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Spinach and tomato consumption increases lymphocyte DNA resistance to oxidative stress but this is not related to cell carotenoid concentrations
Abstract
The increased consumption of fruit and vegetables has been linked to protection against different chronic diseases, but the dietary constituents responsible for this association have not been clearly identified.
We evaluated the effect of spinach and spinach+tomato puree consumption on cell DNA resistance to an oxidative stress.
To this aim, in a dietary controlled intervention study, 9 healthy female volunteers consumed a basal diet low in carotenoids (< 600 microg/day) enriched with daily portions (150 g) of spinach (providing about 9 mg lutein, 0.6 mg zeaxanthin, 4 mg beta-carotene) for 3 weeks (from day 0 to day 21) followed by a 2 week wash-out period (basal diet) and finally another 3 weeks (from day 35 to day 56) of diet enriched with daily portions of spinach (150 g) + tomato puree (25 g, providing about 7 mg lycopene, 0.3 mg beta-carotene). At the beginning and the end of each period of vegetable intake, blood samples were collected for lymphocyte separation. Carotenoid concentrations of lymphocytes were determined by HPLC and DNA damage was evaluated by the comet assay following an ex vivo treatment with H(2)O(2).
During the first period of spinach consumption, lymphocyte lutein concentration did not increase significantly (from 1.6 to 2.2 micromol/10(12) cells) while lycopene and beta-carotene concentrations decreased significantly (from 1.0 to 0.1 micromol/10(12) cells, P < 0.001, and from 2.2 to 1.2 micromol/10(12) cells, P < 0.05, respectively). Lutein and lycopene concentrations increased after spinach+tomato puree consumption (from 1.2 to 3.5 micromol/10(12) cells, P < 0.01, and from 0.1 to 0.7 micromol/10(12) cells, P < 0.05, respectively). The increase may be attributed to the addition of tomato puree to spinach; however, the different concentrations of carotenoids in lymphocytes registered at the beginning of the two intervention periods may have affected the results. DNA resistance to H(2)O(2) insult increased significantly after both the enriched diets (P < 0.01); however, no "additive effect" was seen after spinach + tomato puree consumption. In the spinach + tomato intervention period an inverse correlation was observed between lymphocyte lycopene concentration and DNA damage, but this seems not able to explain the protection observed.
The consumption of carotenoid-rich foods even for a short period of time gives protection against oxidative stress. The results obtained seem to suggest that this protective role is not specifically related to carotenoids. However they may contribute together with other substances present in vegetables to lymphocyte resistance to oxidative damage.
... Ten studies focused on a population diagnosed with ≥1 CVD risk factors (12,16,17,21,34,46,49,50,33,26), 30 studies looked at the effects of lycopene intervention on healthy individuals (3, 13, 18, 19, 22-25, 35-37, 40, 42, 45, 47, 44, 51, 52, 31, 28-30, 32, 38, 39, 14, 41, 48, 53, 54), and 3 involved both groups (20,43,27). 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). ...
... 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). ...
... Studies included in this review were heterogeneous with regard to the delivery of lycopene as an intervention. Fifteen studies used lycopene supplementation (13, 16, 17, 19-21, 24, 42, 33, 31, 26, 38, 32, 29, 53), whereas 22 used a wholefood approach (3,12,14,22,23,25,34,35,36,37,45,46,47,44,50,51,52,39,30,29,54,41,27), with the remaining 6 studies using both supplements and dietary lycopene delivery (18,40,49,28,48,43). Of the studies that used a whole-food approach, 15 used tomato juice (12,14,25,34,37,45,46,49,47,50,51,52,28,30,54), 10 used tomato paste (22,23,37,40,49,39,29,41,43,27), 4 used raw tomato (3,22,36,44), and 3 paired their tomato product with extra-virgin olive oil (EVOO) to improve the bioavailability (22,25,39). ...
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.
... Table 1 provides an overview of the effect of the regular consumption of tomatoes and tomato products on DNA damage in lymphocytes or peripheral blood mononuclear cells (PBMCs) from healthy volunteers. In the majority of studies published, changes in the mean extent of DNA strand breaks in vivo did not occur after the daily intake of tomato puré e [7][8][9], tomato extract [10] or a soft drink enriched with tomato extract [11 ] for 2-4 weeks. Beneficial effects on that biomarker were only reported by Pool-Zobel et al. [12], who used a higher dose of lycopene (40 mg as tomato juice). ...
... An evaluation of the DNA strand breaks induced by hydrogen peroxide or ferric ion challenge ex vivo revealed an increased resistance of PBMCs against reactive oxygen species (ROS) when tomatoes or tomato products were administered in all studies [7][8][9]14,15 ], except for the study by Pool-Zobel et al. [12]. These effects did not only occur by supplementation with tomatoes or tomato products in addition to a diet low in carotenoids [7][8][9]14], but also in addition to a diet without any restrictions [15 ]. ...
... An evaluation of the DNA strand breaks induced by hydrogen peroxide or ferric ion challenge ex vivo revealed an increased resistance of PBMCs against reactive oxygen species (ROS) when tomatoes or tomato products were administered in all studies [7][8][9]14,15 ], except for the study by Pool-Zobel et al. [12]. These effects did not only occur by supplementation with tomatoes or tomato products in addition to a diet low in carotenoids [7][8][9]14], but also in addition to a diet without any restrictions [15 ]. Lycopene is the only carotenoid whose concentration increased in all intervention studies not only in plasma [7,10,13], but also in leukocytes [8,9,14,15 ]. ...
Based on epidemiological data, regular consumption of tomatoes, tomato products (TTP), and isolated lycopene is postulated to contribute to the prevention of prostate cancer (PCA), whereas epidemiological data for the prevention of benign prostate hyperplasia (BPH) are scarce. There is a body of in vitro evidence that lycopene protects from DNA damage by increasing antioxidant protection. Moreover, lycopene induces apoptosis and phase II enzymes and inhibits the IGF-1 pathway, which might prevent the development and progression of PCA. Furthermore, lycopene reduces the synthesis of 5-?-dihydrotestosterone stimulating the growth of the prostate gland. The protective effect of TTP and/or lycopene on the development of PCA can only be verified by intervention studies. Since an intervention study with the endpoint PCA would last several years, the benefit from diet or nutrients can only be assessed by suitable surrogate markers that are associated with PCA, such as DNA damage and changes in the insulin-like growth factor I (IGF-1) signaling pathway. The therapeutic value of TPP and/or lycopene for treatment of PCA was evaluated by consideration of intervention studies in which clinically or prognostically relevant parameters were measured. The same procedure was applied for the therapy of BPH.
... Lediglich in der Studie von Pool-Zobel et al. [27] zeigte sich keine Wirkung. Diese Effekte wurden sowohl bei zusätzlichem Verzehr von Tomaten oder Tomatenprodukten unter Einhaltung einer karotinoidarmen Kost [28,30,34,35] als auch bei Studien ohne diätetische Restriktionen [29] beobachtet. Die DNA-Strangbrüche ex vivo waren umso geringer, je höher die Lykopinkonzentration in den Leukozyten war [28,30]. ...
... Diese Effekte wurden sowohl bei zusätzlichem Verzehr von Tomaten oder Tomatenprodukten unter Einhaltung einer karotinoidarmen Kost [28,30,34,35] als auch bei Studien ohne diätetische Restriktionen [29] beobachtet. Die DNA-Strangbrüche ex vivo waren umso geringer, je höher die Lykopinkonzentration in den Leukozyten war [28,30]. ...
... Lykopin war das einzige Karotinoid, dessen Konzentration in allen Studien zur Wirkung von Tomaten und Tomatenprodukten auf DNA-Schäden sowohl im Plasma [31,34] als auch in Leukozyten anstieg [28,30,35] ...
Tomatoes are discussed to have an important role in the prevention of and therapy for prostate cancer (PCA). Whether or not they are also useful in the primary and secondary prevention of benign prostate hyperplasia (BPH) is not clear. This review summarises the results of original contributions with a focus on interventional studies. Whereas epidemiological studies on BPH prevention provide no evidence for a preventive potential of tomatoes and tomato products, the majority of interventional trials points to an increased DNA resistance against oxidative-induced damage. Even though their effect on a surrogate marker of the IGF pathway cannot be evaluated so far due to insufficient data, the consumption of tomatoes and tomato products may probably protect from PCA - at least when considering low-grade PCA. Thus, regular consumption of these foods can be recommended for the prevention of PCA. Tomato products might also be useful in the therapy for BPH and PCA. The intake of isolated lycopene does not protect from the development of PCA. However, in the doses achieved by consumption of tomato products, lycopene ingestion might also be effective in PCA therapy.
... Spinach is a rich source of chemoprotective substances such as folic acid, flavonoids, lutein, zeaxanthine, ß-carotene and chlorophylls [2][3][4], which may contribute to the maintenance of the genetic material. The latter compounds are potent antioxidants, and a recent in vitro study showed that the 2,2 0 -azinobis-(3-ethylbenzothiazoline-6-sulphonic) acid (ATBS) radical scavenging activity and also the oxygen radical absorbance capacity (ORAC) values and metal chelating properties of spinach are higher than those of other commonly consumed vegetables such as carrots, tomatoes, potatoes, green beans and kale [5]. ...
... Results of an older single cell gel electrophoresis (SCGE) study by Pool-Zobel and coworkers [6] indicated that the consumption of the vegetable may protect humans against formation of single-and double-strand breaks but not against formation of oxidised purines in lymphocytes, while Porrini et al. [3] found in a more recent small trial substantial reduction in DNA migration induced by reactive oxygen species (ROS) in the same experimental system after a 3-week intervention period. Comparisons with findings of earlier investigations indicate that spinach may have a high protective potency as in many human intervention trials with other types of plant foods no evidence for protective effects was seen (details see [7][8][9]). ...
... The main aim of the present study was to investigate the potential DNA-protective properties of spinach in more detail. Therefore, we conducted an intervention trial which had, for reasons of comparison, a similar design as the aforementioned Italian study [3]. However, we analysed DNA migration additionally at different time points and included further endpoints of DNA stability. ...
A controlled intervention trial was conducted to assess the impact of spinach consumption on DNA stability in lymphocytes and on health-related biochemical parameters.
The participants (n = 8) consumed homogenised spinach (225 g/day/person) over a period of 16 days. DNA migration was monitored in single cell gel electrophoresis-comet assays under standard conditions, which reflect single- and double-strand breaks, after treatment of nuclei with lesion-specific enzymes (formamidopyrimidine glycosylase, FPG and endonuclease III, ENDO III) and after treatment of intact cells with H(2)O(2) before, during and after intervention.
While no reduction in DNA damage was observed under standard conditions after different time intervals of spinach intake, other endpoints, namely ROS sensitivity and DNA migration attributable to the formation of oxidatively damaged DNA bases (i.e. pyrimidines-ENDO III-sensitive sites and purines-FPG sensitive sites) were reduced 6 h after consumption of the first portion and after 11 days of continuous consumption. In the case of ENDO III-sensitive sites, also after 16 days, a decrease in comet formation was observed. At the end of a 40 days washout period, the DNA stability parameters were not significantly different from the background values. Other biochemical parameters which were significantly altered by spinach intake were the folate (+27%) and homocysteine (-16%) concentrations in blood, and it was found in an earlier human study that folate may prevent oxidative damage to DNA bases.
Taken together, our results show that moderate consumption of spinach causes protection against oxidative DNA damage in humans and that this phenomenon is paralleled by alterations of health-related biochemical parameters.
... Lediglich in der Studie von Pool-Zobel et al. [27] zeigte sich keine Wirkung. Diese Effekte wurden sowohl bei zusätzlichem Verzehr von Tomaten oder Tomatenprodukten unter Einhaltung einer karotinoidarmen Kost [28,30,34,35] als auch bei Studien ohne diätetische Restriktionen [29] beobachtet. Die DNA-Strangbrüche ex vivo waren umso geringer, je höher die Lykopinkonzentration in den Leukozyten war [28,30]. ...
... Diese Effekte wurden sowohl bei zusätzlichem Verzehr von Tomaten oder Tomatenprodukten unter Einhaltung einer karotinoidarmen Kost [28,30,34,35] als auch bei Studien ohne diätetische Restriktionen [29] beobachtet. Die DNA-Strangbrüche ex vivo waren umso geringer, je höher die Lykopinkonzentration in den Leukozyten war [28,30]. ...
... Lykopin war das einzige Karotinoid, dessen Konzentration in allen Studien zur Wirkung von Tomaten und Tomatenprodukten auf DNA-Schäden sowohl im Plasma [31,34] als auch in Leukozyten anstieg [28,30,35] ...
Tomatoes are discussed to have an important role in the prevention of and therapy for prostate cancer (PCA). Whether or not they are also useful in the primary and secondary prevention of benign prostate hyperplasia (BPH) is not clear. This review summarises the results of original contributions with a focus on interventional studies. Whereas epidemiological studies on BPH prevention provide no evidence for a preventive potential of tomatoes and tomato products, the majority of interventional trials points to an increased DNA resistance against oxidative-induced damage. Even though their effect on a surrogate marker of the IGF pathway cannot be evaluated so far due to insufficient data, the consumption of tomatoes and tomato products may probably protect from PCA--at least when considering low-grade PCA. Thus, regular consumption of these foods can be recommended for the prevention of PCA. Tomato products might also be useful in the therapy for BPH and PCA. The intake of isolated lycopene does not protect from the development of PCA. However, in the doses achieved by consumption of tomato products, lycopene ingestion might also be effective in PCA therapy.
... Based on previous studies, dietary intake of foods rich in a variety of antioxidants, such as fruits, vegetables, nuts and whole grain, has a protective role against oxidative stress related diseases or chronic inflammation states (Åsgård et al., 2007;Yu et al., 2016). Fruit and vegetables as a source of essential nutrients such as plant proteins, potassium, magnesium, vitamin C, folate and other bioactive components possess notable antioxidant (Alonso et al., 2004;Rodríguez et al., 2005) and anti-inflammatory capacities (Porrini et al., 2002;Esmaillzadeh et al., 2006), which can have a modulatory role in low-grade inflammation or processes mediated by oxidative stress (Hermsdorff et al., 2010). Furthermore, regular consumption of whole grains is inversely associated with diseases of an inflammatory origin, through providing phytochemicals and several unique bioactive compounds that may have a synergetic effect in combination with fruit and vegetables (Fardet, 2010;Jideani et al., 2014). ...
... Still, the exact anti-inflammatory mechanism of fruit and vegetable intake remains unknown, but can be attributed to the antioxidant capacity of the components of fruit and vegetables such as potassium, magnesium, fiber, folate, vitamin C and so on (Rodríguez et al., 2005;Esmaillzadeh et al., 2006). Therefore, antioxidant properties of fruit and vegetables constituents (specially flavonoids and carotenoids) can play an effective role in reducing oxidative stress and low-grade inflammation (Porrini et al., 2002;Holt et al., 2009). In the current study, consumption of fruit and vegetables was inversely associated with P53 expression in VAT of obese individuals, suggesting a beneficial role of high fruit and vegetables consumption on management of P53 metabolic stressors such as ROS, and then improving the chronic inflammatory status such as obesity (Krstic et al., 2018). ...
Objective:
The present study investigates the association of dietary intake of fruit and green Vegetables with PTEN and P53 mRNA gene expression in visceral (VAT) and subcutaneous adipose tissues (SAT) of obese and non-obese adults.
Methods:
VAT and SAT were obtained from 151 individuals, aged ∼40 years, who had undergone elective abdominal surgery. The participants were grouped according to their body mass index (BMI), as obese (BMI > 30 kg/m2) and non-obese (BMI=18.5-30 kg/m2). Dietary intakes were obtained using a valid and reliable food-frequency questionnaire (FFQ). Real-time PCR was carried out for PTEN and P53 mRNA expressions. Associations between expression levels and dietary parameters were analyzed.
Results:
P53 mRNA expression of obese participants was significantly higher than the non-obese, only in VAT (p<0.001). After adjusting for total energy intake, age and BMI, fruit intake was inversely associated with P53 gene expression in both VAT (β=-0.38, P=0.01) and SAT (β=-0.35, P=0.03) among non-obese participants. Furthermore, fruit consumption was inversely associated with P53 gene expression in obese individuals, only in VAT (β=-0.21, P=0.05). More so, intake of green vegetables in obese subjects was negatively associated with P53 gene expression in VAT (β=-0.27, P=0.01) and SAT (β=-0.28, P<0.001). On the other hand, after adjustment for total energy intake, age and BMI, a positive association was observed between fruit intake and PTEN in VAT (β=0.27, P=0.01) and SAT (β=0.34, P<0.001) among obese participants. In addition, dietary consumption of fruits in non-obese individuals was negatively associated with PTEN expression in SAT (β=-0.48, P<0.001).
Conclusion:
Dietary intake of fruit and green vegetables was associated with P53 gene expression in VAT and SAT of obese participants, suggesting their protective role in regulating P53 mRNA expression in adipose tissue. Furthermore, higher fruit intake was inversely associated with PTEN mRNA levels in non-obese participants, implying the anti-adipogenic role of PTEN gene expression.
... In another clinical study, participants used a spinach-fortified diet (150 g / day) for three weeks. The results showed that spinach reduced DNA damage in lymphocytes as well as increased serum lutein [35]. In a larger study with 48 healthy men and women as participants, the consumption of spinach (20 grams per day for 3 weeks) in the intervention group led to increased plasma lutein and red blood cell glutathione reductase activity compared to the control group [36]. ...
Background:
Spinach is a widely cultivated dark leafy vegetable highly regarded for its medicinal properties in traditional Persian medicine. It is rich in vitamins, minerals, flavonoids, carotenoids, and other bioactive compounds, and this review aims to explore the historical applications of spinach in Persian medicine and juxtapose them with current scientific evidence. Despite its historical significance, there remains a need to comprehensively evaluate and integrate traditional knowledge with modern research on the therapeutic benefits of spinach.
Methods
To achieve this, a comprehensive search was conducted in Persian medicine references and scientific databases to gather information on the traditional uses, chemical composition, and pharmacological effects of spinach. Studies that met the inclusion criteria were meticulously categorized, and relevant data were analyzed to draw insightful comparisons.
Results
Persian medicine describes spinach as a nutrient-rich, laxative, and fast-digesting agent with therapeutic effects on inflammation, lung diseases, back pain, sore throats, jaundice, urinary disorders, joint pain, eye inflammation, insomnia, dementia, and more. Modern studies have substantially corroborated these traditional uses, revealing that spinach possesses antioxidant, anti-inflammatory, anti-cancer, blood sugar-lowering, lipid-lowering, anti-obesity, neurological, ocular, and musculoskeletal effects.
Conclusion
Spinach exhibits a wide range of beneficial effects on various health conditions. Its widespread availability, low cost, and exceptional nutritional richness position it as a promising candidate for further investigation. Future studies should explore the clinical effectiveness of spinach in various diseases, while taking into consideration the principles emphasized in Persian medicine to guide research and inform therapeutic strategies.
... Nuts and cooked tomato sauce using OO highlight the protective role against oxidative DNA damage [48][49][50]. This defense phenomenon was found in intervention studies in the human population after the consumption of tomato [51,52], broccoli [53,54], spinach [55,56], and blueberries [57,58]. In addition, a study in rats fed with a diet enriched with VOO found an association with less damage in the genetic material in peripheral blood cells vs. rats fed with sunflower oil [59]. ...
The life expectancy of the global population has increased. Aging is a natural physiological process that poses major challenges in an increasingly long-lived and frail population. Several molecular mechanisms are involved in aging. Likewise, the gut microbiota, which is influenced by environmental factors such as diet, plays a crucial role in the modulation of these mechanisms. The Mediterranean diet, as well as the components present in it, offer some proof of this. Achieving healthy aging should be focused on the promotion of healthy lifestyle habits that reduce the development of pathologies that are associated with aging, in order to increase the quality of life of the aging population. In this review we analyze the influence of the Mediterranean diet on the molecular pathways and the microbiota associated with more favorable aging patterns, as well as its possible role as an anti-aging treatment.
... Thus, the use of antioxidants could be beneficial for CML patients. Spinach leaves extract was reported for its antioxidant activity in several clinical studies (Cao et al. 1998;Castenmiller et al. 1999;Pool-Zobel et al. 1997;Porrini et al. 2002). Therefore, the antioxidant activity of the spinach extract or its isolated compounds in addition to the antileukemic activities of the isolated compounds might work in symphony to improve CML disease, but this still needs further in vivo and preclinical investigations. ...
Spinacia oleracea L., Amaranthaceae, leaves cultivated in Egypt demonstrated a potential antileukemic activity against the chronic myeloid leukemia, K562 cell line. Thus, the aim of this study is to carry out a phytochemical investigation of S. oleracea leaves as well as the isolation of its antileukemic phytoconstituents. Phytochemical investigation of S. oleracea leaves resulted in the isolation of seventeen known compounds. The biological study revealed that compounds hexaprenol, phytol, and 18-[(1-oxohexadecyl) oxy]-9-octadecenoic acid exhibited a remarkable antiproliferative activity against K562 cells in vitro . A mechanistic in silico study showed that hexaprenol, phytol, and 18-[(1-oxohexadecyl) oxy]-9-octadecenoic acid exhibited a strong binding affinity towards topoisomerase (docking score −12.50, −9.19, and −13.29 kcal/mol, respectively), and showed as well a strong binding affinity towards Abl kinase (docking score −11.91, −9.35, and −12.59 kcal/mol, respectively). Molecular dynamics study revealed that 18-[(1-oxohexadecyl) oxy]-9-octadecenoic acid produced stable complexes with both topoisomerase and Abl kinase with RMSD values of 1.81 and 1.85 Å, respectively. As a result of our findings, we recommend more in vivo and preclinical studies to confirm the potential benefit of spinach leaves for chronic myeloid leukemia patients.
Graphical Abstract
... This may cause permanent distortion of the tissue, interfering its function. Also inflammation might induce infiltration .On other hand tomato 5%,spinach10% and "Jew's mallow" 5% induced significant decreases in lymphocytes level compared with control positive group( p≤0.05).These results are in agreement with Porrini et al., (2002).who found that lycopene decreased significantly lymphocytes , and this reduction was due to the consumption of carotenoid-rich foods which even for a short period of time gives protection against oxidative stress. ...
... The antioxidant effect is not related to the increase in carotenoid concentration in lymphocytes (Moser et al., 2011). Further clarification was provided by Porrini, Riso, and Oriani (2002) in 9 healthy female volunteers who followed a diet rich in spinach, limiting other carotenoid sources. HPLC analysis revealed a non-significant increase in carotenoid concentration in lymphocytes. ...
... Bioactives and bioactive-rich foods can exert a protective effect against oxidative stress resulting in lower DNA damage. For instance, DNA damage protection has been observed in several human intervention studies following the consumption of tomato [11,12], broccoli [13,14], spinach [15,16], blueberry [17,18], orange juice [19,20], nuts [21,22], green tea [23,24], and coffee [25,26]. Most of these foods are present in the Mediterranean diet (MD) and represent a rich sources of bioactive compounds such as vitamins, carotenoids, glucosinolates, and polyphenols acting as antioxidants or activators of endogenous multiple defense systems [27,28]. ...
The Mediterranean diet (MD) is characterized by high consumption of fruits, vegetables, cereals, potatoes, poultry, beans, nuts, lean fish, dairy products, small quantities of red meat, moderate alcohol consumption, and olive oil. Most of these foods are rich sources of bioactive compounds which may play a role in the protection of oxidative stress including DNA damage. The present review provides a summary of the evidence deriving from human intervention studies aimed at evaluating the impact of Mediterranean diet on markers of DNA damage, DNA repair, and telomere length. The few results available show a general protective effect of MD alone, or in combination with bioactive-rich foods, on DNA damage. In particular, the studies reported a reduction in the levels of 8-hydroxy-2′–deoxyguanosine and a modulation of DNA repair gene expression and telomere length. In conclusion, despite the limited literature available, the results obtained seem to support the beneficial effects of MD dietary pattern in the protection against DNA damage susceptibility. However, further well-controlled interventions are desirable in order to confirm the results obtained and provide evidence-based conclusions.
... It contains several active components, including flavonoids (Table 2), exhibit antioxidative, antiproliferative, and anti-inflammatory properties in biological systems. Spinach extracts have numerous healthy effects, such as chemo-and central nervous system protection, anticancer and anti-aging functions (Porrini et al., 2002;Lomnitski et al., 2003;USDA, 2015).The concentration of arsenic in root was high (83.10 mg As/kg) in glassworks (Gadderås), Sweden followed by shoot (7.0310 mg As/kg) (Bergqvist et al., 2014). ...
... italica) was reported to act against and provide protection from liver cancer in animals [15]. In humans, glycosides are involved in reducing DNA damage in lymphocytes [16,17]. There was significant anti-nutritional activity in animals when they were fed with GSLs [14]. ...
Myrosinase, which is present in cruciferous plant species, plays an important role in the hydrolysis of glycosides such as glucosinolates and is involved in plant defense. Brassicaceae myrosinases are diverse although they share common ancestry, and structural knowledge about myrosinases from cabbage (Brassica oleracea) was needed. To address this, we constructed a three-dimensional model structure of myrosinase based on Sinapis alba structures using Iterative Threading ASSEmbly Refinement server (I-TASSER) webserver, and refined model coordinates were evaluated with ProQ and Verify3D. The resulting model was predicted with β/α fold, ten conserved N-glycosylation sites, and three disulfide bridges. In addition, this model shared features with the known Sinapis alba myrosinase structure. To obtain a better understanding of myrosinase-sinigrin interaction, the refined model was docked using Autodock Vina with crucial key amino acids. The key nucleophile residues GLN207 and GLU427 were found to interact with sinigrin to form a hydrogen bond. Further, 20-ns molecular dynamics simulation was performed to examine myrosinase-sinigrin complex stability, revealing that residue GLU207 maintained its hydrogen bond stability throughout the entire simulation and structural orientation was similar to that of the docked state. This conceptual model should be useful for understanding the structural features of myrosinase and their binding orientation with sinigrin.
... One study (n = 60) in relatively healthy individuals [164] and 2 studies (n = 40 and n = 57) in individuals with type 2 diabetes, who are in a relatively pro-oxidant state, showed decreased lipid peroxidation rates [181] and decreased susceptibility of low-density lipoproteins to oxidation [159] after daily consumption of tomatoes or tomato juice. Others have reported less susceptibility to oxidation of DNA [182,183] and low density lipoprotein [184] after tomato product consumption delivering approximately half (or more) of the lycopene dose typically used in lycopene supplementation studies. These data suggest that the health benefits of tomato/tomato product consumption are not solely because of lycopene content, but rather the result of the combination of nutrients and bioactive constituents delivered when the whole food is consumed. ...
Vegetables are considered essential for well-balanced diets since they supply vitamins, minerals, dietary fiber, and phy-tochemicals. Each vegetable group contains a unique combination and amount of these phytonutriceuticals, which distinguishes them from other groups and vegetables whithin their own group. In the daily diet vegetables have been strongly associated with improvement of gastrointestinal health, good vision, and reduced risk of heart disease, stroke, chronic diseases such as diabetes, and some forms of cancer. Some phytochemicals of vegetables are strong antioxi-dants and are thought to reduce the risk of chronic disease by protecting against free radical damage, by modifying metabolic activation and detoxification of carcinogens, or even by influencing processes that alter the course of tumor cells. All the vegetables may offer protection to humans against chronic diseases. Nutrition is both a quantity and a quality issue, and vegetables in all their many forms ensure an adequate intake of most vitamins and nutrients, dietary fibers, and phytochemicals which can bring a much-needed measure of balance back to diets contributing to solve many of these nutrition problems. The promotion of healthy vegetable products has coincided with a surging consumer interested in the healthy functionality of food. Because each vegetable contains a unique combination of phytonutriceuticals, a great diversity of vegetables should be eaten to ensure that individual's diet includes a combination of phytonutriceu-ticals and to get all the health benefits. This article makes a review and discusses the nutritional quality and health benefits of the major groups of vegetables. More interdisciplinary work is required that inVol.ves nutritional and food scientists as well as others from biomedical fields to ascertain the thrue function of specific phytonutriceuticals.
... One study (n = 60) in relatively healthy individuals [480] and two studies (n = 40 and n = 57) in individuals with type 2 diabetes, who are in a relatively pro-oxidant state, showed decreased lipid peroxidation rates [497] and decreased susceptibility of low-density lipoproteins to oxidation [475] after daily consumption of tomatoes or tomato juice. Others have reported less susceptibility to oxidation of DNA [498, 499] and low-density lipoprotein [500] after tomato product consumption delivering approximately half (or more) of the lycopene dose typically used in lycopene supplementation studies. These data suggest that the health benefits of tomato/tomato product consumption are not solely because of lycopene content but rather the result of the combination of nutrients and bioactive constituents delivered when the whole food is consumed. ...
... Estudios realizados en humanos muestran que el consumo de tomate y productos a base de esta hortaliza, por un tiempo determinado, puede aumentar la protección del ADN ante el daño inducido por ROS (27,(40)(41)(42). Este efecto que puede explicarse por la sinergia de los diferentes antioxidantes presentes en el tomate (43). ...
Cardiovascular diseases (CVD) are the main cause of mortality worldwide. To prevent CVD it is recommended to quit smoking, the practice of physical activity and the consumption of healthy food. In this context, numerous studies have shown the importance of a frequent consumption of fruits and vegetables (at least 5 a day). It has been described an inverse relationship between vegetables consumption and the risk of developing CVD, which is mainly explained by its antioxidant activity, and in some cases lipid-lowering and antiplatelet effects. In this sense, the increase in regular consumption of tomato (Solanum lycopersicum L.) and related products, can improve the some cardiovascular parameters. The current lifestyle favors the consumption of processed foods, a situation that may affect the stability of tomato components and their physicochemical properties. This review addresses the antioxidant activities, lipid-lowering and antiaggregant properties of tomato, as well as the effect of processing and storage. Additionally, a summary of some patents associated with beneficial effects on health. As bibliographic source was mainly used, the terms used in the search were: antiplatelet, tomato, and platelet, antioxidant, among others, then search the full texts of items of common interest.
... Estudios realizados en humanos muestran que el consumo de tomate y productos a base de esta hortaliza, por un tiempo determinado, puede aumentar la protección del ADN ante el daño inducido por ROS (27,(40)(41)(42). Este efecto que puede explicarse por la sinergia de los diferentes antioxidantes presentes en el tomate (43). ...
Cardiovascular diseases (CVD) are the main cause of mortality worldwide. To prevent CVD it is recommended to quit smoking, the practice of physical activity and the consumption of healthy food. In this context, numerous studies have shown the importance of frequent consumption of fruits and vegetables (at least5 a day). It has been described an inverse relationship between vegetables consumption and the risk of developing CVD, which is mainly explained by its antioxidant activity, and in some cases lipid-lowering and platelet effects. In this sense, the increase in regular consumption of tomato (Solanum lycopersicum L.) and related products, can improve the some cardiovascular parameters. The current lifestyle favors the consumption of processed foods, a situation that may affect the stability of tomato components and their physicochemical properties. This review addresses the antioxidant activities, lipid-lowering and antiaggregant properties of tomato, as well as the effect of processing and storage. Additionally, a summary of some patents associated with beneficial effects on health. As bibliographic source www.pubmed.org was mainly used, the terms used in the search were and platelet, tomato, and platelet, antioxidant, among others, then search the full texts of items of common interest.
... However, one study (n = 60) in relatively healthy individuals 33 and 2 studies (n = 40 and n = 57) in individuals with type 2 diabetes, who are in a relatively pro-oxidant state, showed decreased lipid peroxidation rates 64 and decreased susceptibility of low-density lipoproteins (LDL) to oxidation 35 after daily consumption of tomatoes or tomato juice. Others have reported less susceptibility to oxidation of DNA 65,66 and LDL 67 after tomato product consumption delivering approximately half (or more) of the lycopene dose typically used in lycopene supplementation studies. These data suggest that the health benefits of tomato/tomato product consumption are not solely because of lycopene content, but rather the result of the combination of nutrients and bioactive constituents delivered when the whole food is consumed. ...
Tomatoes and tomato products are one of the most familiar vegetables in the American diet. Quantitatively, they are the most consumed nonstarchy vegetable and are the most significant source of dietary lycopene; a powerful antioxidant that has greater bioavailability after cooking and processing (eg, canning). A large body of research supports an inverse relationship between consuming tomatoes and tomato products and risk of certain cancers, while emerging research is exploring the protective relationship between tomato intake and a host of conditions, including cardiovascular disease, osteoporosis, ultraviolet light—induced skin damage, and cognitive dysfunction. Initial studies of tomato consumption and disease risk reduction focused on lycopene and antioxidant activity. More recent hypotheses recognize the advantages of the whole tomato; and hence, research on the role of tomato products in health and disease risk reduction extends beyond antioxidant function to include other protective mechanisms such as antithrombotic and anti-inflammatory functions. Increasing daily vegetable intake in the American diet offers the potential to yield significant health benefits. In addition to the specific benefits of tomato consumption, encouraging greater tomato and tomato product consumption may help increase overall vegetable intake because of their wide availability, well-established acceptability, cost-effectiveness, and convenience of multiple forms. Leveraging emerging science about tomatoes and tomato products may be one simple and effective strategy to help individuals increase vegetable intake, leading to improved overall eating patterns, and ultimately, better health.
... Dietary antioxidant supplementation with SFN in humans induces antioxidant genes in vivo (25), alters HDAC activity in peripheral blood mononuclear cells (26) and protects cells from diverse types of toxic environmental exposures (27). For example, dietary antioxidants seem to increase resistance to oxidative stress and mutagenicity in human lymphocytes (28,29), and this is likely due to activation of the NRF2 antioxidant pathway. Thus, activation of the NRF2-mediated pathway is increasingly proposed as a way to prevent or treat disease, including cancer (30), cardiovascular (31), obesity (32,33) and neurodegenerative disease (34). ...
Cellular oxidative and electrophilic stress triggers a protective response in mammals regulated by NRF2 (nuclear factor (erythroid-derived)
2-like; NFE2L2) binding to deoxyribonucleic acid-regulatory sequences near stress-responsive genes. Studies using Nrf2-deficient mice suggest
that hundreds of genes may be regulated by NRF2. To identify human NRF2-regulated genes, we conducted chromatin immunoprecipitation
(ChIP)-sequencing experiments in lymphoid cells treated with the dietary isothiocyanate, sulforaphane (SFN) and carried out
follow-up biological experiments on candidates. We found 242 high confidence, NRF2-bound genomic regions and 96% of these
regions contained NRF2-regulatory sequence motifs. The majority of binding sites were near potential novel members of the
NRF2 pathway. Validation of selected candidate genes using parallel ChIP techniques and in NRF2-silenced cell lines indicated
that the expression of about two-thirds of the candidates are likely to be directly NRF2-dependent including retinoid X receptor
alpha (RXRA). NRF2 regulation of RXRA has implications for response to retinoid treatments and adipogenesis. In mouse, 3T3-L1 cells’ SFN treatment affected Rxra
expression early in adipogenesis, and knockdown of Nrf2-delayed Rxra expression, both leading to impaired adipogenesis.
... Similarly, higher fruit content in an energy-restricted diet improved antioxidant status in overweight/obese women during weight loss, with a reduction in malondialdehyde:TAC ratio (42) . The consumption of tomato and spinach has also enhanced plasma antioxidant capacity and prevented oxidative stress in healthy young adults (43,44) . In addition, the resistance to oxidative modification of LDL was enhanced in the 2 h period after banana meal (400 g) consumption (45) . ...
The aim of the present cross-sectional study was to assess the potential relationships between fruit and vegetable (FV) consumption and some oxidative stress markers in young adults, with particular emphasis on fibre and vitamin C intake. The study enrolled 246 healthy subjects (eighty-eight men and 158 women), with a mean age of 22 (sd 3) years and a mean BMI of 21·9 (sd 2·8) kg/m2. Dietary intake, anthropometry, blood pressure, lifestyle features and blood biochemical data were assessed with validated procedures. Those subjects in the highest tertile (T) of FV consumption ( ≥ 705 g/d) had statistically lower oxidised LDL (ox-LDL) concentrations as well as higher plasma total antioxidant capacity (TAC) and glutathione peroxidase (GPx) activity (P for trend <0·05), after adjusting for sex, age, energy intake, physical activity, smoking, BMI, vitamin supplement use and other confounding factors. Moreover, plasma ox-LDL concentrations showed a decreasing trend and TAC an increasing trend across tertiles of fibre (T3: ≥14 g/d) and vitamin C (T3: ≥150 mg/d) from FV intake, while GPx activity was positively associated with vitamin C intake (P for trend < 0·05). In conclusion, greater FV consumption was independently associated with reduced ox-LDL as well as increased TAC and GPx activity in healthy young adults, with dietary fibre and vitamin C from FV clearly being implicated in this beneficial relationship.
... l ADN cromosómico ( Szeto Benzoe , 2002 , Collins et al . , 2001 ) . Muchos estudios epidemiológicos muestran los efectos preventivos de los antioxidantes en el origen y la evolución de diversas enfermedades ( Moller Loft , 2002 ) . El consumo de carotinoides , de té , de soja , de dietas ricas en fruta y verdura protege frente al daño oxidativo ( Porrini et al . , 2002 ) , lo cual se relaciona con un menor riesgo de cáncer ( Astley et al . , 2002 ) y otras patologías . En pacientes diabéticos , por ejemplo , se ha demostrado que se produce una disminución en el daño oxidativo en el ADN , aportando suplementos de sustancias antioxidantes en la dieta ( Sardas et al . , 2001 ) - De forma complementaria , ...
Tesis Univ. Granada. Departamento de Pediatría. Leída el 15 de junio de 2007
... Consumption of Brussels sprouts, spinach, watercress, or a sprouting vegetable mixture (containing broccoli, radish, alfalfa and clover) significantly reduced DNA damage in lymphocytes, following treatment (ex vivo) with H 2 O 2 , and as measured via 8-oxodG excretion [243,244]. A good correlation has been observed between DNA damage occurring in colonocytes and the levels observed in lymphocytes of subjects participating in supplementation studies [245]. ...
Glucosinolates (GLSs) are found in Brassica vegetables. Examples of these sources include cabbage, Brussels sprouts, broccoli, cauliflower and various root vegetables (e.g. radish and turnip). A number of epidemiological studies have identified an inverse association between consumption of these vegetables and the risk of colon and rectal cancer. Animal studies have shown changes in enzyme activities and DNA damage resulting from consumption of Brassica vegetables or isothiocyanates, the breakdown products (BDP) of GLSs in the body. Mechanistic studies have begun to identify the ways in which the compounds may exert their protective action but the relevance of these studies to protective effects in the human alimentary tract is as yet unproven. In vitro studies with a number of specific isothiocyanates have suggested mechanisms that might be the basis of their chemoprotective effects. The concentration and composition of the GLSs in different plants, but also within a plant (e.g. in the seeds, roots or leaves), can vary greatly and also changes during plant development. Furthermore, the effects of various factors in the supply chain of Brassica vegetables including breeding, cultivation, storage and processing on intake and bioavailability of GLSs are extensively discussed in this paper.
... In addition, butyrate production after the consumption of dietary fiber could have an inhibitory effect on the NFκB and a stimulatory effect on PPAR-α activation, with subsequent lower expression of ICAM1 and VCAM1 genes [46], although this mechanism deserves further research. Furthermore , fruits and vegetables contain several flavonoids and carotenoids with recognized antioxidant properties, which may play a role in the inverse relationship between intake of fruits and vegetables and inflammatory status [9,38,47]. In fact, several in vitro studies have evidenced an anti-inflammatory effect of flavonoids and carotenoids , by an inhibition of NFκB activity, through suppressing the activation-related phosphorylation, and inhibiting the nuclear translocation484950. ...
Fruits and vegetables are important sources of fiber and nutrients with a recognized antioxidant capacity, which could have beneficial effects on the proinflammatory status as well as some metabolic syndrome and cardiovascular disease features. The current study assessed the potential relationships of fruit and vegetable consumption with the plasma concentrations and mRNA expression values of some proinflammatory markers in young adults.
One-hundred and twenty healthy subjects (50 men/70 women; 20.8 +/- 2.6 y; 22.3 +/- 2.8 kg/m2) were enrolled. Experimental determinations included anthropometry, blood pressure and lifestyle features as well as blood biochemical and inflammatory measurements. The mRNA was isolated from peripheral blood mononuclear cells (PBMC) and the gene expression concerning selected inflammatory markers was assessed by quantitative real-time PCR. Nutritional intakes were estimated by a validated semi-quantitative food-frequency questionnaire.
The highest tertile of energy-adjusted fruit and vegetable consumption (>660 g/d) was associated with lower plasma concentrations of C-reactive protein (CRP) and homocysteine and with lower ICAM1, IL1R1, IL6, TNFalpha and NFkappaB1 gene expression in PBMC (P for trend < 0.05), independently of gender, age, energy intake, physical activity, smoking, body mass index, systolic blood pressure and circulating non-esterified fatty acids. In addition, plasma CRP, homocysteine and TNFalpha concentrations and ICAM1, TNFalpha and NFkappaB1 gene expression in PBMC showed a descending trend as increased fiber intake (>19.5 g/d) from fruits and vegetables (P for trend < 0.05). Furthermore, the participants within the higher tertile (>11.8 mmol/d) of dietary total antioxidant capacity showed lower plasma CRP and mRNA values of ICAM1, IL1R1, IL6, TNFalpha and NFkappaB1 genes (P for trend < 0.05). The inverse association between fruit and vegetable consumption and study proinflammatory markers followed the same trend and remained statistically significant, after the inclusion of other foods/nutrients in the linear regression models.
A higher fruit and vegetable consumption was independently associated not only with reduced CRP and homocysteine concentrations but also with a lower mRNA expression in PBMC of some relevant proinflammatory markers in healthy young adults.
... With the parent study recruiting participants based on UGT1A1 genotypes, we could explore the role of UGT1A1*28 polymorphism on DNA damage and repair measures. The 2-wk wash-out period was chosen based on the outcomes of the parent study (a study of glucuronidation in humans); the duration is also commonly used in dietary intervention studies using the Comet assay to measure DNA damage endpoints (23,(28)(29)(30)(31). Another strength is that all slides in this study were scored by one technician to minimize interscorer variation. ...
Epidemiologic studies have examined the association between fruit and vegetable (F&V) consumption and the risk of cancer. Several cancer-preventive mechanisms have been proposed, such as antioxidant properties and modulation of biotransformation enzyme activities; both may be associated with reducing DNA damage and hence the mutation rate. We investigated, in a randomized, controlled, crossover feeding trial, the effect of 10 servings/day of botanically defined F&V for 2 wk on endogenous DNA damage; resistance to gamma -irradiation damage; and DNA repair capacity in lymphocytes, measured by the Comet assay. We also explored the association between the UGT1A1*28 polymorphism and serum bilirubin concentrations and DNA damage and repair measures. Healthy men (n = 11) and women (n = 17), age 20 to 40 yr, provided blood samples at the end of each feeding period. Overall, F&V did not affect DNA damage and repair measures in lymphocytes. The number of UGT1A1*28 alleles was inversely associated with sensitivity to gamma -irradiation exposure and DNA repair capacity, but a biological mechanism to explain this association is unclear. A larger sample size is needed to investigate the association between bilirubin concentrations and endogenous DNA damage. With inconsistent findings in the literature, additional dietary intervention studies on the effect of F&V on DNA damage and repair are needed.
... In fact, we obtained a decrease of H 2 0 2 -induced DNA damage after 10 days consumption of 200 g broccoli/day. Comparable data have been obtained in previous studies carried out in our laboratory with other fruits and vegetables (i.e., tomatoes, spinach, oranges, etc.), providing demonstration of the protective efficacy of vegetable intake (25)(26)(27). ...
Cruciferous vegetables (CVs) have been widely studied for their anticarcinogenic properties. The aim of the present study was to evaluate the protective effect of broccoli intake in smokers and nonsmokers. Twenty young healthy males (10 smokers and 10 nonsmokers) were randomized in a cross-over design and received a portion of broccoli (200 g) or maintained a controlled diet for 10 days each. The two periods were separated by a wash-out period (20 days). Blood samples were collected at 0, 10, 30, and 40 days and used for the evaluation of DNA damage, insulin-like growth factor-I (IGF-I) and histone deacetylase (HDAC). Ex vivo protection from H(2)O(2)-induced DNA damage and endogenous DNA damage were evaluated in lymphocytes by means of the comet assay. Strand breaks decreased significantly after the broccoli diet in smokers as well as in nonsmokers (-22.2%; P < 0.0001), whereas oxidized purines decreased significantly only in smokers (-51.0%; P < 0.0001). Broccoli intake did not modify HDAC activity and IGF-I serum levels. Our results strengthen the importance of consuming CVs to increase cell protection against DNA damage. Future investigation, with different amount of broccoli and/or different time of exposure, is needed to understand the lack of effect on HDAC activity and IGF-I levels.
... Consumption of Brussels sprouts, spinach, watercress, or a sprouting vegetable mixture (containing broccoli, radish, alfalfa and clover) significantly reduced DNA damage in lymphocytes, following treatment (ex vivo) with H 2 O 2 , and as measured via 8-oxodG excretion [243,244]. A good correlation has been observed between DNA damage occurring in colonocytes and the levels observed in lymphocytes of subjects participating in supplementation studies [245]. ...
Glucosinolates (GLSs) are found in Brassica vegetables. Examples of these sources include cabbage, Brussels sprouts, broccoli, cauliflower and various root vegetables (e.g. radish and turnip). A number of epidemiological studies have identified an inverse association between consumption of these vegetables and the risk of colon and rectal cancer. Animal studies have shown changes in enzyme activities and DNA damage resulting from consumption of Brassica vegetables or isothiocyanates, the breakdown products (BDP) of GLSs in the body. Mechanistic studies have begun to identify the ways in which the compounds may exert their protective action but the relevance of these studies to protective effects in the human alimentary tract is as yet unproven. In vitro studies with a number of specific isothiocyanates have suggested mechanisms that might be the basis of their chemoprotective effects. The concentration and composition of the GLSs in different plants, but also within a plant (e.g. in the seeds, roots or leaves), can vary greatly and also changes during plant development. Furthermore, the effects of various factors in the supply chain of Brassica vegetables including breeding, cultivation, storage and processing on intake and bioavailability of GLSs are extensively discussed in this paper.
... Clinical studies have further demonstrated that dietary consumption of tomato products, containing lycopene, reduce biomarkers of oxidative stress (cellular DNA damage and biomarkers of lipid oxidation) in healthy subjects, smokers, and type 2 diabetics [9][10][11][12][13]. While effects on lipid peroxidation have been somewhat conflicting [14][15][16], several studies have consistently shown a significant decrease in lymphocyte DNA damage, following dietary intervention with tomato products in healthy human volunteers [12,[17][18][19]. However, these studies do not suggest a role of lycopene per se, since tomato products contain several antioxidants, including carotenoids, lycopene, vitamins E and C and polyphenols, and each of these can interact to confer a preventive benefit against oxidativestress associated diseases [20]. ...
While tomato product supplementation, containing antioxidant carotenoids, including lycopene, decreases oxidative stress, the role of purified lycopene as an antioxidant remains unclear. Thus, we tested the effects of different doses of purified lycopene supplementation on biomarkers of oxidative stress in healthy volunteers.
This was a double-blind, randomized, placebo-controlled trial, examining the effects of 8-week supplementation of purified lycopene, on plasma lycopene levels, biomarkers of lipid peroxidation {LDL oxidizability, malondialdehyde & hydroxynonenals (MDA & HNE), urinary F(2)-isoprostanes}, and markers of DNA damage in urine and lymphocytes. Healthy adults (n = 77, age > or = 40 years), consumed a lycopene-restricted diet for 2 weeks, and were then randomized to receive 0, 6.5, 15, or 30 mg lycopene/day for 8 weeks, while on the lycopene-restricted diet. Blood and urine samples were collected at the beginning and end of Week 2 of lycopene-restricted diet, and at end of Week 10 of the study.
Independent of the dose, plasma lycopene levels significantly increased in all lycopene supplemented groups versus placebo (p < 0.05). ANOVA revealed a significant decrease in DNA damage by the comet assay (p = 0.007), and a significant decrease in urinary 8-hydroxy deoxoguanosine (8-OHdG) at 8 weeks versus baseline (p = 0.0002), with 30 mg lycopene/day. No significant inter- or intra-group differences were noted for glucose, lipid profile, or other biomarkers of lipid peroxidation at any dose/time point.
Thus, purified lycopene was bioavailable and was shown to decrease DNA oxidative damage and urinary 8-OHdG at the high dose.
Vegetables come in varied colors, forms, and tastes. Health specialists highly encourage inclusion of vegetables in one’s diet due to their inherent nutritional worth. This chapter will cover selected vegetables from wide-ranging families like roots, stems, leafy greens, and cruciferous varieties. The broad choice of the designated vegetables is predicated on popular household preferences, nourishing value, and health benefits. These vegetables are also in common use and are obtainable at the market. The health features of the vegetables are covered in such a way that they provide the distinctive phytonutrient quality coupled with prominent health findings.
Overwhelming evidence indicates that diets rich in fruits and vegetables are protective against common chronic diseases, such as cancer, obesity and cardiovascular disease. Leafy green vegetables, in particular, are recognized as having substantial health-promoting activities that are attributed to the functional properties of their nutrients and non-essential chemical compounds. Spinach (Spinacia oleracea L.) is widely regarded as a functional food due to its diverse nutritional composition, which includes vitamins and minerals, and to its phytochemicals and bioactives that promote health beyond basic nutrition. Spinach-derived phytochemicals and bioactives are able to (i) scavenge reactive oxygen species and prevent macromolecular oxidative damage, (ii) modulate expression and activity of genes involved in metabolism, proliferation, inflammation, and antioxidant defence, and (iii) curb food intake by inducing secretion of satiety hormones. These biological activities contribute to the anti-cancer, anti-obesity, hypoglycemic, and hypolipidemic properties of spinach. Despite these valuable attributes, spinach consumption remains low in comparison to other leafy green vegetables. This review examines the functional properties of spinach in cell culture, animals and humans with a focus on the molecular mechanisms by which spinach-derived non-essential phytochemicals and bioactives, such as glycolipids and thylakoids, impart their health benefits.
There have been numerous reviews that have appeared in the last few years detailing various aspects of the antioxidant action of carotenoids (1-3), although the existence of an antioxidative effect has been questioned by some (4).
Results of intervention studies suggest that the daily consumption of one portion of tomatoes or tomato products increases the resistance of leucocytes against breaks of the DNA cord. In view of a correlation existing between DNA-cord breaks in leucocytes and in prostate tissue, it may be that a corresponding nutritional behaviour reduces the risk of prostate carcinoma. Because the data available are insufficient it is not sure whether a regular consumption of these products is therapeutically effective in patients with carcinoma of the prostate. Nor can the effects of tomatoes and tomato products be exclusively attributed to individual carotenoids; part of these effects seems to be produced by other components, The complete network of components could also be needed for preventive action.
Phytochemicals, which are naturally according compounds in plant foods, are reported to provide various biological functions in humans. In particular, plant pigment phytochemicals, carotenoids and flavonoids, are the most extensively studied phytochemicals for their antioxidant functions as well as potential preventive medicinal benefits such as maintaining inflammation balance, reducing the risk of certain cancers, and promoting cardiovascular, neurocognitive, eye, and bone health in humans. The plant pigment phytochemical content in plants can vary according to but not limited to the varieties, genotypes, culture conditions, maturity, storage conditions, and thermal processing. In addition, their bioavailability in humans can be affected by various factors such as food matrix, structure, interactions with other nutrients, site of absorption, and their metabolism. Currently proposed biological functions of plant pigment phytochmicals in humans and various factors affecting such functions are discussed in this review. © Springer-Verlag Berlin Heidelberg 2014. All rights are reserved.
An antioxidant may be broadly defined as “any substance that when present at low concentrations compared to those of an oxidizable substrate, significantly delays or prevents oxidation” (1). Carotenoids are often regarded as dietary antioxidants, but how effective are they? Although more than 600 naturally occurring carotenoids have been identified (2), only 40 of these are ingested in the human diet, but fewer than 20, including both polar xanthophylls and apolar cyclic and acyclic carotenes from dietary sources, have been found in plasma and tissues (3,4). Trace levels of a number of carotenoid metabolites and potential oxidation products of dietary carotenoids (4), including, for example, 2,6-cyclolyopene-1,5- diols (5), anhydrolutein (6), and acycloretinol (7), have also been detected. Although a number of these oxidation products may be produced by interaction of carotenoids with reactive oxygen species (ROS) under controlled conditions (8,9; see below), their functional significance (if any) in biological tissues is not yet understood (see Ref. 10).
Carotenoids are ubiquitous components of edible fruits and vegetables and represent an important group of potential chemopreventive agents. In this regard, the most extensively studied carotenoid has been b-carotene, which has provitamin A activity. However, other carotenoids, such as lycopene, do not have provitamin A activity but show a higher potential to suppress experimental carcinogenesis. Carotenoids are thought to reduce the damage caused by free radicals to cell membranes and associated receptors, modulate cell immune responses, and inhibit initiated tumor cells. This chapter gives an account of the major natural carotenoids and reviews studies on their cancer-preventive activities.
Export Date: 18 October 2014
This study was designed to investigate the effect of dandelion juice supplementation on attenuation of oxidative stress and hangover after drinking alcohol in healthy college male students. This human trial was conducted by two phase cross over design with two weeks wash out period. The subjects (age years) were volunteers who had more than 72 g of ethanol drinking capacity. Dandelion group was given dandelion juice 220 mL daily for 7 days. Biochemical markers were determined in blood samples taken at 0 and 150 minutes after administration 72 g of alcohol. The levels of plasma glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, lactate dehydrogenase and bilirubin, the indicators of liver cell damage, were not significantly different between groups. No significant differences in lymphocyte DNA damage level between groups was observed. However, plasma acetaldehyde dehydrogenase (ALDH) and high density lipoprotein cholesterol levels were significantly (p
Objective: To review the effects of tomato product supplementation, containing lycopene, on biomarkers of oxidative stress and carcinogenesis in human clinical trials.
Results: Supplementation of tomato products, containing lycopene, has been shown to lower biomarkers of oxidative stress and carcinogenesis in healthy and type II diabetic patients, and prostate cancer patients, respectively. Processed tomato products like tomato juice, tomato paste, tomato puree, tomato ketchup and tomato oleoresin have been shown to provide bioavailable sources of lycopene, with consequent increases in plasma lycopene levels versus baseline. Dietary fats enhance this process and should be consumed together with food sources of lycopene. The mechanisms of action involve protection of plasma lipoproteins, lymphocyte DNA and serum proteins against oxidative damage, and anticarcinogenic effects, including reduction of prostate-specific antigen, upregulation of connexin expression and overall decrease in prostate tumor aggressiveness. There is limited in vivo data on the health benefits of lycopene alone. Most of the clinical trials with tomato products suggest a synergistic action of lycopene with other nutrients, in lowering biomarkers of oxidative stress and carcinogenesis.
Conclusions: Consumption of processed tomato products, containing lycopene, is of significant health benefit and can be attributed to a combination of naturally occurring nutrients in tomatoes. Lycopene, the main tomato carotenoid, contributes to this effect, but its role per se remains to be investigated.
Sponsorship: This study was supported by Human Nutrition Fund, Texas. AB wrote the first draft which was finalized by VI. VI also designed Figure 1.
European Journal of Clinical Nutrition (2007) 61, 295–303. doi:10.1038/sj.ejcn.1602510; published online 16 August 2006
Broccoli is a rich source of bioactive compounds (i.e. glucosinolates, carotenoids, vitamin C and folate) that may exert an antioxidant effect and reduce oxidative damage. The objective of this pilot study was to investigate the effect of broccoli consumption on carotenoids, vitamin C and folate absorption, glutathione S-transferase (GST) activity, and oxidatively induced DNA damage in male smokers.
Ten healthy subjects consumed a single portion of steamed broccoli (250 g) with cooked pasta. Blood was drawn at baseline and at 3, 6 and 24 h from consumption.
Broccoli significantly (P ≤ 0.01) increased plasma level of vitamin C and folate (+35% and 70%, respectively) at 3 h, and β-carotene (+8%) at 6 h. A modulation of GST activity occurred in plasma 6 h after broccoli consumption. A significant (P ≤ 0.01) reduction of the levels of H2 O2 -induced DNA damage (-18%) was observed in blood mononuclear cells 24 h after broccoli intake in GSTM1 positive, but not in GSTM1 null subjects.
One portion of broccoli increased plasma antioxidant levels, modulated plasma GST activity and improved cell resistance against H2 O2 -induced DNA damage in healthy smokers. These results support the importance of consuming fruit and vegetable regularly. © 2013 Society of Chemical Industry.
Abstract Lycopene is a potentially useful compound for preventing and treating cardiovascular diseases and cancers. Studies on the effects of lycopene on oxidative stress offer insights into its mechanism of action and provide evidence-based rationale for its supplementation. In this analysis, randomized controlled trials of the effects of oral lycopene supplementation on any valid outcomes of oxidative stress were identified and pooled through a search of international journal databases and reference lists of relevant publications. Two reviewers extracted data from each of the identified studies. Only studies of sufficient quality were included. Twelve parallel trials and one crossover trial were included in the systematic review, and six trials provided data for quantitative meta-analysis. Our results indicate that lycopene supplementation significantly decreases the DNA tail length, as determined using comet assays, with a mean difference (MD) of -6.27 [95% confidence interval (CI) -10.74, -1.90] (P=.006) between the lycopene intervention groups and the control groups. Lycopene supplementation does not significantly prolong the lag time of low-density lipoprotein (MD 3.76 [95% CI -2.48, 10.01]; P=.24). Lycopene possibly alleviates oxidative stress; however, biomarker research for oxidative stress needs be more consistent with the outcomes in lycopene intervention trials for disease prevention.
Carotenoids are commonly present exclusively in flora and microbes where they perform critical functions in photosynthesis and photoprotection. These lipophilic molecules are not synthesized by vertebrates and invertebrates. Carotenoids are recognized as high-value antioxidant food supplements and their antioxidant activity may be higher than β-carotene and ??-tocopherol leading to a prevention of lipid peroxidation. In addition, other beneficial effects of carotenoids are well established. These include reduction in gastric inflammation, bacterial load reduction in H-pylori infected humans and mice, age related macular degeneration, prevention of carcinogenesis, atherosclerosis, cardiovascular ailments etc. Epidemiology and clinical studies have shown that each carotenoid has its own individual characteristics. For example β-cryptoxanthin has been shown to be potent in lung cancer and lycopene is inversely associated with prostate cancer and astaxanthin inhibits LDL oxidation. Over 700 natural carotenoids with diverse molecular structures have been identified with potential medical benefits. However, only a handful of carotenoids, such as α-carotene, β- carotene, astaxanthin, β-cryptoxanthin, lycopene, canthaxanthin, lutein and zeaxanthin have been explored for their health benefits. Leutin and zeaxanthin are commonly found in human fluids including macula. This review summarizes role of these two carotenoids in age related macular degeneration.
Introduction Nutritional Characteristics Of Tomato Epidemiological Studies On Tomato And Cancer Mechanistic Studies Evaluating A Potential Protective Role Of Tomato In Cancer Development Intervention Studies Conclusion
We evaluated the chemopreventive efficacy of tomato lycopene at three different concentrations on DMBA-induced hamster buccal pouch (HBP) carcinogenesis. Hamsters were divided into eight groups. The right buccal pouches of animals in group 1 were painted with 0.5 per cent DMBA three times a week. Animals in groups 2 to 4 painted with DMBA as in group 1, received in addition, intragastric administration of tomato lycopene of concentrations 2.5, 5 and 10 mg/kg bw respectively three times a week on days alternate to DMBA application. Groups 5 through 7 were given tomato lycopene alone while group 8 served as untreated control. All the animals were killed after an experimental period of 14 weeks. Lipid peroxidation and the status of enzymic antioxidants in the buccal pouch, liver and erythrocytes of hamsters in all the groups were assessed. All the hamsters painted with DMBA alone, developed oral squamous cell carcinomas. Diminished lipid peroxidation in the HBP tumors was accompanied by decreased activities of superoxide dismutase and catalase with increase in glutathione peroxidase. However, in the liver and erythrocytes of tumor-bearing animals increased lipid peroxidation was associated with compromised antioxidant defenses. Administration of tomato paste containing 5mg/kg bw of lycopene inhibited HBP tumor development as revealed by decreased tumour incidence and tumour burden. We suggest that tomato lycopene exerts its chemopreventive effects by modulating the oxidant-antioxidant profile in the target organ as well as in the liver and erythrocytes.
Cardiovascular disease (CVD) is the leading cause of death in Western societies and accounts for up to a third of all deaths worldwide. In comparison to the Northern European or other Western countries, the Mediterranean area has lower rates of mortality from cardiovascular diseases and cancer, and this is attributed, at least in part, to the so-called Mediterranean diet, which is rich in plantderived bioactive phytochemicals. Identification of the active constituents of the Mediterranean diet is therefore crucial to the formulation of appropriate dietary guidelines. Lycopene is a natural carotenoid found in tomato, an essential component of the Mediterranean diet, which, although belonging to the carotenoid family, does not have pro-vitamin A activity but many other biochemical functions as an antioxidant scavenger, hypolipaemic agent, inhibitor of pro-inflammatory and pro-thrombotic factors, thus potentially of benefit in CVD. In particular, the review intends to conduct a systematic analysis of the literature (epidemiological studies and interventional trials) in order to critically evaluate the association between lycopene (or tomato products) supplementation and cardiovascular diseases and/or cardiovascular disease risk factors progression, and to prepare provision of evidence-based guidelines for patients and clinicians. Several reports have appeared in support of the role of lycopene in the prevention of CVD, mostly based on epidemiological studies showing a dose-response relationship between lycopene and CVD. A less clear and more complex picture emerges from the interventional trials, where several works have reported conflicting results. Although many aspects of lycopene in vivo metabolism, functions and clinical indications remain to be clarified, supplementation of low doses of lycopene has been already suggested as a preventive measure for contrasting and ameliorating many aspects of CVD.
Among Functional Foods there are many different "traditional" foods rich in specific compounds shown to produce an effect or modulate a function in our organism. However, in most cases, e. g. in tomato, the evidence has not been sufficient to obtain an official health claim. Nevertheless it is important to investigate further the effects of vegetables in our diet and to communicate correctly their advantages for health. Different works were performed in my laboratory on cruciferous vegetables which contain a lot of active compounds such as vitamins, minerals, carotenoids and glucosinolates. Glucosinolates are metabolised and absorbed as isothiocyanates that can affect the activity of enzymes involved both in the antioxidant defence system and in the detoxification from xenobiotics.. Promising are the preliminary results of human intervention studies demonstrating that the regular intake of broccoli for a relatively short period of time could significantly affect glutathione-S-transferase (GST) activity and cell protection against DNA damage. The entity of the protective effect registered seems also related to the genetic characteristic (GSTM1 polimorphysm) of the subjects considered. These results support the use of the nutrigenetic approach also to study functional foods (e. g. for specific groups of population).
The present study was undertaken to examine whether lycopene is able to counteract 7-ketocholesterol (7-KC)-induced oxidative stress and apoptosis in human macrophages. Human THP-1 macrophages were exposed to 7-KC (10-25 microM) alone and in combination with lycopene (0.5-2 microM), and we monitored changes in cell oxidative status [reactive oxygen species (ROS) production, NOX-4, hsp70 and hsp90 expressions, 8-OHdG formation] and in cell proliferation and apoptosis. After 24 h of treatment, lycopene significantly reduced the increase in ROS production and in 8-OHdG formation induced by the oxysterol in a dose-dependent manner. Moreover, the carotenoid strongly prevented the increase of NOX-4, hsp70 and hsp90 expressions as well as the phosphorylation of the redox-sensitive p38, JNK and ERK1/2 induced by the oxysterol. The attenuation of 7-KC-induced oxidative stress by lycopene coincided with a normalization of cell growth in human macrophages. Lycopene prevented the arrest in G0/G1 phase of cell cycle induced by the oxysterol and counteracted the increased expression of p53 and p21. Concomitantly, it inhibited 7-KC-induced apoptosis, by limiting caspase-3 activation and the modulatory effects of 7-KC on AKT, Bcl-2, Bcl-xL and Bax. Comparing the effects of lycopene, beta-carotene and (5Z)-lycopene on ROS production, cell growth and apoptosis show that lycopene and its isomer were more effective than beta-carotene in counteracting the dangerous effects of 7-KC in human macrophages. Our study suggests that lycopene may act as a potential antiatherogenic agent by preventing 7-KC-induced oxidative stress and apoptosis in human macrophages.
This article has three objectives: to describe the biologically plausible mechanistic pathways by which exposure to particulate matter (PM) may lead to adverse perinatal outcomes of low birth weight (LBW), intrauterine growth retardation (IUGR), and preterm delivery (PTD); review evidence showing that nutrition affects biologic pathways; and explain mechanisms by which nutrition may modify the impact of PM exposure on perinatal outcomes. We propose an interdisciplinary framework that brings together maternal and infant nutrition, air pollution exposure assessment, and cardiopulmonary and perinatal epidemiology. Five possible biologic mechanisms have been put forth in the emerging environmental sciences literature and provide corollaries for the proposed framework. The literature indicates that the effects of PM on LBW, PTD, and IUGR may manifest through the cardiovascular mechanisms of oxidative stress, inflammation, coagulation, endothelial function, and hemodynamic responses. PM exposure studies relating mechanistic pathways to perinatal outcomes should consider the likelihood that biologic responses and adverse birth outcomes may be derived from both PM and non-PM sources. We present strategies for empirically testing the proposed model and developing future research efforts.
OBJECTIVE--To evaluate the relationships between dietary intake of carotenoids and vitamins A, C, and E and the risk of neovascular age-related macular degeneration (AMD), the leading cause of irreversible blindness among adults. DESIGN--The multicenter Eye Disease Case-Control Study. SETTING--Five ophthalmology centers in the United States. PATIENTS--A total of 356 case subjects who were diagnosed with the advanced stage of AMD within 1 year prior to their enrollment, aged 55 to 80 years, and residing near a participating clinical center. The 520 control subjects were from the same geographic areas as case subjects, had other ocular diseases, and were frequency-matched to cases according to age and sex. MAIN OUTCOME MEASURES--The relative risk for AMD was estimated according to dietary indicators of antioxidant status, controlling for smoking and other risk factors, by using multiple logistic-regression analyses. RESULTS--A higher dietary intake of carotenoids was associated with a lower risk for AMD. Adjusting for other risk factors for AMD, we found that those in the highest quintile of carotenoid intake had a 43% lower risk for AMD compared with those in the lowest quintile (odds ratio, 0.57; 95% confidence interval, 0.35 to 0.92; P for trend = .02). Among the specific carotenoids, lutein and zeaxanthin, which are primarily obtained from dark green, leafy vegetables, were most strongly associated with a reduced risk for AMD (P for trend = .001). Several food items rich in carotenoids were inversely associated with AMD. In particular, a higher frequency of intake of spinach or collard greens was associated with a substantially lower risk for AMD (P for trend < .001). The intake of preformed vitamin A (retinol) was not appreciably related to AMD. Neither vitamin E nor total vitamin C consumption was associated with a statistically significant reduced risk for AMD, although a possibly lower risk for AMD was suggested among those with higher intake of vitamin C, particularly from foods. CONCLUSION--Increasing the consumption of foods rich in certain carotenoids, in particular dark green, leafy vegetables, may decrease the risk of developing advanced or exudative AMD, the most visually disabling form of macular degeneration among older people. These findings support the need for further studies of this relationship.
Lung cancer and cardiovascular disease are major causes of death in the United States. It has been proposed that carotenoids and retinoids are agents that may prevent these disorders.
We conducted a multicenter, randomized, double-blind, placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers, former smokers, and workers exposed to asbestos. The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day on the primary end point, the incidence of lung cancer, were compared with those of placebo.
A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up (mean length of follow-up, 4.0 years). The active-treatment group had a relative risk of lung cancer of 1.28 (95 percent confidence interval, 1.04 to 1.57; P=0.02), as compared with the placebo group. There were no statistically significant differences in the risks of other types of cancer. In the active-treatment group, the relative risk of death from any cause was 1.17 (95 percent confidence interval, 1.03 to 1.33); of death from lung cancer, 1.46 (95 percent confidence interval, 1.07 to 2.00); and of death from cardiovascular disease, 1.26 (95 percent confidence interval, 0.99 to 1.61). On the basis of these findings, the randomized trial was stopped 21 months earlier than planned; follow-up will continue for another 5 years.
After an average of four years of supplementation, the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer, cardiovascular disease, and any cause in smokers and workers exposed to asbestos.
Increased interest in the potential cardio-protective effects of fruit and vegetables is currently unsupported by systematic reviews of the reported associations of these foods with risk.
All ecological, case-control, cohort studies and unconfounded trials in humans were eligible for inclusion. Eligible outcomes were symptomatic coronary heart disease, stroke and total circulatory disease. Only studies of diet that reported on fresh fruit and vegetables or a nutrient which could serve as a proxy (reversing the usual direction of inference) were included. MEDLINE (1966-1995) and EMBASE (1980-1995) were searched using the terms cerebrovascular disorder, coronary heart disease, fruit(s) and vegetable(s) as keywords. Personal bibliographies, books and reviews were also searched, as were citations in located reports.
For coronary heart disease nine of ten ecological studies, two of three case-control studies and six of 16 cohort studies found a significant protective association with consumption of fruit and vegetables or surrogate nutrients. For stroke three of five ecological studies, none (of one) case-control study and six of eight cohort studies found a significant protective association with consumption of fruit and vegetables or surrogate nutrients. For total circulatory disease, one of two cohort studies reported a significant protective association. No attempt was made to arrive at a summary measure of the association because of the differences in study type, study quality and the different exposure measures used.
Although null findings may be underreported the results are consistent with a strong protective effect of fruit and vegetables for stroke and a weaker protective effect on coronary heart disease. Greater use of food-based hypotheses and analyses, would complement existing nutrient-based analyses and help guide the search for underlying causes.
To evaluate the effect of an increased dietary intake of fruit and vegetables on susceptibility of LDL to oxidation in smokers and nonsmokers.
A descriptive and prospective study.
Joseph Fourier University, Grenoble.
Volunteers were age and sex matched in the smoking and nonsmoking groups and were recruited by announcement.
Increased intake of fruits and vegetables for two weeks providing 30 mg/day of carotenoids.
Circulating levels of beta-carotene, lutein, lycopene, alpha-tocopherol; susceptibility of LDL to oxidation. Cu-Zn superoxide dismutase (Cu-Zn SOD), and Se glutathione peroxidase (Se-GSH-Px) activities and reduced (GSH) and oxidized (GSSG) glutathione.
At entry (week 0: W0) smokers exhibited a lower plasma carotene level but the plasma parameters of oxidative stress and LDL oxidizability were not different from nonsmokers. After two weeks of increased intake of fruits and vegetables the circulating levels of carotenoids increased in smokers 23% and 11% in nonsmokers. At the same time the resistance of LDL to oxidation increased by 14% in smokers (P < or = 0.05) and by 28% in nonsmokers (P < or = 0.025). The mean whole blood GSH level was higher in smokers at entry but returned to a concentration similar to nonsmokers at the end of the study.
This pilot study indicates that an increased, carotenoid rich food intake through its inhibitory effect on the susceptibility of LDL to oxidation may be an interesting approach to reduce the risk of atherosclerosis both in smokers and nonsmokers.
Carotenoids are dietary antioxidants transported with plasma lipoproteins, primarily low-density lipoprotein (LDL). In this study in vitro methods were used to increase the amounts of specific, individual carotenoids in LDL. By addition of carotenoid to isolated LDL or to serum, followed by (re)isolation of the lipoproteins, samples of LDL were enriched 4- to 150-fold with lutein, 2- to 15-fold with lycopene, or 3- to 25-fold with β-carotene. Enrichment with specific carotenoids was achieved without affecting the electrophoretic mobility of the lipoprotein, its cholesterol to protein ratio, or the levels of other cartenoids or α-tocopherol. The distributions among lipoproteins of carotenoid added to serum were similar, but not identical, to the distributions of the endogenous carotenoids. In particular, for added lutein, a greater proportion was found in HDL, and for added β-carotene, more was found in very low-density lipoprotein (VLDL). We then studied the effect of enriching LDL with specific carotenoids on its susceptibility to oxidation by copper ions. Lutein, β-cryptoxanthin, lycopene, and β-carotene, the four major plasma carotenoids, and α-tocopherol were destroyed before the formation of lipid peroxidation products. The rates of destruction of the individual carotenoids differed; lycopene was destroyed most rapidly and lutein most slowly. Upon oxidation of β-carotene-enriched LDL, the rates of destruction of β-carotene, lycopene, and lutein were slowed and the lag times before the initiation of lipid peroxidation increased from 19 to 65 min. Neither effect was observed in LDL enriched with lutein or lycopene. Thus, β-carotene was unique among the carotenoids studied in having a small, but significant effect on LDL oxidation in vitro.
The antioxidant hypothesis postulates that suboptimal levels of principal antioxidant micronutrients are hitherto underrated risk factors for cardiovascular diseases. Complementary observational data consistently suggest optimal, i.e., potentially protective plasma levels of approximately >50 μmol/L of vitamin C, >30 μmol/L of lipid-standardized vitamin E (α-tocopherol/cholesterol ratio >5.2 μmol/mmol), and >0.4 μmol/L β (>0.5 μmol/L total)-carotene. Relative risks are doubled at >25 to 50% lower values. Suboptimal levels of each factor increase the risk singly, or in combination risk increases multiplicatively. They can be stronger predictors of coronary heart disease than classical risk factors such as hypercholesterolemia and hypertension, at least in Northern Europe. In male Americans, the relative risk of cardiovascular diseases was substantially reduced by daily intake of >130 mg of vitamin C, >100 IU of vitamin E (100 mg of d,l- or 74 mg of d-α-acetyl-tocopherol) in all subjects, and by >9 mg of β-carotene, but only in smokers—in comparison with a suboptimal intake that very probably permits only suboptimal plasma levels. Antioxidant deficits can be avoided by “prudent diets” rich in fruits/vegetables, and net vitamin E (high vitamin E/polyunsaturated fatty acids ratio) as is common in European communities where premature cardiovascular death is low. These essential antioxidants may be crucial components of such protective diets but other, presumably synergistic constituents await evaluation, e.g., carotenoids other than β-carotene, phenols/bioflavonoids, minerals such as potassium and selenium, fibers, mono- and n-3 polyenic fatty acids, and oxygen-sensitive B vitamins such as folate.
Human metabolism of carotenoids is of interest not only because of the provitamin A function of certain carotenoids, but also because these compounds have been associated with reducing risks of certain cancers and chronic diseases. Full understanding of carotenoid metabolism is complicated by a number of factors: variations in physiochemical properties among carotenoids; altered carotenoid utilization as a result of the normal vicissitudes of lipid absorption and transport; divergence in metabolic fate within the intestinal enterocyte (especially carotenoid cleavage to retinoids); differences in packaging and transport in lipoproteins; dissimilarity in tissue uptake of specific carotenoids; and the possible isomerization of carotenoids within tissues. Hampering research progress is the lack of animal models that perfectly mimic human carotenoid metabolism and the limited number of carotenoids approved for human consumption in a pure form.
Low intake of vegetables, fruits, and carotenoids is consistently associated with increased risk of lung cancer in both prospective and retrospective studies. In addition, low levels of beta-carotene in serum or plasma are consistently associated with the subsequent development of lung cancer. The simplest explanation is that beta-carotene is protective. Since retinol (preformed vitamin A) is not related in a similar manner to lung cancer risk, beta-carotene appears to function through a mechanism that does not require conversion into vitamin A. However, the importance of other carotenoids and other constituents of vegetables and fruit has not been adequately explored. Both prospective and retrospective studies suggest that vegetable and fruit intake may reduce the risk of cancers of the mouth, pharynx, larynx, esophagus, stomach, colon, rectum, bladder, and cervix. But because of fewer studies and less consistency among studies, the epidemiologic evidence is at present less persuasive than for lung cancer.
To examine prospectively the relationship between dietary fiber and risk of coronary heart disease.
Cohort study.
In 1986, a total of 43,757 US male health professionals 40 to 75 years of age and free from diagnosed cardiovascular disease and diabetes completed a detailed 131-item dietary questionnaire used to measure usual intake of total dietary fiber and specific food sources of fiber.
Fatal and nonfatal myocardial infarction (MI).
During 6 years of follow-up, we documented 734 cases of MI (229 were fatal coronary heart disease). The age-adjusted relative risk (RR) for total MI was 0.59 (95% confidence interval [CI], 0.46 to 0.76) among men in the highest quintile of total dietary fiber intake (median, 28.9 g/d) compared with men in the lowest quartile (median, 12.4 g/d). The inverse association was strongest for fatal coronary disease (RR, 0.45; 95% CI, 0.28 to 0.72). After controlling for smoking, physical activity and other known nondietary cardiovascular risk factors, dietary saturated fat, vitamin E, total energy intake, and alcohol intake, the RRs were only modestly attenuated. A 10-g increase in total dietary fiber corresponded to an RR for total MI of 0.81 (95% CI, 0.70 to 0.93). Within the three main food contributors to total fiber intake (vegetable, fruit, and cereal), cereal fiber was most strongly associated with a reduced risk of total MI (RR, 0.71; 95% CI, 0.55 to 0.91 for each 10-g increase in cereal fiber per day).
Our results suggest an inverse association between fiber intake and MI. These results support current national dietary guidelines to increase dietary fiber intake and suggest that fiber, independent of fat intake, is an important dietary component for the prevention of coronary disease.
Among patients with breast cancer, tumors that contain estrogen receptors (ER) are associated with improved survival and better response to hormone therapy than those not expressing these receptors. The purpose of these case comparison studies was to examine the relationship between carotenoids, vitamin A, and the tumor ER status in women at diagnosis of primary breast cancer. The focus of the first study was the relationship between dietary intake and ER status, and the focus of the second study was the relationship between ER status and the plasma carotenoid, retinol, and tocopherol concentrations. We evaluated tumor ER status and self-reported dietary intake in 142 women and plasma concentrations of carotenoids, retinol, and tocopherols in 149 women, at diagnosis of breast cancer, before any medical or surgical treatment. In the first study the overall odds of ER-positive status were increased in relation to number of mammograms in the past five years, number of breast-fed babies, dietary carotenoid intake, and more frequent intake of yellow and green vegetables. Overall odds of ER-positive status were decreased in relation to years of oral contraceptive use and preformed vitamin A intake. In the second study older women, women with higher plasma lutein concentration, and women not using beta-carotene supplements were more likely to be ER positive, when data were adjusted for body mass index and factors that may influence breast cancer risk or hormonal status. Significant independent relationships between plasma retinol or tocopherol concentrations and ER status were not observed. The strong and independent relationships between carotenoid intake, plasma lutein concentration, and ER status may relate to observations linking a carotenoid-rich diet with improved prognosis after diagnosis of breast cancer.
In this review of the scientific literature on the relationship between vegetable and fruit consumption and risk of cancer, results from 206 human epidemiologic studies and 22 animal studies are summarized. The evidence for a protective effect of greater vegetable and fruit consumption is consistent for cancers of the stomach, esophagus, lung, oral cavity and pharynx, endometrium, pancreas, and colon. The types of vegetables or fruit that most often appear to be protective against cancer are raw vegetables, followed by allium vegetables, carrots, green vegetables, cruciferous vegetables, and tomatoes. Substances present in vegetables and fruit that may help protect against cancer, and their mechanisms, are also briefly reviewed; these include dithiolthiones, isothiocyanates, indole-3-carbinol, allium compounds, isoflavones, protease inhibitors, saponins, phytosterols, inositol hexaphosphate, vitamin C, D-limonene, lutein, folic acid, beta carotene, lycopene, selenium, vitamin E, flavonoids, and dietary fiber. Current US vegetable and fruit intake, which averages about 3.4 servings per day, is discussed, as are possible noncancer-related effects of increased vegetable and fruit consumption, including benefits against cardiovascular disease, diabetes, stroke, obesity, diverticulosis, and cataracts. Suggestions for dietitians to use in counseling persons toward increasing vegetable and fruit intake are presented.
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.
Several lines of evidence suggest that carotenoids may have a beneficial effect on health as a result of their antioxidant properties. In addition to beta-carotene, five other carotenoids are recovered in noticeable amounts from human plasma and tissues. Although the effect of beta-carotene on in vivo lipid peroxidation has been documented, few data are available on the effects of the other carotenoids. We evaluated the ability of the main human carotenoids to reduce lipid peroxidation by determining the correlations between plasma carotenoid concentration and plasma antioxidant capacity (in 79 healthy volunteers) and between carotenoid status and breath pentane excretion (in a subgroup of 24 subjects). Carotenoid intake was assessed by means of a 3-day food recall. Carotenoid status was evaluated by measurement of beta-carotene, lycopene, lutein/zeaxanthin, and alpha-carotene in plasma and buccal mucosal cells. Antioxidant status was evaluated by measurement of the total antioxidant capacity of the plasma. Oxidative stress status was evaluated by breath pentane measurements. Food recall data and the carotenoid concentrations in plasma and buccal mucosal cells showed that the subjects had normal carotenoid intake and normal carotenoid status. The total antioxidant capacity of the plasma was not related to the concentration of any specific carotenoid. The level of expired air pentane was not related to the carotenoid status of the subjects. These results show that normal concentrations of carotenoids in plasma and tissues are not correlated with these clinical markers of antioxidant and oxidative stress status.
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.
Many epidemiological studies have identified a protection against cancer associated with consumption of fruit and vegetables. One factor in this protection may be the enhancement of cellular DNA repair activity by micronutrients, such as carotenoids, found in these foods.
To measure the capacity of lymphocytes isolated from volunteers supplemented with beta-carotene, lutein or lycopene to recover from DNA damage induced in vitro by treatment with H2O2.
Healthy volunteers were given supplements of lutein (15 mg/day), lycopene (15 mg/day) and beta-carotene (15 mg/day), each for 1 week, the supplementation periods being separated by 3-week wash-out periods. Blood samples were taken at the beginning and end of each supplementation, and at 1 week and 3 weeks during the wash-out period. Carotenoid levels were measured in plasma. Lymphocytes were isolated and frozen. Subsequently, they were treated with 100 microM H2O2 and incubated for up to 24 h; DNA damage was measured with the comet assay (single cell gel electrophoresis) after 0, 2, 4, 8 and 24 h.
Increases of 2- to 3-fold in mean plasma lutein and beta-carotene concentrations were seen at the end of the respective supplementation periods; they returned virtually to basal levels after wash-out. Lycopene concentrations were less affected by supplementation, and were more variable. H2O2-induced DNA strand breaks were apparently only slowly rejoined by the lymphocytes. The rejoining of breaks in the first few hours appeared substantially faster in lymphocytes following supplementation with beta-carotene, but no such effect was seen with lutein. In those individuals who showed increases in lycopene concentrations, the recovery was significantly faster. Lymphocytes that were not treated with H2O2 showed a transient increase in DNA breakage to about double the background level in 2 h, presumably as a result of exposure to atmospheric oxygen; this effect, too, was relieved by supplementation with lycopene or beta-carotene.
While certain carotenoids appear to enhance recovery from oxidative damage, this is probably in fact an antioxidant protective effect against additional damage induced by atmospheric oxygen, rather than a stimulation of DNA repair.
Vegeta-bles, fruit, and cancer prevention: a re-view
- Ka Steinmetz
- Potter
Steinmetz KA, Potter JD (1996) Vegeta-bles, fruit, and cancer prevention: a re-view. J Am Diet Assoc 96:1027–1039
Effects of a combination of β-carotene and vitamin A on lung cancer
- Omenn Gs
- Goodman Ge
- Balmes J Thornquist Md
- Mr Cullen
- A Glass
- Meyskens F Keogh Jp
- Williams Jh S Barnhart
- Hammer
Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, Keogh JP, Meyskens F, Valaris B, Williams JH, Barnhart S, Hammer S (1996) Effects of a combination of β-carotene and vitamin A on lung cancer
Nu-trition and cancer: a summary of evi-dence
- Willet Wc
Willet WC, Trichoupoulos D (1997) Nu-trition and cancer: a summary of evi-dence. Cancer Cause Control 7:178–180