query: plant-based diet

positive: The spermicidal potency of Coca-Cola and Pepsi-Cola. The inhibitory effect of Old Coke, caffeine-free New Coke, New Coke, Diet Coke and Pepsi-Cola on human sperm motility was studied with a trans-membrane migration method. None of them could decrease sperm motility to less than 70% of control within one hour. A previous study which claimed a marked variation of spermicidal potencies among different formulations of Coca-Cola could not be confirmed. Even if cola has a spermicidal effect, its potency is relatively weak as compared with other well-known spermicidal agents.

positive: Dietary fat and semen quality among men attending a fertility clinic BACKGROUND The objective of this study was to examine the relation between dietary fats and semen quality parameters. METHODS Data from 99 men with complete dietary and semen quality data were analyzed. Fatty acid levels in sperm and seminal plasma were measured using gas chromatography in a subgroup of men (n = 23). Linear regression was used to determine associations while adjusting for potential confounders. RESULTS Men were primarily Caucasian (89%) with a mean (SD) age of 36.4 (5.3) years; 71% were overweight or obese; and 67% were never smokers. Higher total fat intake was negatively related to total sperm count and concentration. Men in the highest third of total fat intake had 43% (95% confidence interval (CI): 62–14%) lower total sperm count and 38% (95% CI: 58–10%) lower sperm concentration than men in the lowest third (Ptrend = 0.01). This association was driven by intake of saturated fats. Levels of saturated fatty acids in sperm were also negatively related to sperm concentration (r= −0.53), but saturated fat intake was unrelated to sperm levels (r = 0.09). Higher intake of omega-3 polyunsaturated fats was related to a more favorable sperm morphology. Men in the highest third of omega-3 fatty acids had 1.9% (0.4–3.5%) higher normal morphology than men in the lowest third (Ptrend = 0.02). CONCLUSIONS In this preliminary cross-sectional study, high intake of saturated fats was negatively related to sperm concentration whereas higher intake of omega-3 fats was positively related to sperm morphology. Further, studies with larger samples are now required to confirm these findings.

positive: Heavy metals in commercial fish in New Jersey. Levels of contaminants in fish are of particular interest because of the potential risk to humans who consume them. While attention has focused on self-caught fish, most of the fish eaten by the American public comes from commercial sources. We sampled 11 types of fish and shellfish obtained from supermarkets and specialty fish markets in New Jersey and analyzed them for arsenic, cadmium, chromium, lead, manganese, mercury, and selenium. We test the null hypothesis that metal levels do not vary among fish types, and we consider whether the levels of any metals could harm the fish themselves or their predators or pose a health risk for human consumers. There were significant interspecific differences for all metals, and no fish types had the highest levels of more than two metals. There were few significant correlations (Kendall tau) among metals for the three most numerous fish (yellowfin tuna, bluefish, and flounder), the correlations were generally low (below 0.40), and many correlations were negative. Only manganese and lead positively were correlated for tuna, bluefish, and flounder. The levels of most metals were below those known to cause adverse effects in the fish themselves. However, the levels of arsenic, lead, mercury, and selenium in some fish were in the range known to cause some sublethal effects in sensitive predatory birds and mammals and in some fish exceeded health-based standards. The greatest risk from different metals resided in different fish; the species of fish with the highest levels of a given metal sometimes exceeded the human health guidance or standards for that metal. Thus, the risk information given to the public (mainly about mercury) does not present a complete picture. The potential of harm from other metals suggests that people not only should eat smaller quantities of fish known to accumulate mercury but also should eat a diversity of fish to avoid consuming unhealthy quantities of other heavy metals. However, consumers should bear in mind that standards have a margin of safety.

positive: A prospective study of intake of trans-fatty acids from ruminant fat, partially hydrogenated vegetable oils, and marine oils and mortality from CVD. Trans-fatty acids (TFA) have adverse effects on blood lipids, but whether TFA from different sources are associated with risk of CVD remains unresolved. The objective of the present study was to evaluate the association between TFA intake from partially hydrogenated vegetable oils (PHVO), partially hydrogenated fish oils (PHFO) and ruminant fat (rTFA) and risks of death of CVD, CHD, cerebrovascular diseases and sudden death in the Norwegian Counties Study, a population-based cohort study. Between 1974 and 1988, participants were examined for up to three times. Fat intake was assessed with a semi-quantitative FFQ. A total of 71,464 men and women were followed up through 2007. Hazard ratios (HR) and 95 % CI were estimated with Cox regression. Energy from TFA was compared to energy from all other sources, carbohydrates or unsaturated cis-fatty acids with different multivariable models. During follow-up, 3870 subjects died of CVD, 2383 of CHD, 732 of cerebrovascular diseases and 243 of sudden death. Significant risks, comparing highest to lowest intake category, were found for: TFA from PHVO and CHD (HR 1.23 (95 % CI 1.00, 1.50)) and cerebrovascular diseases (HR 0.65 (95 % CI 0.45, 0.94)); TFA from PHFO and CVD (HR 1.14 (95 % CI 1.03, 1.26)) and cerebrovascular diseases (HR 1.32 (95 % CI 1.04, 1.69)); and rTFA intake and CVD (HR 1.30 (95 % CI 1.05, 1.61)), CHD (HR 1.50 (95 % CI 1.11, 2.03)) and sudden death (HR 2.73 (95 % CI 1.19, 6.25)) in women. These associations with rTFA intake were not significant in men (P interaction ≥ 0.01). The present study supports that TFA intake, irrespective of source, increases CVD risk. Whether TFA from PHVO decreases risk of cerebrovascular diseases warrants further investigation.

positive: Trans Fat Consumption and Aggression Background Dietary trans fatty acids (dTFA) are primarily synthetic compounds that have been introduced only recently; little is known about their behavioral effects. dTFA inhibit production of omega-3 fatty acids, which experimentally have been shown to reduce aggression. Potential behavioral effects of dTFA merit investigation. We sought to determine whether dTFA are associated with aggression/irritability. Methodolgy/Prinicpal Findings We capitalized on baseline dietary and behavioral assessments in an existing clinical trial to analyze the relationship of dTFA to aggression. Of 1,018 broadly sampled baseline subjects, the 945 adult men and women who brought a completed dietary survey to their baseline visit are the target of this analysis. Subjects (seen 1999–2004) were not on lipid medications, and were without LDL-cholesterol extremes, diabetes, HIV, cancer or heart disease. Outcomes assessed adverse behaviors with impact on others: Overt Aggression Scale Modified-aggression subscale (primary behavioral endpoint); Life History of Aggression; Conflict Tactics Scale; and self-rated impatience and irritability. The association of dTFA to aggression was analyzed via regression and ordinal logit, unadjusted and adjusted for potential confounders (sex, age, education, alcohol, and smoking). Additional analyses stratified on sex, age, and ethnicity, and examined the prospective association. Greater dTFA were strongly significantly associated with greater aggression, with dTFA more consistently predictive than other assessed aggression predictors. The relationship was upheld with adjustment for confounders, was preserved across sex, age, and ethnicity strata, and held cross-sectionally and prospectively. Conclusions/Significance This study provides the first evidence linking dTFA with behavioral irritability and aggression. While confounding is always a concern in observational studies, factors including strength and consistency of association, biological gradient, temporality, and biological plausibility add weight to the prospect of a causal connection. Our results may have relevance to public policy determinations regarding dietary trans fats. Clinicaltrials.gov # NCT00330980

positive: Investigating the role of perceived stress on bacterial flora activity and salivary cortisol secretion: a possible mechanism underlying susceptibil... This study examined the impact of academic stress on salivary cortisol concentrations and lactic acid bacteria activity. Whole, unstimulated saliva samples and faecal samples were collected from 23 healthy undergraduate students (23.0+/-6.8 years; range 18-44) over two 1-week periods: during the beginning of semester (low-stress baseline condition) and during the first week of exams (high-stress condition). Students also completed a series of questionnaires measuring perceived levels of stress, gastrointestinal symptoms, and nutritional intake. Significant findings indicated that faecal lactic acid bacterial levels were lower during the high-stress condition. Paralleling this, students rated perceived levels of stress as being greater during the exam period compared to the baseline condition. The findings from this study have provided further insight into the link between stress and gastrointestinal flora activity in humans.

positive: Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and... In a previous clinical study, a probiotic formulation (PF) consisting of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (PF) decreased stress-induced gastrointestinal discomfort. Emerging evidence of a role for gut microbiota on central nervous system functions therefore suggests that oral intake of probiotics may have beneficial consequences on mood and psychological distress. The aim of the present study was to investigate the anxiolytic-like activity of PF in rats, and its possible effects on anxiety, depression, stress and coping strategies in healthy human volunteers. In the preclinical study, rats were daily administered PF for 2 weeks and subsequently tested in the conditioned defensive burying test, a screening model for anti-anxiety agents. In the clinical trial, volunteers participated in a double-blind, placebo-controlled, randomised parallel group study with PF administered for 30 d and assessed with the Hopkins Symptom Checklist (HSCL-90), the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale, the Coping Checklist (CCL) and 24 h urinary free cortisol (UFC). Daily subchronic administration of PF significantly reduced anxiety-like behaviour in rats (P < 0·05) and alleviated psychological distress in volunteers, as measured particularly by the HSCL-90 scale (global severity index, P < 0·05; somatisation, P < 0·05; depression, P < 0·05; and anger-hostility, P < 0·05), the HADS (HADS global score, P < 0·05; and HADS-anxiety, P < 0·06), and by the CCL (problem solving, P < 0·05) and the UFC level (P < 0·05). L. helveticus R0052 and B. longum R0175 taken in combination display anxiolytic-like activity in rats and beneficial psychological effects in healthy human volunteers.

positive: Dietary fat and meat intakes and risk of reflux esophagitis, Barrett’s esophagus and esophageal adenocarcinoma The aim of this study was to investigate whether dietary fat and meat intakes are associated with reflux esophagitis (RE), Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). In this all-Ireland case-control study, dietary intake data was collected using a food frequency questionnaire in 219 RE patients, 220 BE patients, 224 EAC patients, and 256 frequency-matched controls between 2002 and 2005. Unconditional multiple logistic regression analysis was used to examine the association between dietary variables and disease risk using quartiles of intake, to attain odds ratios (OR) and 95% confidence intervals (95%CI), while adjusting for potential confounders. Patients in the highest quartile of total fat intake had a higher risk of RE (OR=3.54; 95%CI=1.32–9.46) and EAC (OR=5.44; 95%CI=2.08–14.27). A higher risk of RE and EAC was also reported for patients in the highest quartile of saturated fat intake (OR=2.79; 95%CI=1.11–7.04; OR=2.41; 95%CI=1.14–5.08, respectively) and monounsaturated fat intake (OR=2.63; 95%CI=1.01–6.86; OR=5.35; 95%CI=2.14–13.34, respectively). Patients in the highest quartile of fresh red meat intake had a higher risk of EAC (OR=3.15; 95%CI=1.38–7.20). Patients in the highest category of processed meat intake had a higher risk of RE (OR=4.67; 95%CI=1.71–12.74). No consistent associations were seen for BE with either fat or meat intakes. Further studies, investigating the association between dietary fat and food sources of fat are needed to confirm these results.

positive: Strawberry fields forever? On the basis of copious preclinical data supporting the preventive efficacy of small fruits such as berries and grapes, Chen and colleagues conducted a randomized (noncomparative) phase II trial evaluating two doses of strawberry powder (60 g/d or 30 g/d for six months) to prevent esophageal cancer in China (reported in this issue of the journal, beginning on page 41); 60 g/d reduced the histologic grade of dysplastic lesions and reduced localized biomarkers, whereas 30 g/d was not effective. Fundamental questions remain such as the best formulation of strawberry powder, the active components associated with powder, and the actual mechanism of action, and standardized preparations will be required to permit the widespread use of strawberry powder with a predicable outcome. Clearly, however, this work is a good example of proof-of-principle and highlights the important role of diet, nutrition, and natural products in cancer prevention. ©2012 AACR.

positive: Randomized phase II trial of lyophilized strawberries in patients with dysplastic precancerous lesions of the esophagus. Dysplasia is a histologic precursor of esophageal squamous cell carcinoma (SCC). We previously showed that dietary freeze-dried, or lyophilized, strawberry powder inhibits N-nitrosomethylbenzylamine-induced SCC in the rat esophagus. On the basis of this observation, we conducted a randomized (noncomparative) phase II trial in China to investigate the effects of two doses of freeze-dried strawberries in patients with esophageal dysplastic lesions in a high-risk area for esophageal cancer. We randomly assigned 75 patients identified by endoscopy to have dysplastic esophageal premalignant lesions to receive freeze-dried strawberry powder at either 30 g/d (37 patients) or 60 g/d (38 patients) for six months; the powder was mixed with water and drunk. After six months, we assessed the changes in histologic grade of these lesions (primary endpoint) in a blinded fashion. The dose of 30 g/d, did not significantly affect histology or any other measured parameter. The dose of 60 g/d, however, reduced the histologic grade of dysplastic premalignant lesions in 29 (80.6%) of the 36 patients at this dose who were evaluated for histology (P < 0.0001). The strawberry powder was well tolerated, with no toxic effects or serious adverse events. Strawberries (60 g/d) also reduced protein expression levels of inducible nitric oxide synthase (iNOS) by 79.5% (P < 0.001), cyclooxygenase-2 (COX-2) by 62.9% (P < 0.001), phospho-nuclear factor kappa B (NFκB)-p65 (pNFκB-p65) by 62.6% (P < 0.001), and phospho-S6 (pS6) by 73.2% (P < 0.001). Freeze-dried strawberries (60 g/d) also significantly inhibited the Ki-67 labeling index by 37.9% (P = 0.023). Our present results indicate the potential of freeze-dried strawberry powder for preventing human esophageal cancer, supporting further clinical testing of this natural agent in this setting. ©2011 AACR.

positive: Dietary patterns and the risk of esophageal cancer. BACKGROUND: The role of dietary habits on esophageal cancer risk has been rarely considered in terms of dietary patterns. PATIENTS AND METHODS: We analyzed data from an Italian case-control study, including 304 cases with squamous cell carcinoma of the esophagus and 743 hospital controls. Dietary habits were evaluated using a food frequency questionnaire. A posteriori dietary patterns were identified through principal component factor analysis performed on 28 selected nutrients. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained from multiple logistic regression models applied on quartiles of factor scores, adjusting for potential confounding variables. RESULTS: We identified five major dietary patterns, named 'animal products and related components', 'vitamins and fiber', 'starch-rich', 'other polyunsaturated fatty acids and vitamin D', and 'other fats'. The 'animal products and related components' pattern was positively related to esophageal cancer (OR = 1.64, 95% CI:1.06-2.55, for the highest versus the lowest quartile of factor scores category). The 'vitamins and fiber' (OR = 0.50, 95% CI: 0.32-0.78) and the 'other polyunsaturated fatty acids and vitamin D' (OR = 0.48, 95% CI: 0.31-0.74) were inversely related to esophageal cancer. No significant association was observed for the other patterns. CONCLUSION: Our findings suggest that a diet rich in foods from animal origin and poor in foods containing vitamins and fiber increase esophageal cancer risk.

positive: Dietary patterns and risk of oesophageal cancers: a population-based case-control study. Epidemiological studies investigating the association between dietary intake and oesophageal cancer have mostly focused on nutrients and food groups instead of dietary patterns. We conducted a population-based case-control study, which included 365 oesophageal adenocarcinoma (OAC), 426 oesophagogastric junction adenocarcinoma (OGJAC) and 303 oesophageal squamous cell carcinoma (OSCC) cases, with frequency matched on age, sex and geographical location to 1580 controls. Data on demographic, lifestyle and dietary factors were collected using self-administered questionnaires. We used principal component analysis to derive three dietary patterns: 'meat and fat', 'pasta and pizza' and 'fruit and vegetable', and unconditional logistic regression models to estimate risks of OAC, OGJAC and OSCC associated with quartiles (Q) of dietary pattern scores. A high score on the meat-and-fat pattern was associated with increased risk of all three cancers: multivariable-adjusted OR 2·12 (95 % CI 1·30, 3·46) for OAC; 1·88 (95% CI 1·21, 2·94) for OGJAC; 2·84 (95% CI 1·67, 4·83) for OSCC (P-trend <0·01 for all three cancers). A high score on the pasta-and-pizza pattern was inversely associated with OSCC risk (OR 0·58, 95 % CI 0·36, 0·96, P for trend=0·009); and a high score on the fruit-and-vegetable pattern was associated with a borderline significant decreased risk of OGJAC (OR for Q4 v. Q1 0·66, 95% CI 0·42, 1·04, P=0·07) and significantly decreased risk of OSCC (OR 0·41, 95% CI 0·24, 0·70, P for trend=0·002). High-fat dairy foods appeared to play a dominant role in the association between the meat-and-fat pattern and risk of OAC and OGJAC. Further investigation in prospective studies is needed to confirm these findings.

positive: Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis Intestinal microbiota metabolism of choline/phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). Herein we demonstrate that intestinal microbiota metabolism of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis. Omnivorous subjects are shown to produce significantly more TMAO than vegans/vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. Specific bacterial taxa in human feces are shown to associate with both plasma TMAO and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predict increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (MI, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice significantly altered cecal microbial composition, markedly enhanced synthesis of TMA/TMAO, and increased atherosclerosis, but not following suppression of intestinal microbiota. Dietary supplementation of TMAO, or either carnitine or choline in mice with intact intestinal microbiota, significantly reduced reverse cholesterol transport in vivo. Intestinal microbiota may thus participate in the well-established link between increased red meat consumption and CVD risk.

positive: Effect of flax seed ingestion on the menstrual cycle. Lignans are a group of phytochemicals shown to have weakly estrogenic and antiestrogenic properties. Two specific lignans, enterodiol and enterolactone, are absorbed after formation in the intestinal tract from plant precursors particularly abundant in fiber-rich food and are excreted in the urine. We evaluated the effect of the ingestion of flax seed powder, known to produce high concentrations of urinary lignans, on the menstrual cycle in 18 normally cycling women, using a balanced randomized cross-over design. Each subject consumed her usual omnivorous, low fiber (control) diet for 3 cycles and her usual diet supplemented with flax seed for another 3 cycles. The second and third flax cycles were compared to the second and third control cycles. Three anovulatory cycles occurred during the 36 control cycles, compared to none during the 36 flax seed cycles. Compared to the ovulatory control cycles, the ovulatory flax cycles were consistently associated with longer luteal phase (LP) lengths (mean +/- SEM, 12.6 +/- 0.4 vs. 11.4 +/- 0.4 days; P = 0.002). There were no significant differences between flax and control cycles for concentrations of either estradiol or estrone during the early follicular phase, midfollicular phase, or LP. Although flax seed ingestion had no significant effect on LP progesterone concentrations, the LP progesterone/estradiol ratios were significantly higher during the flax cycles. Midfollicular phase testosterone concentrations were slightly higher during flax cycles. Flax seed ingestion had no effect on early follicular phase concentrations of DHEA-S, PRL, or sex hormone-binding globulin. Our data suggest a significant specific role for lignans in the relationship between diet and sex steroid action, and possibly between diet and the risk of breast and other hormonally dependent cancers.

positive: Vegetarian vs nonvegetarian diets, dietary restraint, and subclinical ovulatory disturbances: prospective 6-mo study. Ovulatory function was prospectively assessed over 6 mo in 23 vegetarians and 22 nonvegetarians with clinically normal menstrual cycles. Subjects were 20-40 y of age, of stable weight (body mass index, in kg/m2, of 18-25), on current diets for > or = 2 y, and not using oral contraceptives. Quantitative analysis of basal body temperature records classified cycles as normally ovulatory, short luteal phase (< 10 d), or anovulatory. Subjects completed the Three-Factor Eating Questionnaire (subjects completed the Three-Factor Eating Questionnaire (subscales for restraint, hunger, and disinhibition) and kept three 3-d food records. Vegetarians had lower BMIs (21.1 +/- 2.3 vs 22.7 +/- 1.9, P < 0.05), percentage body fat (24.0 +/- 5.5% vs 27.4 +/- 5.1%, P < 0.05), and restraint scores (6.4 +/- 4.4 vs 9.5 +/- 3.7, P < 0.05). Mean cycle lengths were similar, but vegetarians had longer luteal phase lengths (11.2 +/- 2.6 vs 9.1 +/- 3.8 d, P < 0.05). Cycle types also differed (chi 2 = 9.64, P < 0.01): vegetarians had fewer anovulatory cycles (4.6% vs 15.1% of cycles). Compared with those with restraint scores below the median, highly restrained women had fewer ovulatory cycles (3.6 +/- 2.3 vs 5.0 +/- 1.4, P < 0.05) and shorter mean luteal phase lengths (7.4 +/- 4.1 vs 10.7 +/- 3.1 d, P < 0.05). We conclude that ovulatory disturbances and restrained eating are less common among vegetarians, and that restraint influences ovulatory function.

positive: Effect of a low-fat high-carbohydrate diet on symptoms of cyclical mastopathy. 21 patients with severe persistent cyclical mastopathy of at least 5 years' duration were randomised to a control group who received general dietary advice or to an intervention group who were taught how to reduce the fat content of their diet to 15% of calories while increasing complex carbohydrate consumption to maintain caloric intake. Both groups were followed for 6 months with food records and measurement of plasma hormone and lipid levels. Severity of symptoms was recorded with daily diaries and patients were assessed at the beginning and end of the study by a physician who was unaware of their dietary regimen. After 6 months there was a significant reduction in the intervention group in the severity of premenstrual breast tenderness and swelling. Physical examination showed reduced breast swelling, tenderness, and nodularity in 6 of 10 patients in the intervention group and 2 of 9 patients in the control group.

positive: Diet and sex-hormone binding globulin, dysmenorrhea, and premenstrual symptoms. OBJECTIVE: To test the hypothesis that a low-fat, vegetarian diet reduces dysmenorrhea and premenstrual symptoms by its effect on serum sex-hormone binding globulin concentration and estrogen activity. METHODS: In a crossover design, 33 women followed a low-fat, vegetarian diet for two menstrual cycles. For two additional cycles, they followed their customary diet while taking a supplement placebo pill. Dietary intake, serum sex-hormone binding globulin concentration, body weight, pain duration and intensity, and premenstrual symptoms were assessed during each study phase. RESULTS: Mean (+/- standard deviation [SD]) serum sex-hormone binding globulin concentration was higher during the diet phase (46.7 +/- 23.6 nmol/L) than during the supplement phase (39.3 +/- 19.8 nmol/L, P < .001). Mean (+/- SD) body weight was lower during the diet (66.1 +/- 11.3 kg) compared with the supplement phase (67.9 +/- 12.1 kg, P < .001). Mean dysmenorrhea duration fell significantly from baseline (3.9 +/- 1.7 days) to diet phase (2.7 +/- 1.9 days) compared with change from baseline to supplement phase (3.6 +/- 1.7 days, P < .01). Pain intensity fell significantly during the diet phase, compared with baseline, for the worst, second-worst, and third-worst days, and mean durations of premenstrual concentration, behavioral change, and water retention symptoms were reduced significantly, compared with the supplement phase. CONCLUSION: A low-fat vegetarian diet was associated with increased serum sex-hormone binding globulin concentration and reductions in body weight, dysmenorrhea duration and intensity, and premenstrual symptom duration. The symptom effects might be mediated by dietary influences on estrogen activity.

positive: Is there a role for surgery in the treatment of mastalgia? Breast pain is a common condition affecting most women at some stage in their reproductive life. Mastalgia is resistant to treatment in 6% of cyclical and 26% non-cyclical patients. Surgery is not widely used to treat this condition and only considered in patients with severe mastalgia resistant to medication. The aims of this study were to audit the efficacy of surgery in severe treatment resistant mastalgia and to assess patient satisfaction following surgery. This is a retrospective review of the medical records of all patients seen in mastalgia clinic in the University Hospital of Wales, Cardiff since 1973. A postal questionnaire was distributed to all patients who had undergone surgery. Results showed that of the 1054 patients seen in mastalgia clinic, 12 (1.2%) had undergone surgery. Surgery included 8 subcutaneous mastectomies with implants (3 bilateral, 5 unilateral), 1 bilateral simple mastectomy and 3 quadrantectomies (1 having a further simple mastectomy). The median duration of symptoms was 6.5 years (range 2-16 years). Five patients (50%) were pain free following surgery, 3 developed capsular contractures and 2 wound infections with dehiscence. Pain persisted in both patients undergoing quadrantectomy. We conclude that surgery for mastalgia should only be considered in a minority of patients. Patients should be informed of possible complications inherent of reconstructive surgery and warned that in 50% cases their pain will not be improved.

positive: Cinnamon intake lowers fasting blood glucose: meta-analysis. Cinnamon, the dry bark and twig of Cinnamomum spp., is a rich botanical source of polyphenolics that has been used for centuries in Chinese medicine and has been shown to affect blood glucose and insulin signaling. Cinnamon's effects on blood glucose have been the subject of many clinical and animal studies; however, the issue of cinnamon intake's effect on fasting blood glucose (FBG) in people with type 2 diabetes and/or prediabetes still remains unclear. A meta-analysis of clinical studies of the effect of cinnamon intake on people with type 2 diabetes and/or prediabetes that included three new clinical trials along with five trials used in previous meta-analyses was done to assess cinnamon's effectiveness in lowering FBG. The eight clinical studies were identified using a literature search (Pub Med and Biosis through May 2010) of randomized, placebo-controlled trials reporting data on cinnamon and/or cinnamon extract and FBG. Comprehensive Meta-Analysis (Biostat Inc., Englewood, NJ, USA) was performed on the identified data for both cinnamon and cinnamon extract intake using a random-effects model that determined the standardized mean difference ([i.e., Change 1(control) - Change 2(cinnamon)] divided by the pooled SD of the post scores). Cinnamon intake, either as whole cinnamon or as cinnamon extract, results in a statistically significant lowering in FBG (-0.49±0.2 mmol/L; n=8, P=.025) and intake of cinnamon extract only also lowered FBG (-0.48 mmol/L±0.17; n=5, P=.008). Thus cinnamon extract and/or cinnamon improves FBG in people with type 2 diabetes or prediabetes.

positive: Molecular mimicry between HLA-DR alleles associated with rheumatoid arthritis and Proteus mirabilis as the Aetiological basis for autoimmunity. Molecular mimicry is one of the pathological mechanisms proposed to explain the association between microorganisms and autoimmune diseases. This review deals with the association between bacteria and rheumatic diseases with a special emphasis on rheumatoid arthritis where upper urinary tract infection by Proteus mirabilis is the possible cause of this severe, arthritic condition. Prospective trials involving anti-Proteus therapy should be carried out.

positive: Rheumatoid arthritis treated with vegetarian diets. The notion that dietary factors may influence rheumatoid arthritis (RA) has been a part of the folklore of the disease, but scientific support for this has been sparse. In a controlled, single-blind trial we tested the effect of fasting for 7-10 d, then consuming an individually adjusted, gluten-free, vegan diet for 3.5 mo, and then consuming an individually adjusted lactovegetarian diet for 9 mo on patients with RA. For all clinical variables and most laboratory variables measured, the 27 patients in the fasting and vegetarian diet groups improved significantly compared with the 26 patients in the control group who followed their usual omnivorous diet throughout the study period. One year after the patients completed the trial, they were reexamined. Compared with baseline, the improvements measured were significantly greater in the vegetarians who previously benefited from the diet (diet responders) than in diet nonresponders and omnivores. The beneficial effect could not be explained by patients' psychologic characteristics, antibody activity against food antigens, or changes in concentrations of prostaglandin and leukotriene precursors. However, the fecal flora differed significantly between samples collected at time points at which there was substantial clinical improvement and time points at which there were no or only minor improvements. In summary, the results show that some patients with RA can benefit from a fasting period followed by a vegetarian diet. Thus, dietary treatment may be a valuable adjunct to the ordinary therapeutic armamentarium for RA.

positive: Decrease in anti-Proteus mirabilis but not anti-Escherichia coli antibody levels in rheumatoid arthritis patients treated with fasting and a one year vegetarian diet. OBJECTIVE: To measure Proteus mirabilis and Escherichia coli antibody levels in patients with rheumatoid arthritis (RA) during treatment by vegetarian diet. METHODS: Sera were collected from 53 RA patients who took part in a controlled clinical trial of fasting and a one year vegetarian diet. P mirabilis and E coli antibody levels were measured by an indirect immunofluorescence technique and an enzyme immunoassay, respectively. RESULTS: The patients on the vegetarian diet had a significant reduction in the mean anti-proteus titres at all time points during the study, compared with baseline values (all p < 0.05). No significant change in titre was observed in patients who followed an omnivorous diet. The decrease in anti-proteus titre was greater in the patients who responded well to the vegetarian diet compared with diet non-responders and omnivores. The total IgG concentration and levels of antibody against E coli, however, were almost unchanged in all patient groups during the trial. The decrease from baseline in proteus antibody levels correlated significantly (p < 0.001) with the decrease in a modified Stoke disease activity index. CONCLUSION: The decrease in P mirabilis antibody levels in the diet responders and the correlation between the decrease in proteus antibody level and decrease in disease activity supports the suggestion of an aetiopathogenetic role for P mirabilis in RA.

positive: Determination of urinary lignans and phytoestrogen metabolites, potential antiestrogens and anticarcinogens, in urine of women on various habitual ... Recently two groups of compounds with diphenolic structure, the lignans and the isoflavonic phytoestrogens, were detected and identified in human urine and other biological fluids. These compounds are of great biological interest because they exhibit both in vitro and in vivo weak estrogenic and sometimes also antiestrogenic activities and many plant lignans have been shown to have anticarcinogenic, antiviral, antifungal and other interesting biological effects. The compounds found in relatively large amounts (10-1000 times more than estrogens) in urine are modified by intestinal bacteria from plant lignans and phytoestrogens, which are present in fiber-rich food such as grain and beans. They bind with low affinity to estrogen receptors and preliminary results suggest that they may induce production of sex hormone binding globulin (SHBG) in the liver and in this way may influence sex hormone metabolism and biological effects. Five compounds, the lignans enterolactone (Enl), enterodiol (End) and the isoflavonic phytoestrogen metabolites daidzein (Da), equol (Eq) and O-desmethylangolensin (O-Dma) were measured in urine by gas chromatography-mass spectrometry (selected ion monitoring) using deuterated internal standards in 5 groups of women (total number 53). The members of three dietary groups (omnivores, lactovegetarians and macrobiotics) were living in Boston and of two groups in Helsinki (omnivores and lactovegetarians). Until now measurements have been carried out in 94 72-h samples. The highest mean excretion of the most abundant compound, enterolactone, was found in the macrobiotic group and the lowest in the omnivoric groups. Total mean 24-h excretion of enterolactone was 17,680 nmol in the macrobiotics, 4,170 nmol in the Boston lactovegetarians, 3,650 nmol in the Helsinki lactovegetarians, 2,460 nmol in the Helsinki omnivores and 2,050 nmol in the Boston omnivores. The other diphenols followed approximately the same pattern. In an earlier study the lowest excretion of enterolactone (1,040 nmol/24 h) was found in a group of postmenopausal apparently healthy breast cancer patients living in Boston. It is concluded that further studies are necessary to elucidate the possible role of these compounds in cancer and other diseases. However, the evidence obtained until now seems to justify the conclusion that these compounds may be among the dietary factors affording protection against hormone-dependent cancers in vegetarians and semivegetarians.

positive: Molecular mimicry in the autoimmune pathogenesis of rheumatic heart disease. Molecular mimicry is a hallmark of the pathogenesis of rheumatic fever where the streptococcal group A carbohydrate epitope, N-acetyl glucosamine, and the a-helical coiled-coil streptococcal M protein structurally mimic cardiac myosin in the human disease, rheumatic carditis, and in animal models immunized with streptococcal M protein and cardiac myosin. Recent studies have unraveled the potential pathogenic mechanisms by which the immune response against the group A streptococcus attacks the rheumatic valve leading to chronic rheumatic heart disease. Both B- and T-cell responses are involved in the process, and evidence for the hypotheses of molecular mimicry and epitope spreading are reviewed.

positive: Rheumatoid Arthritis is an Autoimmune Disease Triggered by Proteus Urinary Tract Infection Rheumatoid arthritis (RA) is a chronic and disabling polyarthritic disease, which affects mainly women in middle and old age. Extensive evidence based on the results of various microbial, immunological and molecular studies from different parts of the world, shows that a strong link exists between Proteus mirabilis microbes and RA. We propose that sub-clinical Proteus urinary tract infections are the main triggering factors and that the presence of molecular mimicry and cross-reactivity between these bacteria and RA-targeted tissue antigens assists in the perpetuation of the disease process through production of cytopathic auto-antibodies. Patients with RA especially during the early stages of the disease could benefit from Proteus anti-bacterial measures involving the use of antibiotics, vegetarian diets and high intake of water and fruit juices such as cranberry juice in addition to the currently employed treatments.

positive: Evidence that patients with rheumatoid arthritis have asymptomatic 'non-significant' Proteus mirabilis bacteriuria more frequently than healthy con... OBJECTIVES: patients with rheumatoid arthritis (RA) are reported to have in their sera raised levels of antibody specific to Proteus mirabilis. The aim of the study was to verify this and to determine an explanation for it by investigating the frequency of P. mirabilis urinary tract infection in RA patients and matched controls. METHODS: freshly voided urine was examined for the presence, number and identity of infecting bacteria. The levels of antibody in blood and in urine of the IgM, IgA and IgG classes to the common O serotypes of P. mirabilis and the antigens to which they reacted were determined by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. RESULTS: analysis of urine from 76 patients with RA and 48 age- and gender-matched healthy controls showed that only two (4%) of the control urines but 25 (33%) of those from the RA patients were infected. The commonest infecting organism in the RA patients' urine was Proteus mirabilis which occurred twice as frequently as Escherichia coli. Proteus mirabilis was found in 52% of the infected urines of the RA patients and was always detected as a pure growth and usually in insignificant (< 10(4)/ml) numbers. It is highly improbable that this finding was the outcome of differences in age, physical ability or medication between the RA and control patient groups. Comparison of antibody levels to P. mirabilis by ELISA showed RA patients had raised (P < 0.0001, P = 0.001, P = 0.0063) levels of IgA, IgG and IgM respectively in their sera and raised (P < 0.0001, P < 0.0001, P = 0.0001) levels of IgG, IgM and IgA respectively in their urine compared with the control group. It was not possible to detect an antibody reacting to a P. mirabilis antigen that was specific to the RA patients. CONCLUSION: the results confirm that RA patients have raised levels of antibody to P. mirabilis not only in blood but also in urine and suggest that this arises because RA patients have an asymptomatic, non-significant P. mirabilis bacteriuria more frequently or more prolonged than control patients. This may be the trigger for their RA condition.

positive: Systematic literature review on economic implications and pharmacoeconomic issues of rheumatoid arthritis. OBJECTIVES: To provide a state of the art of economic analyses applied to rheumatoid arthritis (RA). METHODS: A systematic literature review on economic consequences and pharmacoeconomic issues of RA was performed. RESULTS: 127 valid articles were examined in this review. Generally, the financial impact of RA is substantial for health-care systems and society worldwide, although differences exist among national economies. Both direct and indirect (i.e. loss of productivity) costs contribute to economic burden of RA and must be taken into account when estimating overall impact to society. Disease severity, disease activity, age and socioeconomic status have been found to be the most relevant predictors of cost increase in RA. Moreover, introduction of biological anti-rheumatic agents has significantly raised direct medical costs in certain patients, but has also led to marked improvements in reducing disease activity, joint damage, and productivity loss in many of these patients. RA has also a significant impact on all aspects of quality of life; recent publications on health utility scores showed RA to be one of the diseases associated with poorest quality of life. CONCLUSIONS: RA represents a clinical and economic burden for healthcare systems. Although attributable RA costs have been extensively evaluated over the last decades, several issues, especially concerning the use of expensive therapies, must be addressed and frequently updated. Future research should also provide health economic evidence from usual practice settings, and on the economic impact of different therapeutic approaches to pursue specific clinical targets in individual patients.

positive: An uncooked vegan diet shifts the profile of human fecal microflora: computerized analysis of direct stool sample gas-liquid chromatography profiles of bacterial cellular fatty acids. The effect of an uncooked extreme vegan diet on fecal microflora was studied by direct stool sample gas-liquid chromatography (GLC) of bacterial cellular fatty acids and by quantitative bacterial culture by using classical microbiological techniques of isolation, identification, and enumeration of different bacterial species. Eighteen volunteers were divided randomly into two groups. The test group received an uncooked vegan diet for 1 month and a conventional diet of mixed Western type for the other month of the study. The control group consumed a conventional diet throughout the study period. Stool samples were collected. Bacterial cellular fatty acids were extracted directly from the stool samples and measured by GLC. Computerized analysis of the resulting fatty acid profiles was performed. Such a profile represents all bacterial cellular fatty acids in a sample and thus reflects its microflora and can be used to detect changes, differences, or similarities of bacterial flora between individual samples or sample groups. GLC profiles changed significantly in the test group after the induction and discontinuation of the vegan diet but not in the control group at any time, whereas quantitative bacterial culture did not detect any significant change in fecal bacteriology in either of the groups. The results suggest that an uncooked extreme vegan diet alters the fecal bacterial flora significantly when it is measured by direct stool sample GLC of bacterial fatty acids.

positive: Rheumatoid arthritis is caused by a Proteus urinary tract infection. Genetic, molecular and biological studies indicate that rheumatoid arthritis (RA), a severe arthritic disorder affecting approximately 1% of the population in developed countries, is caused by an upper urinary tract infection by the microbe, Proteus mirabilis. Elevated levels of specific antibodies against Proteus bacteria have been reported from 16 different countries. The pathogenetic mechanism involves six stages triggered by cross-reactive autoantibodies evoked by Proteus infection. The causative amino acid sequences of Proteus namely, ESRRAL and IRRET, contain arginine doublets which can be acted upon by peptidyl arginine deiminase thereby explaining the early appearance of anti-citrullinated protein antibodies in patients with RA. Consequently, RA patients should be treated early with anti-Proteus antibiotics as well as biological agents to avoid irreversible joint damages. © 2013 APMIS. Published by John Wiley & Sons Ltd.

positive: An update on bioactive plant lignans. Lignans are a class of secondary plant metabolites produced by oxidative dimerization of two phenylpropanoid units. Although their molecular backbone consists only of two phenylpropane (C6-C3) units, lignans show an enormous structural diversity. There is a growing interest in lignans and their synthetic derivatives due to applications in cancer chemotherapy and various other pharmacological effects. This review deals with lignans possessing anticancer, antioxidant, antimicrobial, anti-inflammatory and immunosuppressive activities, and comprises the data reported in more than 100 peer-reviewed articles, so as to highlight the recently reported bioactive lignans that could be a first step towards the development of potential new therapeutic agents.

positive: Rheumatoid arthritis is caused by Proteus: the molecular mimicry theory and Karl Popper. Rheumatoid arthritis is a crippling and disabling joint disease affecting over 20 million people. It occurs predominantly in women and smokers, and affects the HLA-DR1/4 individuals who carry the "shared epitope" of amino acids EQRRAA. The cause of this disease was investigated by the methods of the philosopher of science Karl Popper who suggested that scientific research should be based on bold conjectures and critical refutations. The "Popper sequences" generate new facts which then change or alter the original problem. The new facts must then be explained by any new theory. Using the "molecular mimicry" model, it was found that Proteus bacteria possess an amino acid sequence ESRRAL in haemolysin which resembles the, shared epitope, and another sequence in urease which resembles type XI collagen. Antibodies to Proteus bacteria have been found in 14 different countries. It would appear that rheumatoid arthritis is caused by an upper urinary tract infection by Proteus bacteria. Anti-Proteus therapy should be assessed in the management of this disease separately or in conjunction with existing modalities of therapy.

positive: Rheumatoid arthritis is linked to Proteus--the evidence. Rheumatoid arthritis (RA) is a chronic inflammatory arthritic and potentially disabling condition, mainly affecting women of middle age and having characteristic clinical features. Various microbial agents were implicated in the causation of RA. Extensive literature based on the results of various genetic, microbiological, molecular, and immunological studies carried out by independent research groups supports the role of Proteus mirabilis bacteria in the etiopathogenesis of RA. New diagnostic markers and criteria and the use of a novel therapeutic protocol in the form of antibiotic and dietary measures are suggested to be used together with current treatments in the management of RA. Prospective longitudinal studies with the use of antimicrobial measures in patients with RA are required to establish the therapeutic benefit of this microbe-disease association.

positive: Rheumatic fever: from sore throat to autoimmune heart lesions. Molecular mimicry between streptococci and heart components has been proposed as the triggering factor leading to autoimmunity in rheumatic heart disease (RHD). In this review, we present data from cellular autoimmune responses, focusing on the interactions between HLA class II molecules, streptococcal peptides and heart tissue proteins and T-cell receptor (TCR) usage. HLA-DR7DR53 associated with DQ molecules seem to be related with the development of valvular lesions in severe RHD patients. DR7DR53 molecules were also involved in the recognition of an immunodominant M5 peptide in these patients. T cells infiltrating RHD hearts displayed several oligoclonal expansions. Intralesional T-cell clones presenting identical TCR-BVBJ AVAJ and -CDR3 sequences were able to recognize several antigens with little or low homology, showing an intramolecular degenerate pattern of antigen recognition. Peripheral blood mononuclear cells of rheumatic fever (RF) patients produced proinflammatory cytokines, and intralesional mononuclear cells from severe RHD patients produced predominantly Th1-type cytokines. These results illustrate the complex mechanisms leading to heart tissue damage in RF/RHD patients. Copyright 2004 S. Karger AG, Basel

positive: Changes of faecal flora in rheumatoid arthritis during fasting and one-year vegetarian diet. The beneficial effect of a 1-yr vegetarian diet in RA has recently been demonstrated in a clinical trial. We have analysed stool samples of the 53 RA patients by using direct stool sample gas-liquid chromatography of bacterial cellular fatty acids. Based on repeated clinical assessments disease improvement indices were constructed for the patients. At each time point during the intervention period the patients in the diet group were then assigned either to a group with a high improvement index (HI) or a group with a low improvement index (LI). Significant alteration in the intestinal flora was observed when the patients changed from omnivorous to vegan diet. There was also a significant difference between the periods with vegan and lactovegetarian diets. The faecal flora from patients with HI and LI differed significantly from each other at 1 and 13 months during the diet. This finding of an association between intestinal flora and disease activity may have implications for our understanding of how diet can affect RA.

positive: Faecal microbial flora and disease activity in rheumatoid arthritis during a vegan diet. To clarify the role of the faecal flora in the diet-induced decrease of rheumatoid arthritis (RA) activity, 43 RA patients were randomized into two groups: the test group to receive living food, a form of uncooked vegan diet rich in lactobacilli, and the control group to continue their ordinary omnivorous diets. Based on clinical assessments before, during and after the intervention period, a disease improvement index was constructed for each patient. According to the index, patients were assigned either to a group with a high improvement index (HI) or to a group with a low improvement index (LO). Stool samples collected from each patient before the intervention and at 1 month were analysed by direct stool sample gas-liquid chromatography of bacterial cellular fatty acids. This method has proved to be a simple and sensitive way to detect changes and differences in the faecal microbial flora between individual stool samples or groups of them. A significant, diet-induced change in the faecal flora (P = 0.001) was observed in the test group, but not in the control group. Further, in the test group, a significant (P = 0.001) difference was detected between the HI and LO categories at 1 month, but not in the pre-test samples. We conclude that a vegan diet changes the faecal microbial flora in RA patients, and changes in the faecal flora are associated with improvement in RA activity.

positive: Uncooked, lactobacilli-rich, vegan food and rheumatoid arthritis. We tested the effects of an uncooked vegan diet, rich in lactobacilli, in rheumatoid patients randomized into diet and control groups. The intervention group experienced subjective relief of rheumatic symptoms during intervention. A return to an omnivorous diet aggravated symptoms. Half of the patients experienced adverse effects (nausea, diarrhoea) during the diet and stopped the experiment prematurely. Indicators of rheumatic disease activity did not differ statistically between groups. The positive subjective effect experienced by the patients was not discernible in the more objective measures of disease activity (Health Assessment Questionnaire, duration of morning stiffness, pain at rest and pain on movement). However, a composite index showed a higher number of patients with 3-5 improved disease activity measures in the intervention group. Stepwise regression analysis associated a decrease in the disease activity (measured as change in the Disease Activity Score, DAS) with lactobacilli-rich and chlorophyll-rich drinks, increase in fibre intake, and no need for gold, methotrexate or steroid medication (R2=0.48, P=0.02). The results showed that an uncooked vegan diet, rich in lactobacilli, decreased subjective symptoms of rheumatoid arthritis. Large amounts of living lactobacilli consumed daily may also have positive effects on objective measures of rheumatoid arthritis.

negative: The effect of a plant-based low-carbohydrate ("Eco-Atkins") diet on body weight and blood lipid concentrations in hyperlipidemic subjects. BACKGROUND: Low-carbohydrate, high-animal protein diets, which are advocated for weight loss, may not promote the desired reduction in low-density lipoprotein cholesterol (LDL-C) concentration. The effect of exchanging the animal proteins and fats for those of vegetable origin has not been tested. Our objective was to determine the effect on weight loss and LDL-C concentration of a low-carbohydrate diet high in vegetable proteins from gluten, soy, nuts, fruits, vegetables, cereals, and vegetable oils compared with a high-carbohydrate diet based on low-fat dairy and whole grain products. METHODS: A total of 47 overweight hyperlipidemic men and women consumed either (1) a low-carbohydrate (26% of total calories), high-vegetable protein (31% from gluten, soy, nuts, fruit, vegetables, and cereals), and vegetable oil (43%) plant-based diet or (2) a high-carbohydrate lacto-ovo vegetarian diet (58% carbohydrate, 16% protein, and 25% fat) for 4 weeks each in a parallel study design. The study food was provided at 60% of calorie requirements. RESULTS: Of the 47 subjects, 44 (94%) (test, n = 22 [92%]; control, n = 22 [96%]) completed the study. Weight loss was similar for both diets (approximately 4.0 kg). However, reductions in LDL-C concentration and total cholesterol-HDL-C and apolipoprotein B-apolipoprotein AI ratios were greater for the low-carbohydrate compared with the high-carbohydrate diet (-8.1% [P = .002], -8.7% [P = .004], and -9.6% [P = .001], respectively). Reductions in systolic and diastolic blood pressure were also seen (-1.9% [P = .052] and -2.4% [P = .02], respectively). CONCLUSION: A low-carbohydrate plant-based diet has lipid-lowering advantages over a high-carbohydrate, low-fat weight-loss diet in improving heart disease risk factors not seen with conventional low-fat diets with animal products.

negative: The effect of combining plant sterols, soy protein, viscous fibers, and almonds in treating hypercholesterolemia. Reductions in low-density lipoprotein-cholesterol (LDL-C) result from diets containing almonds, or diets that are either low in saturated fat or high in viscous fibers, soy proteins, or plant sterols. We have therefore combined all of these interventions in a single diet (portfolio diet) to determine whether cholesterol reductions could be achieved of similar magnitude to those reported in recent statin trials which reduced cardiovascular events. Twenty-five hyperlipidemic subjects consumed either a portfolio diet (n=13), very low in saturated fat and high in plant sterols (1.2 g/1,000 kcal), soy protein (16.2 g/1,000 kcal), viscous fibers (8.3 g/1,000 kcal), and almonds (16.6 g/1,000 kcal), or a low-saturated fat diet (n=12) based on whole-wheat cereals and low-fat dairy foods. Fasting blood, blood pressure, and body weight were obtained at weeks 0, 2, and 4 of each phase. LDL-C was reduced by 12.1% +/- 2.4% (P<.001) on the low-fat diet and by 35.0% +/- 3.1% (P<.001) on the portfolio diet, which also reduced the ratio of LDL-C to high-density lipoprotein-cholesterol (HDL-C) significantly (30.0% +/- 3.5%; P<.001). The reductions in LDL-C and the LDL:HDL-C ratio were both significantly lower on the portfolio diet than on the control diet (P<.001 and P<.001, respectively). Mean weight loss was similar on test and control diets (1.0 kg and 0.9 kg, respectively). No difference was seen in blood pressure, HDL-C, serum triglycerides, lipoprotein(a) [Lp(a)], or homocysteine concentrations between diets. Combining a number of foods and food components in a single dietary portfolio may lower LDL-C similarly to statins and so increase the potential effectiveness of dietary therapy.

negative: Shared signals and the potential for phylogenetic espionage between plants and animals. Until recently, the study and understanding of plant and animal signalling and response mechanisms have developed independently. Recent biochemical and molecular work is producing a growing list of elements involved in responses to biotic and abiotic stimuli that are very similar across kingdoms. Some of the more interesting examples of these include prostaglandin/octadecanoid-mediated responses to wounding, steroid-based signalling systems, and pathogen-recognition mechanisms. Some of these similarities probably represent evolutionary convergence; others may be ancestral to plants and animals. Ecological and evolutionary implications of such overlaps include the existence of pathogens that can cause disease in plants and animals, the ability of herbivores to manipulate plant responses, usurpation of microbial mechanisms and genes by herbivorous animals and plants, evolution of plant defenses exploiting shared signals in animals, and the medicinal use of plants by humans. Comparative study of the signalling and response mechanisms used by plants, animals, and microbes provides novel and useful insights to the ecology and evolution of interactions across kingdoms.

negative: Plasma adiponectin concentrations are associated with body composition and plant-based dietary factors in female twins. Circulating adiponectin is emerging as an important link between obesity, type 2 diabetes, and cardiovascular disease (CVD). However, the spectrum of lifestyle factors that modulate the adiponectin concentration remains to be elucidated, particularly among women. We conducted a cross-sectional study of 877 female twin pairs from the TwinsUK adult twin registry. Using a co-twin design, we examined dietary and body composition influences on adiponectin by conducting matched, within-pair analyses to eliminate confounding. Following multivariable adjustment within-twin pairs, significant influences on adiponectin (log-transformed, percent change per SD of the dietary/body composition variable) were observed for nonstarch polysaccharides (3.25%; 95% CI: 0.06, 6.54; P < 0.05) and magnesium intake (3.80%; 95%CI: 0.17, 7.57; P < 0.05), with a trend toward an association for fruit and vegetable (F&V) intakes (2.55%; 95% CI: -0.26, 5.45; P = 0.08). These modest positive associations cannot be explained by confounding through other lifestyle factors shared by the twins. A significant relationship between adiponectin and 3 derived dietary patterns (F&V, dieting, traditional English), carbohydrate, protein, trans fat, and alcohol intake was also observed. Strong inverse associations with adiponectin were observed for BMI (-10.72%; 95% CI: -13.78, -7.55), total (-6.89%: 95% CI: -10.34, -3.30; P < 0.05), and central fat mass (-12.50%; 95% CI: -15.82, -9.05; P < 0.05); these relationships were significant both when twins were analyzed as individuals and when characteristics were contrasted within-twin pairs, suggesting a direct effect. We observed modest associations between dietary factors and adiponectin in female twins, independent of adiposity, and report strong inverse associations with body composition. These data reinforce the importance of weight maintenance and increasing consumption of diets rich in plant-based foods to prevent CVD and type 2 diabetes.

negative: Omega-3 fatty acids and antioxidants in edible wild plants. Human beings evolved on a diet that was balanced in the omega-6 and omega-3 polyunsaturated fatty acids (PUFA), and was high in antioxidants. Edible wild plants provide alpha-linolenic acid (ALA) and higher amounts of vitamin E and vitamin C than cultivated plants. In addition to the antioxidant vitamins, edible wild plants are rich in phenols and other compounds that increase their antioxidant capacity. It is therefore important to systematically analyze the total antioxidant capacity of wild plants and promote their commercialization in both developed and developing countries. The diets of Western countries have contained increasingly larger amounts of linoleic acid (LA), which has been promoted for its cholesterol-lowering effect. It is now recognized that dietary LA favors oxidative modification of low density lipoprotein (LDL) cholesterol and increases platelet response to aggregation. In contrast, ALA intake is associated with inhibitory effects on the clotting activity of platelets, on their response to thrombin, and on the regulation of arachidonic acid (AA) metabolism. In clinical studies, ALA contributed to lowering of blood pressure, and a prospective epidemiological study showed that ALA is inversely related to the risk of coronary heart disease in men. Dietary amounts of LA as well as the ratio of LA to ALA appear to be important for the metabolism of ALA to longer-chain omega-3 PUFAs. Relatively large reserves of LA in body fat. as are found in vegans or in the diet of omnivores in Western societies, would tend to slow down the formation of long-chain omega-3 fatty acids from ALA. Therefore, the role of ALA in human nutrition becomes important in terms of long-term dietary intake. One advantage of the consumption of ALA over omega-3 fatty acids from fish is that the problem of insufficient vitamin E intake does not exist with high intake of ALA from plant sources.

negative: Effects of dietary proteins on plasma lipoprotein levels in normal subjects: interaction with dietary cholesterol. We have compared the effects of dietary soy protein and casein in diets low in cholesterol (less than 100 mg/d) and in diets enriched in cholesterol (500 mg/d) to examine whether the level of cholesterol intake affects the response of plasma lipoproteins to dietary proteins of plant and animal origin. Normal men and women consumed formula diets containing 20% of calories as soy protein or casein, 27% as fat and 53% as carbohydrate in 2 crossover studies. The dietary periods lasted for 31 days and were separated by a month-long interim period on self-chosen food. Following an initial reduction of plasma total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels on all diets, the plasma lipid and lipoprotein concentrations stabilized. On low-cholesterol diets the concentration of each of the major lipoprotein classes were similar during the soy and the casein dietary periods. On cholesterol-enriched diets, the concentration of LDL-C stabilized at a 16% lower level on soy protein than on the casein diet (p less than 0.02), while the concentration of high-density lipoprotein-cholesterol (HDL-C) was 16% higher (p less than 0.01). Since the difference in LDL-C (p less than 0.05) and in HDL-C (p less than 0.025) levels on casein and on soy protein diets were significantly greater on the high than on the low cholesterol intake, the findings indicate that the level of dietary cholesterol may determine whether plant and animal dietary proteins have similar or different effects on plasma LDL-C and HDL-C concentrations.

negative: Immunity: plants as effective mediators. In the domain of nutrition, exploring the diet-health linkages is major area of research. The outcomes of such interventions led to widespread acceptance of functional and nutraceutical foods; however, augmenting immunity is a major concern of dietary regimens. Indeed, the immune system is incredible arrangement of specific organs and cells that enabled humans to carry out defense against undesired responses. Its proper functionality is essential to maintain the body homeostasis. Array of plants and their components hold immunomodulating properties. Their possible inclusion in diets could explore new therapeutic avenues to enhanced immunity against diseases. The review intended to highlight the importance of garlic (Allium sativum), green tea (Camellia sinensis), ginger (Zingiber officinale), purple coneflower (Echinacea), black cumin (Nigella sativa), licorice (Glycyrrhiza glabra), Astragalus and St. John's wort (Hypericum perforatum) as natural immune boosters. These plants are bestowed with functional ingredients that may provide protection against various menaces. Modes of their actions include boosting and functioning of immune system, activation and suppression of immune specialized cells, interfering in several pathways that eventually led to improvement in immune responses and defense system. In addition, some of these plants carry free radical scavenging and anti-inflammatory activities that are helpful against cancer insurgence. Nevertheless, interaction between drugs and herbs/botanicals should be well investigated before recommended for their safe use, and such information must be disseminated to the allied stakeholders.

negative: Antimicrobial Traits of Tea- and Cranberry-Derived Polyphenols against Streptococcus mutans There are over 750 species of bacteria that inhabit the human oral cavity, but only a small fraction of those are attributed to causing plaque-related diseases such as caries. Streptococcus mutans is accepted as the main cariogenic agent and there is substantial knowledge regarding the specific virulence factors that render the organism a pathogen. There has been rising interest in alternative, target-specific treatment options as opposed to nonspecific mechanical plaque removal or application of broad-spectrum antibacterials that are currently in use. The impact of diet on oral health is undeniable, and this is directly observable in populations that consume high quantities of polyphenol-rich foods or beverages. Such populations have low caries incidence and better overall oral health. Camellia sinensis, the plant from which various forms of tea are derived, and Vaccinium macrocarpon (American cranberry fruit) have received notable attention both for their prevalence in the human diet as well as for their unique composition of polyphenols. The biologically active constituents of these plants have demonstrated potent enzyme-inhibitory properties without being bactericidal, a key quality that is important in developing therapies that will not cause microorganisms to develop resistance. The aim of this review is to consider studies that have investigated the feasibility of tea, cranberry, and other select plant derivatives as a potential basis for alternative therapeutic agents against Streptococcus mutans and to evaluate their current and future clinical relevance.

negative: Do phytoestrogens reduce the risk of breast cancer and breast cancer recurrence? What clinicians need to know. Oestrogen is an important determinant of breast cancer risk. Oestrogen-mimicking plant compounds called phytoestrogens can bind to oestrogen receptors and exert weak oestrogenic effects. Despite this activity, epidemiological studies suggest that the incidence of breast cancer is lower in countries where the intake of phytoestrogens is high, implying that these compounds may reduce breast cancer risk, and possibly have an impact on survival. Isoflavones and lignans are the most common phytoestrogens in the diet. In this article, we present findings from human observational and intervention studies related to both isoflavone and lignan exposure and breast cancer risk and survival. In addition, the clinical implications of these findings are examined in the light of a growing dietary supplement market. An increasing number of breast cancer patients seek to take supplements together with their standard treatment in the hope that these will either prevent recurrence or treat their menopausal symptoms. Observational studies suggest a protective effect of isoflavones on breast cancer risk and the case may be similar for increasing lignan consumption although evidence so far is inconsistent. In contrast, short-term intervention studies suggest a possible stimulatory effect on breast tissue raising concerns of possible adverse effects in breast cancer patients. However, owing to the dearth of human studies investigating effects on breast cancer recurrence and survival the role of phytoestrogens remains unclear. So far, not enough clear evidence exists on which to base guidelines for clinical use, although raising patient awareness of the uncertain effect of phytoestrogens is recommended.

negative: Cancer mortality in workers employed in cattle, pigs, and sheep slaughtering and processing plants. OBJECTIVES: We studied mortality in two separate cohorts of workers in abattoirs (N=4996) and meat processing plants (N=3642) belonging to a meatcutters' union, because they were exposed to viruses that cause cancer in food animals, and also to chemical carcinogens at work. METHODS: Standardized mortality ratios (SMRs) and proportional mortality ratios (PMRs) were estimated for each cohort as a whole and in subgroups defined by race and sex, using the US general population mortality rates for comparison. Study subjects were followed up from January 1950 to December 2006, during which time over 60% of them died. RESULTS: An excess of deaths from cancers of the base of the tongue, esophagus, lung, skin, bone and bladder, lymphoid leukemia, and benign tumors of the thyroid and other endocrine glands, and possibly Hodgkin's disease, was observed in abattoir and meat processing workers. Significantly lower SMRs were recorded for cancer of the thymus, mediastinum, pleura, etc., breast cancer, and non-Hodgkin's lymphoma. CONCLUSION: This study confirms the excess occurrence of cancer in workers in abattoirs and meat processing plants, butchers, and meatcutters, previously reported in this cohort and other similar cohorts worldwide. Large nested case-control studies are now needed to examine which specific occupational and non-occupational exposures are responsible for the excess. There is now sufficient evidence for steps to be taken to protect workers from carcinogenic exposures at the workplace. There are also serious implications for the general population which may also be exposed to some of these viruses. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

negative: Angina pectoris and atherosclerotic risk factors in the multisite cardiac lifestyle intervention program. Cardiovascular symptom relief is a major indicator for revascularization procedures. To examine the effects of intensive lifestyle modification on symptom relief, we investigated changes in angina pectoris, coronary risk factors, quality of life, and lifestyle behaviors in patients with stable coronary artery disease enrolled in the multisite cardiac lifestyle intervention program, an ongoing health insurance-covered lifestyle intervention conducted at 22 sites in the united states. Patients with coronary artery disease (nonsmokers; 757 men, 395 women; mean age 61 years) were asked to make changes in diet (10% calories from fat, plant based), engage in moderate exercise (3 hours/week), and practice stress management (1 hour/day). At baseline, 108 patients (43% women) reported mild angina and 174 patients (37% women) reported limiting angina. By 12 weeks, 74% of these patients were angina free, and an additional 9% moved from limiting to mild angina. This improvement in angina was significant for patients with mild and limiting angina at baseline regardless of gender (p <0.01). Significant improvements in cardiac risk factors, quality of life, and lifestyle behaviors were observed, and patients with angina who became angina free by 12 weeks showed the greatest improvements in exercise capacity, depression, and health-related quality of life (p <0.05). In conclusion, the observed improvements in angina in patients making intensive lifestyle changes could drastically reduce their need for revascularization procedures.

negative: Melatonin in traditional Mediterranean diets. Compared with other industrialized countries, the lower incidence of chronic-degenerative disorders in Mediterranean populations has been emphasized in recent decades. The health-promoting effects arising from Mediterranean dietary habits have been attributed to the large intake of plant foodstuffs rich in bioactive phytochemicals, such as melatonin. Recently, it has been suggested that melatonin present in edible plants may improve human health, by virtue of its biological activities and its good bioavailability. Plant melatonin, besides contributing to optimize the physiological functions regulated, in humans, by endogenous melatonin, may be involved in nutritional therapy to reduce the risk of cancer, cardiovascular and neurodegenerative diseases in western populations. In this view, the presence of melatonin in some Mediterranean foods and beverages adds a new element to the hypothesis of health benefits associated to Mediterranean dietary patterns, although the available data are still preliminary and incomplete.

negative: Plant foods and the risk of cerebrovascular diseases: a potential protection of fruit consumption. Studies on the association between plant foods and cerebrovascular diseases have given contradictory results suggesting the existence of some effect-modifying factors. The present study determines whether the consumption of plant foods (i.e. fruits and berries, vegetables, and cereals) predicts a decreased cerebrovascular disease incidence in a population with low fruit and vegetable and high wholegrain intake. This cohort study on 3932 men and women was based on data from the Finnish Mobile Clinic Health Examination Survey, conducted in 1968-72. The participants were 40-74 years of age and free of cardiovascular diseases at baseline. Data on the plant food consumption were derived from a 1-year dietary history interview. During a 24-year follow-up 625 cases of cerebrovascular diseases occurred, leading to either hospitalisation or death. An inverse association was found between fruit consumption and the incidence of cerebrovascular diseases, ischaemic stroke and intracerebral haemorrhage. The adjusted relative risks (RR) between the highest and lowest quartiles of intake of any cerebrovascular disease, ischaemic stroke and intracerebral haemorrhage were 0.75 (95 % CI 0.59, 0.94), 0.73 (95 % CI 0.54, 1.00) and 0.47 (95 % CI 0.24, 0.92), respectively. These associations were primarily due to the consumption of citrus fruits and occurred only in men. Total consumption of vegetables or cereals was not associated with the cerebrovascular disease incidence. The consumption of cruciferous vegetables, however, predicted a reduced risk of cerebrovascular diseases (RR 0.79; 95 % CI 0.63, 0.99), ischaemic stroke (RR 0.67; 95 % CI 0.49, 0.92) and intracerebral haemorrhage (RR 0.49; 95 % CI 0.25, 0.98). In conclusion, the consumption of fruits, especially citrus, and cruciferous vegetables may protect against cerebrovascular diseases.

negative: Differential Effects of Glyphosate and Roundup on Human Placental Cells and Aromatase Roundup is a glyphosate-based herbicide used worldwide, including on most genetically modified plants that have been designed to tolerate it. Its residues may thus enter the food chain, and glyphosate is found as a contaminant in rivers. Some agricultural workers using glyphosate have pregnancy problems, but its mechanism of action in mammals is questioned. Here we show that glyphosate is toxic to human placental JEG3 cells within 18 hr with concentrations lower than those found with agricultural use, and this effect increases with concentration and time or in the presence of Roundup adjuvants. Surprisingly, Roundup is always more toxic than its active ingredient. We tested the effects of glyphosate and Roundup at lower nontoxic concentrations on aromatase, the enzyme responsible for estrogen synthesis. The glyphosate-based herbicide disrupts aromatase activity and mRNA levels and interacts with the active site of the purified enzyme, but the effects of glyphosate are facilitated by the Roundup formulation in microsomes or in cell culture. We conclude that endocrine and toxic effects of Roundup, not just glyphosate, can be observed in mammals. We suggest that the presence of Roundup adjuvants enhances glyphosate bioavailability and/or bioaccumulation.

negative: Role of maca (Lepidium meyenii) consumption on serum interleukin-6 levels and health status in populations living in the Peruvian central Andes over 4000 m of altitude Lepidium meyenii (Maca) is a plant that grows at over 4000 meters above sea level in the central Peruvian Andes. The hypocotyls of this plant are traditionally consumed for their nutritional and medicinal properties. The aim of this study was to determine the health status based on a health related quality of life (HRQL) questionnaire (SF-20) and serum levels of interleukin 6 (IL-6) in subjects that are maca consumers. For this, a cross-sectional study was designed to be performed in 50 subjects from Junin (4100 m): 27 subjects were maca consumers and 23 were non-consumers. The SF-20 survey is used to obtain a summary measure of health status. The stand up from a chair and sit down (SUCSD) test (to assess lower-extremity function), hemoglobin measurement, blood pressure, sexual hormone levels, serum IL-6 levels and the score of chronic mountain sickness (CMS) were evaluated. Testosterone/estradiol ratio (P≪0.05), IL-6 (P<0.05) and CMS score were lower, whereas the health status score was higher, in maca consumers when compared to non-consumers (P<0.01). A greater proportion of maca consumers successfully completed the SUCSD test compared to non-consumers (P<0.01), showing a significant association with lower values of serum IL-6 (P<0.05). In conclusion, consumption of maca was associated with low serum IL-6 levels and in turn with better health status scores in the SF-20 survey and low chronic mountain sickness scores.

negative: Flatulence--causes, relation to diet and remedies. In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.

negative: mTORC1 activity as a determinant of cancer risk--rationalizing the cancer-preventive effects of adiponectin, metformin, rapamycin, and low-protein ... Increased plasma levels of adiponectin, metformin therapy of diabetes, rapamycin administration in transplant patients, and lifelong consumption of low-protein plant-based diets have all been linked to decreased risk for various cancers. These benefits may be mediated, at least in part, by down-regulated activity of the mTORC1 complex, a key regulator of protein translation. By boosting the effective availability of the translation initiator eIF4E, mTORC1 activity promotes the translation of a number of "weak" mRNAs that code for proteins, often up-regulated in cancer, that promote cellular proliferation, invasiveness, and angiogenesis, and that abet cancer promotion and chemoresistance by opposing apoptosis. Measures which inhibit eIF4E activity, either directly or indirectly, may have utility not only for cancer prevention, but also for the treatment of many cancers in which eIF4E drives malignancy. Since eIF4E is overexpressed in many cancers, strategies which target eIF4E directly--some of which are now being assessed clinically--may have the broadest efficacy in this regard. Many of the "weak" mRNAs coding for proteins that promote malignant behavior or chemoresistance are regulated transcriptionally by NF-kappaB and/or Stat3, which are active in a high proportion of cancers; thus, regimens concurrently targeting eIF4E, NF-kappaB, and Stat3 may suppress these proteins at both the transcriptional and translational levels, potentially achieving a very marked reduction in their expression. Copyright © 2011 Elsevier Ltd. All rights reserved.

negative: Review of the efficacy of green tea, isoflavones and aloe vera supplements based on randomised controlled trials. We assess the evidence for health benefits of three commonly consumed plant food supplements (PFS), green tea, isoflavone and aloe vera, based on published systematic reviews of randomised controlled trials (RCTs). Whilst the potential benefits of green tea have been reported in a wide range of health areas, it is only in the area of the metabolic syndrome that the number of RCTs is approaching sufficient to judge such efficacy. Isoflavone supplements are widely used, and RCTs indicate that they affect bone resorption at lower doses in postmenopausal women undergoing estrogen-related bone loss, but this is only translated to attenuation of bone loss at higher doses of isoflavones. A systematic review on RCTs concluded that the effects of isoflavones on hot flashes in postmenopausal women were highly variable and no conclusions could be drawn. Despite the popularity of aloe vera as a PFS, the evaluation of its efficacy as a coadjuvant therapy for certain metabolic or digestive pathologies remains scarce; it constitutes a typical example of a naturally occurring ingredient whose efficacy in topical applications presupposes its efficacy in systemic applications. Nevertheless, its possible toxic effects on oral consumption call for caution in its utility as a PFS. Since 2007, efficacy evaluation of PFS in Europe has been covered by European Union Nutrition and Health Claims legislation. The European Food Safety Authority has adopted an approach relying on RCTs, while medicinal effects are accepted based on traditional use. In general, there are insufficient RCTs for claims to be made, and conclusive results on PFS should be obtained in the future by conducting studies with more homogeneous populations, by using supplements with optimised and measured bioavailability, and by conducting larger RCTs.

negative: Radioprotection by plant products: present status and future prospects. The development of radioprotective agents has been the subject of intense research in view of their potential for use within a radiation environment, such as space exploration, radiotherapy and even nuclear war. However, no ideal, safe synthetic radioprotectors are available to date, so the search for alternative sources, including plants, has been on going for several decades. In Ayurveda, the traditional Indian system of medicine, several plants have been used to treat free radical-mediated ailments and, therefore, it is logical to expect that such plants may also render some protection against radiation damage. A systematic screening approach can provide leads to identifying potential new candidate drugs from plant sources, for mitigation of radiation injury. This article reviews some of the most promising plants, and their bioactive principles, that are widely used in traditional systems of medicine, and which have rendered significant radioprotection in both in vitro and in vivo model systems. Plants and their constituents with pharmacological activities that may be relevant to amelioration of radiation-mediated damage, including antiemetic, antiinflammatory, antioxidant, cell proliferative, wound healing and haemopoietic stimulatories are also discussed. Copyright (c) 2005 John Wiley & Sons, Ltd.

negative: Cognitive performance among the elderly in relation to the intake of plant foods. The Hordaland Health Study. Fruits and vegetables are among the most nutritious and healthy of foods, and are related to the prevention of many chronic diseases. The aim of the study was to examine the relationship between intake of different plant foods and cognitive performance in elderly individuals in a cross-sectional study. Two thousand and thirty-one elderly subjects (aged 70-74 years; 55% women) recruited from the general population in Western Norway underwent extensive cognitive testing and completed a comprehensive FFQ. The cognitive test battery covered several domains (Kendrick Object Learning Test, Trail Making Test--part A, modified versions of the Digit Symbol Test, Block Design, Mini-Mental State Examination and Controlled Oral Word Association Test). A validated and self-reported FFQ was used to assess habitual food intake. Subjects with intakes of >10th percentile of fruits, vegetables, grain products and mushrooms performed significantly better in cognitive tests than those with very low or no intake. The associations were strongest between cognition and the combined intake of fruits and vegetables, with a marked dose-dependent relationship up to about 500 g/d. The dose-related increase of intakes of grain products and potatoes reached a plateau at about 100-150 g/d, levelling off or decreasing thereafter, whereas the associations were linear for mushrooms. For individual plant foods, the positive cognitive associations of carrots, cruciferous vegetables, citrus fruits and high-fibre bread were most pronounced. The only negative cognitive association was with increased intake of white bread. In the elderly, a diet rich in plant foods is associated with better performance in several cognitive abilities in a dose-dependent manner.

negative: Economic burden of a gluten-free diet. BACKGROUND: Coeliac disease is a common, autoimmune disorder, for which the only treatment is lifelong adherence to a gluten-free diet. This study evaluates the economic burden of adhering to a gluten-free diet. METHODS: A market basket of products identified by name brand, weight or package size for both regular wheat-based products and gluten-free counterparts was developed. The differences in price between purchase venues, both type of store (general grocery store, an upscale grocery store and a health food store and four internet-based grocery sites) and region was also analysed. RESULTS: Availability of gluten-free products varied between the different venues, regular grocery stores carried 36%, while upscale markets carried 41%, and health food stores 94%, compared with 100% availability on the internet. Overall, every gluten-free product was more expensive than their wheat-based counterpart (P <or= 0.05). Bread and pasta was twice as expensive as their wheat-based counterparts. Cost was affected more by shopping venue than geographic location. CONCLUSIONS: This study demonstrated that gluten-free foods have poor availability and are more expensive than their gluten-containing counterparts. The impact of these findings on dietary compliance and the quality of life needs to be addressed.

negative: Clinical events in prostate cancer lifestyle trial: results from two years of follow-up. OBJECTIVES: Previous research has demonstrated that patients with prostate cancer participating in the Prostate Cancer Lifestyle Trial had a reduction in prostate-specific antigen (PSA) levels, inhibition of LNCaP cell growth, and fewer prostate cancer-related clinical events at the end of 1 year compared with controls. The aim of this study was to examine the clinical events in this trial during a 2-year period. METHODS: The Prostate Cancer Lifestyle Trial was a 1-year randomized controlled clinical trial of 93 patients with early-stage prostate cancer (Gleason score <7, PSA 4-10 ng/mL) undergoing active surveillance. The patients in the experimental arm were encouraged to adopt a low-fat, plant-based diet, to exercise and practice stress management, and to attend group support sessions. The control patients received the usual care. RESULTS: By 2 years of follow-up, 13 of 49 (27%) control patients and 2 of 43 (5%) experimental patients had undergone conventional prostate cancer treatment (radical prostatectomy, radiotherapy, or androgen deprivation, P < .05). No differences were found between the groups in other clinical events (eg, cardiac), and no deaths occurred. Three of the treated control patients but none of the treated experimental patients had a PSA level of >or=10 ng/mL, and 1 treated control patient but no treated experimental patients had a PSA velocity of >2 ng/mL/y before treatment. No significant differences were found between the untreated experimental and untreated control patients in PSA change or velocity at the end of 2 years. CONCLUSIONS: Patients with early-stage prostate cancer choosing active surveillance might be able to avoid or delay conventional treatment for at least 2 years by making changes in their diet and lifestyle.

negative: Curcumin and cancer: an "old-age" disease with an "age-old" solution. Cancer is primarily a disease of old age, and that life style plays a major role in the development of most cancers is now well recognized. While plant-based formulations have been used to treat cancer for centuries, current treatments usually involve poisonous mustard gas, chemotherapy, radiation, and targeted therapies. While traditional plant-derived medicines are safe, what are the active principles in them and how do they mediate their effects against cancer is perhaps best illustrated by curcumin, a derivative of turmeric used for centuries to treat a wide variety of inflammatory conditions. Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called "curry powder") that has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4) and inflammation (NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). The activity of curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets. Thus an "old-age" disease such as cancer requires an "age-old" treatment.

negative: Reducing the staggering costs of environmental disease in children, estimated at $76.6 billion in 2008. A 2002 analysis documented $54.9 billion in annual costs of environmentally mediated diseases in US children. However, few important changes in federal policy have been implemented to prevent exposures to toxic chemicals. We therefore updated and expanded the previous analysis and found that the costs of lead poisoning, prenatal methylmercury exposure, childhood cancer, asthma, intellectual disability, autism, and attention deficit hyperactivity disorder were $76.6 billion in 2008. To prevent further increases in these costs, efforts are needed to institute premarket testing of new chemicals; conduct toxicity testing on chemicals already in use; reduce lead-based paint hazards; and curb mercury emissions from coal-fired power plants.

negative: Adherence to WCRF/AICR cancer prevention recommendations and risk of post-menopausal breast cancer Background In 2007 the World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) released eight recommendations related to body fatness, physical activity and diet aimed at preventing the most common cancers worldwide. However, limited information exists on the association between meeting these recommendations and risks of specific cancers, including breast cancer. Methods We operationalized six recommendations (related to body fatness, physical activity, foods that promote weight gain, plant foods, red and processed meats, and alcohol) and examined their association with invasive breast cancer incidence over 6.7 years of follow-up in the VITamins And Lifestyle (VITAL) study cohort. Participants included 30,797 post-menopausal women ages 50–76 years at baseline in 2000–2002 with no history of breast cancer. Breast cancers (n=899) were tracked through the Western Washington Surveillance, Epidemiology and End Results (SEER) database. Results Breast cancer risk was reduced by 60% in women who met at least five recommendations compared to those who met none (HR: 0.40; 95% CI: 0.25–0.65; Ptrend<0.001). Further analyses that sequentially removed individual recommendations least associated with reduced risk suggested that this reduction is due to meeting recommendations related to body fatness, plant foods and alcohol (HR for meeting vs. not meeting these three recommendations: 0.38; 95% CI: 0.25–0.58; Ptrend <0.001). Conclusions Meeting the WCRF/AICR cancer prevention recommendations, specifically those related to alcohol, body fatness and plant foods, is associated with reduced post-menopausal breast cancer incidence. Impact Increased adherence to the WCRF/AICR cancer prevention recommendations could substantially reduce post-menopausal breast cancer risk in US women.

negative: Translocation of Crohn's disease Escherichia coli across M-cells: contrasting effects of soluble plant fibres and emulsifiers Background Crohn's disease is common in developed nations where the typical diet is low in fibre and high in processed food. Primary lesions overlie Peyer's patches and colonic lymphoid follicles where bacterial invasion through M-cells occurs. We have assessed the effect of soluble non-starch polysaccharide (NSP) and food emulsifiers on translocation of Escherichia coli across M-cells. Methods To assess effects of soluble plant fibres and food emulsifiers on translocation of mucosa-associated E coli isolates from Crohn's disease patients and from non-Crohn's controls, we used M-cell monolayers, generated by co-culture of Caco2-cl1 and Raji B cells, and human Peyer's patches mounted in Ussing chambers. Results E coli translocation increased across M-cells compared to parent Caco2-cl1 monocultures; 15.8-fold (IQR 6.2–32.0) for Crohn's disease E coli (N=8) and 6.7-fold (IQR 3.7–21.0) for control isolates (N=5). Electron microscopy confirmed E coli within M-cells. Plantain and broccoli NSP markedly reduced E coli translocation across M-cells at 5 mg/ml (range 45.3–82.6% inhibition, p<0.01); apple and leek NSP had no significant effect. Polysorbate-80, 0.01% vol/vol, increased E coli translocation through Caco2-cl1 monolayers 59-fold (p<0.05) and, at higher concentrations, increased translocation across M-cells. Similarly, E coli translocation across human Peyer's patches was reduced 45±7% by soluble plantain NSP (5 mg/ml) and increased 2-fold by polysorbate-80 (0.1% vol/vol). Conclusions Translocation of E coli across M-cells is reduced by soluble plant fibres, particularly plantain and broccoli, but increased by the emulsifier Polysorbate-80. These effects occur at relevant concentrations and may contribute to the impact of dietary factors on Crohn's disease pathogenesis.

negative: Detection and quantification of the antioxidant melatonin in Montmorency and Balaton tart cherries (Prunus cerasus). The antioxidant melatonin was recently identified in a variety of edible plants and seeds in high concentrations. In plants, as in animals, melatonin is believed to function as a free radical scavenger and possibly in photoperiodism. In this study, melatonin was detected and quantified in fresh-frozen Balaton and Montmorency tart cherries (Prunus cerasus) using high-performance liquid chromatography. Both cherry species contain high levels of melatonin compared to the melatonin concentrations in the blood of mammals. Montmorency cherries (13.46 +/- 1.10 ng/g) contain approximately 6 times more melatonin than do Balaton cherries (2.06 +/- 0.17 ng/g). Neither the orchard of origin nor the time of harvest influenced the amount of melatonin in fresh cherries. The implication of the current findings is that consuming cherries could be an important source of dietary melatonin inasmuch as melatonin is readily absorbed when taken orally. Also, previously published data and the results presented here show that melatonin is not only endogenously produced but also present in the diet.

negative: Increased prevalence of constipation in pre-school children is attributable to under-consumption of plant foods: A community-based study. AIM: To evaluate consumption of foods rich in dietary fibre and its relation to the prevalence of constipation in pre-school children. METHODS: In total, 368 children aged 3-5 years were randomly selected from kindergartens in Hong Kong. Constipation was confirmed by Rome-criteria. Children with normal bowel habits served as non-constipated controls. Consumption of vegetables, fruits, whole-grain cereals and fluid were determined using a 3-day food record. RESULTS: A total of 28.8% children were reported to have constipation. Median dietary fibre intake of constipated children was significantly lower than non-constipated children (3.4 g/d (inter-quartile range (IQR): 2.3-4.6 g/d) vs. 3.8 g/d (IQR: 2.7-4.9 g/d); P = 0.044) corresponding to 40% reference dietary fibre intake. Constipated children also had significantly lower intakes of vitamin C (P = 0.041), folate (P = 0.043) and magnesium (P = 0.002). Fruit intake and total plant foods intake were significantly lower in the constipated than non-constipated children: (61 g/d (IQR: 23.8-115 g/d) vs. 78 g/d (IQR: 41.7-144.6 g/d); P = 0.047) and (142.5 g/d (IQR: 73.7-214.7 g/d) vs. 161.1 g/d (IQR: 98.3-233.3 g/d); P = 0.034), respectively. Total fluid intake did not differ between groups but milk intake among the constipated children was marginally higher than the non-constipated children (P = 0.055) CONCLUSION: Insufficient dietary fibre intake is common in Hong Kong pre-school children. Constipated children had significantly lower intakes of dietary fibre and micronutrients including vitamin C, folate and magnesium than non-constipated counterparts which was attributable to under-consumption of plant foods. However, milk intake was marginally higher in the constipated children. More public education is necessary for parents to help develop healthy dietary habit and bowel habit in early life in order to prevent childhood constipation.

negative: Is concordance with World Cancer Research Fund/American Institute for Cancer Research guidelines for cancer prevention related to subsequent risk o... BACKGROUND: In 2007 the World Cancer Research Fund (WCRF) and the American Institute of Cancer Research (AICR) issued 8 recommendations (plus 2 special recommendations) on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence. OBJECTIVE: We aimed to investigate whether concordance with the WCRF/AICR recommendations was related to cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. DESIGN: The present study included 386,355 EPIC participants from 9 European countries. At recruitment, dietary, anthropometric, and lifestyle information was collected. A score was constructed based on the WCRF/AICR recommendations on weight management, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, alcoholic drinks, and breastfeeding for women; the score range was 0-6 for men and 0-7 for women. Higher scores indicated greater concordance with WCRF/AICR recommendations. The association between the score and cancer risk was estimated by using multivariable Cox regression models. RESULTS: Concordance with the score was significantly associated with decreased risk of cancer. A 1-point increment in the score was associated with a risk reduction of 5% (95% CI: 3%, 7%) for total cancer, 12% (95% CI: 9%, 16%) for colorectal cancer, and 16% (95% CI: 9%, 22%) for stomach cancer. Significant associations were also observed for cancers of the breast, endometrium, lung, kidney, upper aerodigestive tract, liver, and esophagus but not for prostate, ovarian, pancreatic, and bladder cancers. CONCLUSION: Adherence to the WCRF/AICR recommendations for cancer prevention may lower the risk of developing most types of cancer.

negative: Complexity of the heat stress response in plants. Plants have evolved a variety of responses to elevated temperatures that minimize damage and ensure protection of cellular homeostasis. New information about the structure and function of heat stress proteins and molecular chaperones has become available. At the same time, transcriptome analysis of Arabidopsis has revealed the involvement of factors other than classical heat stress responsive genes in thermotolerance. Recent reports suggest that both plant hormones and reactive oxygen species also contribute to heat stress signaling. Additionally, an increasing number of mutants that have altered thermotolerance have extended our understanding of the complexity of the heat stress response in plants.

negative: Endocrine disruptors and hypospadias: role of genistein and the fungicide vinclozolin. OBJECTIVES: The phytoestrogen (plant estrogen) genistein, present in soy products, is of interest because in utero exposure to genistein can cause hypospadias in our mouse model and maternal consumption of soy is prevalent in human populations. Another compound of interest is the fungicide vinclozolin, which also causes hypospadias in the mouse and rat and can occur concurrently with genistein in the diet as a residue on exposed foods. A study in the United Kingdom found no relationship between a maternal organic vegetarian diet and hypospadias frequency, but women who consumed nonorganic vegetarian diets had a greater percentage of sons with hypospadias. Because nonorganic diets can include residues of pesticides such as vinclozolin, we sought to assess the interaction of realistic daily exposures to genistein and vinclozolin and their effects on the incidence of hypospadias. METHODS: Pregnant mice were fed a soy-free diet and orally gavaged from gestational days 13 to 17 with 0.17 mg/kg/day of genistein, 10 mg/kg/day of vinclozolin, or genistein and vinclozolin together at the same doses, all in 100 microL of corn oil. The controls received the corn oil vehicle. The male fetuses were examined at gestational day 19 for hypospadias, both macroscopically and histologically. RESULTS: We identified no hypospadias in the corn oil group. The incidence of hypospadias was 25% with genistein alone, 42% with vinclozolin alone, and 41% with genistein and vinclozolin together. CONCLUSIONS: These findings support the idea that exposure to these compounds during gestation could contribute to the development of hypospadias.