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MED-1296 | Natural immunomodulators are getting more and more popular. The popularity, however, often brings over-optimistic claims and mediocre effects. The purpose of the present study was to directly compare eleven most commonly used immunomodulators. Through testing both cellular and humoral branches of immune reactions, we found that most of the immunomodulators tested have limited, if any, effects, with glucan being consistently the most active molecule strongly stimulating every reaction evaluated. These data were also confirmed using a Lewis lung cancer model, where only glucan and resveratrol lowered the number of metastases. |
MED-1299 | OBJECTIVE: Several studies have shown a baker's yeast beta-1,3/1,6-d-glucan, extracted from Saccharomyces cerevisiae, is effective in reducing the incidence of cold and flu symptoms. This study evaluated the effect of a specific beta-glucan supplement (Wellmune) on upper respiratory tract symptoms and psychological well-being in women with moderate levels of psychological stress. METHODS: Healthy women (38 ± 12 years old) prescreened for moderate levels of psychological stress, self-administered a placebo (n = 38) or 250 mg of Wellmune (n = 39) daily for 12 weeks. We used the Profile of Mood States (POMS) psychological survey to assess changes in mental/physical energy levels (vigor) and overall well-being (global mood state). A quantitative health perception log was used to track upper respiratory symptoms. RESULTS: Subjects in the Wellmune group reported fewer upper respiratory symptoms compared to placebo (10% vs 29%), better overall well-being (global mood state: 99 ± 19 vs 108 ± 23, p < 0.05), and superior mental/physical energy levels (vigor: 19.9 ± 4.7 vs 15.8 ± 6.3, p < 0.05). CONCLUSIONS: These data show that daily dietary supplementation with Wellmune reduces upper respiratory symptoms and improves mood state in stressed subjects, and thus it may be a useful approach for maintaining immune protection against daily stressors. |
MED-1303 | The aim of the present review article is to summarize the available information related to the availability, production, chemical composition, pharmacological activity, and traditional uses of Avena sativa to highlight its potential to contribute to human health. Oats are now cultivated worldwide and form an important dietary staple for the people in number of countries. Several varieties of oats are available. It is a rich source of protein, contains a number of important minerals, lipids, β-glucan, a mixed-linkage polysaccharide, which forms an important part of oat dietary fiber, and also contains various other phytoconstituents like avenanthramides, an indole alkaloid-gramine, flavonoids, flavonolignans, triterpenoid saponins, sterols, and tocols. Traditionally oats have been in use since long and are considered as stimulant, antispasmodic, antitumor, diuretic, and neurotonic. Oat possesses different pharmacological activities like antioxidant, anti-inflammatory, wound healing, immunomodulatory, antidiabetic, anticholesterolaemic, etc. A wide spectrum of biological activities indicates that oat is a potential therapeutic agent. |
MED-1304 | Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world and its incidence is increasing rapidly. NAFLD is a spectrum ranging from simple steatosis, which is relatively benign hepatically, to nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis. Obesity, insulin resistance, type 2 diabetes mellitus, and dyslipidemia are the most important risk factors for NAFLD. Due to heavy enrichment with metabolic risk factors, individuals with NAFLD are at significantly higher risk for cardiovascular disease. Individuals with NAFLD have higher incidence of type 2 diabetes. The diagnosis of NAFLD requires imaging evidence of hepatic steatosis in the absence of competing etiologies including significant alcohol consumption. Liver biopsy remains the gold standard for diagnosing NASH and for determining prognosis. Weight loss remains a cornerstone of treatment. Weight loss of ∼5% is believed to improve steatosis, whereas ∼10% weight loss is necessary to improve steatohepatitis. A number of pharmacologic therapies have been investigated to treat NASH, and agents such as vitamin E and thiazolidinediones have shown promise in select patient subgroups. |
MED-1305 | This viewpoint aims to 1) review the available scientific literature on the relationship between whole grain consumption and body weight regulation; 2) evaluate the potential mechanisms whereby whole grain intake may help reduce overweight and 3) try to understand why epidemiological studies and clinical trials provide diverging results on this topic. All the prospective epidemiological studies demonstrate that a higher intake of whole grains is associated with lower BMI and body weight gain. However, these results do not clarify whether whole grain consumption is simply a marker of a healthier lifestyle or a factor favoring "per se" lower body weight. Habitual whole grain consumption seems to cause lower body weight by multiple mechanisms such as lower energy density of whole grain based products, lower glycemic index, fermentation of non digestible carbohydrates (satiety signals) and finally by modulating intestinal microflora. In contrast with epidemiological evidence, the results of few clinical trials do not confirm that a whole grain low-calorie diet is more effective in reducing body weight than a refined cereal diet, but their results may have been affected by small sample size or short duration of the intervention. Therefore, further intervention studies with adequate methodology are needed to clarify this question. For the time being, whole grain consumption can be recommended as one of the features of the diet that may help control body weight but also because is associated with a lower risk to develop type 2 diabetes, cardiovascular diseases and cancer. Copyright © 2011 Elsevier B.V. All rights reserved. |
MED-1307 | Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States. While the American Association for the Study of Liver Diseases guidelines define NAFLD as hepatic steatosis detected either on histology or imaging without a secondary cause of abnormal hepatic fat accumulation, no imaging modality is recommended as standard of care for screening or diagnosis. Bedside ultrasound has been evaluated as a non-invasive method of diagnosing NAFLD with the presence of characteristic sonographic findings. Prior studies suggest characteristic sonographic findings for NAFLD include bright hepatic echoes, increased hepatorenal echogenicity, vascular blurring of portal or hepatic vein and subcutaneous tissue thickness. These sonographic characteristics have not been shown to aid bedside clinicians easily identify potential cases of NAFLD. While sonographic findings such as attenuation of image, diffuse echogenicity, uniform heterogeneous liver, thick subcutaneous depth, and enlarged liver filling of the entire field could be identified by clinicians from bedside ultrasound. The accessibility, ease of use, and low-side effect profile of ultrasound make bedside ultrasound an appealing imaging modality in the detection of hepatic steatosis. When used with appropriate clinical risk factors and steatosis involves greater than 33% of the liver, ultrasound can reliably diagnose NAFLD. Despite the ability of ultrasound in detecting moderate hepatic steatosis, it cannot replace liver biopsy in staging the degree of fibrosis. The purpose of this review is to examine the diagnostic accuracy, utility, and limitations of ultrasound in the diagnosis of NAFLD and its potential use by clinicians in routine practices. |
MED-1309 | Obesity is associated with a great diversity of diseases including non-alcoholic fatty liver disease. Our recent report suggested that oat, rich in beta-glucan, had a metabolic-regulating and liver-protecting effect in an animal model. In this study, we performed a clinical trial to further confirm the effect of oat. Subjects with BMI ≥27 and aged 18-65, were randomly divided into a control (n=18) and an oat-treated (n=16) group, taking a placebo or beta glucan-containing oat cereal, respectively, for 12 weeks. Our data showed that consumption of oat reduced body weight, BMI, body fat and the waist-to-hip ratio. Profiles of hepatic function, including AST, but especially ALT, were useful resources to help in the evaluation of the liver, since both showed decrements in patients with oat consumption. Nevertheless, anatomic changes were still not observed by ultrasonic image analysis. Ingestion of oat was well tolerated and there was no adverse effect during the trial. In conclusion, consumption of oat reduced obesity, abdominal fat, and improved lipid profiles and liver functions. Taken as a daily supplement, oat could act as an adjuvant therapy for metabolic disorders. |
MED-1312 | The aim of this study was to evaluate the antiinflammatory effect of oatmeal extract oligomer on skin fragments stimulated by a neuromediator, vasoactive intestinal peptide (VIP). Skin fragments (from plastic surgery) were maintained in survival conditions for 6 h. To induce inflammation, VIP was placed in contact with dermis by culture medium. Histological analysis was then performed on hematoxylin- and eosin-stained slides. Edema was evaluated with semiquantitative scores. Vasodilation was studied by quantifying the percentage of dilated vessels according to scores and by measuring their surface by morphometrical image analysis. TNF-alpha dosage was made on culture supernatants. Vasodilation was significantly increased after application of VIP. After treatment with oatmeal extract oligomer, the mean surface of dilated vessels and edema were significantly decreased compared with VIP-treated skin. Moreover, treatment with this extract decreased TNF-alpha. |
MED-1314 | The use of epidermal growth factor receptor (EGFR) inhibitors for the treatment of solid tumours is increasing. However, the tolerability profile for EGFR-inhibitors, such as the monoclonal antibody cetuximab and the tyrosine kinase inhibitor erlotinib, is characterised by a unique group of skin reactions dominated by an acneiform eruption, xerosis, eczema and changes in the hair and nails. The possibility that this skin toxicity correlates with anti-tumour activity offers the potential to titrate dosing on a case-by-case basis. These skin effects may constitute a significant obstacle to treatment compliance. Accordingly, there is a need for consistent, multi-disciplinary management strategies that will allow patients to receive the recommended dosages of such targeted therapies. The eruption responds well to some acne therapies and xerosis can be controlled by standard emollients. Here we present an overview of the treatment options for skin reactions that are available today, and evaluate some of the ways in which the treatment of such EGFR-inhibitor-related skin reactions may be improved in the future. Evidence-based studies are needed to determine the best way to manage these effects. |
MED-1315 | PURPOSE: The EGFR-independent activation of the RAS/RAF/MEK/MAPK pathway is one of the resistance mechanisms to cetuximab. EXPERIMENTAL DESIGN: We have evaluated, in vitro and in vivo, the effects of BAY 86-9766, a selective MEK1/2 inhibitor, in a panel of human colorectal cancer cell lines with primary or acquired resistance to cetuximab. RESULTS: Among the colorectal cancer cell lines, five with a KRAS mutation (LOVO, HCT116, HCT15, SW620, and SW480) and one with a BRAF mutation (HT29) were resistant to the antiproliferative effects of cetuximab, whereas two cells (GEO and SW48) were highly sensitive. Treatment with BAY 86-9766 determined dose-dependent growth inhibition in all cancer cells, including two human colorectal cancer cells with acquired resistance to cetuximab (GEO-CR and SW48-CR), with the exception of HCT15 cells. Combined treatment with cetuximab and BAY 86-9766 induced a synergistic antiproliferative and apoptotic effects with blockade in the MAPK and AKT pathway in cells with either primary or acquired resistance to cetuximab. The synergistic antiproliferative effects were confirmed using other two selective MEK1/2 inhibitors, selumetinib and pimasertib, in combination with cetuximab. Moreover, inhibition of MEK expression by siRNA restored cetuximab sensitivity in resistant cells. In nude mice bearing established human HCT15, HCT116, SW48-CR, and GEO-CR xenografts, the combined treatment with cetuximab and BAY 86-9766 caused significant tumor growth inhibition and increased mice survival. CONCLUSION: These results suggest that activation of MEK is involved in both primary and acquired resistance to cetuximab and the inhibition of EGFR and MEK could be a strategy for overcoming anti-EGFR resistance in patients with colorectal cancer. ©2014 American Association for Cancer Research. |
MED-1316 | Oatmeal has been used for centuries as a soothing agent to relieve itch and irritation associated with various xerotic dermatoses. In 1945, a ready to use colloidal oatmeal, produced by finely grinding the oat and boiling it to extract the colloidal material, became available. Today, colloidal oatmeal is available in various dosage forms from powders for the bath to shampoos, shaving gels, and moisturizing creams. Currently, the use of colloidal oatmeal as a skin protectant is regulated by the U.S. Food and Drug Administration (FDA) according to the Over-The-Counter Final Monograph for Skin Protectant Drug Products issued in June 2003. Its preparation is also standardized by the United States Pharmacopeia. The many clinical properties of colloidal oatmeal derive from its chemical polymorphism. The high concentration in starches and beta-glucan is responsible for the protective and water-holding functions of oat. The presence of different types of phenols confers antioxidant and anti-inflammatory activity. Some of the oat phenols are also strong ultraviolet absorbers. The cleansing activity of oat is mostly due to saponins. Its many functional properties make colloidal oatmeal a cleanser, moisturizer, buffer, as well as a soothing and protective anti-inflammatory agent. |
MED-1317 | A high intake of whole grain foods is associated with reduced risk of colon cancer, but the mechanism underlying this protection has yet to be elucidated. Chronic inflammation and associated cyclooxygenase-2 (COX-2) expression in the colon epithelium are causally related to epithelial carcinogenesis, proliferation, and tumor growth. We examined the effect of avenanthramides (Avns), unique polyphenols from oats with anti-inflammatory properties, on COX-2 expression in macrophages, colon cancer cell lines, and on proliferation of human colon cancer cell lines. We found that Avns-enriched extract of oats (AvExO) had no effect on COX-2 expression, but it did inhibit COX enzyme activity and prostaglandin E(2) (PGE(2)) production in lipopolysaccharide-stimulated mouse peritoneal macrophages. Avns (AvExO, Avn-C, and the methylated form of Avn-C (CH3-Avn-C)) significantly inhibited cell proliferation of both COX-2-positive HT29, Caco-2, and LS174T, and COX-2-negative HCT116 human colon cancer cell lines, CH3-Avn-C being the most potent. However, Avns had no effect on COX-2 expression and PGE(2) production in Caco-2 and HT29 colon cancer cells. These results indicate that the inhibitory effect of Avns on colon cancer cell proliferation may be independent of COX-2 expression and PGE(2) production. Thus, Avns might reduce colon cancer risk through inhibition of macrophage PGE(2) production and non-COX-related antiproliferative effects in colon cancer cells. Interestingly, Avns had no effect on cell viability of confluence-induced differentiated Caco-2 cells, which display the characteristics of normal colonic epithelial cells. Our results suggest that the consumption of oats and oat bran may reduce the risk of colon cancer not only because of their high fiber content but also due to Avns, which attenuate proliferation of colonic cancer cells. |
MED-1318 | BACKGROUND: Rice consumption has been associated with risk of type 2 diabetes, but its relation with cardiovascular disease (CVD) is limited. OBJECTIVE: We examined the association between rice consumption and risk of CVD incidence and mortality in a Japanese population. DESIGN: This was a prospective study in 91,223 Japanese men and women aged 40-69 y in whom rice consumption was determined and updated from 3 self-administered food-frequency questionnaires, each 5 y apart. Follow-up for incidence was from 1990 to 2009 in cohort I and 1993 to 2007 in cohort II and for mortality was from 1990 to 2009 in cohort I and 1993 to 2009 in cohort II. HRs and 95% CIs of CVD incidence and mortality were calculated according to quintiles of cumulative average rice consumption. RESULTS: In 15-18 y of follow-up, we ascertained 4395 incident cases of stroke, 1088 incident cases of ischemic heart disease (IHD), and 2705 deaths from CVD. Rice consumption was not associated with risk of incident stroke or IHD; the multivariable HR (95% CI) in the highest compared with lowest rice consumption quintiles was 1.01 (0.90, 1.14) for total stroke and 1.08 (0.84, 1.38) for IHD. Similarly, there was no association between rice consumption and risk of mortality from CVD; the HR (95% CI) for mortality from total CVD was 0.97 (0.84, 1.13). There were no interactions with sex or effect modifications by body mass index for any endpoint. CONCLUSION: Rice consumption is not associated with risk of CVD morbidity or mortality. © 2014 American Society for Nutrition. |
MED-1319 | A comprehensive ecologic survey of dietary, life-style, and mortality characteristics of 65 counties in rural China showed that diets are substantially richer in foods of plant origin when compared with diets consumed in the more industrialized, Western societies. Mean intakes of animal protein (about one-tenth of the mean intake in the United States as energy percent), total fat (14.5% of energy), and dietary fiber (33.3 g/d) reflected a substantial preference for foods of plant origin. Mean plasma cholesterol concentration, at approximately 3.23-3.49 mmol/L, corresponds to this dietary life-style. The principal hypothesis under investigation in this paper is that chronic degenerative diseases are prevented by an aggregate effect of nutrients and nutrient-intake amounts that are commonly supplied by foods of plant origin. The breadth and consistency of evidence for this hypothesis was investigated with multiple intake-biomarker-disease associations, which were appropriately adjusted. There appears to be no threshold of plant-food enrichment or minimization of fat intake beyond which further disease prevention does not occur. These findings suggest that even small intakes of foods of animal origin are associated with significant increases in plasma cholesterol concentrations, which are associated, in turn, with significant increases in chronic degenerative disease mortality rates. |
MED-1320 | Context Because of a different degree of processing and nutrient contents, brown rice and white rice may have different effects on risk of type 2 diabetes. Objective To prospectively examine white rice and brown rice consumptions in relation to type 2 diabetes risk in US men and women aged 26–87 yr. Design and Setting The Health Professionals Follow-up Study (1986–2006) and the Nurses’ Health Study I (1984–2006) and II (1991–2005). Participants We prospectively ascertained diet, lifestyle practices, and disease status among 39,765 men and 157,463 women in these cohorts. All participants were free of diabetes, cardiovascular disease, and cancer at baseline. Intake of white rice, brown rice, other foods, and nutrients was assessed at baseline and updated every 2–4 years. Results During 3,318,196 person-years of follow-up, we documented 10,507 incident cases of type 2 diabetes. After multivariate adjustment for age and other lifestyle and dietary risk factors, higher intake of white rice was associated with a higher risk of type 2 diabetes. The pooled relative risk (95% confidence interval) of type 2 diabetes comparing ≥5 servings/week with <1 serving/month of white rice was 1.17 (1.02, 1.36). In contrast, high brown rice intake was associated with a lower risk of type 2 diabetes: The pooled multivariate relative risk (95% confidence interval) was 0.89 (0.81, 0.97) for ≥ 2 servings/week of brown rice as compared with <1 serving/month. We estimated that replacing 50 grams/day (cooked, equivalent to ⅓ serving/day) intake of white rice with the same amount of brown rice was associated with a 16% (95% confidence interval: 9%, 21%) lower risk of type 2 diabetes, whereas the same replacement with whole grains as a group was associated with a 36% (95% confidence interval: 30%, 42%) lower diabetes risk. Conclusions Substitution of whole grains, including brown rice, for white rice may lower risk of type 2 diabetes. These data support the recommendation that most carbohydrate intake should come from whole grains rather than refined grains to facilitate the prevention of type 2 diabetes. |
MED-1321 | Phospholipids (PLs) are a major class of lipid in rice grain. Although PLs are only a minor nutrient compared to starch and protein, they may have both nutritional and functional significance. We have systemically reviewed the literature on the class, distribution and variation of PLs in rice, their relation to rice end-use quality and human health, as well as available methods for analytical profiling. Phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and their lyso forms are the major PLs in rice. The deterioration of PC in rice bran during storage was considered as a trigger for the degradation of rice lipids with associated rancid flavour in paddy and brown rice. The lyso forms in rice endosperm represent the major starch lipid, and may form inclusion complexes with amylose, affecting the physicochemical properties and digestibility of starch, and hence its cooking and eating quality. Dietary PLs have a positive impact on several human diseases and reduce the side-effects of some drugs. As rice has long been consumed as a staple food in many Asian countries, rice PLs may have significant health benefits for those populations. Rice PLs may be influenced both by genetic (G) and environmental (E) factors, and resolving G×E interactions may allow future exploitation of PL composition and content, thus boosting rice eating quality and health benefits for consumers. We have identified and summarised the different methods used for rice PL analysis, and discussed the consequences of variation in reported PL values due to inconsistencies between methods. This review enhances the understanding of the nature and importance of PLs in rice and outlines potential approaches for manipulating PLs to improve the quality of rice grain and other cereals. Copyright © 2013 Elsevier Ltd. All rights reserved. |
MED-1322 | Several studies have suggested a protective effect of intake of whole grains, but not refined grains on type 2 diabetes risk, but the dose-response relationship between different types of grains and type 2 diabetes has not been established. We conducted a systematic review and meta-analysis of prospective studies of grain intake and type 2 diabetes. We searched the PubMed database for studies of grain intake and risk of type 2 diabetes, up to June 5th, 2013. Summary relative risks were calculated using a random effects model. Sixteen cohort studies were included in the analyses. The summary relative risk per 3 servings per day was 0.68 (95% CI 0.58-0.81, I(2) = 82%, n = 10) for whole grains and 0.95 (95% CI 0.88-1.04, I(2) = 53%, n = 6) for refined grains. A nonlinear association was observed for whole grains, p nonlinearity < 0.0001, but not for refined grains, p nonlinearity = 0.10. Inverse associations were observed for subtypes of whole grains including whole grain bread, whole grain cereals, wheat bran and brown rice, but these results were based on few studies, while white rice was associated with increased risk. Our meta-analysis suggests that a high whole grain intake, but not refined grains, is associated with reduced type 2 diabetes risk. However, a positive association with intake of white rice and inverse associations between several specific types of whole grains and type 2 diabetes warrant further investigations. Our results support public health recommendations to replace refined grains with whole grains and suggest that at least two servings of whole grains per day should be consumed to reduce type 2 diabetes risk. |
MED-1323 | Background: Fat and protein sources may influence whether low-carbohydrate diets are associated with type 2 diabetes (T2D). Objective: The objective was to compare the associations of 3 low-carbohydrate diet scores with incident T2D. Design: A prospective cohort study was conducted in participants from the Health Professionals Follow-Up Study who were free of T2D, cardiovascular disease, or cancer at baseline (n = 40,475) for up to 20 y. Cumulative averages of 3 low-carbohydrate diet scores (high total protein and fat, high animal protein and fat, and high vegetable protein and fat) were calculated every 4 y from food-frequency questionnaires and were associated with incident T2D by using Cox models. Results: We documented 2689 cases of T2D during follow-up. After adjustments for age, smoking, physical activity, coffee intake, alcohol intake, family history of T2D, total energy intake, and body mass index, the score for high animal protein and fat was associated with an increased risk of T2D [top compared with bottom quintile; hazard ratio (HR): 1.37; 95% CI: 1.20, 1.58; P for trend < 0.01]. Adjustment for red and processed meat attenuated this association (HR: 1.11; 95% CI: 0.95, 1.30; P for trend = 0.20). A high score for vegetable protein and fat was not significantly associated with the risk of T2D overall but was inversely associated with T2D in men aged <65 y (HR: 0.78; 95% CI: 0.66, 0.92; P for trend = 0.01, P for interaction = 0.01). Conclusions: A score representing a low-carbohydrate diet high in animal protein and fat was positively associated with the risk of T2D in men. Low-carbohydrate diets should obtain protein and fat from foods other than red and processed meat. |
MED-1324 | Six noninsulin-dependent diabetic subjects received meals containing 25 g carbohydrate either as potato or as spaghetti. The meals were repeated with the addition of 25 g protein and with 25 g protein and 25 g fat. Blood glucose and insulin responses were measured for 4 h after the test meal. When carbohydrate was given alone, the blood glucose and serum insulin increments were higher for the potato meal. The addition of protein increased the insulin responses to both carbohydrates and slightly reduced the glycemic response to mashed potato (F = 2.04, p less than 0.05). The further addition of fat reduced the glycemic response to mashed potato (F = 14.63, p less than 0.001) without any change in the blood glucose response to spaghetti (F = 0.94, NS). The different responses to coingestion of protein and fat reduced the difference between the glycemic responses to the two carbohydrates. |
MED-1326 | BACKGROUND: Because of the rapid change in lifestyle in China, there is concern that diabetes may become epidemic. We conducted a national study from June 2007 through May 2008 to estimate the prevalence of diabetes among Chinese adults. METHODS: A nationally representative sample of 46,239 adults, 20 years of age or older, from 14 provinces and municipalities participated in the study. After an overnight fast, participants underwent an oral glucose-tolerance test, and fasting and 2-hour glucose levels were measured to identify undiagnosed diabetes and prediabetes (i.e., impaired fasting glucose or impaired glucose tolerance). Previously diagnosed diabetes was determined on the basis of self-report. RESULTS: The age-standardized prevalences of total diabetes (which included both previously diagnosed diabetes and previously undiagnosed diabetes) and prediabetes were 9.7% (10.6% among men and 8.8% among women) and 15.5% (16.1% among men and 14.9% among women), respectively, accounting for 92.4 million adults with diabetes (50.2 million men and 42.2 million women) and 148.2 million adults with prediabetes (76.1 million men and 72.1 million women). The prevalence of diabetes increased with increasing age (3.2%, 11.5%, and 20.4% among persons who were 20 to 39, 40 to 59, and > or = 60 years of age, respectively) and with increasing weight (4.5%, 7.6%, 12.8%, and 18.5% among persons with a body-mass index [the weight in kilograms divided by the square of the height in meters] of < 18.5, 18.5 to 24.9, 25.0 to 29.9, and > or = 30.0, respectively). The prevalence of diabetes was higher among urban residents than among rural residents (11.4% vs. 8.2%). The prevalence of isolated impaired glucose tolerance was higher than that of isolated impaired fasting glucose (11.0% vs. 3.2% among men and 10.9% vs. 2.2% among women). CONCLUSIONS: These results indicate that diabetes has become a major public health problem in China and that strategies aimed at the prevention and treatment of diabetes are needed. 2010 Massachusetts Medical Society |
MED-1327 | Whole-grain and high fiber intakes are routinely recommended for prevention of vascular diseases; however, there are no comprehensive and quantitative assessments of available data in humans. The aim of this study was to systematically examine longitudinal studies investigating whole-grain and fiber intake in relation to risk of type 2 diabetes (T2D), cardiovascular disease (CVD), weight gain, and metabolic risk factors. We identified 45 prospective cohort studies and 21 randomized-controlled trials (RCT) between 1966 and February 2012 by searching the Cumulative Index to Nursing and Allied Health Literature, Cochrane, Elsevier Medical Database, and PubMed. Study characteristics, whole-grain and dietary fiber intakes, and risk estimates were extracted using a standardized protocol. Using random effects models, we found that compared with never/rare consumers of whole grains, those consuming 48-80 g whole grain/d (3-5 serving/d) had an ~26% lower risk of T2D [RR = 0.74 (95% CI: 0.69, 0.80)], ~21% lower risk of CVD [RR = 0.79 (95% CI: 0.74, 0.85)], and consistently less weight gain during 8-13 y (1.27 vs 1.64 kg; P = 0.001). Among RCT, weighted mean differences in post-intervention circulating concentrations of fasting glucose and total and LDL-cholesterol comparing whole-grain intervention groups with controls indicated significantly lower concentrations after whole-grain interventions [differences in fasting glucose: -0.93 mmol/L (95% CI: -1.65, -0.21), total cholesterol: -0.83 mmol/L (-1.23, -0.42); and LDL-cholesterol: -0.82 mmol/L (-1.31, -0.33)]. [corrected] Findings from this meta-analysis provide evidence to support beneficial effects of whole-grain intake on vascular disease prevention. Potential mechanisms responsible for whole grains' effects on metabolic intermediates require further investigation in large intervention trials. |
MED-1328 | BACKGROUND: In 2010, overweight and obesity were estimated to cause 3·4 million deaths, 3·9% of years of life lost, and 3·8% of disability-adjusted life-years (DALYs) worldwide. The rise in obesity has led to widespread calls for regular monitoring of changes in overweight and obesity prevalence in all populations. Comparable, up-to-date information about levels and trends is essential to quantify population health effects and to prompt decision makers to prioritise action. We estimate the global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013. METHODS: We systematically identified surveys, reports, and published studies (n=1769) that included data for height and weight, both through physical measurements and self-reports. We used mixed effects linear regression to correct for bias in self-reports. We obtained data for prevalence of obesity and overweight by age, sex, country, and year (n=19,244) with a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs). FINDINGS: Worldwide, the proportion of adults with a body-mass index (BMI) of 25 kg/m(2) or greater increased between 1980 and 2013 from 28·8% (95% UI 28·4-29·3) to 36·9% (36·3-37·4) in men, and from 29·8% (29·3-30·2) to 38·0% (37·5-38·5) in women. Prevalence has increased substantially in children and adolescents in developed countries; 23·8% (22·9-24·7) of boys and 22·6% (21·7-23·6) of girls were overweight or obese in 2013. The prevalence of overweight and obesity has also increased in children and adolescents in developing countries, from 8·1% (7·7-8·6) to 12·9% (12·3-13·5) in 2013 for boys and from 8·4% (8·1-8·8) to 13·4% (13·0-13·9) in girls. In adults, estimated prevalence of obesity exceeded 50% in men in Tonga and in women in Kuwait, Kiribati, Federated States of Micronesia, Libya, Qatar, Tonga, and Samoa. Since 2006, the increase in adult obesity in developed countries has slowed down. INTERPRETATION: Because of the established health risks and substantial increases in prevalence, obesity has become a major global health challenge. Not only is obesity increasing, but no national success stories have been reported in the past 33 years. Urgent global action and leadership is needed to help countries to more effectively intervene. FUNDING: Bill & Melinda Gates Foundation. Copyright © 2014 Elsevier Ltd. All rights reserved. |
MED-1329 | White rice-based foods, which are high in refined carbohydrates, are widely consumed in China. A case-control study was conducted to investigate the association between white rice-based food consumption and the risk of ischemic stroke in the southern Chinese population. Information on diet and lifestyle was obtained from 374 incident ischemic stroke patients and 464 hospital-based controls. Logistic regression analyses were performed to assess the effects of rice-based foods on stroke risk. The mean weekly intake of rice foods appeared to be significantly higher in cases than in controls. Increased consumptions of cooked rice, congee, and rice noodle were associated with a higher risk for ischemic stroke after controlling for confounding factors. The corresponding adjusted odds ratios (with 95% confidence intervals) for the highest versus lowest intake level were 2.73 (1.31-5.69), 2.93 (1.68-5.13), and 2.03 (1.40-2.94), with significant dose-response relationships observed. The results provide evidence of a positive association between habitual rice food consumption and the risk of ischemic stroke in Chinese adults. Copyright © 2010 National Stroke Association. Published by Elsevier Inc. All rights reserved. |
MED-1330 | AIMS: To systematically review trends in diabetes mellitus (DM) prevalence in adults in China over the last 10 years and to identify the determinants of these trends. METHODS: A systematic search was conducted for studies published between 2000 and 2010. Studies reporting DM prevalence were included if they met the pre-determined criteria. The prevalence estimates and reported determinants of these studies were compared. RESULTS: Twenty-five manuscripts, reporting on 22 studies, were selected for inclusion in the review. There has been an increase in DM prevalence from 2.6% to 9.7% in China over the past decade. DM prevalence is strongly associated with age and is higher in urban residents compared with rural populations. Some studies found a difference in DM prevalence between males and females, but this finding was not consistent. Other commonly reported associations with DM included family history, obesity and hypertension. CONCLUSION: Over the period of 2000-2010, we identify a significant increase in DM prevalence at the national level. It is important for all levels of government to develop more effective strategies to prevent and manage this rising diabetes epidemic. There is also an important need for more large-scale studies of diabetes in the western and central regions of China. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved. |
MED-1331 | Many changes in diet and in physical activity are occurring simultaneously in the developing world. These diet shifts include large increases in energy density, in the proportion of the population consuming a high fat diet and in animal product intake. Animal source foods (ASF) play a major role in these diet shifts. This article documents the large shifts in the composition of diets and obesity across the developing world and notes that these changes are accelerating. Using China as a case study, evidence of the speeding up of this process is presented in descriptive and more rigorous dynamic longitudinal analysis. The implications of these changes for dietary and obesity patterns and cardiovascular disease are great. Indeed, developing countries are at a point where the prevalence of obesity is greater than that of undernutrition and concerns related to intake of saturated fat and energy imbalance must be considered more seriously by the agriculture sector. Current agriculture development policy in many developing countries focuses on livestock promotion and does not consider the potential adverse health consequences of this strategy. Although linkages between ASF intake and obesity cannot be established as clearly as they are for high ASF intakes, heart disease and cancer, the potential adverse health effects linked with an increased ASF intake should no longer be ignored. |
MED-1332 | Background The definition of incident type 2 diabetes varies across studies; hence, the actual incidence of type 2 diabetes in Japan is unclear. Here, we reviewed the various definitions of incident type 2 diabetes used in previous epidemiologic studies and estimated the diabetes incidence rate in Japan. Methods We searched for related literature in the MEDLINE, EMBASE, and Ichushi databases through September 2012. Two reviewers selected studies that evaluated incident type 2 diabetes in the Japanese population. Results From 1824 relevant articles, we included 33 studies with 386,803 participants. The follow-up period ranged from 2.3 to 14 years and the studies were initiated between 1980 and 2003. The random-effects model indicated that the pooled incidence rate of diabetes was 8.8 (95% confidence interval, 7.4–10.4) per 1000 person-years. We observed a high degree of heterogeneity in the results (I2 = 99.2%; p < 0.001), with incidence rates ranging from 2.3 to 52.6 per 1000 person-years. Three studies based their definition of incident type 2 diabetes on self-reports only, 10 on laboratory data only, and 20 on self-reports and laboratory data. Compared with studies defining diabetes using laboratory data (n = 30; pooled incidence rate = 9.6; 95% confidence interval = 8.3–11.1), studies based on self-reports alone tended to show a lower incidence rate (n = 3; pooled incidence rate = 4.0; 95% confidence interval = 3.2–5.0; p for interaction < 0.001). However, stratified analyses could not entirely explain the heterogeneity in the results. Conclusions Our systematic review and meta-analysis indicated the presence of a high degree of heterogeneity, which suggests that there is a considerable amount of uncertainty regarding the incidence of type 2 diabetes in Japan. They also suggested that laboratory data may be important for the accurate estimation of the incidence of type 2 diabetes. |
MED-1333 | New epidemiology confirms that glucose intolerance is a risk factor for pancreatic cancer, and that this association cannot be accounted for by an adverse impact of early pancreatic cancer on beta cell function. Previous reports indicate that risk for pancreatic cancer is increased in adult-onset diabetics. Since streptozotocin diabetes inhibits carcinogen-mediated induction of pancreatic cancer in hamsters, the most reasonable interpretation of these findings is that insulin (or some other beta cell product) acts as a promoter for pancreatic carcinogenesis. This view is consistent with a report that human pancreatic adenocarcinomas express insulin receptors that can stimulate mitosis; an additional possibility is that high insulin levels indirectly promote pancreatic carcinogenesis by boosting effective IGF-I activity via hepatic actions. In international ecologic epidemiology, pancreatic cancer rates correlate tightly with dietary intake of animal products; this may reflect the fact that vegan diets are associated with low diurnal insulin secretion. There is also suggestive evidence that macrobiotic vegan diets, which are low in glycemic index, may increase mean survival time in pancreatic cancer. However, other types of diets associated with decreased postprandial insulin response, such as high-protein diets or 'Mediterranean' diets high in oleic acid, may also have the potential for pancreatic cancer prevention. The huge increases of age-adjusted pancreatic cancer mortality in Japan and among African-Americans during the last century imply that pancreatic cancer is substantially preventable; a low-insulin-response diet coupled with exercise training, weight control, and smoking avoidance, commendable for a great many other reasons, may slash pancreatic cancer mortality dramatically. Copyright 2001 Harcourt Publishers Ltd. |
MED-1334 | By 2002, China’s prevalence of overweight and obesity among adults was 18.9 percent and 2.9 percent, respectively. The Chinese traditional diet has been replaced by the “Western diet” and major declines in all phases of activity and increased sedentary activity as the main reasons explaining the rapid increase in overweight and obesity, bring major economic and health costs. The Nutrition Improvement Work Management Approach was released in 2010. Overweight and obesity prevention-related policies were added to national planning for disease prevention and control. The Guidelines for Prevention and Control of Overweight and Obesity of Chinese Adults and the School-age Children and Teenagers Overweight and Obesity Prevention and Control Guidelines in China were promulgated in 2003 and 2007, respectively. Few education programs have been implemented. Selected academic intervention research projects dominate with a focus on reducing child obesity and promoting healthier diets; increasing physical activity and reducing sedentary time; and facilitating changes in family, school, social, and cultural environments. Intervention samples are small and have not addressed the increasing rates of obesity throughout the entire population. Government provision of effective policy measures, multisectoral cooperation and increasing corporate social responsibility are keys to curb the trend toward overweight and obesity in China. |
MED-1335 | AIMS: Diabetes rates are especially high in China. Risk of Type 2 diabetes increases with high intakes of white rice, a staple food of Chinese people. Ethnic differences in postprandial glycaemia have been reported. We compared glycaemic responses to glucose and five rice varieties in people of European and Chinese ethnicity and examined possible determinants of ethnic differences in postprandial glycaemia. METHODS: Self-identified Chinese (n = 32) and European (n = 31) healthy volunteers attended on eight occasions for studies following ingestion of glucose and jasmine, basmati, brown, Doongara(®) and parboiled rice. In addition to measuring glycaemic response, we investigated physical activity levels, extent of chewing of rice and salivary α-amylase activity to determine whether these measures explained any differences in postprandial glycaemia. RESULTS: Glycaemic response, measured by incremental area under the glucose curve, was over 60% greater for the five rice varieties (P < 0.001) and 39% greater for glucose (P < 0.004) amongst Chinese compared with Europeans. The calculated glycaemic index was approximately 20% greater for rice varieties other than basmati (P = 0.01 to 0.05). Ethnicity [adjusted risk ratio 1.4 (1.2-1.8) P < 0.001] and rice variety were the only important determinants of incremental area under the glucose curve. CONCLUSIONS: Glycaemic responses following ingestion of glucose and several rice varieties are appreciably greater in Chinese compared with Europeans, suggesting the need to review recommendations regarding dietary carbohydrate amongst rice-eating populations at high risk of diabetes. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK. |
MED-1337 | Milk contains calcium, phosphorus, and protein and is fortified with vitamin D in the United States. All these ingredients may improve bone health. However, the potential benefit of milk on hip fracture prevention is not well established. The objective of this study was to assess the association of milk intake with risk of hip fracture based on a meta-analysis of cohort studies in middle-aged or older men and women. Data sources for this study were English and non-English publications via Medline (Ovid, PubMed) and EMBASE search up to June 2010, experts in the field, and reference lists. The idea was to compare prospective cohort studies on the same scale so that we could calculate the relative risk (RR) of hip fracture per glass of milk intake daily (approximately 300 mg calcium per glass of milk). Pooled analyses were based on random effects models. The data were extracted by two independent observers. The results show that in women (6 studies, 195,102 women, 3574 hip fractures), there was no overall association between total milk intake and hip fracture risk (pooled RR per glass of milk per day = 0.99; 95% confidence interval [CI] 0.96-1.02; Q-test p = .37). In men (3 studies, 75,149 men, 195 hip fractures), the pooled RR per daily glass of milk was 0.91 (95% CI 0.81-1.01). Our conclusion is that in our meta-analysis of cohort studies, there was no overall association between milk intake and hip fracture risk in women but that more data are needed in men. Copyright © 2011 American Society for Bone and Mineral Research. |
MED-1338 | Objective To examine whether high milk consumption is associated with mortality and fractures in women and men. Design Cohort studies. Setting Three counties in central Sweden. Participants Two large Swedish cohorts, one with 61 433 women (39-74 years at baseline 1987-90) and one with 45 339 men (45-79 years at baseline 1997), were administered food frequency questionnaires. The women responded to a second food frequency questionnaire in 1997. Main outcome measure Multivariable survival models were applied to determine the association between milk consumption and time to mortality or fracture. Results During a mean follow-up of 20.1 years, 15 541 women died and 17 252 had a fracture, of whom 4259 had a hip fracture. In the male cohort with a mean follow-up of 11.2 years, 10 112 men died and 5066 had a fracture, with 1166 hip fracture cases. In women the adjusted mortality hazard ratio for three or more glasses of milk a day compared with less than one glass a day was 1.93 (95% confidence interval 1.80 to 2.06). For every glass of milk, the adjusted hazard ratio of all cause mortality was 1.15 (1.13 to 1.17) in women and 1.03 (1.01 to 1.04) in men. For every glass of milk in women no reduction was observed in fracture risk with higher milk consumption for any fracture (1.02, 1.00 to 1.04) or for hip fracture (1.09, 1.05 to 1.13). The corresponding adjusted hazard ratios in men were 1.01 (0.99 to 1.03) and 1.03 (0.99 to 1.07). In subsamples of two additional cohorts, one in males and one in females, a positive association was seen between milk intake and both urine 8-iso-PGF2α (a biomarker of oxidative stress) and serum interleukin 6 (a main inflammatory biomarker). Conclusions High milk intake was associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women. Given the observational study designs with the inherent possibility of residual confounding and reverse causation phenomena, a cautious interpretation of the results is recommended. |
MED-1339 | BACKGROUND: Short-term studies established that calcium influences bone accretion during growth. Whether long-term supplementation influences bone accretion in young adults is not known. OBJECTIVE: This study evaluated the long-term effects of calcium supplementation on bone accretion among females from childhood to young adulthood. DESIGN: A 4-y randomized clinical trial recruited 354 females in pubertal stage 2 and optionally was extended for an additional 3 y. The mean dietary calcium intake of the participants over 7 y was approximately 830 mg/d; calcium-supplemented persons received an additional approximately 670 mg/d. Primary outcome variables were distal and proximal radius bone mineral density (BMD), total-body BMD (TBBMD), and metacarpal cortical indexes. RESULTS: Multivariate analyses of the primary outcomes indicated that calcium-supplementation effects vary over time. Follow-up univariate analyses indicated that all primary outcomes were significantly larger in the supplemented group than in the placebo group at the year 4 endpoint. However, at the year 7 endpoint, this effect vanished for TBBMD and distal radius BMD. Longitudinal models for TBBMD and proximal radius BMD, according to the time since menarche, showed a highly significant effect of supplementation during the pubertal growth spurt and a diminishing effect thereafter. Post hoc stratifications by compliance-adjusted total calcium intake and by final stature or metacarpal total cross-sectional area showed that calcium effects depend on compliance and body frame. CONCLUSIONS: Calcium supplementation significantly influenced bone accretion in young females during the pubertal growth spurt. By young adulthood, significant effects remained at metacarpals and at the forearm of tall persons, which indicated that the calcium requirement for growth is associated with skeletal size. These results may be important for both primary prevention of osteoporosis and prevention of bone fragility fractures during growth. |
MED-1340 | Importance Milk consumption during adolescence is recommended to promote peak bone mass and thereby reduce fracture risk in later life. However, its role in hip fracture prevention is not established and high consumption may adversely influence risk by increasing height. Objective To determine whether milk consumption during teenage years influences risk of hip fracture in older adults and to investigate the role of attained height in this association. Design Prospective cohort study over 22 years of follow-up Setting United States Participants Over 96,000 Caucasian postmenopausal women from the Nurses’ Health Study and men age 50 and older from the Health Professionals Follow-up Study Exposures Frequency of consumption of milk and other foods during ages 13–18 and attained height were reported at baseline. Current diet, weight, smoking, physical activity, medication use, and other risk factors for hip fractures were reported on biennial questionnaires. Main Outcome Measures Cox proportional hazards models were used to calculate relative risks (RR) of first incident hip fracture from low-trauma events per glass (8 fl oz or 240 mL) of milk consumed per day during teenage years. Results Over follow-up, 1226 hip fractures were identified in women and 490 in men. After controlling for known risk factors and current milk consumption, each additional glass of milk per day during teenage years was associated with a significant 9% higher risk of hip fracture in men (RR=1.09, 95% CI 1.01–1.17). The association was attenuated when height was added to the model (RR=1.06, 95% CI 0.98–1.14). Teenage milk consumption was not associated with hip fractures in women (RR=1.00, 95% CI 0.95–1.05 per glass per day). Conclusion and Relevance Greater milk consumption during teenage years was not associated with a lower risk of hip fracture in older adults. The positive association observed in men was partially mediated through attained height. |
MED-1341 | SUMMARY: This study evaluated bone health in adults with galactosemia. Associations between bone mineral density (BMD) and nutritional and biochemical variables were explored. Calcium level predicted hip and spine BMD, and gonadotropin levels were inversely associated with spinal BMD in women. These results afford insights into management strategies for these patients. INTRODUCTION: Bone loss is a complication of galactosemia. Dietary restriction, primary ovarian insufficiency in women, and disease-related alterations of bone metabolism may contribute. This study examined relationships between clinical factors and BMD in patients with galactosemia. METHODS: This cross-sectional sample included 33 adults (16 women) with classic galactosemia, mean age 32.0 ± 11.8 years. BMD was measured by dual-energy X-ray absorptiometry, and was correlated with age, height, weight, fractures, nutritional factors, hormonal status, and bone biomarkers. RESULTS: There was a significant difference in hip BMD between women and men (0.799 vs. 0.896 g/cm(2), p = 0.014). The percentage of subjects with BMD-Z <-2.0 was also greater for women than men [33 vs. 18 % (spine), 27 vs. 6 % (hip)], and more women reported sustaining fractures. Bivariate analyses yielded correlations between BMI and BMD-Z [at the hip in women (r = 0.58, p < 0.05) and spine in men (r = 0.53, p < 0.05)]. In women, weight was also correlated with BMD-Z (r = 0.57, p < 0.05 at hip), and C-telopeptides (r = -0.59 at spine and -0.63 hip, p < 0.05) and osteocalcin (r = -0.71 at spine and -0.72 hip, p < 0.05) were inversely correlated with BMD-Z. In final regression models, higher gonadotropin levels were associated with lower spinal BMD in women (p = 0.017); serum calcium was a significant predictor of hip (p = 0.014) and spine (p = 0.013) BMD in both sexes. CONCLUSIONS: Bone density in adults with galactosemia is low, indicating the potential for increased fracture risk, the etiology of which appears to be multifactorial. |
MED-1344 | Is it ever right to prescribe placebos to patients in clinical practice? The General Medical Council is ambivalent about the issue; the American Medical Association asserts that placebos can be administered only if the patient is (somehow) 'informed'. The potential problem with placebos is that they may involve deception: indeed, if this is the case, an ethical tension arises over the patient's autonomy and the physician's requirement to be open and honest, and the notion that medical care should be the primary concern. This paper examines the case of depression as an entry point for understanding the complexities of the prescription of placebos. Recent important meta-analyses of antidepressants claim that they are not significantly more effective in a clinical setting than placebos. Given that antidepressants have numerous adverse side effects and are hugely expensive, this provocative research has serious potential ethical and practical implications for patients and medical providers. Should placebos be prescribed in place of antidepressants? The case of depression highlights another important issue which medical ethical codes have hitherto overlooked: well-being is not synonymous with being realistic about oneself, one's circumstances and the future. While severely depressed individuals are unduly pessimistic about themselves and the world around them, treatment of depressed individuals can be deemed successful when patients have successfully attained those positive illusions that are indicative of psychological health. This is exactly what successful psychological treatments of depression seem to achieve. It is therefore possible that there may be a limited unavoidable role for deception in medicine. |
MED-1348 | Background Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance. Yet, the efficacy of the antidepressants may also depend on the severity of initial depression scores. The purpose of this analysis is to establish the relation of baseline severity and antidepressant efficacy using a relevant dataset of published and unpublished clinical trials. Methods and Findings We obtained data on all clinical trials submitted to the US Food and Drug Administration (FDA) for the licensing of the four new-generation antidepressants for which full datasets were available. We then used meta-analytic techniques to assess linear and quadratic effects of initial severity on improvement scores for drug and placebo groups and on drug–placebo difference scores. Drug–placebo differences increased as a function of initial severity, rising from virtually no difference at moderate levels of initial depression to a relatively small difference for patients with very severe depression, reaching conventional criteria for clinical significance only for patients at the upper end of the very severely depressed category. Meta-regression analyses indicated that the relation of baseline severity and improvement was curvilinear in drug groups and showed a strong, negative linear component in placebo groups. Conclusions Drug–placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication. Editors' Summary Background. Everyone feels miserable occasionally. But for some people—those with depression—these sad feelings last for months or years and interfere with daily life. Depression is a serious medical illness caused by imbalances in the brain chemicals that regulate mood. It affects one in six people at some time during their life, making them feel hopeless, worthless, unmotivated, even suicidal. Doctors measure the severity of depression using the “Hamilton Rating Scale of Depression” (HRSD), a 17–21 item questionnaire. The answers to each question are given a score and a total score for the questionnaire of more than 18 indicates severe depression. Mild depression is often treated with psychotherapy or talk therapy (for example, cognitive–behavioral therapy helps people to change negative ways of thinking and behaving). For more severe depression, current treatment is usually a combination of psychotherapy and an antidepressant drug, which is hypothesized to normalize the brain chemicals that affect mood. Antidepressants include “tricyclics,” “monoamine oxidases,” and “selective serotonin reuptake inhibitors” (SSRIs). SSRIs are the newest antidepressants and include fluoxetine, venlafaxine, nefazodone, and paroxetine. Why Was This Study Done? Although the US Food and Drug Administration (FDA), the UK National Institute for Health and Clinical Excellence (NICE), and other licensing authorities have approved SSRIs for the treatment of depression, some doubts remain about their clinical efficacy. Before an antidepressant is approved for use in patients, it must undergo clinical trials that compare its ability to improve the HRSD scores of patients with that of a placebo, a dummy tablet that contains no drug. Each individual trial provides some information about the new drug's effectiveness but additional information can be gained by combining the results of all the trials in a “meta-analysis,” a statistical method for combining the results of many studies. A previously published meta-analysis of the published and unpublished trials on SSRIs submitted to the FDA during licensing has indicated that these drugs have only a marginal clinical benefit. On average, the SSRIs improved the HRSD score of patients by 1.8 points more than the placebo, whereas NICE has defined a significant clinical benefit for antidepressants as a drug–placebo difference in the improvement of the HRSD score of 3 points. However, average improvement scores may obscure beneficial effects between different groups of patient, so in the meta-analysis in this paper, the researchers investigated whether the baseline severity of depression affects antidepressant efficacy. What Did the Researchers Do and Find? The researchers obtained data on all the clinical trials submitted to the FDA for the licensing of fluoxetine, venlafaxine, nefazodone, and paroxetine. They then used meta-analytic techniques to investigate whether the initial severity of depression affected the HRSD improvement scores for the drug and placebo groups in these trials. They confirmed first that the overall effect of these new generation of antidepressants was below the recommended criteria for clinical significance. Then they showed that there was virtually no difference in the improvement scores for drug and placebo in patients with moderate depression and only a small and clinically insignificant difference among patients with very severe depression. The difference in improvement between the antidepressant and placebo reached clinical significance, however, in patients with initial HRSD scores of more than 28—that is, in the most severely depressed patients. Additional analyses indicated that the apparent clinical effectiveness of the antidepressants among these most severely depressed patients reflected a decreased responsiveness to placebo rather than an increased responsiveness to antidepressants. What Do These Findings Mean? These findings suggest that, compared with placebo, the new-generation antidepressants do not produce clinically significant improvements in depression in patients who initially have moderate or even very severe depression, but show significant effects only in the most severely depressed patients. The findings also show that the effect for these patients seems to be due to decreased responsiveness to placebo, rather than increased responsiveness to medication. Given these results, the researchers conclude that there is little reason to prescribe new-generation antidepressant medications to any but the most severely depressed patients unless alternative treatments have been ineffective. In addition, the finding that extremely depressed patients are less responsive to placebo than less severely depressed patients but have similar responses to antidepressants is a potentially important insight into how patients with depression respond to antidepressants and placebos that should be investigated further. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050045. |
MED-1349 | Antidepressants are supposed to work by fixing a chemical imbalance, specifically, a lack of serotonin in the brain. Indeed, their supposed effectiveness is the primary evidence for the chemical imbalance theory. But analyses of the published data and the unpublished data that were hidden by drug companies reveals that most (if not all) of the benefits are due to the placebo effect. Some antidepressants increase serotonin levels, some decrease it, and some have no effect at all on serotonin. Nevertheless, they all show the same therapeutic benefit. Even the small statistical difference between antidepressants and placebos may be an enhanced placebo effect, due to the fact that most patients and doctors in clinical trials successfully break blind. The serotonin theory is as close as any theory in the history of science to having been proved wrong. Instead of curing depression, popular antidepressants may induce a biological vulnerability making people more likely to become depressed in the future. |
MED-1352 | Antidepressant medications are the first-line treatment for people meeting current diagnostic criteria for major depressive disorder. Most antidepressants are designed to perturb the mechanisms that regulate the neurotransmitter serotonin – an evolutionarily ancient biochemical found in plants, animals, and fungi. Many adaptive processes evolved to be regulated by serotonin, including emotion, development, neuronal growth and death, platelet activation and the clotting process, attention, electrolyte balance, and reproduction. It is a principle of evolutionary medicine that the disruption of evolved adaptations will degrade biological functioning. Because serotonin regulates many adaptive processes, antidepressants could have many adverse health effects. For instance, while antidepressants are modestly effective in reducing depressive symptoms, they increase the brain’s susceptibility to future episodes after they have been discontinued. Contrary to a widely held belief in psychiatry, studies that purport to show that antidepressants promote neurogenesis are flawed because they all use a method that cannot, by itself, distinguish between neurogenesis and neuronal death. In fact, antidepressants cause neuronal damage and mature neurons to revert to an immature state, both of which may explain why antidepressants also cause neurons to undergo apoptosis (programmed death). Antidepressants can also cause developmental problems, they have adverse effects on sexual and romantic life, and they increase the risk of hyponatremia (low sodium in the blood plasma), bleeding, stroke, and death in the elderly. Our review supports the conclusion that antidepressants generally do more harm than good by disrupting a number of adaptive processes regulated by serotonin. However, there may be specific conditions for which their use is warranted (e.g., cancer, recovery from stroke). We conclude that altered informed consent practices and greater caution in the prescription of antidepressants are warranted. |
MED-1353 | Depression is a potentially life-threatening disorder affecting millions of people across the globe. It is a huge burden to both the individual and society, costing over £9 billion in 2000 alone: the World Health Organisation (WHO) cited it as the third leading cause of global disability in 2004 (first in the developed world), and project it will be the leading cause by 2030. The serendipitous discovery of antidepressants has revolutionized both our understanding and management of depression: however, their efficacy in the treatment of depression has long been debated and recently been brought very much into the public limelight by a controversial publication by Kirsch, in which the role of placebo response in antidepressant efficacy trials is highlighted. Whilst antidepressants offer benefits in both the short and long term, important problems persist such as intolerability, delayed therapeutic onset, limited efficacy in milder depression and the existence of treatment-resistant depression. |
MED-1354 | Context Antidepressant medications represent the best established treatment for Major Depressive Disorder (MDD), but there is little evidence that they have a specific pharmacological effect relative to pill-placebo for patients with less severe depression. Objective To estimate the relative benefit of medication vs placebo across a wide range of initial symptom severity in patients diagnosed with depression. Data Sources Pubmed, PsycINFO, and the Cochrane Library databases were searched from January 1980 through March 2009, along with references from meta-analyses and reviews. Study Selection Randomized placebo-controlled trials of FDA approved antidepressants in the treatment of Major or Minor Depressive Disorder were selected. Studies were included if their authors provided the requisite original data, they comprised adult outpatients, included a medication vs placebo comparison for at least 6 weeks, did not exclude patients on the basis of a placebo washout period, and utilized the Hamilton Rating Scale for Depression. Data from six studies (718 patients) were included. Data Extraction Individual patient-level data were obtained from study authors. Results Medication vs placebo differences varied substantially as a function of baseline severity. Among patients with Hamilton scores below 23, Cohen’s d-type effect sizes for the difference between medication and placebo were estimated to be < .20 (a standard definition of a small effect). Estimates of the magnitude of the superiority of medication over placebo increased with increases in baseline Hamilton severity and crossed the NICE threshold for a clinically significant difference at a baseline score of 25. Conclusions The magnitude of benefit of antidepressant medication compared with placebo increases with severity of depression symptoms, and may be minimal or nonexistent, on average, in patients with mild or moderate symptoms. For patients with very severe depression, the benefit of medications over placebo is substantial. |
MED-1356 | BACKGROUND: The objective of this study was to determine the association between regular physical activity and mental disorders among adults in the United States. METHODS: Multiple logistic regression analyses were used to compare the prevalence of mental disorders among those who did and did not report regular physical activity using data from the National Comorbidity Survey (n = 8098), a nationally representative sample of adults ages 15-54 in the United States. CONCLUSIONS: Slightly over one-half of adults reported regular physical activity (60.3%). Regular physical activity was associated with a significantly decreased prevalence of current major depression and anxiety disorders, but was not significantly associated with other affective, substance use, or psychotic disorders. The association between regular physical activity and lower prevalence of current major depression (OR = 0.75 (0.6,0.94)), panic attacks (OR = 0.73 (0.56, 0.96)), social phobia (OR = 0.65 (0.53, 0.8)), specific phobia (OR = 0.78 (0.63, 0.97)), and agoraphobia (OR = 0.64 (0.43, 0.94)) persisted after adjusting for differences in sociodemographic characteristics, self-reported physical disorders, and comorbid mental disorders. Self-reported frequency of physical activity also showed a dose-response relation with current mental disorders. DISCUSSION: These data document a negative association between regular physical activity and depressive and anxiety disorders among adults in the U.S. population. Future research that investigates the mechanism of this association using longitudinal data to examine the link between physical activity and incident and recurrent mental disorders across the lifespan is needed. |
MED-1357 | BACKGROUND: Previous observational and interventional studies have suggested that regular physical exercise may be associated with reduced symptoms of depression. However, the extent to which exercise training may reduce depressive symptoms in older patients with major depressive disorder (MDD) has not been systematically evaluated. OBJECTIVE: To assess the effectiveness of an aerobic exercise program compared with standard medication (ie, antidepressants) for treatment of MDD in older patients, we conducted a 16-week randomized controlled trial. METHODS: One hundred fifty-six men and women with MDD (age, > or = 50 years) were assigned randomly to a program of aerobic exercise, antidepressants (sertraline hydrochloride), or combined exercise and medication. Subjects underwent comprehensive evaluations of depression, including the presence and severity of MDD using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and Hamilton Rating Scale for Depression (HAM-D) and Beck Depression Inventory (BDI) scores before and after treatment. Secondary outcome measures included aerobic capacity, life satisfaction, self-esteem, anxiety, and dysfunctional cognitions. RESULTS: After 16 weeks of treatment, the groups did not differ statistically on HAM-D or BDI scores (P = .67); adjustment for baseline levels of depression yielded an essentially identical result. Growth curve models revealed that all groups exhibited statistically and clinically significant reductions on HAM-D and BDI scores. However, patients receiving medication alone exhibited the fastest initial response; among patients receiving combination therapy, those with less severe depressive symptoms initially showed a more rapid response than those with initially more severe depressive symptoms. CONCLUSIONS: An exercise training program may be considered an alternative to antidepressants for treatment of depression in older persons. Although antidepressants may facilitate a more rapid initial therapeutic response than exercise, after 16 weeks of treatment exercise was equally effective in reducing depression among patients with MDD. |
MED-1358 | This paper documents the recent (1976-1995) literature on the acute mood effects associated with participation in single sessions of exercise. Issues regarding experimental design, "ecological validity' and the operational definition of mood are addressed. Results from these studies suggest that both clinical and nonclinical subjects may benefit acutely from even a single bout of exercise. Finally, possible mechanisms and recommendations for future research are discussed. |
MED-1359 | Previous meta-analyses investigating the effect of exercise on depression have included trials where the control condition has been categorized as placebo despite the fact that this particular placebo intervention (e.g., meditation, relaxation) has been recognized as having an antidepressant effect. Because meditation and mindfulness-based interventions are associated with depression reduction, it is impossible to separate the effect of the physical exercise from the meditation-related parts. The present study determined the efficacy of exercise in reducing symptoms of depression compared with no treatment, placebo conditions or usual care among clinically defined depressed adults. Of 89 retrieved studies, 15 passed the inclusion criteria of which 13 studies presented sufficient information for calculating effect sizes. The main result showed a significant large overall effect favoring exercise intervention. The effect size was even larger when only trials that had used no treatment or placebo conditions were analyzed. Nevertheless, effect size was reduced to a moderate level when only studies with high methodological quality were included in the analysis. Exercise may be recommended for people with mild and moderate depression who are willing, motivated, and physically healthy enough to engage in such a program. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. |
MED-1360 | Objective To assess whether patients receiving aerobic exercise training performed either at home or in a supervised group setting achieve reductions in depression comparable to standard antidepressant medication (sertraline) and greater reductions in depression compared to placebo controls. Methods Between October 2000 and November 2005, we performed a prospective, randomized controlled trial (SMILE study) with allocation concealment and blinded outcome assessment in a tertiary care teaching hospital. A total of 202 adults (153 women; 49 men) diagnosed with major depression were assigned randomly to one of four conditions: supervised exercise in a group setting; home-based exercise; antidepressant medication (sertraline, 50–200 mg daily); or placebo pill for 16 weeks. Patients underwent the structured clinical interview for depression and completed the Hamilton Depression Rating Scale (HAM-D). Results After 4 months of treatment, 41% of the participants achieved remission, defined as no longer meeting the criteria for major depressive disorder (MDD) and a HAM-D score of <8. Patients receiving active treatments tended to have higher remission rates than the placebo controls: supervised exercise = 45%; home-based exercise = 40%; medication = 47%; placebo = 31% (p = .057). All treatment groups had lower HAM-D scores after treatment; scores for the active treatment groups were not significantly different from the placebo group (p = .23). Conclusions The efficacy of exercise in patients seems generally comparable with patients receiving antidepressant medication and both tend to be better than the placebo in patients with MDD. Placebo response rates were high, suggesting that a considerable portion of the therapeutic response is determined by patient expectations, ongoing symptom monitoring, attention, and other nonspecific factors. |
MED-1362 | The aim of this research study was to meta-analyze the effects of adherence to Mediterranean diet (MD) on overall cancer risk, and different cancer types. Literature search was performed using the electronic databases MEDLINE, SCOPUS and EMBASE until January 10, 2014. Inclusion criteria were cohort or case-control studies. Study specific risk ratios (RRs) were pooled using a random effect model by the Cochrane software package Review Manager 5.2. Twenty-one cohort studies including 1,368,736 subjects and 12 case-control studies with 62,725 subjects met the objectives and were enclosed for meta-analyses. The highest adherence to MD category resulted in a significantly risk reduction for overall cancer mortality/incidence (cohort; RR: 0.90, 95% CI 0.86-0.95, p < 0.0001; I(2) = 55%), colorectal (cohort/case-control; RR: 0.86, 95% CI 0.80-0.93, p < 0.0001; I(2) = 62%], prostate (cohort/case-control; RR: 0.96, 95% CI 0.92-0.99, p = 0.03; I(2) = 0%) and aerodigestive cancer (cohort/case-control; RR: 0.44, 95% CI 0.26-0.77, p = 0.003; I(2) = 83%). Nonsignificant changes could be observed for breast cancer, gastric cancer and pancreatic cancer. The Egger regression tests provided limited evidence of substantial publication bias. High adherence to a MD is associated with a significant reduction in the risk of overall cancer mortality (10%), colorectal cancer (14%), prostate cancer (4%) and aerodigestive cancer (56%). © 2014 UICC. |
MED-1363 | Dietary guidelines to promote good health are usually based on foods, nutrients, and dietary patterns predictive of chronic disease risk in epidemiologic studies. However, sound nutritional recommendations for cardiovascular prevention should be based on the results of large randomized clinical trials with "hard" end-points as the main outcome. Such evidence has been obtained for the Mediterranean diet from the PREDIMED (Prevención con Dieta Mediterránea) trial and the Lyon Heart Study. The traditional Mediterranean diet was that found in olive growing areas of Crete, Greece, and Southern Italy in the late 1950s. Their major characteristics include: a) a high consumption of cereals, legumes, nuts, vegetables, and fruits; b) a relatively high-fat consumption, mostly provided by olive oil; c) moderate to high fish consumption; d) poultry and dairy products consumed in moderate to small amounts; e) low consumption of red meats, and meat products; and f) moderate alcohol intake, usually in the form of red wine. However, these protective effects of the traditional Mediterranean diet may be even greater if we upgrade the health effects of this dietary pattern changing the common olive oil used for extra-virgin olive oil, increasing the consumption of nuts, fatty fish and whole grain cereals, reducing sodium intake, and maintaining a moderate consumption of wine with meals. © 2013 Elsevier B.V. All rights reserved. |
MED-1365 | The effects of bread consumption change over time on anthropometric measures have been scarcely studied. We analysed 2213 participants at high risk for CVD from the PREvención con DIeta MEDiterránea (PREDIMED) trial to assess the association between changes in the consumption of bread and weight and waist circumference gain over time. Dietary habits were assessed with validated FFQ at baseline and repeatedly every year during 4 years of follow-up. Using multivariate models to adjust for covariates, long-term weight and waist circumference changes according to quartiles of change in energy-adjusted white and whole-grain bread consumption were calculated. The present results showed that over 4 years, participants in the highest quartile of change in white bread intake gained 0·76 kg more than those in the lowest quartile (P for trend = 0·003) and 1·28 cm more than those in the lowest quartile (P for trend < 0·001). No significant dose-response relationships were observed for change in whole-bread consumption and anthropometric measures. Gaining weight (>2 kg) and gaining waist circumference (>2 cm) during follow-up was not associated with increase in bread consumption, but participants in the highest quartile of changes in white bread intake had a reduction of 33 % in the odds of losing weight (>2 kg) and a reduction of 36 % in the odds of losing waist circumference (>2 cm). The present results suggest that reducing white bread, but not whole-grain bread consumption, within a Mediterranean-style food pattern setting is associated with lower gains in weight and abdominal fat. |
MED-1366 | My concern about diet as a public health problem began in the early 1950s in Naples, where we observed very low incidences of coronary heart disease associated with what we later came to call the "good Mediterranean diet." The heart of this diet is mainly vegetarian, and differs from American and northern European diets in that it is much lower in meat and dairy products and uses fruit for dessert. These observations led to our subsequent research in the Seven Countries Study, in which we demonstrated that saturated fat is the major dietary villain. Today, the healthy Mediterranean diet is changing and coronary heart disease is no longer confined to medical textbooks. Our challenge is to persuade children to tell their parents to eat as Mediterraneans do. |
MED-1371 | Epidemiological evidence suggests that the Mediterranean diet (MD) could reduce the risk of breast cancer (BC). As evidence from the prospective studies remains scarce and conflicting, we investigated the association between adherence to the MD and risk of BC among 335,062 women recruited from 1992 to 2000, in ten European countries, and followed for 11 years on average. Adherence to the MD was estimated through an adapted relative Mediterranean diet (arMED) score excluding alcohol. Cox proportional hazards regression models were used while adjusting for BC risk factors. A total of 9,009 postmenopausal and 1,216 premenopausal first primary incident invasive BC were identified (5,862 estrogen or progesterone receptor positive [ER+/PR+] and 1,018 estrogen and progesterone receptor negative [ER-/PR-]). The arMED was inversely associated with the risk of BC overall and in postmenopausal women (high vs. low arMED score; hazard ratio [HR] = 0.94 [95% confidence interval [CI]: 0.88, 1.00] ptrend = 0.048, and HR = 0.93 [95% CI: 0.87, 0.99] ptrend = 0.037, respectively). The association was more pronounced in ER-/PR- tumors (HR = 0.80 [95% CI: 0.65, 0.99] ptrend = 0.043). The arMED score was not associated with BC in premenopausal women. Our findings show that adherence to a MD excluding alcohol was related to a modest reduced risk of BC in postmenopausal women, and this association was stronger in receptor-negative tumors. The results support the potential scope for BC prevention through dietary modification. Copyright © 2012 UICC. |
MED-1373 | The endothelium is involved in many of the processes related to the development of atherosclerosis, which is considered an inflammatory disease. Actually, traditional risk factors for atherosclerosis predispose to endothelial dysfunction, which is manifested as an increase in the expression of specific cytokines and adhesion molecules. There are firm evidence supporting the beneficial effects of olive oil, the most genuine component of the Mediterranean diet. Although the effects of olive oil and other oleic acid-rich dietary oils on atherosclerosis and plasma lipids are well known, the roles of minor components have been less investigated. Minor components constitute only 1-2% of virgin olive oil (VOO) and are composed of hydrocarbons, polyphenols, tocopherols, sterols, triterpenoids and other components usually found in traces. Despite their low concentration, non-fatty acid constituents may be of importance because studies comparing monounsaturated dietary oils have reported different effects on cardiovascular disease. Most of these compounds have demonstrated antioxidant, anti-inflammatory and hypolipidemic properties. In this review, we summarize current knowledge on the effects of these compounds contained in VOO on vascular dysfunction and the mechanisms by which they modulate endothelial activity. Such mechanisms involve the release of nitric oxide, eicosanoids (prostaglandins and leukotrienes) and adhesion molecules, in most cases by activation of nuclear factor kappaB by reactive oxygen species. |
MED-1374 | The Mediterranean diet has been linked to a number of health benefits, including reduced mortality risk and lower incidence of cardiovascular disease. Definitions of the Mediterranean diet vary across some settings, and scores are increasingly being employed to define Mediterranean diet adherence in epidemiological studies. Some components of the Mediterranean diet overlap with other healthy dietary patterns, whereas other aspects are unique to the Mediterranean diet. In this forum article, we asked clinicians and researchers with an interest in the effect of diet on health to describe what constitutes a Mediterranean diet in different geographical settings, and how we can study the health benefits of this dietary pattern. |
MED-1375 | BACKGROUND: Vegetarian diets have been associated with reduced mortality. Because a pure vegetarian diet might not easily be embraced by many individuals, consuming preferentially plant-derived foods would be a more easily understood message. A provegetarian food pattern (FP) emphasizing preference for plant-derived foods might reduce all-cause mortality. OBJECTIVE: The objective was to identify the association between an a priori-defined provegetarian FP and all-cause mortality. DESIGN: We followed 7216 participants (57% women; mean age: 67 y) at high cardiovascular risk for a median of 4.8 y. A validated 137-item semiquantitative food-frequency questionnaire was administered at baseline and yearly thereafter. Fruit, vegetables, nuts, cereals, legumes, olive oil, and potatoes were positively weighted. Added animal fats, eggs, fish, dairy products, and meats or meat products were negatively weighted. Energy-adjusted quintiles were used to assign points to build the provegetarian FP (range: 12-60 points). Deaths were confirmed by review of medical records and the National Death Index. RESULTS: There were 323 deaths during the follow-up period (76 from cardiovascular causes, 130 from cancer, 117 for noncancer, noncardiovascular causes). Higher baseline conformity with the provegetarian FP was associated with lower mortality (multivariable-adjusted HR for ≥ 40 compared with <30 points: 0.59; 95% CI: 0.40, 0.88). Similar results were found with the use of updated information on diet (RR: 0.59; 95% CI: 0.39, 0.89). CONCLUSIONS: Among omnivorous subjects at high cardiovascular risk, better conformity with an FP that emphasized plant-derived foods was associated with a reduced risk of all-cause mortality. This trial was registered at www.controlled-trials.com as ISRCTN35739639. © 2014 American Society for Nutrition. |
MED-1376 | Background. There are places around the world where people live longer and they are active past the age of 100 years, sharing common behavioral characteristics; these places (i.e., Sardinia in Italy, Okinawa in Japan, Loma Linda in California and Nicoya Peninsula in Costa Rica) have been named the “Blue Zones”. Recently it was reported that people in Ikaria Island, Greece, have also one of the highest life expectancies in the world, and joined the “Blue Zones”. The aim of this work work was to evaluate various demographic, lifestyle and psychological characteristics of very old (>80 years) people participated in Ikaria Study. Methods. During 2009, 1420 people (aged 30+) men and women from Ikaria Island, Greece, were voluntarily enrolled in the study. For this work, 89 males and 98 females over the age of 80 yrs were studied (13% of the sample). Socio-demographic, clinical, psychological and lifestyle characteristics were assessed using standard questionnaires and procedures. Results. A large proportion of the Ikaria Study's sample was over the age of 80; moreover, the percent of people over 90 were much higher than the European population average. The majority of the oldest old participants reported daily physical activities, healthy eating habits, avoidance of smoking, frequent socializing, mid-day naps and extremely low rates of depression. Conclusion. Modifiable risk factors, such as physical activity, diet, smoking cessation and mid-day naps, might depict the “secrets” of the long-livers; these findings suggest that the interaction of environmental, behavioral together with clinical characteristics may determine longevity. This concept must be further explored in order to understand how these factors relate and which are the most important in shaping prolonged life. |
MED-1377 | Increased attention in dietary research and guidance has been focused on dietary patterns, rather than on single nutrients or food groups, because dietary components are consumed in combination and correlated with one another. However, the collective body of research on the topic has been hampered by the lack of consistency in methods used. We examined the relationships between 4 indices—the Healthy Eating Index–2010 (HEI-2010), the Alternative Healthy Eating Index–2010 (AHEI-2010), the alternate Mediterranean Diet (aMED), and Dietary Approaches to Stop Hypertension (DASH)—and all-cause, cardiovascular disease (CVD), and cancer mortality in the NIH-AARP Diet and Health Study (n = 492,823). Data from a 124-item food-frequency questionnaire were used to calculate scores; adjusted HRs and 95% CIs were estimated. We documented 86,419 deaths, including 23,502 CVD- and 29,415 cancer-specific deaths, during 15 y of follow-up. Higher index scores were associated with a 12–28% decreased risk of all-cause, CVD, and cancer mortality. Specifically, comparing the highest with the lowest quintile scores, adjusted HRs for all-cause mortality for men were as follows: HEI-2010 HR: 0.78 (95% CI: 0.76, 0.80), AHEI-2010 HR: 0.76 (95% CI: 0.74, 0.78), aMED HR: 0.77 (95% CI: 0.75, 0.79), and DASH HR: 0.83 (95% CI: 0.80, 0.85); for women, these were HEI-2010 HR: 0.77 (95% CI: 0.74, 0.80), AHEI-2010 HR: 0.76 (95% CI: 0.74, 0.79), aMED HR: 0.76 (95% CI: 0.73, 0.79), and DASH HR: 0.78 (95% CI: 0.75, 0.81). Similarly, high adherence on each index was protective for CVD and cancer mortality examined separately. These findings indicate that multiple scores reflect core tenets of a healthy diet that may lower the risk of mortality outcomes, including federal guidance as operationalized in the HEI-2010, Harvard’s Healthy Eating Plate as captured in the AHEI-2010, a Mediterranean diet as adapted in an Americanized aMED, and the DASH Eating Plan as included in the DASH score. |
MED-1378 | Longevity is a very complex phenomenon, because many environmental, behavioral, socio-demographic and dietary factors influence the physiological pathways of aging and life-expectancy. Nutrition has been recognized to have an important impact on overall mortality and morbidity; and its role in extending life expectancy has been the object of extensive scientific research. This paper reviews the pathophysiological mechanisms that potentially link aging with diet and the scientific evidence supporting the anti-aging effect of the traditional Mediterranean diet, as well as of some specific foods. The diet and several of its components have additionally been shown to have beneficial effects on the co-morbidities typical of elderly populations. Furthermore, the epigenetic effects of diet on the aging process - through calorie restriction and the consumption of foods like red wine, orange juice, probiotics and prebiotics - have attracted scientific interest. Some, such as dark chocolate, red wine, nuts, beans, avocados are being promoted as anti-aging foods, due to their anti-oxidative and anti-inflammatory properties. Finally, an important moderator in the relationship between diet, longevity and human health remains the socio-economic status of individual, as a healthy diet, due to its higher cost, is closely related to higher financial and educational status. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved. |
MED-1380 | Objective To investigate the relative importance of the individual components of the Mediterranean diet in generating the inverse association of increased adherence to this diet and overall mortality. Design Prospective cohort study. Setting Greek segment of the European Prospective Investigation into Cancer and nutrition (EPIC). Participants 23 349 men and women, not previously diagnosed with cancer, coronary heart disease, or diabetes, with documented survival status until June 2008 and complete information on nutritional variables and important covariates at enrolment. Main outcome measure All cause mortality. Results After a mean follow-up of 8.5 years, 652 deaths from any cause had occurred among 12 694 participants with Mediterranean diet scores 0-4 and 423 among 10 655 participants with scores of 5 or more. Controlling for potential confounders, higher adherence to a Mediterranean diet was associated with a statistically significant reduction in total mortality (adjusted mortality ratio per two unit increase in score 0.864, 95% confidence interval 0.802 to 0.932). The contributions of the individual components of the Mediterranean diet to this association were moderate ethanol consumption 23.5%, low consumption of meat and meat products 16.6%, high vegetable consumption 16.2%, high fruit and nut consumption 11.2%, high monounsaturated to saturated lipid ratio 10.6%, and high legume consumption 9.7%. The contributions of high cereal consumption and low dairy consumption were minimal, whereas high fish and seafood consumption was associated with a non-significant increase in mortality ratio. Conclusion The dominant components of the Mediterranean diet score as a predictor of lower mortality are moderate consumption of ethanol, low consumption of meat and meat products, and high consumption of vegetables, fruits and nuts, olive oil, and legumes. Minimal contributions were found for cereals and dairy products, possibly because they are heterogeneous categories of foods with differential health effects, and for fish and seafood, the intake of which is low in this population. |
MED-1381 | Perhaps one of the most unexpected and novel findings in nutritional epidemiology in the past 5 y has been that nut consumption seems to protect against ischemic heart disease (IHD). Frequency and quantity of nut consumption have been documented to be higher in vegetarian than in nonvegetarian populations. Nuts also constitute an important part of other plant-based diets, such as Mediterranean and Asian diets. In a large, prospective epidemiologic study of Seventh-day Adventists in California, we found that frequency of nut consumption had a substantial and highly significant inverse association with risk of myocardial infarction and death from IHD. The Iowa Women's Health Study also documented an association between nut consumption and decreased risk of IHD. The protective effect of nuts on IHD has been found in men and women and in the elderly. Importantly, nuts have similar associations in both vegetarians and nonvegetarians. The protective effect of nut consumption on IHD is not offset by increased mortality from other causes. Moreover, frequency of nut consumption has been found to be inversely related to all-cause mortality in several population groups such as whites, blacks, and the elderly. Thus, nut consumption may not only offer protection against IHD, but also increase longevity. |
MED-1383 | BACKGROUND AND AIMS: The intake of antioxidant-rich foods may increase the blood levels of non enzymatic antioxidant capacity (NEAC). NEAC takes into account all antioxidants from food and synergistic effects between them. We examined the effect of a 1-year intervention with Mediterranean diet on plasma NEAC and assessed whether it was related to baseline NEAC levels. METHODS AND RESULTS: Five hundred sixty-four participants at high cardiovascular risk were randomly selected from the PREDIMED (Prevención con DIeta MEDiterránea) Study, a large 3-arm randomized clinical trial. Blood NEAC levels were measured at baseline and after 1-year of dietary intervention with 1) a Mediterranean diet supplemented with virgin olive oil (MED + VOO); 2) a Mediterranean diet supplemented with nuts (MED + nuts), or 3) a control low-fat diet. Plasma NEAC was analyzed using FRAP (ferric reducing antioxidant potential) and TRAP (total radical-trapping antioxidant parameter) assays. Plasma FRAP levels increased after 1-year of intervention with MED + VOO [72.0 μmol/L (95% CI, 34.2-109.9)] and MED + nuts [48.9 μmol/L (24.3-73.5)], but not after the control low-fat diet [13.9 μmol/L (-11.9 to 39.8)]. Participants in the lowest quartile of plasma FRAP at baseline significantly increased their levels after any intervention, while those in the highest quartile decreased. Similar results occurred with TRAP levels. CONCLUSIONS: This study shows that a 1-year of MED diet intervention increases plasma TAC level in subjects at high risk for cardiovascular disease. Moreover, the effectiveness of dietary supplementation with antioxidants may be related to baseline levels of plasma NEAC. © 2013 Elsevier B.V. All rights reserved. |
MED-1387 | BACKGROUND: Epidemiologic studies have shown inverse associations between nut consumption and diabetes, cardiovascular disease (CVD), and all-cause mortality, but results have not been consistent. OBJECTIVE: We assessed the relation between nut intake and incidence of type 2 diabetes, CVD, and all-cause mortality. DESIGN: We searched PubMed and EMBASE for all prospective cohort studies published up to March 2013 with RRs and 95% CIs for outcomes of interest. A random-effects model was used to pool risk estimates across studies. RESULTS: In 31 reports from 18 prospective studies, there were 12,655 type 2 diabetes, 8862 CVD, 6623 ischemic heart disease (IHD), 6487 stroke, and 48,818 mortality cases. The RR for each incremental serving per day of nut intake was 0.80 (95% CI: 0.69, 0.94) for type 2 diabetes without adjustment for body mass index; with adjustment, the association was attenuated [RR: 1.03; 95% CI: 0.91, 1.16; NS]. In the multivariable-adjusted model, pooled RRs (95% CIs) for each serving per day of nut consumption were 0.72 (0.64, 0.81) for IHD, 0.71 (0.59, 0.85) for CVD, and 0.83 (0.76, 0.91) for all-cause mortality. Pooled RRs (95% CIs) for the comparison of extreme quantiles of nut intake were 1.00 (0.84, 1.19; NS) for type 2 diabetes, 0.66 (0.55, 0.78) for IHD, 0.70 (0.60, 0.81) for CVD, 0.91 (0.81, 1.02; NS) for stroke, and 0.85 (0.79, 0.91) for all-cause mortality. CONCLUSIONS: Our meta-analysis indicates that nut intake is inversely associated with IHD, overall CVD, and all-cause mortality but not significantly associated with diabetes and stroke. The inverse association between the consumption of nuts and diabetes was attenuated after adjustment for body mass index. These findings support recommendations to include nuts as part of a healthy dietary pattern for the prevention of chronic diseases. © 2014 American Society for Nutrition. |
MED-1388 | OBJECTIVE: The aim of this study was to assess the association between nut consumption and all-cause mortality after 5-y follow-up in a Spanish cohort. METHODS: The SUN (Seguimiento Universidad de Navarra, University of Navarra Follow-up) project is a prospective cohort study, formed by Spanish university graduates. Information is gathered by mailed questionnaires collected biennially. In all, 17 184 participants were followed for up to 5 y. Baseline nut consumption was collected by self-reported data, using a validated 136-item semi-quantitative food frequency questionnaire. Information on mortality was collected by permanent contact with the SUN participants and their families, postal authorities, and the National Death Index. The association between baseline nut consumption and all-cause mortality was assessed using Cox proportional hazards models to adjust for potential confounding. Baseline nut consumption was categorized in two ways. In a first analysis energy-adjusted quintiles of nut consumption (measured in g/d) were used. To adjust for total energy intake the residuals method was used. In a second analysis, participants were categorized into four groups according to pre-established categories of nut consumption (servings/d or servings/wk). Both analyses were adjusted for potential confounding factors. RESULTS: Participants who consumed nuts ≥2/wk had a 56% lower risk for all-cause mortality than those who never or almost never consumed nuts (adjusted hazard ratio, 0.44; 95% confidence intervals, 0.23-0.86). CONCLUSION: Nut consumption was significantly associated with a reduced risk for all-cause mortality after the first 5 y of follow-up in the SUN project. Copyright © 2014 Elsevier Inc. All rights reserved. |
MED-1389 | BACKGROUND & AIMS: Metabolic syndrome (MetS), in which a non-classic feature is an increase in systemic oxidative biomarkers, presents a high risk of diabetes and cardiovascular disease (CVD). Adherence to the Mediterranean Diet (MedDiet) is associated with a reduced risk of MetS. However, the effect of the MedDiet on biomarkers for oxidative damage has not been assessed in MetS individuals. We have investigated the effect of the MedDiet on systemic oxidative biomarkers in MetS individuals. METHODS: Randomized, controlled, parallel clinical trial in which 110 female with MetS, aged 55-80, were recruited into a large trial (PREDIMED Study) to test the efficacy of the traditional MedDiet on the primary prevention of CVD. Participants were assigned to a low-fat diet or two traditional MedDiets (MedDiet + virgin olive oil or MedDiet + nuts). Both MedDiet group participants received nutritional education and either free extra virgin olive oil for all the family (1 L/week), or free nuts (30 g/day). Diets were ad libitum. Changes in urine levels of F2-Isoprostane (F2-IP) and the DNA damage base 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) were evaluated at 1-year trial. RESULTS: After 1-year urinary F2-IP decreased in all groups, the decrease in MedDiet groups reaching a borderline significance versus that of the Control group. Urinary 8-oxo-dG was also reduced in all groups, with a higher decrease in both MedDiet groups versus the Control one (P < 0.001). CONCLUSIONS: MedDiet reduces oxidative damage to lipids and DNA in MetS individuals. Data from this study provide evidence to recommend the traditional MedDiet as a useful tool in the MetS management. Registered under Clinical Trials.gov Identifier no. NCT00123456. Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. |
MED-1390 | Background It is unknown whether individuals at high cardiovascular risk sustain a benefit in cardiovascular disease from increased olive oil consumption. The aim was to assess the association between total olive oil intake, its varieties (extra virgin and common olive oil) and the risk of cardiovascular disease and mortality in a Mediterranean population at high cardiovascular risk. Methods We included 7,216 men and women at high cardiovascular risk, aged 55 to 80 years, from the PREvención con DIeta MEDiterránea (PREDIMED) study, a multicenter, randomized, controlled, clinical trial. Participants were randomized to one of three interventions: Mediterranean Diets supplemented with nuts or extra-virgin olive oil, or a control low-fat diet. The present analysis was conducted as an observational prospective cohort study. The median follow-up was 4.8 years. Cardiovascular disease (stroke, myocardial infarction and cardiovascular death) and mortality were ascertained by medical records and National Death Index. Olive oil consumption was evaluated with validated food frequency questionnaires. Multivariate Cox proportional hazards and generalized estimating equations were used to assess the association between baseline and yearly repeated measurements of olive oil intake, cardiovascular disease and mortality. Results During follow-up, 277 cardiovascular events and 323 deaths occurred. Participants in the highest energy-adjusted tertile of baseline total olive oil and extra-virgin olive oil consumption had 35% (HR: 0.65; 95% CI: 0.47 to 0.89) and 39% (HR: 0.61; 95% CI: 0.44 to 0.85) cardiovascular disease risk reduction, respectively, compared to the reference. Higher baseline total olive oil consumption was associated with 48% (HR: 0.52; 95% CI: 0.29 to 0.93) reduced risk of cardiovascular mortality. For each 10 g/d increase in extra-virgin olive oil consumption, cardiovascular disease and mortality risk decreased by 10% and 7%, respectively. No significant associations were found for cancer and all-cause mortality. The associations between cardiovascular events and extra virgin olive oil intake were significant in the Mediterranean diet intervention groups and not in the control group. Conclusions Olive oil consumption, specifically the extra-virgin variety, is associated with reduced risks of cardiovascular disease and mortality in individuals at high cardiovascular risk. Trial registration This study was registered at controlled-trials.com (http://www.controlled-trials.com/ISRCTN35739639). International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005. |
MED-1393 | OBJECTIVE: The Prevención con Dieta Mediterránea (PREDIMED) trial showed that a Mediterranean diet (MedDiet) supplemented with either extra virgin olive oil or 30 g/d of mixed nuts reduced incident cardiovascular events compared with a control (low fat) diet. The mechanisms of cardiovascular protection afforded by MedDiets remain to be uncovered. We assessed the effect of both supplemented MedDiets on internal carotid intima-media thickness (ICA-IMT) and plaque height, the ultrasound features that best predict future cardiovascular events, in subjects at high cardiovascular risk. APPROACH AND RESULTS: In a PREDIMED subcohort (n=175), plaque height and carotid IMT of 3 prespecified segments (ICA, bifurcation, and common) were sonographically assessed at baseline and after intervention for a mean of 2.4 years. We evaluated 164 subjects with complete data. In a multivariate model, mean ICA-IMT progressed in the control diet group (mean [95% confidence interval], 0.052 mm [-0.014 to 0.118 mm]), whereas it regressed in the MedDiet+nuts group (-0.084 mm [-0.158 to -0.010 mm]; P=0.024 versus control). Similar results were observed for maximum ICA-IMT (control, 0.188 mm [0.077 to 0.299 mm]; MedDiet+nuts, -0.030 mm [-0.153 to 0.093 mm]; P=0.034) and maximum plaque height (control, 0.106 mm [0.001 to 0.210 mm]; MedDiet+nuts, -0.091 mm [-0.206 to 0.023 mm]; P=0.047). There were no changes in ICA-IMT or plaque after the MedDiet+extra virgin olive oil. CONCLUSIONS: Compared with a control diet, consumption of a MedDiet supplemented with nuts is associated with delayed progression of ICA-IMT and plaque. The results contribute mechanistic evidence for the reduction of cardiovascular events observed in the PREDIMED trial. CLINICAL TRIAL REGISTRATION URL: http://www.controlled-trials.com. Unique identifier: ISRCTN35739639. |
MED-1394 | BACKGROUND: Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events. METHODS: In a multicenter trial in Spain, we randomly assigned participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years. RESULTS: A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported. CONCLUSIONS: Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events. (Funded by the Spanish government's Instituto de Salud Carlos III and others; Controlled-Trials.com number, ISRCTN35739639.). |
MED-1395 | In a prospective, randomised single-blinded secondary prevention trial we compared the effect of a Mediterranean alpha-linolenic acid-rich diet to the usual post-infarct prudent diet. After a first myocardial infarction, patients were randomly assigned to the experimental (n = 302) or control group (n = 303). Patients were seen again 8 weeks after randomisation, and each year for 5 years. The experimental group consumed significantly less lipids, saturated fat, cholesterol, and linoleic acid but more oleic and alpha-linolenic acids confirmed by measurements in plasma. Serum lipids, blood pressure, and body mass index remained similar in the 2 groups. In the experimental group, plasma levels of albumin, vitamin E, and vitamin C were increased, and granulocyte count decreased. After a mean follow up of 27 months, there were 16 cardiac deaths in the control and 3 in the experimental group; 17 non-fatal myocardial infarction in the control and 5 in the experimental groups: a risk ratio for these two main endpoints combined of 0.27 (95% CI 0.12-0.59, p = 0.001) after adjustment for prognostic variables. Overall mortality was 20 in the control, 8 in the experimental group, an adjusted risk ratio of 0.30 (95% CI 0.11-0.82, p = 0.02). An alpha-linolenic acid-rich Mediterranean diet seems to be more efficient than presently used diets in the secondary prevention of coronary events and death. |
MED-1397 | 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. |
MED-1398 | The concept that the Mediterranean diet was associated with a lower incidence of cardiovascular disease (CVD) was first proposed in the 1950s. Since then, there have been randomized controlled trials and large epidemiological studies that reported associations with lower CVD: in 1994 and 1999, the reports of the intermediate and final analyses of the trial Lyon Diet Heart Study; in 2003, a major epidemiological study in Greece showing a strong inverse association between a Mediterranean score and the risk of cardiovascular complications; in 2011-2012, several reports showing that even non-Mediterranean populations can gain benefits from long-term adhesion to the Mediterranean diet; and in 2013, the PREDIMED trial showing a significant risk reduction in a low-risk population. Contrary to the pharmacological approach of cardiovascular prevention, the adoption of the Mediterranean diet has been associated with a significant reduction in new cancers and overall mortality. Thus, in terms of evidence-based medicine, the full adoption of a modern version of the Mediterranean diet pattern can be considered one of the most effective approaches for the prevention of fatal and nonfatal CVD complications. |
MED-1399 | BACKGROUND: The Lyon Diet Heart Study is a randomized secondary prevention trial aimed at testing whether a Mediterranean-type diet may reduce the rate of recurrence after a first myocardial infarction. An intermediate analysis showed a striking protective effect after 27 months of follow-up. This report presents results of an extended follow-up (with a mean of 46 months per patient) and deals with the relationships of dietary patterns and traditional risk factors with recurrence. METHODS AND RESULTS: Three composite outcomes (COs) combining either cardiac death and nonfatal myocardial infarction (CO 1), or the preceding plus major secondary end points (unstable angina, stroke, heart failure, pulmonary or peripheral embolism) (CO 2), or the preceding plus minor events requiring hospital admission (CO 3) were studied. In the Mediterranean diet group, CO 1 was reduced (14 events versus 44 in the prudent Western-type diet group, P=0.0001), as were CO 2 (27 events versus 90, P=0.0001) and CO 3 (95 events versus 180, P=0. 0002). Adjusted risk ratios ranged from 0.28 to 0.53. Among the traditional risk factors, total cholesterol (1 mmol/L being associated with an increased risk of 18% to 28%), systolic blood pressure (1 mm Hg being associated with an increased risk of 1% to 2%), leukocyte count (adjusted risk ratios ranging from 1.64 to 2.86 with count >9x10(9)/L), female sex (adjusted risk ratios, 0.27 to 0. 46), and aspirin use (adjusted risk ratios, 0.59 to 0.82) were each significantly and independently associated with recurrence. CONCLUSIONS: The protective effect of the Mediterranean dietary pattern was maintained up to 4 years after the first infarction, confirming previous intermediate analyses. Major traditional risk factors, such as high blood cholesterol and blood pressure, were shown to be independent and joint predictors of recurrence, indicating that the Mediterranean dietary pattern did not alter, at least qualitatively, the usual relationships between major risk factors and recurrence. Thus, a comprehensive strategy to decrease cardiovascular morbidity and mortality should include primarily a cardioprotective diet. It should be associated with other (pharmacological?) means aimed at reducing modifiable risk factors. Further trials combining the 2 approaches are warranted. |
MED-1400 | BACKGROUND: The Mediterranean diet has long been reported to be protective against the occurrence of several different health outcomes. OBJECTIVE: We aimed to update our previous meta-analysis of published cohort prospective studies that investigated the effects of adherence to the Mediterranean diet on health status. DESIGN: We conducted a comprehensive literature search through electronic databases up to June 2010. RESULTS: The updated review process showed 7 prospective studies published in the past 2 y that were not included in the previous meta-analysis (1 study for overall mortality, 3 studies for cardiovascular incidence or mortality, 1 study for cancer incidence or mortality, and 2 studies for neurodegenerative diseases). These recent studies included 2 health outcomes not previously investigated (ie, mild cognitive impairment and stroke). The meta-analysis for all studies with a random-effects model that was conducted after the inclusion of these recent studies showed that a 2-point increase in adherence to the Mediterranean diet was associated with a significant reduction of overall mortality [relative risk (RR) = 0.92; 95% CI: 0.90, 0.94], cardiovascular incidence or mortality (RR = 0.90; 95% CI: 0.87, 0.93), cancer incidence or mortality (RR = 0.94; 95% CI: 0.92, 0.96), and neurodegenerative diseases (RR = 0.87; 95% CI: 0.81, 0.94). The meta-regression analysis showed that sample size was the most significant contributor to the model because it significantly influenced the estimate of the association for overall mortality. CONCLUSION: This updated meta-analysis confirms, in a larger number of subjects and studies, the significant and consistent protection provided by adherence to the Mediterranean diet in relation to the occurrence of major chronic degenerative diseases. |
MED-1402 | OBJECTIVE: To update previous meta-analyses of cohort studies that investigated the association between the Mediterranean diet and health status and to utilize data coming from all of the cohort studies for proposing a literature-based adherence score to the Mediterranean diet. DESIGN: We conducted a comprehensive literature search through all electronic databases up to June 2013. SETTING: Cohort prospective studies investigating adherence to the Mediterranean diet and health outcomes. Cut-off values of food groups used to compute the adherence score were obtained. SUBJECTS: The updated search was performed in an overall population of 4 172 412 subjects, with eighteen recent studies that were not present in the previous meta-analyses. RESULTS: A 2-point increase in adherence score to the Mediterranean diet was reported to determine an 8 % reduction of overall mortality (relative risk = 0·92; 95 % CI 0·91, 0·93), a 10 % reduced risk of CVD (relative risk = 0·90; 95 % CI 0·87, 0·92) and a 4 % reduction of neoplastic disease (relative risk = 0·96; 95 % CI 0·95, 0·97). We utilized data coming from all cohort studies available in the literature for proposing a literature-based adherence score. Such a score ranges from 0 (minimal adherence) to 18 (maximal adherence) points and includes three different categories of consumption for each food group composing the Mediterranean diet. CONCLUSIONS: The Mediterranean diet was found to be a healthy dietary pattern in terms of morbidity and mortality. By using data from the cohort studies we proposed a literature-based adherence score that can represent an easy tool for the estimation of adherence to the Mediterranean diet also at the individual level. |
MED-1404 | OBJECTIVE: The purpose of this work was to meta-analyze prospective studies that have evaluated the effect of a Mediterranean diet on the development of type 2 diabetes. MATERIALS/METHODS: PubMed, Embase and the Cochrane Central Register of Controlled Trials databases were searched up to 20 November 2013. English language publications were allocated; 17 original research studies (1 clinical trial, 9 prospective and 7 cross-sectional) were identified. Primary analyses were limited to prospective studies and clinical trials, yielding to a sample of 136,846 participants. A systematic review and a random effects meta-analysis were conducted. RESULTS: Higher adherence to the Mediterranean diet was associated with 23% reduced risk of developing type 2 diabetes (combined relative risk for upper versus lowest available centile: 0.77; 95% CI: 0.66, 0.89). Subgroup analyses based on region, health status of participants and number of confounders controlling for, showed similar results. Limitations include variations in Mediterranean diet adherence assessment tools, confounders' adjustment, duration of follow up and number of events with diabetes. CONCLUSIONS: The presented results are of major public health importance, since no consensus exists concerning the best anti-diabetic diet. Mediterranean diet could, if appropriately adjusted to reflect local food availability and individual's needs, constitute a beneficial nutritional choice for the primary prevention of diabetes. Copyright © 2014 Elsevier Inc. All rights reserved. |
MED-1405 | Background Polyphenols may lower the risk of cardiovascular disease (CVD) and other chronic diseases due to their antioxidant and anti-inflammatory properties, as well as their beneficial effects on blood pressure, lipids and insulin resistance. However, no previous epidemiological studies have evaluated the relationship between the intake of total polyphenols intake and polyphenol subclasses with overall mortality. Our aim was to evaluate whether polyphenol intake is associated with all-cause mortality in subjects at high cardiovascular risk. Methods We used data from the PREDIMED study, a 7,447-participant, parallel-group, randomized, multicenter, controlled five-year feeding trial aimed at assessing the effects of the Mediterranean Diet in primary prevention of cardiovascular disease. Polyphenol intake was calculated by matching food consumption data from repeated food frequency questionnaires (FFQ) with the Phenol-Explorer database on the polyphenol content of each reported food. Hazard ratios (HR) and 95% confidence intervals (CI) between polyphenol intake and mortality were estimated using time-dependent Cox proportional hazard models. Results Over an average of 4.8 years of follow-up, we observed 327 deaths. After multivariate adjustment, we found a 37% relative reduction in all-cause mortality comparing the highest versus the lowest quintiles of total polyphenol intake (hazard ratio (HR) = 0.63; 95% CI 0.41 to 0.97; P for trend = 0.12). Among the polyphenol subclasses, stilbenes and lignans were significantly associated with reduced all-cause mortality (HR =0.48; 95% CI 0.25 to 0.91; P for trend = 0.04 and HR = 0.60; 95% CI 0.37 to 0.97; P for trend = 0.03, respectively), with no significant associations apparent in the rest (flavonoids or phenolic acids). Conclusions Among high-risk subjects, those who reported a high polyphenol intake, especially of stilbenes and lignans, showed a reduced risk of overall mortality compared to those with lower intakes. These results may be useful to determine optimal polyphenol intake or specific food sources of polyphenols that may reduce the risk of all-cause mortality. Clinical trial registration ISRCTN35739639. |
MED-1406 | The relation between dietary magnesium intake and cardiovascular disease (CVD) or mortality was evaluated in several prospective studies, but few of them have assessed the risk of all-cause mortality, which has never been evaluated in Mediterranean adults at high cardiovascular risk. The aim of this study was to assess the association between magnesium intake and CVD and mortality risk in a Mediterranean population at high cardiovascular risk with high average magnesium intake. The present study included 7216 men and women aged 55-80 y from the PREDIMED (Prevención con Dieta Mediterránea) study, a randomized clinical trial. Participants were assigned to 1 of 2 Mediterranean diets (supplemented with nuts or olive oil) or to a control diet (advice on a low-fat diet). Mortality was ascertained by linkage to the National Death Index and medical records. We fitted multivariable-adjusted Cox regressions to assess associations between baseline energy-adjusted tertiles of magnesium intake and relative risk of CVD and mortality. Multivariable analyses with generalized estimating equation models were used to assess the associations between yearly repeated measurements of magnesium intake and mortality. After a median follow-up of 4.8 y, 323 total deaths, 81 cardiovascular deaths, 130 cancer deaths, and 277 cardiovascular events occurred. Energy-adjusted baseline magnesium intake was inversely associated with cardiovascular, cancer, and all-cause mortality. Compared with lower consumers, individuals in the highest tertile of magnesium intake had a 34% reduction in mortality risk (HR: 0.66; 95% CI: 0.45, 0.95; P < 0.01). Dietary magnesium intake was inversely associated with mortality risk in Mediterranean individuals at high risk of CVD. This trial was registered at controlled-trials.com as ISRCTN35739639. |
MED-1408 | OBJECTIVE: This meta-analysis aims to quantitatively synthesize all studies that examine the association between adherence to a Mediterranean diet and risk of stroke, depression, cognitive impairment, and Parkinson disease. METHODS: Potentially eligible publications were those providing effect estimates of relative risk (RR) for the association between Mediterranean diet and the aforementioned outcomes. Studies were sought in PubMed up to October 31, 2012. Maximally adjusted effect estimates were extracted; separate analyses were performed for high and moderate adherence. RESULTS: Twenty-two eligible studies were included (11 covered stroke, 9 covered depression, and 8 covered cognitive impairment; only 1 pertained to Parkinson's disease). High adherence to Mediterranean diet was consistently associated with reduced risk for stroke (RR = 0.71, 95% confidence interval [CI] = 0.57-0.89), depression (RR = 0.68, 95% CI = 0.54-0.86), and cognitive impairment (RR = 0.60, 95% CI = 0.43-0.83). Moderate adherence was similarly associated with reduced risk for depression and cognitive impairment, whereas the protective trend concerning stroke was only marginal. Subgroup analyses highlighted the protective actions of high adherence in terms of reduced risk for ischemic stroke, mild cognitive impairment, dementia, and particularly Alzheimer disease. Meta-regression analysis indicated that the protective effects of Mediterranean diet in stroke prevention seemed more sizeable among males. Concerning depression, the protective effects of high adherence seemed independent of age, whereas the favorable actions of moderate adherence seemed to fade away with more advanced age. INTERPRETATION: Adherence to a Mediterranean diet may contribute to the prevention of a series of brain diseases; this may be of special value given the aging of Western societies. © 2013 American Neurological Association. |
MED-1409 | This study compares the prevalence of coronary heart disease (CHD), risk factors (RF), and cardiovascular diseases (CVD) among Cretan men from a rural area examined in 1960 and 1991. The study population consisted of 148 men in 1960 and 42 men in 1991 of the same age group (fifty-five to fifty-nine years old) and from the same rural area. All men had a complete examination of the cardiovascular system and a resting electrocardiogram (ECG). Systolic BP (SBP) > or = 140 mmHg was found in 42.6% of the subjects in 1960 and in 45.2% in 1991 (NS). Diastolic BP > or = 95 mmHG was found in 14.9% of the subjects in 1960 as opposed to 33.3% in 1991 (P < 0.02). Total serum cholesterol (TSCH) > or = 260 mg/dL approximately 6.7 mmol/L) was found in 12.8% of the subjects in 1960 and in 28.6% in 1991 (P < 0.01). Heavy smokers ( > or = 20 cigarettes/daily) were 27.0% in 1960 as compared with 35.7% in 1991 (:NS); 5.4% of the subjects in 1960 had light physical activity (PA) as compared with 14.3% in 1991 (P < 0.01); 74.7% of the subjects were farmers in 1960 as compared with 43.6% in 1991 (P < 0.1). The prevalence of CHD was 0.7% in 1960 as compared with 9.5% in 1991 (P < 0.001). Hypertensive heart disease was found in 3.4% of the subjects in 1960 and 4.8% in 1991 (NS). The prevalence of all major CVD was much higher in 1991 (19.1%) as compared with 1960 (8.8%) (P < 0.01). In conclusion, the prevalence of CHD RF and CVD was much higher in 1991 than in 1960 for Cretan men of the same age group. This higher prevalence seems to be related to dietary and life-style changes that have taken place in Crete during the last thirty years. |
MED-1410 | In 15 cohorts of the Seven Countries Study, comprising 11,579 men aged 40-59 years and "healthy" at entry, 2,288 died in 15 years. Death rates differed among cohorts. Differences in mean age, blood pressure, serum cholesterol, and smoking habits "explained" 46% of variance in death rate from all causes, 80% from coronary heart disease, 35% from cancer, and 45% from stroke. Death rate differences were unrelated to cohort differences in mean relative body weight, fatness, and physical activity. The cohorts differed in average diets. Death rates were related positively to average percentage of dietary energy from saturated fatty acids, negatively to dietary energy percentage from monounsaturated fatty acids, and were unrelated to dietary energy percentage from polyunsaturated fatty acids, proteins, carbohydrates, and alcohol. All death rates were negatively related to the ratio of monounsaturated to saturated fatty acids. Inclusion of that ratio with age, blood pressure, serum cholesterol, and smoking habits as independent variables accounted for 85% of variance in rates of deaths from all causes, 96% coronary heart disease, 55% cancer, and 66% stroke. Oleic acid accounted for almost all differences in monounsaturates among cohorts. All-cause and coronary heart disease death rates were low in cohorts with olive oil as the main fat. Causal relationships are not claimed but consideration of characteristics of populations as well as of individuals within populations is urged in evaluating risks. |
MED-1411 | OBJECTIVES: The aim of this study was to meta-analyze epidemiological studies and clinical trials that have assessed the effect of a Mediterranean diet on metabolic syndrome (MS) as well as its components. BACKGROUND: The Mediterranean diet has long been associated with low cardiovascular disease risk in adult population. METHODS: The authors conducted a systematic review and random effects meta-analysis of epidemiological studies and randomized controlled trials, including English-language publications in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials until April 30, 2010; 50 original research studies (35 clinical trials, 2 prospective and 13 cross-sectional), with 534,906 participants, were included in the analysis. RESULTS: The combined effect of prospective studies and clinical trials showed that adherence to the Mediterranean diet was associated with reduced risk of MS (log hazard ratio: -0.69, 95% confidence interval [CI]: -1.24 to -1.16). Additionally, results from clinical studies (mean difference, 95% CI) revealed the protective role of the Mediterranean diet on components of MS, like waist circumference (-0.42 cm, 95% CI: -0.82 to -0.02), high-density lipoprotein cholesterol (1.17 mg/dl, 95% CI: 0.38 to 1.96), triglycerides (-6.14 mg/dl, 95% CI: -10.35 to -1.93), systolic (-2.35 mm Hg, 95% CI: -3.51 to -1.18) and diastolic blood pressure (-1.58 mm Hg, 95% CI: -2.02 to -1.13), and glucose (-3.89 mg/dl, 95% CI:-5.84 to -1.95), whereas results from epidemiological studies also confirmed those of clinical trials. CONCLUSIONS: These results are of considerable public health importance, because this dietary pattern can be easily adopted by all population groups and various cultures and cost-effectively serve for primary and secondary prevention of the MS and its individual components. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. |
MED-1412 | Mean faecal pH values did not differ significantly in groups of rural South African Black schoolchildren of 10--12 years who ate their traditional high-fibre low-fat diet, and urban dwellers who consumed a partially westernized diet. However, both means were significantly lower than those of groups of White schoolchildren. In feeding studies of 5 days' duration, mean faecal pH value of Black children became significantly less acid when white bread replaced maize meal, and became significantly more acid when a supplement of 6 oranges was consumed daily. Supplements which consisted of skim milk, butter, and sugar had no significant effect on mean faecal pH value. In White children in an institution, the mean pH value of faeces became significantly more acid when a supplement of 6 oranges, although not of bran 'crunchies', was consumed daily. |
MED-1413 | The human oro-gastrointestinal (GI) tract is a complex system, consisting of oral cavity, pharynx, oesophagus, stomach, small intestine, large intestine, rectum and anus, which all together with the accessory digestive organs constitute the digestive system. The function of the digestive system is to break down dietary constituents into small molecules and then absorb these for subsequent distribution throughout the body. Besides digestion and carbohydrate metabolism, the indigenous microbiota has an important influence on host physiological, nutritional and immunological processes, and commensal bacteria are able to modulate the expression of host genes that regulate diverse and fundamental physiological functions. The main external factors that can affect the composition of the microbial community in generally healthy adults include major dietary changes and antibiotic therapy. Changes in some selected bacterial groups have been observed due to controlled changes to the normal diet e.g. high-protein diet, high-fat diet, prebiotics, probiotics and polyphenols. More specifically, changes in the type and quantity of non-digestible carbohydrates in the human diet influence both the metabolic products formed in the lower regions of the GI tract and the bacterial populations detected in faeces. The interactions between dietary factors, gut microbiota and host metabolism are increasingly demonstrated to be important for maintaining homeostasis and health. Therefore the aim of this review is to summarise the effect of diet, and especially dietary interventions, on the human gut microbiota. Furthermore, the most important confounding factors (methodologies used and intrinsic human factors) in relation to gut microbiota analyses are elucidated. |
MED-1414 | Considerable evidence suggests that the carcinogens or co-carcinogens responsible for the development of colorectal cancer are either bacterially degraded bile acids or cholesterol. It is proposed that a high colonic pH promotes co-carcinogen formation from these substances and that acidification of the colon either by dietary fibre (following its bacterial digestion to short-chain fatty acids) or milk (in lactose-intolerant individuals) may prevent this process. |
MED-1415 | BACKGROUND/OBJECTIVES: Consisting of ≈10(14) microbial cells, the intestinal microbiota represents the largest and the most complex microbial community inhabiting the human body. However, the influence of regular diets on the microbiota is widely unknown. SUBJECTS/METHODS: We examined faecal samples of vegetarians (n=144), vegans (n=105) and an equal number of control subjects consuming ordinary omnivorous diet who were matched for age and gender. We used classical bacteriological isolation, identification and enumeration of the main anaerobic and aerobic bacterial genera and computed absolute and relative numbers that were compared between groups. RESULTS: Total counts of Bacteroides spp., Bifidobacterium spp., Escherichia coli and Enterobacteriaceae spp. were significantly lower (P=0.001, P=0.002, P=0.006 and P=0.008, respectively) in vegan samples than in controls, whereas others (E. coli biovars, Klebsiella spp., Enterobacter spp., other Enterobacteriaceae, Enterococcus spp., Lactobacillus spp., Citrobacter spp. and Clostridium spp.) were not. Subjects on a vegetarian diet ranked between vegans and controls. The total microbial count did not differ between the groups. In addition, subjects on a vegan or vegetarian diet showed significantly (P=0.0001) lower stool pH than did controls, and stool pH and counts of E. coli and Enterobacteriaceae were significantly correlated across all subgroups. CONCLUSIONS: Maintaining a strict vegan or vegetarian diet results in a significant shift in the microbiota while total cell numbers remain unaltered. |
MED-1416 | Mean faecal urobilinogen levels and the pH of stools were both found to be higher in subjects from a population group at high risk of developing cancer of the colon than in subjects matched for age, sex and socioeconomic status from a low-risk population group. An alkaline reaction of the colon contents seems to have a tumorigenic effect by a direct action on the mucus of the mucous cells. An acidic reaction, on the other hand, appears to be protective. These differences are dependent on the patterns of diet and manner of eating. Proper mastication of food, roughage, cellulose and vegetable fibre, and short-chain fatty acids of milk and fermented milk products in the diet appear to be protective. |
MED-1417 | Background: Epidemiologic studies have suggested that most cases of sporadic colon cancer can be attributed to diet. The recognition that colonic microbiota have a major influence on colonic health suggests that they might mediate colonic carcinogenesis. Objective: To examine the hypothesis that the influence of diet on colon cancer risk is mediated by the microbiota through their metabolites, we measured differences in colonic microbes and their metabolites in African Americans with a high risk and in rural native Africans with a low risk of colon cancer. Design: Fresh fecal samples were collected from 12 healthy African Americans aged 50–65 y and from 12 age- and sex-matched native Africans. Microbiomes were analyzed with 16S ribosomal RNA gene pyrosequencing together with quantitative polymerase chain reaction of the major fermentative, butyrate-producing, and bile acid–deconjugating bacteria. Fecal short-chain fatty acids were measured by gas chromatography and bile acids by liquid chromatography–mass spectrometry. Results: Microbial composition was fundamentally different, with a predominance of Prevotella in native Africans (enterotype 2) and of Bacteroides in African Americans (enterotype 1). Total bacteria and major butyrate-producing groups were significantly more abundant in fecal samples from native Africans. Microbial genes encoding for secondary bile acid production were more abundant in African Americans, whereas those encoding for methanogenesis and hydrogen sulfide production were higher in native Africans. Fecal secondary bile acid concentrations were higher in African Americans, whereas short-chain fatty acids were higher in native Africans. Conclusion: Our results support the hypothesis that colon cancer risk is influenced by the balance between microbial production of health-promoting metabolites such as butyrate and potentially carcinogenic metabolites such as secondary bile acids. |
MED-1418 | Hydrogen sulfide (H(2)S) is produced by indigenous sulfate-reducing bacteria in the large intestine and represents an environmental insult to the colonic epithelium. Clinical studies have linked the presence of either sulfate-reducing bacteria or H(2)S in the colon with chronic disorders such as ulcerative colitis and colorectal cancer, although at this point, the evidence is circumstantial and underlying mechanisms remain undefined. We showed previously that sulfide at concentrations similar to those found in the human colon induced genomic DNA damage in mammalian cells. The present study addressed the nature of the DNA damage by determining if sulfide is directly genotoxic or if genotoxicity requires cellular metabolism. We also questioned if sulfide genotoxicity is mediated by free radicals and if DNA base oxidation is involved. Naked nuclei from untreated Chinese hamster ovary cells were treated with sulfide; DNA damage was induced by concentrations as low as 1 micromol/L. This damage was effectively quenched by cotreatment with butylhydroxyanisole. Furthermore, sulfide treatment increased the number of oxidized bases recognized by formamidopyrimidine [fapy]-DNA glycosylase. These results confirm the genotoxicity of sulfide and strongly implicate that this genotoxicity is mediated by free radicals. These observations highlight the possible role of sulfide as an environmental insult that, given a predisposing genetic background, may lead to genomic instability or the cumulative mutations characteristic of colorectal cancer. |
MED-1419 | To determine the effects of different diets on the genotoxicity of human faecal water, a diet rich in fat, meat and sugar but poor in vegetables and free of wholemeal products (diet 1) was consumed by seven healthy volunteers over a period of 12 days. One week after the end of this period, the volunteers started to consume a diet enriched with vegetables and wholemeal products but poor in fat and meat (diet 2) over a second period of 12 days. The genotoxic effect of faecal waters obtained after both diets was assessed with the single cell gel electrophoresis (Comet assay) using the human colon adenocarcinoma cell line HT29 clone 19a as a target. The fluorescence and length of the tails of the comet images reflects the degree of DNA damage in single cells. The mean DNA damage, expressed as the ratio of tail intensity (fluorescence in the tail) to total intensity of the comet after incubation with faecal water from volunteers consuming diet 1 was about twice as high as for diet 2. The susceptibility of the cells incubated with faecal water to DNA damage caused by additional hydrogen peroxide treatment showed no significant differences between the two diets. Generation of oxidized pyrimidine and purine bases revealed no differences after pretreatment with both types of faecal water. The results indicate that diets high in fat and meat but low in dietary fibre increase the genotoxicity of faecal water to colonic cells and may contribute to an enhanced risk of colorectal cancer. |
MED-1421 | BACKGROUND: Hydrogen sulfide is a luminally acting, bacterially derived cell poison that has been implicated in ulcerative colitis. Sulfide generation in the colon is probably driven by dietary components such as sulfur-containing amino acids (SAAs) and inorganic sulfur (eg, sulfite). OBJECTIVE: We assessed the contribution of SAAs from meat to sulfide production by intestinal bacteria with use of both a model culture system in vitro and an in vivo human feeding study. DESIGN: Five healthy men were housed in a metabolic suite and fed a sequence of 5 diets for 10 d each. Meat intake ranged from 0 g/d with a vegetarian diet to 600 g/d with a high-meat diet. Fecal sulfide and urinary sulfate were measured in samples collected on days 9 and 10 of each diet period. Additionally, 5 or 10 g bovine serum albumin or casein/L was added to batch cultures inoculated with feces from 4 healthy volunteers. Concentrations of sulfide, ammonia, and Lowry-reactive substances were measured over 48 h. RESULTS: Mean (+/-SEM) fecal sulfide concentrations ranged from 0.22 +/- 0.02 mmol/kg with the 0-g/d diet to 3.38 +/- 0.31 mmol/kg with the 600-g/d diet and were significantly related to meat intake (P: < 0.001). Sulfide formation in fecal batch cultures supplemented with both bovine serum albumin and casein correlated with protein digestion, as measured by the disappearance of Lowry-reactive substances and the appearance of ammonia. CONCLUSION: Dietary protein from meat is an important substrate for sulfide generation by bacteria in the human large intestine. |
MED-1425 | We examined the correlation between the incidence of Crohn disease and dietary change in a relatively homogeneous Japanese population. The incidence and daily intake of each dietary component were compared annually from 1966 to 1985. The univariate analysis showed that the increased incidence of Crohn disease was strongly (P < 0.001) correlated with increased dietary intake of total fat (r = 0.919). animal fat (r = 0.880), n-6 polyunsaturated fatty acids (r = 0.883), animal protein (r = 0.908), milk protein (r = 0.924), and the ratio of n-6 to n-3 fatty acid intake (r = 0.792). It was less correlated with intake of total protein (r = 0.482, P < 0.05), was not correlated with intake of fish protein (r = 0.055, P > 0.1), and was inversely correlated with intake of vegetable protein (r = -0.941, P < 0.001). The multivariate analysis showed that increased intake of animal protein was the strongest independent factor with a weaker second factor, an increased ration of n-6 to n-3 polyunsaturated fatty acids. The present study in association with reported clinical studies suggests that increased dietary intake of animal protein and n-6 polyunsaturated fatty acids with less n-3 polyunsaturated fatty acids may contribute to the development of Crohn disease. |
MED-1431 | Objective: Several studies report that diabetes increases risk of cognitive impairment; some have hypothesized that advanced glycation end products (AGEs) underlie this association. AGEs are cross-linked products that result from reactions between glucose and proteins. Little is known about the association between peripheral AGE concentration and cognitive aging. Methods: We prospectively studied 920 elders without dementia, 495 with diabetes and 425 with normal glucose (mean age 74.0 years). Using mixed models, we examined baseline AGE concentration, measured with urine pentosidine and analyzed as tertile, and performance on the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and repeatedly over 9 years. Incident cognitive impairment (a decline of >1.0 SD on each test) was analyzed with logistic regression. Results: Older adults with high pentosidine level had worse baseline DSST score (p=0.05) but not different 3MS score (p=0.32). On both tests, there was a more pronounced 9-year decline in those with high and mid pentosidine level compared to those in the lowest tertile (3MS 7.0, 5.4, and 2.5 point decline, p overall <0.001; DSST 5.9, 7.4, and 4.5 point decline, p=0.03). Incident cognitive impairment was higher in those with high or mid pentosidine level than those in the lowest tertile (3MS: 24% vs 17%, odds ratio=1.55; 95% confidence interval 1.07–2.26; DSST: 31% vs 22%, odds ratio=1.62; 95% confidence interval 1.13–2.33). There was no interaction between pentosidine level, diabetes status, and cognitive decline. Multivariate adjustment for age, sex, race, education, hypertension, cardiovascular disease, estimated glomerular filtration rate, and diabetes diminished results somewhat but overall patterns remained similar. Conclusion: High peripheral AGE level is associated with greater cognitive decline in older adults with and without diabetes. |
MED-1432 | Sirtuins (SIRTs), a family of nicotinamide adenine dinucleotide (NAD)-dependent deacetylases, are emerging as key molecules that regulate aging and age-related diseases including cancers, metabolic disorders, and neurodegenerative diseases. Seven isoforms of SIRT (SIRT1–7) have been identified in mammals. SIRT1 and 6, mainly localized in the nucleus, regulate transcription of genes and DNA repair. SIRT3 in the mitochondria regulates mitochondrial bioenergetics. Initial studies in yeasts, nematodes, and flies indicated a strong connection of SIRT with the life-prolonging effects of calorie restriction (CR), a robust experimental intervention for longevity in a range of organisms. However, subsequent studies reported controversial findings regarding SIRT roles in the effect of CR. This review describes the functional roles of mammalian SIRTs and discusses their relevance to mechanisms underlying the longevity effect of CR. |
MED-1433 | Advanced glycation end products (AGEs) are a heterogeneous, complex group of compounds that are formed when reducing sugar reacts in a non-enzymatic way with amino acids in proteins and other macromolecules. This occurs both exogenously (in food) and endogenously (in humans) with greater concentrations found in older adults. While higher AGEs occur in both healthy older adults and those with chronic diseases, research is progressing to both quantify AGEs in food and in people, and to identify mechanisms that would explain why some human tissues are damaged, and others are not. In the last twenty years, there has been increased evidence that AGEs could be implicated in the development of chronic degenerative diseases of aging, such as cardiovascular disease, Alzheimer’s disease and with complications of diabetes mellitus. Results of several studies in animal models and humans show that the restriction of dietary AGEs has positive effects on wound healing, insulin resistance and cardiovascular diseases. Recently, the effect of restriction in AGEs intake has been reported to increase the lifespan in animal models. This paper will summarize the work that has been published for both food AGEs and in vivo AGEs and their relation with aging, as well as provide suggestions for future research. |
MED-1434 | Silent information regulator two proteins (sirtuins or SIRTs) are a group of histone deacetylases whose activities are dependent on and regulated by nicotinamide adenine dinucleotide (NAD+). They suppress genome-wide transcription, yet upregulate a select set of proteins related to energy metabolism and pro-survival mechanisms, and therefore play a key role in the longevity effects elicited by calorie restriction. Recently, a neuroprotective effect of sirtuins has been reported for both acute and chronic neurological diseases. The focus of this review is to summarize the latest progress regarding the protective effects of sirtuins, with a focus on SIRT1. We first introduce the distribution of sirtuins in the brain and how their expression and activity are regulated. We then highlight their protective effects against common neurological disorders, such as cerebral ischemia, axonal injury, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis. Finally, we analyze the mechanisms underlying sirtuin-mediated neuroprotection, centering on their non-histone substrates such as DNA repair enzymes, protein kinases, transcription factors, and coactivators. Collectively, the information compiled here will serve as a comprehensive reference for the actions of sirtuins in the nervous system to date, and will hopefully help to design further experimental research and expand sirtuins as therapeutic targets in the future. |
MED-1435 | Age-related loss of brain tissue has been inferred from cross-sectional neuroimaging studies, but direct measurements of gray and white matter changes from longitudinal studies are lacking. We quantified longitudinal magnetic resonance imaging (MRI) scans of 92 nondemented older adults (age 59-85 years at baseline) in the Baltimore Longitudinal Study of Aging to determine the rates and regional distribution of gray and white matter tissue loss in older adults. Using images from baseline, 2 year, and 4 year follow-up, we found significant age changes in gray (p < 0.001) and white (p < 0.001) volumes even in a subgroup of 24 very healthy elderly. Annual rates of tissue loss were 5.4 +/- 0.3, 2.4 +/- 0.4, and 3.1 +/- 0.4 cm3 per year for total brain, gray, and white volumes, respectively, and ventricles increased by 1.4 +/- 0.1 cm3 per year (3.7, 1.3, 2.4, and 1.2 cm3, respectively, in very healthy). Frontal and parietal, compared with temporal and occipital, lobar regions showed greater decline. Gray matter loss was most pronounced for orbital and inferior frontal, cingulate, insular, inferior parietal, and to a lesser extent mesial temporal regions, whereas white matter changes were widespread. In this first study of gray and white matter volume changes, we demonstrate significant longitudinal tissue loss for both gray and white matter even in very healthy older adults. These data provide essential information on the rate and regional pattern of age-associated changes against which pathology can be evaluated and suggest slower rates of brain atrophy in individuals who remain medically and cognitively healthy. |
MED-1436 | PURPOSE OF REVIEW: Sirtuins are a family of enzymes highly conserved in evolution and involved in mechanisms known to promote healthy ageing and longevity. This review aims to discuss recent advances in understanding the role of sirtuins, in particular mammalian SIRT1, in promoting longevity and its potential molecular basis for neuroprotection against cognitive ageing and Alzheimer's disease pathology. RECENT FINDINGS: Accumulative increase in oxidative stress during ageing has been shown to decrease SIRT1 activity in catabolic tissue, possibly by direct inactivation by reactive oxygen. SIRT1 overexpression prevents oxidative stress-induced apoptosis and increases resistance to oxidative stress through regulation of the FOXO family of forkhead transcription factors. In addition, resveratrol strongly stimulates SIRT1 deacetylase activity in a dose-dependent manner by increasing its binding affinity to both the acetylated substrate and NAD(+). Recently, SIRT1 has been shown to affect amyloid production through its influence over the ADAM10 gene. Upregulation of SIRT1 can also induce the Notch pathway and inhibit mTOR signalling. SUMMARY: Recent studies have revealed some of the mechanisms and pathways that are associated with the neuroprotective effects of SIRT1. |
MED-1437 | Longevity, lifespan, cancer, cellular transformation, energy, calorie restriction, diabetes--what can tie together such a diversity of hot topics in biomedical research? Emerging findings suggest that the answer lies in understanding the functions of the recently discovered family of proteins known as Sirtuins. Barcelona hosted the first scientific meeting completely focused on these evolutionary conserved protein deacetylases, bringing together experts in the biochemistry to cellular biology, mice models, drug targeting and pathophysiology of these molecules. Their work, summarized here, establishes the Sirtuins as major players in cellular homeostasis and human diseases that act through a whole range of biochemical substrates and physiological processes. Undoubtedly, this is an increasingly expanding field that it is here to stay and growth. |
MED-1438 | Background Advanced glycations end products increase oxidant stress, inflammation, and neurotoxicity. Serum levels are increased in diabetes and aging. We examined the relationship between serum methylglyoxal derivatives (sMG), and cognitive decline, in 267 non-demented elderly. Methods Tobit mixed regression models assessed the association of baseline sMG with cognitive decline in the Mini Mental State Exam (MMSE) over time, controlling for sociodemographic factors (age, sex, and years of education), cardiovascular risk factors (diabetes and presence of an APOE4 allele), and kidney function. sMG was assessed by ELISA. Results The fully adjusted model showed an annual decline of 0.26 MMSE points per unit increase in baseline sMG (p=0.03). Significance was unchanged as additional risk factors were added to the model. The interactions of sMG with diabetes, sex, age, kidney function, and APOE4 genotype were not significant. Conclusions Higher levels of baseline sMG were associated with a faster rate of cognitive decline, after adjusting for several sociodemographic and clinical characteristics. This relationship did not differ by sex, APOE4 genotype, or diabetes status suggesting its generality. Since subjects were cognitively normal at the beginning of the study, elevated sMG may be indicative of brain cell injury initiated before clinically evident cognitive compromise. |
MED-1439 | BACKGROUND AND PURPOSE: The purpose of this study is to investigate the longitudinal age-related changes in human brain volume using stereological methods. METHODS: Sixty-six older participants (34 men, 32 women, age [mean +/- SD] 78.9 +/- 3.3 years, range 74-87 years) with normal baseline and follow-up examinations underwent 2 MRIs (magnetic resonance imaging) of the brain on average 4.4 years apart. The volumes of the cerebrum (defined as cortex, basal ganglia, thalamus, and white matter), lateral ventricles, and cerebellum were estimated on the 2 MRIs using an unbiased stereological method (Cavalieri principle). RESULTS: The annual decrease (mean +/- SD) of the cerebral volume was 2.1% +/- 1.6% (P < .001). The average volume of the lateral ventricles on the second MRI was increased by 5.6% +/- 3.6% per year (P < .001). The average volume of the cerebellum on the second MRI was decreased by 1.2% +/- 2.2% per year (P < .001). Even though the average cerebral volume was significantly different between men and women on initial MRI and second MRI, the percentage change of the age-related cerebral volume decrease in male and female brains between initial MRI and second MRI were identical. CONCLUSIONS: The findings showed that there was age-related atrophy of cerebrum and cerebellum and age-related disproportional enlargement of lateral ventricles in normal older men and women. |
MED-1440 | Aging and metabolism-related disorders are risk factors for Alzheimer disease (AD). Since sirtuins may increase the lifespan through regulation of cellular metabolism, we compared the concentration of sirtuin 1 (SIRT1) in the brains of AD patients (n = 19) and controls (n = 22) using Western immunoblots and in situ hybridization. We report a significant reduction of SIRT1 (mRNA: −29%; protein: −45%) in the parietal cortex of AD patients, but not in the cerebellum. Further analyses in a second cohort of 36 subjects confirmed that cortical SIRT1 was decreased in the cortex of AD patients but not in individuals with mild cognitive impairment. SIRT1 mRNA and its translated protein correlated negatively with the duration of symptoms (mRNA: r2 = −0.367; protein: r2 = −0.326) and the accumulation of paired helical filament tau (mRNA: r2 = −0.230; protein: r2 = −0.119), but weakly with insoluble amyloid-β(Aβ42 (mRNA: r2 = −0.090; protein: r2 = −0.072). A significant relationship between SIRT1 levels and global cognition scores proximate to death was also found (r2 = +0.09; p = 0.049). In contrast, cortical SIRT1 levels remained unchanged in a triple-transgenic animal model of AD. Collectively, our results indicate that loss of SIRT1 is closely associated with the accumulation of Aβ and tau in the cerebral cortex of patients with AD. |
MED-1441 | Most ethnic foods and cooking practices have incorporated the use of spices and other food additives. Many common spices have crossed cultural boundaries and appear in multiple ethnic cuisines. Recent studies have demonstrated that many of these ingredients possess antimicrobial properties against common food spoilage microorganisms. We developed a laboratory exercise that promotes the use of scientific methodology to evaluate the effectiveness of salsa components at inhibiting the growth of undesirable microorganisms. Tomato, onion, garlic, cilantro, and jalapeño were tested for antimicrobial properties against a representative fungus, Saccharomyces cerevisiae, and the common food spoilage bacteria Staphylococcus aureus, Bacillus cereus, and Escherichia coli. Each component was ethanol extracted and a modification of the Kirby-Bauer method of antimicrobial sensitivity was employed. Garlic demonstrated the greatest inhibitory effects against all organisms tested. Onion demonstrated a slight inhibition of all four organisms, while cilantro showed some inhibition of all three bacteria but no effect against the fungus. Jalapeño may have slightly inhibited E. coli and S. aureus, as evidenced by a consistently measured increase in the zone of inhibition that was not statistically significant when compared to that of the control. Following the initial exercise, students were given the opportunity to repeat the exercise using other spices such as cinnamon, clove, nutmeg, and coriander. Student learning outcomes were evaluated using preliminary and secondary surveys, mainly focusing on definitions of science and hypothesis as well as the process of science. Students enjoyed this exercise and met the learning goals of understanding the process and methodology of science, as well as the interdisciplinarity inherent in the sciences. Student learning was evidenced by an increase in the number of correct responses on the secondary survey in comparison to the preliminary. |
MED-1442 | We explored genetic influences on the perception of taste and smell stimuli. Adult twins rated the chemosensory aspects of water, sucrose, sodium chloride, citric acid, ethanol, quinine hydrochloride, phenylthiocarbamide (PTC), potassium chloride, calcium chloride, cinnamon, androstenone, Galaxolide™, cilantro, and basil. For most traits, individual differences were stable over time and some traits were heritable (h2 from 0.41 to 0.71). Subjects were genotyped for 44 single nucleotide polymorphisms within and near genes related to taste and smell. The results of these association analyses confirmed previous genotype–phenotype results for PTC, quinine, and androstenone. New associations were detected for ratings of basil and a bitter taste receptor gene, TAS2R60, and between cilantro and variants in three genes (TRPA1, GNAT3, and TAS2R50). The flavor of ethanol was related to variation within an olfactory receptor gene (OR7D4) and a gene encoding a subunit of the epithelial sodium channel (SCNN1D). Our study demonstrates that person-to-person differences in the taste and smell perception of simple foods and drinks are partially accounted for by genetic variation within chemosensory pathways. |