we have evaluated the influence of cryopreservation on endogenous and induced DNA strand breakage, altered bases (oxidized purines, oxidized pyrimidines and misincorporated uracil), antioxidant capacity and DNA repair capability in human peripheral blood lymphocytes. Neither isolation nor freezing increased DNA strand breakage above endogenous levels found in freshly isolated human lymphocytes. Oxidized bases (both pyrimidines and purines) and misincorporated uracil, were similar for fresh and frozen lymphocytes. Fresh and frozen lymphocytes responded almost identically to hydrogen peroxide. Quercetin-mediated cytoprotection against hydrogen peroxide-induced strand breakage was maintained in cryopreserved lymphocytes after short-term (24 h) and longer term (2 months) storage compared with freshly isolated and treated cells. Hydrogen peroxide-induced DNA strand breakage was repaired in fresh lymphocytes. Cryopreserved lymphocytes were unable to repair oxidantinduced DNA strand breaks. Frozen human lymphocytes can therefore be successfully used for most aspects of DNA damage biomonitoring, but not for repair.
To evaluate whether deficient DNA repair contributes to elevated DNA damage and breast carcinogenesis, we used the comet assay (single-cell alkaline gel electrophoresis) to measure the levels of DNA damage in peripheral lymphocytes from 70 breast cancer cases and 70 controls. DNA damage, measured as the comet tail moment, was not influenced by age, family history (FH), age at menarche, age at first birth or parity. The results showed that cancer cases had significantly higher DNA damage compared with controls; the comet tail moments (mean SD) for cases and controls were: 10.78 3.63 and 6.86 2.76 (P 5 0.001) for DNA damage at baseline (DB), 21.24 4.88 and 14.97 4.18 (P 5 0.001) for DNA damage after exposure to 6 Gy of ionizing radiation (DIR), and 14.76 5.35 and 9.75 3.35 (P 5 0.001) for DNA damage remaining after 10 min repair following exposure to 6 Gy of IR (DRP), respectively. Body mass index (BMI) affected DNA damage differently for cases and controls. Damage decreased with increasing BMI for controls, while damage increased with increasing BMI for cases. Above-median DNA damage was significantly associated with breast cancer risk; the age-adjusted odds ratio (OR)a 13.44 [95% confidence interval (CI)a 5.97‐30.24] for DB, 13.65 (6.07‐ 30.71) for DIR and 6.54 (3.11‐13.79) for DRP, respectively. This association was stronger in women with above-median BMI. Our results, although based on a relatively small group of subjects, indicate that elevated DNA damage is significantly associated with breast cancer risk and warrant larger studies to further define the molecular mechanisms of DNA damage/repair in breast cancer susceptibility.
Background Previous studies of diet and coronary heart disease (CHD) have focused on intake of nutrients rather than whole foods. Because of the findings that dietary fibre, folate and antioxidants may be protective for CHD, increased intake of vegetables has been recommended. However, due to the chemical and physical complexity of vegetables, the effects of individual nutrients may differ if eaten as whole foods. Moreover, little is known about the direct association between vegetable intake and risk of CHD.
Methods We prospectively evaluated the relation between vegetable intake and CHD risk in the Physicians' Health Study, a randomized trial of aspirin and beta-carotene among 22 071 US male physicians aged 40–84 years in 1982. In this analysis, we included 15 220 men without heart disease, stroke or cancer at baseline who provided information on their vegetable intake at baseline, and in the 2nd, 4th and 6th years of follow-up using a simple semiquantitative food frequency questionnaire including eight vegetables. We confirmed 1148 incident cases of CHD (387 incident cases of myocardial infarction and 761 incident cases of coronary artery bypass grafting or percutaneous transluminal coronary angioplasty) during 12 years of follow-up.
Results After adjusting for age, randomized treatment, body mass index (BMI), smoking, alcohol intake, physical activity, history of diabetes, history of hypertension, history of high cholesterol, and use of multivitamins, men who consumed at least 2.5 servings/day of vegetables had a relative risk (RR) of 0.77 (95% CI : 0.60–0.98) for CHD, compared with men in the lowest category (<1 serving/day). Adjusting for the same covariates in an analysis of the overall trend that considered intake of vegetables as a continuous variable, we found a RR of 0.83 (95% CI : 0.71–0.98) for risk of CHD for each additional serving/day of vegetables. The inverse relation between vegetable intake and CHD risk was more evident among men with a BMI ≥25 (RR = 0.71, 95% CI : 0.51–0.99) or current smokers (RR = 0.40, 95% CI : 0.18–0.86) comparing highest to the lowest categories of intake.
Conclusions Our results suggest an inverse association between vegetable intake and risk of CHD. These prospective data support current dietary guidelines to increase vegetable intake for the prevention of CHD.
