The possible role of female sex hormones in milk from pregnant cows in the development of breast, ovarian and corpus uteri cancers.

The continued increase in incidence of some hormone-related cancers worldwide is of great concern. Although estrogen-like substances in the environment were blamed for this increase, the possible role of endogenous estrogens from food has not been widely discussed. We are particularly concerned about cows' milk, which contains a considerable quantity of estrogens. When we name cows' milk as one of the important routes of human exposure to estrogens, the general response of Western people is that "man has been drinking cows' milk for around 2000 years without apparent harm." However, the milk that we are now consuming is quite different from that consumed 100 years ago. Unlike their pasture-fed counterparts of 100 years ago, modern dairy cows are usually pregnant and continue to lactate during the latter half of pregnancy, when the concentration of estrogens in blood, and hence in milk, increases. The correlation of incidence and mortality rates with environmental variables in worldwide countries provides useful clues to the etiology of cancer. In this study, we correlated incidence rates for breast, ovarian, and corpus uteri cancers (1993-97 from Cancer Incidence in Five Continents) with food intake (1961-97 from FAOSTAT) in 40 countries. Meat was most closely correlated with the breast cancer incidence (r=0.827), followed by milk (0.817) and cheese (0.751). Stepwise multiple-regression analysis (SMRA) identified meat as the factor contributing most greatly to the incidence of breast cancer ([R]=0.862). Milk was most closely correlated with the incidence of ovarian cancer (r=0.779), followed by animal fats (0.717) and cheese (0.697). SMRA revealed that milk plus cheese make the greatest contribution to the incidence of ovarian cancer ([R]=0.767). Milk was most closely correlated with corpus uteri cancer (r=0.814), followed by cheese (0.787). SMRA revealed that milk plus cheese make the most significant contribution to the incidence of corpus uteri cancer ([R]=0.861). In conclusion, increased consumption of animal-derived food may have adverse effects on the development of hormone-dependent cancers. Among dietary risk factors, we are most concerned with milk and dairy products, because the milk we drink today is produced from pregnant cows, in which estrogen and progesterone levels are markedly elevated.


Acne, dairy and cancer

A potent link to dairy seems to exist for three hormone-responsive glands. Acne, breast cancer and prostate cancer have all been linked epidemiologically to dairy intake. Although mechanisms postulated here remain to be accurately defined, the likely link involves Insulin-like Growth Factor-1 as a general stimulant, synergized by the steroid hormones present in milk. The IGF-1 may be either absorbed from milk, or stimulated by its ingestion, or both. The 5alpha-reduced compound 5alpha-pregnanedione (5α-P) present in milk is a direct precursor of dihydrotestosterone and may act through that pathway in prostate cancer, but 5α-P has also recently been shown to be capable of inducing estrogen receptors in breast cancer cells, upregulating cancer cells' sensitivity to estrogen. The introduction of exogenous hormones and growth factors into tissues that have not evolved defensive feedback inhibition of their corresponding endogenous sources is postulated as a direct stimulatory threat to these organ systems, whether for hyperplasia or neoplasia.


Exposure to exogenous estrogen through intake of commercial milk produced from pregnant cows.

BACKGROUND: Modern genetically improved dairy cows continue to lactate throughout almost the entire pregnancy. Therefore, recent commercial cow's milk contains large amounts of estrogens and progesterone. With regard to the exposure of prepubertal children to exogenous estrogens, the authors are particularly concerned about commercial milk produced from pregnant cows. The purpose of the present study was therefore to examine concentrations of serum and urine sex hormones after the intake of cow milk. METHODS: Subjects were seven men, six prepubertal children, and five women. The men and children drank 600 mL/m(2) of cow milk. Urine samples were collected 1 h before the milk intake and four times every hour after intake. In men the serum samples were obtained before and 15, 30, 45, 60, 90 and 120 min after milk intake. Women drank 500 mL of cow's milk every night for 21 days beginning on the first day of the second menstruation. In three successive menstrual cycles, the day of ovulation was examined using an ovulation checker. RESULTS: After the intake of cow milk, serum estrone (E1) and progesterone concentrations significantly increased, and serum luteinizing hormone, follicle-stimulating hormone and testosterone significantly decreased in men. Urine concentrations of E1, estradiol, estriol and pregnanediol significantly increased in all adults and children. In four out of five women, ovulation occurred during the milk intake, and the timing of ovulation was similar among the three menstrual cycles. CONCLUSIONS: The present data on men and children indicate that estrogens in milk were absorbed, and gonadotropin secretion was suppressed, followed by a decrease in testosterone secretion. Sexual maturation of prepubertal children could be affected by the ordinary intake of cow milk.


Soybean isoflavone exposure does not have feminizing effects on men: a critical examination of the clinical evidence.

OBJECTIVE: To critically evaluate the clinical evidence, and when not available, the animal data, most relevant to concerns that isoflavone exposure in the form of supplements or soy foods has feminizing effects on men. DESIGN: Medline literature review and cross-reference of published data. RESULT(S): In contrast to the results of some rodent studies, findings from a recently published metaanalysis and subsequently published studies show that neither isoflavone supplements nor isoflavone-rich soy affect total or free testosterone (T) levels. Similarly, there is essentially no evidence from the nine identified clinical studies that isoflavone exposure affects circulating estrogen levels in men. Clinical evidence also indicates that isoflavones have no effect on sperm or semen parameters, although only three intervention studies were identified and none were longer than 3 months in duration. Finally, findings from animal studies suggesting that isoflavones increase the risk of erectile dysfunction are not applicable to men, because of differences in isoflavone metabolism between rodents and humans and the excessively high amount of isoflavones to which the animals were exposed. CONCLUSION(S): The intervention data indicate that isoflavones do not exert feminizing effects on men at intake levels equal to and even considerably higher than are typical for Asian males. Copyright 2010. Published by Elsevier Inc.


Consumption of animal products, their nutrient components and postmenopausal circulating steroid hormone concentrations.

BACKGROUND/OBJECTIVES: Little is known about nutritional factors that influence circulating concentrations of steroid hormones, which are consistently associated with risk of breast cancer for postmenopausal women. We aimed to investigate the association between consumption of animal products and the plasma concentrations of steroid hormones and sex hormone-binding globulin (SHBG). SUBJECTS/METHODS: Cross-sectional analysis was conducted on plasma from 766 naturally postmenopausal women. We measured plasma concentrations of steroid hormones and SHBG, and estimated dietary intakes using a 121-item food frequency questionnaire. Log-transformed values of hormone concentrations were regressed on quartiles of intake of meat and dairy products among food items, and fats, proteins and cholesterol among nutrient intake. RESULTS: Total red and fresh red meat consumption was negatively associated with SHBG levels (P for trend=0.04 and <0.01, respectively). Mean SHBG concentrations were approximately 8% and 13% lower for women in the highest quartile compared with the lowest quartile of total red and fresh red meat consumption, respectively. Positive associations were observed between dairy product consumption and total and free estradiol concentrations (P for trend=0.02 and 0.03, respectively). Mean concentrations of total and free estradiol were 15 and 14% higher for women in the highest quartile of dairy product consumption than for those in the lowest quartile, respectively. No associations were observed with consumption of processed meat, chicken, fish, eggs, cholesterol, fats or protein. CONCLUSIONS: Our study suggests that greater consumption of total red and fresh red meat and dairy products might influence circulating concentrations of SHBG and estradiol, respectively. Confirmation and further investigation is required.


Comparison of sex hormonal and metabolic profiles between omnivores and vegetarians in pre- and post-menopausal women.

The purpose of the present study was to investigate the sex hormonal and metabolic profiles in vegetarians and compare these with the profiles in omnivores. The design of the present study was cross-sectional. The study sample of pre- and post-menopausal women included forty-one omnivores and twenty-one vegetarians. Thereafter we determined: (1) plasma sex hormones, (2) fasting insulin, NEFA as well as apo-A and apo-B, (3) BMI, (4) a dietary profile (3 d dietary records), (5) physical activity and (6) total faecal excretion per 72 h and total urinary excretion per 72 h. Vegetarians showed higher levels of sex hormone-binding globulin (SHBG), apo-A, total faecal excretion per 72 h and total fibre intake as well as lower levels of apo-B, free oestradiol, free testosterone, dehydroepiandrosterone sulfate (DHEA-s) and BMI. Interestingly, after controlling for BMI, significant differences between groups still persisted except for apo-B. Moreover, stepwise regression analysis showed that total fibre intake explained 15.2 % of the variation in SHBG in our cohort, which accounted for the greatest source of unique variance. Results of the present study indicate that pre- and post-menopausal vegetarians present higher concentrations of SHBG, which could be explained, in part, by higher levels of fibre intake. This may explain, at least in part, the lower risk of developing type 2 diabetes.


Meats, processed meats, obesity, weight gain and occurrence of diabetes among adults: findings from Adventist Health Studies.

AIM: To examine the relation between meat intake and diabetes occurrence in adults. METHODS: In a prospective cohort study we examined the relation between diet and incident diabetes recorded among 8,401 cohort members (ages 45-88 years) of the Adventist Mortality Study and Adventist Health Study (California, USA) who were non-diabetic at baseline. During the 17-year follow-up, we identified 543 incident diabetes cases. RESULTS: (1) Subjects who were weekly consumers of all meats were 29% (OR = 1.29; 95% CI 1.08, 1.55) more likely (relative to zero meat intake) to develop diabetes. (2) Subjects who consumed any processed meats (salted fish and frankfurters) were 38% (OR = 1.38; 95% CI 1.05-1.82) more likely to develop diabetes. (3) Long-term adherence (over a 17-year interval) to a diet that included at least weekly meat intake was associated with a 74% increase (OR = 1.74; 95% CI 1.36-2.22) in odds of diabetes relative to long-term adherence to a vegetarian diet (zero meat intake). Further analyses indicated that some of this risk may be attributable to obesity and/or weight gain--both of which were strong risk factors in this cohort. It is noteworthy that even after control for weight and weight change, weekly meat intake remained an important risk factor (OR = 1.38; 95% CI 1.06-1.68) for diabetes [corrected]. CONCLUSIONS: Our findings raise the possibility that meat intake, particularly processed meats, is a dietary risk factor for diabetes. 2008 S. Karger AG, Basel.


Sex Hormone-Binding Globulin (SHBG), estradiol and breast cancer.

The human serum Sex Hormone-Binding Globulin (SHBG) plays an important role in breast cancer pathophysiology and risk definition, since it regulates the bioavailable fraction of circulating estradiol. We here summarize data reported over the years concerning the involvement of SHBG and SHBG polymorphisms in the definition of breast cancer risk. We also report what is known about the direct action of SHBG in breast cancer cells, illustrating its interaction with these cells and the subsequent initiation of a specific intracellular pathway leading to cross-talk with the estradiol-activated pathway and, finally, to the inhibition of several effects of estradiol in breast cancer cells. In conclusion, as a result of its unique property of regulating the estrogen free fraction and cross-talking with the estradiol pathways, by inhibiting estradiol-induced breast cancer cell growth and proliferation, SHBG is associated with a reduced risk of developing the neoplasm after estrogen exposure. 2009 Elsevier Ireland Ltd. All rights reserved.


The microbiome and obesity: is obesity linked to our gut flora?

The human gut is a lush microbial ecosystem containing about 100 trillion microorganisms, whose collective genome, the microbiome, contains 100-fold more genes than the entire human genome. The symbiosis of our extended genome plays a role in host homeostasis and energy extraction from diet. In this article, we summarize some of the studies that have advanced the understanding of the microbiome and its effects on metabolism, obesity, and health. Metagenomic studies demonstrated that certain mixes of gut microbiota may protect or predispose the host to obesity. Furthermore, microbiota transplantation studies in germ-free murine models showed that the efficient energy extraction traits of obese-type gut flora are transmissible. The proposed methods by which the microbiome may contribute to obesity include increasing dietary energy harvest, promoting fat deposition, and triggering systemic inflammation. Future treatments for obesity may involve modulation of gut microbiota using probiotics or prebiotics.


Probiotic effects on cold and influenza-like symptom incidence and duration in children.

OBJECTIVE: Probiotic consumption effects on cold and influenza-like symptom incidence and duration were evaluated in healthy children during the winter season. METHODS: In this double-blind, placebo-controlled study, 326 eligible children (3-5 years of age) were assigned randomly to receive placebo (N = 104), Lactobacillus acidophilus NCFM (N = 110), or L acidophilus NCFM in combination with Bifidobacterium animalis subsp lactis Bi-07 (N = 112). Children were treated twice daily for 6 months. RESULTS: Relative to the placebo group, single and combination probiotics reduced fever incidence by 53.0% (P = .0085) and 72.7% (P = .0009), coughing incidence by 41.4% (P = .027) and 62.1% (P = .005), and rhinorrhea incidence by 28.2% (P = .68) and 58.8% (P = .03), respectively. Fever, coughing, and rhinorrhea duration was decreased significantly, relative to placebo, by 32% (single strain; P = .0023) and 48% (strain combination; P < .001). Antibiotic use incidence was reduced, relative to placebo, by 68.4% (single strain; P = .0002) and 84.2% (strain combination; P < .0001). Subjects receiving probiotic products had significant reductions in days absent from group child care, by 31.8% (single strain; P = .002) and 27.7% (strain combination; P < .001), compared with subjects receiving placebo treatment. CONCLUSION: Daily dietary probiotic supplementation for 6 months was a safe effective way to reduce fever, rhinorrhea, and cough incidence and duration and antibiotic prescription incidence, as well as the number of missed school days attributable to illness, for children 3 to 5 years of age.


An obesity-associated gut microbiome with increased capacity for energy harvest.

The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.


Gut microbiota composition is associated with body weight, weight gain and biochemical parameters in pregnant women.

Obesity is associated with complications during pregnancy and increased health risks in the newborn. The objective of the present study was to establish possible relationships between gut microbiota, body weight, weight gain and biochemical parameters in pregnant women. Fifty pregnant women were classified according to their BMI in normal-weight (n 34) and overweight (n 16) groups. Gut microbiota composition was analysed by quantitative real-time PCR in faeces and biochemical parameters in plasma at 24 weeks of pregnancy. Reduced numbers of Bifidobacterium and Bacteroides and increased numbers of Staphylococcus, Enterobacteriaceae and Escherichia coli were detected in overweight compared with normal-weight pregnant women. E. coli numbers were higher in women with excessive weight gain than in women with normal weight gain during pregnancy, while Bifidobacterium and Akkermansia muciniphila showed an opposite trend. In the whole population, increased total bacteria and Staphylococcus numbers were related to increased plasma cholesterol levels. Increased Bacteroides numbers were related to increased HDL-cholesterol and folic acid levels, and reduced TAG levels. Increased Bifidobacterium numbers were related to increased folic acid levels. Increased Enterobacteriaceae and E. coli numbers were related to increased ferritin and reduced transferrin, while Bifidobacterium levels showed the opposite trend. Therefore, gut microbiota composition is related to body weight, weight gain and metabolic biomarkers during pregnancy, which might be of relevance to the management of the health of women and infants.


Dietary predictors of 5-year changes in waist circumference.

BACKGROUND: Previous studies on the association between macronutrient intake and the development of abdominal obesity, which carries an increased health risk, have not shown a consistent pattern, possibly due to mixed effects of other aspects of the food intake. OBJECTIVE: This study investigated the association between intake from 21 food and beverage groups and the subsequent 5-year difference in waist circumference. METHODS: The study population consisted of 22,570 women and 20,126 men, aged 50 to 64 years at baseline, with complete data on baseline and follow-up waist circumference, baseline diet (192 items food frequency questionnaire), body mass index, and selected potential confounders (eg, smoking status, sport activities, and intake of alcoholic beverages). Multiple linear regression analyses were performed. RESULTS: For women, 5-year difference in waist circumference was inversely related to intake from red meat, vegetables, fruit, butter, and high-fat dairy products, whereas intake from potatoes, processed meat, poultry, and snack foods was positively associated. For men, red meat and fruit intakes were inversely associated with 5-year difference in waist circumference, whereas snack foods intake was positively associated. Sex differences occurred for vegetables, high-fat dairy products, and processed meat. CONCLUSIONS: The results suggest that a diet low in fruits and red meat and high in snack foods was associated with larger waist circumference gains in both sexes. Furthermore, in women a diet low in vegetables, butter, and high-fat dairy products, and high in poultry, potatoes, and processed meat were likely determinants of subsequent gain at the waist.


Viral obesity: fact or fiction?

The aetiology of obesity is multifactorial. An understanding of the contributions of various causal factors is essential for the proper management of obesity. Although it is primarily thought of as a condition brought on by lifestyle choices, recent evidence shows there is a link between obesity and viral infections. Numerous animal models have documented an increased body weight and a number of physiologic changes, including increased insulin sensitivity, increased glucose uptake and decreased leptin secretion that contribute to an increase in body fat in adenovirus-36 infection. Other viral agents associated with increasing obesity in animals included canine distemper virus, rous-associated virus 7, scrapie, Borna disease virus, SMAM-1 and other adenoviruses. This review attempted to determine if viral infection is a possible cause of obesity. Also, this paper discussed mechanisms by which viruses might produce obesity. Based on the evidence presented in this paper, it can be concluded that a link between obesity and viral infections cannot be ruled out. Further epidemiologic studies are needed to establish a causal link between the two, and determine if these results can be used in future management and prevention of obesity.


Association of adenovirus infection with human obesity.

We previously reported that chickens infected with the avian adenovirus SMAM-1 developed a unique syndrome characterized by excessive intra-abdominal fat deposition accompanied by paradoxically low serum cholesterol and triglyceride levels. There have been no previous reports of avian adenoviruses infecting humans. We screened the serum of 52 humans with obesity in Bombay, India, for antibodies against SMAM-1 virus using the agar gel precipitation test (AGPT) method. Bodyweights and serum cholesterol and triglyceride levels were compared in SMAM-1-positive (P-AGPT) and SMAM-1-negative (N-AGPT) groups. Ten subjects were positive for antibodies to SMAM-1, and 42 subjects did not have antibodies. The P-AGPT group had a significantly higher bodyweight (p < 0.02) and body mass index (p < 0.001) (95.1 +/- 2.1 kg and 35.3 +/- 1.5 kg/m2, respectively) compared with the N-AGPT group (80.1 +/- 0.6 kg and 30.7 +/- 0.6 kg/m2, respectively). Also, the P-AGPT group had significantly lower serum cholesterol (p < 0.02) and triglyceride (p < 0.001) values (4.65 mmol/L and 1.45 mmol/L, respectively) compared with the N-AGPT group (5.51 mmol/L and 2.44 mmol/L, respectively). Two subjects positive for SMAM-1 antibodies had antibodies against each others' serum, suggesting the presence of antigens in one or both. When these two serum samples were inoculated into chicken embryos, macroscopic lesions compatible with SMAM-1 infection developed. The inoculation of serum from N-AGPT subjects did not produce such lesions. The presence of increased obesity, antibodies to SMAM-1, reduced levels of blood lipids, and viremia that produces a typical infection in chicken embryos suggests that SMAM-1, or a serologically similar human virus, may be involved in the cause of obesity in some humans.


Infectobesity: obesity of infectious origin.

The rapid increase in obesity and the associated health care costs have prompted a search for better approaches for its prevention and management. Such efforts may be facilitated by better understanding the etiology of obesity. Of the several etiological factors, infection, an unusual causative factor, has recently started receiving greater attention. In the last two decades, 10 adipogenic pathogens were reported, including human and nonhuman viruses, scrapie agents, bacteria, and gut microflora. Some of these pathogens are associated with human obesity, but their causative role in human obesity has not been established. This chapter presents information about the natural hosts, signs and symptoms, and pathogenesis of the adipogenic microorganisms. If relevant to humans, "Infectobesity" would be a relatively novel, yet extremely significant concept. A new perspective about the infectious etiology of obesity may stimulate additional research to assess the contribution of hitherto unknown pathogens to human obesity and possibly to prevent or treat obesity of infectious origins.


Effect of adenovirus infection on adiposity in chicken.

Excessive fat accumulation has been observed in the field in chickens infected with adenovirus. In the present study this has been verified under experimental conditions. Chickens inoculated with adenovirus showed lesser weight gain but excessive adiposity compared to normal control chickens. These changes could not be explained by variation in food consumption. Chickens acquiring adenovirus naturally from the inoculated group showed similar adiposity. Serum cholesterol and triglyceride levels of inoculated and naturally infected chickens were significantly lower compared to those of the control group. Such an association between adenovirus infection and adiposity has been shown, probably, for the first time, which might help in further understanding of the complex problem of obesity.


From the Cover: The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake

Numerous clinical trials using folic acid for prevention of cardiovascular disease, stroke, cognitive decline, and neural tube defects have been completed or are underway. Yet, all functions of folate are performed by tetrahydrofolate and its one-carbon derivatives. Folic acid is a synthetic oxidized form not significantly found in fresh natural foods; to be used it must be converted to tetrahydrofolate by dihydrofolate reductase (DHFR). Increasing evidence suggests that this process may be slow in humans. Here we show, using a sensitive assay we developed, that the reduction of folic acid by DHFR per gram of human liver (n = 6) obtained from organ donors or directly from surgery is, on average, less than 2% of that in rat liver at physiological pH. Moreover, in contrast to rats, there was almost a 5-fold variation of DHFR activity among the human samples. This limited ability to activate the synthetic vitamer raises issues about clinical trials using high levels of folic acid. The extremely low rate of conversion of folic acid suggests that the benefit of its use in high doses will be limited by saturation of DHFR, especially in individuals possessing lower than average activity. These results are also consistent with the reports of unmetabolized folic acid in plasma and urine.


Non-anaemic pregnant women should not take iron supplements.

(1) Iron-deficiency anaemia during pregnancy increases the risk of low birth weight and preterm birth; (2) In a randomised double-blind placebo-controlled trial, iron supplementation in pregnant women with haemoglobin levels of at least 13.2 g/100 ml at the beginning of the 2nd trimester was associated with low birth weight and maternal hypertension; (3) In a trial in women with haemoglobin levels of at least 11.5 g/100 ml who took supplemental iron, haemoglobin levels above 14.5 g/100 ml at 28 weeks of gestation were associated with an 8-fold increase in the risk of preterm birth and a 6-fold increase in the risk of low birth weight; (4) An epidemiological study showed a link between high maternal haemoglobin levels and low birth weight; (5) In practice, iron supplements should not be taken by pregnant women whose haemoglobin levels exceed 11 g/100 ml during the 1st and 3rd trimesters and 10.5 g/100 ml during the 2nd trimester.


First trimester curtailment of iron absorption: innate suppression of a teratogen?

In human pregnancies, maternal absorption of iron is markedly curtailed in the first trimester. In a murine model, iron was teratogenic in the analogous embryonic period. Although iron is a weak mutagen, it is a powerful oxidant and a catalyst of formation of hydroxyl radicals. Studies are needed to determine if there might be an association of first trimester iron supplementation with miscarriage/fetal abnormalities.


Caffeine in pregnancy.

Caffeine is probably the most frequently ingested pharmacologically active substance in the world. It is found in common beverages (coffee, tea, soft drinks), in products containing cocoa or chocolate, and in medications. Because of its wide consumption at different levels by most segments of the population, the public and the scientific community have expressed interest in the potential for caffeine to produce adverse effects on human health. Reproductive-aged and pregnant women are 'at risk' subgroups of the population who may require specific advice on moderating their daily caffeine intake. This article highlights the implications of caffeine intake in pregnancy, reviews the latest evidence-based information available on this subject, and offers recommendations (practical advice) for the obstetrician-gynecologists proving peripartum care to these potentially complicated pregnancies.


Green tea consumption and mortality among Japanese elderly people: the prospective Shizuoka elderly cohort.

PURPOSE: To investigate the association between green tea consumption and mortality from all causes, cancer, and cardiovascular disease (CVD) among elderly people. METHODS: In a population-based, prospective cohort study, a total of 14,001 elderly residents (aged 65-84 years), randomly chosen from all 74 municipalities in Shizuoka, Japan, completed questionnaires that included items about frequency of green tea consumption. They were followed for up to 6 years, from December 1999 to March 2006. Consequently, 12,251 subjects were analyzed to estimate the hazard ratios (HRs) for all-cause mortality, cancer, and CVD. RESULTS: Among 64,002 person-years, 1,224 deaths were identified (follow-up rate, 71.6%). The multivariate HRs and 95% confidence intervals (CIs) for CVD mortality compared those who consumed seven or more cups per day with those who consumed less than one cup per day, were 0.24 (0.14-0.40), 0.30 (0.15-0.61), and 0.18 (0.08-0.40) for total participants, men, and women, respectively. Although green tea consumption was not inversely associated with cancer mortality, green tea consumption and colorectal cancer mortality were inversely associated with a moderate dose-response relationship. CONCLUSIONS: Green tea consumption is associated with reduced mortality from all causes and CVD. This study also suggests that green tea could have protective effects against colorectal cancer.


Laboratory, Epidemiological, and Human Intervention Studies Show That Tea (Camellia sinensis) May Be Useful in the Prevention of Obesity

Tea (Camellia sinensis, Theaceae) and tea polyphenols have been studied for the prevention of chronic diseases, including obesity. Obesity currently affects >20% of adults in the United States and is a risk factor for chronic diseases such as type II diabetes, cardiovascular disease, and cancer. Given this increasing public health concern, the use of dietary agents for the prevention of obesity would be of tremendous benefit. Whereas many laboratory studies have demonstrated the potential efficacy of green or black tea for the prevention of obesity, the underlying mechanisms remain unclear. The results of human intervention studies are mixed and the role of caffeine has not been clearly established. Finally, there is emerging evidence that high doses of tea polyphenols may have adverse side effects. Given that the results of scientific studies on dietary components, including tea polyphenols, are often translated into dietary supplements, understanding the potential toxicities of the tea polyphenols is critical to understanding their potential usefulness in preventing obesity. In this review, we will critically evaluate the evidence for the prevention of obesity by tea, discuss the relevance of proposed mechanisms in light of tea polyphenol bioavailability, and review the reports concerning the toxic effects of high doses of tea polyphenols and the implication that this has for the potential use of tea for the prevention of obesity. We hope that this review will expose areas for further study and encourage research on this important public health issue.


Green tea: nature's defense against malignancies.

The current practice of introducing phytochemicals to support the immune system or fight against diseases is based on centuries old traditions. Nutritional support is a recent advancement in the domain of diet-based therapies; green tea and its constituents are one of the important components of these strategies to prevent and cure various malignancies. The anti-carcinogenic and anti-mutagenic activities of green tea were highlighted some years ago suggesting that it could reduce the prevalence of cancer and even provide protection. The pharmacological actions of green tea are mainly attributed to polyphenols that includes epigallocatechin-3-gallate (EGCG), epicatechin, epicatechin-3-gallate, epigallocatechin. Green tea and its components effectively mitigate cellular damage arising due to oxidative stress. Green tea is supposed to enhance humoral and cell-mediated immunity, decreasing the risk of certain cancers, and may have certain advantage in treating inflammatory disorders. Much of the cancer chemopreventive properties of green tea are mediated by EGCG that induces apoptosis and promotes cell growth arrest, by altering the expression of cell cycle regulatory proteins, activating killer caspases, and suppressing nuclear factor kappa-B activation. Besides, it regulates and promotes IL-23 dependent DNA repair and stimulates cytotoxic T cells activities in a tumor microenvironment. It also blocks carcinogenesis by modulating the signal transduction pathways involved in cell proliferation, transformation, inflammation and metastasis. The review is intended to highlight the chemistry of green tea, its antioxidant potential, its immunopotentiating properties and mode of action against various cancer cell lines that showed its potential as a chemopreventive agent against colon, skin, lung, prostate, and breast cancer.


Inhibitory effect of tea polyphenols on local tissue damage induced by snake venoms.

The methanolic extract of fresh tea leaves of Camellia sinensis L. (Theaceae) (CS) was assayed for its potential to inhibit enzymes with hydrolytic activity in Naja naja kaouthia Lesson (Elapidae) and Calloselasma rhodostoma Kuhl (Viperidae) venoms. These snake venom enzymes are responsible for the early effects of envenomation, such as local tissue damage and inflammation. The CS extract inhibited phospholipase A(2), proteases, hyaluronidase and L-amino acid oxidase in both venoms by in vitro neutralization and inhibited the hemorrhagic and the dermonecrotic activities of the venoms in vivo. It is suggested that the inhibitory potential of the CS extract against local tissue damage induced by snake venoms may be attributed to complexation and chelation between the venom proteins and the phenolic contents of the extract.


Tea Consumption and Risk of Type 2 Diabetes: A Meta-Analysis of Cohort Studies

ABSTRACT BACKGROUND Tea consumption has been extensively studied in relation to various diseases, several epidemiologic studies have been performed to investigate the association of tea consumption with type 2 diabetes; however, the results of these studies were not entirely consistent. OBJECTIVE To conduct a meta-analysis of studies that assessed the association of tea consumption and the risk of type 2 diabetes. RESEARCH DESIGN AND METHODS We performed a systematic literature search through November 2008 in PUBMED, MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews. The search was limited to English-language studies. Studies were excluded if they were type 1 diabetes, animal studies. Nine cohort studies were identified by two authors, and summary relative risks (RRs) were calculated using a random-effects model. RESULTS We identified nine cohort studies, including 324,141 participants and 11,400 incident cases of type 2 diabetes with follow-up ranging from 5 to 18 years. The summary adjusted RR did not show that tea consumption was associated with a reduced type 2 diabetes risk (RR, 0.96; 95% confidence interval (CI), 0.92–1.01). Evidence from the results of our stratified analyses revealed that tea consumption ≥4 cups per day (RR, 0.8; 95% CI, 0.7–0.93) might play a role in the prevention of type 2 diabetes. However, no statistically significant association was observed for sex and the follow-up durations stratified between tea consumption and type 2 diabetes. CONCLUSIONS This meta-analysis indicates that tea consumption ≥4 cups per day may lower the risk of type 2 diabetes.


Association between green tea consumption and tooth loss: cross-sectional results from the Ohsaki Cohort 2006 Study.

OBJECTIVE: To examine the association between green tea consumption and tooth loss. METHODS: We analyzed cross-sectional data from the Ohsaki Cohort 2006 Study. Usable self-administered questionnaires about green tea consumption and tooth loss were returned from 25,078 persons (12,019 men and 13,059 women) aged 40 to 64 years in Japan. Multivariate logistic regression analysis was used to calculate odds ratios (ORs) for tooth loss using 3 cut-off points of 10, 20, and 25 teeth relative to each category of green tea consumption. RESULTS: Consumption of > or = 1 cup/day of green tea was significantly associated with decreased odds for tooth loss, and the association appeared to fit a threshold model. In men, the multivariate-adjusted ORs for tooth loss with a cut-off point of <20 teeth associated with different frequencies of green tea consumption were 1.00 (reference) for <1 cup/day, 0.82 (95% CI, 0.74-0.91) for 1-2 cups/day, 0.82 (95% CI, 0.73-0.92) for 3-4 cups/day, and 0.77 (95% CI, 0.66-0.89) for > or = 5 cups/day. The corresponding data for women and the results for cut-off points of 10 and 25 teeth were essentially the same. CONCLUSIONS: The present findings indicate an association of green tea consumption with decreased odds for tooth loss. Copyright 2010 Elsevier Inc. All rights reserved.


Survey of commercially available chocolate- and cocoa-containing products in the United States. 2. Comparison of flavan-3-ol content with nonfat co...

A survey of a broad range of chocolate- and cocoa-containing products marketed in the United States was conducted to provide a more detailed analysis of flavan-3-ol monomers, oligomers, and polymers, which can be grouped into a class of compounds called procyanidins. Samples consisted of the three or four top-selling products within the following six categories: natural cocoa powder, unsweetened baking chocolate, dark chocolate, semisweet baking chips, milk chocolate, and chocolate syrup. Composite samples were characterized for percent fat (% fat), percent nonfat cocoa solids (% NFCS), antioxidant level by ORAC, total polyphenols, epicatechin, catechin, total monomers, and flavan-3-ol oligomers and polymers (procyanidins). On a gram weight basis epicatechin and catechin content of the products follow in decreasing order: cocoa powder > baking chocolate > dark chocolate = baking chips > milk chocolate > chocolate syrup. Analysis of the monomer and oligomer profiles within product categories shows there are two types of profiles: (1) products that have high monomers with decreasing levels of oligomers and (2) products in which the level of dimers is equal to or greater than the monomers. Results show a strong correlation (R(2) = 0.834) of epicatechin to the level of % NFCS and also very good correlations for N = 2-5 oligomers to % NFCS. A weaker correlation was observed for catechin to % NFCS (R(2) = 0.680). Other analyses show a similar high degree of correlation with epicatechin and N = 2-5 oligomers to total polyphenols, with catechin being less well correlated to total polyphenols. A lesser but still good correlation exists between the calculated percent cacao (calcd % cacao) content, a proxy for percent cacao, and these same flavanol measures, with catechin again showing a lesser degree of correlation to calcd % cacao. Principal component analysis (PCA) shows that the products group discretely into five classes: (1) cocoa powder, (2) baking chocolate, (3) dark chocolate and semisweet chips, (4) milk chocolates, and (5) syrup. PCA also shows that most factors group closely together including the antioxidant activity, total polyphenols, and the flavan-3-ol measures with the exception of catechin and % fat in the product, which group separately. Because catechin distribution appears to be different from the other flavan-3-ol measures, an analysis of the epicatechin to catechin ratio was done, indicating there is a >5-fold variation in this measure across the products studied. The cocoa-containing products tested range from cocoa powder with 227.34 +/- 17.23 mg of procyanidins per serving to 25.75 +/- 9.91 mg of procyanidins per serving for chocolate syrup. These results are discussed with respect to other studies on commercial products, the bioavailability of the flavanols, and the possible role of processing on the amount of catechin in products.


Childhood soy intake and breast cancer risk in Asian American women.

INTRODUCTION: Historically, breast cancer incidence has been substantially higher in the United States than in Asia. When Asian women migrate to the United States, their breast cancer risk increases over several generations and approaches that for U.S. Whites. Thus, modifiable factors, such as diet, may be responsible. METHODS: In this population-based case-control study of breast cancer among women of Chinese, Japanese, and Filipino descent, ages 20 to 55 years, and living in San Francisco-Oakland (California), Los Angeles (California) and Oahu (Hawaii), we interviewed 597 cases (70% of those eligible) and 966 controls (75%) about adolescent and adult diet and cultural practices. For subjects with mothers living in the United States (39% of participants), we interviewed mothers of 99 cases (43% of eligible) and 156 controls (40%) about the daughter's childhood exposures. Seventy-three percent of study participants were premenopausal at diagnosis. RESULTS: Comparing highest with lowest tertiles, the multivariate relative risks (95% confidence interval) for childhood, adolescent, and adult soy intake were 0.40 (0.18-0.83; P(trend) = 0.03), 0.80 (0.59-1.08; P(trend) = 0.12), and 0.76 (0.56-1.02; P(trend) = 0.04), respectively. Inverse associations with childhood intake were noted in all three races, all three study sites, and women born in Asia and the United States. Adjustment for measures of westernization attenuated the associations with adolescent and adult soy intake but did not affect the inverse relationship with childhood soy intake. DISCUSSION: Soy intake during childhood, adolescence, and adult life was associated with decreased breast cancer risk, with the strongest, most consistent effect for childhood intake. Soy may be a hormonally related, early-life exposure that influences breast cancer incidence.


Soy Isoflavones and Risk of Cancer Recurrence in a Cohort of Breast Cancer Survivors: Life After Cancer Epidemiology (LACE) Study

Purpose Soy isoflavones, structurally similar to endogenous estrogens, may affect breast cancer through both hormonally-mediated and non-hormonally related mechanisms. Although the effects of soy are not well understood, some breast cancer survivors increase their soy intake post-diagnosis in attempt to improve their prognosis. Therefore, we examined the role of soy isoflavone intake and the risk of breast cancer recurrence by hormone receptor status, menopausal status, and tamoxifen therapy. Materials and methods A cohort of 1954 female breast cancer survivors, diagnosed during 1997–2000, was prospective followed for 6.31 years and 282 breast cancer recurrences were ascertained. Isoflavone intake was assessed by mailing modified Block and supplemental soy food frequency questionnaires to participants, on average 23 months post-diagnosis. Risk of breast cancer recurrence, measured by hazard ratios (HR) and 95% confidence intervals (CI), was estimated using multivariable delayed-entry Cox proportional hazards models. Results Suggestive trends for a reduced risk of cancer recurrence were observed with increasing quintiles of daidzein and glycetin intake compared to no intake among postmenopausal women (P for trend: P = .08 for daidzein, P = .06 for glycetin) and among tamoxifen users (P = .10 for daidzein, P = .05 for glycetin). Among postmenopausal women treated with tamoxifen, there was an approximately 60% reduction in breast cancer recurrence comparing the highest to the lowest daidzein intakes (>1453 micrograms (µg)/day versus < 7.7 µg/day) (HR, 0.48; 95% CI, 0.21–0.79, P = .008). Conclusion Soy isoflavones consumed at levels comparable to those in Asian populations may reduce the risk of cancer recurrence in women receiving tamoxifen therapy and moreover, appears not to interfere with tamoxifen efficacy. Further confirmation is required in other large prospective studies before recommendations regarding soy intake can be issued to breast cancer survivors.


Adolescent and adult soy food intake and breast cancer risk: results from the Shanghai Women's Health Study

Background: Soy food is a rich source of isoflavones—a class of phytoestrogens that has both antiestrogenic and anticarcinogenic properties. Objective: The objective was to evaluate the association of adolescent and adult soy food intake with breast cancer risk in a cohort of 73,223 Chinese women who participated in the Shanghai Women's Health Study. Design: A validated food-frequency questionnaire was used to assess usual dietary intake during adulthood and adolescence. After a mean follow-up of 7.4 y, 592 incident cases of breast cancer were identified for longitudinal analyses by using Cox regressions. Results: Adult soy food consumption, measured either by soy protein or isoflavone intake, was inversely associated with the risk of premenopausal breast cancer, and the association was highly statistically significant (P for trend < 0.001). The multivariate-adjusted relative risks (RRs) for the upper intake quintile compared with the lowest quintile were 0.41 (95% CI: 0.25, 0.70) for soy protein intake and 0.44 (95% CI: 0.26, 0.73) for isoflavone intake. High intake of soy foods during adolescence was also associated with a reduced risk of premenopausal breast cancer (RR: 0.57; 95% CI: 0.34, 0.97). Women who consumed a high amount of soy foods consistently during adolescence and adulthood had a substantially reduced risk of breast cancer. No significant association with soy food consumption was found for postmenopausal breast cancer. Conclusion: This large, population-based, prospective cohort study provides strong evidence of a protective effect of soy food intake against premenopausal breast cancer.


Intensity and timing of physical activity in relation to postmenopausal breast cancer risk: the prospective NIH-AARP Diet and Health Study

Background Despite strong evidence of an inverse association of physical activity with postmenopausal breast cancer risk, whether a certain intensity or time of life of physical activity is most effective for lowering breast cancer risk is not known. Methods In 118,899 postmenopausal women in the prospective NIH-AARP Diet and Health Study, we examined the relations of light and moderate-to-vigorous intensity physical activity during four periods of life ("historical": ages 15-18, 19-29, 35-39 years; "recent": past 10 years) to postmenopausal breast cancer risk. Physical activity was assessed by self-report at baseline, and 4287 incident breast cancers were identified over 6.6 years of follow-up. Results In age-adjusted and multivariate Cox regression models, >7 hours/week of moderate-to-vigorous activity during the past 10 years was associated with 16% reduced risk of postmenopausal breast cancer (RR:0.84; 95%CI:0.76,0.93) compared with inactivity. The association remained statistically significant after adjustment for BMI (RR:0.87; 95%CI:0.78,0.96). Neither moderate-to-vigorous activity during other periods of life nor light intensity activity during any period of life was related to breast cancer risk, and associations did not vary by tumor characteristics. Conclusion A high level of recent, but not historical, physical activity of moderate-to-vigorous intensity is associated with reduced postmenopausal breast cancer risk. More precise recall of recent physical activity than activity in the distant past is one possible explanation for our findings.


Effects of Aerobic Exercise on Mild Cognitive Impairment

Objectives To examine the effects of aerobic exercise on cognition and other biomarkers associated with Alzheimer disease pathology for older adults with mild cognitive impairment, and assess the role of sex as a predictor of response. Design Six-month, randomized, controlled, clinical trial. Setting Veterans Affairs Puget Sound Health Care System clinical research unit. Participants Thirty-three adults (17 women) with amnestic mild cognitive impairment ranging in age from 55 to 85 years (mean age,70 years). Intervention Participants were randomized either to a high-intensity aerobic exercise or stretching control group. The aerobic group exercised under the supervision of a fitness trainer at 75% to 85% of heart rate reserve for 45 to 60 min/d, 4 d/wk for 6 months. The control group carried out supervised stretching activities according to the same schedule but maintained their heart rate at or below 50% of their heart rate reserve. Before and after the study, glucometabolic and treadmill tests were performed and fat distribution was assessed using dual-energy x-ray absorptiometry. At baseline, month 3, and month 6, blood was collected for assay and cognitive tests were administered. Main Outcome Measures Performance measures on Symbol-Digit Modalities, Verbal Fluency, Stroop, Trails B, Task Switching, Story Recall, and List Learning. Fasting plasma levels of insulin, cortisol, brain-derived neurotrophic factor, insulinlike growth factor-I, and β-amyloids 40 and 42. Results Six months of high-intensity aerobic exercise had sex-specific effects on cognition, glucose metabolism, and hypothalamic-pituitary-adrenal axis and trophic activity despite comparable gains in cardiorespiratory fitness and body fat reduction. For women, aerobic exercise improved performance on multiple tests of executive function, increased glucose disposal during the metabolic clamp, and reduced fasting plasma levels of insulin, cortisol, and brain-derived neurotrophic factor. For men, aerobic exercise increased plasma levels of insulinlike growth factor I and had a favorable effect only on Trails B performance. Conclusions This study provides support, using rigorous controlled methodology, for a potent nonpharma-cologic intervention that improves executive control processes for older women at high risk of cognitive decline. Moreover, our results suggest that a sex bias in cognitive response may relate to sex-based differences in glucometabolic and hypothalamic-pituitary-adrenal axis responses to aerobic exercise.


The risks of copper toxicity contributing to cognitive decline in the aging population and to Alzheimer's disease.

It is a pleasure and an honor to contribute a paper to a special issue of the Journal of the American College of Nutrition honoring Stanley Wallach and Pearl Small. In this brief review I advance the hypothesis that copper toxicity is the major cause of the epidemic of mild cognitive impairment and Alzheimer's disease engulfing our aging population. This epidemic is recent, exploding in the last 50-60 years. The disease was virtually unknown 100 years ago. And it involves only developed countries that use copper plumbing. Something in our environment associated with development is poisoning the minds of our aged. The epidemic is associated with the use of copper plumbing, and the taking of copper in multi-mineral supplements. Food copper (organic copper) is processed by the liver and is transported and sequestered in a safe manner. Inorganic copper, such as that in drinking water and copper supplements, largely bypasses the liver and enters the free copper pool of the blood directly. This copper is potentially toxic because it may penetrate the blood/brain barrier. I review a web of animal and human data that tightens the noose around the hypothesis that copper toxicity is causing the epidemic of Alzeimer's disease and loss of cognition in our aging population.


Bovine spongiform encephalopathy and aquaculture.

Dietary consumption of fish is widely recommended because of the beneficial effects of omega-3 polyunsaturated fatty acids on the risks of cardiovascular and Alzheimer's diseases. The American Heart Association currently recommends eating at least two servings of fish per week. We are concerned that consumption of farmed fish may provide a means of transmission of infectious prions from cows with bovine spongiform encephalopathy to humans, causing variant Creutzfeldt Jakob disease.


Evaluation of the Possible Transmission of BSE and Scrapie to Gilthead Sea Bream (Sparus aurata)

In transmissible spongiform encephalopathies (TSEs), a group of fatal neurodegenerative disorders affecting many species, the key event in disease pathogenesis is the accumulation of an abnormal conformational isoform (PrPSc) of the host-encoded cellular prion protein (PrPC). While the precise mechanism of the PrPC to PrPSc conversion is not understood, it is clear that host PrPC expression is a prerequisite for effective infectious prion propagation. Although there have been many studies on TSEs in mammalian species, little is known about TSE pathogenesis in fish. Here we show that while gilthead sea bream (Sparus aurata) orally challenged with brain homogenates prepared either from a BSE infected cow or from scrapie infected sheep developed no clinical prion disease, the brains of TSE-fed fish sampled two years after challenge did show signs of neurodegeneration and accumulation of deposits that reacted positively with antibodies raised against sea bream PrP. The control groups, fed with brains from uninfected animals, showed no such signs. Remarkably, the deposits developed much more rapidly and extensively in fish inoculated with BSE-infected material than in the ones challenged with the scrapie-infected brain homogenate, with numerous deposits being proteinase K-resistant. These plaque-like aggregates exhibited congophilia and birefringence in polarized light, consistent with an amyloid-like component. The neurodegeneration and abnormal deposition in the brains of fish challenged with prion, especially BSE, raises concerns about the potential risk to public health. As fish aquaculture is an economically important industry providing high protein nutrition for humans and other mammalian species, the prospect of farmed fish being contaminated with infectious mammalian PrPSc, or of a prion disease developing in farmed fish is alarming and requires further evaluation.


Community-acquired methicillin-resistant Staphylococcus aureus: what do we need to know?

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a matter of concern worldwide, in particular in the USA. For the analysis of emergence and spread, clear definitions based on epidemiological origin are needed for discrimination between CA-MRSA, healthcare-associated community MRSA, and healthcare-associated MRSA (HA-MRSA). Although its role in pathogenesis is currently under debate, the capability for Panton-Valentine leukocidin formation is associated with the majority of CA-MRSA isolates from North America and from Europe. Most CA-MRSA isolates are attributed to clonal lineages different from HA-MRSA; there are, however, clonal lineages from which both HA-MRSA and CA-MRSA have been reported (e.g. ST1, ST5, ST8, and ST22); CA-MRSA ST8 (USA300), which is most frequent in the USA, has meanwhile been reported from Europe. CA-MRSA ST80 is widely disseminated in Europe; because of its pronounced oxacillin heteroresistance phenotype, cefoxitin-based assays are advisable for reliable detection. So far, CA-MRSA infections seem to be much less frequent in Europe than in the USA, where patients with particular predispositions and low social status are at especial risk.


Increasing incidence of community-associated atypical Clostridium difficile disease in children.

Forty-one children with a variety of gastrointestinal complaints were diagnosed with Clostridium difficile infections as part of a routine screen over 3 years. The infection had not been suspected prior to the screen. Each child responded to treatment with metronidazole with resolution of their symptoms. These data suggest that community-associated C difficile is increasing and may produce atypical disease and lead to misdiagnosis.


Clostridium difficile in food--innocent bystander or serious threat?

Clostridium difficile is a critically important cause of disease in humans, particularly in hospitalized individuals. Three major factors have raised concern about the potential for this pathogen to be a cause of foodborne disease: the increasing recognition of community-associated C. difficile infection, recent studies identifying C. difficile in food animals and food, and similarities in C. difficile isolates from animals, food and humans. It is clear that C. difficile can be commonly found in food animals and food in many regions, and that strains important in human infections, such as ribotype 027/NAP1/toxinotype III and ribotype 078/toxinotype V, are often present. However, it is currently unclear whether ingestion of contaminated food can result in colonization or infection. Many questions remain unanswered regarding the role of C. difficile in community-associated diarrhoea: its source when it is a food contaminant, the infective dose, and the association between ingestion of contaminated food and disease. The significant role of this pathogen in human disease and its potential emergence as an important community-associated pathogen indicate that careful evaluation of different sources of exposure, including food, is required, but determination of the potential role of food in C. difficile infection may be difficult.


Varied prevalence of Clostridium difficile in an integrated swine operation.

The objectives of this study were to compare the prevalence of Clostridium difficile (Cd) among different age and production groups of swine in a vertically integrated swine operation in Texas in 2006 and to compare our isolates to other animal and human isolates. Results are based on 131 Cd isolates from 1008 swine fecal samples and pork trim samples (overall prevalence of 13%). The prevalence (number positive/number tested in production type) of Cd was different between the groups (P<or=0.001), and was highest among suckling piglets at 50.0% (61/122), followed by 23.8% (34/143) for lactating sows and effluent from the farrowing barn, 8.4% (10/119) for nursery, 6.5% (4/62) for pork products, 3.9% (15/382) for grower-finisher, and 3.9% (7/180) for breeding boars and sows. Of the 131 isolates, 122 were positive by PCR for both toxins A (tcdA) and B (tcdB) genes, 129 isolates harbored a 39 base pair deletion in the tcdC gene, 120 isolates were toxinotype V, and all 131 of the isolates were positive for the binary toxin gene cdtB. All isolates were resistant to cefoxitin, ciprofloxacin, and imipenem, whereas all were sensitive to metronidazole, piperacillin/tazobactam, amoxicillin/clavulanic acid, and vancomycin. The majority of isolates were resistant to clindamycin; resistant or intermediate to ampicillin; and sensitive to tetracycline and chloramphenicol. There was an increased (P</=0.001) number of isolates for the timeframe of September to February compared to March to August.


Efficacy of cleaning products for C difficile

OBJECTIVE To review the evidence for the efficacy of products used for environmental or hand cleaning on the rates of Clostridium difficile–associated diarrhea (CDAD). QUALITY OF EVIDENCE MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched for articles pertinent to the efficacy of cleaning products against C difficile or studies with outcomes related to rates of CDAD. Evidence was level II. MAIN MESSAGE Minimizing the incidence of CDAD in geriatric rehabilitation units is essential to achieving the goals of increasing patient function and independence for discharge into the community. Attention to environmental control of C difficile and its spores by health care workers and patient visitors is an important secondary prevention strategy. CONCLUSION Chlorine-releasing agents are more effective than detergents for killing spores produced by C difficile. No level I evidence is available to determine if the use of chlorine-releasing agents has an effect on rates of CDAD. Hand-washing is currently the recommended strategy for reducing transmission of C difficile. Alcohol gels do not inactivate C difficile spores; however, increased use of alcohol hand gel has not been associated with higher rates of CDAD. Résumé OBJECTIF Examiner les preuves indiquant que les produits utilisés pour nettoyer l’environnement et les mains sont efficaces pour réduire le taux de diarrhée due au Clostridium difficile (DDCD). QUALITÉ DES PREUVES On a consulté MEDLINE, EMBASE et la Cochrane Database of Systematic Reviews en retenant les articles portant sur l’efficacité des agents de nettoyage contre le C difficile ou les études traitant de questions liées aux taux de DDCD. Les preuves étaient de niveau II. PRINCIPAL MESSAGE La réduction de l’incidence de la DDCD dans les unités de réadaptation gériatrique est une condition essentielle pour accroître l’état fonctionnel et l’indépendance des patients qui retournent dans la communauté. Pour les intervenants et pour les visiteurs des patients, le contrôle du C difficile et de ses spores dans l’environnement est primordial comme stratégie de prévention secondaire. Les agents qui libèrent du chlore sont plus efficaces que les détergents pour tuer les spores du C difficile. Il n’existe pas de preuves de niveau I indiquant que l’utilisation d’agents libérant du chlore influence les taux de DDCD. Le lavage des mains est la stratégie présentement recommandée pour réduire la transmission du C difficile. Les gels d’alcool n’inactivent pas les spores du C difficile; toutefois, une utilisation accrue de gels d’alcool n’a pas entraîné d’augmentation du taux de DDCD.


Clostridium difficile in Retail Meat Products, USA, 2007

To determine the presence of Clostridium difficile, we sampled cooked and uncooked meat products sold in Tucson, Arizona. Forty-two percent contained toxigenic C. difficile strains (either ribotype 078/toxinotype V [73%] or 027/toxinotype III [NAP1 or NAP1-related; 27%]). These findings indicate that food products may play a role in interspecies C. difficile transmission.


Detection and characterization of Clostridium difficile in retail chicken.

AIMS: This study was designed to evaluate the prevalence of Clostridium difficile contamination of retail chicken. METHODS AND RESULTS: Chicken legs, thighs and wings were purchased using a standardized method from retail outlets across Ontario, Canada. Selective culture was used for qualitative and quantitative detection of C. difficile. Clostridium difficile was isolated from 26/203 (12.8%) chicken samples; 10/111 (9.0%) thighs, 13/72 (18%) wings and 3/20 (15%) legs (P = 0.19). All isolates were ribotype 078, a strain that has been associated with food animals and potentially community-associated disease in humans. All positive samples were positive only on enrichment culture. CONCLUSIONS: Clostridium difficile could be found relatively commonly in retail chicken meat, albeit at low levels. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to report C. difficile in chicken meat. Contamination of meat with C. difficile strains implicated in human infections raises concerns about food as a source of C. difficile infection. The relevance of food contamination is completely unclear at this point but food should be investigated as a source of infection.


Methicillin-resistant Staphylococcus aureus (MRSA) in food production animals.

Until recently, reports on methicillin-resistant Staphylococcus aureus (MRSA) in food production animals were mainly limited to occasional detections in dairy cattle mastitis. However, since 2005 a MRSA clone, CC398, has been reported colonizing pigs, veal calves and broiler chickens and infecting dairy cows. Many aspects of its prevalence in pigs remain unclear. In other livestock, colonizing capacity and reservoir status still require elucidation. MRSA CC398 has also been detected in meat, but, as for other MRSA, the risk this poses is somewhat unclear. Currently, the most worrying aspect of MRSA CC398 appears to be its capacity to spread to humans. This might complicate MRSA control measures in human healthcare, urging research into risk factors and transmission routes. Although infections with MRSA CC398 are much less reported than carriage, more investigation into its pathogenic potential is required. Moreover, the origin and evolution of this clone remain unknown.


Methicillin-Resistant Staphylococcus aureus (MRSA) Strain ST398 Is Present in Midwestern U.S. Swine and Swine Workers

Background Recent research has demonstrated that many swine and swine farmers in the Netherlands and Canada are colonized with MRSA. However, no studies to date have investigated carriage of MRSA among swine and swine farmers in the United States (U.S.). Methods We sampled the nares of 299 swine and 20 workers from two different production systems in Iowa and Illinois, comprising approximately 87,000 live animals. MRSA isolates were typed by pulsed field gel electrophoresis (PFGE) using SmaI and EagI restriction enzymes, and by multi locus sequence typing (MLST). PCR was used to determine SCCmec type and presence of the pvl gene. Results In this pilot study, overall MRSA prevalence in swine was 49% (147/299) and 45% (9/20) in workers. The prevalence of MRSA carriage among production system A's swine varied by age, ranging from 36% (11/30) in adult swine to 100% (60/60) of animals aged 9 and 12 weeks. The prevalence among production system A's workers was 64% (9/14). MRSA was not isolated from production system B's swine or workers. Isolates examined were not typeable by PFGE when SmaI was used, but digestion with EagI revealed that the isolates were clonal and were not related to common human types in Iowa (USA100, USA300, and USA400). MLST documented that the isolates were ST398. Conclusions These results show that colonization of swine by MRSA was very common on one swine production system in the midwestern U.S., suggesting that agricultural animals could become an important reservoir for this bacterium. MRSA strain ST398 was the only strain documented on this farm. Further studies are examining carriage rates on additional farms.


Isolation and Characterization of Methicillin-Resistant Staphylococcus aureus Strains from Louisiana Retail Meats

We investigated the prevalence of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) in 120 retail meat samples from 30 grocery stores in Baton Rouge, LA. S. aureus strains were recovered from 45.6% of pork samples and 20% of beef samples, whereas MRSA strains were isolated from six meat samples (five pork samples and one beef sample). The MRSA isolates were of two strain types (clones), one harboring Panton-Valentine leucocidin and belonging to pulsed-field gel electrophoresis type USA300 and the other one belonging to USA100.


Effectiveness of alcohol-based hand rubs for removal of Clostridium difficile spores from hands.

BACKGROUND: Alcohol-based hand rubs (ABHRs) are an effective means of decreasing the transmission of bacterial pathogens. Alcohol is not effective against Clostridium difficile spores. We examined the retention of C. difficile spores on the hands of volunteers after ABHR use and the subsequent transfer of these spores through physical contact. METHODS: Nontoxigenic C. difficile spores were spread on the bare palms of 10 volunteers. Use of 3 ABHRs and chlorhexidine soap-and-water washing were compared with plain water rubbing alone for removal of C. difficile spores. Palmar cultures were performed before and after hand decontamination by means of a plate stamping method. Transferability of C. difficile after application of ABHR was tested by having each volunteer shake hands with an uninoculated volunteer. RESULTS: Plain water rubbing reduced palmar culture counts by a mean (+/- standard deviation [SD]) of 1.57 +/- 0.11 log10 colony-forming units (CFU) per cm2, and this value was set as the zero point for the other products. Compared with water washing, chlorhexidine soap washing reduced spore counts by a mean (+/- SD) of 0.89 +/- 0.34 log10 CFU per cm2; among the ABHRs, Isagel accounted for a reduction of 0.11 +/- 0.20 log10 CFU per cm2 (P = .005), Endure for a reduction of 0.37 +/- 0.42 log10 CFU per cm2 (P = .010), and Purell for a reduction of 0.14 +/- 0.33 log10 CFU per cm2 (P = .005). There were no statistically significant differences between the reductions achieved by the ABHRs; only Endure had a reduction statistically different from that for water control rubbing (P = .040). After ABHR use, handshaking transferred a mean of 30% of the residual C. difficile spores to the hands of recipients. CONCLUSIONS: Hand washing with soap and water is significantly more effective at removing C. difficile spores from the hands of volunteers than are ABHRs. Residual spores are readily transferred by a handshake after use of ABHR.


Risk factors associated with colibacillosis outbreaks in caged layer flocks.

Colibacillosis appears to be of increasing significance in layer flocks, but there have been no studies of the risk factors associated with outbreaks. This study aimed to investigate the possible associations between risk factors of non-infectious nature and outbreaks of mortality due to colibacillosis in flocks of caged layer hens. Information on management, biosecurity measures and housing conditions was collected in 20 flocks suffering from the disease and in 20 clinically healthy control flocks. The data were processed using multiple logistic regression. The statistical analysis demonstrated that an increase in the distance to the nearest poultry farm by 1 km was associated with a six-fold decreased risk of an outbreak of colibacillosis (odds ratio=0.16). Furthermore, a 1 l increase in cage volume per hen was associated with a 33% decrease in the risk of an outbreak (odds ratio=0.75). It was concluded that the distance between poultry farms and the hen density in the cages are important risk factors for outbreaks of colibacillosis in flocks of layer hens.


Medical and economic impact of extraintestinal infections due to Escherichia coli: focus on an increasingly important endemic problem.

Escherichia coli is probably the best-known bacterial species and one of the most frequently isolated organisms from clinical specimens. Despite this, underappreciation and misunderstandings exist among medical professionals and the lay public alike regarding E. coli as an extraintestinal pathogen. Underappreciated features include (i) the wide variety of extraintestinal infections E. coli can cause, (ii) the high incidence and associated morbidity, mortality, and costs of these diverse clinical syndromes, (iii) the pathogenic potential of different groups of E. coli strains for causing intestinal versus extraintestinal disease, and (iv) increasing antimicrobial resistance. In this era in which health news often sensationalizes uncommon infection syndromes or pathogens, the strains of E. coli that cause extraintestinal infection are an increasingly important endemic problem and underappreciated "killers". Billions of health care dollars, millions of work days, and hundreds of thousands of lives are lost each year to extraintestinal infections due to E. coli. New treatments and prevention measures will be needed for improved outcomes and a diminished disease burden.


Presence and Characterization of Shiga Toxin-Producing Escherichia coli and Other Potentially Diarrheagenic E. coli Strains in Retail Meats

To determine the presence of Shiga toxin-producing Escherichia coli (STEC) and other potentially diarrheagenic E. coli strains in retail meats, 7,258 E. coli isolates collected by the U.S. National Antimicrobial Resistance Monitoring System (NARMS) retail meat program from 2002 to 2007 were screened for Shiga toxin genes. In addition, 1,275 of the E. coli isolates recovered in 2006 were examined for virulence genes specific for other diarrheagenic E. coli strains. Seventeen isolates (16 from ground beef and 1 from a pork chop) were positive for stx genes, including 5 positive for both stx1 and stx2, 2 positive for stx1, and 10 positive for stx2. The 17 STEC strains belonged to 10 serotypes: O83:H8, O8:H16, O15:H16, O15:H17, O88:H38, ONT:H51, ONT:H2, ONT:H10, ONT:H7, and ONT:H46. None of the STEC isolates contained eae, whereas seven carried enterohemorrhagic E. coli (EHEC) hlyA. All except one STEC isolate exhibited toxic effects on Vero cells. DNA sequence analysis showed that the stx2 genes from five STEC isolates encoded mucus-activatable Stx2d. Subtyping of the 17 STEC isolates by pulsed-field gel electrophoresis (PFGE) yielded 14 distinct restriction patterns. Among the 1,275 isolates from 2006, 11 atypical enteropathogenic E. coli (EPEC) isolates were identified in addition to 3 STEC isolates. This study demonstrated that retail meats, mainly ground beef, were contaminated with diverse STEC strains. The presence of atypical EPEC strains in retail meat is also of concern due to their potential to cause human infections.


Antimicrobial-resistant and extraintestinal pathogenic Escherichia coli in retail foods.

BACKGROUND: Extraintestinal Escherichia coli infections are associated with specialized extraintestinal pathogenic E. coli (ExPEC) strains and, increasingly, with antimicrobial resistance. The food supply may disseminate ExPEC and antimicrobial-resistant E. coli. METHODS: In a prospective survey of 1648 diverse food items from 10 retail markets in the Minneapolis-St. Paul area during 2001-2003, selective cultures and disk-diffusion assays for the isolation and characterization of antimicrobial-resistant E. coli and polymerase chain reaction-based assays and O serotyping to define ExPEC-associated traits were performed. RESULTS: E. coli contamination exhibited a prevalence gradient from miscellaneous foods (9%), through beef or pork (69%), to poultry (92%; P<.001). Among E. coli-positive samples, similar prevalence gradients were detected for antimicrobial resistance (27%, 85%, and 94% of samples, respectively; P<.001) and ExPEC contamination (4%, 19%, and 46%, respectively; P<.001). By multivariate analysis, beef or pork and poultry from natural-food stores exhibited reduced risks of E. coli contamination and antimicrobial resistance. Indirect evidence suggested on-farm selection of resistance. Four food-source ExPEC isolates (from pea pods, turkey parts, ground pork, and vegetable dip) closely resembled selected human clinical isolates by O antigen and genomic profile. CONCLUSIONS: Retail foods may be an important vehicle for community-wide dissemination of antimicrobial-resistant E. coli and ExPEC, which may represent a newly recognized group of medically significant foodborne pathogens.


Food Reservoir for Escherichia coli Causing Urinary Tract Infections

Closely related strains of Escherichia coli have been shown to cause extraintestinal infections in unrelated persons. This study tests whether a food reservoir may exist for these E. coli. Isolates from 3 sources over the same time period (2005–2007) and geographic area were compared. The sources comprised prospectively collected E. coli isolates from women with urinary tract infection (UTI) (n = 353); retail meat (n = 417); and restaurant/ready-to-eat foods (n = 74). E. coli were evaluated for antimicrobial drug susceptibility and O:H serotype and compared by using 4 different genotyping methods. We identified 17 clonal groups that contained E. coli isolates (n = 72) from >1 source. E. coli from retail chicken (O25:H4-ST131 and O114:H4-ST117) and honeydew melon (O2:H7-ST95) were indistinguishable from or closely related to E. coli from human UTIs. This study provides strong support for the role of food reservoirs or foodborne transmission in the dissemination of E. coli causing common community-acquired UTIs.


Bowel function measurements of individuals with different eating patterns.

Bowel function was assessed in 51 subjects: 10 women and seven men who habitually consumed an omnivorous, vegetarian, or vegan diet. The subjects on these diets had a mean intake of fibre of 23 g, 37 g, and 47 g respectively. Mean transit times were variable and not significantly different between the groups. Vegans, however, had a greater frequency of defecation and passed softer stools. All measurements of bowel function were significantly correlated with total dietary fibre. As dietary fibre increased mean transit time decreased, stool frequency increased and the stools became softer. Men produced a greater quantity of softer, less formed faeces than women. During the luteal phase of the menstrual cycle women excreted harder stools and had a significantly longer mean transit time. The finding that mean transit time was more highly correlated with faecal form than any of the other bowel function measurements could be of practical importance.


Fish-induced keriorrhea.

Many deep-sea fishes store large amounts of wax esters in their body for buoyancy control. Some of them are frequently caught as by-catch of tuna and other fishes. The most noteworthy ones include escolar and oilfish. The accumulation of the indigestible wax esters in the rectum through consumption of these fish engenders discharges or leakage per rectum as orange or brownish green oil, but without noticeable loss of water. This physiological response is called keriorrhea, which is variously described as "oily diarrhea," "oily orange diarrhea," or "orange oily leakage" by the mass media and bloggers on the internet. Outbreaks of keriorrhea have been repeatedly reported across continents. Additional symptoms including nausea, vomiting, abdominal cramps, and diarrhea were complained by the victims. They are probably due to anxiety or panic when suffering from keriorrhea. Escolar and oilfish are banned from import and sale in Italy, Japan, and South Korea. Rapid detection of the two fishes is imperative to ensure proper labeling and safeguarding of the public before and after any keriorrhea outbreak.


Much meat, much malady: changing perceptions of the epidemiology of hepatitis E.

Hepatitis E, which is caused by hepatitis E virus (HEV), may now be considered a zoonosis as well as an anthroponosis. Pigs, boars and deer have been identified as reservoirs, and their flesh and entrails--as meat and offal--as vehicles of HEV transmission. Shellfish also act as vehicles. Dietary, gastronomic and culinary preferences influence how extensively HEV conveyed by these vehicles can be inactivated before their ingestion by the host. Another route of infection is paved by HEV that is enterically shed by humans and by live animals into the environment. Although anthroponotic transmission of HEV is primarily environmental, zoonotic transmission may proceed along both foodborne and environmental routes.


Detection and characterization of infectious Hepatitis E virus from commercial pig livers sold in local grocery stores in the USA.

Hepatitis E virus (HEV) is a zoonotic pathogen of which pigs are reservoirs. To determine the presence of HEV RNA in commercial pig livers sold in local grocery stores in the USA, 127 packages of commercial pig liver were purchased and tested by a universal RT-PCR assay capable of detecting all four known HEV genotypes. Among the 127 livers tested, 14 were positive for HEV RNA. Sequence and phylogenetic analyses revealed that the 14 isolates all belonged to genotype 3. An animal study was subsequently conducted in pigs to determine whether the PCR-positive pig livers still contained infectious virus. The results showed that pigs inoculated with two of the three PCR-positive pig-liver homogenates became infected, as evidenced by the detection of faecal virus shedding, viraemia and seroconversion. The data demonstrated that commercial pig livers sold in grocery stores are contaminated by HEV and that the contaminating virus remains infectious, thus raising a public-health concern for food-borne HEV infection.


National mortality rates from chronic liver disease and consumption of alcohol and pig meat.

A correlation between national pig-meat consumption and mortality rates from chronic liver disease (CLD) across developed countries was reported in 1985. One possible mechanism explaining this may be hepatitis E infection spread via pig meat. We aimed to re-examine the original association in more recent international data. Regression models were used to estimate associations between national pig-meat consumption and CLD mortality, adjusting for confounders. Data on CLD mortality, alcohol consumption, hepatitis B virus (HBV) and hepatitis C virus (HCV) seroprevalence for 18 developed countries (1990-2000) were obtained from WHO databases. Data on national pig-meat and beef consumption were obtained from the UN database. Univariate regression showed that alcohol and pig-meat consumption were associated with mortality from CLD, but beef consumption, HBV and HCV seroprevalence were not. A 1 litre per capita increase in alcohol consumption was associated with an increase in mortality from CLD in excess of 1.6 deaths/100,000 population. A 10 kg higher national annual average per capita consumption of pork meat was associated with an increase in mortality from CLD of between 4 and 5 deaths/100,000 population. Multivariate regression showed that alcohol, pig-meat consumption and HBV seroprevalence were independently associated with mortality from CLD, but HCV seroprevalence was not. Pig-meat consumption remained independently associated with mortality from CLD in developed countries in the 1990-2000 period. Further work is needed to establish the mechanism.


Hepatitis E virus load in swine organs and tissues at slaughterhouse determined by real-time RT-PCR.

Although uncommon in North America, Hepatitis E virus (HEV) has been identified in some industrialized countries in patients without a history of travel to HEV-endemic countries. Its presence is ubiquitous worldwide in swine populations. Zoonotic transmission of swine HEV to non human primates has been achieved experimentally and transmission of HEV after ingestion of contaminated raw or undercooked meat is well documented. In Canada, so far, no HEV outbreak has been documented but HEV genotype 3 strains have been identified in sera and faecal samples of swine origin. The objective of the present study was to determine the viral load of HEV in liver, loin, bladder, hepatic lymph node, bile, tonsil, plasma and faeces samples of 43 pigs at slaughter. Feline calicivirus (FCV) was used as sample process control to validate the RNA extraction process, as a confirmation of the absence of sample inhibitors and as an amplification control. Using FCV/HEV multiplex TaqMan RT-qPCR system, HEV RNA was detected in 14 out of the 43 animals tested. HEV was detected in lymph nodes (11/43), bladder (10/43), liver (9/43), bile (8/43), faeces (6/43), tonsils (3/43), plasma (1/43) samples from infected animals. No HEV-positive loin samples were observed. Viral loads of 10(3) to 10(7) copies/g were estimated in positive liver and bile samples. Crown Copyright 2010. Published by Elsevier B.V. All rights reserved.


Thermal stability of hepatitis E virus.

The thermal stability of virulent hepatitis E virus (HEV) and hepatitis A virus (HAV) was compared. Fecal suspensions of virus were heated to temperatures between 45 degrees C and 70 degrees C, and residual infectivity was determined in a cell culture system that was permissive for both viruses. Although HEV was less stable than was HAV, some HEV would most likely survive the internal temperatures of rare-cooked meat.


Sporadic acute or fulminant hepatitis E in Hokkaido, Japan, may be food-borne, as suggested by the presence of hepatitis E virus in pig liver as food.

Among ten patients who contracted sporadic acute or fulminant hepatitis E between 2001 and 2002 in Hokkaido, Japan, nine (90 %) had a history of consuming grilled or undercooked pig liver 2-8 weeks before the disease onset. We tested packages of raw pig liver sold in grocery stores as food in Hokkaido for the presence of hepatitis E virus (HEV) RNA by RT-PCR. Pig liver specimens from seven (1.9 %) of 363 packages had detectable HEV RNA. Partial sequence analyses revealed that the seven swine HEV isolates belonged to genotype III or IV. One swine HEV isolate (swJL145) from a packaged pig liver had 100 % identity with the HE-JA18 isolate recovered from an 86-year-old patient in Hokkaido. Two swine HEV isolates (swJL234 and swJL325) had 98.5-100 % identity with the HE-JA4 isolate obtained from a 44-year-old patient in Hokkaido. These results indicate that inadequately cooked pig liver may transmit HEV to humans.


Pork intake and human papillomavirus-related disease.

Clinical and ecological evidence supporting an association between human papillomavirus (HPV)-related tumors and dietary factors are presented. Abstinence from high intake of fried pork (600-1,000 g/day) was associated with regression of an urethral condyloma in a healthy 19-year-old man treated with interferon gamma. International correlations suggest that pork intake is positively associated with incidence of cervical cancer, a disease also related to HPV. Pork meat or dietary factors associated with pork meat consumption may be involved in the development of HPV-related diseases.


Mortality from malignant diseases-update of the Baltimore union poultry cohort.

We previously studied mortality up to 1989 in 2,639 members of a local union who had ever worked in poultry slaughtering and processing plants, because they were exposed to oncogenic viruses present in poultry. In this report, cancer mortality was updated to the year 2003 for 2,580 of the 2,639 subjects who worked exclusively in poultry plants. Mortality in poultry workers was compared with that in the US general population through the estimation of proportional mortality and standardized mortality ratios separately for each race/sex group and for the whole cohort. Compared to the US general population, an excess of cancers of the buccal and nasal cavities and pharynx (base of the tongue, palate and other unspecified mouth, tonsil and oropharynx, nasal cavity/middle ear/accessory sinus), esophagus, recto-sigmoid/rectum/anus, liver and intrabiliary system, myelofibrosis, lymphoid leukemia and multiple myeloma was observed in particular subgroups or in the entire poultry cohort. We hypothesize that oncogenic viruses present in poultry, and exposure to fumes, are candidates for an etiologic role to explain the excess occurrence of at least some of these cancers in the poultry workers. Larger studies which can control for confounding factors are urgently needed to determine the significance of these findings.


Cancer incidence in British vegetarians

Background: Few prospective studies have examined cancer incidence among vegetarians. Methods: We studied 61 566 British men and women, comprising 32 403 meat eaters, 8562 non-meat eaters who did eat fish (‘fish eaters') and 20 601 vegetarians. After an average follow-up of 12.2 years, there were 3350 incident cancers of which 2204 were among meat eaters, 317 among fish eaters and 829 among vegetarians. Relative risks (RRs) were estimated by Cox regression, stratified by sex and recruitment protocol and adjusted for age, smoking, alcohol, body mass index, physical activity level and, for women only, parity and oral contraceptive use. Results: There was significant heterogeneity in cancer risk between groups for the following four cancer sites: stomach cancer, RRs (compared with meat eaters) of 0.29 (95% CI: 0.07–1.20) in fish eaters and 0.36 (0.16–0.78) in vegetarians, P for heterogeneity=0.007; ovarian cancer, RRs of 0.37 (0.18–0.77) in fish eaters and 0.69 (0.45–1.07) in vegetarians, P for heterogeneity=0.007; bladder cancer, RRs of 0.81 (0.36–1.81) in fish eaters and 0.47 (0.25–0.89) in vegetarians, P for heterogeneity=0.05; and cancers of the lymphatic and haematopoietic tissues, RRs of 0.85 (0.56–1.29) in fish eaters and 0.55 (0.39–0.78) in vegetarians, P for heterogeneity=0.002. The RRs for all malignant neoplasms were 0.82 (0.73–0.93) in fish eaters and 0.88 (0.81–0.96) in vegetarians (P for heterogeneity=0.001). Conclusion: The incidence of some cancers may be lower in fish eaters and vegetarians than in meat eaters.


Diet, Lifestyle, and Acute Myeloid Leukemia in the NIH–AARP Cohort

The relation between diet, lifestyle, and acute myeloid leukemia was assessed in a US cohort of 491,163 persons from the NIH–AARP Diet and Health Study (1995–2003). A total of 338 incident cases of acute myeloid leukemia were ascertained. Multivariate Cox models were utilized to estimate hazard ratios and 95% confidence intervals. Compared with those for never smokers, hazard ratios were 1.29 (95% confidence interval: 0.95, 1.75), 1.79 (95% confidence interval: 1.32, 2.42), 2.42 (95% confidence interval: 1.63, 3.57), and 2.29 (85% confidence interval: 1.38, 3.79) for former smokers who smoked ≤1 or >1 pack/day and for current smokers who smoked ≤1 or >1 pack/day, respectively. Higher meat intake was associated with an increased risk of acute myeloid leukemia (hazard ratio = 1.45, 95% confidence interval: 1.02, 2.07 for the fifth vs. first quintile; P for trend = 0.06); however, there were no clear effects of meat-cooking method or doneness level. Individuals who did not drink coffee appeared to have a higher risk of acute myeloid leukemia than those who drank various quantities of coffee. Neither fruit nor vegetable intake was associated with acute myeloid leukemia. This large prospective study identified smoking and meat intake as risk factors for acute myeloid leukemia.


Sweets, sweetened beverages, and risk of pancreatic cancer in a large population-based case–control study

Objective We examined the associations between sweets, sweetened and unsweetened beverages, and sugars and pancreatic cancer risk. Methods We conducted a population-based case–control study (532 cases, 1,701 controls) and used multivariate logistic regression models to calculate odds ratios (OR) and 95% confidence intervals (CI). Because associations were often different by sex, we present results for men and women combined and separately. Results Among men, greater intakes of total and specific sweets were associated with pancreatic cancer risk (total sweets: OR = 1.9, 95% CI: 1.0, 3.6; sweet condiments: OR = 1.9, 95% CI: 1.2, 3.1; chocolate candy: OR = 2.4, 95% CI: 1.1, 5.0; other mixed candy bars: OR = 3.3, 95% CI: 1.5, 7.3 for 1 + servings/day versus none/rarely). Sweets were not consistently associated with risk among women. Sweetened beverages were not associated with increased pancreatic cancer risk. In contrast, low-calorie soft drinks were associated with increased risk among men only; while other low-/non-caloric beverages (e.g., coffee, tea, and water) were unassociated with risk. Of the three sugars assessed (lactose, fructose, and sucrose), only the milk sugar lactose was associated with pancreatic cancer risk (OR = 2.0, 95% CI: 1.5, 2.7 comparing extreme quartiles). Conclusion These results provide limited support for the hypothesis that sweets or sugars increase pancreatic cancer risk.


Dietary Fatty Acids and Pancreatic Cancer in the NIH-AARP Diet and Health Study

Background Previous research relating dietary fat, a modifiable risk factor, to pancreatic cancer has been inconclusive. Methods We prospectively analyzed the association between intakes of fat, fat subtypes, and fat food sources and exocrine pancreatic cancer in the National Institutes of Health–AARP Diet and Health Study, a US cohort of 308 736 men and 216 737 women who completed a 124-item food frequency questionnaire in 1995–1996. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models, with adjustment for energy intake, smoking history, body mass index, and diabetes. Statistical tests were two-sided. Results Over an average follow-up of 6.3 years, 865 men and 472 women were diagnosed with exocrine pancreatic cancer (45.0 and 34.5 cases per 100 000 person-years, respectively). After multivariable adjustment and combination of data for men and women, pancreatic cancer risk was directly related to the intakes of total fat (highest vs lowest quintile, 46.8 vs 33.2 cases per 100 000 person-years, HR = 1.23, 95% CI = 1.03 to 1.46; Ptrend  = .03), saturated fat (51.5 vs 33.1 cases per 100 000 person-years, HR = 1.36, 95% CI = 1.14 to 1.62; Ptrend < .001), and monounsaturated fat (46.2 vs 32.9 cases per 100 000 person-years, HR = 1.22, 95% CI = 1.02 to 1.46; Ptrend = .05) but not polyunsaturated fat. The associations were strongest for saturated fat from animal food sources (52.0 vs 32.2 cases per 100 000 person-years, HR = 1.43, 95% CI = 1.20 to 1.70; Ptrend < .001); specifically, intakes from red meat and dairy products were both statistically significantly associated with increased pancreatic cancer risk (HR = 1.27 and 1.19, respectively). Conclusion In this large prospective cohort with a wide range of intakes, dietary fat of animal origin was associated with increased pancreatic cancer risk.


4. Chronic pancreatitis and pancreatic cancer, lifestyle-related diseases.

In Japan, the number of patients with both chronic pancreatitis (CP) and pancreatic cancer (PC) is increasing. A nationwide survey on CP revealed that the total number of patients treated for CP in Japan in 2002 was estimated as 45,200 (95% confidence interval, 35,600-54,700), and 20,137 patients died of PC in 2002. Alcoholic pancreatitis was the most common type of pancreatitis (67.5 %). Cigarette smoking was an independent and significant risk factor for CP. The risks of pancreatic and nonpancreatic cancers increased in the course of CP. While alcohol consumption may increase the risk of PC via CP, smoking was important as a risk factor for both CP and PC. The increasing incidence of PC was closely related to the increasing intake of animal fat. Lifestyle in patients with CP appeared to be the same as that in patients with PC. Environmental factors such as lifestyle in combination with genetic factors may increase the risk for both CP and PC. Therefore, changing and improving lifestyle habits such as drinking, smoking and nutrition may reduce the risks for both CP and PC.


Pancreatic cancer: a review of the evidence on causation.

Pancreatic cancer kills more than 250,000 people each year worldwide and has a poor prognosis. The aim of this article is to critically review the epidemiologic evidence for exposures that may either increase or decrease the risk. A Medline search was performed for epidemiologic studies and reviews published up to April 2007. Consistent evidence of a positive association was found for family history and cigarette smoking. Many studies documented a positive association with diabetes mellitus and chronic pancreatitis, although the etiologic mechanisms are unclear. Other associations were detected, but the results were either inconsistent or from few studies. These included positive associations with red meat, sugar, fat, body mass index, gallstones, and Helicobacter pylori, and protective effects of increasing parity, dietary folate, aspirin, and statins. There was no evidence linking alcohol or coffee consumption with an increased risk of pancreatic cancer. The associations with many exposures need to be clarified from further epidemiologic work in which there is both precise measurement of risk factors, adjustment for potential confounders, and, for dietary studies, information recorded on the method of food preparation and pattern of consumption. Such work is important to reduce the incidence of this fatal disease.


Macronutrients, fatty acids, cholesterol and pancreatic cancer.

A role of diet and nutrition in pancreatic carcinogenesis has been suggested, but the association between selected macronutrients, fatty acids, cholesterol and pancreatic cancer remains controversial. We analysed data from a hospital-based case-control study conducted in Italy between 1991 and 2008, including 326 cases (174 men and 152 women) with incident pancreatic cancer, and 652 controls (348 men and 304 women) frequency-matched to cases by sex, age and study centre. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multiple logistic regression models conditioned on age, sex and study centre, and adjusted for year of interview, education, tobacco smoking, history of diabetes and energy intake. A positive association was found for animal proteins (OR=1.85 for the highest versus the lowest quintile of intake; 95% CI: 1.15-2.96; p for trend=0.039), whereas a negative association was observed for sugars (OR=0.52; 95% CI: 0.31-0.86; p for trend=0.003). Non-significant negative associations emerged for vegetable proteins (OR=0.69) and polyunsaturated fatty acids (OR=0.67). In conclusion, a diet poor in animal proteins and rich in sugars (mainly derived from fruit) appears to have a beneficial effect on pancreatic cancer risk. Copyright (c) 2009 Elsevier Ltd. All rights reserved.