Showing papers in "Journal of Nutrition in 2006"

Fruit and Vegetable Consumption and Risk of Coronary Heart Disease: A Meta-Analysis of Cohort Studies

Abstract: The consumption of fruit and vegetables is associated with a reduced rate of coronary heart disease (CHD) in observational cohorts. The purpose of this study was to assess the strength of this association in a meta-analysis. Cohort studies were selected if they reported relative risks (RRs) and 95% CI for coronary heart disease or mortality and if they presented a quantitative assessment of fruit and vegetable intake. The pooled RRs were calculated for each additional portion of fruit and/or vegetables consumed per day, and the linearity of the associations were examined. Nine studies were eligible for inclusion in the meta-analysis that consisted of 91,379 men, 129,701 women, and 5,007 CHD events. The risk of CHD was decreased by 4% [RR (95% CI): 0.96 (0.93-0.99), P = 0.0027] for each additional portion per day of fruit and vegetable intake and by 7% [0.93 (0.89-0.96), P < 0.0001] for fruit intake. The association between vegetable intake and CHD risk was heterogeneous (P = 0.0043), more marked for cardiovascular mortality [0.74 (0.75-0.84), P < 0.0001] than for fatal and nonfatal myocardial infarction [0.95 (0.92-0.99), P = 0.0058]. Visual inspection of the funnel plot suggested a publication bias, although not statistically significant. Therefore, the reported RRs are probably overestimated. This meta-analysis of cohort studies shows that fruit and vegetable consumption is inversely associated with the risk of CHD. The causal mechanism of this association, however, remains to be demonstrated.

The Sulfur-Containing Amino Acids: An Overview

Abstract: Methionine, cysteine, homocysteine, and taurine are the 4 common sulfur-containing amino acids, but only the first 2 are incorporated into proteins. Sulfur belongs to the same group in the periodic table as oxygen but is much less electronegative. This difference accounts for some of the distinctive properties of the sulfur-containing amino acids. Methionine is the initiating amino acid in the synthesis of virtually all eukaryotic proteins; N-formylmethionine serves the same function in prokaryotes. Within proteins, many of the methionine residues are buried in the hydrophobic core, but some, which are exposed, are susceptible to oxidative damage. Cysteine, by virtue of its ability to form disulfide bonds, plays a crucial role in protein structure and in protein-folding pathways. Methionine metabolism begins with its activation to S-adenosylmethionine. This is a cofactor of extraordinary versatility, playing roles in methyl group transfer, 5'-deoxyadenosyl group transfer, polyamine synthesis, ethylene synthesis in plants, and many others. In animals, the great bulk of S-adenosylmethionine is used in methylation reactions. S-Adenosylhomocysteine, which is a product of these methyltransferases, gives rise to homocysteine. Homocysteine may be remethylated to methionine or converted to cysteine by the transsulfuration pathway. Methionine may also be metabolized by a transamination pathway. This pathway, which is significant only at high methionine concentrations, produces a number of toxic endproducts. Cysteine may be converted to such important products as glutathione and taurine. Taurine is present in many tissues at higher concentrations than any of the other amino acids. It is an essential nutrient for cats.

The Growing Problem of Obesity in Dogs and Cats

Abstract: Obesity is defined as an accumulation of excessive amounts of adipose tissue in the body, and is the most common nutritional disorder in companion animals. Obesity is usually the result of either excessive dietary intake or inadequate energy utilization, which causes a state of positive energy balance. Numerous factors may predispose an individual to obesity including genetics, the amount of physical activity, and the energy content of the diet. The main medical concern of obesity relates to the many disease associations that accompany the adiposity. Numerous studies demonstrated that obesity can have detrimental effects on the health and longevity of dogs and cats. The problems to which obese companion animals may be predisposed include orthopedic disease, diabetes mellitus, abnormalities in circulating lipid profiles, cardiorespiratory disease, urinary disorders, reproductive disorders, neoplasia (mammary tumors, transitional cell carcinoma), dermatological diseases, and anesthetic complications. The main therapeutic options for obesity in companion animals include dietary management and increasing physical activity. Although no pharmaceutical compounds are yet licensed for weight loss in dogs and cats, it is envisaged that such agents will be available in the future. Dietary therapy forms the cornerstone of weight management in dogs and cats, but increasing exercise and behavioral management form useful adjuncts. There is a need to increase the awareness of companion animal obesity as a serious medical concern within the veterinary profession.

Biofortification of Staple Food Crops

Abstract: Deficiencies of vitamin A, iron, and zinc affect over one-half of the world's population. Progress has been made to control micronutrient deficiencies through supplementation and food fortification, but new approaches are needed, especially to reach the rural poor. Biofortification (enriching the nutrition contribution of staple crops through plant breeding) is one option. Scientific evidence shows this is technically feasible without compromising agronomic productivity. Predictive cost-benefit analyses also support biofortification as being important in the armamentarium for controlling micronutrient deficiencies. The challenge is to get producers and consumers to accept biofortified crops and increase their intake of the target nutrients. With the advent of good seed systems, the development of markets and products, and demand creation, this can be achieved.

The USDA Automated Multiple-Pass Method Accurately Estimates Group Total Energy and Nutrient Intake

Abstract: The imperative to address the national obesity epidemic has stimulated efforts to develop accurate dietary assessment methods suitable for large-scale applications. This study evaluated the performance of the USDA Automated Multiple-Pass Method (AMPM), the computerized dietary recall designed for the National Health and Nutrition Examination Survey dietary survey, and 2 epidemiological methods [the Block food-frequency questionnaire (Block) and National Cancer Institute's Diet History Questionnaire (DHQ)] using doubly labeled water (DLW) total energy expenditure (TEE) and 14-d estimated food record (FR) absolute nutrient intake as criterion measures. Twenty highly motivated, normal-weight-stable, premenopausal women participated in a free-living study that included 2 unannounced AMPM recalls and completion of the Block and DHQ. AMPM and FR total energy intake (TEI) did not differ significantly from DLW TEE [AMPM: 8982 +/- 2625 kJ; FR: 8416 +/- 2217; DLW: 8905 +/- 1881 (mean +/- SD)]. Conversely, the questionnaires underestimated TEI by approximately 28% (Block: 6365 +/- 2193; DHQ: 6215 +/- 1976; P < 0.0001 vs. DLW). Pearson correlation coefficients for DLW TEE with each dietary method TEI showed a stronger linear relation for AMPM (r = 0.53; P = 0.02) and FR (r = 0.41; P = 0.07) than for the Block (r = 0.25; P = 0.29) and DHQ (r = 0.15; P = 0.53). Most mean absolute FR nutrient intakes were closely approximated by the AMPM but were significantly underestimated by the questionnaires. In highly motivated premenopausal women, the AMPM provides valid measures of group total energy and nutrient intake whereas the Block and DHQ yield underestimations.

Clarifying the Real Bioactive Constituents of Garlic

Abstract: Compounds in garlic work synergistically to produce various effects, but, because of garlic's chemical complexity, processing methods yield preparations with differing efficacy and safety. Although thiosulfinates such as allicin have been long misunderstood to be active compounds due to their characteristic odor, it is not necessary for garlic preparations to contain such odorous compounds to be effective, and they decompose and disappear during any processing. Garlic exhibits hypolipidemic, antiplatelet, and procirculatory effects. It prevents cold and flu symptoms through immune enhancement and demonstrates anticancer and chemopreventive activities. In addition, aged garlic extract possesses hepatoprotective, neuroprotective, antioxidative activities, whereas other preparations may stimulate oxidation. Additional effects may be caused by S-allylcysteine, S-allyl mercaptocysteine), saponins, Nalpha-fructosyl arginine, and other substances formed during a long-term extraction process. Although not all of active ingredients of garlic are known, and allicin-like transient components are not directly active, ample research suggests that an allicin-free garlic preparation that is standardized with a bioavailable component such as S-allylcysteine, is active and various effects of garlic may be attributed to it. Furthermore, various chemical constituents in garlic products, including nonsulfur compounds such as saponins, may contribute to the essential biological activities of garlic. Further studies are needed to confirm their bioavailability and associated activities.

Signaling Pathways and Molecular Mechanisms through which Branched-Chain Amino Acids Mediate Translational Control of Protein Synthesis

Abstract: BCAAs stimulate protein synthesis in in vitro preparations of skeletal muscle. Likewise, the stimulation of protein synthesis in skeletal muscle produced by intake of a mixed meal is due largely to BCAAs. Of the three BCAAs, leucine is the one primarily responsible for the stimulation of protein synthesis under these circumstances. The stimulatory effect of leucine on protein synthesis is mediated through upregulation of the initiation of mRNA translation. A number of mechanisms, including phosphorylation of ribosomal protein S6 Kinase, eukaryotic initiation factor (eIF)4E binding protein-1, and eIF4G, contribute to the effect of leucine on translation initiation. These mechanisms not only promote global translation of mRNA but also contribute to processes that mediate discrimination in the selection of mRNA for translation. A key component in a signaling pathway controlling these phosphorylation-induced mechanisms is the protein kinase, termed the mammalian target of rapamycin (mTOR). The activity of mTOR toward downstream targets is controlled in part through its interaction with the regulatory-associated protein of mTOR (known as raptor) and the G protein beta-subunit-like protein. Signaling through mTOR is also controlled by upstream members of the pathway such as the Ras homolog enriched in brain (Rheb), a GTPase that activates mTOR, and tuberin (also known as TSC2), a GTPase-activating protein, which, with its binding partner hamartin (also known as TSC1), acts to repress mTOR. Candidates for mediating the action of leucine to stimulate signaling through the mTOR pathway include TSC2, Rheb, and raptor. The current state of our understanding of how leucine acts on these signaling pathways and molecular mechanisms to stimulate protein synthesis in skeletal muscle is summarized in this article.

Measuring Household Food Insecurity: Why It's So Important and Yet So Difficult to Do

Abstract: Food insecurity is a daily reality for hundreds of millions of people around the world. Although its most extreme manifestations are often obvious, many other households facing constraints in their access to food are less identifiable. Operational agencies lack a method for differentiating households at varying degrees of food insecurity in order to target and evaluate their interventions. This chapter provides an overview of a set of papers associated with a research initiative that seeks to identify more precise, yet simple, measures of household food insecurity. The overview highlights three main conceptual developments associated with practical approaches to measuring constraints in access to food: 1) a shift from using measures of food availability and utilization to measuring "inadequate access"; 2) a shift from a focus on objective to subjective measures; and 3) a growing emphasis on fundamental measurement as opposed to reliance on distal, proxy measures. Further research is needed regarding 1) how well measures of household food insecurity designed for chronically food-insecure contexts capture the processes leading to, and experience of, acute food insecurity, 2) the impact of short-term shocks, such as major floods or earthquake, on household behaviors that determine responses to food security questions, 3) better measurement of the interaction between severity and frequency of household food insecurity behaviors, and 4) the determination of whether an individual's response to survey questions can be representative of the food insecurity experiences of all members of the household.

The Hordaland Homocysteine Study: A Community-Based Study of Homocysteine, Its Determinants, and Associations with Disease

Abstract: The Hordaland Homocysteine Study (HHS) is a population-based study of more than 18,000 men and women in the county of Hordaland in Western Norway. The first investigation (HHS-I) took place in 1992-93, when the subjects were aged 40-67 y. In 1997-99, a follow-up study (HHS-II) of 7,053 subjects was carried out. In this large population, plasma levels of total homocysteine (tHcy) are associated with several physiologic and lifestyle factors and common diseases. Increasing age, male sex, smoking, coffee consumption, high blood pressure, unfavorable lipid profile, high creatinine, and the MTHFR 677C > T polymorphism are among the factors associated with increased tHcy levels; physical activity, moderate alcohol consumption, and a good folate or vitamin B-12 status are associated with lower tHcy levels. Subjects with raised tHcy levels have increased risk of cardiovascular morbidity, cardiovascular and noncardiovascular mortality, and are more likely to suffer from depression and from cognitive deficit (elderly). Among women, raised tHcy levels are associated with decreased bone mineral density and increased risk of osteoporosis. Women with raised tHcy levels also have an increased risk of having suffered from pregnancy complications and an adverse pregnancy outcome. Significant associations between tHcy and clinical outcomes are usually observed for tHcy levels > 15 micromol/L, but for most conditions, there is a continuous concentration-response relation with no apparent threshold concentration. Overall, the findings from HHS indicate that a raised tHcy level is associated with multiple clinical conditions, whereas a low tHcy level is associated with better physical and mental health.

Branched-Chain Amino Acids: Enzyme and Substrate Regulation

Abstract: The three branched-chain amino acids (BCAAs) are the most hydrophobic of the amino acids and play crucial roles in determining the structures of globular proteins as well as the interaction of the transmembrane domains of membranous proteins with phospholipid bilayers. However, the three BCAAs do not behave identically. In terms of protein secondary structure, valine and isoleucine exhibit a definite preference for the beta-structure, whereas leucine has a higher preference for the alpha-helix. Although mutation of one BCAA to another is commonly regarded as conservative, there are well-documented examples of such substitutions that have a significant effect on protein function. The occurrence of BCAA in nature is, therefore, attributable to their primary role in protein structure, not to their secondary metabolic roles. These functions are important for almost all proteins; therefore, BCAA commonly account for approximately 20-25% of most dietary proteins. Dietary BCAA largely escape first-pass splanchnic metabolism. The first steps in their catabolism are common to all three, involving the BCAA aminotransferase (BCAT) and branched-chain alpha-keto acid dehydrogenase (BCKD). Their further metabolism employs distinct pathways to different end-products (glucose and/or ketone bodies). However, the fact that the flux-generating step for the catabolism of the three BCAAs occurs at one of the common steps indicates that the production of these downstream products are not individually regulated and, hence, may not play important individual roles. The catabolism of the BCAAs is highly regulated by both allosteric and covalent mechanisms. BCKD is inhibited by phosphorylation and activated by dephosphorylation. Allosteric inhibition of the kinase by the branched-chain keto acids (BCKA) (particularly by alpha-ketoisocaproate) serves both as a mechanism for promoting the catabolism of excess quantities of these amino acids as well as for conserving low concentrations of these dietary essential amino acids. Cytosolic and mitochondrial isoenzymes of BCAT have been identified. They are thought to play an important role in brain neurotransmitter metabolism.

Pomegranate Juice Ellagitannin Metabolites Are Present in Human Plasma and Some Persist in Urine for Up to 48 Hours

Abstract: Ellagitannins (ETs) from pomegranate juice (PJ) are reported to have numerous biological properties, but their absorption and metabolism in humans are poorly understood. To investigate the pharmacokinetics of pomegranate ETs, 18 healthy volunteers were given 180 mL of PJ concentrate, and blood samples were obtained for 6 h afterwards. Twenty-four-hour urine collections were obtained on the day before (-1), the day of (0), and the day after (+1) the study. Ellagic acid (EA) was detected in plasma of all subjects with a maximum concentration of 0.06 +/- 0.01 micromol/L, area under concentration time curve of 0.17 +/- 0.02 (micromol x h) x L(-1), time of maximum concentration of 0.98 +/- 0.06 h, and elimination half-life of 0.71 +/- 0.08 h. EA metabolites, including dimethylellagic acid glucuronide (DMEAG) and hydroxy-6H-benzopyran-6-one derivatives (urolithins), were also detected in plasma and urine in conjugated and free forms. DMEAG was found in the urine obtained from 15 of 18 subjects on d 0, but was not detected on d -1 or +1, demonstrating its potential as a biomarker of intake. Urolithin A-glucuronide was found in urine samples from 11 subjects on d 0 and in the urine from 16 subjects on d +1. Urolithin B-glucuronide was found in the urine of 3 subjects on d 0 and in the urine of 5 subjects on d +1. Urolithins, formed by intestinal bacteria, may contribute to the biological effects of PJ as they may persist in plasma and tissues and account for some of the health benefits noted after chronic PJ consumption. Whether genetic polymorphisms in EA-metabolizing enzymes (e.g., catechol-O-methyl transferase and glucuronosyl transferase) are related to variations in response to PJ remains to be established.

Mammalian Cysteine Metabolism: New Insights into Regulation of Cysteine Metabolism

Abstract: The mammalian liver tightly regulates its free cysteine pool, and intracellular cysteine in rat liver is maintained between 20 and 100 nmol/g even when sulfur amino acid intakes are deficient or excessive. By keeping cysteine levels within a narrow range and by regulating the synthesis of glutathione, which serves as a reservoir of cysteine, the liver addresses both the need to have adequate cysteine to support normal metabolism and the need to keep cysteine levels below the threshold of toxicity. Cysteine catabolism is tightly regulated via regulation of cysteine dioxygenase (CDO) levels in the liver, with the turnover of CDO protein being dramatically decreased when intracellular cysteine levels increase. This occurs in response to changes in the intracellular cysteine concentration via changes in the rate of CDO ubiquitination and degradation. Glutathione synthesis also increases when intracellular cysteine levels increase as a result of increased saturation of glutamate-cysteine ligase (GCL) with cysteine, and this contributes to removal of excess cysteine. When cysteine levels drop, GCL activity increases, and the increased capacity for glutathione synthesis facilitates conservation of cysteine in the form of glutathione (although the absolute rate of glutathione synthesis still decreases because of the lack of substrate). This increase in GCL activity is dependent on up-regulation of expression of both the catalytic and modifier subunits of GCL, resulting in an increase in total catalytic subunit plus an increase in the catalytic efficiency of the enzyme. An important role of cysteine utilization for coenzyme A synthesis in maintaining cellular cysteine levels in some tissues, and a possible connection between the necessity of controlling cellular cysteine levels to regulate the rate of hydrogen sulfide production, have been suggested by recent literature and are areas that deserve further study.

Unmetabolized Folic Acid in Plasma Is Associated with Reduced Natural Killer Cell Cytotoxicity among Postmenopausal Women

Abstract: Folic acid (FA) supplements and food fortification are used to prevent neural tube defects and to lower plasma homocysteine. Through exposure to food fortification and vitamin supplement use, large populations in the United States and elsewhere have an unprecedented high FA intake. We evaluated dietary and supplemental intakes of folate and FA in relation to an index of immune function, natural killer cell (NK) cytotoxicity, among 105 healthy, postmenopausal women. Among women with a diet low in folate ( 400 microg/d had reduced NK cytotoxicity compared with those consuming a low-folate diet and no supplements (P = 0.02). Prompted by this observation, we assessed the presence of unmetabolized FA in plasma as a biochemical marker of excess FA. Unmetabolized folic acid was detected in 78% of plasma samples from fasting participants. We found an inverse relation between the presence of unmetabolized FA in plasma and NK cytotoxicity. NK cytotoxicity was approximately 23% lower among women with detectable folic acid (P = 0.04). This inverse relation was stronger among women >or= 60 y old and more pronounced with increasing unmetabolized FA concentrations (P-trend = 0.002). Because of the increased intake of FA in many countries, our findings highlight the need for further studies on the effect of long-term high FA intake on immune function and health.

Structure of the Blood–Brain Barrier and Its Role in the Transport of Amino Acids

Abstract: Brain capillary endothelial cells form the blood-brain barrier (BBB). They are connected by extensive tight junctions, and are polarized into luminal (blood-facing) and abluminal (brain-facing) plasma membrane domains. The polar distribution of transport proteins mediates amino acid (AA) homeostasis in the brain. The existence of two facilitative transporters for neutral amino acids (NAAs) on both membranes provides the brain access to essential AAs. Four Na(+)-dependent transporters of NAA exist in the abluminal membranes of the BBB. Together these systems have the capability to actively transfer every naturally occurring NAA from the extracellular fluid (ECF) to endothelial cells and from there into circulation. The presence of Na(+)-dependent carriers on the abluminal membrane provides a mechanism by which NAA concentrations in the ECF of brain are maintained at approximately 10% those of the plasma. Also present on the abluminal membrane are at least three Na(+)-dependent systems transporting acidic AAs (EAAT) and a Na(+)-dependent system transporting glutamine (N). Facilitative carriers for glutamine and glutamate are found only in the luminal membrane of the BBB. This organization promotes the net removal of acidic- and nitrogen-rich AAs from the brain and accounts for the low level of glutamate penetration into the central nervous system. The presence of a gamma-glutamyl cycle at the luminal membrane and Na(+)-dependent AA transporters at the abluminal membrane may serve to modulate movement of AAs from blood to the brain. The gamma-glutamyl cycle is expected to generate pyroglutamate (synonymous with oxyproline) within the endothelial cells. Pyroglutamate stimulates secondary active AA transporters at the abluminal membrane, thereby reducing the net influx of AAs to the brain. It is now clear that BBB participates in the active regulation of the AA content of the brain.

Commonalities in the Experience of Household Food Insecurity across Cultures: What Are Measures Missing?

Abstract: This paper hypothesizes that there is a common "core" to the household food insecurity experience that goes beyond insufficient food quantity and that transcends culture. The paper for the first time employs an exploratory approach to identify cross-cultural commonalities of the food insecurity experience as captured in 22 scales and related ethnographies derived from 15 different countries. The constant comparative method was used to code elements of the food insecurity experience expressed in the ethnographies and to regroup them into domains and subdomains. This typology was then applied to ascertain which experiential domains and subdomains were measured (or not) across all 22 studies. Survey data from 11 of the studies were then analyzed to assess similarities in the relative frequency with which culturally diverse households responded to questionnaire items related to these common domains/subdomains. The analysis confirmed that insufficient food quantity, inadequate food quality, and uncertainty and worry about food were a significant part of the food insecurity experience in all sampled cultures; concerns about social unacceptability emerged in all ethnographic accounts. Several subdomains were identified, such as concern over food safety and meal pattern disruption, with potentially important consequences for physical and psychological well-being. The comparative survey data showed that the relative frequency at which populations responded to domain-related questionnaire items was similar across all but a few cultures. Future food insecurity assessments should consider these core domains and subdomains as the starting point for measures that can generate rich information to inform food security policies and programs.

Garlic and Cardiovascular Disease: A Critical Review

Abstract: Epidemiologic studies show an inverse correlation between garlic consumption and progression of cardiovascular disease. Cardiovascular disease is associated with multiple factors such as raised serum total cholesterol, raised LDL and an increase in LDL oxidation, increased platelet aggregation, hypertension, and smoking. Numerous in vitro studies have confirmed the ability of garlic to reduce these parameters. Thus, garlic has been shown to inhibit enzymes involved in lipid synthesis, decrease platelet aggregation, prevent lipid peroxidation of oxidized erythrocytes and LDL, increase antioxidant status, and inhibit angiotension-converting enzyme. These findings have also been addressed in clinical trials. The studies point to the fact that garlic reduces cholesterol, inhibits platelet aggregation, reduces blood pressure, and increases antioxidant status. Since 1993, 44% of clinical trials have indicated a reduction in total cholesterol, and the most profound effect has been observed in garlic's ability to reduce the ability of platelets to aggregate. Mixed results have been obtained in the area of blood pressure and oxidative-stress reduction. The findings are limited because very few trials have addressed these issues. The negative results obtained in some clinical trials may also have resulted from usage of different garlic preparations, unknown active constituents and their bioavalability, inadequate randomization, selection of inappropriate subjects, and short duration of trials. This review analyzes in vitro and in vivo studies published since 1993 and concludes that although garlic appears to hold promise in reducing parameters associated with cardiovascular disease, more in-depth and appropriate studies are required.

Development of a Universally Applicable Household Food Insecurity Measurement Tool: Process, Current Status, and Outstanding Issues

Abstract: The United States Public Law 480 Title II food aid program is the largest U.S. government program directed at reducing hunger, malnutrition, and food insecurity in the developing world. USAID and Title II implementing partners face challenges in measuring the success of Title II programs in reducing household food insecurity because of the technical difficulty and cost of collecting and analyzing data on traditional food security indicators, such as per capita income and caloric adequacy. The Household Food Insecurity Access Scale (HFIAS) holds promise as an easier and more user-friendly approach for measuring the access component of household food security. To support the consistent and comparable collection of the HFIAS, efforts are under way to develop a guide with a standardized questionnaire and data collection and analysis instructions. A set of domains have been identified that is deemed to capture the universal experience of the access component of household food insecurity across countries and cultures. Based on these domains, a set of questions has been developed with wording that is deemed to be universally appropriate, with minor adaptation to local contexts. These underlying suppositions, based on research in multiple countries, are being verified by potential users of the guide. The key remaining issue relates to the process for creating a categorical indicator of food insecurity status from the HFIAS.

Psychosocial Factors and Socioeconomic Indicators Are Associated with Household Food Insecurity among Pregnant Women

Abstract: Household food insecurity has been associated with several negative health outcomes, yet little is known about the prevalence and correlates of household food insecurity during pregnancy. This study was conducted as part of the Pregnancy, Infection, and Nutrition prospective cohort study to identify risk factors of preterm birth. The USDA 18-item scale was used to assess the prevalence of food insecurity among pregnant women with incomes

Quercetin Induces Apoptosis via Caspase Activation, Regulation of Bcl-2, and Inhibition of PI-3-Kinase/Akt and ERK Pathways in a Human Hepatoma Cell Line (HepG2)

Abstract: Dietary polyphenols have been associated with the reduced risk of chronic diseases such as cancer, but the precise underlying mechanism of protection remains unclear. The aim of this study was to investigate the effect of quercetin on the activation of the apoptotic pathway in a human hepatoma cell line (HepG2). Treatment of cells for 18 h with quercetin induced cell death in a dose-dependent manner; however, a shorter treatment (4 h) had no effect on cell viability. Incubation of HepG2 cells with quercetin for 18 h induced apoptosis by the activation of caspase-3 and -9, but not caspase-8. Moreover, this flavonoid decreased the Bcl-xL:Bcl-xS ratio and increased translocation of Bax to the mitochondrial membrane. A sustained inhibition of the major survival signals, Akt and extracellular regulated kinase (ERK), also occurred in quercetin-treated cells. These data suggest that quercetin may induce apoptosis by direct activation of caspase cascade (mitochondrial pathway) and by inhibiting survival signaling in HepG2.

Vitamin D and African Americans

Abstract: Vitamin D insufficiency is more prevalent among African Americans (blacks) than other Americans and, in North America, most young, healthy blacks do not achieve optimal 25-hydroxyvitamin D [25(OH)D] concentrations at any time of year. This is primarily due to the fact that pigmentation reduces vitamin D production in the skin. Also, from about puberty and onward, median vitamin D intakes of American blacks are below recommended intakes in every age group, with or without the inclusion of vitamin D from supplements. Despite their low 25(OH)D levels, blacks have lower rates of osteoporotic fractures. This may result in part from bone-protective adaptations that include an intestinal resistance to the actions of 1,25(OH)2D and a skeletal resistance to the actions of parathyroid hormone (PTH). However, these mechanisms may not fully mitigate the harmful skeletal effects of low 25(OH)D and elevated PTH in blacks, at least among older individuals. Furthermore, it is becoming increasingly apparent that vitamin D protects against other chronic conditions, including cardiovascular disease, diabetes, and some cancers, all of which are as prevalent or more prevalent among blacks than whites. Clinicians and educators should be encouraged to promote improved vitamin D status among blacks (and others) because of the low risk and low cost of vitamin D supplementation and its potentially broad health benefits.

Epigallocatechin Gallate Supplementation Alleviates Diabetes in Rodents

Abstract: As the prevalence of type 2 diabetes mellitus is increasing at an alarming rate, effective nutritional and exercise strategies for the prevention of this disease are required. Specific dietary components with antidiabetic efficacy could be one aspect of these strategies. This study investigated the antidiabetic effects of the most abundant green tea catechin, epigallocatechin gallate (EGCG, TEAVIGO), in rodent models of type 2 diabetes mellitus and H4IIE rat hepatoma cells. We assessed glucose and insulin tolerance in db/db mice and ZDF rats after they ingested EGCG. Using gene microarray and real-time quantitative RT-PCR we investigated the effect of EGCG on gene expression in H4IIE rat hepatoma cells as well as in liver and adipose tissue of db/db mice. EGCG improved oral glucose tolerance and blood glucose in food-deprived rats in a dose-dependent manner. Plasma concentrations of triacylglycerol were reduced and glucose-stimulated insulin secretion was enhanced. In H4IIE cells, EGCG downregulated genes involved in gluconeogenesis and the synthesis of fatty acids, triacylgycerol, and cholesterol. EGCG decreased the mRNA expression of phosphoenolpyruvate carboxykinase in H4IIE cells as well as in liver and adipose tissue of db/db mice. Glucokinase mRNA expression was upregulated in the liver of db/db mice in a dose-dependent manner. This study shows that EGCG beneficially modifies glucose and lipid metabolism in H4IIE cells and markedly enhances glucose tolerance in diabetic rodents. Dietary supplementation with EGCG could potentially contribute to nutritional strategies for the prevention and treatment of type 2 diabetes mellitus.

Potential Importance of Leucine in Treatment of Obesity and the Metabolic Syndrome

Abstract: Diets with total protein intake >1.5 g.kg(-1).d(-1) and carbohydrate intake <150 g/d are effective for treatment of obesity, type 2 diabetes, and the Metabolic Syndrome. These diets improve body composition and enhance glycemic control. During weight loss, protein-rich diets reduce loss of lean tissue and increase loss of body fat. Specific mechanisms to explain each of these clinical outcomes remain to be fully elucidated. We propose that keys to understanding the relationship between dietary protein and carbohydrates are the relationships between the branched-chain amino acid leucine and insulin and glucose metabolism. Leucine is known to interact with the insulin signaling pathway to stimulate downstream signal control of protein synthesis, resulting in maintenance of muscle protein during periods of restricted energy intake. Leucine also appears to modulate insulin signaling and glucose use by skeletal muscle. Whereas total protein is important in providing substrates for gluconeogenesis, leucine appears to regulate oxidative use of glucose by skeletal muscle through stimulation of glucose recycling via the glucose-alanine cycle. These mechanisms produce protein sparing and provide a stable glucose environment with low insulin responses during energy-restricted periods.

Recent Advances on Structure, Metabolism, and Function of Human Milk Oligosaccharides

Abstract: Human milk is often the sole dietary source for the first few months in life. It contains all the nutrients necessary for the infant to thrive, but also ingredients that may provide health benefits beyond those of traditional nutrients. Human milk oligosaccharides (HMO) comprise part of these functional ingredients; 1 L of mature human milk contains approximately 5-10 g unbound oligosaccharides, and >130 different HMO have been identified. Both their high amount and structural diversity are unique to humans. Only trace amounts of these oligosaccharides are present in mature bovine milk and, as a consequence, in bovine milk-based infant formula. The potential health benefits of HMO that were uncovered over the years may affect breast-fed infants both locally and systemically. Recent advances in glycobiology and nutrition, including the use of stable isotopes, frontal-affinity chromatography, glycan microarrays, MS, and automated solid-phase carbohydrate synthesis, will help verify hypotheses and unravel the mysteries behind HMO.

Branched-Chain Amino Acids Activate Key Enzymes in Protein Synthesis after Physical Exercise

Abstract: BCAAs (leucine, isoleucine, and valine), particularly leucine, have anabolic effects on protein metabolism by increasing the rate of protein synthesis and decreasing the rate of protein degradation in resting human muscle. Also, during recovery from endurance exercise, BCAAs were found to have anabolic effects in human muscle. These effects are likely to be mediated through changes in signaling pathways controlling protein synthesis. This involves phosphorylation of the mammalian target of rapamycin (mTOR) and sequential activation of 70-kD S6 protein kinase (p70 S6 kinase) and the eukaryotic initiation factor 4E-binding protein 1. Activation of p70 S6 kinase, and subsequent phopsphorylation of the ribosomal protein S6, is associated with enhanced translation of specific mRNAs. When BCAAs were supplied to subjects during and after one session of quadriceps muscle resistance exercise, an increase in mTOR, p70 S6 kinase, and S6 phosphorylation was found in the recovery period after the exercise with no effect of BCAAs on Akt or glycogen synthase kinase 3 (GSK-3) phosphorylation. Exercise without BCAA intake led to a partial phosphorylation of p70 S6 kinase without activating the enzyme, a decrease in Akt phosphorylation, and no change in GSK-3. It has previously been shown that leucine infusion increases p70 S6 kinase phosphorylation in an Akt-independent manner in resting subjects; however, a relation between mTOR and p70 S6 kinase has not been reported previously. The results suggest that BCAAs activate mTOR and p70 S6 kinase in human muscle in the recovery period after exercise and that GSK-3 is not involved in the anabolic action of BCAAs on human muscle.

Method of Defining Equol-Producer Status and Its Frequency among Vegetarians

Abstract: 7-Hydroxy-3-(4'-hydroxyphenyl)-chroman (S-equol) is a specific end-metabolite formed in the biotransformation of the dietary soy isoflavones daidzin and daidzein by intestinal bacteria. The frequency of equol production varies among individuals and populations, and it is suggested that the efficacy of soy foods differs depending on the ability of an individual to produce equol. To develop a standardized approach to define equol-producer status that can be universally adopted to differentiate these 2 distinct populations, we measured isoflavones in serum and urine collected from a cohort of 41 healthy adults, comprising 29 vegetarians and 12 nonvegetarians, after consuming 2 x 250 mL/d soy milk on 3 consecutive days. Serum and urinary daidzein and S-equol concentrations were analyzed by MS. Serum S-equol and daidzein concentrations ranged from 10.3-139 nmol/L (2.5-33.6 microg/L) and 16-1401 nmol/L (4.0-356 microg/L), respectively, whereas in urine the corresponding concentrations ranged from 16-12,574 nmol/L (4-3043 microg/L) and 539-26,834 nmol/L (137-6816 microg/L), respectively. The log10-transformed urinary S-equol:daidzein ratio provided a clearer distinction of equol-producer status than the absolute serum or urinary S-equol concentrations because it is independent of isoflavone intake and minimizes interindividual variation in isoflavone pharmacokinetics or differences in analytical methodologies. A threshold value for the log10-transformed urinary S-equol:daidzein ratio of -1.75 provided a demarcation to define equol-producer status. The frequency of equol producers in the vegetarians was 59%, similar to the reported frequency in Japanese adults consuming soy, and much higher than for nonvegetarian adults (25%), suggesting that dietary components other than soy influence S-equol synthesis by intestinal bacteria.

Child Food Insecurity Increases Risks Posed by Household Food Insecurity to Young Children's Health

Abstract: The US Food Security Scale (USFSS) measures household and child food insecurity (CFI) separately. Our goal was to determine whether CFI increases risks posed by household food insecurity (HFI) to child health and whether the Food Stamp Program (FSP) modifies these effects. From 1998 to 2004, 17,158 caregivers of children ages 36 mo were interviewed in six urban medical centers. Interviews included demographics, the USFSS, child health status, and hospitalization history. Ten percent reported HFI, 12% HFI and CFI (H&CFI). Compared with food-secure children, those with HFI had significantly greater adjusted odds of fair/poor health and being hospitalized since birth, and those with H&CFI had even greater adverse effects. Participation in the FSP modified the effects of FI on child health status and hospitalizations, reducing, but not eliminating, them. Children in FSP-participating households that were HFI had lower adjusted odds of fair/poor health [1.37 (95% CI, 1.06-1.77)] than children in similar non-FSP households [1.61 (95% CI, 1.31-1.98)]. Children in FSP-participating households that were H&CFI also had lower adjusted odds of fair/poor health [1.72 (95% CI, 1.34-2.21)] than in similar non-FSP households [2.14 (95% CI, 1.81-2.54)]. HFI is positively associated with fair/poor health and hospitalizations in young children. With H&CFI, odds of fair/poor health and hospitalizations are even greater. Participation in FSP reduces, but does not eliminate, effects of FI on fair/poor health.

Daily Polyphenol Intake in France from Fruit and Vegetables

Abstract: The objective of this study was to create a French database on the polyphenol content of fruit and vegetables as uncooked fruits and vegetables and then to evaluate polyphenol intake through fruit and vegetable consumption in France. To achieve this, we used the Folin-Ciocalteu method adapted to fruit and vegetable polyphenol quantitation (1). Vegetables with the highest polyphenol concentration were artichokes, parsley, and brussels sprouts [.250 mg of gallic acid equivalent (GAE)/100 g fresh edible portion (FEP)]; fruits with the highest concentrations were strawberries, lychees, and grapes (.180 mg of GAE/100 g FEP). Conversely, melons (Cantaloupe cv.) and avocados had the lowest polyphenol concentration for fruits and vegetables, respectively. Based on fruit consumption data, apples and strawberries are the main sources of polyphenols in the French diet, whereas potatoes, lettuces, and onions are the most important vegetable sources. Total polyphenol intake from fruit is about 3 times higher than from vegetables, due to the lower polyphenol

Leucine Regulates Translation Initiation of Protein Synthesis in Skeletal Muscle after Exercise

Abstract: High-performance physical activity and postexercise recovery lead to significant changes in amino acid and protein metabolism in skeletal muscle. Central to these changes is an increase in the metabolism of the BCAA leucine. During exercise, muscle protein synthesis decreases together with a net increase in protein degradation and stimulation of BCAA oxidation. The decrease in protein synthesis is associated with inhibition of translation initiation factors 4E and 4G and ribosomal protein S6 under regulatory controls of intracellular insulin signaling and leucine concentrations. BCAA oxidation increases through activation of the branched-chain alpha-keto acid dehydrogenase (BCKDH). BCKDH activity increases with exercise, reducing plasma and intracellular leucine concentrations. After exercise, recovery of muscle protein synthesis requires dietary protein or BCAA to increase tissue levels of leucine in order to release the inhibition of the initiation factor 4 complex through activation of the protein kinase mammalian target of rapamycin (mTOR). Leucine's effect on mTOR is synergistic with insulin via the phosphoinositol 3-kinase signaling pathway. Together, insulin and leucine allow skeletal muscle to coordinate protein synthesis with physiological state and dietary intake.

Bioavailability Is Improved by Enzymatic Modification of the Citrus Flavonoid Hesperidin in Humans: A Randomized, Double-Blind, Crossover Trial

Abstract: Hesperidin is the predominant polyphenol consumed from citrus fruits and juices. However, hesperidin is proposed to have limited bioavailability due to the rutinoside moiety attached to the flavonoid. The aim of this study was to demonstrate in human subjects that the removal of the rhamnose group to yield the corresponding flavonoid glucoside (i.e., hesperetin-7-glucoside) will improve the bioavailability of the aglycone hesperetin. Healthy volunteers (n=16) completed the double-blind, randomized, crossover study. Subjects randomly consumed hesperetin equivalents supplied as orange juice with natural hesperidin ("low dose"), orange juice treated with hesperidinase enzyme to yield hesperetin-7-glucoside, and orange juice fortified to obtain 3 times more hesperidin than naturally present ("high dose"). The area under the curve (AUC) for total plasma hesperetin of subjects consuming hesperetin-7-glucoside juice was 2-fold higher than that of subjects consuming the "low" dose hesperidin juice [3.45+/-1.27 vs. 1.16+/-0.52 mmol/(L.h), respectively, P>0.0001]. The AUC for hesperetin after consuming the hesperetin-7-glucoside juice was improved to the level of the "high" dose hesperidin juice [4.16+/-1.50 mmol/(L.h)]. The peak plasma concentrations (C(max)) of hesperetin were 4-fold higher (2.60+/-1.07 mmol/L, P<0.0001) after subjects consumed hesperetin-7-glucoside juice compared with those consuming "low" dose hesperidin juice (0.48 +/- 0.27 mmol/L), and 1.5-fold higher than those consuming "high" dose hesperidin juice (1.05+/-0.25 mmol/L). The corresponding T(max) was much faster (0.6+/-0.1 h, P<0.0001) after subjects consumed hesperetin-7-glucoside juice compared with "low" dose (7.0+/-3.0 h) and "high" dose (7.4+/-2.0 h) hesperidin juices. The results of this study demonstrated that the bioavailability of hesperidin was modulated by enzymatic conversion to hesperetin-7-glucoside, thus changing the absorption site from the colon to the small intestine. This may affect future interventions concerning the health benefits of citrus flavonoids.

Diet Quality Is Associated with the Risk of Estrogen Receptor–Negative Breast Cancer in Postmenopausal Women

Abstract: Emerging evidence suggests that diet quality indices may serve as prognostic indicators of disease. However, the ability of these indices to predict breast cancer risk has not been evaluated previously. We assessed the association between several diet quality scores and the risk of breast cancer in postmenopausal women. The indices we used were the Healthy Eating Index (HEI), Alternate Healthy Eating Index (AHEI), Diet Quality Index-Revised (DQI-R), Recommended Food Score (RFS), and the alternate Mediterranean Diet Score (aMed). We calculated diet quality indices from dietary information collected in FFQ administered 5 times between 1984 and 1998 among women in the Nurses' Health Study cohort. Relative risks (RR) were computed using Cox proportional hazards models and adjusted for known risk factors for breast cancer. Separate analyses were conducted for estrogen receptor positive (ER+) and negative (ER-) tumors. Between 1984 and 2002, we documented 3,580 cases of breast cancer, of which 2,367 were ER+, and 575 were ER-. We did not observe any association between the diet quality indices and total or ER+ breast cancer risk. However, for ER- breast cancer, after adjusting for potential confounders, the RR comparing highest to lowest quintiles were 0.78 (95% CI=0.59-1.04, P for trend=0.01) for the AHEI, 0.69 (95% CI=0.51-0.94, P for trend=0.003) for the RFS, and 0.79 (95% CI=0.60-1.03, P for trend=0.03) for the aMed. These observations appeared to be the result of an inverse association (P for trend=0.01) with the vegetable component of the scores. We conclude that women who scored high in AHEI, RFS, and aMed had a lower risk of ER- breast cancer. The HEI and DQI-R appeared to be of limited value in predicting breast cancer risk.