Effect of omega-3 fatty acids supplementation during pregnancy on lung function in preschoolers: a clinical trial.

RATIONALE: Prenatal omega-3 fatty acids improve alveolarization, diminish inflammation, and improve pulmonary growth, but it is unclear whether these outcomes translate into improved postnatal lung function. OBJECTIVE: We assessed the effect of prenatal supplementation with docosahexaenoic acid (DHA) on offspring lung function through 60 months of age. METHODS: We included a cohort of 772 Mexican preschoolers whose mothers participated in a clinical trial (NCT00646360) of supplementation with DHA or a placebo from week 18-22 of gestation through delivery. MEASUREMENTS: The children were followed after birth and anthropometric measurements and forced oscillation tests were performed at 36, 48, and 60 months of age. The effect of DHA was tested using a longitudinal mixed effect models. RESULTS: Overall, mean (Standard Deviation) of the measurements of respiratory system resistance and respiratory system reactance at 6, 8, and 10 Hz during follow up period were 11.3 (2.4), 11.1 (2.4), 10.3 (2.2) and -5.2 (1.6), -4.8 (1.7), -4.6 (1.6), respectively. There were no significant differences in pulmonary function by treatment group. DHA did not affect the average lung function or the trajectories through 60 months. CONCLUSIONS: Prenatal DHA supplementation did not influence pulmonary function in this cohort of Mexican preschoolers.

Impact of thearubigins on the estimation of total dietary flavonoids in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Thearubigins (TR) are polymeric flavanol-derived compounds formed during the fermentation of tea leaves. Comprising ∼70% of total polyphenols in black tea, TR may contribute majorly to its beneficial effects on health. To date, there is no appropriate food composition data on TR, although several studies have used data from the US Department of Agriculture (USDA) database to estimate TR intakes. We aimed to estimate dietary TR in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and assess the impact of including TR or not in the calculation of the total dietary flavonoid intake. Dietary data were collected using a single standardized 24-h dietary recall interviewer-administered to 36 037 subjects aged 35-74 years. TR intakes were calculated using the USDA database. TR intakes ranged from 0.9 mg/day in men from Navarra and San Sebastian in Spain to 532.5 mg/day in men from UK general population. TR contributed <5% to the total flavonoid intake in Greece, Spain and Italy, whereas in the UK general population, TR comprised 48% of the total flavonoids. High heterogeneity in TR intake across the EPIC countries was observed. This study shows that total flavonoid intake may be greatly influenced by TR, particularly in high black tea-consuming countries. Further research on identification and quantification of TR is needed to get more accurate dietary TR estimations.

Dietary intakes and food sources of phytoestrogens in the European Prospective Investigation into Cancer and Nutrition (EPIC) 24-hour dietary recall cohort.

BACKGROUND/OBJECTIVES: Phytoestrogens are estradiol-like natural compounds found in plants that have been associated with protective effects against chronic diseases, including some cancers, cardiovascular diseases and osteoporosis. The purpose of this study was to estimate the dietary intake of phytoestrogens, identify their food sources and their association with lifestyle factors in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. SUBJECTS/METHODS: Single 24-hour dietary recalls were collected from 36,037 individuals from 10 European countries, aged 35-74 years using a standardized computerized interview programe (EPIC-Soft). An ad hoc food composition database on phytoestrogens (isoflavones, lignans, coumestans, enterolignans and equol) was compiled using data from available databases, in order to obtain and describe phytoestrogen intakes and their food sources across 27 redefined EPIC centres. RESULTS: Mean total phytoestrogen intake was the highest in the UK health-conscious group (24.9 mg/day in men and 21.1 mg/day in women) whereas lowest in Greece (1.3 mg/day) in men and Spain-Granada (1.0 mg/day) in women. Northern European countries had higher intakes than southern countries. The main phytoestrogen contributors were isoflavones in both UK centres and lignans in the other EPIC cohorts. Age, body mass index, educational level, smoking status and physical activity were related to increased intakes of lignans, enterolignans and equol, but not to total phytoestrogen, isoflavone or coumestan intakes. In the UK cohorts, the major food sources of phytoestrogens were soy products. In the other EPIC cohorts the dietary sources were more distributed, among fruits, vegetables, soy products, cereal products, non-alcoholic and alcoholic beverages. CONCLUSIONS: There was a high variability in the dietary intake of total and phytoestrogen subclasses and their food sources across European regions.

Dietary beta-carotene, vitamin C and E intake and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).

So far, studies on dietary antioxidant intake, including beta-carotene, vitamin C and vitamin E, and breast cancer risk are inconclusive. Thus, we addressed this question in the European Prospective Investigation into Cancer and Nutrition. During a median follow-up time of 8.8 years, 7,502 primary invasive breast cancer cases were identified. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). All analyses were run stratified by menopausal status at recruitment and, additionally, by smoking status, alcohol intake, use of exogenous hormones and use of dietary supplements. In the multivariate analyses, dietary intake of beta-carotene, vitamin C and E was not associated with breast cancer risk in premenopausal [highest vs. lowest quintile: HR, 1.04 (95% CI, 0.85-1.27), 1.12 (0.92-1.36) and 1.11 (0.84-1.46), respectively] and postmenopausal women [0.93 (0.82-1.04), 0.98 (0.87-1.11) and 0.92 (0.77-1.11), respectively]. However, in postmenopausal women using exogenous hormones, high intake of beta-carotene [highest vs. lowest quintile; HR 0.79 (95% CI, 0.66-0.96), P (trend) 0.06] and vitamin C [0.88 (0.72-1.07), P (trend) 0.05] was associated with reduced breast cancer risk. In addition, dietary beta-carotene was associated with a decreased risk in postmenopausal women with high alcohol intake. Overall, dietary intake of beta-carotene, vitamin C and E was not related to breast cancer risk in neither pre- nor postmenopausal women. However, in subgroups of postmenopausal women, a weak protective effect between beta-carotene and vitamin E from food and breast cancer risk cannot be excluded.

Air pollution, oxidative stress and dietary supplementation: a review.

The aim of the present review was to provide an up-to-date overview of the biological and epidemiological evidence of the role of oxidative stress as a major underlying feature of the toxic effect of air pollutants, and the potential role of dietary supplementation in enhancing antioxidant defences. A bibliographic search was conducted through PubMed. The keywords used in the search were "air pollutant", "oxidative stress", "inflammation", "antioxidant polyunsaturated fatty acids" and "genetics". In addition, the authors also searched for biomarkers of oxidative stress and nutrients. The review presents the most recent data on: the biological and epidemiological evidence of the oxidative stress response to air pollutants; the role of dietary supplementation as a modulator of these effects; and factors of inter-individual variation in human response. The methodology for further epidemiological studies will be discussed in order to improve the current understanding on how nutritional factors may act. There is substantial evidence that air pollution exposure results in increased oxidative stress and that dietary supplementation may play a modulating role on the acute effect of air pollutants. Further epidemiological studies should address the impact of supplementation strategies in the prevention of air-pollution-related long-term effects in areas where people are destined to be exposed for the distant future.

GSTM1 and GSTP1 and respiratory health in asthmatic children exposed to ozone.

Acute exposure to ozone has been related to a wide spectrum of health effects in susceptible individuals. Genetic factors may influence interindividual variation in ozone response. The current authors investigated the relationships between common polymorphisms in two genes involved in response to oxidative stress, i.e. glutathione S-transferases M1 (GSTM1) and P1 (GSTP1), and both respiratory symptoms and lung function in response to ozone among childhood asthmatics. A total of 151 asthmatic children, who were participants in a randomised controlled trial of antioxidant vitamin supplementation in Mexico City, were studied. Children were genotyped using PCR methods and followed from October 1998-April 2000. Increases in reported breathing difficulty were associated with ozone exposure in children with GSTM1 null (8%, 95% confidence interval (CI) 1-15%, per 20-ppb increase in 1-h maximum daily average over 7 days) or GSTP1 Valine/Valine (Val/Val) genotypes (14%, 95% CI 5-25%). In children with both GSTM1 null and GSTP1 Val/Val genotypes, the increase in breathing difficulty associated with a 20-ppb increase in ozone exposure was even greater (21%, 95% CI 5-39%). GSTP1 genotypes were not significantly associated with ozone-related lung function changes. In conclusion, asthmatic children with glutathione S-transferase M1 null and glutathione S-transferase P1 Valine/Valine genotypes appear more susceptible to developing respiratory symptoms related to ozone exposure.

Fruit and vegetable intakes and asthma in the E3N study.

BACKGROUND: A study was undertaken to investigate whether dietary intake predicted the prevalence of adult asthma among French women participating in the E3N study. METHODS: Of 68 535 women who completed a food frequency questionnaire in 1993 which included 238 food items, 2145 (3.1%) reported having asthma. The distribution of food intake was divided into quartiles (Q(1)-Q(4)) and the prevalence of asthma was compared between the different quartiles (lowest as reference) using logistic regression models on cross sectional data. RESULTS: After adjusting for age, body mass index, menopausal status, smoking status, total caloric intake, physical activity, and use of dietary supplements, women who had a greater intake of tomatoes (OR(Q1-Q4) 0.85 95% CI 0.75 to 0.96, test for trend p = 0.02), carrots (OR(Q1-Q4) 0.81 95% CI 0.72 to 0.92, test for trend p = 0.0003), and leafy vegetables (OR(Q1-Q4) 0.82 95% CI 0.73 to 0.93, test for trend p = 0.0009) had a lower prevalence of asthma. Apples were marginally related to the prevalence of asthma. No other fruits or vegetables were significantly associated with asthma prevalence. CONCLUSIONS: These results suggest that the intake of some vegetables may decrease the prevalence of adult asthma.

Nutrition and lung health.

Several lung diseases have been associated with oxidative stress and linked to oxidant insults such as cigarette smoke, air pollutants and infections. Consequently, dietary factors and nutrients with a potential protective role in the oxidative process and inflammatory response have been implicated in the genesis or evolution of these diseases. These nutrients include fruits and vegetables, antioxidant vitamins such as vitamin C, vitamin E, betacarotene and other carotenoids, vitamin A, fatty acids and some minerals such as sodium, magnesium and selenium. This article reviews the potential mechanisms by which dietary factors may affect respiratory health, and discusses epidemiological evidence for the link between diet and lung diseases. Most of the available evidence on the effect of dietary factors on the risk for obstructive lung diseases are derived from cross-sectional studies. These studies suggest that antioxidant vitamins, particularly vitamin C, and to a lesser extent other antioxidants, have a protective effect against lung diseases. However, the few intervention studies have not been conclusive. High intake of fresh fruit and some vegetables appears to have a beneficial effect on lung health and their consumption should be recommended on a daily basis. Supplementation of vitamin C and other antioxidants could be proposed in subjects with additional oxidative stress challenge, such as exposure to high levels of air pollution. Subjects with impaired immune response could also benefit from vitamin A and zinc supplementation. Further studies are needed to determine the impact of diet on the incidence and evolution of lung diseases.

Antioxidant supplementation and nasal inflammatory responses among young asthmatics exposed to high levels of ozone.

The inflammatory response to ozone in atopic asthma suggests that soluble mediators of inflammation are released in response to oxidant stress. Antioxidants may alleviate additional oxidative stress associated with photochemical oxidant pollution. This study investigates the impact of antioxidant supplementation on the nasal inflammatory response to ozone exposure in atopic asthmatic children. We conducted a randomized trial using a double-blinded design. Children with asthma (n = 117), residents of Mexico City, were given randomly a daily supplement of vitamins (50 mg/day of vitamin E and 250 mg/day of vitamin C) or placebo. Nasal lavages were performed three times during the 4-month follow-up and analysed for content of interleukin-6 (IL-6), IL-8, uric acid and glutathione (GSx). IL-6 levels in the nasal lavage were increased significantly in the placebo group after ozone exposure while no increase was observed in the supplement group. The difference in response to ozone exposure between the two groups was significant (P = 0.02). Results were similar for IL-8, but with no significant difference between the groups (P = 0.12). GSx decreased significantly in both groups. Uric acid decreased slightly in the placebo group. Our data suggest that vitamin C and E supplementation above the minimum dietary requirement in asthmatic children with a low intake of vitamin E might provide some protection against the nasal acute inflammatory response to ozone.

Genetic polymorphism of GSTM1 and antioxidant supplementation influence lung function in relation to ozone exposure in asthmatic children in Mexico City.

BACKGROUND: We recently reported that antioxidant supplementation with vitamins C and E mitigated ozone related decline in forced expiratory flow (FEF(25-75)) in 158 asthmatic children in an area with high ozone exposure in Mexico City. METHODS: A study was undertaken to determine whether deletion of glutathione S-transferase M1 (GSTM1 null genotype), a gene involved in response to oxidative stress, influences ozone related decline in FEF(25-75) and the benefit of antioxidant supplementation. RESULTS: GSTM1 null children receiving placebo had significant ozone related decrements in FEF(25-75) (percentage change per 50 ppb of ozone 2.9 (95% CI -5.2 to -0.6), p=0.01); GSTM1 positive children did not. Conversely, the effect of antioxidants was stronger in children with the GSTM1 null genotype. CONCLUSIONS: Asthmatic children with a genetic deficiency of GSTM1 may be more susceptible to the deleterious effects of ozone on the small airways and might derive greater benefit from antioxidant supplementation.

Diet and obstructive lung diseases.

The results presented in this review suggest that the impact of nutrition on obstructive lung disease is most evident for antioxidant vitamins, particularly vitamin C and, to a lesser extent, vitamin E. By decreasing oxidant insults to the lung, antioxidants could modulate the development of chronic lung diseases and lung function decrement. Antioxidant vitamins could also play an important role in gene-environment interactions in complex lung diseases such as childhood asthma. Data also suggest that omega-3 fatty acids may have a potentially protective effect against airway hyperreactivity and lung function decrements; however, relevant data are still sparse. Although epidemiologic data suggest that consumption of fresh fruit may reduce risk of noncarcinogenic airway limitation, there are no clear data on which nutrients might be most relevant. While some studies evaluate daily intake of vitamin C, other studies use fruit consumption as a surrogate for antioxidant intake. Given the dietary intercorrelations among antioxidant vitamins, particularly vitamin C, beta-carotene, and flavonoids, as well as other micronutrients, it may be difficult to isolate a specific effect. Some population subgroups with higher levels of oxidative stress, such as cigarette smokers, may be more likely to benefit from dietary supplementation, since some studies have suggested that antioxidant intake may have a greater impact in this group. Studies of lung function decrement and COPD in adults suggest that daily intake of vitamin C at levels slightly exceeding the current Recommended Dietary Allowance (60 mg/day among nonsmokers and 100 mg/day among smokers) may have a protective effect (20). In the Schwartz and Weiss (85) and Britton et al. (87) studies, an increase of 40 mg/day in vitamin C intake led to an approximate 20-ml increase in FEV1. Daily mean vitamin C intakes in these studies were 66 mg and 99.2 mg, respectively, and the highest intake level (178 mg/day) was approximately three times the Recommended Dietary Allowance. Although the amplitude of the effect was modest, if these effects accumulate over 20-30 years, they could have a meaningful impact on the rate at which pulmonary function declines, particularly in symptomatic subjects (85). Longitudinal data support the hypothesis that fresh fruit consumption has a beneficial impact on the lung (95). Among children, consumption of fresh fruit, particularly fruit high in vitamin C, has been related to a lower prevalence of asthma symptoms and higher lung function (64). This effect was observed event at low levels of fruit consumption (one or two servings per week vs. less than one serving per week), which suggests that a small increase in dietary intake could have a beneficial effect. Consumption of fish has also been related to lower airway hyperreactivity among children (75) and higher lung function in adults (100); however, longitudinal data do not provide evidence that increased omega-3 fatty acid intake protects against lung disease (101). Experimental studies of persons with asthma suggest that magnesium infusion may have a place in the acute treatment of asthma, but it does not seem to have long-term benefits. The studies of sodium, selenium, and fish oils do not show convincing evidence of clinical benefits. Studies of vitamin C supplementation suggest a short-term protective effect on airway responsiveness and pulmonary function. It remains to be proven whether consistent use of vitamin C would have a protective effect on the evolution of chronic asthma. Results from supplementation studies conducted among subjects exposed to high levels of oxidants (57-60) suggest that daily intake of antioxidant vitamins exceeding the Recommended Dietary Allowance may have a beneficial effect on lung airways and that intake higher than the Recommended Dietary Allowance should be recommended for populations chronically exposed to photooxidant air pollutants (such as ozone), cigarette smoking, or vigorous exercise. It is difficult to determine the amounts of antioxidant vitamins that people should consume. In particular, although vitamin C was shown to have maximum bioavailability when given in a single dose of 200 mg (102), experiments on which this finding was based were conducted under normal conditions. Guidelines from the US National Cancer Institute (103) recommend consumption of five servings of fruit and vegetables daily, corresponding to a vitamin C intake exceeding 200 mg. Dietary surveys carried out in the US population indicate that less than 12 percent of US children and adults meet this recommended level of intake (104). Diet appears to be an important cofactor in the development of obstructive lung disease, although data are still sparse. There is a need for further research in experimental and epidemiologic settings to better understand the physiologic effects of antioxidant vitamins, omega-3 fatty acids, and other nutrients on lung tissues. The impact of diet on the incidence and evolution of asthma and COPD should be investigated using a cohort design that accounts for known risk factors. This will allow researchers to evaluate the exposure-disease relation over an adequate time frame and obtain insight into the causality of the relation. Some of these studies should enroll infants and young children to determine the impact of early diet on respiratory health. Research should also focus on the equally challenging policy issues--namely, finding effective methods of convincing people to increase their daily consumption of fresh fruits and vegetables, to stop smoking cigarettes, and to minimize their environmental and occupational exposure to pollutants and other agents that cause respiratory disease.

Antioxidant supplementation and respiratory functions among workers exposed to high levels of ozone.

Ozone exposure has been related to adverse respiratory effects, in particular to lung function decrements. Antioxidant vitamins are free-radical scavengers and could have a protective effect against photo-oxidant exposure. To evaluate whether acute effects of ozone on lung functions could be attenuated by antioxidant vitamin supplementation, we conducted a randomized trial using a double-blind crossover design. Street workers (n = 47) of Mexico City were randomly assigned to take daily a supplement (75 mg vitamin E, 650 mg vitamin C, 15 mg beta carotene) or a placebo and were followed from March to August 1996. Pulmonary function tests were done twice a week at the end of the workday. During the follow-up, the mean 1-h maximum ozone level was 123 ppb (SD = 40). During the first phase, ozone levels were inversely associated with FVC (beta = -1.60 ml/ppb), FEV1 (beta = -2.11 ml/ppb), and FEF25-75 (beta = -4.92 ml/ppb) (p < 0.05) in the placebo group but not in the supplement group. The difference between the two groups was significant for FVC, FEV1, and FEF25-75 (p < 0.01). During the second phase, similar results were observed, but the lung function decrements in the placebo group were smaller, suggesting that the supplementation may have had a residual protective effect on the lung. These results need to be confirmed in larger supplementation studies.

Dietary and environmental determinants of blood and bone lead levels in lactating postpartum women living in Mexico City.

Despite the recent declines in environmental lead exposure in the United States and Mexico, the potential for delayed toxicity from bone lead stores remains a significant public health concern. Some evidence indicates that mobilization of lead from bone may be markedly enhanced during the increased bone turnover of pregnancy and lactation, resulting in lead exposure to the fetus and the breast-fed infant. We conducted a cross-sectional investigation of the interrelationships between environmental, dietary, and lifestyle histories, blood lead levels, and bone lead levels among 98 recently postpartum women living in Mexico City. Lead levels in the patella (representing trabecular bone) and tibia (representing cortical bone) were measured by K X-ray fluorescence (KXRF). Multivariate linear regression models showed that significant predictors of higher blood lead included a history of preparing or storing food in lead-glazed ceramic ware, lower milk consumption, and higher levels of lead in patella bone. A 34 micrograms/g increase in patella lead (from the medians of the lowest to the highest quartiles) was associated with an increase in blood lead of 2.4 micrograms/dl. Given the measurement error associated with KXRF and the extrapolation of lead burden from a single bone site, this contribution probably represents an underestimate of the influence of trabecular bone on blood lead. Significant predictors of bone lead in multivariate models included years living in Mexico City, lower consumption of high calcium content foods, and nonuse of calcium supplements for the patella and years living in Mexico City, older age, and lower calcium intake for tibia bone. Low consumption of milk and cheese, as compared to the highest consumption category (every day), was associated with an increase in tibia bone lead of 9.7 micrograms Pb/g bone mineral. The findings of this cross-sectional study suggest that patella bone is a significant contributor to blood lead during lactation and that consumption of high calcium content foods may protect against the accumulation of lead in bone.

Food predictors of plasma beta-carotene and alpha-tocopherol: validation of a food frequency questionnaire.

Nutrient intakes from a food frequency questionnaire are usually calculated as the product of frequency of intake and nutrient composition of the food, summed over the food items. This involves assumptions about the accuracy of recording, food composition data, stability during storage and preparation, and bioavailability. This usual method of calculation was compared with one using empirical weights derived by multivariate linear regression. Food intakes reported on a food frequency questionnaire by Boston, Massachusetts, area subjects in 1982-1985 were used to predict plasma levels of beta-carotene among 370 male and female nonsmokers and plasma levels of alpha-tocopherol among 339 male and female nonusers of vitamin supplements. Nutrient intake computed using empirical weights yielded a significant correlation with plasma beta-carotene (r = 0.43, p = 0.0001), similar to the correlation using nutrient intake calculated from food composition tables (r = 0.38, p = 0.0001). However, the use of empirical weights significantly improved the correlation of vitamin E intake with plasma alpha-tocopherol levels (r = 0.32, p = 0.0001), compared with the weak correlation obtained using the food composition table method to calculate intake (r = 0.16). The results support the validity of published food composition data used to compute carotenoid intake and illustrate the potential utility of empirically derived weights for foods to predict plasma levels of some nutrients.