query: Optimal Phytosterol Dose

positive: Divergent changes in serum sterols during a strict uncooked vegan diet in patients with rheumatoid arthritis. The effects of a strict uncooked vegan diet on serum lipid and sterol concentrations were studied in patients with rheumatoid arthritis. The subjects were randomized into a vegan diet group (n 16), who consumed a vegan diet for 2-3 months, or into a control group (n 13), who continued their usual omnivorous diets. Serum total and LDL-cholesterol and -phospholipid concentrations were significantly decreased by the vegan diet. The levels of serum cholestanol and lathosterol also decreased, but serum cholestanol:total cholesterol and lathosterol:total cholesterol did not change. The effect of a vegan diet on serum plant sterols was divergent as the concentration of campesterol decreased while that of sitosterol increased. This effect resulted in a significantly greater sitosterol:campesterol value in the vegan diet group than in the control group (1.48 (SD 0.39) v. 0.72 (SD 0.14); P < 0.001). A higher concentration of campesterol compared with sitosterol is normal in omnivorous subjects and can be explained by lower absorption and esterification rates of sitosterol. Our results suggest that a strict uncooked vegan diet changes the relative absorption rates of these sterols and/or their biliary clearance.

positive: Phytosterol composition of nuts and seeds commonly consumed in the United States. Phytosterols were quantified in nuts and seeds commonly consumed in the United States. Total lipid extracts were subjected to acid hydrolysis and then alkaline saponfication, and free sterols were analyzed as trimethylsilyl derivatives by capillary GC-FID and GC-MS. Delta5-Avenasterol was quantified after alkaline saponification plus direct analysis of the glucoside. Sesame seed and wheat germ had the highest total phytosterol content (400-413 mg/100 g) and Brazil nuts the lowest (95 mg/100 g). Of the products typically consumed as snack foods, pistachio and sunflower kernel were richest in phytosterols (270-289 mg/100 g). beta-Sitosterol, Delta5-avenasterol, and campesterol were predominant. Campestanol ranged from 1.0 to 12.7 mg/100 g. Only 13 mg/100 g beta-sitosterol was found in pumpkin seed kernel, although total sterol content was high (265 mg/100 g). Phytosterol concentrations were greater than reported in existing food composition databases, probably due to the inclusion of steryl glycosides, which represent a significant portion of total sterols in nuts and seeds.

positive: Cultural and historical aspects of Mediterranean nuts with emphasis on their attributed healthy and nutritional properties. BACKGROUND AND AIMS: Nuts have been part of the human diet since prehistoric times. The aim of the present article is to describe the most important historical and cultural aspects of nut consumption throughout history. DATA SYNTHESIS: We discuss the following historical aspects of nuts originating in the Mediterranean: prehistory, the Egyptian civilization, their spread through the Mediterranean region by the Greek, Phoenician and Roman civilizations, and their reintroduction into Europe by means of the Al-Andalus culture. Particular emphasis is placed on the healthy and nutritional attributes that nuts have had throughout history. We also consider the role of the first globalization of food--the exchange of nuts between continents--and discuss the symbolism that nuts have had for humans throughout history in the context of cultural aspects of the Mediterranean region. CONCLUSIONS: Nuts and fruits are probably the earliest foods consumed by humans and are considered to be important because of their nutritional properties. Nuts have also been used in the past by different civilizations as drugs to prevent or treat several diseases. Copyright © 2010 Elsevier B.V. All rights reserved.

positive: Nut consumption and blood lipid levels: a pooled analysis of 25 intervention trials. BACKGROUND: Epidemiological studies have consistently associated nut consumption with reduced risk for coronary heart disease. Subsequently, many dietary intervention trials investigated the effects of nut consumption on blood lipid levels. The objectives of this study were to estimate the effects of nut consumption on blood lipid levels and to examine whether different factors modify the effects. METHODS: We pooled individual primary data from 25 nut consumption trials conducted in 7 countries among 583 men and women with normolipidemia and hypercholesterolemia who were not taking lipid-lowering medications. In a pooled analysis, we used mixed linear models to assess the effects of nut consumption and the potential interactions. RESULTS: With a mean daily consumption of 67 g of nuts, the following estimated mean reductions were achieved: total cholesterol concentration (10.9 mg/dL [5.1% change]), low-density lipoprotein cholesterol concentration (LDL-C) (10.2 mg/dL [7.4% change]), ratio of LDL-C to high-density lipoprotein cholesterol concentration (HDL-C) (0.22 [8.3% change]), and ratio of total cholesterol concentration to HDL-C (0.24 [5.6% change]) (P < .001 for all) (to convert all cholesterol concentrations to millimoles per liter, multiply by 0.0259). Triglyceride levels were reduced by 20.6 mg/dL (10.2%) in subjects with blood triglyceride levels of at least 150 mg/dL (P < .05) but not in those with lower levels (to convert triglyceride level to millimoles per liter, multiply by 0.0113). The effects of nut consumption were dose related, and different types of nuts had similar effects on blood lipid levels. The effects of nut consumption were significantly modified by LDL-C, body mass index, and diet type: the lipid-lowering effects of nut consumption were greatest among subjects with high baseline LDL-C and with low body mass index and among those consuming Western diets. CONCLUSION: Nut consumption improves blood lipid levels in a dose-related manner, particularly among subjects with higher LDL-C or with lower BMI.

positive: Effects of dietary protein on composition and metabolism of plasma lipoproteins in rabbits. Changes in the concentration and composition of serum VLDL, LDL, and HDL were studied in rabbits transferred from Chow diets to cholesterol-free, semipurified diets containing casein or isolated soy protein. During the first week on the casein diet, there was a marked increase in LDL-cholesterol and these higher levels were maintained during the subsequent 3 weeks of the study. Similar but less marked changes were obtained with the soy protein diet. When the percent composition of the particles was determined, both VLDL and LDL had a higher proportion of cholesterol. Turnover studies indicated that the FCRs for radiolabelled VLDL and LDL were reduced in casein-fed animals compared to those fed soy protein. The elevated LDL levels in casein-fed rabbits were primarily due to a reduction in receptor-mediated catabolism of LDL-apo B. Receptor-independent removal in the two groups was similar. These studies show that the hypercholesterolemia in casein-fed rabbits, compared to those fed soy protein, is associated with cholesterol enrichment of LDL and impaired receptor-dependent removal of LDL-apo B.

positive: 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.

positive: The Collateral Network Concept: A Reassessment of the Anatomy of Spinal Cord Perfusion OBJECTIVE Prevention of paraplegia following repair of thoracoabdominal aortic aneurysms (TAAA) requires understanding the anatomy and physiology of the blood supply to the spinal cord. Recent laboratory studies and clinical observations suggest that a robust collateral network must exist to explain preservation of spinal cord perfusion when segmental vessels are interrupted. An anatomical study was undertaken. METHODS Twelve juvenile Yorkshire pigs underwent aortic cannulation and infusion of a low-viscosity acrylic resin at physiological pressures. After curing of the resin and digestion of all organic tissue, the anatomy of the blood supply to the spinal cord was studied grossly and using light and electron microscopy. RESULTS All vascular structures ≥ 8μm in diameter were preserved. Thoracic and lumbar segmental arteries (SAs) give rise not only to the anterior spinal artery (ASA), but to an extensive paraspinous network feeding the erector spinae, iliopsoas, and associated muscles. The ASA, mean diameter 134±20 μm, is connected at multiple points to repetitive circular epidural arteries with mean diameters of 150±26 μm. The capacity of the paraspinous muscular network is 25-fold the capacity of the circular epidural arterial network and ASA combined. Extensive arterial collateralization is apparent between the intraspinal and paraspinous networks, and within each network. Only 75% of all SAs provide direct ASA-supplying branches. CONCLUSIONS The ASA is only one component of an extensive paraspinous and intraspinal collateral vascular network. This network provides an anatomic explanation of the physiological resiliency of spinal cord perfusion when SAs are sacrificed during TAAA repair.

positive: Atherosclerosis and disc degeneration/low-back pain--a systematic review. OBJECTIVES: Atherosclerosis can obstruct branching arteries of the abdominal aorta, including four paired lumbar arteries and the middle sacral artery that feed the lumbar spine. The diminished blood flow could result in various back problems. The aim of this systematic literature review was to assess associations between atherosclerosis and disc degeneration (DD) or low-back pain (LBP). DATA SOURCES: A systematic search of the Medline/PubMed database for all original articles on atherosclerosis and DD/LBP published until October 2008. The search was performed with the medical subject headings atherosclerosis, cardiovascular risk factor, or vascular disease and keywords "disc degeneration", "disc herniation", and "back pain" on the basis of MeSH tree and as a text search. In addition reference lists were studied and searched manually. Observational studies investigating the association of atherosclerosis or its risk factors and lumbar DD/LBP were selected. REVIEW METHODS: The following data were extracted: study characteristics, duration of follow-up, year of publication, findings of atherosclerosis/cardiovascular risk factors and DD/LBP. Disc herniation was regarded as a form of disc degeneration and cardiovascular risk factors were regarded as surrogate for atherosclerosis in epidemiological studies. RESULTS: One hundred and seventy-nine papers were identified. After exclusion of case reports, letters, editorials, papers not related to the lumbar spine, and animal studies, 25 papers were included. Post-mortem studies showed an association between atheromatous lesions in the aorta and DD, as well as between occluded lumbar arteries and life-time LBP. In clinical studies, aortic calcification was associated with LBP, and stenosis of lumbar arteries was associated with both DD and LBP. In epidemiological studies, smoking and high serum cholesterol levels were found to have the most consistent associations with DD and LBP. CONCLUSION: Aortic atherosclerosis and stenosis of the feeding arteries of the lumbar spine were associated with DD and LBP. Cardiovascular risk factors had weaker associations, being clearly apparent only in cohorts on elderly people or in large study samples. More prospective clinical studies are needed to further clarify the association of atherosclerosis and low-back disorders.

positive: Hyperlipidemia and sexual function in premenopausal women. INTRODUCTION: No reported studies exist assessing the relationship between sexual function and hyperlipidemia in women. AIM: In this study, we assessed the domains of sexual function in a representative sample of sexually active premenopausal women with hyperlipidemia, but without cardiovascular disease, as compared with an age-matched female population without hyperlipidemia. METHODS: To be enrolled in the study, women had to meet at least one of the following criteria for the diagnosis of hyperlipidemia: low-density lipoprotein (LDL) cholesterol levels >160 mg/dL; high-density lipoprotein (HDL) cholesterol levels <50 mg/dL; or triglyceride levels >150 mg/dL. Lipid parameters were assessed and verified on blood taken at least twice in the hospital during the screening phase. Four hundred forty-one premenopausal women with hyperlipidemia were compared with 115 age-matched premenopausal women without hyperlipidemia. MAIN OUTCOME MEASURES: We used the Female Sexual Function Index (FSFI) for assessing the key dimensions of female sexual function. RESULTS: The two groups were well matched for age and smoking prevalence. Compared with women of the control group, women with hyperlipidemia had reduced mean global FSFI score (22.8 +/- 6.8 vs. 29.4 +/- 4.9, P < 0.001). Individual analysis of the different domains showed that women with hyperlipidemia reported significantly lower arousal, orgasm, lubrication, and satisfaction scores than control women. Based on the total FSFI score, 51% of women with hyperlipidemia had scores of 26 or less, indicating sexual dysfunction, as compared with 21% of women without hyperlipidemia (P < 0.001). Based on a more conservative analysis including women under the lower quartile of the distribution of FSFI score, 32% of women with hyperlipidemia had scores of 23 or less, as compared with 9% of women without hyperlipidemia (P < 0.001). Multiple regression analysis identified age, body mass index, HDL-cholesterol and triglycerides as independent predictors of FSFI score. CONCLUSIONS: Women with hyperlipidemia have significantly lower FSFI-domain scores as compared with age-matched women without hyperlipidemia. HDL cholesterol and triglyceride levels were independently associated with the FSFI score.

positive: Preventing and arresting coronary atherosclerosis. The good news about coronary atherosclerosis is that it takes an awful lot of plaque before symptoms of myocardial ischemia occur. The bad news is that despite the need for large quantities of plaque for symptoms to occur, nevertheless nearly half of us in the United States eventually have the necessary quantity. Atherosclerosis is infrequently hereditary in origin. Most of us get atherosclerosis because we consume too much fat, cholesterol, and calories. The consequence is an elevated ( > 150 mg/dl) serum total cholesterol level, and the higher the number is above 150, the greater is the quantity of plaque deposited in our arteries. If the serum total cholesterol level can be prevented from rising to more than 150 mg/dl, plaques are not laid down; if elevated levels are lowered to 150 mg/dl, further plaque does not form, and parts of those present may vanish. A fruit-vegetarian-starch diet is necessary as a rule to achieve the 150 mg/dl level in most adults. Lipid-lowering drugs are required in the patients with familial hypercholesterolemia and in most patients with atherosclerotic events. The best news about atherosclerosis is that it can be prevented in those without the hereditary form, and it can be arrested by lowering elevated serum total (and LDL) cholesterol to the 150 mg/dl level.

positive: Effects of kiwifruit consumption on serum lipid profiles and antioxidative status in hyperlipidemic subjects. Cardiovascular disease (CVD) is the most important adult health problem in the world. Epidemiological studies and laboratory experiments have shown that fruit and vegetable consumption has protective effects against CVD. The purpose of the study was to investigate the effects of consumption of two kiwifruit per day on the lipid profile, antioxidants and markers of lipid peroxidation in hyperlipidemic adult men and women in Taiwan. Forty-three subjects who had hyperlipidemia, including 13 males and 30 females, participated in this study. They were asked to consume two kiwifruit per day for 8 weeks. Anthropometric measurements were made. Before the intervention and at 4 and 8 weeks of the intervention, fasting blood samples were analyzed for total cholesterol, triacylglycerol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein cholesterol (HDL-C). Additionally vitamin E and vitamin C, the malondialdehyde + 4-hydroxy-2(E)-nonenal concentration, and the lag time of LDL oxidation were determined. No significant differences from baseline to 8 weeks of the intervention were detected for triacylglycerol, total cholesterol, or LDL cholesterol. However, after 8 weeks of consumption of kiwifruit, the HDL-C concentration was significantly increased and the LDL cholesterol/HDL-C ratio and total cholesterol/HDL-C ratio were significantly decreased. Vitamin C and vitamin E also increased significantly. In addition, the lag time of LDL oxidation and malondialdehyde + 4-hydroxy-2(E)-nonenal had significantly changed at 4 and 8 weeks during the kiwifruit intervention. Regular consumption of kiwifruit might exert beneficial effects on the antioxidative status and the risk factors for CVD in hyperlipidemic subjects.

positive: The effect of strawberries in a cholesterol-lowering dietary portfolio. Effective diets reduce blood lipids and oxidative damage, both of which have been linked to the complications of diabetes and coronary heart disease. Our objective was to assess the effect of adding strawberries, as a source of antioxidants, to improve the antioxidant effect of a cholesterol-lowering diet (dietary portfolio). To this end, 28 hyperlipidemic subjects who had followed the dietary portfolio consisting of soy, viscous fiber, plant sterol, and nuts for a mean of 2.5 years were randomized to receive supplements of strawberries (454 g/d, 112 kcal) or additional oat bran bread (65 g/d, 112 kcal, approximately 2 g beta-glucan) (control) in a randomized 1-month crossover study with a 2-week washout. Strawberry supplementation resulted in a greater reduction in oxidative damage to low-density lipoprotein (LDL) measured as thiobarbituric acid-reactive substances in the LDL fraction (P = .014). At the end of the strawberry period, reductions in LDL cholesterol and in the ratio of total to high-density lipoprotein cholesterol were maintained close to 1-year values at -13.4% +/- 2.1% and -15.2% +/- 1.7%, respectively (P < .001), and were similar to the post-oat bran bread values. Strawberries also improved the palatability of the diet. We conclude that strawberry supplementation reduced oxidative damage to LDL while maintaining reductions in blood lipids and enhancing diet palatability. Added fruit may improve the overall utility of diets designed to lower coronary heart disease risk.

positive: Cola intake and serum lipids in the Oslo Health Study. Soft drinks can be a major source of sucrose, which may influence serum lipid concentration. We have examined the association between intake frequency of various types of soft drinks and the concentration of serum triglycerides (TG) and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol in the cross-sectional Oslo Health Study. A total of 14 188 subjects of the altogether 18,770 participants of the study had data on intake frequency of colas and non-colas, with or without sugar. The population sample consisted of both sexes and 3 age groups: group 1 (30 years of age), group 2 (40 and 45 years of age), and group 3 (59-60 years of age). In both sexes, HDL decreased and TG increased significantly (p < 0.001) with increasing intake frequency of colas. In contrast, no consistent associations were found between the reported intake of non-cola soft drinks and the serum lipids. We found no significant differences related to the reported presence or absence of sugar in the soft drinks. In multiple linear regression analyses, the colas vs. serum lipid associations prevailed (p < 0.001) after including 13 possible confounders: sex; age group; time since last meal; physical activity; intake of alcohol, coffee, cheese, fruit and (or) berries, and fatty fish; smoking; length of education; use of cholesterol-lowering drugs; and intake of non-colas. Thus, the self-reported intake frequency of colas, but not other soft drinks, was negatively associated with serum HDL, and positively associated with TG and LDL.

positive: Whole-grain ready-to-eat oat cereal, as part of a dietary program for weight loss, reduces low-density lipoprotein cholesterol in adults with overw... OBJECTIVE: Weight loss and consumption of viscous fibers both lower low-density lipoprotein (LDL) cholesterol levels. We evaluated whether or not a whole-grain, ready-to-eat (RTE) oat cereal containing viscous fiber, as part of a dietary program for weight loss, lowers LDL cholesterol levels and improves other cardiovascular disease risk markers more than a dietary program alone. DESIGN: Randomized, parallel-arm, controlled trial. SUBJECTS/SETTING: Free-living, overweight and obese adults (N=204, body mass index 25 to 45) with baseline LDL cholesterol levels 130 to 200 mg/dL (3.4 to 5.2 mmol/L) were randomized; 144 were included in the main analysis of participants who completed the trial without significant protocol violations. INTERVENTION: Two portions per day of whole-grain RTE oat cereal (3 g/day oat b-glucan) or energy-matched low-fiber foods (control), as part of a reduced energy ( approximately 500 kcal/day deficit) dietary program that encouraged limiting consumption of foods high in energy and fat, portion control, and regular physical activity. MAIN OUTCOME MEASURES: Fasting lipoprotein levels, waist circumference, triceps skinfold thickness, and body weight were measured at baseline and weeks 4, 8, 10, and 12. RESULTS: LDL cholesterol level was reduced significantly more with whole-grain RTE oat cereal vs control (-8.7+/-1.0 vs -4.3+/-1.1%, P=0.005). Total cholesterol (-5.4+/-0.8 vs -2.9+/-0.9%, P=0.038) and non-high-density lipoprotein-cholesterol (-6.3+/-1.0 vs -3.3+/-1.1%, P=0.046) were also lowered significantly more with whole-grain RTE oat cereal, whereas high-density lipoprotein and triglyceride responses did not differ between groups. Weight loss was not different between groups (-2.2+/-0.3 vs -1.7+/-0.3 kg, P=0.325), but waist circumference decreased more (-3.3+/-0.4 vs -1.9+/-0.4 cm, P=0.012) with whole-grain RTE oat cereal. Larger reductions in LDL, total, and non-high-density lipoprotein cholesterol levels and waist circumference were evident as early as week 4 in the whole-grain RTE oat cereal group. CONCLUSIONS: Consumption of a whole-grain RTE oat cereal as part of a dietary program for weight loss had favorable effects on fasting lipid levels and waist circumference. Copyright 2010 American Dietetic Association. Published by Elsevier Inc. All rights reserved.

positive: Antiallergic activities of pigmented rice bran extracts in cell assays. Using a panel of chemical, biochemical, and cell assays, we determined inhibitory effects of extracts of the pigmented black rice brans on in vitro allergic reactions. Ethanol-water (70% v/v) extracts from 5 pigmented brans were found to be more effective than an extract from a nonpigmented rice cultivar in suppressing the release of histamine and beta-hexosaminidase from basophilic RBL-2H3 cells stimulated with both Ionophore A23187 and immunoglobulin E (IgE)-antigen complexes. Suppression was also obtained with A23187-stimulated rat peritoneal mast cells. The extent of inhibition of these 2 markers of the immune response was accompanied by an influx of calcium ions. The inhibition of the immune process by the pigmented brans was confirmed by the observed modulation of the proinflammatory cytokine gene expressions and cytokine release, as indicated by the reduction in tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-4, and IL-6 mRNA expressions determined with the reverse transcription-polymerase chain reaction (RT-PCR). Reduction of TNF-alpha, IL-1beta, and IL-6 protein release from both the cultured cell line and peritoneal cells was further confirmed by enzyme-linked immunoadsorbent assays. Rice bran from the LK1-3-6-12-1-1 cultivar was the most effective inhibitor in all assays. This particular rice variety merits further evaluation as part of a human diet to ascertain its potential to protect against allergic diseases such as hay fever and asthma.

negative: The optimal diet for women with polycystic ovary syndrome? An optimal diet is one that not only prevents nutrient deficiencies by providing sufficient nutrients and energy for human growth and reproduction, but that also promotes health and longevity and reduces the risk of diet-related chronic diseases. The composition of the optimal diet for women with polycystic ovary syndrome (PCOS) is not yet known, but such a diet must not only assist short term with weight management, symptoms and fertility, but also specifically target the long-term risks of type 2 diabetes, CVD and certain cancers. With insulin resistance and compensatory hyperinsulinaemia now recognised as a key factor in the pathogenesis of PCOS, it has become clear that reducing insulin levels and improving insulin sensitivity are an essential part of management. Diet plays a significant role in the regulation of blood glucose and insulin levels, yet research into the dietary management of PCOS is lacking and most studies have focused on energy restriction rather than dietary composition per se. On the balance of evidence to date, a diet low in saturated fat and high in fibre from predominantly low-glycaemic-index-carbohydrate foods is recommended. Because PCOS carries significant metabolic risks, more research is clearly needed.

negative: Phytochemicals and cancer risk: a review of the epidemiological evidence. A number of epidemiological studies have investigated associations between various phytochemicals and cancer risk. Phytoestrogens and carotenoids are the two most commonly studied classes of phytochemicals; phytosterols, isothiocyanates, and chlorophyll also have been investigated, although to a much lesser extent. Because there have been no systematic reviews of the literature on all phytochemicals and cancer risk to date, this article systematically reviews 96 published epidemiological studies that examined associations between phytochemicals and cancer risk. Most studies found null associations between individual phytochemicals and cancer risk at various sites. In addition, results from past studies have been largely inconsistent, and observed associations have been of relatively modest magnitude. The most consistent protective effects were observed for higher levels--dietary intake, serum, plasma, or urinary metabolites--of β-carotene and renal cell cancer, β-cryptoxanthin and lung cancer, isothiocyanates and lung cancer, isothiocyanates and gastrointestinal cancer, lignans and postmenopausal breast cancer, and flavonoids and lung cancer. Although elevated risk of certain cancers with higher levels of certain phytochemicals was observed, an insufficient pool of studies examining the same associations or inconsistent findings across studies limit the ability to conclude that any one phytochemical increases cancer risk. Additional research is needed to support previously identified associations in cases where only one study has examined a particular relationship. Importantly, continued research efforts are needed to evaluate the cumulative and interactive effects of numerous phytochemicals and phytochemical-rich foods on cancer risk.

negative: Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal. The normal low-density lipoprotein (LDL) cholesterol range is 50 to 70 mg/dl for native hunter-gatherers, healthy human neonates, free-living primates, and other wild mammals (all of whom do not develop atherosclerosis). Randomized trial data suggest atherosclerosis progression and coronary heart disease events are minimized when LDL is lowered to <70 mg/dl. No major safety concerns have surfaced in studies that lowered LDL to this range of 50 to 70 mg/dl. The current guidelines setting the target LDL at 100 to 115 mg/dl may lead to substantial undertreatment in high-risk individuals.

negative: Mechanistic examination of walnuts in prevention of breast cancer. Walnuts contain bioactive molecules that may contribute to their beneficial effects, including alpha-linolenic acid (ALA) and phytosterols. In these studies, extracts of walnut, purified compounds, or postprandial serum were examined for effects on breast cancer cell proliferation and gene expression. Extracts derived from walnut oil decreased proliferation of MCF-7 cells, as did ALA and β-sitosterol. The gene expression response of ALA in the mouse breast cancer cell line TM2H indicates this molecule has multiple cellular targets with peroxisome proliferator-activated receptor (PPAR) target genes, liver X receptor (LXR), and farnesoid X receptor (FXR) target genes being affected. In transactivation assays, walnut oil extracts increased activity of FXR to a greater extent than the other tested nuclear receptors. When examined separately, walnut components ALA and β-sitosterol were the most efficacious activators of FXR. When serum from individuals fed walnut components were applied to MCF-7 cells, there was a correlation between body mass index and breast cancer cell proliferation in vitro. Taken together, these data support an effect of walnut and its bioactive constituents on mammary epithelial cells and that multiple molecular targets may be involved.

negative: Effects of plant-based diets on plasma lipids. Dyslipidemia is a primary risk factor for cardiovascular disease, peripheral vascular disease, and stroke. Current guidelines recommend diet as first-line therapy for patients with elevated plasma cholesterol concentrations. However, what constitutes an optimal dietary regimen remains a matter of controversy. Large prospective trials have demonstrated that populations following plant-based diets, particularly vegetarian and vegan diets, are at lower risk for ischemic heart disease mortality. The investigators therefore reviewed the published scientific research to determine the effectiveness of plant-based diets in modifying plasma lipid concentrations. Twenty-seven randomized controlled and observational trials were included. Of the 4 types of plant-based diets considered, interventions testing a combination diet (a vegetarian or vegan diet combined with nuts, soy, and/or fiber) demonstrated the greatest effects (up to 35% plasma low-density lipoprotein cholesterol reduction), followed by vegan and ovolactovegetarian diets. Interventions allowing small amounts of lean meat demonstrated less dramatic reductions in total cholesterol and low-density lipoprotein levels. In conclusion, plant-based dietary interventions are effective in lowering plasma cholesterol concentrations.

negative: Effects of a natural extract of (-)-hydroxycitric acid (HCA-SX) and a combination of HCA-SX plus niacin-bound chromium and Gymnema sylvestre extrac... AIM: The efficacy of optimal doses of highly bioavailable (-)-hydroxycitric acid (HCA-SX) alone and in combination with niacin-bound chromium (NBC) and a standardized Gymnema sylvestre extract (GSE) on weight loss in moderately obese subjects was evaluated by monitoring changes in body weight, body mass index (BMI), appetite, lipid profiles, serum leptin and excretion of urinary fat metabolites. HCA-SX has been shown to reduce appetite, inhibit fat synthesis and decrease body weight without stimulating the central nervous system. NBC has demonstrated its ability to maintain healthy insulin levels, while GSE has been shown to regulate weight loss and blood sugar levels. METHODS: A randomized, double-blind, placebo-controlled human study was conducted in Elluru, India for 8 weeks in 60 moderately obese subjects (ages 21-50, BMI >26 kg/m(2)). Subjects were randomly divided into three groups. Group A was administered HCA-SX 4667 mg, group B was administered a combination of HCA-SX 4667 mg, NBC 4 mg and GSE 400 mg, while group C was given placebo daily in three equally divided doses 30-60 min before meals. All subjects received a 2000 kcal diet/day and participated in supervised walking. RESULTS: At the end of 8 weeks, body weight and BMI decreased by 5-6% in both groups A and B. Food intake, total cholesterol, low-density lipoproteins, triglycerides and serum leptin levels were significantly reduced in both groups, while high-density lipoprotein levels and excretion of urinary fat metabolites increased in both groups. A marginal or non-significant effect was observed in all parameters in group C. CONCLUSION: The present study shows that optimal doses of HCA-SX and, to a greater degree, the combination of HCA-SX, NBC and GSE can serve as an effective and safe weight-loss formula that can facilitate a reduction in excess body weight and BMI, while promoting healthy blood lipid levels.

negative: The Effects of Phytosterols Present in Natural Food Matrices on Cholesterol Metabolism and LDL-Cholesterol: A Controlled Feeding Trial Background/Objectives Extrinsic phytosterols supplemented to the diet reduce intestinal cholesterol absorption and plasma LDL-cholesterol. However, little is known about their effects on cholesterol metabolism when given in native, unpurified form and in amounts achievable in the diet. The objective of this investigation was to test the hypothesis that intrinsic phytosterols present in unmodified foods alter whole-body cholesterol metabolism. Subjects/Methods Twenty out of 24 subjects completed a randomized, crossover feeding trial where all meals were provided by a metabolic kitchen. Each subject consumed two diets for 4 weeks each. The diets differed in phytosterol content (phytosterol-poor diet, 126 mg phytosterols/2000 kcal; phytosterol-abundant diet, 449 mg/2000 kcal) but were otherwise matched for nutrient content. Cholesterol absorption and excretion were determined by gas chromatograph/mass spectrometry after oral administration of stable isotopic tracers. Results The phytosterol-abundant diet resulted in lower cholesterol absorption [54.2 ± 2.2 % (95% confidence interval, 50.5%, 57.9%) vs. 73.2 ± 1.3% (69.5%, 76.9%), P<0.0001] and 79% higher fecal cholesterol excretion [1322 ± 112 (1083.2, 1483.3) vs. 739 ± 97 mg/day (530.1, 930.2), P<0.0001] relative to the phytosterol-poor diet. Plasma lathosterol/cholesterol ratio rose 82% [from 0.71 ± 0.11 (0.41, 0.96) to 1.29 ± 0.14 μg/mg (0.98, 1.53), (P<0.0001)]. LDL-cholesterol was similar between diets. Conclusions Intrinsic phytosterols at levels present in a healthy diet are biologically active and have large effects on whole body cholesterol metabolism not reflected in circulating LDL. More work is needed to assess the effects of phytosterol-mediated fecal cholesterol excretion on coronary heart disease risk in humans.

negative: Dietary flaxseed lignan extract lowers plasma cholesterol and glucose concentrations in hypercholesterolaemic subjects. Lignans, derived from flaxseed, are phyto-oestrogens being increasingly studied for their health benefits. An 8-week, randomised, double-blind, placebo-controlled study was conducted in fifty-five hypercholesterolaemic subjects, using treatments of 0 (placebo), 300 or 600 mg/d of dietary secoisolariciresinol diglucoside (SDG) from flaxseed extract to determine the effect on plasma lipids and fasting glucose levels. Significant treatment effects were achieved (P < 0.05 to < 0.001) for the decrease of total cholesterol (TC), LDL-cholesterol (LDL-C) and glucose concentrations, as well as their percentage decrease from baseline. At weeks 6 and 8 in the 600 mg SDG group, the decreases of TC and LDL-C concentrations were in the range from 22.0 to 24.38 % respectively (all P < 0.005 compared with placebo). For the 300 mg SDG group, only significant differences from baseline were observed for decreases of TC and LDL-C. A substantial effect on lowering concentrations of fasting plasma glucose was also noted in the 600 mg SDG group at weeks 6 and 8, especially in the subjects with baseline glucose concentrations > or = 5.83 mmol/l (lowered 25.56 and 24.96 %; P = 0.015 and P = 0.012 compared with placebo, respectively). Plasma concentrations of secoisolariciresinol (SECO), enterodiol (ED) and enterolactone were all significantly raised in the groups supplemented with flaxseed lignan. The observed cholesterol-lowering values were correlated with the concentrations of plasma SECO and ED (r 0.128-0.302; P < 0.05 to < 0.001). In conclusion, dietary flaxseed lignan extract decreased plasma cholesterol and glucose concentrations in a dose-dependent manner.

negative: Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial. CONTEXT: Regular intake of cocoa-containing foods is linked to lower cardiovascular mortality in observational studies. Short-term interventions of at most 2 weeks indicate that high doses of cocoa can improve endothelial function and reduce blood pressure (BP) due to the action of the cocoa polyphenols, but the clinical effect of low habitual cocoa intake on BP and the underlying BP-lowering mechanisms are unclear. OBJECTIVE: To determine effects of low doses of polyphenol-rich dark chocolate on BP. DESIGN, SETTING, AND PARTICIPANTS: Randomized, controlled, investigator-blinded, parallel-group trial involving 44 adults aged 56 through 73 years (24 women, 20 men) with untreated upper-range prehypertension or stage 1 hypertension without concomitant risk factors. The trial was conducted at a primary care clinic in Germany between January 2005 and December 2006. INTERVENTION: Participants were randomly assigned to receive for 18 weeks either 6.3 g (30 kcal) per day of dark chocolate containing 30 mg of polyphenols or matching polyphenol-free white chocolate. MAIN OUTCOME MEASURES: Primary outcome measure was the change in BP after 18 weeks. Secondary outcome measures were changes in plasma markers of vasodilative nitric oxide (S-nitrosoglutathione) and oxidative stress (8-isoprostane), and bioavailability of cocoa polyphenols. RESULTS: From baseline to 18 weeks, dark chocolate intake reduced mean (SD) systolic BP by -2.9 (1.6) mm Hg (P < .001) and diastolic BP by -1.9 (1.0) mm Hg (P < .001) without changes in body weight, plasma levels of lipids, glucose, and 8-isoprostane. Hypertension prevalence declined from 86% to 68%. The BP decrease was accompanied by a sustained increase of S-nitrosoglutathione by 0.23 (0.12) nmol/L (P < .001), and a dark chocolate dose resulted in the appearance of cocoa phenols in plasma. White chocolate intake caused no changes in BP or plasma biomarkers. CONCLUSIONS: Data in this relatively small sample of otherwise healthy individuals with above-optimal BP indicate that inclusion of small amounts of polyphenol-rich dark chocolate as part of a usual diet efficiently reduced BP and improved formation of vasodilative nitric oxide. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00421499.

negative: Phytoestrogen consumption and association with breast, prostate and colorectal cancer in EPIC Norfolk. Phytoestrogens are polyphenolic secondary plant metabolites that have structural and functional similarities to 17beta-oestradiol and have been associated with a protective effect against hormone-related cancers. Most foods in the UK only contain small amounts of phytoestrogens (median content 21 microg/100 g) and the highest content is found in soya and soya-containing foods. The highest phytoestrogen content in commonly consumed foods is found in breads (average content 450 microg/100 g), the main source of isoflavones in the UK diet. The phytoestrogen consumption in cases and controls was considerably lower than in Asian countries. No significant associations between phytoestrogen intake and breast cancer risk in a nested case-control study in EPIC Norfolk were found. Conversely, colorectal cancer risk was inversely associated with enterolignan intake in women but not in men. Prostate cancer risk was positively associated with enterolignan intake, however this association became non-significant when adjusting for dairy intake, suggesting that enterolignans can act as a surrogate marker for dairy or calcium intake. 2010 Elsevier Inc. All rights reserved.

negative: Low Vitamin D Status: Definition, Prevalence, Consequences and Correction Vitamin D is obtained from cutaneous production when 7-dehydrocholesterol is converted to vitamin D3 (cholecalciferol) by ultraviolet B radiation or by oral intake of vitamin D2 (ergocalciferol) and D3. An individual's vitamin D status is best evaluated by measuring the circulating 25-hydroxyvitamin D [25(OH)D] concentration. Though controversy surrounds the definition of low vitamin D status, there is increasing agreement that the optimal circulating 25(OH)D level should be ~30-32 ng/ml or above. Using this definition, it has been is estimated that approximately three quarters of all adults in the United States are low. Classically, low vitamin D status has skeletal consequences such as osteomalacia/rickets. More recently, associations between low vitamin D status and increased risk for various non-skeletal morbidities have been recognized; whether all of these associations are causally related to low vitamin D status remains to be determined. To achieve optimal vitamin D status, daily intakes of at least 1000 IU or more of vitamin D are required. The risk of toxicity with “high” amounts of vitamin D intake is low. Substantial between-individual variability exists in response to the same administered vitamin D dose. When to monitor 25(OH)D levels has received little attention. Supplementation with vitamin D3 may be preferable to vitamin D2.

negative: Curcumin (diferuloylmethane) delivery methods: a review. Curcumin interacts with a large number of extra- and intracellular targets in a biphasic dose-dependent manner. It controls inflammation, oxidative stress, cell survival, cell secretion, homeostasis, and proliferation. Its mechanisms of action are generally directed toward cells that exhibit disordered physiology or blatant mutation-based abnormal states. Optimizing preventative or therapeutic applications require delivering appropriate quantities of curcumin to lesioned cellular targets. Since diseased conditions anatomically are located from topical to systemic sites, efficient application of curcumin requires specific lesion-oriented delivery methods, representatives of which are here reviewed. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

negative: Oral sildenafil citrate (viagra) for erectile dysfunction: a systematic review and meta-analysis of harms. OBJECTIVES: To summarize and compare evidence on harms in sildenafil- and placebo-treated men with erectile dysfunction (ED) in a systematic review and meta-analysis. METHODS: Randomized placebo-controlled trials (RCTs) were identified using an electronic search in MEDLINE, EMBASE, PsycINFO, SCOPUS, and Cochrane CENTRAL. The rates of any adverse events (AEs), most commonly reported AEs, withdrawals because of adverse events, and serious adverse events were ascertained and compared between sildenafil and placebo groups. The results of men with ED were stratified by clinical condition(s). Statistical heterogeneity was explored. Meta-analyses based on random-effects model were also performed. RESULTS: A total of 49 RCTs were included. Sildenafil-treated men had a higher risk for all-cause AEs (RR = 1.56, 95% CI: 1.38, 1.76), headache, flushing, dyspepsia, and visual disturbances compared with placebo-treated men. The magnitude of excess risk was greater in fixed- than in flexible-dose trials. The rates of serious adverse events and withdrawals because of adverse events did not differ in sildenafil vs placebo groups. A higher dose of sildenafil corresponded to a greater risk of AEs. The increased risk of harms was observed within and across clinically defined specific groups of patients. CONCLUSIONS: There was a lack of RCTs reporting long-term (>6 months) harms data. In short-term trials, men with ED randomized to sildenafil had an increased risk of all-cause any AEs, headache, flushing, dyspepsia, and visual disturbances. The exploration of different modes of dose optimization of sildenafil may be warranted.

negative: Symptomatic efficacy of avocado-soybean unsaponifiables (ASU) in osteoarthritis (OA) patients: a meta-analysis of randomized controlled trials. OBJECTIVE: To evaluate the efficacy of preparations with avocado-soybean unsaponifiables (ASUs) in osteoarthritis (OA) patients using meta-analysis on randomized controlled trials (RCTs). METHOD: RCTs from systematic searches were included if they explicitly stated that hip and/or knee OA patients were randomized to either ASU or placebo. The co-primary outcome was reduction in pain and Lequesne index, leading to effect size (ES), calculated as the standardized mean difference. As secondary analysis, the number of responders to therapy was analyzed as odds ratios (ORs). Restricted maximum likelihood methods were applied for the meta-analyses, using mixed effects models. RESULTS: Four trials--all supported by the manufacturer--were included, with 664 OA patients with either hip (41.4%) or knee (58.6%) OA allocated to either 300 mg ASU (336) or placebo (328). Average trial duration was 6 months (range: 3-12 months). Though based on heterogeneous results, the combined pain reduction favored ASU (I(2) = 83.5%, ES = 0.39 [95% confidence intervals: 0.01-0.76], P=0.04). Applying the Lequesne index also favored ASU (I(2) = 61.0%, ES = 0.45 [0.21-0.70], P = 0.0003). Secondarily, the number of responders following ASU compared to placebo (OR = 2.19, P = 0.007) corresponded to a number needed to treat of six (4-21) patients. CONCLUSIONS: Based on the available evidence, patients may be recommended to give ASU a chance for e.g., 3 months. Meta-analysis data support better chances of success in patients with knee OA than in those with hip OA.

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: Effects of almond consumption on the reduction of LDL-cholesterol: a discussion of potential mechanisms and future research directions. Diet plays a seminal role in the prevention and treatment of cardiovascular disease. Consumption of tree nuts has been shown to reduce low-density lipoprotein cholesterol (LDL-C), a primary target for coronary disease prevention, by 3-19%. Almonds have been found to have a consistent LDL-C-lowering effect in healthy individuals, and in individuals with high cholesterol and diabetes, in both controlled and free-living settings. Almonds are low in saturated fatty acids, rich in unsaturated fatty acids, and contain fiber, phytosterols, and plant protein. Other cardioprotective nutrients unique to almonds include α-tocopherol, arginine, magnesium, copper, manganese, calcium, and potassium. Mechanisms responsible for the LDL-C reduction observed with almond consumption are likely associated with the nutrients almonds provide. Biologically active by nature, these nutrients target primary mechanistic routes of LDL-C reduction, including decreased (re)absorption of cholesterol and bile acid, increased bile acid and cholesterol excretion, and increased LDL-C receptor activity. The nutrients present in almonds may regulate enzymes involved in de novo cholesterol synthesis and bile acid production. Research is needed to understand all mechanisms by which almonds reduce cardiovascular disease risk. © 2011 International Life Sciences Institute.

negative: A multicenter randomized controlled trial of a plant-based nutrition program to reduce body weight and cardiovascular risk in the corporate setting: the GEICO study Background/objectives: To determine the effects of a low-fat plant-based diet program on anthropometric and biochemical measures in a multicenter corporate setting. Subjects/methods: Employees from 10 sites of a major US company with body mass index ⩾25 kg/m2 and/or previous diagnosis of type 2 diabetes were randomized to either follow a low-fat vegan diet, with weekly group support and work cafeteria options available, or make no diet changes for 18 weeks. Dietary intake, body weight, plasma lipid concentrations, blood pressure and glycated hemoglobin (HbA1C) were determined at baseline and 18 weeks. Results: Mean body weight fell 2.9 kg and 0.06 kg in the intervention and control groups, respectively (P<0.001). Total and low-density lipoprotein (LDL) cholesterol fell 8.0 and 8.1 mg/dl in the intervention group and 0.01 and 0.9 mg/dl in the control group (P<0.01). HbA1C fell 0.6 percentage point and 0.08 percentage point in the intervention and control group, respectively (P<0.01). Among study completers, mean changes in body weight were −4.3 kg and −0.08 kg in the intervention and control groups, respectively (P<0.001). Total and LDL cholesterol fell 13.7 and 13.0 mg/dl in the intervention group and 1.3 and 1.7 mg/dl in the control group (P<0.001). HbA1C levels decreased 0.7 percentage point and 0.1 percentage point in the intervention and control group, respectively (P<0.01). Conclusions: An 18-week dietary intervention using a low-fat plant-based diet in a corporate setting improves body weight, plasma lipids, and, in individuals with diabetes, glycemic control.

negative: The association between dietary lignans, phytoestrogen-rich foods, and fiber intake and postmenopausal breast cancer risk: a German case-control st... Phytoestrogens are structurally similar to estrogens and may affect breast cancer risk by mimicking estrogenic/antiestrogenic properties. In Western societies, whole grains and possibly soy foods are rich sources of phytoestrogens. A population-based case-control study in German postmenopausal women was used to evaluate the association of phytoestrogen-rich foods and dietary lignans with breast cancer risk. Dietary data were collected from 2,884 cases and 5,509 controls using a validated food-frequency questionnaire, which included additional questions phytoestrogen-rich foods. Associations were assessed using conditional logistic regression. All analyses were adjusted for relevant risk and confounding factors. Polytomous logistic regression analysis was performed to evaluate the associations by estrogen receptor (ER) status. High and low consumption of soybeans as well as of sunflower and pumpkin seeds were associated with significantly reduced breast cancer risk compared to no consumption (OR = 0.83, 95% CI = 0.70-0.97; and OR = 0.66, 95% CI = 0.77-0.97, respectively). The observed associations were not differential by ER status. No statistically significant associations were found for dietary intake of plant lignans, fiber, or the calculated enterolignans. Our results provide evidence for a reduced postmenopausal breast cancer risk associated with increased consumption of sunflower and pumpkin seeds and soybeans.

negative: Plant Sterols as Anticancer Nutrients: Evidence for Their Role in Breast Cancer While many factors are involved in the etiology of cancer, it has been clearly established that diet significantly impacts one’s risk for this disease. More recently, specific food components have been identified which are uniquely beneficial in mitigating the risk of specific cancer subtypes. Plant sterols are well known for their effects on blood cholesterol levels, however research into their potential role in mitigating cancer risk remains in its infancy. As outlined in this review, the cholesterol modulating actions of plant sterols may overlap with their anti-cancer actions. Breast cancer is the most common malignancy affecting women and there remains a need for effective adjuvant therapies for this disease, for which plant sterols may play a distinctive role.

negative: Prostate cancer and inositol hexaphosphate: efficacy and mechanisms. There are now extensive scientific data suggesting the potential role of dietary and non-dietary phytochemicals in the prevention and control of prostate cancer (PCA) growth and progression. PCA is a disease of elderly male populations with a relatively slower rate of growth and progression as compared to most other cancers and, therefore, is a candidate disease for preventive intervention. Overall, PCA growth and progression involve aberrant mitogenic and survival signaling and deregulated cell cycle progression, accompanied by gradual accumulation of genetic and epigenetic changes over a period of years. Several mechanisms, including overexpression of growth, survival and angiogenic factors and their receptors, together with a loss/decrease of tumor suppressor p53, retinoblastoma and cyclin-dependent kinase inhibitor, have been implicated in PCA growth and progression. Therefore, phytochemicals targeting these molecular events could have a promising role in PCA prevention and/or therapy. Inositol hexaphosphate (IP6) is a major constituent of most cereals, legumes, nuts, oil seeds and soybean. Taken orally as an over-the-counter dietary/nutrient supplement, and is recognised as offering several health benefits without any known toxicity. In vitro anticancer efficacy of IP6 has been observed in many human, mouse and rat prostate cancer cells. Completed studies also show that oral feeding of IP6 inhibits human PCA xenograft growth in nude mice without toxicity. In a recently completed pilot study, we observed similar preventive effects of IP6 on prostate tumorigenesis in the TRAMP model. Mechanistic studies indicate that IP6 targets mitogenic and survival signaling, as well as cell cycle progression, in PCA cells. IP6 is also shown to target molecular events associated with angiogenesis. Moreover, IP6 has pleiotropic molecular targets for its overall efficacy against PCA and, therefore, could be a suitable candidate agent for preventive intervention of this malignancy in humans.

negative: Evaluation of a real-time polymerase chain reaction (PCR) assay for detection of anisakis simplex parasite as a food-borne allergen source in seafo... Anisakis simplex has been recognized as an important cause of disease in humans and as a food-borne allergen source. Actually, this food-borne parasite was recently identified as an emerging food safety risk. An A. simplex -specific primer-probe system based on a real-time polymerase chain reaction (PCR) detection assay has been successfully optimized and validated with seafood samples. In addition, a DNA extraction procedure has been optimized to detect the presence of the nematode in food samples. The assay is a very reliable, specific, and sensitive methodology to detect the presence of traces of this parasite in seafood products, including highly processed samples. As a result, 13 sequences of cytochrome c oxidase II gene were obtained and scrutinized to calculate intra- and interspecific variabilities of 0 and 35-67%, respectively. Finally, an efficiency of 2.07 +/- 0.14 of the assay was calculated, and a limit of detection of 40 ppm parasite in 25 g of sample was also optimized. Actually, the presence of this parasite in several seafood products has been demonstrated, enforcing the necessity of a design for a good manufacturing practice protocol for the processing industry to minimize the presence of this parasite as a food-borne allergen source in seafood products.

negative: Clinical efficacy of apple polyphenol for treating cedar pollinosis. A double-blind comparative study was conducted on cedar pollinosis patients in order to evaluate the treatment efficacy of apple polyphenol (Ap). Ap was administered (500 mg) once daily for 12 weeks, starting about 2 weeks prior to cedar pollen dispersion. Pollinosis symptoms during the study were evaluated according to the classification in the guidelines for allergic rhinitis diagnosis and treatment. The results show that the sneezing score was significantly lower for the Ap group than with the placebo group during the early period of pollen dispersion and during the main dispersion period. In addition, no adverse reactions were induced by Ap during the study. These results suggest that Ap may alleviate the symptoms of cedar pollinosis.

negative: Ascorbic acid prevents the dose-dependent inhibitory effects of polyphenols and phytates on nonheme-iron absorption. The effects of maize-bran phytate and of a polyphenol (tannic acid) on iron absorption from a white-bread meal were tested in 199 subjects. The phytate content was varied by adding different concentrations of phytate-free and ordinary maize bran. Iron absorption decreased progressively when maize bran containing increasing amounts of phytate phosphorous (phytate P) (from 10 to 58 mg) was given. The inhibitory effect was overcome by 30 mg ascorbic acid. The inhibitory effects of tannic acid (from 12 to 55 mg) were also dose dependent. Studies suggested that greater than or equal to 50 mg ascorbic acid would be required to overcome the inhibitory effects on iron absorption of any meal containing greater than 100 mg tannic acid. Our findings indicate that it may be possible to predict the bioavailability of iron in a diet if due account is taken of the relative content in the diet of the major promoters and inhibitors of iron absorption.

negative: Determination of volatile nitrosamines in meat products by microwave-assisted extraction and dispersive liquid-liquid microextraction coupled to ga... Microwave-assisted extraction (MAE) and dispersive liquid-liquid microextraction (DLLME) coupled with gas chromatography-mass spectrometry (GC-MS) were evaluated for use in the extraction and preconcentration of volatile nitrosamines in meat products. Parameters affecting MAE, such as the extraction solvent used, and DLLME, including the nature and volume of the extracting and disperser solvents, extraction time, salt addition and centrifugation time, were optimized. In the MAE method, 0.25g of sample mass was extracted in 10mL NaOH (0.05M) in a closed-vessel system. For DLLME, 1.5mL of methanol (disperser solvent) containing 20μL of carbon tetrachloride (extraction solvent) was rapidly injected by syringe into 5mL of the sample extract solution (previously adjusted to pH 6), thereby forming a cloudy solution. Phase separation was performed by centrifugation, and a volume of 3μL of the sedimented phase was analyzed by GC-MS. The enrichment factors provided by DLLME varied from 220 to 342 for N-nitrosodiethylamine and N-nitrosopiperidine, respectively. The matrix effect was evaluated for different samples, and it was concluded that sample quantification can be carried out by aqueous calibration. Under the optimized conditions, detection limits ranged from 0.003 to 0.014ngmL(-1) for NPIP and NMEA, respectively (0.12-0.56ngg(-1) in the meat products). Copyright © 2011 Elsevier B.V. All rights reserved.

negative: The DietCompLyf study: a prospective cohort study of breast cancer survival and phytoestrogen consumption. DietCompLyf is a multi-centre prospective study designed to investigate associations between phytoestrogens - naturally occurring plant compounds with oestrogenic properties - and other diet and lifestyle factors with breast cancer recurrence and survival. 3159 women with grades I-III breast cancer were recruited 9-15 months post-diagnosis from 56 UK hospitals. Detailed information on clinico-pathological, diet, lifestyle and quality of life is collected annually up to 5 years. Biological samples have also been collected as a resource for subsequent evaluation. The characteristics of the patients and associations between pre-diagnosis intake of phytoestrogens (isoflavones and lignans; assessed using the EPIC-Norfolk UK 130 question food frequency questionnaire) and breast cancer (i) risk factors and (ii) prognostic factors are described for 1797 women who had complete data for all covariates and phytoestrogens of interest. Isoflavone intakes were higher in the patients who were younger at diagnosis, in the non-smokers, those who had breast-fed and those who took supplements. Lignan intakes were higher in patients with a higher age at diagnosis, in ex-smokers, those who had breast-fed, who took supplements, had a lower BMI at diagnosis, lower age at menarche and were nulliparous. No significant associations between pre-diagnosis phytoestrogen intake and factors associated with improved breast cancer prognosis were observed. The potential for further exploration of the relationship between phytoestrogens and breast cancer recurrence and survival, and for the establishment of evidence to improve dietary and lifestyle advice offered to patients following breast cancer diagnosis using DietCompLyf data is discussed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

negative: Evolution of Inflammatory Diseases The association of inflammation with modern human diseases (e.g. obesity, cardiovascular disease, type 2 diabetes mellitus, cancer) remains an unsolved mystery of current biology and medicine. Inflammation is a protective response to noxious stimuli that unavoidably occurs at a cost to normal tissue function. This fundamental tradeoff between the cost and benefit of the inflammatory response has been optimized over evolutionary time for specific environmental conditions. Rapid change of the human environment due to niche construction outpaces genetic adaptation through natural selection, leading increasingly to a mismatch between the modern environment and selected traits. Consequently, multiple tradeoffs that affect human physiology are not optimized to the modern environment, leading to increased disease susceptibility. Here we examine the inflammatory response from an evolutionary perspective. We discuss unique aspects of the inflammatory response and its evolutionary history that can help explain the association between inflammation and modern human diseases.

negative: Dietary seaweed modifies estrogen and phytoestrogen metabolism in healthy postmenopausal women. Seaweed and soy foods are consumed daily in Japan, where breast cancer rates for postmenopausal women are significantly lower than in the West. Likely mechanisms include differences in diet, especially soy consumption, and estrogen metabolism. Fifteen healthy postmenopausal women participated in this double-blind trial of seaweed supplementation with soy challenge. Participants were randomized to 7 wk of either 5 g/d seaweed (Alaria) or placebo (maltodextrin). During wk 7, participants also consumed a daily soy protein isolate (2 mg isoflavones/kg body weight). After a 3-wk washout period, participants were crossed over to the alternate supplement schedule. There was an inverse correlation between seaweed dose (mg/kg body weight) and serum estradiol (E2) (seaweed-placebo = y = -2.29 x dose + 172.3; r = -0.70; P = 0.003), [corrected] which was linear across the range of weights. Soy supplementation increased urinary daidzein, glycitein, genistein, and O-desmethylangolensin (P = 0.0001) and decreased matairesinol and enterolactone (P < 0.05). Soy and seaweed plus soy (SeaSoy) increased urinary excretion of 2-hydroxyestrogen (2-OHE) (P = 0.0001) and the ratio of 2-OHE:16alpha-hydroxyestrone (16alphaOHE(1)) (P = 0.01). For the 5 equol excretors, soy increased urinary equol excretion (P = 0.0001); the combination of SeaSoy further increased equol excretion by 58% (P = 0.0001). Equol producers also had a 315% increase in 2:16 ratio (P = 0.001) with SeaSoy. Seaweed favorably alters estrogen and phytoestrogen metabolism and these changes likely include modulation of colonic bacteria.

negative: Simultaneous analysis of serotonin, melatonin, piceid and resveratrol in fruits using liquid chromatography tandem mass spectrometry. An analytical method was developed for the simultaneous quantification of serotonin, melatonin, trans- and cis-piceid, and trans- and cis-resveratrol using reversed-phase high performance liquid chromatography coupled to mass spectrometry (HPLC-MS) with electrospray ionization (ESI) in both positive and negative ionization modes. HPLC optimal analytical separation was achieved using a mixture of acetonitrile and water with 0.1% formic acid as the mobile phase in linear gradient elution. The mass spectrometry parameters were optimized for reliable quantification and the enhanced selectivity and sensitivity selected reaction monitoring mode (SRM) was applied. For extraction, the direct analysis of initial methanol extracts was compared with further ethyl acetate extraction. In order to demonstrate the applicability of this analytical method, serotonin, melatonin, trans- and cis-piceid, and trans- and cis-resveratrol from 24 kinds of commonly consumed fruits were quantified. The highest serotonin content was found in plantain, while orange bell peppers had the highest melatonin content. Grape samples possessed higher trans- and cis-piceid, and trans- and cis-resveratrol contents than the other fruits. The results indicate that the combination of HPLC-MS detection and simple sample preparation allows the rapid and accurate quantification of serotonin, melatonin, trans- and cis-piceid, and trans- and cis-resveratrol in fruits. Copyright © 2011 Elsevier B.V. All rights reserved.

negative: Evidence-based care of women with a multiple pregnancy. Women with a multiple pregnancy face greater risks for themselves and their infants than women pregnant with one child. Pre-pregnancy care should focus on avoiding multiple pregnancy. Early prenatal care centres on determining chorionicity and screening for fetal anomalies, with later care focusing on the presentation, prediction and management of preterm birth, and intrauterine growth restriction. The optimal timing and mode of birth are the focus of current multicentre, randomised, controlled trials. However, the data from such trials on care for women with a multiple pregnancy are limited. Many areas of care require better-quality information, including when using assisted reproductive techniques, the optimal number of embryos to be transferred, care after the diagnosis of chorionicity, and the benefits of specialised multiple pregnancy clinics. Better-quality information is required to inform clinical practice for women with complications of multiple pregnancy, including monoamniotic twin pregnancy, treatment of twin-to-twin transfusion syndrome, and care following single intrauterine fetal death.

negative: Vitamin D and sterol composition of 10 types of mushrooms from retail suppliers in the United States. Vitamin D(2) (ergocalciferol) and sterols were analyzed in mushrooms sampled nationwide in the United States to update the USDA Nutrient Database for Standard Reference. Vitamin D(2) was assayed using HPLC with [(3)H]-vitamin D(3) internal standard and sterols by GC-FID mass spectrometric (MS) confirmation. Vitamin D(2) was low (0.1-0.3 μg/100 g) in Agaricus bisporus (white button, crimini, portabella) and enoki, moderate in shiitake and oyster (0.4-0.7 μg/100 g), and high in morel, chanterelle, maitake (5.2-28.1 μg/100 g) and UV-treated portabella (3.4-20.9 μg/100 g), with significant variability among composites for some types. Ergosterol (mg/100 g) was highest in maitake and shiitake (79.2, 84.9) and lowest in morel and enoki (26.3, 35.5); the range was <10 mg/100 g among white button composites but 12-50 mg/100 g among samples of other types. All mushrooms contained ergosta-5,7-dienol (22,23-dihydroergosterol) (3.53-18.0 mg/100 g) and (except morel) ergosta-7-enol. Only morel contained brassicasterol (28.6 mg/100 g) and campesterol (1.23-4.54 mg/100 g) and no ergosta-7,22-dienol. MS was critical in distinguishing campesterol from ergosta-7,22-dienol.

negative: Effects of antiplatelet components of tomato extract on platelet function in vitro and ex vivo: a time-course cannulation study in healthy humans. BACKGROUND: Natural antithrombotic agents that influence platelet function are of potential interest for primary prevention of cardiovascular disease. Previous reports showed that tomato extracts inhibit platelet aggregation in vitro, but little is known of the active components, their mode of action, or their efficacy in vivo. OBJECTIVE: The objectives of the study were to examine the antiplatelet activity of specific tomato components by in vitro experimentation and to establish their ex vivo efficacy in healthy humans. DESIGN: The mechanisms of action of antiplatelet components isolated from tomato extracts were examined in vitro. A 7-h time-course study was carried out in cannulated human subjects (n = 23) to determine the ex vivo efficacy of a supplement drink containing tomato extract and the onset and duration of antiplatelet effects. RESULTS: The inhibition of ADP-, collagen-, thrombin-, and arachidonate-mediated platelet aggregation by tomato extract components appears to be linked to the inhibition of glycoprotein IIb/IIIa and platelet secretory mechanisms. We found a significant inhibition of baseline platelet function, from 2.9 +/- 1.4% (optimal ADP concentrations; P = 0.03) to 20.0 +/- 4.9% (suboptimal ADP concentrations; P < 0.001), 3 h after supplementation with a dose of tomato extract equivalent to 6 tomatoes. The observed effects persisted for >12 h. Coagulation variables were not affected. CONCLUSIONS: The ingestion of tomato components with in vitro antiplatelet activity significantly affects ex vivo platelet function. The reported cardioprotective effects of tomatoes are potentially linked to a modulation of platelet function.

negative: Optimized LC/MS/MS analysis of morphine and codeine in poppy seed and evaluation of their fate during food processing as a basis for risk analysis. The opiate alkaloids present in poppy seed intended for use in food recently have raised major concerns. An efficient method for routine analysis of morphine and codeine using liquid chromatography in combination with tandem mass spectrometry on a triple quadrupole instrument (LC/MS/MS) was therefore developed. The optimal sample preparation was found to be cold extraction of 10 g of unground poppy seed with 30 mL of methanol containing 0.1% acetic acid for 60 min shaken at 250 rpm. The fate of morphine during food processing was also studied. All experiments led to a significant reduction of morphine and codeine. For poppy cake only 16-50% of the morphine was recovered, and in poppy buns at the highest temperature (220 degrees C) only 3% of the original morphine content was found. Ground poppy seed showed significantly lower recoveries than untreated seed. Morphine elimination during food processing has to be taken into account in the current discussion about its maximum limits in poppy seed.