Showing papers in "Journal of Nutrition in 2005"

Circulating 25-Hydroxyvitamin D Levels Indicative of Vitamin D Sufficiency: Implications for Establishing a New Effective Dietary Intake Recommendation for Vitamin D

Abstract: It has been more than 3 decades since the first assay assessing circulating 25-hydroxyvitamin D [25(OH)D] in human subjects was performed and led to the definition of "normal" nutritional vitamin D status, i.e., vitamin D sufficiency. Sampling human subjects, who appear to be free from disease, and assessing "normal" circulating 25(OH)D levels based on a Gaussian distribution of these values is now considered to be a grossly inaccurate method of identifying the normal range. Several factors contribute to the inaccuracy of this approach, including race, lifestyle habits, sunscreen usage, age, latitude, and inappropriately low dietary intake recommendations for vitamin D. The current adult recommendations for vitamin D, 200-600 IU/d, are very inadequate when one considers that a 10-15 min whole-body exposure to peak summer sun will generate and release up to 20,000 IU vitamin D-3 into the circulation. We are now able to better identify sufficient circulating 25(OH)D levels through the use of specific biomarkers that appropriately increase or decrease with changes in 25(OH)D levels; these include intact parathyroid hormone, calcium absorption, and bone mineral density. Using these functional indicators, several studies have more accurately defined vitamin D deficiency as circulating levels of 25(OH)D < or = 80 nmol or 32 microg/L. Recent studies reveal that current dietary recommendations for adults are not sufficient to maintain circulating 25(OH)D levels at or above this level, especially in pregnancy and lactation.

Dietary Protein Restriction of Pregnant Rats Induces and Folic Acid Supplementation Prevents Epigenetic Modification of Hepatic Gene Expression in the Offspring

Abstract: Environmental constraints during early life result in phenotypic changes that can be associated with increased disease risk in later life. This suggests persistent alteration of gene transcription. DNA methylation, which is largely established in utero, provides a causal mechanism by which unbalanced prenatal nutrition results in such altered gene expression. We investigated the effect of unbalanced maternal nutrition on the methylation status and expression of the glucocorticoid receptor (GR) and peroxisomal proliferator-activated receptor (PPAR) genes in rat offspring after weaning. Dams were fed a control protein (C; 180 g/kg protein plus 1 mg/kg folic acid), restricted protein (R; 90 g/kg casein plus 1 mg/kg folic acid), or restricted protein plus 5 mg/kg folic acid (RF) diet throughout pregnancy. Pups were killed 6 d after weaning (n = 10 per group). Gene methylation was determined by methylation-sensitive PCR and mRNA expression by semiquantitative RT-PCR. PPARalpha gene methylation was 20.6% lower (P < 0.001) and expression 10.5-fold higher in R compared with C pups. GR gene methylation was 22.8% lower (P < 0.05) and expression 200% higher (P < 0.01) in R pups than in C pups. The RF diet prevented these changes. PPARgamma methylation status and expression did not differ among the groups. Acyl-CoA oxidase expression followed that of PPARalpha. These results show that unbalanced prenatal nutrition induces persistent, gene-specific epigenetic changes that alter mRNA expression. Epigenetic regulation of gene transcription provides a strong candidate mechanism for fetal programming.

Food insecurity affects school children's academic performance, weight gain, and social skills

Abstract: Food insecurity has been associated with diverse developmental consequences for U.S. children primarily from cross-sectional studies. We used longitudinal data to investigate how food insecurity over time related to changes in reading and mathematics test performance, weight and BMI, and social skills in children. Data were from the Early Childhood Longitudinal Study-Kindergarten Cohort, a prospective sample of approximately 21,000 nationally representative children entering kindergarten in 1998 and followed through 3rd grade. Food insecurity was measured by parent interview using a modification of the USDA module in which households were classified as food insecure if they reported > or =1 affirmative response in the past year. Households were grouped into 4 categories based on the temporal occurrence of food insecurity in kindergarten and 3rd grade. Children's academic performance, height, and weight were assessed directly. Children's social skills were reported by teachers. Analyses examined the effects of modified food insecurity on changes in child outcomes using lagged, dynamic, and difference (i.e., fixed-effects) models and controlling for child and household contextual variables. In lagged models, food insecurity was predictive of poor developmental trajectories in children before controlling for other variables. Food insecurity thus serves as an important marker for identifying children who fare worse in terms of subsequent development. In all models with controls, food insecurity was associated with outcomes, and associations differed by gender. This study provides the strongest empirical evidence to date that food insecurity is linked to specific developmental consequences for children, and that these consequences may be both nutritional and nonnutritional.

Food Choices and Diet Costs: an Economic Analysis

Abstract: Obesity in the United States is a socioeconomic issue. It is related to limited social and economic resources and may be linked to disparities in access to healthy foods. Added sugars and added fats are far more affordable than are the recommended "healthful" diets based on lean meats, whole grains, and fresh vegetables and fruit. There is an inverse relationship between energy density of foods (kJ/g) and energy cost ($/MJ), such that energy-dense grains, fats, and sweets represent the lowest-cost dietary options to the consumer. Good taste, high convenience, and the low cost of energy-dense foods, in conjunction with large portions and low satiating power, may be the principal reasons for overeating and weight gain. Financial disparities in access to healthier diets may help explain why the highest rates of obesity and diabetes are found among minorities and the working poor. If so, then encouraging low-income households to consume more costly foods is not an effective strategy for public health. What is needed is a comprehensive policy approach that takes behavioral nutrition and the economics of food choice into account.

Consumption of Trans Fatty Acids Is Related to Plasma Biomarkers of Inflammation and Endothelial Dysfunction

Abstract: Trans fatty acid intake has been associated with a higher risk of cardiovascular disease. The relation is explained only partially by the adverse effect of these fatty acids on the lipid profile. We examined whether trans fatty acid intake could also affect biomarkers of inflammation and endothelial dysfunction including C-reactive protein (CRP), interleukin-6 (IL-6), soluble tumor necrosis factor receptor 2 (sTNFR-2), E-selectin, and soluble cell adhesion molecules (sICAM-1 and sVCAM-1). We conducted a cross-sectional study of 730 women from the Nurses' Health Study I cohort, aged 43-69 y, free of cardiovascular disease, cancer, and diabetes at time of blood draw (1989-1990). Dietary intake was assessed by a validated FFQ in 1986 and 1990. CRP levels were 73% higher among those in the highest quintile of trans fat intake, compared with the lowest quintile. IL-6 levels were 17% higher, sTNFR-2 5%, E-selectin 20%, sICAM-1 10%, and sVCAM-1 levels 10% higher. Trans fatty acid intake was positively related to plasma concentration of CRP (P = 0.009), sTNFR-2 (P = 0.002), E-selectin (P = 0.003), sICAM-1 (P = 0.007), and sVCAM-1 (P = 0.001) in linear regression models after controlling for age, BMI, physical activity, smoking status, alcohol consumption, intake of monounsaturated, polyunsaturated, and saturated fatty acids, and postmenopausal hormone therapy. In conclusion, this study suggests that higher intake of trans fatty acids could adversely affect endothelial function, which might partially explain why the positive relation between trans fat and cardiovascular risk is greater than one would predict based solely on its adverse effects on lipids.

The Vitamin D Epidemic and its Health Consequences

Abstract: Vitamin D deficiency is now recognized as an epidemic in the United States. The major source of vitamin D for both children and adults is from sensible sun exposure. In the absence of sun exposure 1000 IU of cholecalciferol is required daily for both children and adults. Vitamin D deficiency causes poor mineralization of the collagen matrix in young children's bones leading to growth retardation and bone deformities known as rickets. In adults, vitamin D deficiency induces secondary hyperparathyroidism, which causes a loss of matrix and minerals, thus increasing the risk of osteoporosis and fractures. In addition, the poor mineralization of newly laid down bone matrix in adult bone results in the painful bone disease of osteomalacia. Vitamin D deficiency causes muscle weakness, increasing the risk of falling and fractures. Vitamin D deficiency also has other serious consequences on overall health and well-being. There is mounting scientific evidence that implicates vitamin D deficiency with an increased risk of type I diabetes, multiple sclerosis, rheumatoid arthritis, hypertension, cardiovascular heart disease, and many common deadly cancers. Vigilance of one's vitamin D status by the yearly measurement of 25-hydroxyvitamin D should be part of an annual physical examination.

The influence of vitamin D on bone health across the life cycle : The vitamin D epidemic and its health consequences

Abstract: Vitamin D deficiency is now recognized as an epidemic in the United States. The major source of vitamin D for both children and adults is from sensible sun exposure. In the absence of sun exposure 1000 IU of cholecalciferol is required daily for both children and adults. Vitamin D deficiency causes poor mineralization of the collagen matrix in young children's bones leading to growth retardation and bone deformities known as rickets. In adults, vitamin D deficiency induces secondary hyperparathyroidism, which causes a loss of matrix and minerals, thus increasing the risk of osteoporosis and fractures. In addition, the poor mineralization of newly laid down bone matrix in adult bone results in the painful bone disease of osteomalacia. Vitamin D deficiency causes muscle weakness, increasing the risk of falling and fractures. Vitamin D deficiency also has other serious consequences on overall health and well-being. There is mounting scientific evidence that implicates vitamin D deficiency with an increased risk of type I diabetes, multiple sclerosis, rheumatoid arthritis, hypertension, cardiovascular heart disease, and many common deadly cancers. Vigilance of one's vitamin D status by the yearly measurement of 25-hydroxyvitamin D should be part of an annual physical examination.

Nutritional, dietary and postprandial oxidative stress

Abstract: Nutritional, or dietary oxidative stress denotes a disturbance of the redox state resulting from excess oxidative load or from inadequate nutrient supply favoring prooxidant reactions. Low intake or impaired availability of dietary antioxidants including vitamins E and C, carotenoids, polyphenols, and other micronutrients (e.g., selenium) weakens the antioxidant network. Postprandial oxidative stress, as a subform of nutritional oxidative stress, ensues from sustained postprandial hyperlipidemia and/or hyperglycemia and is associated with a higher risk for atherosclerosis, diabetes, and obesity. In Western societies, a significant part of the day is spent in the postprandial state. Unsaturated fatty acids incorporated into LDL and oxidized LDL are an atherogenic factor. Lipid hydroperoxides present in the diet are absorbed, contributing to the prooxidant load. In hyperlipidemic and hyperglycemic subjects, endothelium-dependent vasodilation is impaired in the postprandial state, making postprandial oxidative stress an important factor modulating cardiovascular risk. Postprandial oxidative stress is attenuated when dietary antioxidants are supplied together with a meal rich in oxidized or oxidizable lipids. Ingestion of dietary polyphenols, e.g., from wine, cocoa, or tea, improves endothelial dysfunction and lowers the susceptibility of LDL lipids to oxidation. Polyphenols affect endothelial function not solely as antioxidants but also as modulatory signaling molecules.

The Immunological Components of Human Milk and Their Effect on Immune Development in Infants

Abstract: There have been considerable advances in our understanding of the diverse mixture of bioactive components in human milk that influence the immune status of infants by not only providing protection but also facilitating development, tolerance, and an appropriate inflammatory response. It could be suggested that milk is the communication vehicle between the maternal immune system and the infant, a system actively directing and educating the immune, metabolic, and microflora systems within the infant, while conferring multiple means of protection from pathogens. The physiological and protective functions of many of the immune components in human milk have been deduced not from studies in infants but from what is known in other species and in vitro models. This update briefly reviews immune development in infants and focuses on current knowledge of how both the "classical" immune and the nonimmune ingredients found in mature human milk promote immune development, facilitate the development of tolerance, and regulate the inflammatory response of infants.

Vitamin D intake: a global perspective of current status.

Abstract: Global high prevalence of vitamin D insufficiency and re-emergence of rickets and the growing scientific evidence linking low circulating 25-hydroxyvitmain D to increased risk of osteoporosis, diabetes, cancer, and autoimmune disorders have stimulated recommendations to increase sunlight (UVB) exposure as a source of vitamin D. However, concern over increased risk of melanoma with unprotected UVB exposure has led to the alternative recommendation that sufficient vitamin D should be supplied through dietary sources alone. Here, we examine the adequacy of vitamin D intake worldwide and evaluate the ability of current fortification policies and supplement use practices among various countries to meet this recommendation. It is evident from our review that vitamin D intake is often too low to sustain healthy circulating levels of 25-hydroxyvitmain D in countries without mandatory staple food fortification, such as with milk and margarine. Even in countries that do fortify, vitamin D intakes are low in some groups due to their unique dietary patterns, such as low milk consumption, vegetarian diet, limited use of dietary supplements, or loss of traditional high fish intakes. Our global review indicates that dietary supplement use may contribute 6-47% of the average vitamin D intake in some countries. Recent studies demonstrate safety and efficacy of community-based vitamin D supplementation trials and food staple fortification introduced in countries without fortification policies. Reliance on the world food supply as an alternative to UVB exposure will necessitate greater availability of fortified food staples, dietary supplement use, and/or change in dietary patterns to consume more fish.

Tissue Distribution of Quercetin in Rats and Pigs

Abstract: Quercetin is a dietary polyphenolic compound with potentially beneficial effects on health. Claims that quercetin has biological effects are based mainly on in vitro studies with quercetin aglycone. However, quercetin is rapidly metabolized, and we have little knowledge of its availability to tissues. To assess the long-term tissue distribution of quercetin, 2 groups of rats were given a 0.1 or 1% quercetin diet [∼50 or 500 mg/kg body weight (wt)] for 11 wk. In addition, a 3-d study was done with pigs fed a diet containing 500 mg quercetin/kg body wt. Tissue concentrations of quercetin and quercetin metabolites were analyzed with an optimized extraction method. Quercetin and quercetin metabolites were widely distributed in rat tissues, with the highest concentrations in lungs (3.98 and 15.3 nmol/g tissue for the 0.1 and 1% quercetin diet, respectively) and the lowest in brain, white fat, and spleen. In the short-term pig study, liver (5.87 nmol/g tissue) and kidney (2.51 nmol/g tissue) contained high concentrations of quercetin and quercetin metabolites, whereas brain, heart, and spleen had low concentrations. These studies have for the first time identified target tissues of quercetin, which may help to understand its mechanisms of action in vivo. © 2005 American Society for Nutritional Sciences.

Fatty acid regulation of hepatic gene transcription.

Abstract: Dietary fat regulates gene expression by controlling the activity or abundance of key transcription factors. In vitro binding and cell culture studies have identified many transcription factors as prospective targets for fatty acid regulation, including peroxisome proliferator-activated receptors (PPARalpha, beta, gamma1, and gamma2), sterol regulatory element binding protein-1c (SREBP-1c), hepatic nuclear factors (HNF-4alpha and gamma), retinoid X receptor (RXRalpha), liver X receptor (LXRalpha), and others. In vivo studies established that PPARalpha- and SREBP-1c-regulated genes are key targets for PUFA control of hepatic gene expression. PUFA activate PPARalpha by direct binding, leading to the induction of hepatic fatty acid oxidation. PUFA inhibit hepatic fatty acid synthesis by suppressing SREBP-1c nuclear abundance through several mechanisms, including suppression of SREBP-1c gene transcription and enhancement of proteasomal degradation and mRNA(SREBP1c) decay. Changes in intracellular nonesterified fatty acids (NEFA) correlate well with changes in PPARalpha activity and mRNA(SREBP-1c) abundance. Several mechanisms regulate intracellular NEFA composition, including fatty acid transport, acyl CoA synthetases and thioesterases, fatty acid elongases and desaturases, neutral and polar lipid lipases, and fatty acid oxidation. Many of these mechanisms are regulated by PPARalpha or SREBP-1c. Together, these mechanisms control hepatic lipid composition and affect whole-body lipid composition.

Interventions Designed to Increase Adult Fruit and Vegetable Intake Can Be Effective: A Systematic Review of the Literature

Abstract: International recommendations advise increasing intakes of fruit and vegetables to help reduce the burden of chronic diseases worldwide. This project systematically reviewed evidence on the effectiveness of interventions and programs promoting fruit and/or vegetable intake in adults. In April 2004, we contacted experts in the field and searched 14 publication databases. We considered all papers published in English, French, Spanish, Portuguese, Russian, Danish, Norwegian, and Swedish, and reporting on interventions and promotion programs encouraging higher intakes of fruit and/or vegetables in free-living not acutely ill adults, with follow-up periods > or = 3 mo, that measured change in intake and had a control group. Forty-four studies (mainly from developed countries) were included in the review and stratified by study setting. Larger effects were generally observed in individuals with preexisting health disorders. In primary prevention interventions in healthy adults, fruit and vegetable intake was increased by approximately 0.1-1.4 serving/d. Consistent positive effects were seen in studies involving face-to-face education or counseling, but interventions using telephone contacts or computer-tailored information appeared to be a reasonable alternative. Community-based multicomponent interventions also had positive findings. This literature review suggests that small increases in fruit and vegetable intake are possible in population subgroups, and that these can be achieved by a variety of approaches. More research is required to examine the effectiveness of specific components of interventions in different populations, particularly less developed countries. There is also a need for a better assessment of the effectiveness and cost-effectiveness of large community-based interventions.

Mechanisms by which dietary fatty acids modulate plasma lipids.

Abstract: Dietary fatty acids have a considerable effect on plasma LDL cholesterol (LDL-C) concentrations and therefore on the risk for coronary heart disease. Numerous studies have been conducted in animal models to elucidate the mechanisms by which different types of fatty acids modulate plasma cholesterol concentrations. In addition, multiple clinical trials and epidemiological data have demonstrated the effects of fatty acids in determining the concentrations of circulating LDL. SFAs and trans fatty acids have a detrimental effect on plasma lipids, whereas PUFAs of the (n-6) family and monounsaturated fatty acids decrease plasma LDL-C concentrations. Among the SFAs, stearic acid (18:0) appears to have a neutral effect on LDL-C, while lauric (12:0), myristic (14:0), and palmitic (16:0) acids are considered to be hypercholesterolemic. SFAs increase plasma LDL-C by increasing the formation of LDL in the plasma compartment and by decreasing LDL turnover. Although unsaturated fatty acids increase cholesterol synthesis, they also increase hepatic LDL receptor number and LDL turnover in vivo. Fatty acids are also ligands of important regulatory elements, which can play a role in determining plasma cholesterol. This article presents a summary of the major effects of various types of fatty acids on plasma lipid concentrations and the mechanisms involved.

Human-Milk Glycans That Inhibit Pathogen Binding Protect Breast-feeding Infants against Infectious Diarrhea

Abstract: Breast-feeding is a highly effective strategy for preventing morbidity and mortality in infancy. The human-milk glycans, which include oligosaccharides in their free and conjugated forms, constitute a major and an innate immunologic mechanism by which human milk protects breast-fed infants against infections. The glycans found in human milk function as soluble receptors that inhibit pathogens from adhering to their target receptors on the mucosal surface of the host gastrointestinal tract. The alpha1,2-linked fucosylated glycans, which require the secretor gene for expression in human milk, are the dominant glycan structure found in the milk of secretor mothers, who constitute the majority ( approximately 80%) of mothers worldwide. In vitro and in vivo binding studies have demonstrated that alpha1,2-linked fucosylated glycans inhibit binding by campylobacter, stable toxin of enterotoxigenic Escherichia coli, and major strains of caliciviruses to their target host cell receptors. Consistent with these findings, recently published epidemiologic data demonstrate that higher relative concentrations of alpha1,2-linked fucosylated glycans in human milk are associated with protection of breast-fed infants against diarrhea caused by campylobacter, caliciviruses, and stable toxin of enterotoxigenic E. coli, and moderate-to-severe diarrhea of all causes. These novel data open the potential for translational research to develop the human-milk glycans as a new class of antimicrobial agents that prevent infection by acting as pathogen anti-adhesion agents.

Branched-Chain Amino Acids and Brain Function

Abstract: Branched-chain amino acids (BCAAs) influence brain function by modifying large, neutral amino acid (LNAA) transport at the blood-brain barrier. Transport is shared by several LNAAs, notably the BCAAs and the aromatic amino acids (ArAAs), and is competitive. Consequently, when plasma BCAA concentrations rise, which can occur in response to food ingestion or BCAA administration, or with the onset of certain metabolic diseases (e.g., uncontrolled diabetes), brain BCAA concentrations rise, and ArAA concentrations decline. Such effects occur acutely and chronically. Such reductions in brain ArAA concentrations have functional consequences: biochemically, they reduce the synthesis and the release of neurotransmitters derived from ArAAs, notably serotonin (from tryptophan) and catecholamines (from tyrosine and phenylalanine). The functional effects of such neurochemical changes include altered hormonal function, blood pressure, and affective state. Although the BCAAs thus have biochemical and functional effects in the brain, few attempts have been made to characterize time-course or dose-response relations for such effects. And, no studies have attempted to identify levels of BCAA intake that might produce adverse effects on the brain. The only "model" of very high BCAA exposure is a very rare genetic disorder, maple syrup urine disease, a feature of which is substantial brain dysfunction but that probably cannot serve as a useful model for excessive BCAA intake by normal individuals. Given the known biochemical and functional effects of the BCAAs, it should be a straightforward exercise to design studies to assess dose-response relations for biochemical and functional effects and, in this context, to explore for adverse effect thresholds.

Maternal Iron Deficiency Anemia Affects Postpartum Emotions and Cognition

Abstract: The aim of this study was to determine whether iron deficiency anemia (IDA) in mothers alters their maternal cognitive and behavioral performance, the mother-infant interaction, and the infant's development. This article focuses on the relation between IDA and cognition as well as behavioral affect in the young mothers. This prospective, randomized, controlled, intervention trial was conducted in South Africa among 3 groups of mothers: nonanemic controls and anemic mothers receiving either placebo (10 microg folate and 25 mg vitamin C) or daily iron (125 mg FeS0(4), 10 microg folate, 25 mg vitamin C). Mothers of full-term normal birth weight babies were followed from 10 wk to 9 mo postpartum (n = 81). Maternal hematologic and iron status, socioeconomic, cognitive, and emotional status, mother-infant interaction, and the development of the infants were assessed at 10 wk and 9 mo postpartum. Behavioral and cognitive variables at baseline did not differ between iron-deficient anemic mothers and nonanemic mothers. However, iron treatment resulted in a 25% improvement (P < 0.05) in previously iron-deficient mothers' depression and stress scales as well as in the Raven's Progressive Matrices test. Anemic mothers administered placebo did not improve in behavioral measures. Multivariate analysis showed a strong association between iron status variables (hemoglobin, mean corpuscular volume, and transferrin saturation) and cognitive variables (Digit Symbol) as well as behavioral variables (anxiety, stress, depression). This study demonstrates that there is a strong relation between iron status and depression, stress, and cognitive functioning in poor African mothers during the postpartum period. There are likely ramifications of this poorer "functioning" on mother-child interactions and infant development, but the constraints around this relation will have to be defined in larger studies.

The Tomato As a Functional Food

Abstract: Tomatoes are the fourth most commonly consumed fresh vegetable and the most frequently consumed canned vegetable in the American diet. There is emerging epidemiology data supporting the connection between increased tomato consumption and reduced risk for both cardiovascular disease and prostate cancer. Here we will summarize the nutrient and the phytochemical content of tomatoes and tomato products, and how these bioactive components might act together to modulate disease development. Recent animal studies have investigated tomatoes, lycopene, and prostate cancer using the N-methyl-N-nitrosourea and Dunning rat models. These animal studies also suggest that diets containing tomatoes may decrease the risk or the progression of prostate cancer. Due to the frequency and the extent of tomato consumption, the supporting epidemiological and animal data, which connect increased intakes with decreased cancer and cardiovascular disease risk, tomato's role in the American diet is of undeniable importance as part of a healthy diet.

Cardioprotective Effects of Dietary Polyphenols

Abstract: Dietary polyphenols have been shown to possess cardioprotective effects. For example, the most noted role of grape polyphenols is in the French Paradox, in which a diet high in saturated fat accompanied by regular consumption of red wine is associated with a low risk of coronary heart disease (CHD). Initially, the paradox was thought to be driven by the postulated major action of grape polyphenols in inhibiting LDL oxidation. Although many studies have shown inhibitory effects of polyphenols on LDL oxidation, there have been an equal number of studies that showed a null effect on this variable. Although there are contrasting viewpoints on the effects of polyphenols on LDL oxidation variables, there is increasing evidence that these compounds possess additional cardioprotective functions including altering hepatic cholesterol absorption, triglyceride assembly and secretion, the processing of lipoproteins in plasma, and inflammation. It is the purpose of this review to examine recent information on the multiple functions of dietary polyphenols, with an emphasis on grape polyphenols, in decreasing the risk of CHD by improving plasma lipid profiles and reducing inflammation.

Oral Leucine Administration Stimulates Protein Synthesis in Rat Skeletal Muscle

Abstract: Oral administration of a single bolus of leucine in an amount equivalent to the daily intake (1.35 g/kg body wt) enhances skeletal muscle protein synthesis in food-deprived rats. To elucidate whether smaller amounts of leucine can also stimulate protein synthesis, rats were administered the amino acid at concentrations ranging from 0.068 to 1.35 g/kg body wt by oral gavage. Thirty minutes following the administration of doses of leucine as low as 0.135 g/kg body wt, skeletal muscle protein synthesis was significantly greater than control values. The increase in protein synthesis was associated with changes in the regulation of biomarkers of mRNA translation initiation as evidenced by upregulated phosphorylation of the translational repressor, eukaryotic initiation factor (eIF)4E-binding protein 1 (4E-BP1), the association of eIF4G with the mRNA cap binding protein eIF4E, and the phosphorylation of the 70-kDa ribosomal protein S6 kinase. Alterations in the phosphorylation of eIF4G, as well as the association of 4E-BP1 with eIF4E, were observed following leucine administration; however, these changes appeared to be biphasic with maximal changes occurring when circulating insulin concentrations were elevated. Thus it appears that leucine administration affects mRNA translation and skeletal muscle protein synthesis through modulation of multiple biomarkers of mRNA translation. The ability of small doses of leucine to stimulate skeletal muscle protein synthesis suggests that future research on the regulation of skeletal muscle protein synthesis by orally administered leucine will be feasible in humans.

Dietary Protein and Exercise Have Additive Effects on Body Composition during Weight Loss in Adult Women

Abstract: This study examined the interaction of 2 diets (high protein, reduced carbohydrates vs. low protein, high carbohydrates) with exercise on body composition and blood lipids in women (n = 48, approximately 46 y old, BMI = 33 kg/m(2)) during weight loss. The study was a 4-mo weight loss trial using a 2 x 2 block design (Diet x Exercise). Diets were equal in total energy (7.1 MJ/d) and lipids ( approximately 30% energy intake) but differed in protein content and the ratio of carbohydrate:protein at 1.6 g/(kg . d) and 3.5 (CHO group), respectively. Exercise comparisons were lifestyle activity (control) vs. a supervised exercise program (EX: 5 d/wk walking and 2 d/wk resistance training). Subjects in the PRO and PRO + EX groups lost more total weight and fat mass and tended to lose less lean mass (P = 0.10) than the CHO and CHO + EX groups. Exercise increased loss of body fat and preserved lean mass. The combined effects of diet and exercise were additive for improving body composition. Serum lipid profiles improved in all groups, but changes varied among diet treatments. Subjects in the CHO groups had larger reductions in total cholesterol and LDL cholesterol, whereas subjects in the PRO groups had greater reductions in triacylglycerol and maintained higher concentrations of HDL cholesterol. This study demonstrated that a diet with higher protein and reduced carbohydrates combined with exercise additively improved body composition during weight loss, whereas the effects on blood lipids differed between diet treatments.

Grape Polyphenols Exert a Cardioprotective Effect in Pre- and Postmenopausal Women by Lowering Plasma Lipids and Reducing Oxidative Stress

Abstract: To evaluate the effects of grape polyphenols on plasma lipids, inflammatory cytokines, and oxidative stress, 24 pre- and 20 postmenopausal women were randomly assigned to consume 36 g of a lyophilized grape powder (LGP) or a placebo for 4 wk. The LGP consisted of 92% carbohydrate and was rich in flavans, anthocyanins, quercetin, myricetin, kaempferol, and resveratrol. After a 3-wk washout period, subjects were assigned to the alternate treatment for an additional 4 wk. The placebo consisted of an equal ratio of fructose and dextrose and was similar in appearance and energy content (554 kJ) to LGP. Plasma triglyceride concentrations were reduced by 15 and 6% in pre- and postmenopausal women, respectively (P < 0.01) after LGP supplementation. In addition, plasma LDL cholesterol and apolipoproteins B and E were lower due to LGP treatment (P < 0.05). Further, cholesterol ester transfer protein activity was decreased by approximately 15% with intake of LGP (P < 0.05). In contrast to these beneficial effects on plasma lipids, LDL oxidation was not modified by LGP treatment. However, whole-body oxidative stress as measured by urinary F(2)-isoprostanes was significantly reduced after LGP supplementation. LGP also decreased the levels of plasma tumor necrosis factor-alpha, which plays a major role in the inflammation process. Through alterations in lipoprotein metabolism, oxidative stress, and inflammatory markers, LGP intake beneficially affected key risk factors for coronary heart disease in both pre- and postmenopausal women.

Dietary l-Arginine Supplementation Reduces Fat Mass in Zucker Diabetic Fatty Rats

Abstract: This study was conducted to test the hypothesis that dietary supplementation of arginine, the physiologic precursor of nitric oxide (NO), reduces fat mass in the Zucker diabetic fatty (ZDF) rat, a genetically obese animal model of type-II diabetes mellitus. Male ZDF rats, 9 wk old, were pair-fed Purina 5008 diet and received drinking water containing arginine-HCl (1.51%) or alanine (2.55%, isonitrogenous control) for 10 wk. Serum concentrations of arginine and NO(x) (oxidation products of NO) were 261 and 70% higher, respectively, in arginine-supplemented rats than in control rats. The body weights of arginine-treated rats were 6, 10, and 16% lower at wk 4, 7, and 10 after the treatment initiation, respectively, compared with control rats. Arginine supplementation reduced the weight of abdominal (retroperitoneal) and epididymal adipose tissues (45 and 25%, respectively) as well as serum concentrations of glucose (25%), triglycerides (23%), FFA (27%), homocysteine (26%), dimethylarginines (18-21%), and leptin (32%). The arginine treatment enhanced NO production (71-85%), lipolysis (22-24%), and the oxidation of glucose (34-36%) and octanoate (40-43%) in abdominal and epididymal adipose tissues. Results of the microarray analysis indicated that arginine supplementation increased adipose tissue expression of key genes responsible for fatty acid and glucose oxidation: NO synthase-1 (145%), heme oxygenase-3 (789%), AMP-activated protein kinase (123%), and peroxisome proliferator-activated receptor gamma coactivator-1alpha (500%). The induction of these genes was verified by real-time RT-PCR analysis. In sum, arginine treatment may provide a potentially novel and useful means to enhance NO synthesis and reduce fat mass in obese subjects with type-II diabetes mellitus.

d-Lactate in Human and Ruminant Metabolism

Abstract: D-lactate is normally present in the blood of mammals at nanomolar concentrations due to methylglyoxal metabolism; millimolar d-lactate concentrations can arise due to excess gastrointestinal microbial production. Grain overload in ruminants, short-bowel syndrome in humans, and diarrhea in calves can all result in profound D-lactic acidemia, with remarkably similar neurological manifestations. In the past, D-lactate was thought to be excreted mainly in the urine, and metabolized slowly by the enzyme d-alpha-hydroxy acid dehydrogenase. More recent studies reported that mammals have a relatively high capacity for D-lactate metabolism and identified a putative mammalian D-lactate dehydrogenase. A growing body of literature is also emerging describing subclinical elevation of D-lactate as an indicator of sepsis and trauma. This article describes advances in the understanding of D-lactate metabolism, D-lactic acidosis in ruminants and humans, and subclinical elevation of d-lactate.

Quercetin Decreases Oxidative Stress, NF-κB Activation, and iNOS Overexpression in Liver of Streptozotocin-Induced Diabetic Rats

Abstract: Increasing evidence in both experimental and clinical studies suggests that oxidative stress is involved in the pathogenesis and progression of diabetic tissue damage. This study investigated the protective effects of quercetin treatment on oxidative stress, nuclear factor (NF)-kappaB activation and expression of inducible nitric oxide synthase (iNOS) in streptozotocin-induced diabetic rats. Male Wistar rats were divided into 4 groups: control rats, control rats treated daily with quercetin (150 micromol/kg, i.p.), untreated diabetic rats, and diabetic rats treated with quercetin. Diabetes was induced by a single i.p. injection of streptozotocin (70 mg/kg). Eight weeks later we measured TBARS and hydroperoxide-initiated chemiluminescence (QL) in liver as markers of oxidative stress, and activities of the antioxidant enzymes catalase, superoxide dismutase (SOD), and glutathione peroxidase, NF-kappaB activation by an electrophoretic mobility shift assay and expression of IkappaB kinases (IKKalpha and IKKbeta), the inhibitor IkappaB (IkappaBalpha and IkappaBbeta), and iNOS by Western blot. The plasma glucose concentration was significantly increased in diabetic rats and was not changed by quercetin. Streptozotocin administration induced significant increases in hepatic TBARS concentration, QL, and SOD and catalase activities that were prevented by quercetin. Activation of NF-kappaB, induction of IKKalpha and iNOS protein levels, and increased degradation of IkappaBalpha were also observed in streptozotocin-treated rats. All of those effects were abolished by quercetin. These findings suggest that quercetin treatment, by abolishing the IKK/NF-kappaB signal transduction pathway, may block the production of noxious mediators involved in the development of early diabetes tissue injury and in the evolution of late complications.

Dietary Energy Density Determined by Eight Calculation Methods in a Nationally Representative United States Population

Abstract: Dietary energy density [kcal/g (kJ/g)] influences energy intake under controlled laboratory conditions. Little is known about the energy density of the diets of free-living persons. Because energy density investigations are a relatively new endeavor, there are neither standard calculation methods nor published nationally representative values. This paper examines the calculation of energy density based on systematic exclusion of beverage categories, presents data on variability, and compares values by sex, age, and race/ethnicity in a representative sample of U.S. adults. Mean daily dietary energy density values for adults (aged >19 y) were calculated using two 24-h recalls from the Continuing Survey of Food Intakes by Individuals 1994-1996 based on food, food and liquid meal replacements, food and alcohol, food and juice, food and milk, food and juice and milk, food and energy-containing beverages, and food and all beverages. Energy density varied by calculation method, ranging from 0.94 to 1.85 kcal/g (3.93-7.74 kJ/g). Intraindividual-to-interindividual CV ratios were highest for the food and energy-containing beverages calculation. Men reported diets with a higher energy density than women for all calculation methods (P < 0.0001). There were differences by race/ethnicity and an inverse linear trend for age. These data indicate that beverage inclusion schemes should be clearly defined when reporting energy density values. In epidemiologic studies, calculations based on food and all beverages and food and energy-containing beverages may diminish associations with outcome variables. These nationally representative data, which provide an important frame of reference for other studies, indicate that dietary energy density differs by sex, age, and race/ethnicity.

Palmitate Activates the NF-κB Transcription Factor and Induces IL-6 and TNFα Expression in 3T3-L1 Adipocytes

Abstract: Fatty acids and their metabolites regulate gene expression and immunological pathways. Furthermore, obese individuals frequently have increased circulating fatty acid concentrations, and localized inflammation in adipose tissue may facilitate the systemic inflammation associated with the insulin resistance of obesity. Although palmitate induces inflammation (i.e., activates proinflammatory pathways) in myotubes, the effects of fatty acids on inflammatory processes in adipocytes have not been established. Therefore, we examined the potential for palmitate, laurate, and docosahexaenoic acid (DHA) to modulate inflammation in 3T3-L1 adipocytes. Palmitate, but not DHA or laurate, induced nuclear factor kappaB (NF-kappaB)-driven luciferase activity and interleukin-6 (IL-6) expression (P 0.05). However, the phosphoinositide-3 kinase (PI3K) inhibitor, wortmannin, alone and additively with palmitate, activated the NF-kappaB reporter gene and induced IL-6 expression (P 0.05). These data indicate that palmitate induces inflammation in adipocytes, and that this is not a generalized effect of all SFA. Furthermore, PI3K may act constitutively to suppress inflammation. Consequently, inhibition of this enzyme may promote and exacerbate the inflammation in adipose tissue that is associated with obesity and insulin resistance.

Redox-Sensitive Transcription Factors as Prime Targets for Chemoprevention with Anti-Inflammatory and Antioxidative Phytochemicals

Abstract: Oxidative stress has been implicated in various pathological conditions including cancer. However, the human body has an intrinsic ability to fight against oxidative stress. A wide array of phase 2 detoxifying or antioxidant enzymes constitutes a fundamental cellular defense system against oxidative and electrophilic insults. Transcriptional activation of genes encoding detoxifying and antioxidant enzymes by NF-E2 related factor 2 (Nrf2), a member of the cap'n'collar family of basic leucine zipper transcription factors, may protect cells and tissues from oxidative damage. Many chemopreventive and chemoprotective phytochemicals have been found to enhance cellular antioxidant capacity through activation of this particular transcription factor, thereby blocking initiation of carcinogenesis. A new horizon in chemoprevention research is the recent discovery of molecular links between inflammation and cancer. Components of the cell signaling pathways, especially those that converge on redox-sensitive transcription factors, including nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1) involved in mediating inflammatory response, have been implicated in carcinogenesis. A wide variety of chemopreventive and chemoprotective agents can alter or correct undesired cellular functions caused by abnormal proinflammatory signal transmission mediated by inappropriately activated NF-kappaB and AP-1. The modulation of cellular signaling by anti-inflammatory phytochemicals hence provides a rational and pragmatic strategy for molecular target-based chemoprevention.

Alive and Dead Lactobacillus rhamnosus GG Decrease Tumor Necrosis Factor-α–Induced Interleukin-8 Production in Caco-2 Cells

Abstract: Certain probiotic bacteria show anti-inflammatory activity after being heat killed, whereas others do not, suggesting that the gastrointestinal environment may alter the activity of probiotic bacteria. Occasionally, probiotics are provided when a patient is also being treated with oral antibiotics; this may have an effect on the probiotic activity. We hypothesized that Lactobacillus rhamnosus GG (LGG) are capable of downregulating tumor necrosis factor-alpha (TNFalpha)-induced interleukin (IL)-8 production under all 3 of these conditions, and that LGG act through the nuclear factor kappaB (NFkappaB)/inhibitor of kappaB (IkappaB) pathway. Caco-2 cells were treated with live or heat-killed LGG in doses ranging from 10(4) to 10(10) cfu/L, in the presence or absence of antibiotics and TNFalpha in the media. TNFalpha-induced production of IL-8 by Caco-2 cells was modulated by LGG under all 3 conditions. However, higher doses of live LGG without TNFalpha in the presence or absence of antibiotics in vitro induced the production of IL-8 (P = 0.001). Heat-killed LGG also blunted the TNFalpha-induced IL-8 production (P < 0.01), but by itself did not increase IL-8 production at higher doses as markedly as live LGG (P < 0.05). LGG reduced the TNFalpha-induced NFkappaB translocation to the nucleus and lessened the decrease in IkappaB in the cytoplasm (P < 0.05). LGG reduced TNFalpha-induced IL-8 production by affecting the NFkappaB/IkappaB pathway in Caco-2 cells. High doses of live LGG markedly increased IL-8 production, but heat-killed LGG caused only a slight increase in IL-8. Thus, heat-killed LGG may effectively ameliorate inflammation with a lower potential than live LGG at high doses to cause inflammation.

Portion Sizes and the Obesity Epidemic

Abstract: The rise in obesity rates over the past 30 y has been paralleled by increases in the portion size of many foods and the prevalence of eating away from home. Foods of particular concern are those that have a high energy density (kJ/g). Many well-controlled, laboratory-based studies have found that large portions of energy-dense foods can lead to excess energy intakes. This influence of large portions on energy intake has been supported by data collected in naturalistic settings. Further research is needed to explore strategies that can be used to moderate the effects of portion size on food consumption. One promising strategy is to reduce the energy density of foods, while maintaining food weight or volume, so that consumers can eat satisfying portions while reducing their energy intakes. There is a need for effective educational messages that not only emphasize limiting the consumption of foods high in energy density, but also encourage the consumption of those with a low energy density, such as fruits and vegetables. The delivery of consistent messages will require more cooperation among the food and restaurant industries, policy makers, and scientists. Effective strategies will also require consumers to understand and accept the importance of eating reasonable portions for better health.