Mauro Serafini

Dietary antioxidant intake and the risk of cardia cancer and noncardia cancer of the intestinal and diffuse types: A population-based case-control study in Sweden

In spite of diverging incidence trends, subsite, and subtype‐specific gastric cancer data on the association with dietary antioxidants are sparse. We aimed to test whether the apparent protective effect of antioxidants is mainly confined to noncardia (distal) cancer of the intestinal subtype, to which most of the incidence decline in gastric cancer has been ascribed. In a Swedish study base (total population 1.3 million), we interviewed 567 cases uniformly classified to subsite (cardia vs. noncardia) and subtype (intestinal vs. diffuse), and 1165 population‐based controls, frequency matched for age and sex. Serologic data on H. pylori status was available for a subset of 542 individuals. Ascorbic acid (vitamin C) was inversely associated with all subsites and subtypes of gastric cancer in a significant dose–response manner (all p<0.05), with risk reductions between 40% and 60%. β‐carotene was also strongly and negatively associated with risk, particularly with the intestinal type. The associations with α‐tocopherol (vitamin E) were less clear. The highest parallel intake of all three antioxidants (quartiles 4), compared to those with the lowest parallel intakes (quartiles 1), was associated with a 70% lower risk of developing noncardia cancer (OR 0.3, 95% CI 0.1–0.9). Our results suggest that antioxidants might be especially beneficial among subjects at increased risk for gastric cancer such as smokers and those infected by H. pylori. We conclude that a high intake of antioxidants, as a consequence of high consumption of fruit and vegetables, may lower the risk not only for gastric cancer of the intestinal type, but also for diffuse type adenocarcinoma and cardia cancer. Int. J. Cancer 87:133–140, 2000.

Dietary total antioxidant capacity and gastric cancer risk in the European prospective investigation into cancer and nutrition study

A high intake of dietary antioxidant compounds has been hypothesized to be an appropriate strategy to reduce gastric cancer (GC) development. We investigated the effect of dietary total antioxidant capacity (TAC) in relation to GC in the European Prospective Investigation into Cancer (EPIC) study including 23 centers in 10 European countries. A total of 521,457 subjects (153,447 men) aged mostly 35–70 years old, were recruited largely between 1992 and 1998. Ferric reducing antioxidant potential (FRAP) and total radical‐trapping antioxidant parameter (TRAP), measuring reducing and chain‐breaking antioxidant capacity were used to measure dietary TAC from plant foods. Dietary antioxidant intake is associated with a reduction in the risk of GC for both FRAP (adjusted HR 0.66; 95%CI (0.46–0.95) and TRAP (adjusted HR 0.61; 95%CI (0.43–0.87) (highest vs. lowest quintile). The association was observed for both cardia and noncardia cancers. A clear effect was observed in smokers with a significant reduction in GC risk for the fifth quintile of intake for both assays (highest vs. lowest quintile: adjusted HR 0.41; 95%CI (0.22–0.76) p for trend <0.001 for FRAP; adjusted HR 0.52; 95%CI (0.28–0.97) p for trend <0.001 for TRAP) but not in nonsmokers. In former smokers, the association with FRAP intake was statistically significant (highest vs. lowest quintile: adjusted HR 0.4; 95%CI (0.21–0.75) p < 0.05); no association was observed for TRAP. Dietary antioxidant capacity intake from different sources of plant foods is associated with a reduction in the risk of GC.

Dietary quercetin intake and risk of gastric cancer: results from a population-based study in Sweden

BACKGROUNDnTo study the impact of the dietary antioxidant quercetin on risk of gastric adenocarcinoma.nnnPATIENTS AND METHODSnUsing data from a large Swedish population-based case-control study of gastric cancer (505 cases and 1116 controls), we studied the association between quercetin and risk of anatomic (cardia/noncardia) and histological (intestinal and diffuse) subtypes of gastric cancer.nnnRESULTSnWe found strong inverse associations between quercetin and the risk of noncardia gastric adenocarcinoma, with an adjusted odds ratio (OR) of 0.57 (95% confidence interval 0.40-0.83) for the highest quintile (≥11.9 mg) of daily quercetin intake relative to the lowest quintile of intake (<4 mg quercetin/day), supported by a significant decreasing linear trend (P value < 0.001). Similar findings were observed for the intestinal and diffuse subtype. For cardia cancer, we found a less evident and nonsignificant inverse relationship. The protection of quercetin appeared to be stronger among female smokers, with the OR leveled of at values <0.2 in quintiles 3-5 (>6 mg quercetin/day).nnnCONCLUSIONSnHigh dietary quercetin intake is inversely related to the risk of noncardia gastric adenocarcinoma, and the protection appears to be particularly strong for women exposed to oxidative stress, such as tobacco smoking.

Dietary flavonoid, lignan and antioxidant capacity and risk of hepatocellular carcinoma in the European prospective investigation into cancer and nutrition study

Limited epidemiological evidence suggests a protective role for plant foods rich in flavonoids and antioxidants in hepatocellular cancer (HCC) etiology. Our aim was to prospectively investigate the association between dietary intake of flavonoids, lignans and nonenzymatic antioxidant capacity (NEAC) and HCC risk. Data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort including 477,206 subjects (29.8% male) recruited from ten Western European countries, was analyzed. Flavonoid, lignan and NEAC intakes were calculated using a compilation of existing food composition databases linked to dietary information from validated dietary questionnaires. Dietary NEAC was based on ferric reducing antioxidant capacity (FRAP) and total radical‐trapping antioxidant parameter (TRAP). Hepatitis B/C status was measured in a nested case–control subset. During a mean follow‐up of 11‐years, 191 incident HCC cases (66.5% men) were identified. Using Cox regression, multivariable adjusted models showed a borderline nonsignificant association of HCC with total flavonoid intake (highest versus lowest tertile, HRu2009=u20090.65, 95% CI: 0.40–1.04; ptrendu2009=u20090.065), but not with lignans. Among flavonoid subclasses, flavanols were inversely associated with HCC risk (HRu2009=u20090.62, 95% CI: 0.39–0.99; ptrendu2009=u20090.06). Dietary NEAC was inversely associated with HCC (FRAP: HR 0.50, 95% CI: 0.31–0.81; ptrendu2009=u20090.001; TRAP: HR 0.49, 95% CI: 0.31–0.79; ptrendu2009=u20090.002), but statistical significance was lost after exclusion of the first 2 years of follow‐up. This study suggests that higher intake of dietary flavanols and antioxidants may be associated with a reduced HCC risk.

Modulation of Plasma Non Enzimatic Antioxidant Capacity (NEAC) by Plant Foods: the Role of Polyphenol

A large body of evidence has described the antioxidant properties of phytochemicals such as PolyPhenols (PP) in different in vitro and ex vivo models. PP have been shown to scavenge oxygen and nitrogen derived free radicals, modulating antioxidant enzymes and cellular redox transcription factors. Dietary intervention studies have shown that consumption of plant foods modulate plasma Non Enzymatic Antioxidant Capacity (NEAC), biomarker of endogenous antioxidant network, in human subjects. However the identification of the molecules responsible for this effect is far to be obtained and evidences of an antioxidant in vivo action of PP are contrasting. There is a clear discrepancy between PP concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the in vivo antioxidant network. The available evidence from human intervention studies on the role of plant foods as modulators of plasma/serum NEAC and the involvement of PP will be presented and critically discussed.

Flavanols, proanthocyanidins and antioxidant activity changes during cocoa (Theobroma cacao L.) roasting as affected by temperature and time of processing.

The effect of roasting on the content of flavanols and proanthocyanidins and on the antioxidant activity of cocoa beans was investigated. Cocoa beans were roasted at three temperatures (125, 135 and 145 °C), for different times, to reach moisture contents of about 2 g 100 g(-1). Flavanols and proanthocyanidins were determined, and the antioxidant activity was tested by total phenolic index (TPI), ferric reducing antioxidant power (FRAP) and total radical trapping antioxidant parameter (TRAP) methods. The rates of flavanol and total proanthocyanidin loss increased with roasting temperatures. Moisture content of the roasted beans being equal, high temperature-short time processes minimised proanthocyanidins loss. Moisture content being equal, the average roasting temperature (135 °C) determined the highest TPI and FRAP values and the highest temperature (145 °C) determined the lowest TPI values. Moisture content being equal, low temperature-long time roasting processes maximised the chain-breaking activity, as determined by the TRAP method.

Dietary total antioxidant capacity and colorectal cancer: A large case–control study in Italy

A favorable role of fruit and vegetables on colorectal cancer risk has been related to the antioxidant properties of their components. We used data from an Italian case–control study including 1,953 patients with incident, histologically confirmed colorectal cancer (1,225 colon and 728 rectal cancers). Controls were 4,154 patients admitted to hospital for acute, non‐neoplastic conditions. A reproducible and valid food frequency questionnaire was used to assess subjects usual diet. Total antioxidant capacity (TAC) was measured using Italian food composition tables in terms of ferric reducing‐antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC) and total radical‐trapping antioxidant parameter (TRAP). We estimated the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) through multiple logistic regression models, including terms for potential confounding factors, and energy intake. TAC was inversely related with colorectal cancer risk: the OR for the highest versus the lowest quintile was 0.68 (95% CI, 0.57–0.82) for FRAP, 0.69 (95% CI, 0.57–0.83) for TEAC and 0.69 (95% CI, 0.57–0.83) for TRAP. Corresponding values, excluding TAC deriving from coffee, were 0.75 (95% CI, 0.61–0.93) for FRAP, 0.76 (95% CI, 0.61–0.93) for TEAC and 0.71 (95% CI, 0.57–0.89) for TRAP. The inverse association was apparently—though not significantly—stronger for rectal than for colon cancer. This is the first case–control study indicating consistent inverse relations between dietary TAC and colorectal cancer risk.

Heme Iron Intake, Dietary Antioxidant Capacity, and Risk of Colorectal Adenomas in a Large Cohort Study of French Women.

Background: Nitrosylated and non-nitrosylated heme iron from red processed and nonprocessed meat have been associated with increased colorectal carcinogenesis. Mechanisms include oxidative processes. It has been hypothesized that dietary antioxidants could counteract the effects of heme iron. We investigated the relationships between heme iron intake and the risk of colorectal adenomas, and a potential interaction with the dietary antioxidant capacity, in the E3N prospective cohort study. Methods: The study included 17,397 women, who underwent at least one colonoscopy. Among them, 1,409 were diagnosed with at least one first colorectal adenoma during the 103,253 person-years of follow-up. Dietary intake was measured by a semiquantitative food history questionnaire. HR estimates and 95% confidence intervals (CI) were obtained from Cox proportional hazards models, adjusted for potential confounders. Results: Heme iron intake was positively associated with colorectal and colon adenoma risks [HR for the fourth vs. first quartile: HR4 = 1.36 (1.13–1.65), Ptrend = 0.001 and HR4 = 1.49; 95% CI, 1.19–1.87; Ptrend = 0.0003, respectively]. Nonnitrosylated and nitrosylated heme iron intakes were, respectively, associated with advanced distal and proximal adenoma risks. There was a dose–effect relationship between the heme iron to total dietary antioxidant capacity ratio and colorectal adenoma risk. Conclusion: In this prospective cohort study, the association between heme iron and colorectal adenoma risk was found to depend on site, nitrosylation or not, and the ratio with the NEAC. Impact: These results emphasize the need for a global assessment of diet when considering nutritional prevention of colorectal carcinogenesis. Cancer Epidemiol Biomarkers Prev; 25(4); 640–7. ©2016 AACR.

Dietary non-enzymatic antioxidant capacity and the risk of myocardial infarction: A case-control study in Italy

BACKGROUND AND AIMSnOxidative processes have been related to atherosclerosis, but there is scanty information on the role of dietary antioxidants in the prevention of acute myocardial infarction (AMI).nnnMETHODS AND RESULTSnThe relationship between non-enzymatic antioxidant capacity (NEAC) and the risk of nonfatal AMI was investigated in a case-control study conducted in Milan, Italy, between 1995 and 2003. Cases were 760 patients below 75 years with a first episode of AMI and controls were 682 patients admitted to hospitals for acute conditions, who completed an interviewer-administered food frequency questionnaire, tested for validity and reproducibility. NEAC (excluding coffee) was measured using Italian food composition tables in terms of ferric reducing-antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC) and total radical-trapping antioxidant parameter (TRAP). The odds ratios (OR) of AMI, and the corresponding 95% confidence intervals (CI), were obtained by multiple logistic regression models including terms for main risk factors of AMI and total energy intake. NEAC was inversely related with the risk of AMI. The ORs for the highest quintile compared with the lowest one were 0.41 (95% CI, 0.27-0.63) for FRAP, 0.42 (95% CI, 0.27-0.65) for TEAC and 0.41 (95% CI, 0.27-0.62) for TRAP, with significant trends in risk. The inverse relationship was apparently stronger in women and in subjects aged ≥ 60 years.nnnCONCLUSIONSnOur results support a favorable role of dietary NEAC in the prevention of AMI, and encourage a high consumption of fruit and vegetables and a moderate consumption of wine and whole cereals.

Non-enzymatic antioxidant capacity and risk of gastric cancer

BACKGROUNDnConsumption of fruit and vegetables has been inversely related to gastric cancer. Two studies found that dietary antioxidant capacity has some role in explaining this association. We investigated the overall antioxidant effect from diet on gastric cancer using three measures of non-enzymatic antioxidant capacity (NEAC).nnnMETHODSnWe used data from an Italian case-control study including 230 patients with incident, histologically confirmed gastric cancer, and 547 frequency matched controls admitted to the same hospitals for acute non-neoplastic diseases. A reproducible and valid food frequency questionnaire was used to assess subjects usual diet. NEAC was measured using Italian food composition tables in terms of Trolox equivalent antioxidant capacity (TEAC), Ferric reducing-antioxidant power (FRAP) and Total radical-trapping antioxidant parameter (TRAP). We estimated the odds ratios (OR) of gastric cancer and the corresponding 95% confidence intervals (CI) using conditional logistic regression models including terms for recognized gastric cancer risk factors and total energy intake.nnnRESULTSnNEAC was inversely related with gastric cancer risk with ORs for the highest versus the lowest quintile of 0.54 (95%CI, 0.33-0.88) for TEAC, 0.67 (95%CI, 0.42-1.07) for FRAP and 0.57 (95%CI, 0.36-0.90) for TRAP.nnnCONCLUSIONSnA diet rich in antioxidant capacity reduced gastric cancer risk, suggesting a high consumption of fruit and vegetables and a moderate consumption of wine and whole cereals.