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Introduction: The effects of antioxidant dietary supplements on response to biological therapies for cancer is unknown. We conducted a scoping review of the available systematic review evidence on this question. Methods and analysis: We searched six databases from inception to August 19, 2022 for systematic reviews of randomized controlled trials of antioxidant dietary supplements used by patients receiving curative chemotherapy, radiotherapy, or other biological therapy for cancer and assessing the impact of supplements on survival, treatment response, or disease progression. We focused on results from reviews at high or moderate AMSTAR-2 quality. Records were selected, data extracted, and AMSTAR-2 ratings assessed independently by two authors. Results: We found 24 systematic reviews with relevant evidence. Reviews were heterogenous in cancers, treatments, and antioxidant dietary supplements assessed. Conclusions across reviews were mixed, ranging from negative to no apparent difference to positive, but always with caveats about the limited size and quality of the evidence. One review was rated 'moderate' on AMSTAR-2; it included one small trial of vitamin C and formed no firm conclusions. Conclusions: We did not find reliable systematic review evidence on the effects of antioxidant dietary supplements upon therapies for cancer. More research is necessary to inform clinical recommendations. [ABSTRACT FROM AUTHOR]

Diverse dietary constituents, encompassing both macro- and micronutrient intakes, have established connections with various cancers, though their specific roles in cervical cancer remain unclear. This study explores dietary intake correlations among women aged 30 yrs and above diagnosed with cervical cancer (n=215), contrasted with women without (n=860). These populations were selected from the 1999–2018cycle of the National Health and Nutrition Examination Survey. The research implemented the univariate analysis and the least absolute shrinkage and selection operator (LASSO) regression to estimate the association of 29 variables with cervical cancer, subsequently identifying the most pertinent variables linked to cervical cancer. Six covariates emerged as significantly associated with cervical cancer in univariate analyses (age, race, fiber, magnesium, caffeine, vitamin C) (p<0.05). In LASSO regression, with the escalating penalty factor (λ), it was discerned that specific covariates, including age, race, fiber, and Vitamin C, consistently remained in the model. Univariate analysis and logistic LASSO regression findings suggested that diets deficient in fiber and vitamin C were related to cervical cancer. [ABSTRACT FROM AUTHOR]

Smoking is a risk factor for gastric cancer (GC) and causes oxidative stress. Antioxidant vitamins may protect against oxidative stress. This study aimed to determine the association between dietary antioxidant vitamin intake and GC risk according to smoking status and the histological subtype. This case-control study included 286 pairs of patients with GC and controls aged 20–79 years enrolled at two hospitals from 2002 to 2006, matched by age (± 2 years), sex, hospital, and participation period (± 1 years). Dietary information was collected using a quantitative food frequency questionnaire (FFQ). When stratified by smoking status, increased intake of vitamin C (OR = 0.38; 95% CI = 0.17–0.84 for highest vs. lowest; P for trend = 0.033) and folate (OR = 0.28; 95% CI = 0.12–0.64 for highest vs. lowest; P for trend = 0.003) decreased GC risk in nonsmokers. Vitamin C (P for interaction = 0.043) and folate (P for interaction =0.015) levels were significantly associated with smoking status. Similar results were observed in nonsmokers with diffuse and mixed types of GC, but not in those with intestinal type of GC. Therefore, we found an inverse association between higher intake of dietary vitamin C and folate with the risk of GC among nonsmokers. These protective associations were strong in nonsmokers with diffuse and mixed types of GC. [ABSTRACT FROM AUTHOR]

Although some epidemiological studies have reported the associations between vitamin C and risk of esophageal cancer, these results are inconsistent. Therefore, we performed an updated meta-analysis to explore the associations between dietary vitamin C intake and risk of esophageal cancer. We used PubMed, Embase, and the Web of Science to screen all published articles, which yielded 18 papers eligible for data extraction (involving 4,126 cases and 36,902 controls), and then pooled the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) using random-effects model. As we detected the associations in highest category and the lowest type of dietary vitamin C intake, we discovered that dietary vitamin C intake was negatively correlated to the risk of esophageal cancer. The analysis of subgroup showed a significant counter proportion between vitamin C and the risk of ESCC and EAC. Moreover, the dose-analysis indicated that if increasing dietary intake of vitamin C of 50 mg/day, esophageal cancer risk dropped down 10% (OR = 0.81, 95%CI: 0.75-0.87). In summary, our study provides a comprehensive and updated epidemiological evidence to elucidate the relationships between dietary vitamin C and reduction of esophageal cancer risk. Nevertheless, we still need larger case-control and cohort studies to confirm these connections. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are important epigenetic regulators in head and neck squamous cell carcinoma (HNSCC), with miR-31 being considered an oncomir and miR-375, a tumor suppressor miR, which are up- and down-regulated in HNSCC, respectively. Nutrients are known to influence miRNA expression; however, this association is poorly explored in HNSCC. This work aimed to identify associations between dietary intake and the expression of miR-31 and miR-375 in patients newly diagnosed with HNSCC. The expression of miR-31 was positively associated with the consumption of iron (β = 16.65) and vitamin C (β = 0.37), and inversely associated with total sugar (β = −0.88), cholesterol (β= −0.23), vitamin B9 (β= −0.37) and zinc (β = −5.66) intake. The expression of miR-375 was positively associated with the consumption of selenium (β = 1.52), vitamin C (β = 0.17) and vitamin D (β = 13.01), and inversely associated with the consumption of added sugar (β = −0.49), phosphorus (β= −0.27) and vitamin B12 (β = −10.80). Our findings showed important associations between dietary intake and miR-31 and miR-375 expression in HNSCC, offering possible directions for further studies investigating how nutrients interfere with carcinogenesis. Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1990972. [ABSTRACT FROM AUTHOR]

This study aimed to compare the dietary intake of carotenoids, tocopherols, ascorbic acid, flavonoids, and dietary total antioxidant capacity (dTAC) and to evaluate relationship of dTAC with serum inflammatory biomarkers in patients with gastrointestinal system (GIS) and non-GIS cancer. In total, 104 adult cancer survivors (52 GIS and 52 non-GIS cancer cases) were included. 24-hour dietary recalls were obtained and dTAC was calculated on the basis of oxygen radical absorption capacity (ORAC), Trolox equivalent antioxidant capacity (TEAC), total radical-trapping antioxidant parameter (TRAP), ferric reducing antioxidant potential (FRAP), and vitamin C equivalents (VCE). Serum C-reactive protein (CRP) level, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were used as inflammatory biomarkers. Routinely analyzed serum CRP, neutrophil, lymphocyte, and platelet levels every day in hospital biochemistry laboratory were obtained from patients' file. There was no significant difference between patients with GIS and non-GIS cancer in terms of dietary intake of carotenoids, tocopherols, and flavonoids. While there was no significant difference between groups in terms of the mean dietary ORAC, TEAC, and FRAP, the mean TRAP of patients with GIS cancer was significantly higher than patients with non-GIS cancer. Serum inflammatory markers (CRP and NLR) were found to have an inverse relationship with dTAC. [ABSTRACT FROM AUTHOR]

Efforts to develop effective drugs targeting PI3K and KRAS signaling pathways in PIK3CA/KRAS-mutant colorectal cancer stem cells (CRCSCs) remain challenging. Finding safe compounds that can easily enter CRCSCs with the ability to target metastasis-driver gene CXCR4 and pluripotency network genes as key upstream and downstream effectors of both PI3K and KRAS signaling pathways may provide promising results. PIK3CA/KRAS-mutant CRCSCs display high expression of glucose transporters (GLUTs) on their cell membrane and a glycolytic phenotype providing an opportunity to deliver antiglycolytic compounds into these cells via the GLUTs. CRC patients with low levels of vitamin C in their plasma show a shorter survival suggesting the ability of this vitamin at the physiologic levels for caspase-3 activation and apoptosis in CRCSCs. Vitamin C in an oxidized form (L-dehydroascorbic acid; L-DHA) with antiglycolytic activity can be taken up into CRC cells via the GLUTs. This may provide selective toxicity on CRCSCs and affect CXCR4 and stemness markers genes expression in these cells. To this end, we treated PIK3CA/KRAS-mutant LS174T cells with high glycolytic activity as an attractive model for CRCSCs with L-DHA equal to the pharmacological levels of vitamin C in human plasma, after which cell numbers, metabolic activity, proliferation-rate, CXCR4 and pluripotency network genes expression, caspase-3 activity with apoptosis were evaluated. 48 h post-treatment with 100- to 1000 µM L-DHA, cell numbers were decreased and measured to be 70–47% control. L-DHA with selective toxicity on LS174T cells diminished metabolic activity and cell proliferation-rate to 1.4–0.8 (Control OD = 1.5) and 92–54.5% respectively with no toxicity on PBMCs. L-DHA decreased CXCR4, Bmi-1, Sox-2 and Oct-4 expression to 45%, 85%, 45% and 48% control respectively followed by caspase-3 reactivation by 2.5 to 4.9-fold increases and induction of apoptosis ranging from 0.5% to 58.3% for 100– to 1000 µM L-DHA. According to our data, CRC stem-like cells were highly sensitive to L-DHA in in-vitro. L-DHA selectively targeted LS174T cells and successfully reactivated caspase-3 and apoptosis in these cells. CXCR4, stemness marker genes and metabolic activity appear to be promising targets of L-DHA. Our results may provide a new therapeutic approach to target selectively GLUT-overexpressing PIK3CA/KRAS-mutant CRCSCs using L-DHA with no toxicity on normal cells. [ABSTRACT FROM AUTHOR]

We assessed the relation between dietary total antioxidant capacity (TAC) and risk of glioma among Iranian adults. Design: A hospital-based case-control study. Setting: This case-control investigation was done in 2011. Usual dietary intakes of participants during the preceding year were examined using a food frequency questionnaire. Data on dietary TAC from foods was gathered from published databases that provided the antioxidant capacity for each food item, measured by ferric reducing antioxidant power. Participants: Cases were individuals with pathologically confirmed glioma that were diagnosed during the last month (n = 128). Controls were individuals, aged between 20 and 75 years, who were hospitalized or were outpatients referred to other wards of the same hospitals (n = 256). Results: Compared with participants in the lowest quartile, those in the highest quartile of dietary TAC had a lower odds of glioma (OR: 0.28, 95%CI: 0.15–0.45). This association was strengthened when potential confounders were taken into account (OR: 0.13; 95%CI: 0.05–0.35). Such inverse association was also seen for men (OR: 0.05, 95%CI: 0.01–0.19), but not for women. Furthermore, significant inverse associations were seen between dietary intakes of vitamin C (OR for Q4 vs. Q1: 0.14, 95%CI: 0.05–0.36; P-trend < 0.01), vitamin B6 (OR for Q4 vs. Q1: 0.35, 95%CI: 0.13–0.97; P-trend = 0.02) and β-carotene (OR for Q3 vs. Q1: 0.43, 95%CI: 0.19–0.98; P-trend = 0.57) and glioma, after controlling for potential covariates. Conclusions: We found that dietary TAC as well as dietary intake of vitamin C, vitamin B6, and β-carotene was inversely associated with odds of glioma in adults. [ABSTRACT FROM AUTHOR]

To assess the effect of sequential treatment with Vitamin C (VC) and Quercetin (Q) on Nrf2-related oxidative stress in PC3 and DU145 cells, viability was measured by MTT assay. Intracellular ROS levels were determined, using 2'-7'-dichlorodihydrofluorescein diacetate fluorescent as a probe. Nrf2 gene expression was investigated by quantitative reverse transcription polymerase chain reaction, and Nrf2 protein levels were defined by western blot analysis. The activity of glutathione peroxidase (GPx), glutathione reductase (GR), nicotinamide adenine dinucleotide phosphate dehydrogenase quinone 1 (NQO1) and hemeoxygenase 1 (HO-1) enzymes were measured. The IC50 values for VC + Q were 263.03–372.1 µM and 144.2–194.1 µM respectively and 200 µM VC + 50 µM Q (dose no.1) and 100 µM VC + 75 µM Q (dose no.2) were selected. Sequential treatment of PC3 cells led to a significant reduction of Nrf2 mRNA expression and protein levels in addition to a significant reduction of GPx, GR and NQO1 enzymatic activity. Although the data was slightly different for DU145 cells after the treatments, in terms of Nrf2 gene expression, we obtained the same results. Our study revealed the significant effects of sequential treatment with VC + Q on Nrf2 suppression in prostate cancer cells. [ABSTRACT FROM AUTHOR]

Much attention has been put on antioxidants as potential preventive and therapeutic agents against cancer. Vitamin C, an important antioxidant with anti-inflammatory and immune system enhancement features, could provide protection against cancer. However, experimental and epidemiologic evidence on vitamin C and cancer risk are still indefinite. Substantial literature reports that cancer patients experience vitamin C deficiency associated with decreased oral intake, infection, inflammation, disease processes, and treatments such as radiation, chemotherapy, and surgery. Studies demonstrate associations between IVC and inflammation biomarkers and propose some amelioration in symptoms, with a possible advantage in quality of life (QoL) when intravenous vitamin C (IVC) alone or in combination with oral vitamin C is administered in oncologic care. While, the anticancer impact of high doses of IVC remains debatable in spite of growing evidence that high dose vitamin C shows anti-tumorigenic activity by elevating the amount of reactive oxygen species (ROS) in cancer cells without meaningful toxicities. Hence, there is an urgent requirement for rigorous and well-controlled assessments of IVC as an adjuvant therapy for cancer before clear conclusions can be drawn. Thus, more clinical trials are required to determine the additive impact of high dose vitamin C in cancer patients. [ABSTRACT FROM AUTHOR]

The aim of this research was to determine how coadministration of ascorbic acid prior to the beginning of X-irradiation influences the lymphocyte DNA damage and also if the kefir supplementation to irradiated mice may alter the recovery procedure of lymphocyte genetic material injury. Following treatment of animals with these agents, the whole-body of mice were irradiated to 6 MV X-rays, then genotoxicity activity was investigated by comet assay. Our results show that the Total Comet Score (TCS) value was 1.39 and 1.5 fold less in the kefir and ascorbic acid groups respectively the following irradiation than in the irradiated mice only. Coadministration of ascorbic acid and kefir with 2 h, before relatively to 2 Gy radiation decreased DNA damage in lymphocyte blood cells. The antioxidant strength of ascorbic acid and kefir were investigated by the study of the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging properties and also ferric reducing antioxidant power (FRAP) assay. Our results revealed that ascorbic acid and kefir show strong antioxidant activity by these methods. According to these results, it seems that ascorbic acid and kefir, as a free radical scavenging capacitiy, protect animal lymphocyte blood cells from radiation-induced DNA injury and genotoxicity. [ABSTRACT FROM AUTHOR]

To study post-diagnosis dietary supplement use in relation to total mortality, cancer mortality and recurrence among cancer survivors. PubMed and Cochrane Library were searched until April 2019 for observational studies (OS) and randomized clinical trials (RCT). Pooled risk ratios (RR) were calculated using random-effects models. Compared to no supplementation, calcium supplementation was associated with lower total (RR = 0.88, 95% confidence interval (CI): 0.77-1.00, I2=0%, four OS) and cancer mortality (RR = 0.71, 95% CI: 0.53-0.95, I2=0%, three OS) among all cancer survivors, and cancer mortality among colorectal cancer survivors (RR = 0.66, 95% CI: 0.47-0.94, I2=0%, two OS). Vitamin D supplementation was associated with lower total mortality (RR = 0.86, 95% CI: 0.76-0.99, I2=0%, three OS and two RCT). Among breast cancer survivors, supplementation with vitamin C (RR = 0.79, 95% CI: 0.68-0.92, I2=0%, four OS), D (RR = 0.85, 95% CI: 0.72-0.99, I2=0%, two OS), and E (RR = 0.76, 95% CI: 0.64-0.90, I2=0%, three OS) was associated with lower total mortality, while multivitamins (RR = 0.79, 95% CI: 0.64-0.97, I2=0%, two OS), vitamin C (RR = 0.76, 95% CI: 0.64-0.91, I2=0%, two OS), and E (RR = 0.69, 95% CI: 0.55-0.85, I2=0%, two OS) with lower cancer recurrence. Conclusions: Findings are mostly based on OS. More RCTs are needed to justify any recommendation for use. [ABSTRACT FROM AUTHOR]

Although several studies have investigated the cytotoxic effects of different Rosa species, there has been only limited research into the cytotoxic effect of Rosa canina. The purpose of this research was to evaluate the antioxidant properties, phenolic characterization, and cytotoxic effects of R. canina on human lung (A549) and prostate (PC-3) cancer cells and the possible mechanisms involved. The antioxidant properties and phenolic characterization of the extract were determined using spectrophotometric methods and RP-HPLC, respectively. The cytotoxic activity of the extract was determined using the MTT assay. The mechanism involved in the extract's cytotoxic effect was then evaluated in terms of apoptosis, the cell cycle, mitochondrial membrane potential (MMP), and caspase activity using fluorometric and luminometric methods. The TPC value of the extract was 58.97 ± 2.22 mg gallic acid equivalents per gram sample, and ascorbic acid and p-coumaric acid were detected as major phenolics in the extract. R. canina extract exhibited a selective cytotoxic effect on A549 and PC-3 cells compared to normal fibroblast cells. The extract induced cell cycle arrest at the G1 phase and apoptosis via reduced MMP and increased caspase activity in these cells. Phytomedical applications of R. canina may represent promising approaches in the treatment of cancer. [ABSTRACT FROM AUTHOR]

There has been accumulating evidence that several micronutrients may play a protective role in the risk of solid cancers. However, their role in hematological malignancies remains to be elucidated; this meta-analysis aims to evaluate the associations between micronutrient intake as well as supplementation and risk of hematological cancer in adults. Eligible cohort studies (examining intake of vitamin A, vitamin C, vitamin D, vitamin E, lycopene, folate, iron, carotenoids, beta-carotene, selenium, pyridoxine) were sought in PubMed up to July 31, 2016. Random-effects models were used for the calculation of pooled relative risks (RR) with their 95% confidence intervals (CI). Twelve cohort studies were deemed eligible. Null associations were noted regarding supplemented vitamin A (pooled relative risk [RR] = 0.92, 95% confidence interval [CI]: 0.80-1.07), supplemented vitamin C (pooled RR = 1.00, 95%CI: 0.90-1.12), total vitamin D (pooled RR = 1.05, 95%CI: 0.91-1.20), supplemented vitamin E (pooled RR = 0.98, 95%CI: 0.88-1.10), and dietary lycopene intake (pooled RR = 1.00, 95%CI: 0.86-1.16) and the risk of non-Hodgkin lymphoma. No summary estimates are provided for other hematological malignancies due to the limited number of studies. Future prospective trials should be conducted for a better understanding of this field; especially regarding Hodgkin lymphoma, leukemia and plasma cell neoplasms, on which data are scarce. [ABSTRACT FROM AUTHOR]

Arsenic trioxide (As2O3) is a promising new regimen for the treatment of acute promyelocytic leukemia (APL). The induction of oxidative stress mediated by reactive oxygen species (ROS) and excessive intracellular calcium influx are the main reasons behind (As2O3) toxicity. Since liver is the major organ for xenobiotic metabolism, it is always under stress. Antioxidant vitamins such as LAscorbic acid (L-AA) and a-Tocopherol (α-TOC) have been proposed to have beneficial effects against a variety of pathological conditions and are known by their free radical scavenging properties. The present study evaluates the curative efficacy of L-AA and a-TOC against As2O3 toxicity using immortalized human Chang liver cells. Our results suggest that L-AA (100 mM) and α-TOC (50 mM) recovered (As2O3) (10 mM) cytotoxicity. Furthermore, (As2O3) treatment showed an increase in lipid peroxidation and depletion in antioxidant status, mitochondrial trans membrane potential and values of total antioxidant capacity. Cotreatment of antioxidant vitamins with (As2O3) resulted in a significant reversal of oxidative stress markers. Our findings substantiate the effect of antioxidant vitamins in protecting the hepatocytes from oxidative stress which may be attributed through Nrf2 (Nuclear factor erythroid 2-related factor 2) mediated upregulation of Bcl2 (B-cell lymphoma 2) expression. [ABSTRACT FROM AUTHOR]

This study assessed dietary and micronutrient intakes of head and neck cancer (HNC) patients at key points in the disease trajectory and evaluated the contribution of oral nutritional supplements (ONS) to micronutrient intake. HNC patients (n = 114) completed a three-day dietary record and a tool to assess Nutrition Impact Scores (NIS) at baseline, post-treatment, and follow-up. Foods were classified into food categories. Micronutrient, protein, and energy intakes were compared to European Society for Parenteral and Enteral Nutrition guidelines for cancer patients. The majority of patients did not meet recommended dietary intakes for vitamins D, E, C, folate, and magnesium at any study time point. Relative to baseline, the proportion of calories from milk, soup, and ONS significantly increased at post-treatment, while grain, meat, potato, baked dessert, and oil and sugar decreased (P < 0.03). At all study time points, patients categorized as high ONS consumers (>15% of total daily calories from ONS) had higher intakes of micronutrients (P < 0.003). They also had a higher NIS (P = 0.006) and experienced greater weight loss (P < 0.04) during the study, despite having similar energy intake to patients consuming <15% kcal from ONS. Fortification of usually consumed foods to improve micronutrient intake among cancer patients should be evaluated. [ABSTRACT FROM AUTHOR]

Introduction:Glioma is the most common adult brain tumors. Dietary factors may play a role in the etiology of glioma. The Index of Nutritional Quality (INQ) provides a general overview for the nutrient content of a food or a diet. This study aimed to investigate the association between INQ and glioma and nutrient intakes.Material and methods:This study was included 128 patients and 256 controls. Dietary intakes of the subjects were evaluated by a food frequency questionnaire (FFQ) and FFQ-derived dietary data were used to calculate INQ scores. Logistic regression was used to calculate the odds ratios and 95% confidence intervals.Results:Cases had higher intake of total fat, saturated fatty acid (SFA), meats, hydrogenated oils and controls had higher intake of monounsaturated fatty acid, polyunsaturated fatty acid, calcium, dairy, fruits, and nuts. Only the INQ of vitamin C, vitamin E, calcium, and fiber are higher in controls. An inverse association was observed between glioma and INQ of calcium, vitamin E, vitamin C, and fiber.Conclusion:The results of this study propose a healthy diet such as high intake of vitamins C and E, calcium, fiber, food groups like fruits and vegetables, and low-fat milk and nuts; and low consumption of total fat, SFA, and red meat may be protective against glioma. [ABSTRACT FROM AUTHOR]

Several clinical trials have produced conflicting results regarding the benefit of antioxidants in cancer therapy thus questioning the incorporation of these substances in standard treatment regimens. Vitamins E and C, selenium, carotenoids, lycopene, soy products, and green tea extract are a few substances with antioxidant properties that have been studied in detail. This article reviews the results generated over the last 20 years through in vitro and in vivo studies in various types of cancers and stages of cancer treatment. Despite the commercial popularity and the multitude of studies examining antioxidant therapy, the true role of antioxidants is yet to be determined, requiring further investigation into its propagative, causal, or protective nature. [ABSTRACT FROM PUBLISHER]

Objective: Prevention by antioxidant agents including vitamin C (VC) and quercetin (QU), which are nontoxic, cost effective, and physiologically bioavailable, is a promising approach in breast cancer handling. The aim of this work is to investigate the influence of VC+QU on cytotoxicity profile of doxorubicin (DOX) plus paclitaxel (PAC) in breast cancer cells. Methods: The effect of each drug on its own or in combination was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Combination indexes were calculated using the Chou–Talalay method. Apoptosis and cell cycle analysis was investigated by flow cytometric assays. Results: Combination treatment with VC+QU plus drugs diminished IC50 value 2.28–7.7 and 10.5–66.6 fold in comparison with the drugs and PAC treatment alone, respectively, in all breast cancer cells and induced apoptosis at the early stages more than the treatment with the drugs alone (P<0.01). A marked reduction in Go/G1 and S phases was reported after combination therapy in MDA-MB 231 and MDA-MB 468 cells. MCF-7 cells demonstrated lower fractions of cells in S phase with no significant changes in G2/M phase (P < 0.01). The same treatment produced a significant increase in S and G2/M phases in A549 cells (P < 0.001). Conclusion: Our results emphasized the importance of VC+QU in combination with the drugs to produce a synergistic antitumor effect in breast cancer cells. [ABSTRACT FROM AUTHOR]

Cancer survivors are motivated to change lifestyle following diagnosis, but studies investigating the outcomes are scarce. The purpose of this study was to examine the associations between antioxidant supplementation and quality of life (QoL) in stage-II colorectal cancer survivors. Four-hundred-fifty-three survivors were enrolled from the North Carolina Cancer Registry from 2009 to 2011. Interview data on demography, treatment, health behaviors, and QoL were collected at diagnosis, and at 12 and 24 mo post-diagnosis. Antioxidant supplementation was self-reported as use of selenium, zinc, beta-carotene, vitamin A, vitamin E, or vitamin C at baseline. Two-hundred-sixty-one subjects completed the 24-mo interview. After adjusting for multiple confounders, there was no association between antioxidant use and the Functional Assessment of Cancer Treatment-Colorectal [β = 1.41; 95% confidence interval (CI): −2.48, 5.30] or the medical outcomes 12-item short form (physical composite score: β = 0.84; 95% CI: −1.39, 3.07; mental composite score: β = −0.61; 95% CI: −2.65, 1.43). This study revealed no benefit of antioxidant use among survivors, possibly explained by a limited sample size of antioxidant users. More prospective studies are necessary to assess the benefits of antioxidants. [ABSTRACT FROM PUBLISHER]

The primary aim of the study was to determine whether plasma concentrations of homocysteine (Hcy), a functional indicator of methyl donor nutrients, are associated with altered risk of higher grades of cervical intraepithelial neoplasia (CIN 2+) and the degree of methylation in long interspersed nucleotide elements (LINE-1s) of peripheral blood mononuclear cells, a potential biomarker of CIN 2+ in a population of women exposed to the United States folic acid fortification program. The secondary aim was to assess the determinants of plasma Hcy in the same population. The study included 457 women diagnosed with either CIN 2+ (cases,n= 132) or ≤ CIN 1 (non-cases,n= 325). Unconditional logistic regression models were used to test the associations after adjusting for relevant risk factors of cervical cancer. Women with higher Hcy concentrations were at a greater risk of being diagnosed with CIN 2+ [odds ratio (OR) = 1.86, P = 0.005]. Higher plasma folate concentrations were a significant determinant of lower Hcy (OR = 0.40, P = 0.0002). Women with higher Hcy concentrations were more likely to have a lower degree of LINE-1 methylation (OR = 2.30, P = 0.0007). These results suggested that further improvement in folate status in this population may be beneficial for lowering Hcy and improving the degree of LINE-1 methylation. [ABSTRACT FROM AUTHOR]

To assess the association between vitamin C intake and cervical neoplasia (CN) risk. Databases including PubMed, Embase, and Springer link were retrieved up to June 10, 2014 with predefined strategy. The combined odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated for overall and subgroup analyses. The publication bias was assessed using Begg's test and Egger's test. Sensitivity analysis was also conducted. Twelve studies consisting of 1 prospective cohort study and 11 case-control studies were included. In overall analysis, vitamin C intake was significantly associated with the reduced risk of CN (OR = 0.58; 95% CI: 0.44 to 0.75; P < 0.001). Subgroup analysis stratified by vitamin C dose indicated all dose categories achieved a reduced CN risk. Furthermore, increased vitamin C intake by 50 mg/day was related to the reduced risk of CN (OR = 0.92; 95% CI: 0.89 to 0.94;P< 0.05). No publication bias was detected by Begg's test (P= 0.169) and no apparent fluctuation was observed in summary OR by sensitivity analysis. Vitamin C intake was inversely associated with the risk of CN and this association was dose-dependent. However, more randomized controlled trials are required for further validation. [ABSTRACT FROM AUTHOR]

Adjuvant Nutritional Intervention in Cancer (ANICA) was a clinical study carried out in Denmark in the 1990s with 32 typical patients with breast cancer, aged 32–81 yr and classified high risk because of tumor spread to the lymph nodes. The patients received standard therapy for their breast cancer, but got from the start additionally an adjuvant therapy in form of a cocktail consisting of vitamin C (2,850 mg/day), vitamin E (2,500 IU/day), beta-carotene (32.5 IU/day), selenium (Se; 387 micrograms/day), various other vitamins and essential trace elements, essential fatty acids (1.2 g gamma-linolenic acid/day and 3.5 g omega-3 PUFAs/day), and coenzyme Q10(CoQ10, 90 mg/day). The protocol was later changed, with reduction of the Se intake and more coenzyme Q10than when the study was started. The average survival of high-risk breast patients in the study was 50% after 5 yr, whereas for low-risk breast cancer patients (without metastases in the axilla when treatment was started), the average survival was 90% after ten years. The main investigator died, and the final report from the ANICA study was therefore never written. However, the published preliminary results from the trial were very promising; it seems, therefore, important to follow-up this study. [ABSTRACT FROM AUTHOR]

Enhanced glucose requirement of cancer cells is associated with an increased glucose transport across plasma membrane that is mediated by a family of facilitated glucose transporter proteins, named GLUTs. GLUT1 is the main transporter in thyroid cancer cells. Glucose is the principal physiological substrate of GLUT1; however, it is also capable of transporting of oxidized form of vitamin C [i.e., dehydroascorbic acid (DHAA) which inside the cells is reduced to ascorbic acid (AA)]. The objective of this study was to determine the effect of normo-, hypo-, and hyperglycemia conditions on GLUT1-dependent intracellular ascorbate accumulation and viability of thyroid cancer cells. GLUT1 seems to be the main DHAA transporter in thyroid cancer cells because its knockdown by RNAi reduced DHAA accumulation by more than 80%. The results showed that in thyroid cancer cells high glucose inhibits both transport of AA and DHAA. Inhibition of vitamin C transport by glucose had a cytotoxic effect on the cells. However, stabilization of vitamin C in one of 2 forms (i.e., AA or DHAA) abolished this effect. These results suggest that cytotoxic effect is rather associated with extracellular accumulation of vitamin C and changes of its oxidation state than with intracellular level of ascorbate. [ABSTRACT FROM AUTHOR]

The aim of this study was to observe effects of ascorbic acid application on pain, performance status, and survival time in cancer patients. A retrospective cohort of 39 patients with bone metastases treated with radiotherapy was identified. All patients were radiotherapy-resistant. Fifteen patients who received chemotherapy, and 15 patients who received an infusion of 2.5 g ascorbic acid were included in the study. Nine control patients were treated with neither chemotherapy nor vitamin C. Eastern Cooperative Oncology Group Performance Status Scale and Visual Analog Scale were used to determine performance status and pain assessments. Survival time and rate in patients were defined. Statistical analyses were performed to compare the results of groups. Performance status was increased in 4 patients of vitamin C group and 1 patient of chemotherapy group, whereas performance status in control group was decreased. A median reduction of 50% in pain was observed among the patients in the vitamin C group. Median survival time was 10 mo in patients receiving ascorbic acid, whereas the chemotherapy and control groups had a median survival of 2 mo. Intravenous vitamin C application seems to reduce pain in patients in comparison to other patients who did not receive it. Patient performance status and survival rate were increased using vitamin C. [ABSTRACT FROM PUBLISHER]

Melanoma is the most serious form of skin cancer affecting mostly people of Caucasian origin and is associated with high exposure to solar ultraviolet (UV) radiation. Antioxidants in the diet are thought to prevent UV-induced DNA damage and oxidative stress and laboratory-based studies have shown that high antioxidant intakes inhibit melanoma development. Corresponding epidemiological evidence is inconsistent, however. We therefore reviewed results from prospective observational studies and randomized controlled trials (RCTs) to clarify whether consumption of antioxidant vitamin C, E (tocopherol), and A (retinol), carotenoids and selenium, as food, supplements, or both, or high fruit and vegetable intake, reduce the incidence of cutaneous melanoma. A total of 9 studies (2 cohort, 1 nested case-control, 6 RCTs) were included. Neither antioxidant nutrients, individually or combined, nor fruit and vegetable intake showed any strong and significant associations with melanoma, though the number of relevant studies was limited and several had methodological shortcomings. In particular, melanoma was not a primary disease outcome in any of the RCTs and therefore, none adequately accounted for potential confounding by sun exposure. In conclusion, available evidence is currently inadequate to assess possible beneficial effects of antioxidant intake on melanoma risk. [ABSTRACT FROM PUBLISHER]

Some studies have considered the association between diet and uterine fibroid risk, but the issue is largely unsettled. To identify potential modifiable risk factors for fibroid development, we have herein systematically reviewed prior publications dealing with this aspect. Comprehensive searches in electronic databases were conducted to collect studies published on association between uterine leiomyomas and both nutrients and food groups. We identified 13 publications deriving from 4 case-control, 3 cross-sectional, and 4 cohort studies. A protective effect has been demonstrated for consumption of fruits and green vegetables in both case-control and cohort studies. Moreover, very recent cross-sectional and case-control studies evaluating serum levels of 25-hydroxyvitamin-D3tend to indicate that vitamin D insufficiency, which may in part be due to the diet intake, may play an important role in the development of uterine fibroids. No association was found with the intake of fibers, vitamin C and E, phytoestrogens and carotenoids, whereas association was controversial for the consumption of meat, fish, dairy products, and vitamin A. Most data have also been discussed herein in light of the available experimental and animal model results. These findings may be useful in devising nutritional strategies to reduce leiomyoma risk in humans. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most common noncutaneous cancer in men in the United States. Several studies have examined the relationship between prostate cancer and antioxidants; however, the results of these studies are inconsistent. This article provides a systematic review of studies on prostate cancer and antioxidant intake from diet and supplements. Tea and coffee appear to offer protection against advanced prostate cancer. Different forms of vitamin E appear to exert different effects on prostate cancer, with alpha-tocopherol potentially increasing and gamma-tocopherol potentially decreasing risk of the disease. There is no strong evidence for a beneficial effect of selenium, vitamin C, or beta-carotene, whereas lycopene appears to be negatively associated with risk of the disease. The effect of dietary antioxidants on prostate cancer remains undefined and inconclusive, with different antioxidants affecting prostate cancer risk differentially. Further studies are needed to clarify the relationship between antioxidants and prostate cancer risk and to delineate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Vitamin C, available in its reduced form (ascorbic acid; AA) and in its oxidized form (dehydroascorbic acid; DHA), may act in physiological conditions as an antioxidant or pro-oxidant. The aim of this study is to evaluate the cytotoxic effects of pharmacological doses of AA in a human colorectal adenocarcinoma cell line (WiDr) in vitro, through spectrophotometry, clonogenic assays and flow cytometry, and in vivo with xenotransplanted Balb/c nu/nu mice. The results show that the reduced form of vitamin C induces an anti-proliferative and cytotoxic effect in adenocarcinoma colorectal cells under study. The results obtained in vivo after treatment with AA showed a large reduction in the rate of tumor growth. Such understanding can guide decisions about which colorectal cancer patients might potentially benefit from vitamin C pharmacologic therapy. [ABSTRACT FROM PUBLISHER]

It has long been a matter of interest whether antioxidant vitamins are protective against colorectal cancer as well as human cancers in general, but epidemiological evidence is inconclusive. We investigated associations of dietary intakes of retinol and antioxidant vitamins with colorectal cancer risk in 816 incident cases of histologically confirmed colorectal cancer and 815 controls randomly selected for the Fukuoka colorectal cancer study in Japan. Dietary intakes were assessed by a PC-assisted interview regarding 148 food items. Statistical adjustment was made for body mass index, physical activity, calcium, and n-3 fatty acid intake and other factors. Retinol intake was significantly, inversely associated with colorectal cancer risk; the odds ratio for the highest vs. lowest was 0.55 (95% CI: 0.35, 0.88; P trend = 0.01) in women, but a modest increase in the risk was observed among men with the highest intake of retinol. Liver was the major source of retinol intake and showed similar associations with colorectal cancer risk in men and women. Intake of carotenes, vitamin C, and vitamin E were not related to colorectal cancer risk in either men or women. The study did not support a hypothesis that dietary intake of antioxidant vitamins is protective in the development of colorectal cancer. [ABSTRACT FROM PUBLISHER]

Ascorbic acid (vitamin C) inhibits cancer cell growth, and there is a controversy regarding the cancer chemoprotective effects of pharmacologic doses of this compound that exhibits prooxidant activity. We hypothesized that the anticancer activity of pharmacologic doses of ascorbic acid (<5 mM) is due, in part, to reactive oxygen species-dependent downregulation of specificity protein (Sp) transcription factors Sp1, Sp3, and Sp4 and Sp-regulated genes. In this study, ascorbic acid (1–3 mM) decreased RKO and SW480 colon cancer cell proliferation and induced apoptosis and necrosis, and this was accompanied by downregulation of Sp1, Sp3, and Sp4 proteins. In addition, ascorbic acid decreased expression of several Sp-regulated genes that are involved in cancer cell proliferation [hepatocyte growth factor receptor (c-Met), epidermal growth factor receptor and cyclin D1], survival (survivin and bcl-2), and angiogenesis [vascular endothelial growth factor (VEGF) and its receptors (VEGFR1 and VEGFR2)]. Other prooxidants such as hydrogen peroxide exhibited similar activities in colon cancer cells, and cotreatment with glutathione inhibited these responses. This study demonstrates for the first time that the anticancer activities of ascorbic acid are due, in part, to ROS-dependent repression of Sp transcription factors. [ABSTRACT FROM PUBLISHER]

Vitamin C in combination with vitamin K3 (vit CK3) has been shown to inhibit tumor growth and lung metastasis in vivo, but the mechanism of action is poorly understood. Herein, C57BL/6 mice were implanted (s.c.) with Lewis lung carcinoma (LLC) for 9 days before injection (i.p.) with low-dose (100 mg vit C/kg + 1 mg vit K3/kg), high-dose (1,000 mg vit C/kg + 10 mg vit K3/kg) vit CK3 twice a week for an additional 28 days. As expected, vit CK3 or cisplatin (6 mg/kg, as a positive control) significantly and dose-dependently inhibited tumor growth and lung metastasis in LLC-bearing mice. Vit CK3 restored the body weight of tumor-bearing mice to the level of tumor-free mice. Vit CK3 significantly decreased activities of plasma metalloproteinase (MMP)-2, -9, and urokinase plasminogen activator (uPA). In lung tissues, vit CK3 1) increased protein expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), TIMP-2, nonmetastatic protein 23 homolog 1 and plasminogen activator inhibitor-1; 2) reduced protein expression of MMP-2 and MMP-9; and 3) inhibited the proliferating cell nuclear antigen (PCNA). These results demonstrate that vit CK3 inhibits primary tumor growth and exhibits antimetastastic potential in vivo through attenuated tumor invasion and proliferation. [ABSTRACT FROM PUBLISHER]

Vitamins are essential nutrients for human metabolism, playing an important role as coenzymes or enzymes in many vital processes for the normal functioning of the body. In recent years, it has become apparent that vitamins are crucial in health and human disease, due to several studies that studied this relationship. Currently, it is known that vitamins can have an important role in the prevention and treatment of cancer, but until now no conclusive results were obtained. In this review, we will present the work and more relevant conclusions obtained in recent years of investigation about the relationship between vitamins and cancer, namely vitamin A, vitamin B complex, vitamin C, vitamin D, vitamin E, and vitamin K. [ABSTRACT FROM AUTHOR]

Oxidation of polyunsaturated fatty acids (PUFAs) releases α,β-unsaturated aldehydes that modify deoxyguanosine (dG) to form cyclic 1,N2-propanodeoxyguanosine adducts. One of the major adducts detected in vivo is acrolein (Acr)-derived 1,N2-propanodeoxyguanosine (Acr-dG). We used a chemical model system to examine the effects of 4 antioxidants known to inhibit fatty acid oxidation on the formation of Acr-dG and 8-oxodeoxyguaonsine (8-oxodG) from the PUFA docosahexaenoic acid (DHA) under oxidative conditions. We found that epigallocatechin gallate (EGCG) and dihydrolipoic acid (DHLA) inhibit both Acr-dG and 8-oxodG formation. In contrast, ascorbic acid and α-tocopherol actually increase Acr-dG at high concentrations and do not show a concentration-dependant inhibition of 8-oxodG. We also studied their effects on blocking Acr-dG formation directly from Acr. EGCG and DHLA can both effectively block Acr-dG formation, but ascorbic acid and α-tocopherol show weak or little effect. These results highlight the complexity of antioxidant mechanisms and also reveal that EGCG and DHLA are effective at suppressing lipid peroxidation-induced Acr-dG and 8-oxodG formation as well as blocking the reaction of dG with Acr. [ABSTRACT FROM AUTHOR]

Antioxidant nutrients and carotenoids have been inconsistently associated with ovarian cancer risk. We examined the relationship between intake of dietary and supplemental antioxidant nutrients including vitamins C, E, and selenium as well as carotenoids and vitamin A and ovarian cancer in 133,614 postmenopausal women enrolled in the Women's Health Initiative (WHI) study. Dietary intake was assessed using a food frequency questionnaire, and ovarian cancer endpoints were centrally adjudicated. Cox regression models were used to estimate the risk for invasive ovarian cancer in relation to each of the antioxidant nutrients and carotenoids under consideration using models stratified for a WHI study component. A total of 451 cases of invasive ovarian cancer were diagnosed over 8.3 yr of follow-up. Dietary intake at baseline was not significantly different for cases vs. controls. Cases reported greater intake of supplemental vitamin C (358.0 mg/day vs. 291.6 mg/day, respectively; P = 0.024). Multivariate modeling (P for trend) of the risk for developing ovarian cancer did not suggest any significant relationships among dietary factors and ovarian cancer risk. The results from this prospective study of well-nourished, postmenopausal women suggest that intake of dietary antioxidants, carotenoids, and vitamin A are not associated with a reduction in ovarian cancer risk. [ABSTRACT FROM AUTHOR]

Previous observational studies suggest that vitamin C may reduce risk of colorectal cancer. Vitamin C transport is facilitated by membrane bound sodium-dependent transporters, SVCT1 (encoded by SLC23A1) and SVCT2 (encoded by SLC23A2). To investigate if common genetic variants in these two genes are associated with risk of colorectal tumor development, we conducted a case-control study of 656 Caucasian advanced distal colorectal adenoma cases and 665 Caucasian sigmoidoscopy-negative controls nested within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The analysis of common single nucleotide polymorphisms in SLC23A1 revealed no association. For SLC23A2, overall, there was no association with haplotypes, but two SNPs located in intron 8 and exon 11 could be associated (odds ratio = 0.49, 95% confidence interval = 0.25-0.95 for haplotype G-C vs. haplotype C-C). The findings should be confirmed in follow-up studies, and further investigation is required to probe the functional basis of this finding. [ABSTRACT FROM AUTHOR]

Abstract: Alliin, a compound derived from garlic, demonstrated dose-dependent inhibition of fibroblast growth factor-2 (FGF2)-induced human endothelial cell (EC) tube formation and angiogenesis in the chick chorioallantoic membrane (CAM) model. Additionally, alliin demonstrated potent inhibition of vascular endothelial growth factor (VEGF)-induced angiogenesis in the CAM model. The antioxidant vitamins C and E significantly (P < 0.001) enhanced the inhibitory efficacy of alliin on FGF2-induced EC tube formation and angiogenesis. Alliin significantly increased (P < 0.01) nitric oxide (NO) release into the CAM fluid, which was further enhanced by vitamins C and E. The NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME) reversed the anti-angiogenesis efficacy of alliin in the CAM model. Vitamins C and E significantly enhanced the anticancer efficacy of alliin in inhibiting colon and fibrosarcoma tumor growth. Alliin significantly inhibited both FGF2 and VEGF secretion from human fibrosarcoma cells in a concentration-dependent manner. Additionally, alliin up-regulated the p53 production in FGF2-stimulated EC. These data indicated a synergistic effect of antioxidants on the anti-angiogenesis and anticancer efficacy of alliin. These data also suggest the implication of cellular NO and p53 as mediators of anti-angiogenesis and anticancer effects of alliin. [ABSTRACT FROM AUTHOR]

Abstract: Redox-active iron present at physiological levels in the pulmonary epithelial lining fluid may lead to damage of lung tissue under some circumstances. For example, factors that increase potential for oxidative stress, such as higher intake of heme iron or higher intake of vitamin C in the presence of high intake of iron, might increase the risk of lung cancer, whereas higher intake of the antioxidant zinc might decrease that risk. During 16 yr of follow-up, 34,708 postmenopausal women, aged 55-69 yr at baseline who completed a food-frequency questionnaire for the Iowa Women's Health Study, were followed for 700 incident lung cancers. When subjects were stratified by intake of vitamin C supplements, among women who took vitamin C supplements of >500 mg/day, after adjusting for age, total energy intake, cigarette smoking, alcohol consumption, and dietary zinc or dietary heme iron intake, relative risks across categories of dietary heme iron intake were 1.0, 0.85, 0.93, 1.32, 1.70, and 3.77 (P for trend = 0.05; P for interaction = 0.08), whereas corresponding figures for dietary zinc intake were 1.0, 1.15, 0.71, 0.84, 0.61, and 0.11 (P for trend = 0.12; P for interaction = 0.04). The strength of the associations of heme iron and zinc intake with lung cancer appeared to be stronger with increasing levels of vitamin C supplement intake. Our results suggest that high dietary heme iron intake may increase the risk of lung cancer, whereas high dietary zinc may decrease the risk of lung cancer among postmenopausal women who consume high-dose vitamin C supplements. This finding may be of particular importance to smokers, for whom vitamin C supplementation is a common recommendation. [ABSTRACT FROM AUTHOR]

Exposure to environmental tobacco smoke (ETS) has been linked to increased risk of lung cancer and cardiovascular diseases in nonsmokers. Current research suggests that some of these diseases are associated with elevated oxidative stress. We investigated the effect of antioxidant (AO) intervention on the lipid peroxidation biomarker F[SUB2]-isoprostanes (F[SUB2]-IsoPs), an index of oxidative stress, in plasma of nonsmokers exposed to ETS (passive smokers). We measured free F[SUB2]-IsoP concentrations in plasma of 67 passive smokers at baseline and after 2 mo of daily intervention with AOs or placebo. The study subjects (47 females, 20 males; mean age 46 ± 15) were randomized into one of three treatment groups: vitamin C, "mixture" (vitamin C, vitamin E, and α-lipoic-acid), and placebo. Investigated confounders included plasma baseline AO levels, lipid and total cholesterol profiles, transferrin saturation, and C-reactive protein. Plasma F[SUB2] IsoP concentrations of subjects in the vitamin C and mixture groups decreased significantly by 17.2 pmol/l (P = 0.0105) and 19.2 pmol/l (P = 0.0083) when compared with the placebo group (11.4% and 12.7%, respectively). Daily AO supplementation (especially with vitamin C) decreases this oxidative stress biomarker in passive smokers. This finding might be of importance for the prevention of ETS-associated adverse health effects in nonsmokers. [ABSTRACT FROM AUTHOR]

Reduced concentration of ascorbic acid (AA) in plasma is often observed in tumor patients. Besides malnutrition, an increased AA consumption in tumor patients is discussed as a main reason for reduced AA concentration in plasma. A reduced AA concentration caused by malnutrition would not influence the total clearance (Cl[sub tot]) of AA in plasma; however, a change in AA consumption would alter the Cl[sub tot]. To investigate this further, a study was carried out on 20 patients hospitalized for major maxillofacial surgery and 20 volunteers. The Cl[sub tot] of AA in plasma after bolus injection of AA (4 mg/kg body wt) in tumor patients was compared with that in volunteers. AA concentration in plasma (P <>tot] was observed for tumor patients (median and 25th and 75th percentiles: 11.5, 8.0, and 14.0 l/h) compared with volunteers (median and 25th and 75th percentiles: 11.3, 9.9, and 13.2 l/h). No indication of an increased consumption of AA in tumor patients could be detected. The lowered concentration of AA in plasma observed in our patients might be the result of a reduced AA intake. [ABSTRACT FROM AUTHOR]