Well-done meat intake and the risk of breast cancer. BACKGROUND: Heterocyclic amines, mutagens formed in meats cooked at high temperatures, have been demonstrated as mammary carcinogens in animals. We conducted a nested, case-control study among 41836 cohort members of the Iowa Women's Health Study to evaluate the potential role of heterocyclic amines and intake of well-done meat in the risk for human breast cancer. METHODS: A questionnaire was mailed to individuals in the cohort who had breast cancer diagnosed during the period from 1992 through 1994 and a random sample of cancer-free cohort members to obtain information on usual intake of meats and on meat preparation practices. Color photographs showing various doneness levels of hamburger, beefsteak, and bacon were included. Multivariate analysis was performed on data from 273 case subjects and 657 control subjects who completed the survey. RESULTS: A dose-response relationship was found between doneness levels of meat consumed and breast cancer risk. The adjusted odds ratios (ORs) for very well-done meat versus rare or medium-done meat were 1.54 (95% confidence interval [CI]=0.96-2.47) for hamburger, 2.21 (95% CI=1.30-3.77) for beef steak, and 1.64 (95% CI=0.92-2.93) for bacon. Women who consumed these three meats consistently very well done had a 4.62 times higher risk (95% CI=1.36-15.70) than that of women who consumed the meats rare or medium done. Risk of breast cancer was also elevated with increasing intake of well-done to very well-done meat. CONCLUSIONS: Consumption of well-done meats and, thus, exposures to heterocyclic amines (or other compounds) formed during high-temperature cooking may play an important role in the risk of breast cancer.


Biomonitoring of Carcinogenic Heterocyclic Aromatic Amines in Hair: A Validation Study A facile method was established to measure heterocyclic aromatic amines (HAAs) accumulated in human hair and rodent fur. The samples were digested by base hydrolysis, and the liberated HAAs were isolated by tandem solvent/solid-phase extraction. Quantification was done by liquid chromatography/tandem mass spectrometry, using a triple stage quadrupole mass spectrometer in the selected reaction monitoring mode. In a pilot study of 12 human volunteers, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was detected in hair of six meat-eaters at levels ranging from 290 to 890 pg/g hair. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-9H-pyrido[2,3-b]indole (AαC) were below the limit of quantification (LOQ) (50 pg/g hair) in hair from meat-eaters and six vegetarians. PhIP was detected in the hair from one vegetarian, and at level just above the LOQ (65 pg/g hair), indicating PhIP exposure occurs primarily through meat consumption. The levels of PhIP in hair samples from two meat-eaters varied by less than 24% over a 6-month interval, signifying that the exposure to PhIP and its accumulation in hair are relatively constant over time. In a controlled feeding study, female C57BL/6 mice were given these HAAs in their drinking water for 1 month, at six daily dose concentrations ranging from 0, 0.080 to 800 µg/kg body weight. PhIP was detected in fur of mice at all doses, whereas AαC and MeIQx were detected in fur at dosages ≥0.8 µg AαC/kg body weight and ≥8 µg MeIQx/kg body weight. There was a strong positive relationship between dosage and each of the HAAs accumulated in fur and their DNA adducts formed in liver and colon (p-values <0.0001); however, the levels of HAA in fur did not correlate to the levels of DNA adducts after adjustment of dose. Thus, hair appears to be a promising long-lived biomarker with by which we can assess the exposure to PhIP, a potential human carcinogen.


Effect of diet on serum albumin and hemoglobin adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in humans. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine formed in meat and fish during cooking and can be used as a model compound for this class of chemicals possibly involved in human carcinogenesis. Knowing the exposure to heterocyclic amines is important for establishing their role in human diseases. Serum albumin (SA) and globin (Gb) adducts were first tested as biomarkers of exposure to PhIP in male Fischer 344 rats given oral doses of 0.1, 0.5, 1 and 10 mg/kg. Blood samples were collected 24 hr after treatment and PhIP released from SA and Gb after acidic hydrolysis was analyzed by gas chromatography-mass spectrometry or liquid chromatography-tandem mass spectrometry. PhIP-SA and Gb adducts increased linearly with the dose. Studies on 35 volunteers with different dietary habits exhibited that diet was a major determinant in the formation of both adducts. PhIP-SA adducts were significantly higher in meat consumers than in vegetarians (6.7 +/- 1.6 and 0.7 +/- 0.3 fmol/mg SA; respectively, mean +/- SE; p = 0.04, Mann-Whitney U test). The Gb adduct pattern was quantitatively lower but paralleled SA (3 +/- 0.8 in meat consumers and 0.3 +/- 0.1 in vegetarians). PhIP-SA adducts were no different in smokers and in non-smokers. The results show for the first time that PhIP-blood protein adducts are present in humans not given the synthetic compound. Both biomarkers appear to be suitable for assessing dietary exposure and internal PhIP dose and may be promising tools for studying the role of heterocyclic amines in the etiology of colon cancer and other diseases. Copyright 2000 Wiley-Liss, Inc.


Formation and biochemistry of carcinogenic heterocyclic aromatic amines in cooked meats. Heteroyclic aromatic amines (HAAs) are a class of hazardous chemicals that are receiving heightened attention as a risk factor for human cancer. HAAs arise during the cooking of meats, fish, and poultry, and several HAAs also occur in tobacco smoke condensate and diesel exhaust. Many HAAs are carcinogenic and induce tumors at multiple sites in rodents. A number of epidemiologic studies have reported that frequent consumption of well-done cooked meats containing HAAs can result in elevated risks for colon, prostate, and mammary cancers. Moreover, DNA adducts of HAAs have been detected in human tissues, demonstrating that HAAs induce genetic damage even though the concentrations of these compounds in cooked meats are generally in the low parts-per-billion (ppb) range. With recent improvements in sensitivity of mass spectrometry instrumentation, HAAs, their metabolites, and DNA adducts can be detected at trace amounts in biological fluids and tissues of humans. The incorporation of HAA biomarkers in epidemologic studies will help to clarify the role of these dietary genotoxicants in the etiology of human cancer.


The cooked meat-derived mammary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine promotes invasive behaviour of breast cancer cells. The cooked meat derived genotoxic carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces cancer of the colon, prostate and mammary gland when fed to rats. Epidemiology studies link these tumours to a Western diet and exposure to heterocyclic amines such as PhIP. We have shown that PhIP is also potently estrogenic and have proposed that this hormonal activity contributes to its target site carcinogenicity. We now postulate that the estrogenic properties of PhIP influence metastatic potential. We have used an in vitro assay for cell invasion based upon digestion and migration through a reconstituted basement membrane model. Zymography and immunoblotting were used to confirm PhIP-mediated changes associated with induction of the invasive phenotype. Treatment of the mammary cancer cell lines MCF-7 and T47D with PhIP induces cells to digest and migrate through a reconstituted basement membrane. The response was dose dependent, observed at sub-nanomolar concentrations of PhIP and was inhibited by the antiestrogen ICI 182,780. The PhIP-induced invasive phenotype was associated with expression of cathepsin D, cyclooxygenase-2 and matrix metalloproteinase activity. These findings emphasise the range and potency of the biological activities associated with this cooked meat product and mechanistically support the tissue-specific carcinogenicity of the chemical. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.


Meat, fat and risk of breast cancer: a case-control study from Uruguay. To examine whether meat intake modifies breast-cancer risk, a case-control study was conducted in Uruguay. Dietary patterns were assessed in detail (for cases, before diagnosis or symptoms occurred) using a food frequency questionnaire involving 64 food items, which allowed total energy intake to be calculated. Nutrient residuals were calculated through regression analysis. After adjustment for potential confounders (which included family history of breast cancer, menopausal status, body-mass index, total energy and total alcohol intake), an increased risk associated with consumption of total meat intake, red meat intake, total fat and saturated fat intake was observed. The strongest effect was observed for red meat intake (OR 4.2, 95% CL 2.3-7.7) for consumption in the upper quartile, after controlling for protein and fat intake. This suggests an independent effect for meat. Since experimental studies have shown a strong effect of heterocyclic amines in rat mammary carcinogenesis, further studies should be performed in human epidemiology, perhaps using biomarkers of heterocyclic amine exposure.


Intake of fried meat and risk of cancer: a follow-up study in Finland. It has been suggested that mutagens in fried meat may be involved in the cancer process. Therefore the relationships between intake of fried meat and subsequent risk of cancers at different sites were studied among 9,990 Finnish men and women, 15-99 years of age and initially free of cancer. The baseline study was carried out in 1966-1972, and cases of cancer were identified through data linkage with the Finnish Cancer Registry. During a 24-year follow-up, 853 cancer cases were diagnosed. The intake of fried meat was estimated from a dietary history interview covering the total diet of the participants during the previous year. There was a positive association between fried meat intake and the risk of female-hormone-related cancers, i.e., cancer of the breast, endometrium and ovary combined. The relative risk of these cancers combined between persons in the highest and lowest tertiles of daily intake of fried meat adjusted for age, personal characteristics and intake of other main food groups was 1.77 (95% confidence interval = 1.11-2.84). Pancreatic and nervous system cancers also presented non-significant suggestive associations. No associations were observed with respect to other single cancer sites studied or to all sites of cancer combined. Further epidemiological efforts are needed to ascertain the potential link between fried-food mutagens and cancer risk.


Detection of PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) in the milk of healthy women. An increased risk of breast cancer has been observed in women who consume "very well-done" meats. Heterocyclic amines are mutagenic and carcinogenic pyrolysis products formed during high temperature cooking of meats. In the present study, human milk samples were analyzed for PhIP, one of the most abundant dietary heterocyclic amine. A protocol was developed with a mixed-mode cation exchange sorbent for the extraction of heterocyclic amines from milk. Milk samples were acquired from healthy Canadian women. With LC/MS analysis and the method of isotope dilution for quantification, levels of PhIP were determined in human milk samples. PhIP was detected in 9 of the 11 milk samples, at levels as high as 59 pg/mL (ppt). No PhIP was detected in the milk of the vegetarian donor. Detection of PhIP in milk indicates that ductal mammary epithelial cells are directly exposed to this carcinogen, suggesting that heterocyclic amines are possible human mammary carcinogens.


Dietary intake of meat and meat-derived heterocyclic aromatic amines and their correlation with DNA adducts in female breast tissue. It was the aim of this study to examine the association of the consumption of meat in general, meat prepared by different cooking methods and the dietary intake of heterocyclic aromatic amines (HCA) with the level of DNA adducts in the breast tissue of women undergoing reduction mammoplasty. Dietary intake of meat and HCA were assessed via questionnaire in 44 women undergoing reduction mammoplasty. DNA adduct analysis in breast tissue was performed by (32)P-postlabelling analysis. Spearman rank correlation coefficients (r) were calculated to examine the association of meat consumption and dietary HCA intake with tissue DNA adduct levels. A median DNA adduct level of 18.45 (interquartile range 12.81-25.65) per 10(9) nucleotides in breast tissue was observed; median HCA intake was 40.43 ng/day (interquartile range 19.55-102.33 ng/day). Total HCA intake (r = 0.33, P = 0.03), consumption of fried meat (r = 0.39, P = 0.01), beef (r = 0.32, P = 0.03) and processed meat (r = 0.51, P = 0.0004) were statistically significantly correlated with the level of DNA adducts in breast tissue. The detected DNA adducts could not be confirmed to be specific HCA-derived DNA adducts by comparison with external standards, using the (32)P-postlabelling assay. We observed strong correlations of dietary HCA intake and consumption of fried and processed meat with DNA adduct levels in breast tissue of 44 women. Since the detected DNA adducts were not necessarily specific only for HCA, it is possible that HCA intake is a surrogate of other genotoxic substances, such as polycyclic aromatic hydrocarbons, in meat prepared at high temperatures.


The cooked food derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine is a potent oestrogen: a mechanistic basis for its tissue-speci... The cooked meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces tumours of the breast, colon and prostate in rats. Here we show that in addition to its well-established genotoxicity, which can be detected at concentrations >10(-6) M, PhIP is also oestrogenic. In COS-1 cells transiently transfected with an oestrogen-responsive reporter gene, PhIP (10(-10)-10(-6) M) mediated transcription through oestrogen receptor (ER) alpha, but not ER-beta, and inhibition by the pure ER antagonist ICI 182 780 demonstrated a requirement for a functional ER. In contrast, the structurally related food-derived carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) failed to induce reporter gene transcription. Additionally, we show that in a hormonally responsive breast cancer cell line (MCF-7 cells), PhIP induced transcriptional activation using endogenously expressed ER. Examination of the genotoxic potential of PhIP using a model mammalian cell mutation assay (hprt(-) locus) demonstrated that the genetic toxicology of PhIP was readily detectable, but separate, in terms of effective concentration, from its oestrogenic activity. To determine whether the oestrogenicity of PhIP could mediate oestrogen-dependent responses such as cell growth, we examined the growth of hormonally responsive cells (MCF-7 cells). We show that PhIP can stimulate cell proliferation and, again, this was dependent upon a functional ER. Using ligand blotting, we further show that PhIP can stimulate the expression of progesterone receptor (PR-A and PR-B) and c-MYC and activate the MAPK signal transduction pathway. These responses were similar to that produced by oestradiol, in terms of temporal aspects, potency and a requirement for a functional ER. Each of these dose-dependent mitogenic responses occurred at concentrations of PhIP ( approximately 10(-9)-10(-11)M) that are likely to be equivalent to systemic human exposure via consumption of cooked meat. Thus PhIP can induce cellular responses that encompass altered gene expression and mitogenesis. We suggest that the combination of genetic toxicology and oestrogen-like promotion of genomic and cellular events provide a mechanism for the tissue-specific tumorigenicity of this compound.


Formation of a mutagenic heterocyclic aromatic amine from creatinine in urine of meat eaters and vegetarians. Liquid chromatography electrospray ionization mass spectrometry (MS) with a triple quadrupole MS was used to identify known and novel heterocyclic aromatic amines (HAAs) in human urine. The identities of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were confirmed by their product ion spectra. The constant neutral loss scan mode was employed to probe for other analytes in urine that display the transition [M+H]+-->[M+H-CH3*]+*, which is common to HAAs containing an N-methylimidazo moiety, and led to the detection of a previously unreported isomer of 8-MeIQx [Holland, R., et al. (2004) Chem. Res. Toxicol. 17, 1121-1136]. We now report the identification of another novel HAA, 2-amino-1-methylimidazo[4,5-b]quinoline (IQ[4,5-b]), an isomer of the powerful animal carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). The amounts of IQ[4,5-b] measured in the urine of human volunteers who consumed grilled beef ranged from 15 to 135% of the ingested dose, while the amounts of 8-MeIQx and PhIP excreted in urine were on average <2% of the ingested dose. Base treatment of urine at 70 degrees C increased the concentrations of 8-MeIQx and PhIP by as much as 6-fold, indicating the presence of phase II conjugates; however, the amount of IQ[4,5-b] increased by more than 100-fold. IQ[4,5-b] was also detected in the urine of vegetarians following base hydrolysis. The formation of IQ[4,5-b], but not IQ, 8-MeIQx, or PhIP, also occurred in urine incubated at 37 degrees C. Creatinine and 2-aminobenzaldehyde are likely precursors of IQ[4,5-b]. The detection of IQ[4,5-b] in the urine of both meat eaters and vegetarians suggests that this HAA may be present in nonmeat staples or that IQ[4,5-b] formation may occur endogenously within the urinary bladder or other biological fluids.


A program consisting of a phytonutrient-rich medical food and an elimination diet ameliorated fibromyalgia symptoms and promoted toxic-element deto... BACKGROUND: An effective treatment for fibromyalgia (FM) has yet to become available. OBJECTIVE: To assess the efficacy ofa lifestyle program consisting of a modified elimination diet and a supplemental medical food on clinical symptoms of FM assessed by the Fibromyalgia Impact Questionnaire (FIQ), FibroQuest Symptoms Survey (FibroQuest), Medical Symptoms Questionnaire (MSQ), metallothionein mRNA expression, and urinary toxic element excretion. METHODS: Eight women (aged 48-74 years) were enrolled in an 8-week pilot trial employing a sequential design. During the initial 4-week Program A (control), participants consumed a modified US Department of Agriculture food pyramid diet and a rice protein powder supplement that provided basic macronutrient support. During the second 4-week Program B (intervention), participants consumed a modified elimination diet and a phytonutrient-rich medical food. RESULTS: Compared to baseline, both programs showed trends toward lower mean FIQ total score, MSQ total score, and FibroQuest total score, FIQ stiffness score, and FibroQuest headaches score. Compared to Program A, Program B resulted in a significant decrease (P< .05) in the FIQpain score and stiffness score. Participants also had better pain tolerance at five tender points during Program B than during Program A. Higher metallothionein mRNA expression was observed during Program B. An increase in creatinine-adjusted mercury excretion and suggestive increase in creatinine-adjusted arsenic excretion were noted when Program B was compared to baseline. Urinary mercury/arsenic concentrations were inversely associated with FIQand FibroQuest scores. CONCLUSIONS: Program B was shown to be a safe and efficacious botanically derived medical food treatment program for the amelioration of FM symptoms.


Mediterranean diet or extended fasting's influence on changing the intestinal microflora, immunoglobulin A secretion and clinical outcome in patients with rheumatoid arthritis and fibromyalgia: an observational study Background Alterations in the intestinal bacterial flora are believed to be contributing factors to many chronic inflammatory and degenerative diseases including rheumatic diseases. While microbiological fecal culture analysis is now increasingly used, little is known about the relationship of changes in intestinal flora, dietary patterns and clinical outcome in specific diseases. To clarify the role of microbiological culture analysis we aimed to evaluate whether in patients with rheumatoid arthritis (RA) or fibromyalgia (FM) a Mediterranean diet or an 8-day fasting period are associated with changes in fecal flora and whether changes in fecal flora are associated with clinical outcome. Methods During a two-months-period 51 consecutive patients from an Integrative Medicine hospital department with an established diagnosis of RA (n = 16) or FM (n = 35) were included in the study. According to predefined clinical criteria and the subjects' choice the patients received a mostly vegetarian Mediterranean diet (n = 21; mean age 50.9 +/-13.3 y) or participated in an intermittent modified 8-day fasting therapy (n = 30; mean age 53.7 +/- 9.4 y). Quantitative aerob and anaerob bacterial flora, stool pH and concentrations of secretory immunoglobulin A (sIgA) were analysed from stool samples at the beginning, at the end of the 2-week hospital stay and at a 3-months follow-up. Clinical outcome was assessed with the DAS 28 for RA patients and with a disease severity rating scale in FM patients. Results We found no significant changes in the fecal bacterial counts following the two dietary interventions within and between groups, nor were significant differences found in the analysis of sIgA and stool ph. Clinical improvement at the end of the hospital stay tended to be greater in fasting vs. non-fasting patients with RA (p = 0.09). Clinical outcome was not related to alterations in the intestinal flora. Conclusion Neither Mediterranean diet nor fasting treatments affect the microbiologically assessed intestinal flora and sIgA levels in patients with RA and FM. The impact of dietary interventions on the human intestinal flora and the role of the fecal flora in rheumatic diseases have to be clarified with newer molecular analysis techniques. The potential benefit of fasting treatment in RA and FM should be further tested in randomised trials.


Potential dietary links to central sensitization in fibromyalgia: past reports and future directions. This article reviews the existing literature on fibromyalgia (FM) and diet, discusses the possible role of diet on central sensitization in FM, proposes a novel hypothesis of possible food-related contributors to central sensitization, and makes recommendations for future dietary research directions.


Diet and disease symptoms in rheumatic diseases--results of a questionnaire based survey. Experiences with food intake, diet manipulations and fast were registered in rheumatic patients. The study was a questionnaire-based survey in which 742 patients participated. It comprised 290 patients with rheumatoid arthritis, 51 patients with juvenile rheumatoid arthritis, 87 patients with ankylosing spondylitis, 51 patients with psoriatic arthropathy, 65 patients with primary fibromyalgia and 34 patients with osteoarthritis. One third of the patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthropathy reported aggravation of disease symptoms after intake of certain foods while 43% of the patients with juvenile rheumatoid arthritis and 42% of the patients with primary fibromyalgia stated the same. Twenty-six percent of the patients with juvenile rheumatoid arthritis and 23% of the patients with rheumatoid arthritis, ankylosing spondylitis and primary fibromyalgia had previously tried certain diets in the attempt to alleviate disease symptoms, whereas 13% of the patients with psoriatic arthropathy and 10% with osteoarthritis had tried diet therapy. Less pain and stiffness were reported by 46% of the patients and 36% reported reduced joint swelling. Similar beneficial effects of diet were also reported in other rheumatic disease groups. Fifteen percent of the patients with rheumatoid arthritis and ankylosing spondylitis had been through a fasting period. Less pain and stiffness were reported by 2/3 of the patients in both groups and half of the patients in both groups reported a reduced number of swollen joints.


Vegan diet alleviates fibromyalgia symptoms. The effect of a strict, low-salt, uncooked vegan diet rich in lactobacteria on symptoms in 18 fibromyalgia patients during and after a 3-month intervention period in an open, non-randomized controlled study was evaluated. As control 15 patients continued their omnivorous diet. The groups did not differ significantly from each other in the beginning of the study in any other parameters except in pain and urine sodium. The results revealed significant improvements in Visual analogue scale of pain (VAS) (p=0.005), joint stiffness (p=0.001), quality of sleep (p=0.0001), Health assessment questionnaire (HAQ) (p=0.031), General health questionnaire (GHQ) (p=0.021), and a rheumatologist's own questionnaire (p=0.038). The majority of patients were overweight to some extent at the beginning of the study and shifting to a vegan food caused a significant reduction in body mass index (BMI) (p=0.0001). Total serum cholesterol showed a statistically significant lowering (p=0.003). Urine sodium dropped to 1/3 of the beginning values (p=0.0001) indicating good diet compliance. It can be concluded that vegan diet had beneficial effects on fibromyalgia symptoms at least in the short run.


Fibromyalgia and nutrition, what do we know? Many people suffer from fibromyalgia (FM) without an effective treatment. They do not have a good quality of life and cannot maintain normal daily activity. Among the different hypotheses for its ethiopathophysiology, oxidative stress is one of the possibilities. Non-scientific information addressed to patients regarding the benefits of nutrition is widely available, and they are used to trying non-evidenced strategies. The aim of this paper is to find out what we know right now from scientific studies regarding fibromyalgia disease and nutritional status, diets and food supplements. A systematic search has been performed on Medline with a wide range of terms about these nutritional issues. The search has been made during 2009, for articles published between 1998 and 2008. TARGET POPULATION: people suffering from FM. Vegetarian diets could have some beneficial effects probably due to the increase in antioxidant intake. There is a high prevalence of obesity and overweight in patients, and weight control seems to be an effective tool to improve the symptoms. Some nutritional deficiencies have been described, it is not clear whether they are directly related to this disease or not. About the usefulness of some food supplements we found very little data, and it seems that more studies are needed to prove which ones could be of help. Dietary advice is necessary to these patients to improve their diets and maintain normal weight. It would be interesting to investigate more in the field of nutrition and FM to reveal any possible relationships.


Reduced plasma fibrinogen, serum peroxides, lipids, and apolipoproteins after a 3-week vegetarian diet. The influence of a 3-week vegetarian diet and fasting on serum concentration of peroxides, lipids, apolipoproteins, and plasma fibrinogen was studied in ten middle-aged fibromyalgia/fibrositis patients (eight women, two men). Mean serum peroxide concentration (estimated as thiobarbituric acid reacting substances) was reduced from 3.60 +/- 0.14 to 2.82 +/- 0.15 umol/l (p = 0.01) and plasma fibrinogen from 3.33 +/- 0.25 to 2.74 +/- 0.15 g/l (p = 0.02). Serum total cholesterol fell from 6.61 +/- 0.50 to 4.83 +/- 0.35 mmol/l (p < 0.0001), apolipoprotein B from 1.77 +/- 0.14 to 1.31 +/- 0.11 g/l (p < 0.0001), and apolipoprotein A from 1.41 +/- 0.09 to 1.23 +/- 0.05 g/l (p = 0.03). High density lipoprotein cholesterol concentration also decreased somewhat (from 1.26 +/- 0.09 to 1.07 +/- 0.04 mmol/l, p = 0.03) An atherogenic index, reflecting the balance between low and high density lipoproteins, was reduced by 31% (from 5.74 +/- 0.79 to 3.97 +/- 0.60, p = 0.02). The results suggest that vegetarian diet/fasting may have a beneficial influence on the concentration of serum peroxides and plasma fibrinogen concentration, and on the serum level of several lipoprotein-related coronary risk factors.


Antiproliferative effects of apple peel extract against cancer cells. Studies have shown an inverse relationship between the consumption of apples and the risk of several cancers. The peels of apple, which have been shown to possess exceptionally high concentrations of antioxidants, are often discarded. In this study, we evaluated the antiproliferative effects of apple peel extract (APE) in variety of cancer cell types. Our data demonstrated that APE, obtained from organic Gala apples, imparted significant reduction in the viability of a variety of cancer cell lines. Further, our data showed a significant decrease in growth and clonogenic survival of human prostate carcinoma CWR22Rnu1 and DU145 cells and breast carcinoma Mcf-7 and Mcf-7:Her18 cells. Also, the antiproliferative effects of APE were found to be accompanied by a G0-G1 phase arrest of prostate and breast cancer cells. Furthermore, APE treatment resulted in a marked concentration-dependent decrease in the protein levels of proliferative cell nuclear antigen, a marker for proliferation. In addition, APE treatment resulted in a marked increase in maspin, a tumor suppressor protein that negatively regulates cell invasion, metastasis, and angiogenesis. Our data suggested that APE possesses strong antiproliferative effects against cancer cells, and apple peels should not be discarded from the diet. Detailed mechanistic studies, especially in appropriate in vivo animal models, are needed to further examine the antiproliferative and preventive effects of APE against cancer.


Development of an ingredient containing apple peel, as a source of polyphenols and dietary fiber. Apple peel is a waste product from dried apple manufacture. The content of phenolic compounds, dietary fiber, and mineral are higher in apple peel, compared to other edible parts of this fruits. The objective of this study was to develop an ingredient from Granny Smith apple peel, using a pilot scale double drum-dryer, as drying technology. The control of all steps to maximize the retention of phenolic compounds and dietary fiber was considered. Operational conditions, such as drying temperature and time were determined, as well as important preprocessing steps like grinding and PPO inhibition. In addition, the physical-chemical characteristics, mineral and sugar content, and technological functional properties such as water retention capacity, solubility index, and dispersability among others, were analyzed. A simple, economical, and suitable pilot scale process, to produce a powder ingredient from apple peel by-product, was obtained. The drying process includes the application of ascorbic acid at 0.5% in the fresh apple peel slurry, drum-dryer operational conditions were 110 degrees C, 0.15 rpm and 0.2 mm drum clearance. The ingredient developed could be considered as a source of phenolic compounds (38.6 mg gallic acid equivalent/g dry base) and dietary fiber (39.7% dry base) in the formulation of foods. Practical Application: A method to develop an ingredient from Granny Smith apple peel using a pilot scale double drum-dryer as drying technology was developed. The method is simple, economical, feasible, and suitable and maximizes the retention of phenolic compounds and dietary fiber present in the raw matter. The ingredient could be used in the formulation of foods.


Assessment of antioxidant activity by using different in vitro methods. In this study, six common tests for measuring antioxidant activity were evaluated by comparing four antioxidants and applying them to beverages (tea and juices): Trolox equivalent antioxidant capacity assay (TEAC I-III assay), Total radical-trapping antioxidant parameter assay (TRAP assay), 2,2-diphenyl-l-picrylhydrazyl assay (DPPH assay), N,N-dimethyl-p-phenylendiamine assay (DMPD assay), Photochemiluminescence assay (PCL assay) and Ferric reducing ability of plasma assay (FRAP assay). The antioxidants included gallic acid representing the group of polyphenols, uric acid as the main antioxidant in human plasma, ascorbic acid as a vitamin widely spread in fruits and Trolox as water soluble vitamin E analogue. The six methods presented can be divided into two groups depending on the oxidising reagent. Five methods use organic radical producers (TEAC I-III, TRAP, DPPH, DMPD, PCL) and one method works with metal ions for oxidation (FRAP). Another difference between these tests is the reaction procedure. Three assays use the delay in oxidation and determine the lag phase as parameter for the antioxidant activity (TEAC I, TRAP, PCL). They determine the delay of radical generation as well as the ability to scavenge the radical. In contrast, the assays TEAC II and III, DPPH, DMPD and FRAP analyse the ability to reduce the radical cation (TEAC II and III, DPPH, DMPD) or the ferric ion (FRAP). The three tests acting by radical reduction use preformed radicals and determine the decrease in absorbance while the FRAP assay measures the formed ferrous ions by increased absorbance. Gallic acid was the strongest antioxidant in all tests with exception of the DMPD assay. In contrast, uric acid and ascorbic acid showed low activity in some assays. Most of the assays determine the antioxidant activity in the micromolar range needing minutes to hours. Only one assay (PCL) is able to analyse the antioxidant activity in the nanomolar range. Black currant juice showed highest antioxidant activity in all tests compared to tea, apple juice and tomato juice. Despite these differences, results of these in vitro assays give an idea of the protective efficacy of secondary plant products. It is strongly recommended to use at least two methods due to the differences between the test systems investigated.


Uric acid: A marker of increased cardiovascular risk. The relationship between uric acid and cardiovascular disease has been known since the 19th century, after that many authors reported the classical association of gout, hypertension, obesity and cardiovascular disease. With the exception of specific genetic defects in purine metabolism, increased uric acid is generally associated with important risk factors for atherosclerosis like hypertension, abdominal obesity, insulin resistance, the metabolic syndrome and renal failure. Studies have clearly shown an association between increased uric acid concentrations with oxidative stress, endothelial dysfunction, inflammation, subclinical atherosclerosis and an increased risk of cardiovascular events. Increased uric acid levels are independent markers of cardiovascular disease risk. Prospective studies are necessary to show that reduction of uric acid levels prevent cardiovascular events.


Serum uric acid level as an independent risk factor for all-cause, cardiovascular, and ischemic stroke mortality: a Chinese cohort study. OBJECTIVE: The association between hyperuricemia and cardiovascular events has been documented in high-risk groups, but is still undetermined in general populations, especially Chinese. This study assessed the temporal association between serum uric acid level, hyperuricemia, and cardiovascular mortality. METHODS: A prospective cohort study of 41,879 men and 48,514 women ages > or = 35 years was conducted using data from the MJ Health Screening Centers in Taiwan. Mortality from all causes, total cardiovascular disease (CVD), ischemic stroke, congestive heart failure, hypertensive disease, and coronary heart disease were compared according to increasing serum uric acid levels. RESULTS: A total of 1,151 (21.2%) events of 5,427 total deaths were ascribed to CVD (mean followup 8.2 years). Hazard ratios (HRs) for hyperuricemia (serum uric acid level >7 mg/dl) were estimated with Cox regression model after adjusting for age, sex, body mass index, cholesterol, triglycerides, diabetes, hypertension, heavy cigarette smoking, and frequent alcohol consumption. In all patients, HRs were 1.16 (P < 0.001) for all-cause mortality, 1.39 (P < 0.001) for total CVD, and 1.35 (P = 0.02) for ischemic stroke. In subgroup analysis, the HRs for cardiovascular risk remained significant in patients with hypertension (1.44, P < 0.001) and in patients with diabetes (1.64, P < 0.001). In addition, in a low metabolic risk subgroup, the HRs for all-cause mortality and total cardiovascular morbidity were 1.24 (P = 0.02) and 1.48 (P = 0.16), respectively. CONCLUSION: Hyperuricemia was an independent risk factor of mortality from all causes, total CVD, and ischemic stroke in the Taiwanese general population, in high-risk groups, and potentially in low-risk groups.


Dietary fiber and breast cancer risk: a systematic review and meta-analysis of prospective studies. BACKGROUND: Evidence from case-control studies suggest that dietary fiber may be inversely related to breast cancer risk, but it is unclear if this is supported by prospective data. We conducted a systematic review and meta-analysis of the evidence from prospective studies. METHODS: PubMed was searched for prospective studies of fiber intake and breast cancer risk until 31st August 2011. Random effects models were used to estimate summary relative risks (RRs). RESULTS: Sixteen prospective studies were included. The summary RR for the highest versus the lowest intake was 0.93 [95% confidence interval (CI) 0.89-0.98, I(2) = 0%] for dietary fiber, 0.95 (95% CI 0.86-1.06, I(2) = 4%) for fruit fiber, 0.99 (95% CI 0.92-1.07, I(2) = 1%) for vegetable fiber, 0.96 (95% CI 0.90-1.02, I(2) = 5%) for cereal fiber, 0.91 (95% CI 0.84-0.99, I(2) = 7%) for soluble fiber and 0.95 (95% CI 0.89-1.02, I(2) = 0%) for insoluble fiber. The summary RR per 10 g/day of dietary fiber was 0.95 (95% CI 0.91-0.98, I(2) = 0%, P(heterogeneity) = 0.82). In stratified analyses, the inverse association was only observed among studies with a large range (≥13 g/day) or high level of intake (≥25 g/day). CONCLUSION: In this meta-analysis of prospective studies, there was an inverse association between dietary fiber intake and breast cancer risk.


Mortality from Western cancers rose dramatically among African-Americans during the 20th century: are dietary animal products to blame? Statistics compiled by the National Cancer Institute indicate that, between 1935 and 1974, age-adjusted mortality from most 'Western' cancers (those of the breast, colon, prostate, pancreas, ovary, and kidney) rose dramatically in African-Americans. This phenomenon is paralleled by marked increases in the incidence of these cancers in Asia and Southern Europe during the latter 20th century, in conjunction with increased intakes of dietary animal products. A credible case can be made that diets rich in animal products work in various complementary ways to up-regulate serum levels of insulin, free IGF-I, and free sex hormones: hormones that appear to have important promotional activity for Western cancers. It seems likely that dietary animal product intake by black Americans increased substantially during the 20th century, and that this fact is primarily responsible for their concurrent marked increase in mortality from Western cancers. A whole-food vegan diet rich in fruits and vegetables, especially if coupled with regular exercise and smoking avoidance, could be expected to have a remarkably positive impact on African-American cancer risk, reversing the increases in cancer risk incurred during the 20th century. Copyright 2001 Harcourt Publishers Ltd.


Use of statistics to assess the global burden of breast cancer. A variety of statistics are used to quantify the burden (occurrence and outcome) of cancer generally and of breast cancer specifically. When undertaking any cancer control program, understanding these statistics, their source, and their quality is important for assessing the current situation, allocating resources to different control strategies, and evaluating progress. Two core statistics are the cancer incidence rate and the cancer mortality rate, which provide estimates of the average risk of acquiring and of dying from the disease, respectively. About 16% of the world's population is covered by registration systems that produce cancer incidence statistics, while mortality data are available for about 29%. Breast cancer incidence and mortality vary considerably by world region. In general, the incidence is high (greater than 80 per 100,000) in developed regions of the world and low (less than 30 per 100,000), though increasing, in developing regions; the range of mortality rates is much less (approximately 6-23 per 100,000) because of the more favorable survival of breast cancer in (high-incidence) developed regions. The incidence of breast cancer is increasing almost everywhere. This unfavorable trend is due in part to increases in risk factors (decreased childbearing and breast-feeding, increased exogenous hormone exposure, and detrimental dietary and lifestyle changes, including obesity and less physical activity). On the other hand, mortality is now decreasing in many high-risk countries due to a combination of intensified early detection efforts and the introduction of mammographic screening, resulting in the diagnosis of more small, early stage tumors, and advances in treatment.


Green Tea and Breast Cancer The identification of modifiable lifestyle factors that could reduce the risk of breast cancer is a research priority. Despite the enormous chemo preventive potential of green tea and compelling evidence from animal studies, its role in breast cancer development in humans is still unclear. Part of the uncertainty is related to the relatively small number of epidemiological studies on green tea and breast cancer and that the overall results from case-control studies and prospective cohort studies are discordant. In addition, the mechanisms by which green tea intake may influence risk of breast cancer in humans remains not well studied. We review the human studies that have evaluated the relationship between green tea intake and four biomarkers (sex steroid hormones, mammographic density, insulin-like growth factor, adiponectin) that are believed to be important in breast cancer development. Results from these biomarker studies are also inconclusive. Limitations of human studies and areas of further investigations are discussed.


Dietary intakes of mushrooms and green tea combine to reduce the risk of breast cancer in Chinese women. To investigate effects of dietary mushrooms and joint effects of mushrooms and green tea on breast cancer, a case-control study was conducted in southeast China in 2004-2005. The incident cases were 1,009 female patients aged 20-87 years with histologically confirmed breast cancer. The 1,009 age-matched controls were healthy women randomly recruited from outpatient breast clinics. Information on frequency and quantity of dietary intake of mushrooms and tea consumption, usual diet, and lifestyle were collected by face-to-face interview using a validated and reliable questionnaire. Compared with nonconsumers, the Odds ratios (Ors) were 0.36 (95% CI = 0.25-0.51) and 0.53 (0.38-0.73) for daily intake of >or=10 g fresh mushrooms and >or=4 g dried mushrooms, based on multivariate logistic regression analysis adjusting for established and potential confounders. There were dose-response relationships with significant tests for trend (p < 0.001). The inverse association was found in both pre- and postmenopausal women. Compared with those who consumed neither mushrooms nor green tea, the ORs were 0.11 (0.06-0.20) and 0.18 (0.11-0.29) for daily high intake of fresh and dried mushrooms combined with consuming beverages made from >or=1.05 g dried green tea leaves per day. The corresponding linear trends were statistically significant for joint effect (p < 0.001). We conclude that higher dietary intake of mushrooms decreased breast cancer risk in pre- and postmenopausal Chinese women and an additional decreased risk of breast cancer from joint effect of mushrooms and green tea was observed. More research is warranted to examine the effects of dietary mushrooms and mechanism of joint effects of phytochemicals on breast cancer.


Meta-analysis of the effect of β-glucan intake on blood cholesterol and glucose levels. OBJECTIVE: A meta-analysis was performed on epidemiologic studies to assess the relation between β-glucan consumption from oats and from barley on blood cholesterol level, triglyceride/triacylglycerol (TGL/TAG) level, and blood glucose level (BGL) in humans. In addition, the effect of β-glucan on total cholesterol (TC) and BGL was translated into an empirical dose-response model. METHODS: Thirty research articles that evaluated the effect of different exposure levels of β-glucan on blood cholesterol and BGL were analyzed, yielding 126 clinical studies. RESULTS: There was a significant inverse relation in TC (-0.60 mmol/L, 95% confidence interval [CI] -0.85 to -0.34), low-density lipoprotein (-0.66 mmol/L, 95% CI -0.96 to -0.36), and TGL/TAG (-0.04 mmol/L, 95% CI -0.15 to 0.07) after consumption of β-glucan. In contrast, an increase in high-density lipoprotein cholesterol was noted (0.03 mmol/L, 95% CI -0.06 to 0.13) with the random-effect model. The analysis showed a significant change in BGL (-2.58 mmol/L, 95% CI -3.22 to -1.84) with high heterogeneity between (I(2) = 97%) and across (τ(2) = 5.88) the studies. The fixed-effect model showed a significant change in TC, low-density lipoprotein, and BGL, whereas it showed no significant changes in high-density lipoprotein and TGL/TAG. The dose-response model showed that a 3-g/d dose of oat or barley β-glucan was sufficient to decrease TC. CONCLUSION: Consumption of 3 g/d of oat or barley β-glucan is sufficient to decrease blood cholesterol, whereas the effect on BGL is still inconclusive, with high heterogeneity, and requires further clinical research studies with longer intervention periods. Copyright © 2011 Elsevier Inc. All rights reserved.


The deadly quartet. Upper-body obesity, glucose intolerance, hypertriglyceridemia, and hypertension. The contribution of obesity to cardiovascular risk has not been adequately appreciated because of a failure to recognize the involvement of upper-body predominance of body weight with hypertension, diabetes, and hypertriglyceridemia even in the absence of significant overall obesity. This article examines the evidence that upper-body obesity, as usually induced by caloric excess in the presence of androgens, mediates these problems by way of hyperinsulinemia. Because of these interrelationships, there is a need to identify and prevent upper-body obesity or, failing that, to provide therapies that will control the associated problems without aggravating hyperinsulinemia.


Epidemiology of the metabolic syndrome in the USA. The metabolic syndrome is a common complex entity that has emerged as a worldwide epidemic and major public health care concern with a prevalence of approximately 25% in the United States. There have been a number of different definitions of the metabolic syndrome but all center around the metabolic abnormalities of central obesity, hypertension, decreased high-density lipoproteins and elevated triglycerides with insulin resistance as the uniting physiologic factor. The importance of the metabolic syndrome is not just related to its high prevalence rate but also because it predicts the development of diabetes and cardiovascular disease. Nonalcoholic fatty liver disease is now recognized to be the hepatic component of the metabolic syndrome, which along with its individual components - particularly diabetes and elevated triglycerides, are the major risk factors for the development of nonalcoholic steatohepatitis (NASH); the most severe form of nonalcoholic fatty liver disease. NASH may progress to cirrhosis, hepatocellular carcinoma, and liver failure. It is currently the third most common cause for liver transplantation and is projected to be the leading cause for liver transplantation in 2020. Weight loss (via diet or bariatric surgery) and vitamin E have recently been demonstrated to be effective treatments of NASH. Although these and other agents may prove to be effective treatments for NASH, the most effective therapeutic strategy would be early screening and intervention to prevent the development of insulin resistance and oxidative stress at a societal level. © 2011 The Author. Journal of Digestive Diseases © 2011 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.


Vegetarian Dietary Patterns Are Associated With a Lower Risk of Metabolic Syndrome OBJECTIVE The study objective was to compare dietary patterns in their relationship with metabolic risk factors (MRFs) and the metabolic syndrome (MetS). RESEARCH DESIGN AND METHODS Cross-sectional analysis of 773 subjects (mean age 60 years) from the Adventist Health Study 2 was performed. Dietary pattern was derived from a food frequency questionnaire and classified as vegetarian (35%), semi-vegetarian (16%), and nonvegetarian (49%). ANCOVA was used to determine associations between dietary pattern and MRFs (HDL, triglycerides, glucose, blood pressure, and waist circumference) while controlling for relevant cofactors. Logistic regression was used in calculating odds ratios (ORs) for MetS. RESULTS A vegetarian dietary pattern was associated with significantly lower means for all MRFs except HDL (P for trend < 0.001 for those factors) and a lower risk of having MetS (OR 0.44, 95% CI 0.30–0.64, P < 0.001) when compared with a nonvegetarian dietary pattern. CONCLUSIONS A vegetarian dietary pattern is associated with a more favorable profile of MRFs and a lower risk of MetS. The relationship persists after adjusting for lifestyle and demographic factors.


A pilot study of potassium supplementation in the treatment of hypokalemic patients with rheumatoid arthritis: a randomized, double-blinded, placeb... Patients with rheumatoid arthritis (RA) have been described as having significantly low serum potassium concentrations than that in healthy subjects. We assessed the therapeutic efficacy and tolerability of oral potassium supplement dissolved in grape juice in female hypokalemic patients with active RA. Thirty-two hypokalemic patients with active RA were investigated in a parallel, randomized design. In addition to their usual medication, the control group received placebo and the intervention group received 6000 mg chloride potassium dissolved in grape juice on 28 consecutive days. The primary outcome parameter was the change of pain on a visual analog scale (VAS). The American College of Rheumatology (ACR) percent response criteria and Disease Activity Score 28 (DAS28, 28-joint count) and the European League Against Rheumatism (EULAR) moderate response were assessed. Mean age was 48.6 +/- 6 years. In the potassium group, 43.75% (7/16) of the patients met the criteria of 33% lower pain intensity compared with 6.25% (1/16) in the placebo group (P < .02) at day 28. Also, 31.25% (5/16) of the patients in the intervention group achieved moderate responses, according to the EULAR criteria. The corresponding percentage for patients receiving placebo was 6.25% (1/16) (P < .05). Potassium supplements appeared to decrease pain intensity. PERSPECTIVE: This article reports a trial evaluating the effect of potassium supplementation in the treatment of pain in hypokalemic patients with rheumatoid arthritis. The elevated serum cortisol and potassium values in the treatment group correlate negatively with patient's assessment of pain intensity, reflecting an anti-pain effect for potassium supplementation.


Changes in nutrient intake and dietary quality among participants with type 2 diabetes following a low-fat vegan diet or a conventional diabetes di... BACKGROUND: Although vegan diets improve diabetes management, little is known about the nutrient profiles or diet quality of individuals with type 2 diabetes who adopt a vegan diet. OBJECTIVE: To assess the changes in nutrient intake and dietary quality among participants following a low-fat vegan diet or the 2003 American Diabetes Association dietary recommendations. DESIGN: A 22-week randomized, controlled clinical trial examining changes in nutrient intake and diet quality. SUBJECTS/SETTING: Participants with type 2 diabetes (n=99) in a free-living setting. RESEARCH DESIGN AND METHODS: Participants were randomly assigned to a low-fat vegan diet or a 2003 American Diabetes Association recommended diet. MAIN OUTCOME MEASURES: Nutrient intake and Alternate Healthy Eating Index (AHEI) scores were collected at baseline and 22 weeks. STATISTICAL ANALYSES PERFORMED: Between-group t tests were calculated for changes between groups and paired comparison t tests were calculated for changes within-group. Pearson's correlation assessed relationship of AHEI score to hemoglobin A1c and body weight changes. RESULTS: Both groups reported significant decreases in energy, protein, fat, cholesterol, vitamin D, selenium, and sodium intakes. The vegan group also significantly reduced reported intakes of vitamin B-12 and calcium, and significantly increased carbohydrate, fiber, total vitamin A activity, beta carotene, vitamins K and C, folate, magnesium, and potassium. The American Diabetes Association recommended diet group also reported significant decreases in carbohydrate and iron, but reported no significant increases. The vegan group significantly improved its AHEI score (P<0.0001), while the American Diabetes Association recommended diet group did not (P=0.7218). The difference in AHEI score at 22 weeks between groups was significant (P<0.0001). With both groups combined, AHEI score was negatively correlated with both changes in hemoglobin A1c value (r=-0.24, P=0.016) and weight (r=-0.27, P=0.007). CONCLUSIONS: Vegan diets increase intakes of carbohydrate, fiber, and several micronutrients, in contrast with the American Diabetes Association recommended diet. The vegan group improved its AHEI score whereas the American Diabetes Association recommended diet group's AHEI score remained unchanged.


Potassium intake, stroke, and cardiovascular disease a meta-analysis of prospective studies. OBJECTIVES: The objective of this study was to assess the relation between the level of habitual potassium intake and the incidence of cardiovascular disease (CVD). BACKGROUND: Prospective cohort studies have evaluated the relationship between habitual potassium intake and incidence of vascular disease, but their results have not been not entirely consistent. METHODS: We performed a systematic search for prospective studies published, without language restrictions (1966 to December 2009). Criteria for inclusion were prospective adult population study, assessment of baseline potassium intake, assessment of vascular events as outcome, and follow-up of at least 4 years. For each study, relative risks (RRs) and 95% confidence intervals (CIs) were extracted and pooled using a random-effect model, weighted for the inverse of the variance. Heterogeneity, publication bias, subgroup, and meta-regression analyses were performed. RESULTS: Eleven studies were identified, providing 15 cohort samples that included 247,510 male and female participants (follow-up 5 to 19 years), 7,066 strokes, 3,058 coronary heart disease (CHD) events, and 2,497 total CVD events. Potassium intake was assessed by 24-h dietary recall (n = 2), food frequency questionnaire (n = 6), or 24-h urinary excretion (n = 3). In the pooled analysis, a 1.64-g (42 mmol) per day higher potassium intake was associated with a 21% lower risk of stroke (RR: 0.79; 95% CI: 0.68 to 0.90; p = 0.0007), with a trend toward lower risk of CHD and total CVD that attained statistical significance after the exclusion of a single cohort, based on sensitivity analysis (RR: 0.93; 95% CI: 0.87 to 0.99; p = 0.03 and RR: 0.74; 95% CI: 0.60 to 0.91; p = 0.0037). CONCLUSIONS: Higher dietary potassium intake is associated with lower rates of stroke and might also reduce the risk of CHD and total CVD. These results support recommendations for higher consumption of potassium-rich foods to prevent vascular diseases. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.


Sodium and potassium intakes among US adults: NHANES 2003–2008 Background: The American Heart Association (AHA), Institute of Medicine (IOM), and US Departments of Health and Human Services and Agriculture (USDA) Dietary Guidelines for Americans all recommend that Americans limit sodium intake and choose foods that contain potassium to decrease the risk of hypertension and other adverse health outcomes. Objective: We estimated the distributions of usual daily sodium and potassium intakes by sociodemographic and health characteristics relative to current recommendations. Design: We used 24-h dietary recalls and other data from 12,581 adults aged ≥20 y who participated in NHANES in 2003–2008. Estimates of sodium and potassium intakes were adjusted for within-individual day-to-day variation by using measurement error models. SEs and 95% CIs were assessed by using jackknife replicate weights. Results: Overall, 99.4% (95% CI: 99.3%, 99.5%) of US adults consumed more sodium daily than recommended by the AHA (<1500 mg), and 90.7% (89.6%, 91.8%) consumed more than the IOM Tolerable Upper Intake Level (2300 mg). In US adults who are recommended by the Dietary Guidelines to further reduce sodium intake to 1500 mg/d (ie, African Americans aged ≥51 y or persons with hypertension, diabetes, or chronic kidney disease), 98.8% (98.4%, 99.2%) overall consumed >1500 mg/d, and 60.4% consumed >3000 mg/d—more than double the recommendation. Overall, <2% of US adults and ∼5% of US men consumed ≥4700 mg K/d (ie, met recommendations for potassium). Conclusion: Regardless of recommendations or sociodemographic or health characteristics, the vast majority of US adults consume too much sodium and too little potassium.


The insulin-like growth factor-I receptor is regulated by CD28 and protects activated T cells from apoptosis. Co-stimulatory signals through the CD28 receptor enhance the survival of T cells that have their antigen receptor (TCR) engaged. Here we show that stimulation through the CD28 receptor in the absence of TCR engagement with either an anti-CD28 cross-linking antibody or the CD80 ligand transiently increases expression of the insulin-like growth factor-I receptor (IGF-IR) on T cells. Antibodies that block signaling through the IGF-IR decrease the survival of T cells activated through the TCR and CD28 in the presence of IL-2 by more than 50%, and also enhance susceptibility to Fas-induced apoptosis. CD28 stimulation increases IGF-IR expression on Jurkat cells, and exogenously added IGF-I can protect these cells from Fas-induced apoptosis. We conclude that CD28-mediated enhancement of IGF-IR expression provides activated T cells with essential survival signals that are independent of survival mediated by IL-2 and Bcl-xl.


Good riddance: Thymocyte clonal deletion prevents autoimmunity. Clonal deletion is arguably the most important mechanism of eliminating self-reactive thymocytes from the T-cell repertoire. Recent work has identified new players in this process. On the thymocyte side, several molecules have been newly implicated in the pathway from initial T-cell receptor signaling through to the final result: gene transcription and thymocyte apoptosis. In addition, several proapoptotic molecules have been found to be necessary for the death of self-reactive thymocytes. On the antigen-presenting cell side, the expression of peripheral self-antigens, regulated at least in part by the autoimmune regulator (AIRE) protein, is crucial for complete elimination of autoreactive thymocytes. The importance of thymic peripheral antigen expression and clonal deletion to self-tolerance is demonstrated in the autoimmune diseases autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy and type-1 diabetes mellitus.


Upregulation of lymphocyte apoptosis as a strategy for preventing and treating autoimmune disorders: a role for whole-food vegan diets, fish oil an... Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which are lymphocyte growth factors, may have the potential to suppress apoptosis in thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food vegan diets may downregulate systemic IGF-I activity, it is proposed that such a diet, in conjunction with fish oil supplementation and treatment with dopamine agonists capable of suppressing prolactin secretion, may have utility for treating and preventing autoimmune disorders. This prediction is consistent with the extreme rarity of autoimmune disorders among sub-Saharan black Africans as long as they followed their traditional quasi-vegan lifestyles, and with recent ecologic studies correlating risks for IDDM and for multiple sclerosis mortality with animal product and/or saturated fat consumption. Moreover, there is evidence that vegan or quasi-vegan diets are useful in the management of rheumatoid arthritis, multiple sclerosis, and possibly SLE. The dopamine agonist bromocryptine exerts anti-inflammatory effects in rodent models of autoimmunity, and there is preliminary evidence that this drug may be clinically useful in several human autoimmune diseases; better tolerated D2-specific agonists such as cabergoline may prove to be more practical for use in therapy. The moderate clinical utility of supplemental fish oil in rheumatoid arthritis and certain other autoimmune disorders is documented. It is not unlikely that extra-thymic anti-inflammatory effects contribute importantly to the clinical utility of vegan diets, bromocryptine, and fish oil in autoimmunity. The favorable impact of low latitude or high altitude on autoimmune risk may be mediated by superior vitamin D status, which is associated with decreased secretion of parathyroid hormone; there are theoretical grounds for suspecting that parathyroid hormone may inhibit apoptosis in thymocytes. Androgens appear to up-regulate thymocyte apoptosis, may be largely responsible for the relative protection from autoimmunity enjoyed by men, and merit further evaluation for the management of autoimmunity in women. It will probably prove more practical to prevent autoimmune disorders than to reverse them once established; a whole-food vegan diet, coupled with fish oil and vitamin D supplementation, may represent a practical strategy for achieving this prevention, while concurrently lowering risk for many other life-threatening 'Western' diseases. Copyright 2001 Harcourt Publishers Ltd.


The rise and fall of horror autotoxicus and forbidden clones. Cui and associates show that healthy individuals have natural autoantibodies (NAAs) specific for myeloperoxidase, proteinase 3, and glomerular basement membrane (GBM) with the same specificity as anti-neutrophil cytoplasmic antibodies and anti-GBM antibodies that are pathogenic. Although Ehrlich proposed horror autotoxicus and Burnet envisioned elimination of forbidden clones, NAAs are present in all healthy individuals and play beneficial homeostatic roles. Pathogenic autoimmunity is dysregulation of natural homeostatic autoimmunity rather than onset of a previously absent self-recognition.


The flip side of immune surveillance: immune dependency. The growths of many and perhaps all tumors may be stimulated rather than inhibited by a quantitatively low level of immunity. The reason tumors have antigens may be that tumors do not develop in vivo in the absence of at least a minimal immune reaction; in this sense, cancer may be considered an autoimmune disease. This review, based largely on the work of our own laboratory, outlines the data showing that the titration of anti-tumor immunity exhibits the phenomenon of hormesis, i.e. the dose-response curve is non-linear such that low levels of immunity are generally stimulatory but larger quantities of the same immune reactants may inhibit tumor growth. Evidence is also reviewed that suggests that the immune response may vary qualitatively and quantitatively during progression, such that there seems to be, during oncogenesis, a very low level of immune reaction that aids initial tumor growth, followed by a larger reaction that may cause remission of early neoplasms, followed, if the neoplasm survives, by a relative immunologic tolerance to the tumor that may be dependent, at least in part, on suppressor cells. This knowledge may help to explain some clinical observations concerning the relationships among tumor types and the organ distribution of metastases.


Immunological enhancement of breast cancer. Breast cancer is a complex disease. Its aetiology is multifactorial, its period of development can span decades, and its clinical course is highly variable. Evaluation of the role of the immune response in either the development or control of breast cancer is also complex. Nevertheless, there is substantial information that in this disease, the immune response is not a host defence reaction and may even serve to facilitate cancer development. This evidence comes from a variety of sources including clinical-pathological investigations in women that show a correlation between the intensity of lymphocytic infiltration into the tumour mass with poor prognosis, studies in breast cancer patients that demonstrate a similar correlation between delayed hypersensitivity reactivity or in vitro assays of immune reactivity to tumour cell membranes or non-specific antigens and poor prognosis, and analyses of cancer incidence in chronically immunosuppressed, kidney transplant recipients who develop an unexpectedly low incidence of breast cancer. The overall conclusions from these human studies are corroborated by observations in mouse mammary tumour models that also demonstrate immune enhancement of breast cell proliferation in vitro and of breast cancer development in vivo. Potential mechanisms for these effects include production, by inflammatory cell infiltrates, of direct or indirect modulators of breast cell growth, e.g. cytokines, peptide or steroid hormones, enzymes involved in steroid metabolism, as well as of antibodies to growth factors or their receptors. These immune facilitatory mechanisms must be overcome if immune-based therapies are to be applied successfully in breast cancer.


Recrudescent Kaposi's sarcoma after initiation of HAART: a manifestation of immune reconstitution syndrome. The objective of this case series and literature review is to characterize the clinical course and prognosis of HIV-infected patients with Kaposi's sarcoma (KS) flare during immune reconstitution inflammatory syndrome (IRIS), a heterogeneous and sometimes fatal disorder of immune perturbation after initiation of highly active antiretroviral therapy (HAART). Medical records of 9 HIV-infected patients with KS flare after virologic and immunologic response to HAART were reviewed from a single institution. An additional 10 cases were abstracted by computerized search of the medical literature. In our single institution series, mean time to onset of KS flare was 5 weeks. Pretreatment mean CD4+ count was 190 cells/mm(3) and mean HIV viral load was 153,934 copies per milliliter. During flare, mean CD4+ count was 256 cells/mm(3) and mean HIV viral load was 1156 copies per milliliter. Similar aggregate results are represented in the literature. Six fatalities are reported, 4 from pulmonary KS and 2 from unrelated causes. Systemic chemotherapy universally led to tumor regression, but was administered in only 10 of 19 cases. In no instance was HAART discontinued. Onset of IRIS-associated KS flare is observed as early as 3 weeks, with most cases diagnosed within 2 months after immunologic and virologic response to HAART. Such a flare does not necessarily portend a poor prognosis. Even for those patients with rapidly symptomatic KS, early systemic chemotherapy is effective in suppressing IRIS-associated flare. Close clinical supervision is warranted for the KS patient initiating, changing, or resuming HAART. Particular vigilance is recommended for pulmonary involvement.


Melanomas in renal transplant recipients. BACKGROUND: It is well documented that renal transplant recipients are at increased risk of developing skin cancers, in particular squamous cell carcinomas. Less extensively reviewed in the literature is the increased incidence of malignant melanoma. We have reviewed 10 patients in the Oxford renal transplant population who developed 12 melanomas following transplantation. OBJECTIVES: To determine the incidence and characteristics of melanoma in renal transplant recipients. METHODS: We reviewed the case notes and pathology of all patients who developed melanoma within the Oxford Renal Transplant Unit. The clinical details were recorded including date of transplant, immunosuppressive therapy, interval between transplant and melanoma, site of occurrence, history of sun exposure, type of clinician diagnosing the melanoma, history of other skin malignancies and outcome. From the histopathology we documented various prognostic factors. RESULTS: Ten patients developed 12 melanomas (one patient had three melanomas) from a population of 1874 transplanted patients. The total number of transplant years was 11 942.2. The incidence of melanoma in our population was 12 per 11 942.2 transplant years, which is approximately 8 times greater than the standardized rate for this region. We found that the mean interval between transplant and melanoma was approximately 11 years (median 8.5). A dermatologist was the diagnosing clinician in at least 67% of cases. Melanomas occurred on the trunk in the majority of cases (58%), followed by the upper limb (25%). All patients apart from one are alive with no recurrence of their melanoma. One patient died as a result of metastatic melanoma. The mean follow-up period following melanoma was 3.7 years. In all patients apart from the patient who died, the melanomas were < 1 mm Breslow thickness. That patient's melanoma was 4.5 mm thick. There was no precursor naevus in eight of the 12 melanomas. In two there was a precursor dysplastic naevus. In the cases in vertical growth phase the tumour-infiltrating lymphocyte response was absent in four cases and nonbrisk in one patient. CONCLUSIONS: In the Oxford transplant population studied melanomas occurred at approximately 8 times the rate in the general population. This is the highest rate reported in the literature. The patients had a better outcome than reported previously. This may be due to detection at a relatively early stage. Renal transplant recipients attend dedicated dermatology clinics in Oxford, which may have contributed to the early diagnosis and good outcome.


Sucrose activates human taste pathways differently from artificial sweetener. Animal models suggest that sucrose activates taste afferents differently than non-caloric sweeteners. Little information exists how artificial sweeteners engage central taste pathways in the human brain. We assessed sucrose and sucralose taste pleasantness across a concentration gradient in 12 healthy control women and applied 10% sucrose and matched sucralose during functional magnet resonance imaging. The results indicate that (1) both sucrose and sucralose activate functionally connected primary taste pathways; (2) taste pleasantness predicts left insula response; (3) sucrose elicits a stronger brain response in the anterior insula, frontal operculum, striatum and anterior cingulate, compared to sucralose; (4) only sucrose, but not sucralose, stimulation engages dopaminergic midbrain areas in relation to the behavioral pleasantness response. Thus, brain response distinguishes the caloric from the non-caloric sweetener, although the conscious mind could not. This could have important implications on how effective artificial sweeteners are in their ability to substitute sugar intake.


Effect of covert nutritive dilution on the spontaneous food intake of obese individuals: a pilot study. The present study investigated the feasibility of a new experimental approach for studying the effect of covert nutritive dilution on the spontaneous food intake of obese individuals. Eight obese subjects were studied as inpatients on a metabolic unit for 15 days during which time they were unaware that their food intake was being monitored. A platter method of food presentation encouraged ad libitum ingestion. Caloric dilution was achieved by replacing sucrose-containing products with aspartame-sweetened analogues in an otherwise normal diet. During the base-line period the subjects spontaneously ate sufficient conventional food to maintain or even slightly increase body weight. Covert substitution of aspartame-sweetened products for their sucrose counterparts resulted in an immediate reduction in spontaneous energy intake of approximately 25%. The aspartame analogues were as well accepted as their conventional counterparts, as indicated by the equal quantity of each consumed. These preliminary results demonstrate that, in a metabolic ward setting, it is possible to maintain the spontaneous food intake of obese individuals at levels sufficient to preserve body weight and arbitrarily to decrease those levels of intake by 25% or more through covert changes in the caloric density of the diet.


Erythritol is a sweet antioxidant. OBJECTIVE: Hyperglycemia, oxidative stress, and the onset and progression of diabetic complications are strongly linked. Reduction of oxidative stress could be of utmost importance in the long-term treatment of diabetic patients. The chronic nature of the disease calls for a mode of antioxidant intake that can be sustained easily, e.g., by the diet. Erythritol, a simple polyol, could be such a compound. It is orally available, well tolerated, and its chemical structure resembles that of mannitol, a well-known hydroxyl radical (HO*) scavenger. METHODS: We studied the antioxidant properties of erythritol in vitro and subsequently determined its antioxidant activity and its vasoprotective effect in the streptozotocin diabetic rat. RESULTS: Erythritol was shown to be an excellent HO* radical scavenger and an inhibitor of 2,2'-azobis-2-amidinopropane dihydrochloride-induced hemolysis but inert toward superoxide radicals. High-performance liquid chromatographic and electron spin resonance spectroscopy studies showed that the reaction of erythritol with hydroxyl radicals resulted in the formation of erythrose and erythrulose by abstraction of a carbon-bound hydrogen atom. In the streptozotocin diabetic rat, erythritol displayed an endothelium-protective effect and, in accordance with the in vitro experiments, erythrose was found in the urine of erythritol-consuming rats. CONCLUSION: Erythritol acts as an antioxidant in vivo and may help protect against hyperglycemia-induced vascular damage. Copyright 2010 Elsevier Inc. All rights reserved.


Human gut microbiota does not ferment erythritol. Erythritol, a naturally occurring polyol, is gaining attention as a bulk sweetener for human nutrition. Industrially, it is produced from glucose by fermentation. From various studies it is known to be non-cariogenic. Moreover, it is rapidly absorbed in the small intestine and quantitatively excreted in the urine. Only about 10 % enters the colon. Earlier in vitro experiments showed that erythritol remained unfermented for a fermentation period of 12 h. In order to investigate whether fresh human intestinal microbiota is able to adapt its enzyme activities to erythritol, a 24 h lasting fermentation was carried out under well-standardised in vitro conditions. For comparison maltitol, lactulose and blank (faecal inoculum only) were incubated as well. Fermentation patterns were established by following total gas production, hydrogen accumulation, changes in pH value, SCFA production and substrate degradation. Taking all fermentation parameters into account, erythritol turned out to be completely resistant to bacterial attack within 24 h, thus excluding an adaptation within that period. Since under in vivo conditions more easily fermentable substrates enter the colon continuously, it seems very unlikely that erythritol will be fermented in vivo.


Formaldehyde, aspartame, and migraines: a possible connection. Aspartame is a widely used artificial sweetener that has been linked to pediatric and adolescent migraines. Upon ingestion, aspartame is broken, converted, and oxidized into formaldehyde in various tissues. We present the first case series of aspartame-associated migraines related to clinically relevant positive reactions to formaldehyde on patch testing.


Aspartame-induced fibromyalgia, an unusual but curable cause of chronic pain. We report for the first time an unusual musculoskeletal adverse effect of aspartame in two patients. A 50-year-old woman had been suffering from widespread pain and fatigue for more than 10 years leading to the diagnosis of fibromyalgia. During a vacation in a foreign country, she did not suffer from painful symptoms since she had forgotten to take her aspartame. All of the symptoms reappeared in the days following her return when she reintroduced aspartame into her daily diet. Thus, aspartame was definitively excluded from her diet, resulting in a complete regression of the fibromyalgia symptoms. A 43-year-old man consulted for a 3-year history of bilateral forearm, wrist, and hand and cervical pain with various unsuccessful treatments. A detailed questioning allowed to find out that he had been taking aspartame for three years. The removal of aspartame was followed by a complete regression of pain, without recurrence. We believe that these patients' chronic pain was due to the ingestion of aspartame, a potent flavouring agent, widely used in food as a calorie-saver. The benefit/ risk ratio of considering the diagnosis of aspartame-induced chronic pain is obvious: the potential benefit is to cure a disabling chronic disease, to spare numerous laboratory and imaging investigations, and to avoid potentially harmful therapies; the potential risk is to temporarily change the patient's diet. Thus, practitioners should ask patients suffering from fibromyalgia about their intake of aspartame. In some cases, this simple question might lead to the resolution of a disabling chronic disease.


Validation of a method for the detection of virulent Yersinia enterocolitica and their distribution in slaughter pigs from conventional and alterna... Various methods have been described in the literature for the detection of virulent Yersinia enterocolitica in pigs. The risk factors for pig herd contamination have yet to be determined. The objective of this study was to validate a sensitive method for the detection of Y. enterocolitica and to describe the distribution of the bacteria in pigs at slaughter from conventional and alternative ("organic") housing systems. First, samples were collected from tonsils, caecum with caecal contents, and the caecal lymph nodes of 60 slaughter pigs. These samples were used to compare the sensitivity of six different laboratory culture methods either in common use or described in the literature with that of a polymerase chain reaction with two primer pairs (multiplex PCR). Then, only PCR was used to examine tonsils, caecum and caecal lymph nodes from two groups of slaughter pigs: 210 from six conventional fattening farms and 200 from three with alternative housing. The results of the multiplex PCR were positive in 28 cases. All culture methods proved inferior to PCR in sensitivity. In the second part of the study, PCR detected 36 (18%) positive pigs from alternative housing and 60 (29%) from conventional housing (p<0.05). The highest rate of Y. enterocolitica contamination was found in tonsils (11% alternative, 22% conventional; p<0.05), followed by caecum (5%, 11%) and lymph nodes (2%, 7%). The housing system appears to be one important factor in the prevalence of this common pathogen in pig herds, as we found important differences between the two systems studied here. In the conventional system, the main risk factors appeared to be sourcing pigs from different pig suppliers, use of commercial feed and transportation to slaughter.


Contamination of carcasses with human pathogenic Yersinia enterocolitica 4/O:3 originates from pigs infected on farms. Pigs are considered as a major reservoir of human pathogenic Yersinia enterocolitica and a source of human yersiniosis. However, the transmission route of Y. enterocolitica from farm to pork is still unclear. The transmission of pathogenic Y. enterocolitica from pigs to carcasses and pluck sets was investigated by collecting samples from 364 individual ear-tagged pigs on the farm and at the slaughterhouse. In addition, isolated strains were analyzed, using pulsed-field gel electrophoresis. Isolation of similar genotypes of pathogenic Y. enterocolitica 4/O:3 in animals on the farm and at the slaughterhouse and in carcasses shows that carcass contamination originates from the strains a pig carries during the fattening period. Direct contamination from the carrier pig to its subsequent pluck set is also the primary contamination route for pluck sets, but cross-contamination appears to have a larger impact on pluck set contamination than on carcasses. In this study, the within-farm prevalence of pathogenic Y. enterocolitica varied from 0% to 100%, indicating specific farm factors affect the prevalence of Y. enterocolitica in pigs. The association of farm factors with the high prevalence of pathogenic Y. enterocolitica on farms was studied for the first time, using correlation and two-level logistic regression analyses. Specific farm factors, i.e. drinking from a nipple, absence of coarse feed or bedding for slaughter pigs, and no access of pest animals to pig house, were associated with a high prevalence of pathogenic Y. enterocolitica 4/O:3.


Prevalence of Yersinia enterocolitica shedding and bioserotype distribution in Ontario finisher pig herds in 2001, 2002, and 2004. We investigated characteristics of Yersinia enterocolitica infection in Ontario finisher pig herds. Our specific objectives were to estimate or test: prevalence of Y. enterocolitica shedding in finisher pigs, bioserotype distribution, agreement between the herd-level tests based on sampling pig and pooled fecal samples, whether bioserotypes cluster by farms, and whether Y. enterocolitica-positive herds cluster spatially. In total, 3747 fecal samples were collected from 100 farms over the years 2001, 2002, and 2004 (250 total herd visits). Fecal samples were tested by culture and positive isolates were biotyped and serotyped. Apparent pig-level prevalence of Y. enterocolitica was 1.8%, 3.2%, and 12.5% in 2001, 2002, and 2004, respectively. Estimated true pig-level prevalence of Y. enterocolitica was 5.1%, 9.1%, and 35.1% in 2001, 2002, and 2004, respectively. Herd-level prevalence was 16.3%, 17.9%, and 37.5% in 2001, 2002, and 2004, respectively. In all years, the most common bioserotype was 4, O:3, followed by bioserotype 2, O:5,27. Kappa between herd-level status based on pig and pooled samples ranged between 0.51 and 0.68 for biotype 1A and bioserotype 4, O:3, respectively. For 4, O:3, a significant bias in discordant pairs was detected, indicating that pig samples were more sensitive than pooled samples in declaring a herd as positive. Farms tended to be repeatedly positive with the same bioserotype, but positive study farms did not cluster spatially (suggesting lack of between herd transmission and lack of a common geographic risk factor). Copyright 2009 Elsevier B.V. All rights reserved.


Annual cost of illness and quality-adjusted life year losses in the United States due to 14 foodborne pathogens. In this article we estimate the annual cost of illness and quality-adjusted life year (QALY) loss in the United States caused by 14 of the 31 major foodborne pathogens reported on by Scallan et al. (Emerg. Infect. Dis. 17:7-15, 2011), based on their incidence estimates of foodborne illness in the United States. These 14 pathogens account for 95 % of illnesses and hospitalizations and 98 % of deaths due to identifiable pathogens estimated by Scallan et al. We estimate that these 14 pathogens cause $14.0 billion (ranging from $4.4 billion to $33.0 billion) in cost of illness and a loss of 61,000 QALYs (ranging from 19,000 to 145,000 QALYs) per year. Roughly 90 % of this loss is caused by five pathogens: nontyphoidal Salmonella enterica ($3.3 billion; 17,000 QALYs), Campylobacter spp. ($1.7 billion; 13,300 QALYs), Listeria monocytogenes ($2.6 billion; 9,400 QALYs), Toxoplasma gondii ($3 billion; 11,000 QALYs), and norovirus ($2 billion; 5,000 QALYs). A companion article attributes losses estimated in this study to the consumption of specific categories of foods. To arrive at these estimates, for each pathogen we create disease outcome trees that characterize the symptoms, severities, durations, outcomes, and likelihoods of health states associated with that pathogen. We then estimate the cost of illness (medical costs, productivity loss, and valuation of premature mortality) for each pathogen. We also estimate QALY loss for each health state associated with a given pathogen, using the EuroQol 5D scale. Construction of disease outcome trees, outcome-specific cost of illness, and EuroQol 5D scoring are described in greater detail in a second companion article.


Ranking the disease burden of 14 pathogens in food sources in the United States using attribution data from outbreak investigations and expert elic... Understanding the relative public health impact of major microbiological hazards across the food supply is critical for a risk-based national food safety system. This study was conducted to estimate the U.S. health burden of 14 major pathogens in 12 broad categories of food and to then rank the resulting 168 pathogen-food combinations. These pathogens examined were Campylobacter, Clostridium perfringens, Escherichia coli O157:H7, Listeria monocytogenes, norovirus, Salmonella enterica, Toxoplasma gondii, and all other FoodNet pathogens. The health burden associated with each pathogen was measured using new estimates of the cost of illness and loss of quality-adjusted life years (QALYs) from acute and chronic illness and mortality. A new method for attributing illness to foods was developed that relies on both outbreak data and expert elicitation. This method assumes that empirical data are generally preferable to expert judgment; thus, outbreak data were used for attribution except where evidence suggests that these data are considered not representative of food attribution. Based on evaluation of outbreak data, expert elicitation, and published scientific literature, outbreak-based attribution estimates for Campylobacter, Toxoplasma, Cryptosporidium, and Yersinia were determined not representative; therefore, expert-based attribution were included for these four pathogens. Sensitivity analyses were conducted to assess the effect of attribution data assumptions on rankings. Disease burden was concentrated among a relatively small number of pathogen-food combinations. The top 10 pairs were responsible for losses of over $8 billion and 36,000 QALYs, or more than 50 % of the total across all pairs. Across all 14 pathogens, poultry, pork, produce, and complex foods were responsible for nearly 60 % of the total cost of illness and loss of QALYs.


Too early to dismiss Yersinia enterocolitica infection in the aetiology of Graves' disease: evidence from a twin case-control study. BACKGROUND: Yersinia enterocolitica (YE) infection has long been implicated in the pathogenesis of Graves' disease (GD). The association between YE and GD could, however, also be due to common genetic or environmental factors affecting the development of both YE infection and GD. This potential confounding can be minimized by investigation of twin pairs discordant for GD. AIM: To examine whether YE infection is associated with GD. DESIGN: We first conducted a classical case-control study of individuals with (61) and without (122) GD, and then a case-control study of twin pairs (36) discordant for GD. METHODS: Immunoglobulin (Ig)A and IgG antibodies to virulence-associated Yersinia outer membrane proteins (YOPs) were measured. MAIN OUTCOME MEASURES: The prevalence of YOP IgA and IgG antibodies. RESULTS: Subjects with GD had a higher prevalence of YOP IgA (49%vs. 34%, P = 0.054) and YPO IgG (51%vs. 35%, P = 0.043) than the external controls. The frequency of chronic YE infection, reflected by the presence of both IgA and IgG YOP antibodies, was also higher among cases than controls (49%vs. 33%, P = 0.042). Similar results were found in twin pairs discordant for GD. In the case-control analysis, individuals with GD had an increased odds ratio (OR) of YE infection: IgA 1.84 (95% CI 0.99-3.45) and IgG 1.90 (95% CI 1.02-3.55). In the co-twin analysis, the twin with GD also had an increased OR of YE infection: IgA 5.5 (95% CI 1.21-24.81) and IgG 5.0 (95% CI 1.10-22.81). CONCLUSION: The finding of an association between GD and YE in the case-control study and within twin pairs discordant for GD supports the notion that YE infection plays an aetiological role in the occurrence of GD, or vice versa. Future studies should examine the temporal relationship of this association in more depth.


Prevalence of Pathogenic Yersinia enterocolitica Strains in Pigs in the United States Yersinia enterocolitica is considered an important food-borne pathogen impacting the pork production and processing industry in the United States. Since this bacterium is a commensal of swine, the primary goal of this study was to determine the prevalence of pathogenic Y. enterocolitica in pigs in the United Sates using feces as the sample source. A total of 2,793 fecal samples were tested for its presence in swine. Fecal samples were collected from late finisher pigs from 77 production sites in the 15 eastern and midwestern pork-producing states over a period of 27 weeks (6 September 2000 to 20 March 2001). The prevalence of ail-positive Y. enterocolitica was determined in samples using both a fluorogenic 5′ nuclease PCR assay and a culture method. The mean prevalence was 13.10% (366 of 2,793 fecal samples tested) when both PCR- and culture-positive results were combined. Forty-one of 77 premises (53.25%) contained at least one fecal sample positive for the ail sequence. The PCR assay indicated a contamination rate of 12.35% (345/2,793) compared to 4.08% (114/2,793) by the culture method. Of the 345 PCR-positive samples, 252 were culture negative, while of the 114 culture-positive samples, 21 were PCR negative. Among 77 premises, the PCR assay revealed a significantly (P < 0.05) higher percentage (46.75%, n = 36 sites) of samples positive for the pathogen (ail sequence) than the culture method (22.08%, n = 17 sites). Thus, higher sensitivity, with respect to number of samples and sites identified as positive for the PCR method compared with the culture method for detecting pathogenic Y. enterocolitica, was demonstrated in this study. The results support the hypothesis that swine are a reservoir for Y. enterocolitica strains potentially pathogenic for humans.


Behavior of Yersinia enterocolitica in Foods Yersinia enterocolitica are ubiquitous, being isolated frequently from soil, water, animals, and a variety of foods. They comprise a biochemically heterogeneous group that can survive and grow at refrigeration temperatures. The ability to propagate at refrigeration temperatures is of considerable significance in food hygiene. Virulent strains of Yersinia invade mammalian cells such as HeLa cells in tissue culture. Two chromosomal genes, inv and ail, were identified for cell invasion of mammalian. The pathogen can cause diarrhoea, appendicitis and post-infection arthritis may occur in a small proportion of cases. The most common transmission route of pathogenic Y. enterocolitica is thought to be fecal-oral via contaminated food. Direct person-to-person contact is rare. Occasionally, pathogenic Y. enterocolitica has been detected in vegetables and environmental water; thus, vegetables and untreated water are also potential sources of human yersiniosis. However, the isolation rates of pathogenic Y. enterocolitica have been low, which may be due to the limited sensitivity of the detection methods. To identify other possible transmission vehicles, different food items should be studied more extensively. Many factors related to the epidemiology of Y. enterocolitica, such as sources, transmission routes, and predominating genotypes remain obscure because of the low sensitivity of detection methods.


Vital signs: incidence and trends of infection with pathogens transmitted commonly through food--foodborne diseases active surveillance network, 10... BACKGROUND: In the United States, contaminated food causes approximately 1,000 reported disease outbreaks and an estimated 48 million illnesses, 128,000 METHODS: The Foodborne Diseases Active Surveillance Network (FoodNet) conducts surveillance among 15% of the U.S. population for laboratory-confirmed infections with nine pathogens transmitted commonly through food. Overall and pathogen-specific changes in incidence were estimated from 1996-1998 to 2010 and from 2006-2008 to 2010.hospitalizations, and 3,000 deaths annually. This report summarizes 2010 surveillance data and describes trends since 1996. RESULTS: A total of 19,089 infections, 4,247 hospitalizations, and 68 deaths were reported from FoodNet sites in 2010. Salmonella infection was the most common infection reported (17.6 illnesses per 100,000 persons) and was associated with the largest number of hospitalizations (2,290) and deaths (29); no significant change in incidence of Salmonella infection has occurred since the start of surveillance during 1996-1998. Shiga toxin-producing Escherichia coli (STEC) O157 infection caused 0.9 illnesses per 100,000. Compared with 1996-1998, overall incidence of infection with six key pathogens in 2010 was 23% lower, and pathogen-specific incidence was lower for Campylobacter, Listeria, STEC O157, Shigella, and Yersinia infection but higher for Vibrio infection. Compared with a more recent period, 2006--2008, incidence in 2010 was lower for STEC O157 and Shigella infection but higher for Vibrio infection. CONCLUSIONS: The incidence of STEC O157 infection has declined to reach the 2010 national health objective target of ≥1 case per 100,000. This success, as well as marked declines since 1996-1998 in overall incidence of six key foodborne infections, demonstrates the feasibility of preventing foodborne illnesses. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Salmonella infection should be targeted because it has not declined significantly in more than a decade, and other data indicate that it is one of the most common foodborne infections, resulting in an estimated $365 million in direct medical costs annually. The prevention measures that reduced STEC O157 infection need to be applied more broadly to reduce Salmonella and other infections. Effective measures from farm to table include preventing contamination of meat during slaughter and of all foods, including produce, during processing and preparation; cooking meat thoroughly; vigorously detecting and investigating outbreaks; and recalling contaminated food.


Prevalence of Yersinia enterocolitica in different phases of production on swine farms. Swine have been identified as the primary reservoir of pathogenic Yersinia enterocolitica (YE), but little research has focused on the epidemiology of YE at the farm level. The objective of this study was to describe the prevalence of YE in different production phases on swine farms. In this cross-sectional study, individual pigs on eight swine operations were sampled for the presence of YE. On each farm, both feces and oral-pharyngeal swabs were collected from pigs in five different production phases: gestating, farrowing, suckling, nursery, and finishing. A pig was considered positive if either sample tested positive. Samples were cultured with cold enrichment followed by isolation on selective media plates. Presumptive isolates were confirmed as YE and assayed for the presence of ail with a multiplex PCR. Of the 2,349 pigs sampled, 120 (5.1%) tested positive, and of those, 51 were ail positive (42.5% of YE isolates). On all farms, there was a trend of increasing prevalence as pigs mature. Less than 1% of suckling piglets tested positive for YE. Only 1.4% (44.4% of which were ail positive) of nursery pigs tested positive, but 10.7% (48.1% of which were ail positive) of finishing pigs harbored YE. Interestingly, gestating sows had the second highest prevalence of YE at 9.1% (26.7% of which were ail positive), yet YE was never detected from the farrowing sows. These results represent the first on-farm description of YE in U.S. herds and provide the initial step for designing future studies of YE.


Yersinia enterocolitica: a brief review of the issues relating to the zoonotic pathogen, public health challenges, and the pork production chain. Yersinia enterocolitica is a zoonotic agent that causes gastrointestinal disease in humans, as well as reactive arthritis and erythema nodosum. Enteropathogenic Yersinia are the etiological agents for yersiniosis, which can be acquired through the consumption of contaminated foods. As porcine animals are the main carriers of Y. enterocolitica, food safety measures to minimize human infection are of increasing interest to the scientific and medical community. In this review, we examine why it is imperative that information on the reservoirs, prevalence, virulence, and ability of this pathogen to survive in different environments is further investigated to provide rational measures to prevent or decrease associated disease risks.