title: Contribution of dietary protein to sulfide production in the large intestine: an in vitro and a controlled feeding study in humans.

text: 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.


title: Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the inc...

text: 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.


title: Influence of dietary protein supplements on the formation of bacterial metabolites in the colon.

text: BACKGROUND: To evaluate the influence of increased dietary protein intake on bacterial colonic metabolism in healthy volunteers. METHODS: Short chain fatty acids, ammonia, and volatile organic compounds in faecal samples, and phenols in the urine of five volunteers were measured after one week of basal nutrient intake and and after one week of a diet supplemented with a protein rich food (Fortimel; Nutricia, Zoetermeer, The Netherlands). Paired t tests and factor analysis were used for statistical analysis. RESULTS: Total energy and resistant carbohydrate intake remained unchanged in each study period. The percentage energy intake delivered as dietary protein, increased significantly (from 15.4% to 23.8%; p = 0.007) during supplement intake. A significant increase in faecal ammonia (p = 0.002), faecal valeric acid (p = 0.02), and urinary p-cresol (p = 0.04) was noted during supplementary protein intake. A total of 120 different volatile compounds were isolated from the faecal samples of which 10 increased significantly during dietary protein supplementation. The change in volatile pattern, especially for S containing metabolites, was clearly shown by a factor analysis model which made a distinction between the two dietary regimens for all volunteers. CONCLUSION: An increase in dietary protein leads to altered products formation by colonic metabolism, mainly reflected by an increase in faecal ammonia, faecal volatile S substances, and urinary p-cresol.


title: Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal.

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


title: Thematic review series: the pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy, part V: the discovery of the s...

text: The first four reviews in this series (Steinberg, D. 2004. J. Lipid Res. 45: 1583-1593; Steinberg, D. 2005. J. Lipid Res. 46: 179-190; Steinberg, D. 2005. J. Lipid Res. 46: 2037-2051; Steinberg, D. 2006. J. Lipid Res. 47: 1-14) traced the gradual accumulation of evidence, evidence of several different kinds, supporting the lipid hypothesis. They tracked the history from Anitschkow's 1913 classic work on the cholesterol-fed rabbit model to the breakthrough 1984 Coronary Primary Prevention Trial, the first large, randomized, double-blind primary intervention trial showing that decreasing blood cholesterol (using cholestyramine) significantly reduces coronary heart disease events. At that point, for the first time, decreasing blood cholesterol levels became an official national public health goal. Still, only a small fraction of patients at high risk were getting appropriate cholesterol-lowering treatment, and a number of important clinical questions remained unanswered. This final review in the series traces the early studies that led to the discovery of the statins and briefly reviews the now familiar large-scale clinical trials demonstrating their safety and their remarkable effectiveness in reducing coronary heart disease morbidity and mortality.


title: Vegetarian diet and cholesterol and triglycerides levels.

text: OBJECTIVE: Compare levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL) and high density lipoprotein (HDL) among vegetarians and omnivores. METHODS: Blood samples were collected from 76 individuals--both males and females--separated in four different diet groups: omnivores, lacto-ovo vegetarians, lacto vegetarians, and restricted vegetarians (or vegans). Dosing was done for: TC, LDL, HDL and TG. RESULTS: Significant difference was reported for TC, LDL and TG levels among the samples. Higher levels were reported by omnivores, with decreased levels for vegetarians as animal products were restricted, with lowest levels having been reported by vegans. Mean and standard deviation for TC were 208.09 +/- 49.09 mg/dl in the group of omnivores, and 141.06 +/- 30.56 mg/dl in the group of vegans (p < 0.001). LDL values for omnivores and vegans were respectively: 123.43 +/- 42.67 mg/dl and 69.28 +/- 29.53 mg/dl (p < 0.001). As for TG, those values were 155.68 +/- 119.84 mg/dl and 81.67 +/- 81.90 mg/dl (p < 0.01). As for HDL level no difference was reported between the samples, but HDL/TC ratio was significantly higher in vegans (p = 0.01). CONCLUSION: Vegetarian diet was associated to lower levels of TG, TC and LDL as compared to the diet of omnivores.


title: Advanced glycation end product level, diabetes, and accelerated cognitive aging

text: 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.


title: Do Sirtuins Promote Mammalian Longevity?: A Critical Review on Its Relevance to the Longevity Effect Induced by Calorie Restriction

text: 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.


title: Dietary Advanced Glycation End Products and Aging

text: 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.


title: Protective effects and mechanisms of sirtuins in the nervous system

text: 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.


title: Longitudinal magnetic resonance imaging studies of older adults: a shrinking brain.

text: 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.


title: Sirtuins in cognitive ageing and Alzheimer's disease.

text: 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.


title: At the crossroad of lifespan, calorie restriction, chromatin and disease: meeting on sirtuins.

text: 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.


title: Serum concentration of an inflammatory glycotoxin, methylglyoxal, is associated with increased cognitive decline in elderly individuals

text: 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.


title: Brain volume changes on longitudinal magnetic resonance imaging in normal older people.

text: 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.


title: SIRT1 Decrease Parallels the Accumulation of tau in Alzheimer Disease

text: 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.


title: The Science of Salsa: Antimicrobial Properties of Salsa Components to Learn Scientific Methodology

text: 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.


title: Genetic Analysis of Chemosensory Traits in Human Twins

text: 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.


title: Anti-inflammatory potential of a lipolotion containing coriander oil in the ultraviolet erythema test.

text: SUMMARY BACKGROUND: Coriander oil is used as an antimicrobial agent and as a natural fragrance. The present study investigated the anti-inflammatory potency of coriander oil in the ultraviolet (UV) erythema test in vivo. METHODS: 40 volunteers were enrolled in this monocentric,randomized,placebo-controlled double-blind study.Test areas on the back were irradiated with the 1.5 fold minimal erythema dose UV-B. Subsequently, the test areas were treated under occlusion for 47 hours with a lipolotion containing 0.5% or 1.0% essential coriander oil. Hydrocortisone (1.0%) and betamethasone valerate (0.1%) in the vehicle served as positive controls.The vehicle was used as place-bo.The effect of the test substances on the UV-induced erythema was measured photometrically after 48 hours.Additionally,the skin tolerance of the test preparations was assessed on non-irradiated skin. RESULTS: Compared to placebo, the lipolotion with 0.5% coriander oil significantly reduced the UV-induced erythema, but it was not as effective as hydrocortisone. The skin tolerance of both coriander oil concentrations was excellent. CONCLUSIONS: The lipolotion containing coriander oil displayed a mild antiinflammatory effect in this study. It could be useful in the concomitant treatment of inflammatory skin diseases.


title: Coriander (Coriandrum sativum L.): a potential source of high-value components for functional foods and nutraceuticals--a review.

text: Coriander (Coriandrum sativum L.), a herbal plant, belonging to the family Apiceae, is valued for its culinary and medicinal uses. All parts of this herb are in use as flavoring agent and/or as traditional remedies for the treatment of different disorders in the folk medicine systems of different civilizations. The plant is a potential source of lipids (rich in petroselinic acid) and an essential oil (high in linalool) isolated from the seeds and the aerial parts. Due to the presence of a multitude of bioactives, a wide array of pharmacological activities have been ascribed to different parts of this herb, which include anti-microbial, anti-oxidant, anti-diabetic, anxiolytic, anti-epileptic, anti-depressant, anti-mutagenic, anti-inflammatory, anti-dyslipidemic, anti-hypertensive, neuro-protective and diuretic. Interestingly, coriander also possessed lead-detoxifying potential. This review focuses on the medicinal uses, detailed phytochemistry, and the biological activities of this valuable herb to explore its potential uses as a functional food for the nutraceutical industry. Copyright © 2012 John Wiley & Sons, Ltd.


title: The effects of a low-fat, plant-based dietary intervention on body weight, metabolism, and insulin sensitivity.

text: PURPOSE: This study investigated the effect of a low-fat, plant-based diet on body weight, metabolism, and insulin sensitivity, while controlling for exercise in free-living individuals. SUBJECTS AND METHODS: In an outpatient setting, 64 overweight, postmenopausal women were randomly assigned to a low-fat, vegan diet or a control diet based on National Cholesterol Education Program guidelines, without energy intake limits, and were asked to maintain exercise unchanged. Dietary intake, body weight and composition, resting metabolic rate, thermic effect of food, and insulin sensitivity were measured at baseline and 14 weeks. RESULTS: Mean +/- standard deviation intervention-group body weight decreased 5.8 +/- 3.2 kg, compared with 3.8 +/- 2.8 kg in the control group (P = .012). In a regression model of predictors of weight change, including diet group and changes in energy intake, thermic effect of food, resting metabolic rate, and reported energy expenditure, significant effects were found for diet group (P < .05), thermic effect of food (P < .05), and resting metabolic rate (P < .001). An index of insulin sensitivity increased from 4.6 +/- 2.9 to 5.7 +/- 3.9 (P = .017) in the intervention group, but the difference between groups was not significant (P = .17). CONCLUSION: Adoption of a low-fat, vegan diet was associated with significant weight loss in overweight postmenopausal women, despite the absence of prescribed limits on portion size or energy intake.


title: Longitudinal association between animal and vegetable protein intake and obesity among adult males in the United States: the Chicago Western Electric Study

text: Literature on the association of protein intake with body weight is inconsistent. Little is known about the relation of long-term protein intake to obesity. This study aimed to determine the association between protein intake and obesity. A cohort of 1,730 employed white men ages 40–55 years from the Chicago Western Electric Study was followed from 1958 to 1966. Diet was assessed twice with Burke’s comprehensive diet history method, at two baseline examinations; height, weight, and other covariates were measured annually by trained interviewers. Generalized estimating equation (GEE) was used to examine the relation of baseline total, animal, and vegetable protein intake to likelihood of being overweight or obese at sequential annual examinations. Dietary animal protein was positively related to overweight and obesity over seven years of follow up. With adjustment for potential confounders (age, education, cigarette smoking, alcohol intake, energy, carbohydrate and saturated fat intake, and history of diabetes or other chronic disease), the odds ratios (95% confidence intervals) for obesity were 4.62 (2.68–7.98, p for trend<0.01) for participants in the highest compared to the lowest quartile of animal protein and 0.58 (0.36, 0.95, p for trend=0.053) for those in the highest quartile of vegetable protein intake. A statistically significant, positive association was seen between animal protein intake and obesity; those in higher quartiles of vegetable protein intake had lower odds of being obese. These results indicate that animal and vegetable protein may relate differently to occurrence of obesity in the long run.


title: Nutrient intake in the GEICO multicenter trial: the effects of a multicomponent worksite intervention

text: Background/objectives: To assess the effects on macro- and micronutrient intake of a nutrition intervention program in corporate settings across the United States. Subjects/methods: Two hundred and ninety-two individuals who were overweight or had type 2 diabetes were recruited from 10 sites of a US insurance company. Two hundred and seventy-one participants completed baseline diet recalls, and 183 participants completed dietary recalls at 18 weeks. Sites were randomly assigned to an intervention group (five sites) or to a control group (five sites) for 18 weeks. At intervention sites, participants were asked to follow a low-fat vegan diet and attend weekly group meetings. At control sites, participants continued their usual diets. At baseline and 18 weeks, participants completed 2-day diet recalls. Between-group differences in changes in nutrient intake were assessed using an analysis of covariance. Results: Compared with those in the control group, intervention-group participants significantly reduced the reported intake of total fat (P=0.02), saturated (P=0.006) and monounsaturated fats (P=0.01), cholesterol (P=0.009), protein (P=0.03) and calcium (P=0.02), and increased the intake of carbohydrate (P=0.006), fiber (P=0.002), β-carotene (P=0.01), vitamin C (P=0.003), magnesium (P=0.04) and potassium (P=0.002). Conclusions: An 18-week intervention program in a corporate setting reduces intake of total fat, saturated fat and cholesterol and increases the intake of protective nutrients, particularly fiber, β-carotene, vitamin C, magnesium and potassium. The reduction in calcium intake indicates the need for planning for this nutrient.


title: The costs of obesity in the workplace.

text: OBJECTIVE: To quantify per capita and aggregate medical expenditures and the value of lost productivity, including absenteeism and presenteeism, because of overweight, and grade I, II, and III obesity among U.S. employees. METHODS: Cross-sectional analysis of the 2006 Medical Expenditure Panel Survey and the 2008 National Health and Wellness Survey. RESULTS: Among men, estimates range from -$322 for overweight to $6087 for grade III obese men. For women, estimates range from $797 for overweight to $6694 for grade III. In aggregate, the annual cost attributable to obesity among full-time employees is $73.1 billion. Individuals with a body mass index >35 represent 37% of the obese population but are responsible for 61% of excess costs. CONCLUSIONS: Successful efforts to reduce the prevalence of obesity, especially among those with a body mass index >35, could result in significant savings to employers.


title: Workplace wellness programs can generate savings.

text: Amid soaring health spending, there is growing interest in workplace disease prevention and wellness programs to improve health and lower costs. In a critical meta-analysis of the literature on costs and savings associated with such programs, we found that medical costs fall by about $3.27 for every dollar spent on wellness programs and that absenteeism costs fall by about $2.73 for every dollar spent. Although further exploration of the mechanisms at work and broader applicability of the findings is needed, this return on investment suggests that the wider adoption of such programs could prove beneficial for budgets and productivity as well as health outcomes.


title: A multicenter randomized controlled trial of a plant-based nutrition program to reduce body weight and cardiovascular risk in the corporate setting: the GEICO study

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


title: The link between workforce health and safety and the health of the bottom line: tracking market performance of companies that nurture a "culture of...

text: OBJECTIVE: To test the hypothesis that comprehensive efforts to reduce a workforce's health and safety risks can be associated with a company's stock market performance. METHODS: Stock market performance of Corporate Health Achievement Award winners was tracked under four different scenarios using simulation and past market performance. RESULTS: A portfolio of companies recognized as award winning for their approach to the health and safety of their workforce outperformed the market. Evidence seems to support that building cultures of health and safety provides a competitive advantage in the marketplace. This research may have also identified an association between companies that focus on health and safety and companies that manage other aspects of their business equally well. CONCLUSIONS: Companies that build a culture of health by focusing on the well-being and safety of their workforce yield greater value for their investors.


title: Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU Study.

text: AIMS/HYPOTHESIS: The amount and quality of fat in the diet could be of importance for development of insulin resistance and related metabolic disorders. Our aim was to determine whether a change in dietary fat quality alone could alter insulin action in humans. METHODS: The KANWU study included 162 healthy subjects chosen at random to receive a controlled, isoenergetic diet for 3 months containing either a high proportion of saturated (SAFA diet) or monounsaturated (MUFA diet) fatty acids. Within each group there was a second assignment at random to supplements with fish oil (3.6 g n-3 fatty acids/d) or placebo. RESULTS: Insulin sensitivity was significantly impaired on the saturated fatty acid diet (-10%, p = 0.03) but did not change on the monounsaturated fatty acid diet (+2%, NS) (p = 0.05 for difference between diets). Insulin secretion was not affected. The addition of n-3 fatty acids influenced neither insulin sensitivity nor insulin secretion. The favourable effects of substituting a monounsaturated fatty acid diet for a saturated fatty acid diet on insulin sensitivity were only seen at a total fat intake below median (37E%). Here, insulin sensitivity was 12.5% lower and 8.8% higher on the saturated fatty acid diet and monounsaturated fatty acid diet respectively (p = 0.03). Low density lipoprotein cholesterol (LDL) increased on the saturated fatty acid diet (+4.1%, p < 0.01) but decreased on the monounsaturated fatty acid diet (MUFA) (-5.2, p < 0.001), whereas lipoprotein (a) [Lp(a)] increased on a monounsaturated fatty acid diet by 12% (p < 0.001). CONCLUSIONS/INTERPRETATION: A change of the proportions of dietary fatty acids, decreasing saturated fatty acid and increasing monounsaturated fatty acid, improves insulin sensitivity but has no effect on insulin secretion. A beneficial impact of the fat quality on insulin sensitivity is not seen in individuals with a high fat intake (> 37E%).


title: Lipotoxicity: Effects of Dietary Saturated and Transfatty Acids

text: The ingestion of excessive amounts of saturated fatty acids (SFAs) and transfatty acids (TFAs) is considered to be a risk factor for cardiovascular diseases, insulin resistance, dyslipidemia, and obesity. The focus of this paper was to elucidate the influence of dietary SFA and TFA intake on the promotion of lipotoxicity to the liver and cardiovascular, endothelial, and gut microbiota systems, as well as on insulin resistance and endoplasmic reticulum stress. The saturated and transfatty acids favor a proinflammatory state leading to insulin resistance. These fatty acids can be involved in several inflammatory pathways, contributing to disease progression in chronic inflammation, autoimmunity, allergy, cancer, atherosclerosis, hypertension, and heart hypertrophy as well as other metabolic and degenerative diseases. As a consequence, lipotoxicity may occur in several target organs by direct effects, represented by inflammation pathways, and through indirect effects, including an important alteration in the gut microbiota associated with endotoxemia. Interactions between these pathways may perpetuate a feedback process that exacerbates an inflammatory state. The importance of lifestyle modification, including an improved diet, is recommended as a strategy for treatment of these diseases.


title: Veganism and its relationship with insulin resistance and intramyocellular lipid.

text: OBJECTIVE: To test the hypothesis that dietary factors in the vegan diet lead to improved insulin sensitivity and lower intramyocellular lipid (IMCL) storage. DESIGN: Case-control study. SETTING: Imperial College School of Medicine, Hammersmith Hospital Campus, London, UK. SUBJECTS: A total of 24 vegans and 25 omnivores participated in this study; three vegan subjects could not be matched therefore the matched results are shown for 21 vegans and 25 omnivores. The subjects were matched for gender, age and body mass index (BMI). INTERVENTIONS: Full anthropometry, 7-day dietary assessment and physical activity levels were obtained. Insulin sensitivity (%S) and beta-cell function (%B) were determined using the homeostatic model assessment (HOMA). IMCL levels were determined using in vivo proton magnetic resonance spectroscopy; total body fat content was assessed by bioelectrical impedance. RESULTS: There was no difference between the groups in sex, age, BMI, waist measurement, percentage body fat, activity levels and energy intake. Vegans had a significantly lower systolic blood pressure (-11.0 mmHg, CI -20.6 to -1.3, P=0.027) and higher dietary intake of carbohydrate (10.7%, CI 6.8-14.5, P<0.001), nonstarch polysaccharides (20.7 g, CI 15.8-25.6, P<0.001) and polyunsaturated fat (2.8%, CI 1.0-4.6, P=0.003), with a significantly lower glycaemic index (-3.7, CI -6.7 to -0.7, P=0.01). Also, vegans had lower fasting plasma triacylglycerol (-0.7 mmol/l, CI -0.9 to -0.4, P<0.001) and glucose (-0.4 mmol/l, CI -0.7 to -0.09, P=0.05) concentrations. There was no significant difference in HOMA %S but there was with HOMA %B (32.1%, CI 10.3-53.9, P=0.005), while IMCL levels were significantly lower in the soleus muscle (-9.7, CI -16.2 to -3.3, P=0.01). CONCLUSION: Vegans have a food intake and a biochemical profile that will be expected to be cardioprotective, with lower IMCL accumulation and beta-cell protective.


title: A high-fat diet coordinately downregulates genes required for mitochondrial oxidative phosphorylation in skeletal muscle.

text: Obesity and type 2 diabetes have been associated with a high-fat diet (HFD) and reduced mitochondrial mass and function. We hypothesized a HFD may affect expression of genes involved in mitochondrial function and biogenesis. To test this hypothesis, we fed 10 insulin-sensitive males an isoenergetic HFD for 3 days with muscle biopsies before and after intervention. Oligonucleotide microarray analysis revealed 297 genes were differentially regulated by the HFD (Bonferonni adjusted P < 0.001). Six genes involved in oxidative phosphorylation (OXPHOS) decreased. Four were members of mitochondrial complex I: NDUFB3, NDUFB5, NDUFS1, and NDUFV1; one was SDHB in complex II and a mitochondrial carrier protein SLC25A12. Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC1) alpha and PGC1beta mRNA were decreased by -20%, P < 0.01, and -25%, P < 0.01, respectively. In a separate experiment, we fed C57Bl/6J mice a HFD for 3 weeks and found that the same OXPHOS and PGC1 mRNAs were downregulated by approximately 90%, cytochrome C and PGC1alpha protein by approximately 40%. Combined, these results suggest a mechanism whereby HFD downregulates genes necessary for OXPHOS and mitochondrial biogenesis. These changes mimic those observed in diabetes and insulin resistance and, if sustained, may result in mitochondrial dysfunction in the prediabetic/insulin-resistant state.


title: Higher insulin sensitivity in vegans is not associated with higher mitochondrial density.

text: BACKGROUND/OBJECTIVES: Vegans have a lower incidence of insulin resistance (IR)-associated diseases and a higher insulin sensitivity (IS) compared with omnivores. The aim of this study was to examine whether the higher IS in vegans relates to markers of mitochondrial biogenesis and to intramyocellular lipid (IMCL) content. SUBJECTS/METHODS: Eleven vegans and 10 matched (race, age, sex, body mass index, physical activity and energy intake) omnivorous controls were enrolled in a case-control study. Anthropometry, bioimpedance (BIA), ultrasound measurement of visceral and subcutaneous fat layer, parameters of glucose and lipid homeostasis, hyperinsulinemic euglycemic clamp and muscle biopsies were performed. Citrate synthase (CS) activity, mitochondrial DNA (mtDNA) and IMCL content were assessed in skeletal muscle samples. RESULTS: Both groups were comparable in anthropometric and BIA parameters, physical activity and protein-energy intake. Vegans had significantly higher glucose disposal (M-value, vegans 8.11±1.51 vs controls 6.31±1.57 mg/kg/min, 95% confidence interval: 0.402 to 3.212, P=0.014), slightly lower IMCL content (vegans 13.91 (7.8 to 44.0) vs controls 17.36 (12.4 to 78.5) mg/g of muscle, 95% confidence interval: -7.594 to 24.550, P=0.193) and slightly higher relative muscle mtDNA amount (vegans 1.36±0.31 vs controls 1.13±0.36, 95% confidence interval:-0.078 to 0.537, P=0.135). No significant differences were found in CS activity (vegans 18.43±5.05 vs controls 18.16±5.41 μmol/g/min, 95% confidence interval: -4.503 to 5.050, P=0.906). CONCLUSIONS: Vegans have a higher IS, but comparable mitochondrial density and IMCL content with omnivores. This suggests that a decrease in whole-body glucose disposal may precede muscle lipid accumulation and mitochondrial dysfunction in IR development.


title: Integrating Mechanisms for Insulin Resistance: Common Threads and Missing Links

text: Insulin resistance is a complex metabolic disorder that defies a single etiological pathway. Accumulation of ectopic lipid metabolites, activation of the unfolded protein response (UPR) pathway and innate immune pathways have all been implicated in the pathogenesis of insulin resistance. However, these pathways are also closely linked to changes in fatty acid uptake, lipogenesis, and energy expenditure that can impact ectopic lipid deposition. Ultimately, accumulation of specific lipid metabolites (diacylglycerols and/or ceramides) in liver and skeletal muscle, may be a common pathway leading to impaired insulin signaling and insulin resistance.


title: Mechanisms underlying skeletal muscle insulin resistance induced by fatty acids: importance of the mitochondrial function

text: Insulin resistance condition is associated to the development of several syndromes, such as obesity, type 2 diabetes mellitus and metabolic syndrome. Although the factors linking insulin resistance to these syndromes are not precisely defined yet, evidence suggests that the elevated plasma free fatty acid (FFA) level plays an important role in the development of skeletal muscle insulin resistance. Accordantly, in vivo and in vitro exposure of skeletal muscle and myocytes to physiological concentrations of saturated fatty acids is associated with insulin resistance condition. Several mechanisms have been postulated to account for fatty acids-induced muscle insulin resistance, including Randle cycle, oxidative stress, inflammation and mitochondrial dysfunction. Here we reviewed experimental evidence supporting the involvement of each of these propositions in the development of skeletal muscle insulin resistance induced by saturated fatty acids and propose an integrative model placing mitochondrial dysfunction as an important and common factor to the other mechanisms.


title: Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy as...

text: Insulin resistance is the best prediction factor for the clinical onset of type 2 diabetes. It was suggested that intramuscular triglyceride store may be a primary pathogenic factor for its development. To test this hypothesis, 14 young lean offspring of type 2 diabetic parents, a model of in vivo insulin resistance with increased risk to develop diabetes, and 14 healthy subjects matched for anthropomorphic parameters and life habits were studied with 1) euglycemic-hyperinsulinemic clamp to assess whole body insulin sensitivity, 2) localized 1H nuclear magnetic resonance (NMR) spectroscopy of the soleus (higher content of fiber type I, insulin sensitive) and tibialis anterior (higher content of fiber type IIb, less insulin sensitive) muscles to assess intramyocellular triglyceride content, 3) 13C NMR of the calf subcutaneous adipose tissue to assess composition in saturated/unsaturated carbons of triglyceride fatty acid chains, and 4) dual X-ray energy absorption to assess body composition. Offspring of diabetic parents, notwithstanding normal fat content and distribution, were characterized by insulin resistance and increased intramyocellular triglyceride content in the soleus (P < 0.01) but not in the tibialis anterior (P = 0.19), but showed a normal content of saturated/unsaturated carbons in the fatty acid chain of subcutaneous adipocytes. Stepwise regression analysis selected intramyocellular triglyceride soleus content and plasma free fatty acid levels as the main predictors of whole body insulin sensitivity. In conclusion, 1H and 13C NMR spectroscopy revealed intramyocellular abnormalities of lipid metabolism associated with whole body insulin resistance in subjects at high risk of developing diabetes, and might be useful tools for noninvasively monitoring these alterations in diabetes and prediabetic states.


title: Role of insulin in the pathogenesis of free fatty acid-induced insulin resistance in skeletal muscle.

text: Insulin resistance is a pathophysiological link of obesity to type 2 diabetes. The initial cause of insulin resistance is critical for prevention and treatment of type 2 diabetes. Lipotoxicity is a well-known concept in the explanation of initiation of insulin resistance. Although there are several prevailing hypotheses about the cellular/molecular mechanisms of lipotoxicity, such as inflammation, oxidative stress, hyperinsulinemia, and ER stress, the relative importance of these hypothesized events remains to be determined. The role of hyperinsulinemia is relatively under documented in the literature for the initiation of insulin resistance. In this review, an interaction of fatty acid and beta-cells, and a synergy between free fatty acids (FFAs) and insulin are emphasized for the role of hyperinsulinemia. This article presents the evidence about FFA-induced insulin secretion in vitro and in vivo, recent advances in the molecular mechanism of FFA action in beta-cells, a role of GPR40 in the development of insulin resistance, and the negative feedback loop of the insulin receptor signal pathway. The negative feedback loop is discussed in detail with a focus on IRS-1 serine kinases. This article provides a substantial support for the role of insulin in the early stages of FFA-associated insulin resistance. The hypothesis of insulin's role in lipotoxicity is referred to as the "insulin hypothesis" in this review. According to this hypothesis, prevention of increased beta-cell response to glucose may be a potential approach for early intervention of metabolic syndrome.


title: Fasting plasma free fatty acids and risk of type 2 diabetes: the atherosclerosis risk in communities study.

text: OBJECTIVE: To evaluate whether plasma levels of free fatty acids (FFAs) are independently associated with incidence of type 2 diabetes. RESEARCH DESIGN AND METHODS: A case-cohort design was used to randomly select 580 incident cases of diabetes and 566 noncases from 10,275 African-American and white men and women in the Atherosclerosis Risk in Communities study, aged 45-64 years and without prevalent diabetes at the baseline exam. Incident diabetes was ascertained at three exams over 9 years of follow-up. FFA levels were measured in plasma samples collected at the baseline exam. RESULTS: At baseline, FFA level was inversely associated with height and positively associated with female sex, BMI, waist circumference, waist-to-hip ratio, heart rate, plasma triglycerides, and an inflammation score quantifying levels of six systemic inflammation markers. Relative risks for incident diabetes (fourth vs. first quartile of FFAs) were increased in a basic model adjusted for age, sex, race, and center (hazard ratio 1.68, 95% CI 1.20-2.34) and in a model further adjusted for baseline fasting glucose, insulin, BMI, waist circumference, triglycerides, and the inflammation score (1.63, 1.04-2.57). Relative risks associated with a greater FFA level were lowest among those of normal weight and highest among the obese, but a formal test of interaction between FFAs and BMI was not statistically significant. CONCLUSIONS: Individuals with higher fasting levels of plasma FFAs were at modestly higher risk of type 2 diabetes in this cohort of middle-aged adults.


title: Effects of intravenous and dietary lipid challenge on intramyocellular lipid content and the relation with insulin sensitivity in humans.

text: An increased intramyocellular lipid (IMCL) content, as quantified by (1)H-magnetic resonance spectroscopy ((1)H-MRS), is associated with reduced insulin sensitivity. At present, it is unclear which factors determine IMCL formation and how rapidly IMCL accumulation can be induced. We therefore studied the impact of hyperinsulinemia and elevated circulating nonesterified fatty acid (NEFA) levels on IMCL formation and insulin sensitivity. We further evaluated the influence of a high-fat diet on IMCL storage. In the infusion protocol, 12 healthy male subjects underwent a 6-h hyperinsulinemic-euglycemic glucose clamp with concomitant infusion of Intralipid plus heparin. IMCL was quantified by (1)H-MRS in soleus (SOL) and tibialis anterior (TA) muscle at baseline and then every hour. IMCL levels started to increase significantly after 2 h, reaching a maximum of 120.8 +/- 3.4% (SOL) and 164.2 +/- 13.8% (TA) of baseline after 6 h (both P < 0.05). In parallel, the glucose infusion rate (GIR) decreased progressively, reaching a minimum of 60.4 +/- 5.4% of baseline after 6 h. Over time, the GIR was strongly correlated with IMCL in TA (r = -0.98, P < or = 0.003) and SOL muscle (r = -0.97, P < or = 0.005). In the diet protocol, 12 male subjects ingested both a high-fat and low-fat diet for 3 days each. Before and after completion of each diet, IMCL levels and insulin sensitivity were assessed. After the high-fat diet, IMCL levels increased significantly in TA muscle (to 148.0 +/- 16.9% of baseline; P = 0.005), but not in SOL muscle (to 114.4 +/- 8.2% of baseline; NS). Insulin sensitivity decreased to 83.3 +/- 5.6% of baseline (P = 0.033). There were no significant changes in insulin sensitivity or IMCL levels after the low-fat diet. The effects of the high-fat diet showed greater interindividual variation than those of the infusion protocol. The data from the lipid infusion protocol suggest a functional relationship between IMCL levels and insulin sensitivity. Similar effects could be induced by a high-fat diet, thereby underlining the physiological relevance of these observations.


title: How free fatty acids inhibit glucose utilization in human skeletal muscle.

text: Rat muscle studies suggest competition between free fatty acids (FFA) and glucose for oxidation, resulting in glucose-6-phosphate accumulation. However, FFA decrease glucose-6-phosphate in human skeletal muscle, indicating direct inhibition of glucose transport/phosphorylation. This mechanism could redirect glucose from muscle to brain during fasting and explain the insulin resistance associated with high-lipid diets and obesity.


title: Adiposity and insulin resistance in humans: the role of the different tissue and cellular lipid depots.

text: Human adiposity has long been associated with insulin resistance and increased cardiovascular risk, and abdominal adiposity is considered particularly adverse. Intra-abdominal fat is associated with insulin resistance, possibly mediated by greater lipolytic activity, lower adiponectin levels, resistance to leptin, and increased inflammatory cytokines, although the latter contribution is less clear. Liver lipid is also closely associated with, and likely to be an important contributor to, insulin resistance, but it may also be in part the consequence of the lipogenic pathway of insulin action being up-regulated by hyperinsulinemia and unimpaired signaling. Again, intramyocellular triglyceride is associated with muscle insulin resistance, but anomalies include higher intramyocellular triglyceride in insulin-sensitive athletes and women (vs men). Such issues could be explained if the "culprits" were active lipid moieties such as diacylglycerol and ceramide species, dependent more on lipid metabolism and partitioning than triglyceride amount. Subcutaneous fat, especially gluteofemoral, appears metabolically protective, illustrated by insulin resistance and dyslipidemia in patients with lipodystrophy. However, some studies suggest that deep sc abdominal fat may have adverse properties. Pericardial and perivascular fat relate to atheromatous disease, but not clearly to insulin resistance. There has been recent interest in recognizable brown adipose tissue in adult humans and its possible augmentation by a hormone, irisin, from exercising muscle. Brown adipose tissue is metabolically active, oxidizes fatty acids, and generates heat but, because of its small and variable quantities, its metabolic importance in humans under usual living conditions is still unclear. Further understanding of specific roles of different lipid depots may help new approaches to control obesity and its metabolic sequelae.


title: Dynamics of fat cell turnover in humans.

text: Obesity is increasing in an epidemic manner in most countries and constitutes a public health problem by enhancing the risk for cardiovascular disease and metabolic disorders such as type 2 diabetes. Owing to the increase in obesity, life expectancy may start to decrease in developed countries for the first time in recent history. The factors determining fat mass in adult humans are not fully understood, but increased lipid storage in already developed fat cells (adipocytes) is thought to be most important. Here we show that adipocyte number is a major determinant for the fat mass in adults. However, the number of fat cells stays constant in adulthood in lean and obese individuals, even after marked weight loss, indicating that the number of adipocytes is set during childhood and adolescence. To establish the dynamics within the stable population of adipocytes in adults, we have measured adipocyte turnover by analysing the integration of 14C derived from nuclear bomb tests in genomic DNA. Approximately 10% of fat cells are renewed annually at all adult ages and levels of body mass index. Neither adipocyte death nor generation rate is altered in early onset obesity, suggesting a tight regulation of fat cell number in this condition during adulthood. The high turnover of adipocytes establishes a new therapeutic target for pharmacological intervention in obesity.


title: Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study.

text: Recent muscle biopsy studies have shown a relation between intramuscular lipid content and insulin resistance. The aim of this study was to test this relation in humans by using a novel proton nuclear magnetic resonance (1H NMR) spectroscopy technique, which enables non-invasive and rapid (approximately 45 min) determination of intramyocellular lipid (IMCL) content. Normal weight non-diabetic adults (n = 23, age 29+/-2 years. BMI = 24.1+/-0.5 kg/m2) were studied using cross-sectional analysis. Insulin sensitivity was assessed by a 2-h hyperinsulinaemic (approximately 450 pmol/l)-euglycaemic (approximately 5 mmol/l) clamp test. Intramyocellular lipid concentrations were determined by using localized 1H NMR spectroscopy of soleus muscle. Simple linear regression analysis showed an inverse correlation (r = -0.579, p = 0.0037) [corrected] between intramyocellular lipid content and M-value (100-120 min of clamp) as well as between fasting plasma non-esterified fatty acid concentration and M-value (r = -0.54, p = 0.0267). Intramyocellular lipid content was not related to BMI, age and fasting plasma concentrations of triglycerides, non-esterified fatty acids, glucose or insulin. These results show that intramyocellular lipid concentration, as assessed non invasively by localized 1H NMR spectroscopy, is a good indicator of whole body insulin sensitivity in non-diabetic, non-obese humans.


title: Overnight lowering of free fatty acids with Acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects.

text: Obesity is commonly associated with elevated plasma free fatty acid (FFA) levels, as well as with insulin resistance and hyperinsulinemia, two important cardiovascular risk factors. What causes insulin resistance and hyperinsulinemia in obesity remains uncertain. Here, we have tested the hypothesis that FFAs are the link between obesity and insulin resistance/hyperinsulinemia and that, therefore, lowering of chronically elevated plasma FFA levels would improve insulin resistance/hyperinsulinemia and glucose tolerance in obese nondiabetic and diabetic subjects. Acipimox (250 mg), a long-acting antilipolytic drug, or placebo was given overnight (at 7:00 P.M., 1:00 A.M., 7:00 A.M.) to 9 lean control subjects, 13 obese nondiabetic subjects, 10 obese subjects with impaired glucose tolerance, and 11 patients with type 2 diabetes. Euglycemic-hyperinsulinemic clamps and oral glucose tolerance tests (75 g) were performed on separate mornings after overnight Acipimox or placebo treatment. In the three obese study groups, Acipimox lowered fasting levels of plasma FFAs (by 60-70%) and plasma insulin (by approximately 50%). Insulin-stimulated glucose uptake during euglycemic-hyperinsulinemic clamping was more than twofold higher after Acipimox than after placebo. Areas under the glucose and insulin curves during oral glucose tolerance testing were both approximately 30% lower after Acipimox administration than after placebo. We conclude that lowering of elevated plasma FFA levels can reduce insulin resistance/hyperinsulinemia and improve oral glucose tolerance in lean and obese nondiabetic subjects and in obese patients with type 2 diabetes.


title: Rapid impairment of skeletal muscle glucose transport/phosphorylation by free fatty acids in humans.

text: The initial effects of free fatty acids (FFAs) on glucose transport/phosphorylation were studied in seven healthy men in the presence of elevated (1.44 +/- 0.16 mmol/l), basal (0.35 +/- 0.06 mmol/l), and low (<0.01 mmol/l; control) plasma FFA concentrations (P < 0.05 between all groups) during euglycemic-hyperinsulinemic clamps. Concentrations of glucose-6-phosphate (G-6-P), inorganic phosphate (Pi), phosphocreatine, ADP, and pH in calf muscle were measured every 3.2 min for 180 min by using 31P nuclear magnetic resonance spectroscopy. Rates of whole-body glucose uptake increased similarly until 140 min but thereafter declined by approximately 20% in the presence of basal and high FFAs (42.8 +/- 3.6 and 41.6 +/- 3.3 vs. control: 52.7 +/- 3.3 micromol x kg(-1) x min(-1), P < 0.05). The rise of intramuscular G-6-P concentrations was already blunted at 45 min of high FFA exposure (184 +/- 17 vs. control: 238 +/- 17 micromol/l, P = 0.008). At 180 min, G-6-P was lower in the presence of both high and basal FFAs (197 +/- 21 and 213 +/- 18 vs. control: 286 +/- 19 micromol/l, P < 0.05). Intramuscular pH decreased by -0.013 +/- 0.001 (P < 0.005) during control but increased by +0.008 +/- 0.002 (P < 0.05) during high FFA exposure, while Pi rose by approximately 0.39 mmol/l (P < 0.005) within 70 min and then slowly decreased in all studies. In conclusion, the lack of an initial peak and the early decline of muscle G-6-P concentrations suggest that even at physiological concentrations, FFAs primarily inhibit glucose transport/phosphorylation, preceding the reduction of whole-body glucose disposal by up to 120 min in humans.


title: Mechanism of free fatty acid-induced insulin resistance in humans.

text: To examine the mechanism by which lipids cause insulin resistance in humans, skeletal muscle glycogen and glucose-6-phosphate concentrations were measured every 15 min by simultaneous 13C and 31P nuclear magnetic resonance spectroscopy in nine healthy subjects in the presence of low (0.18 +/- 0.02 mM [mean +/- SEM]; control) or high (1.93 +/- 0.04 mM; lipid infusion) plasma free fatty acid levels under euglycemic (approximately 5.2 mM) hyperinsulinemic (approximately 400 pM) clamp conditions for 6 h. During the initial 3.5 h of the clamp the rate of whole-body glucose uptake was not affected by lipid infusion, but it then decreased continuously to be approximately 46% of control values after 6 h (P < 0.00001). Augmented lipid oxidation was accompanied by a approximately 40% reduction of oxidative glucose metabolism starting during the third hour of lipid infusion (P < 0.05). Rates of muscle glycogen synthesis were similar during the first 3 h of lipid and control infusion, but thereafter decreased to approximately 50% of control values (4.0 +/- 1.0 vs. 9.3 +/- 1.6 mumol/[kg.min], P < 0.05). Reduction of muscle glycogen synthesis by elevated plasma free fatty acids was preceded by a fall of muscle glucose-6-phosphate concentrations starting at approximately 1.5 h (195 +/- 25 vs. control: 237 +/- 26 mM; P < 0.01). Therefore in contrast to the originally postulated mechanism in which free fatty acids were thought to inhibit insulin-stimulated glucose uptake in muscle through initial inhibition of pyruvate dehydrogenase these results demonstrate that free fatty acids induce insulin resistance in humans by initial inhibition of glucose transport/phosphorylation which is then followed by an approximately 50% reduction in both the rate of muscle glycogen synthesis and glucose oxidation.


title: Free fatty acids and skeletal muscle insulin resistance.

text: PURPOSE OF REVIEW: Acute exposure to fatty acids causes insulin resistance in muscle, and excess dietary lipid and obesity are also strongly associated with muscle insulin resistance. Relevant mechanisms, however, are still not fully elucidated. Here we examine the latest evidence as to why lipids might accumulate in muscle and the possible mechanisms for lipid-induced insulin resistance. RECENT FINDINGS: Muscle lipid metabolites such as long chain fatty acid coenzyme As, diacylglycerol and ceramides may impair insulin signalling directly. Crosstalk between inflammatory signalling pathways and insulin signalling pathways, mitochondrial dysfunction and oxidative stress have also been put forward as major contributors to the development or maintenance of lipid-induced insulin resistance in muscle. Several animal models with gene deletions in pathways of fatty acid synthesis and storage also show increased metabolic rate, reduced intramuscular lipid storage and improved insulin action when challenged with a high lipid load. SUMMARY: Studies in genetic and dietary obese animal models, genetically modified animals and humans with obesity or type 2 diabetes suggest plausible mechanisms for effects of fatty acids, lipid metabolites, inflammatory pathways and mitochondrial dysfunction on insulin action in muscle. Many of these mechanisms, however, have been demonstrated in situations in which lipid accumulation (obesity) already exists. Whether the initial events leading to muscle insulin resistance are direct effects of fatty acids in muscle or are secondary to lipid accumulation in adipose tissue or liver remains to be clarified.


title: Effects of an overnight intravenous lipid infusion on intramyocellular lipid content and insulin sensitivity in African-American versus Caucasian adolescents

text: Objective To explain the predisposition for insulin resistance among African American (AA) adolescents, this study aimed to: 1) examine changes in intramyocellular lipid content (IMCL), and insulin sensitivity with intralipid (IL) infusion; and 2) determine whether the increase in IMCL is comparable between AA and Caucasian adolescents. Materials and Methods Thirteen AA and 15 Caucasian normal-weight adolescents (BMI <85th) underwent a 3-h hyperinsulinemic-euglycemic clamp, on two occasions in random order, after an overnight 12-hr infusion of: 1) 20% IL and 2) normal saline (NS). IMCL was quantified by 1H-magnetic resonance spectroscopy in tibialis anterior muscle before and after IL infusion. Results During IL infusion, plasma TG, glycerol, FFA and fat oxidation increased significantly, with no race differences. Hepatic insulin sensitivity decreased with IL infusion with no difference between the groups. IL infusion was associated with a significant increase in IMCL, which was comparable between AA (Δ 105%; NS: 1.9 ± 0.8 vs. IL: 3.9 ± 1.6 mmol/kg wet weight) and Caucasian (Δ 86%; NS: 2.8 ± 2.1 vs. IL: 5.2 ± 2.4 mmol/kg wet weight), with similar reductions (P<0.01) in insulin sensitivity between the groups (Δ −44%: NS: 9.1 ± 3.3 vs. IL: 5.1 ± 1.8 mg/kg/min per µU/ml in AA) and (Δ−39%: NS: 12.9 ± 6.0 vs. IL: 7.9 ± 3.8 mg/kg/min per µU/ml in Caucasian) adolescents. Conclusions In healthy adolescents, an acute elevation in plasma FFA with IL infusion is accompanied by significant increases in IMCL and reductions in insulin sensitivity with no race differential. Our findings suggest that AA normal-weight adolescents are not more susceptible than Caucasians to FFA-induced IMCL accumulation and insulin resistance.


title: Neanderthal cannibalism at Moula-Guercy, Ardèche, France.

text: The cave site of Moula-Guercy, 80 meters above the modern Rhone River, was occupied by Neanderthals approximately 100,000 years ago. Excavations since 1991 have yielded rich paleontological, paleobotanical, and archaeological assemblages, including parts of six Neanderthals. The Neanderthals are contemporary with stone tools and faunal remains in the same tightly controlled stratigraphic and spatial contexts. The inference of Neanderthal cannibalism at Moula-Guercy is based on comparative analysis of hominid and ungulate bone spatial distributions, modifications by stone tools, and skeletal part representations.


title: Paleolithic nutrition: twenty-five years later.

text: A quarter century has passed since the first publication of the evolutionary discordance hypothesis, according to which departures from the nutrition and activity patterns of our hunter-gatherer ancestors have contributed greatly and in specifically definable ways to the endemic chronic diseases of modern civilization. Refinements of the model have changed it in some respects, but anthropological evidence continues to indicate that ancestral human diets prevalent during our evolution were characterized by much lower levels of refined carbohydrates and sodium, much higher levels of fiber and protein, and comparable levels of fat (primarily unsaturated fat) and cholesterol. Physical activity levels were also much higher than current levels, resulting in higher energy throughput. We said at the outset that such evidence could only suggest testable hypotheses and that recommendations must ultimately rest on more conventional epidemiological, clinical, and laboratory studies. Such studies have multiplied and have supported many aspects of our model, to the extent that in some respects, official recommendations today have targets closer to those prevalent among hunter-gatherers than did comparable recommendations 25 years ago. Furthermore, doubts have been raised about the necessity for very low levels of protein, fat, and cholesterol intake common in official recommendations. Most impressively, randomized controlled trials have begun to confirm the value of hunter-gatherer diets in some high-risk groups, even as compared with routinely recommended diets. Much more research needs to be done, but the past quarter century has proven the interest and heuristic value, if not yet the ultimate validity, of the model.


title: BEYOND THE PALEOLITHIC PRESCRIPTION: INCORPORATING DIVERSITY AND FLEXIBILITY IN THE STUDY OF HUMAN DIET EVOLUTION

text: Evolutionary paradigms of human health and nutrition center on the evolutionary discordance or “mismatch” model whereby human bodies, reflecting adaptations established in the Paleolithic era, are ill-suited to modern industrialized diets resulting in rapidly increasing rates of chronic metabolic disease. Whereas this model remains useful, we argue that its utility in explaining the evolution of human dietary tendencies is limited. The assumption that human diets are mismatched to our evolved biology implies that they are instinctual or genetically determined and rooted in the Paleolithic. We review current research indicating that human eating habits are primarily learned through behavioral, social and physiological mechanisms starting in utero and extending throughout the life course. Those adaptations that appear to be strongly genetic likely reflect Neolithic, rather than Paleolithic, adaptations and are significantly influenced by human niche-constructing behavior. Incorporating a broader understanding of the evolved mechanisms by which humans learn and imprint eating habits and the reciprocal effects of those habits on physiology would provide useful tools for structuring more lasting nutrition interventions.


title: Does hand hygiene compliance among health care workers change when patients are in contact precaution rooms in ICUs?

text: BACKGROUND: Hand hygiene compliance rates among health care workers (HCW) rarely exceed 50%. Contact precautions are thought to increase HCWs' hand hygiene awareness. We sought to determine any differences in hand hygiene compliance rates for HCW between patients in contact precaution and those not in any isolation. METHODS: In a hospital's medical (MICU) and surgical (SICU) intensive care units, a trained observer directly observed hand hygiene by the type of room (contact precaution or noncontact precaution) and the type of HCW (nurse or doctor). RESULTS: The SICU had similar compliance rates (36/75 [50.7%] in contact precaution rooms vs 223/431 [51.7%] compliance in noncontact precaution rooms, P > .5); the MICU also had similar hand hygiene compliance rates (67/132 [45.1%] in contact precaution rooms vs 96/213 [50.8%] in noncontact precaution rooms, P > .10). Hand hygiene compliance rates stratified by HCW were similar with 1 exception. The MICU nurses had a higher rate of hand hygiene compliance in contact precaution rooms than in rooms with noncontact precautions (66.7% vs 51.6%, respectively). CONCLUSION: Compliance with hand hygiene among HCWs did not differ between contact precaution rooms and rooms with noncontact precautions with the exception of the nurses in the MICU. Published by Mosby, Inc.


title: Empirical evaluation of very large treatment effects of medical interventions.

text: CONTEXT: Most medical interventions have modest effects, but occasionally some clinical trials may find very large effects for benefits or harms. OBJECTIVE: To evaluate the frequency and features of very large effects in medicine. DATA SOURCES: Cochrane Database of Systematic Reviews (CDSR, 2010, issue 7). STUDY SELECTION: We separated all binary-outcome CDSR forest plots with comparisons of interventions according to whether the first published trial, a subsequent trial (not the first), or no trial had a nominally statistically significant (P < .05) very large effect (odds ratio [OR], ≥5). We also sampled randomly 250 topics from each group for further in-depth evaluation. DATA EXTRACTION: We assessed the types of treatments and outcomes in trials with very large effects, examined how often large-effect trials were followed up by other trials on the same topic, and how these effects compared against the effects of the respective meta-analyses. RESULTS: Among 85,002 forest plots (from 3082 reviews), 8239 (9.7%) had a significant very large effect in the first published trial, 5158 (6.1%) only after the first published trial, and 71,605 (84.2%) had no trials with significant very large effects. Nominally significant very large effects typically appeared in small trials with median number of events: 18 in first trials and 15 in subsequent trials. Topics with very large effects were less likely than other topics to address mortality (3.6% in first trials, 3.2% in subsequent trials, and 11.6% in no trials with significant very large effects) and were more likely to address laboratory-defined efficacy (10% in first trials,10.8% in subsequent, and 3.2% in no trials with significant very large effects). First trials with very large effects were as likely as trials with no very large effects to have subsequent published trials. Ninety percent and 98% of the very large effects observed in first and subsequently published trials, respectively, became smaller in meta-analyses that included other trials; the median odds ratio decreased from 11.88 to 4.20 for first trials, and from 10.02 to 2.60 for subsequent trials. For 46 of the 500 selected topics (9.2%; first and subsequent trials) with a very large-effect trial, the meta-analysis maintained very large effects with P < .001 when additional trials were included, but none pertained to mortality-related outcomes. Across the whole CDSR, there was only 1 intervention with large beneficial effects on mortality, P < .001, and no major concerns about the quality of the evidence (for a trial on extracorporeal oxygenation for severe respiratory failure in newborns). CONCLUSIONS: Most large treatment effects emerge from small studies, and when additional trials are performed, the effect sizes become typically much smaller. Well-validated large effects are uncommon and pertain to nonfatal outcomes.


title: Estimating Health Care-Associated Infections and Deaths in U.S. Hospitals, 2002

text: SYNOPSIS Objective The purpose of this study was to provide a national estimate of the number of healthcare-associated infections (HAI) and deaths in United States hospitals. Methods No single source of nationally representative data on HAIs is currently available. The authors used a multi-step approach and three data sources. The main source of data was the National Nosocomial Infections Surveillance (NNIS) system, data from 1990–2002, conducted by the Centers for Disease Control and Prevention. Data from the National Hospital Discharge Survey (for 2002) and the American Hospital Association Survey (for 2000) were used to supplement NNIS data. The percentage of patients with an HAI whose death was determined to be caused or associated with the HAI from NNIS data was used to estimate the number of deaths. Results In 2002, the estimated number of HAIs in U.S. hospitals, adjusted to include federal facilities, was approximately 1.7 million: 33,269 HAIs among newborns in high-risk nurseries, 19,059 among newborns in well-baby nurseries, 417,946 among adults and children in ICUs, and 1,266,851 among adults and children outside of ICUs. The estimated deaths associated with HAIs in U.S. hospitals were 98,987: of these, 35,967 were for pneumonia, 30,665 for bloodstream infections, 13,088 for urinary tract infections, 8,205 for surgical site infections, and 11,062 for infections of other sites. Conclusion HAIs in hospitals are a significant cause of morbidity and mortality in the United States. The method described for estimating the number of HAIs makes the best use of existing data at the national level.


title: Patient expectations on lipid-lowering drugs.

text: OBJECTIVE: The objective of this study was to assess expectations of effect when using statins in a treatment population. Further the aim was to examine factors, including history and concurrent risk of coronary heart disease, associated with a higher and lower treatment belief. METHODS: Eight hundred and twenty-nine (829) Swedish patients using statins completed postal questionnaires about their health, life style, cardiovascular risk factors and expectation of the treatment. Expected treatment benefit was used as outcome measurement. RESULTS: A medical history of coronary heart disease did not affect treatment expectations. Patients with a high risk of cardiovascular disease reported a slightly lower expectation of the treatment effect at a 10-year perspective (p<0.01) but not at shorter time perspectives. Low satisfaction with the explanation of the purpose of the treatment and a poor perceived control of own health was associated with a more negative view on treatment benefit. CONCLUSION: The rationale applied by physicians prescribing statins does not seem to relate to the patients' expectations, whereas factors relating to the patient-physician relationship, the social situation and the perceived control of health seem to affect patient belief. PRACTICE IMPLICATIONS: The association between patients' poor satisfaction of treatment explanation and a low belief in treatment benefits emphasizes the importance of the patient-physician communication. It is suggested that clinical tools are developed in order to identify patients with poor belief in treatment benefit since tailored education for this group might reduce the risk of non-compliance and subsequently reduce the risk of coronary heart disease.


title: Patients' Expectations of Screening and Preventive Treatments

text: PURPOSE An informed decision to accept a health care intervention requires an understanding of its likely benefit. This study assessed participants' estimates of the benefit, as well as minimum acceptable benefit, of screening for breast and bowel cancer and medication to prevent hip fracture and cardiovascular disease. METHODS Three general practitioners sent questionnaires to all registered patients aged 50 to 70 years. Patients agreeing to participate in the study were asked to estimate the number of events (fractures or deaths) prevented in a group of 5,000 patients undergoing each intervention over a period of 10 years, and to indicate the minimum number of events avoided by the intervention that they considered justified its use. The proportions of participants that overestimated each intervention's benefit were calculated, and univariate and multivariable analyses of predictors of response were performed. RESULTS The participation rate was 36%: 977 patients were invited to participate in the study, and 354 returned a completed questionnaire. Participants overestimated the degree of benefit conferred by all interventions: 90% of participants overestimated the effect of breast cancer screening, 94% overestimated the effect of bowel cancer screening, 82% overestimated the effect of hip fracture preventive medication, and 69% overestimated the effect of preventive medication for cardiovascular disease. Estimates of minimum acceptable benefit were more conservative, but other than for cardiovascular disease mortality prevention, most respondents indicated a minimum benefit greater than these interventions achieve. A lower level of education was associated with higher estimates of minimum acceptable benefit for all interventions. CONCLUSION Patients overestimated the risk reduction achieved with 4 examples of screening and preventive medications. A lower level of education was associated with higher minimum benefit to justify intervention use. This tendency to overestimate benefits may affect patients' decisions to use such interventions, and practitioners should be aware of this tendency when discussing these interventions with patients.


title: What benefit do patients expect from adding second and third antihypertensive drugs?

text: Aims To discover whether patients have the same expectations of benefit from taking the first and any additional drugs for the treatment of hypertension and to investigate any patient characteristics which predict willingness to take treatment. Methods This was an anonymous questionnaire survey carried out in a single primary care group. A random sample of patients from the practice list stratified by age and gender were surveyed to determine what benefit they required before deciding to receive first and subsequent drugs to treat hypertension. They were asked to indicate the largest number needing treatment for 5 years (NNT5) to prevent myocardial infarction in 1 (smallest benefit) that would persuade them of the need for treatment. Demographic information which might explain variability in enthusiasm for treatment was also collected. Results Participants required far higher benefit to consider drug treatment than expected with a mean NNT5 for the first treatment of 15.0 (95% CI 12.3, 17.8). Marginal benefit demanded for the addition of second and third treatments was at least as great with an NNT5 of 13.2 (95% CI 10.8, 15.7) and NNT5 of 11.0 (95% CI 8.6, 13.4). Additional factors influencing willingness to take treatment were gender with a difference in NNT5 between men and women of 7.1 (95% CI 1.7, 12.5), difficulty in making the decision (very easy vs very difficult) of 14.9 (95% CI 6.0, 23.8), and years in full time education 2.0 (95% CI 0.9, 3.0) for each additional year of education. Any slope of NNT5 with increasing number of tablets disappeared when gender, years in education, and difficulty in reaching a decision were taken into account simultaneously. Conclusions People may have greater expectation of benefit from antihypertensive drug treatment than it provides. They certainly do not view the addition of subsequent drugs as any lesser step than starting the first in terms of the benefit expected. Full understanding of both the risks and benefits may be of critical importance with those spending longer in full time education and those expending more effort in making the decision accepting more treatment. The discrepancy between benefit expected and that available demands further research into methods of determining patients’ expectations and informing individual patient decisions.


title: A way to reverse CAD?

text: PURPOSE: Plant-based nutrition achieved coronary artery disease (CAD) arrest and reversal in a small study. However, there was skepticism that this approach could succeed in a larger group of patients. The purpose of our follow-up study was to define the degree of adherence and outcomes of 198 consecutive patient volunteers who received counseling to convert from a usual diet to plant-based nutrition. METHODS: We followed 198 consecutive patients counseled in plant-based nutrition. These patients with established cardiovascular disease (CVD) were interested in transitioning to plant-based nutrition as an adjunct to usual cardiovascular care. We considered participants adherent if they eliminated dairy, fish, and meat, and added oil. RESULTS: Of the 198 patients with CVD, 177 (89%) were adherent. Major cardiac events judged to be recurrent disease totaled one stroke in the adherent cardiovascular participants—a recurrent event rate of .6%, significantly less than reported by other studies of plant-based nutrition therapy. Thirteen of 21 (62%) nonadherent participants experienced adverse events. CONCLUSION: Most of the volunteer patients with CVD responded to intensive counseling, and those who sustained plant-based nutrition for a mean of 3.7 years experienced a low rate of subsequent cardiac events. This dietary approach to treatment deserves a wider test to see if adherence can be sustained in broader populations. Plant-based nutrition has the potential for a large effect on the CVD epidemic.


title: Are preventive drugs preventive enough? A study of patients' expectation of benefit from preventive drugs.

text: OBJECTIVES: The study aimed to find the threshold of benefit for a hypothetical cholesterol-lowering drug below which the subject would not be prepared to take the drug. We also looked at whether proximity to the target event (myocardial infarction) and the subjects' views on drug taking affected this threshold. DESIGN: We studied 307 subjects using a written questionnaire and interview. Group 1 (102 subjects) had just been discharged from the coronary care unit. Group 2 (105 subjects) were taking cardio-protective drugs but had no recent history of myocardial infarction. Group 3 (100 subjects) had no history of myocardial infarction and were taking no cardio-protective drugs. RESULTS: Median values for the threshold of benefit below which the subject would not take the preventive drug were 20%, 20%, and 30% absolute risk reduction for Groups 1, 2 and 3 respectively. Median values for expectation of average prolongation of life were 12, 12 and 18 months respectively. Only 27% of subjects would take a drug offering 5% or less absolute risk reduction over five years. Subjects' views on medicinal drug taking in general and proximity to the target event were predictors of the acceptance of preventive drugs. Eighty percent of subjects wished to be told the numerical benefit of a preventive drug before starting on it. CONCLUSION: For the majority, the expectation of benefit from a preventive drug is higher than the actual benefit provided by current drug strategies. There is a tension between the patient's right to know about the chance of benefiting from a preventive drug and the likely reduction in uptake if they are so informed.


title: Flaxseed fed pork: n-3 fatty acid enrichment and contribution to dietary recommendations.

text: The potential to increase n-3 fatty acid (FA) intake via flaxseed fed pork is underestimated when restricted to pure longissimus muscle, whereas a combination of muscle and adipose tissue is typically consumed. Presently, the FA content of pigs fed 0%, 5% and 10% dietary flaxseed for 11 weeks was measured in loin, picnic and butt primals (lean muscle with epimysium (L), L plus seam fat (LS), and LS plus 5 mm backfat (LSS)). The n-3 FA content necessary for an enrichment claim in Canada (300 mg/100 g serving) was exceeded in L from all primals when feeding 5% flaxseed, being 4 fold that of controls (P<0.001), with further enrichment from inclusion of associated adipose tissues (P<0.001). Increasing flaxseed feeding levels in combination with adipose tissue inclusion amplified total long chain n-3 FA (P<0.05), particularly 20:5n-3 and 22:5n-3. Flaxseed-fed n-3 FA enriched pork can contribute substantially to daily long chain n-3 FA intakes, particularly for societies with typically low seafood consumption. © 2013.


title: The effects of blood pressure reduction and of different blood pressure-lowering regimens on major cardiovascular events according to baseline bloo...

text: BACKGROUND: The benefits of reducing blood pressure are well established, but there remains uncertainty about whether the magnitude of the effect varies with the initial blood pressure level. The objective was to compare the risk reductions achieved by different blood pressure-lowering regimens among individuals with different baseline blood pressures. METHODS: Thirty-two randomized controlled trials were included and seven comparisons between different types of treatments were made. For each comparison, the primary prespecified analysis included calculation of summary estimates of effect using random-effects meta-analysis for major cardiovascular events in four groups defined by baseline SBP (<140, 140-159, 160-179, and ≥ 180 mmHg). RESULTS: There were 201 566 participants among whom 20 079 primary outcome events were observed. There was no evidence of differences in the proportionate risk reductions achieved with different blood pressure-lowering regimens across groups defined according to higher or lower levels of baseline SBP (all P for trend > 0.17). This finding was broadly consistent for comparisons of different regimens, for DBP categories, and for commonly used blood pressure cut-points. CONCLUSION: It appears unlikely that the effectiveness of blood pressure-lowering treatments depends substantively upon starting blood pressure level. As the majority of patients in the trials contributing to these overviews had a history of hypertension or were receiving background blood pressure-lowering therapy, the findings suggest that additional blood pressure reduction in hypertensive patients meeting initial blood pressure targets will produce further benefits. More broadly, the data are supportive of the utilization of blood pressure-lowering regimens in high-risk patients with and without hypertension.


title: Flaxseed - a miraculous defense against some critical maladies.

text: Presence of omega-3, omega-6 rich oil, alpha-linoleic acid, dietary fibers, secoisolariciresinol diglucoside, protein and minerals in flaxseed constitute a very strong basis for the utilization of flaxseed in various food preparations as a curative agent. An extensive body of literature illustrates that flaxseed has gained a significant position in the domain of nutritional sciences owing to its pivotal role as an antioxidant agent. The review discusses at length, numerous health benefits of flaxseed typically focusing its preventive role against cardiovascular diseases, cancer, diabetes and enhancement of spatial memory. Massive increase in the size of population with a special emphasize to the developing countries, there is an urge for exploration of the alternative dietary resources that can meet the dietary and nutritional needs of forthcoming generations. With respect to its remarkable nutritional importance, the review in question enables researchers engaged in nutritional sciences to further investigate the therapeutic value of flaxseed functional components and their dietary application in various food products and availability in processed foods as well as in the human cell line.


title: Potent antihypertensive action of dietary flaxseed in hypertensive patients.

text: Flaxseed contains ω-3 fatty acids, lignans, and fiber that together may provide benefits to patients with cardiovascular disease. Animal work identified that patients with peripheral artery disease may particularly benefit from dietary supplementation with flaxseed. Hypertension is commonly associated with peripheral artery disease. The purpose of the study was to examine the effects of daily ingestion of flaxseed on systolic (SBP) and diastolic blood pressure (DBP) in peripheral artery disease patients. In this prospective, double-blinded, placebo-controlled, randomized trial, patients (110 in total) ingested a variety of foods that contained 30 g of milled flaxseed or placebo each day over 6 months. Plasma levels of the ω-3 fatty acid α-linolenic acid and enterolignans increased 2- to 50-fold in the flaxseed-fed group but did not increase significantly in the placebo group. Patient body weights were not significantly different between the 2 groups at any time. SBP was ≈ 10 mm Hg lower, and DBP was ≈ 7 mm Hg lower in the flaxseed group compared with placebo after 6 months. Patients who entered the trial with a SBP ≥ 140 mm Hg at baseline obtained a significant reduction of 15 mm Hg in SBP and 7 mm Hg in DBP from flaxseed ingestion. The antihypertensive effect was achieved selectively in hypertensive patients. Circulating α-linolenic acid levels correlated with SBP and DBP, and lignan levels correlated with changes in DBP. In summary, flaxseed induced one of the most potent antihypertensive effects achieved by a dietary intervention.


title: Response surface methodology for predicting quality characteristics of beef patties added with flaxseed and tomato paste.

text: Response surface methodology was used to study the effect of flaxseed flour (FS) and tomato paste (TP) addition, from 0 to 10% and 0 to 20% respectively, on beef patty quality characteristics. The assessed quality characteristics were color (L, a, and b), pH and texture profile analysis (TPA). Also, sensory analysis was performed for the assessment of color, juiciness, firmness, and general acceptance. FS addition reduced L and a values and decreased weight loss of cooked products (P<0.05). An opposite effect was observed when TP was added (P<0.05). All TPA parameters decreased when percentages of FS and TP were increased in the formulation of beef patties. Furthermore, FS and TP addition adversely affected the sensory characteristics of the cooked product (P<0.05); nevertheless, all sensory characteristics evaluated had an acceptable score (>5.6). Thus FS and TP are ingredients that can be used in beef patty preparation. Copyright © 2014 Elsevier Ltd. All rights reserved.