Independently, metformin (MET) and the prebiotic, oligofructose (OFS), have been shown to increase glucagon-like peptide (GLP-1) secretion. Our objective was to determine whether using OFS as an adjunct with MET augments GLP-1 secretion in obese rats. Male, diet-induced obese Sprague Dawley rats were randomized to: 1) high-fat/-sucrose diet [HFHS; control (C); 20% fat, 50% sucrose wt:wt]; 2) HFHS+10% OFS (OFS); 3) HFHS + MET [300 mg/kg/d (MET)]; 4) HFHS+10% OFS+MET (OFS+MET). Body composition, glycemia, satiety hormones, and mechanisms related to dipeptidyl peptidase 4 (DPP4) activity in plasma, hepatic AMP-activated protein kinase (AMPK; Western blots), and gut microbiota (qPCR) were examined. Direct effects of MET and SCFA were examined in human enteroendocrine cells. The interaction between OFS and MET affected fat mass, hepatic TG, secretion of glucose-dependent insulinotropic polypeptide (GIP) and leptin, and AMPKα2 mRNA and phosphorylated acetyl CoA carboxylase (pACC) levels (P < 0.05). Combined, OFS and MET reduced GIP secretion to a greater extent than either treatment alone (P < 0.05). The hepatic pACC level was increased by OFS+MET by at least 50% above all other treatments, which did not differ from each other (P < 0.05). OFS decreased plasma DPP4 activity (P < 0.001). Cecal Bifidobacteria (P < 0.001) were markedly increased and C. leptum decreased (P < 0.001) with OFS consumption. In human enteroendocrine cells, the interaction between MET and SCFA affected GLP-1 secretion (P < 0.04) but was not associated with higher GLP-1 than the highest individual doses. In conclusion, the combined actions of OFS and MET were associated with important interaction effects that have the potential to improve metabolic outcomes associated with obesity.

Oleate (OLE) is the principle fatty acid (FA) in mammalian colostrum, but its role in the energy supply in enterocytes after birth remains unknown. We investigated the metabolic fate of OLE in pig enterocytes at birth (d0) and after 2 d of suckling (d2). Cellular TG and phospholipids (PL) and FA composition were analyzed. Metabolic end-products of [1-¹⁴C]OLE were measured in enterocyte incubations. We characterized intestinal carnitine palmitoyltransferase 1 (CPT1), the key enzyme of mitochondrial FA oxidation. The TG content was 6.6-fold higher in enterocytes from pigs on d 2 than in those obtained on d 0, whereas the PL content did not differ. The level of OLE in TG and PL increased from 15 and 11% of total FA, respectively, in enterocytes from newborn piglets to 30 and 17%, respectively, in those from d2 pigs. The capacity for OLE utilization was 2.8-fold greater in d2 than in d0 pig enterocytes. The oxidation and esterification rates were enhanced in enterocytes from piglets on d 2 compared to those obtained on d 0, by 4- and 2.6-fold, respectively. The predominant OLE fate was the esterification pathway, representing >85% of OLE metabolized in both groups. The limited OLE oxidation observed at d 2 may result from the presence of a highly malonyl-CoA–sensitive CPT1A, because the half maximal inhibitory concentration for malonyl-CoA was 162 ± 25 nmol/L. This study highlighted the high esterification capacity for OLE in the newborn pig intestine, which may preserve this major colostrum FA for delivery to other tissues.

The postprandial metabolism of dietary fats implies that the production of TG-rich lipoproteins (TRL) contributes to the progression of plaque development. TRL and their remnants cause rapid receptor-mediated monocyte/macrophage lipid engorgement via the cell surface apoB48 receptor (apoB48R). However, the mechanistic basis for apoB48 receptor (APOB48R) regulation by postprandial TRL in monocytes and macrophages is not well established. In this study, we investigated the effects of postprandial TRL from healthy volunteers on the expression of APOB48R mRNA and lipid uptake in human THP-1 monocytes and THP-1–derived macrophages. The expression of APOB48R mRNA was upregulated in THP-1 monocytes, but downregulated in THP-1–derived macrophages when treated with postprandial TRL (P < 0.05), in a dose- and time-dependent manner. TG and free cholesterol were dramatically increased in THP-1–derived macrophages (140 and 50%, respectively; P < 0.05) and in THP-1 monocytes (160 and 95%, respectively; P < 0.05). This lipid accumulation was severely decreased (~50%; P < 0.05) in THP-1–derived macrophages by small interfering RNA (siRNA) targeting of APOB48R. Using PPAR and retinoid X receptor (RXR) agonists, antagonists, and siRNA, our data indicate that PPARα, PPAR, and RXRα are involved in postprandial TRL-induced APOB48R transcriptional regulation. Co-incubation with acyl-CoA synthetase or acyl-CoA:cholesterol acyltransferase inhibitors potentiated the effects of postprandial TRL on the expression of APOB48R mRNA in THP-1 monocytes and THP-1–derived macrophages. Our findings collectively suggest that APOB48R represents a molecular target of postprandial TRL via PPAR-dependent pathways in human THP-1 monocytes and macrophages and advance a potentially important link between postprandial metabolism of dietary fats and atherogenesis.

Liver cells respond to copper loading upregulating protective mechanisms. However, to date, except for liver content, there are no good indicators that identify individuals with excess liver copper. We hypothesized that administering high doses of copper to young (5.5 mg Cu · kg^{–1 .} d^–1) and adult (7.5 mg Cu · kg^{–1 .} d^–1) capuchin monkeys would induce detectable liver damage. Study groups included adult monkeys (2 females, 2 males) 3–3.5 y old at enrollment treated with copper for 36 mo (ACu); age-matched controls (1 female, 3 males) that did not receive additional copper (AC); young monkeys (2 female, 2 males) treated from birth with copper for 36 mo (YCu); and young age-matched controls (2 female, 2 males) that did not receive additional copper (YC). We periodically assessed clinical, blood biochemical, and liver histological indicators and at 36 mo the hepatic mRNA abundance of MT2a, APP, DMT1, CTR1, HGF, TGFβ, and NFB only in adult monkeys. After 36 mo, the liver copper concentration was 4–5 times greater in treated monkeys relative to controls. All monkeys remained healthy with normal routine serum biochemical indices and there was no evidence of liver tissue damage. Relative mRNA abundance of HGF, TGFβ and NFB was significantly greater in ACu than in AC monkeys. In conclusion, capuchin monkeys exposed to copper at doses up to 50 times the current upper level enhanced expression of genes related to inflammation and injury without clinical, blood biochemical, or histological evidence of liver damage.

To quantify the energy value of fermentable starch, 10 groups of 14 pigs were assigned to one of two dietary treatments comprising diets containing 45% of either pregelatinized (P) or retrograded (R) corn starch. In both diets, a contrast in natural ¹³C enrichment between the starch and nonstarch components of the diet was created to partition between enzymatic digestion and fermentation of the corn starch. Energy and protein retention were measured using indirect calorimetry after adapting the pigs to the diets for 3 wk. Fecal ¹³C enrichment was higher in the R-fed pigs (P < 0.001) and 43% of the R resisted enzymatic digestion. Energy retained as protein was unaffected and energy retained as fat was 29% lower than in P-fed pigs (P < 0.01). Prior to the morning meal, end products of fermentation substantially contributed to substrate oxidation in the R-fed pigs. During the 3–4 h following both meals, heat production was higher (P < 0.05) in P-fed pigs, but this was not preferentially fueled by glucose from corn starch. Digestible energy intake, metabolizable energy intake, and energy retention were reduced (P < 0.05) in R-fed pigs compared with P-fed pigs by 92, 54, and 33 kJ/(kg^0.75 · d), respectively. Therefore, the energy values of fermented resistant starch were 53, 73, and 83% of the digestible, metabolizable, and net energy values of enzymatically degradable starch, respectively. Creating a contrast in natural ¹³C enrichment between starch and nonstarch dietary components provides a promising, noninvasive, in vivo method for estimating the proportion of dietary starch fermented in the gastrointestinal tract.

The digestive process transforms nutrients and bioactive compounds contained in food to physiologically active compounds. In vitro digestion systems have proven to be powerful tools for understanding and monitoring the complex transformation processes that take place during digestion. Moreover, the investigation of the physiological effects of certain nutrients demands an in vitro digestive process that is close to human physiology. In this study, human digestion was simulated with a 3-step in vitro process that was validated in depth by choosing pasteurized milk as an example of a complex food matrix. The evolution and decomposition of the macronutrients was followed over the entire digestive process to the level of intestinal enterocyte action, using protein and peptide analysis by SDS-PAGE, reversed-phase HPLC, size exclusion HPLC, and liquid chromatography-MS. The mean peptide size after in vitro digestion of pasteurized milk was 5–6 amino acids (AA). Interestingly, mostly essential AA (93.6%) were released during in vitro milk digestion, a significantly different relative distribution compared to the total essential AA concentration of bovine milk (44.5%). All TG were degraded to FFA and monoacylglycerols. Herein, we present a human in vitro digestion model validated for its ability to degrade the macronutrients of dairy products comparable to physiological ranges. It is suited to be used in combination with a human intestinal cell culture system, allowing ex vivo bioavailability measurements and assessment of the bioactive properties of food components.

Though adolescents consume more fructose than any other age group, the relationship between fructose consumption and markers of cardiometabolic risk has not been established in this population. We determined associations of total fructose intake (free fructose plus one-half the intake of free sucrose) with cardiometabolic risk factors and type of adiposity in 559 adolescents aged 14–18 y. Fasting blood samples were measured for glucose, insulin, lipids, adiponectin, and C-reactive protein. Diet was assessed with 4–7 24-h recalls and physical activity (PA) was determined by accelerometry. Fat-free soft tissue (FFST) mass and fat mass were measured by DXA. The s.c. abdominal adipose tissue (SAAT) and visceral adipose tissue (VAT) were assessed using MRI. Multiple linear regression, adjusting for age, sex, race, Tanner stage, FFST mass, fat mass, PA, energy intake, fiber intake, and socioeconomic status, revealed that fructose intake was associated with VAT (β = 0.13; P = 0.03) but not SAAT (P = 0.15). Significant linear upward trends across tertiles of fructose intake were observed for systolic blood pressure, fasting glucose, HOMA-IR, and C-reactive protein after adjusting for the same covariates (all P-trend < 0.04). Conversely, significant linear downward trends across tertiles of fructose intake were observed for plasma HDL-cholesterol and adiponectin (both P-trend < 0.03). When SAAT was added as a covariate, these trends persisted (all P-trend < 0.05). However, when VAT was included as a covariate, it attenuated these trends (all P-trend > 0.05). In adolescents, higher fructose consumption is associated with multiple markers of cardiometabolic risk, but it appears that these relationships are mediated by visceral obesity.

Starchy food products differ in the rate of starch digestion, which can affect their metabolic impact. In this study, we examined how the in vivo starch digestibility is reflected by the glycemic response, because this response is often used to predict starch digestibility. Ten healthy male volunteers [age 21 ± 0.5 y, BMI 23 ± 0.6 kg/m² (mean ± SEM)] participated in a cross-over study, receiving three different meals: pasta with normal wheat bran (PA) and bread with normal (CB) or purple wheat bran (PBB). Purple wheat bran was added in an attempt to decrease the rate of starch digestion. The meals were enriched in ¹³C and the dual isotope technique was applied to calculate the rate of appearance of exogenous glucose (RaE). The ¹³C-isotopic enrichment of glucose in plasma was measured with GC/combustion/isotope ratio MS (IRMS) and liquid chromatography/IRMS. Both IRMS techniques gave similar results. Plasma glucose concentrations [2-h incremental AUC (iAUC)] did not differ between the test meals. The RaE was similar after consumption of CB and PBB, showing that purple wheat bran in bread does not affect in vivo starch digestibility. However, the iAUC of RaE after men consumed PA was less than after they consumed CB (P < 0.0001) despite the similar glucose response. To conclude, the glycemic response does not always reflect the in vivo starch digestibility. This could have implications for intervention studies in which the glycemic response is used to characterize test products.

We examined the effects of oral plasma protein supplements on the pulmonary adaptive immune response in mice challenged with intranasal LPS. C57BL/6 mice were fed a control diet or a diet supplemented with plasma proteins [spray-dried plasma (SDP) 80 g/kg] or with an Ig concentrate [(IC) 20 g/kg] from postnatal d 19 (weaning) until d 34. Mice were challenged with PBS or LPS from Escherichia coli at d 33 and killed 24 h later for leukocyte analyses or at d 34 and killed 6 h later for cytokine determination. LPS induced the activation of T helper (Th) lymphocytes in lung and blood and this response was reduced by SDP and IC (P < 0.05). In both tissues, LPS increased the Th1 and Th2 subpopulations and this effect was inhibited by the two plasma protein supplements (P < 0.05). The LPS challenge increased the expression of all the cytokines studied (P < 0.01). SDP and IC reduced the expression of IFN, IL-5, IL-12p40, IL-12p70, IL-13, and IL-17 in both tissues, whereas they increased the percentage of regulatory Th lymphocytes in lung, even in PBS-treated mice (P < 0.05). LPS reduced the concentration of mature TGFβ1 (P < 0.05) in the lung but did not modify the expression of IL-10. Mice exposed to LPS and supplemented with SDP or IC showed an increased expression of the anti-inflammatory cytokine IL-10 (P < 0.05). Moreover, the two supplements increased the concentration of IL-10 in intestinal mucosa (P < 0.05). Our results show that plasma supplementation reduces the immune response that characterizes the acute lung inflammation syndrome.

Iron (Fe) deficiency anemia is a global health concern and Fe fortification and supplementation are common corrective strategies. Fe is essential not only for the human host but also for nearly all gut bacteria. We studied the impact of Fe deficiency and Fe repletion on the gut microbiota in rats. Weanling rats were fed an Fe-deficient diet for 24 d and then repleted for 13 d with FeSO₄ (n = 15) or electrolytic Fe (n = 14) at 10 and 20 mg Fe · kg diet^–1. In addition, one group of rats (n = 8) received the Fe-deficient diet and one group (n = 3) received a Fe-sufficient control diet for all 37 d. Fecal samples were collected at baseline and after the depletion and repletion periods, and colonic tissues were examined histologically. Microbial metabolite composition in cecal water was measured and fecal samples were analyzed for microbial composition with temporal temperature gradient gel electrophoresis and qPCR. Compared to Fe-sufficient rats, Fe-deficient rats had significantly lower concentrations of cecal butyrate (–87%) and propionate (–72%) and the abundance of dominant species was strongly modified, including greater numbers of lactobacilli and Enterobacteriaceae and a large significant decrease of the Roseburia spp./E. rectale group, a major butyrate producer. Repletion with 20 mg FeSO₄ · kg diet^–1 significantly increased cecal butyrate concentrations and partially restored bacterial populations compared to Fe-deficient rats at endpoint. The effects on the gut microbiota were stronger in rats repleted with FeSO₄ than in rats repleted with electrolytic Fe, suggesting ferrous Fe may be more available for utilization by the gut microbiota than elemental Fe. Repletion with FeSO₄ significantly increased neutrophilic infiltration of the colonic mucosa compared to Fe-deficient rats. In conclusion, Fe depletion and repletion strongly affect the composition and metabolic activity of rat gut microbiota.

The R230C variant of the ATP-binding cassette transporter A1 (ABCA1) gene has been consistently associated with decreased HDL-cholesterol (HDL-C) concentrations in several studies in the Mexican mestizo population. However, information on how diet composition modifies the effect of the ABCA1-R230C variant on HDL-C concentrations is very scarce. The aim of the present study was to analyze whether the effect of ABCA1-R230C on HDL-C concentrations is modulated by dietary factors in a nationwide population sample of 3591 adults from the National Health and Nutrition Survey conducted by the State’s Employees’ Social Security and Social Services Institute. All participants answered a validated questionnaire to assess health status and weekly food consumption. Fasting blood samples were drawn for biochemical analysis and DNA extraction, and the ABCA1-R230C variant was genotyped using TaqMan assays. Statistical analyses consisted of simple linear and multiple regression modeling adjusting for age, BMI, smoking, and alcohol consumption. The overall C risk allele frequency was 9.3% and the variant was significantly associated with low HDL-C concentrations in both sexes. A significant negative correlation between carbohydrate consumption and HDL-C concentrations was observed in women bearing the R230C variant (P = 0.021) and a significant gene-diet interaction was found only in premenopausal women (P = 0.037). In conclusion, the effect of the ABCA1-R230C gene variant on HDL-C concentrations is modulated by carbohydrate intake in premenopausal women. This finding may help design optimized dietary interventions according to sex and ABCA1-R230C genotype.

Coronary heart disease (CHD) is the leading cause of death in women. A nested case-control study tested whether dietary patterns predicted CHD events among 1224 participants in the Women’s Health Initiative-Observational Study (WHI-OS) with centrally confirmed CHD, fatal or nonfatal myocardial infarct compared to 1224 WHI-OS controls matched for age, enrollment date, race/ethnicity, and absence of CHD at baseline or follow-up. The first six principal components explained >75% of variation in dietary intakes and K-mean analysis based on these six components produced three clusters. Diet cluster 1 was rich in carbohydrate, vegetable protein, fiber, dietary vitamin K, folate, carotenoids, α-linolenic acid [18:3(n-3)], linoleic acid [18:2(n-6)], and supplemental calcium and vitamin D. Diet cluster 2 was rich in total and animal protein, arachidonic acid [20:4(n-6)], DHA [22:6(n-3)], vitamin D, and calcium. Diet cluster 3 was rich in energy, total fat, and trans fatty acids (all P < 0.01). Conditional logistic regression analysis demonstrated diet cluster 1 was associated with lower CHD risk than diet cluster 2 (reference group) adjusted for smoking, education, and physical activity [OR = 0.79 (95% CI = 0.64, 0.99); P = 0.038]. This difference was not significant after adjustment for BMI and systolic blood pressure. Diet cluster 3 was associated with higher CHD risk than diet cluster 2 [OR = 1.28 (95% CI = 1.04, 1.57); P = 0.019], but this difference did not remain significant after adjustment for smoking, education, and physical activity. Within this WHI-OS cohort, distinct dietary patterns may be associated with subsequent CHD outcomes.

A sensitive and reliable biomarker has yet to be identified for marginal copper deficiency in humans. The need for such a biomarker is critical, because increased cases of human copper deficiency evolve following bariatric surgery and other secondary factors besides diet. Four experiments were devised to induce marginal copper deficiency through copper-deficient (CuD) diets (5 wk for mice and 4 wk for rats). In Expt. 1 and 2, male postweanling mice were raised in either solid-bottom plastic cages (Expt. 1) or stainless steel hanging cages (Expt. 2) and compared. Postweanling rats (Expt. 3) and adult mice (Expt. 4) were also studied using stainless steel cages. Copper-adequate controls were fed a semipurified diet containing 9 mg Cu/kg. CuD rats exhibited the most severe changes in biomarkers due to copper limitation, including major reductions in plasma ceruloplasmin (Cp) and erythrocyte superoxide dismutase (Sod1) and augmentation in copper chaperone for Sod1 (CCS). The CuD mice in Expt. 2 were more deficient than the CuD mice in Expt. 1, likely due to coprophagia differences. In fact, the CuD mice in Expt. 1 had unaltered Sod1 or Cp levels. Importantly though, these marginally deficient mice and CuD adult mice that had no changes in Cp activity or liver copper level had robust augmentation of CCS. Erythrocyte CCS was the only consistent biomarker to change in copper deficiency for all dietary groups, suggesting that CCS may be an excellent biomarker for human confirmation of marginal copper deficiency.

Mexican American children are disproportionately affected by obesity. Data on how the acculturation process influences diet and body weight among adolescents are limited. We used the data from the 1999–2004 NHANES, restricting to 2286 Mexican American children between 12 and 19 y old. Acculturation was measured by generation status and language preference. Diet was assessed using 24-h diet recall. Multiple linear, Tobit, logistic, and quantile regression models were used. We found, after adjusting for socio-demographic factors, health, dietary intake, physical activity, and sedentary behaviors compared to the first generation, second and third generations had greater odds of overweight and obesity. Adolescents in the second generation had higher BMI Z-scores than adolescents in the first and third generations. Both second and third generation adolescents consumed less fruit, whole fruit, vegetables, grains, and meats but more sweetened beverages, whole grains, saturated fat, sodium, oil, and energy from discretionary foods. Higher language acculturation was associated with poorer diet and greater body weight. Our findings suggest that Mexican American adolescents face challenges in terms of poorer diet and excessive weight gain associated with their immigration experience.

This cross-sectional study examined associations of demographic characteristics, weight status, availability of school vending machines, and behavioral factors with sugar-sweetened beverage (SSB) intake, both overall and by type of SSB, among a nationally representative sample of high school students. The 2010 National Youth Physical Activity and Nutrition Study data for 11,209 students (grades 9–12) were used. SSB intake was based on intake of 4 nondiet beverages [soda, other (i.e., fruit-flavored drinks, sweetened coffee/tea drinks, or flavored milk), sports drinks, and energy drinks]. Nationwide, 64.9% of high school students drank SSB ≥1 time/d, 35.6% drank SSB ≥2 times/d, and 22.2% drank SSB ≥3 times/d. The most commonly consumed SSB was regular soda. Factors associated with a greater odds for high SSB intake (≥3 times/d) were male gender [OR = 1.66 (95% CI = 1.41,1.95); P < 0.05], being non-Hispanic black [OR = 1.87 (95% CI = 1.52, 2.29); P < 0.05], eating at fast-food restaurants 1–2 d/wk or eating there ≥3 d/wk [OR = 1.25 (95% CI = 1.05, 1.50); P < 0.05 and OR = 2.94 (95% CI = 2.31, 3.75); P < 0.05, respectively] and watching television >2 h/d [OR = 1.70 (95% CI = 1.44, 2.01); P < 0.05]. Non-Hispanic other/multiracial [OR = 0.67 (95% CI = 0.47, 0.95); P < 0.05] and being physically active ≥60 min/d on <5 d/wk were associated with a lower odds for high SSB intake [OR = 0.85 (95% CI = 0.76, 0.95); P < 0.05]. Weight status was not associated with SSB intake. Differences in predictors by type of SSB were small. Our findings of significant associations of high SSB intake with frequent fast-food restaurant use and sedentary behaviors may be used to tailor intervention efforts to reduce SSB intake among high-risk populations.

Nonalcoholic fatty liver disease (NAFLD), frequently already present in young subjects, has been linked to reduced growth hormone levels and signaling. Similar hormonal changes occur during metabolic acidosis (MA), which may thus contribute to an increased NAFLD risk. Because subclinical MA can be diet induced, we aimed to examine whether a higher diet-dependent acid load during adolescence is prospectively associated with several currently used NAFLD surrogates in young adulthood. Dietary acidity during adolescence (boys:10–15 y, girls: 9–14 y) was calculated as potential renal acid load (PRAL) from at least three 3-d weighed dietary records according to a published algorithm considering dietary protein and minerals in 145 healthy participants. Routine measurements derived from blood analysis and anthropometric data in participants’ young adulthood (18–25 y) were used to determine the NAFLD surrogates alanine-aminotransferase (ALT), hepatic steatosis index (HSI), and fatty liver index (FLI). Sex-stratified linear regression models, adjusted for dietary fiber, saturated fat, protein, and adolescent BMI SD scores, were run with PRAL as the independent variable. Dietary PRAL during puberty was positively associated with ALT (P = 0.02), HSI (P = 0.002), and FLI (P = 0.005) in adult females but not males. Females with an adolescent dietary acid load in the highest tertile had 3.5, 4.4, and 4.5 higher values of ALT, HSI, and FLI as adults, respectively, compared to females with the lowest PRAL. The present findings suggest that higher dietary acidity in adolescence may be prospectively associated with hepatic lipid accumulation in females. Whether this relationship is due to the higher proton load or rather represents an unhealthy dietary pattern requires further investigation.

Diet quality indices assess compliance with dietary guidelines and represent a measure of healthy dietary patterns. Few studies have compared different approaches to assessing diet quality in the same cohort. Our analysis was based on 972 participants of the British Diet and Nutrition Survey of people aged 65 y and older in 1994/1995 and who were followed-up for mortality status until 2008. Dietary intake was measured via a 4-d weighed food record. Three measures of diet quality were used: the Healthy Diet Score (HDS), the Recommended Food Score (RFS), and the Mediterranean Diet Score (MDS). HR for all-cause mortality were obtained using Cox regression adjusted for age, sex, energy intake, social class, region, smoking, physical activity, and BMI. After adjustment for confounders, the MDS was significantly associated with mortality [highest vs. lowest quartile; HR = 0.78 (95% CI = 0.62–0.98)]. Similarly, the RFS was also associated with mortality [HR = 0.67 (95 % CI = 0.52–0.86)]; however, there were no significant associations for the HDS [HR = 0.99 (95% CI = 0.79–1.24)]. The HDS was not a predictor of mortality is this population, whereas the RFS and the MDS were both associated with all-cause mortality. Simple measures of diet quality using food-based indicators can be useful predictors of longevity.

Few epidemiologic studies have examined the potential cardiovascular mechanisms of tomato-based food products, the primary dietary source of lycopene. We examined the cross-sectional association between tomato-based food product intake and coronary biomarkers in the Women’s Health Study. Tomato-based food products (tomatoes, tomato juice, tomato sauce, pizza) were summed from a semiquantitative FFQ and multiple risk factors ascertained. Plasma from baseline blood samples were assayed for lipids, lipoproteins, hemoglobin A1c, C-reactive protein, fibrinogen, soluble intracellular adhesion molecule-1, and creatinine. A total of 27,261 women aged ≥45 y who were free of cardiovascular disease and cancer provided relevant data for this study. Tomato-based food product intake was modest, with 84% of women consuming <1 serving/d, but those with greater intake had healthier lifestyle and dietary habits. Women consuming ≥10 compared with <1.5 servings/wk of tomato-based food products had significant but clinically modest improvements in total cholesterol (TC) (5.38 vs. 5.51 mmol/L; P = 0.029), the TC:HDL cholesterol ratio (4.08 vs. 4.22; P = 0.046), and hemoglobin A1c (5.02 vs. 5.13%; P < 0.001) in multivariable models. Considering clinical cutpoints, women consuming ≥10 compared with <1.5 servings/wk were 31% (95% CI = 6%, 50%), 40% (95% CI = 13%, 59%), and 66% (95% CI = 20%, 86%) less likely to have elevated TC (≥6.21 mmol/L), LDL cholesterol (≥4.14 mmol/L), and hemoglobin A1c (≥6%), respectively. Other coronary biomarkers were unassociated with tomato-based food products. In conclusion, women consuming ≥10 compared with <1.5 servings/wk of tomato-based food products had clinically modest but significant improvements in TC, the TC:HDL cholesterol ratio, and hemoglobin A1c but not other coronary biomarkers.

Independent association between legume intake and systemic inflammation is not well documented. The traditional Iranian diet provides an opportunity to assess the association between legume intake and health outcomes. This study was carried out to examine legume consumption in relation to serum concentrations of adhesion molecules and inflammatory biomarkers among Iranian women. In this cross-sectional study, 486 Tehrani female teachers were investigated. A trained dietitian administered a validated semiquantitative FFQ for assessment of usual dietary intakes. Legume intake was calculated by summing up the consumption of lentils, peas, chickpeas, different kinds of beans including broad beans, and chickling vetch. To measure serum concentrations of adhesion molecules and inflammatory biomarkers, a fasting blood sample was taken. After statistically controlling for potential confounders, individuals in the highest tertile of legume intake had lower serum concentrations of E-selectin (percent difference between the lowest and highest tertile: –14.1%; P = 0.04), soluble intercellular adhesion molecule-1 (–20.3%; P < 0.01), and soluble vascular cell adhesion molecule-1 (–15.6%; P = 0.01) compared with those in the lowest tertile. Legume intake was inversely associated with serum concentrations of high sensitive CRP (hs-CRP), TNFα, and IL-6, even after controlling for potential confounders and dietary variables (percent difference between the lowest and highest tertile for hs-CRP: –39.2%, P < 0.001; for TNFα: –15.9%, P = 0.04; and for IL-6: –39.5%, P < 0.01). Legume intake and concentrations of serum amyloid A were not correlated. Legume consumption is inversely associated with serum concentrations of adhesion molecules and inflammatory biomarkers among Iranian women.

Hypotheses regarding the role of meat consumption in body weight modulation are contradictory. Prospective studies on an association between meat consumption and BMI change are limited. We assessed the association between meat consumption and change in BMI over time in 3902 men and women aged 55–69 y from the Netherlands Cohort Study. Dietary intake was estimated at baseline using a FFQ. BMI was ascertained through baseline self-reported height (1986) and weight (1986, 1992, and 2000). Analyses were based on sex-specific categories of daily total fresh meat, red meat, beef, pork, minced meat, chicken, processed meat, and fish consumption at baseline. Linear mixed effect modeling adjusted for confounders was used to assess longitudinal associations. Significant cross-sectional differences in BMI between quintiles of total meat intake were observed (P-trend < 0.01; both sexes). No association between total fresh meat consumption and prospective BMI change was observed in men (BMI change highest vs. lowest quintile after 14 y: –0.06 kg/m²; P = 0.75) and women (BMI change: 0.26 kg/m²; P = 0.20). Men with the highest intake of beef experienced a significantly lower increase in BMI after 6 and 14 y than those with the lowest intake (BMI change after 14 y 0.60 kg/m²). After 14 y, a significantly higher increase in BMI was associated with higher intakes of pork in women (BMI change highest vs. lowest quintile: 0.47 kg/m²) and chicken in both sexes (BMI change highest vs. lowest category in both men and women: 0.36 kg/m²). The results remained similar when stratifying on median baseline BMI, and age-stratified analyses yielded mixed results. Differential BMI change effects were observed for several subtypes of meat. However, total meat consumption, or factors directly related to total meat intake, was not strongly associated with weight change during the 14-y prospective follow-up in this elderly population.

Many studies have documented a high prevalence of anemia among tuberculosis (TB) patients and anemia at TB diagnosis has been associated with an increased risk of death. However, little is known about the factors contributing to the development of TB-associated anemia and their importance in TB disease progression. Data from a randomized clinical trial of micronutrient supplementation in patients with pulmonary TB in Tanzania were analyzed. Repeated measures of anemia with iron deficiency, anemia without iron deficiency, and iron deficiency without anemia were assessed as risk factors for treatment failure, TB recurrence, and mortality. The prevalence of anemia (hemoglobin < 110 g/L) at baseline was 64%, more than one-half of which was related to iron deficiency (mean corpuscular volume , 80 fL). We found no evidence of an association between anemia (with or without iron deficiency) or iron deficiency without anemia at baseline and the risk of treatment failure at 1 mo after initiation. Anemia without iron deficiency was associated with an independent, 4-fold increased risk of TB recurrence [adjusted RR = 4.10 (95% CI = 1.88, 8.91); P < 0.001]. Iron deficiency and anemia (with and without iron deficiency) were associated with a 2- to nearly 3-fold independent increase in the risk of death [adjusted RR for iron deficiency without anemia = 2.89 (95% CI = 1.53, 5.47); P = 0.001; anemia without iron deficiency = 2.72 (95% CI = 1.50, 4.93); P = 0.001; iron deficiency anemia = 2.13 (95% CI = 1.10, 4.11); P = 0.02]. Efforts to identify and address the conditions contributing to TB-associated anemia, including iron deficiency, could play an important role in reducing morbidity and mortality in areas heavily affected by TB.

Anemia is highly prevalent globally, estimated at 40–50% in women of reproductive age. Prior studies have produced inconclusive evidence as to the association between maternal anemia and intrauterine growth restriction (IUGR). We conducted a systematic review of the literature containing associations between maternal anemia and small for gestational age (SGA) outcomes (as a proxy for IUGR). A meta-analysis was performed to pool associations, categorized by the hemoglobin cutoffs presented by the authors. We identified 12 studies reporting associations between maternal anemia and SGA. For the meta-analysis, there were 7 associations with a hemoglobin cutoff <110 g/L, 7 with a cutoff <100 g/L, and 5 with a cutoff <90 or <80 g/L. Although the <110- and <100-g/L categories showed no significant relationship with SGA, the <90- or <80-g/L category was associated with a 53% increase in risk of the newborn being SGA [pooled OR = 1.53 (95% CI: 1.24–1.87); P < 0.001]. Moderate to severe, but not mild, maternal anemia appears to have an association with SGA outcomes, but the findings must be viewed with caution due to the great heterogeneity of the studies. Further examination should be conducted using datasets with better standardized definitions and measurements of exposure and outcome.

We evaluated the antiinflammatory activity of soy-derived di- and tripeptides in a dextran sodium sulfate (DSS)-induced pig model of intestinal inflammation. In the DSS-positive control (POS) and DSS-positive with soy peptide treatment (SOY) groups (n = 6/group), DSS was administered to piglets via i.g. catheter for 5 d, followed by a 5-d administration of saline or soy-derived peptides, respectively. A negative control (NEG) group received saline in lieu of the DSS and soy peptides. The severity of inflammation was assessed by clinical signs, morphological and histological measurements, gut permeability, and neutrophil infiltration. Local production of TNF and IL6 were measured by ELISA, colonic and ileal inflammatory gene expression were assessed by real-time RT-PCR, and CD4⁺CD25⁺ lymphocyte populations were analyzed by flow cytometry. Crypt elongation and muscle thickness, d-mannitol gut permeation, colonic expression of the inflammatory mediators IFNG, IL1B, TNF, RORC, and IL17A as well as the FOXP3 T-regulatory transcription factor, and myeloperoxidase activity were lower (P < 0.05) in the SOY pigs than in POS pigs. Messenger RNA levels of ileal IFNG, TNF, IL12B, and IL17A were lower (P < 0.05) and FOXP3 expression was greater (P < 0.05) in SOY piglets than in the POS group. In the mesenteric lymph nodes, CD4⁺CD25⁺ T cells were higher (P < 0.05) in both the POS and SOY groups than in NEG controls. Soy-derived peptides exert antiinflammatory activity in vivo, suggesting their usefulness for the treatment of inflammatory disorders.

Low-glycemic load (GL) diets improve insulin resistance and glucose homeostasis in individuals with diabetes. Less is known about whether low-GL diets, independent of weight loss, improve the health profile for persons without diabetes or other preexisting conditions. We conducted a randomized, cross-over feeding study testing low- compared to High-GL diets on biomarkers of inflammation and adiposity in healthy adults. Eighty participants (n = 40 with BMI 18.5–24.9 kg/m²; n = 40 with BMI 28.0–40.0 kg/m²) completed two 28-d feeding periods in random order where one period was a high-GL diet (mean GL/d = 250) and the other a low-GL diet (mean GL/d = 125). Diets were isocaloric with identical macronutrient content (as percent energy). All food was provided and participants maintained weight and usual physical activity. Height, weight, and DXA were measured at study entry and weight assessed again thrice per week. Blood was drawn from fasting participants at the beginning and end of each feeding period and serum concentrations of high-sensitivity CRP, serum amyloid A, IL-6, leptin, and adiponectin were measured. Linear mixed models tested the intervention effect on the biomarkers; models were adjusted for baseline biomarker concentrations, diet sequence, feeding period, age, sex, and body fat mass. Among participants with high-body fat mass (>32.0% for males and >25.0% for females), the low-GL diet reduced CRP (P = 0.02) and marginally increased adiponectin (P = 0.06). In conclusion, carbohydrate quality, independent of energy, is important. Dietary patterns emphasizing low-GL foods may improve the inflammatory and adipokine profiles of overweight and obese individuals.

Probiotics may modulate the host immune response by mechanisms not yet fully understood. We evaluated the modulation of intestinal and systemic antigen-specific immune response by Lactobacillus rhamnosus GG (LGG) or Bifidobacterium animalis MB5 in tolerized and immunized rats. Three groups of rats received orally LGG, B. animalis, or PBS (control) for 28 d. Each group was divided into two subgroups of tolerized or immunized rats receiving orally ovalbumin (OVA; 7 mg) or PBS on d 7, 9, and 11. All rats were immunized with OVA (300 μg) on d 14 and 21. In tolerized rats, the OVA-induced proliferative response of mesenteric lymph nodes (MLN) and spleen cells did not differ from control, indicating that the two probiotics maintained the tolerance. LGG and B. animalis in immunized rats reduced the OVA-induced proliferative response in MLN (P < 0.01) but not in spleen, whereas the proliferative response to anti-CD3 and concanavalin A of MLN and spleen cells as well as the delayed-type hypersensitivity reaction were not affected by probiotic treatment, indicating OVA-specific hyporesponsiveness restricted to intestinal immunity. This hyporesponsiveness was associated with CD4⁺CD25⁺Foxp3⁺ T cell expansion (P < 0.01) and increased IL-10 and TGFβ after LGG (P < 0.05), and increased apoptosis after B. animalis (P < 0.001) in MLN. In conclusion, we report a novel activity of LGG and B. animalis in inducing OVA-specific hyporesponsiveness in MLN of OVA-immunized rats that can be useful for a therapeutic strategy to prevent undesirable reactions to immunogenic antigens in the gut.

Limited information is available regarding the effects of mild dehydration on cognitive function. Therefore, mild dehydration was produced by intermittent moderate exercise without hyperthermia and its effects on cognitive function of women were investigated. Twenty-five females (age 23.0 ± 0.6 y) participated in three 8-h, placebo-controlled experiments involving a different hydration state each day: exercise-induced dehydration with no diuretic (DN), exercise-induced dehydration plus diuretic (DD; furosemide, 40 mg), and euhydration (EU). Cognitive performance, mood, and symptoms of dehydration were assessed during each experiment, 3 times at rest and during each of 3 exercise sessions. The DN and DD trials in which a volunteer attained a ≥1% level of dehydration were pooled and compared to that volunteer’s equivalent EU trials. Mean dehydration achieved during these DN and DD trials was –1.36 ± 0.16% of body mass. Significant adverse effects of dehydration were present at rest and during exercise for vigor-activity, fatigue-inertia, and total mood disturbance scores of the Profile of Mood States and for task difficulty, concentration, and headache as assessed by questionnaire. Most aspects of cognitive performance were not affected by dehydration. Serum osmolality, a marker of hydration, was greater in the mean of the dehydrated trials in which a ≥1% level of dehydration was achieved (P = 0.006) compared to EU. In conclusion, degraded mood, increased perception of task difficulty, lower concentration, and headache symptoms resulted from 1.36% dehydration in females. Increased emphasis on optimal hydration is warranted, especially during and after moderate exercise.

The fractional absorption of a stable isotope-labeled folate dose can be estimated from the subsequent short-term temporal changes in the concentration of labeled L-5-methyltetrahydrofolate (L-5-methyl-THF) in plasma using mathematical modeling. However, the model is dependent on the use of an accurate value for the apparent volume of distribution of L-5-methyl-THF. Previous studies that estimated the apparent volume of distribution of L-5-methyl-THF used large (nonphysiological) doses of unlabeled folates that are not found to any great extent in the circulatory system. The current study estimates the apparent volume of distribution at steady state in 16 healthy humans aged 18–65 y after an i.v. dose (440 nmol) of a stable isotope-labeled version of the naturally circulating plasma folate, L-5-methyl-THF. Blood was collected from 2 min to 2 h postinjection and plasma assayed by specific and sensitive liquid chromatography-tandem MS. The apparent volume of distribution for L-5-methyl-THF was 32.0 ± 11.6 L (mean ± SD; 392 ± 110 mL/kg bodyweight). There was a positive association with volunteer body weight (r = 0.64; P = 0.010), which allowed a simple linear equation to be developed relating apparent volume of distribution to body weight. This has important implications for predicting apparent absorption of labeled folates in future bioavailability studies.