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1.  Beneficial effects of aged garlic extract and coenzyme Q10 on vascular elasticity and endothelial function: The FAITH randomized clinical trial 
Aged garlic extract (AGE) is associated with a significant decrease in atherosclerotic plaque progression and endothelial function improvement. Similarly, coenzyme Q10 (CoQ10) has significant beneficial effects on endothelial function. A stressful lifestyle is a well-known risk factor for the presence and progression of atherosclerosis. This study investigated the effect of AGE plus CoQ10 on vascular elasticity measured by pulse-wave velocity (PWV) and endothelial function measured by digital thermal monitoring (DTM) in firefighters.
Sixty-five Los-Angeles County firefighters who met the eligibility criteria were enrolled in this placebo-controlled, double-blinded randomized trial. The firefighters were randomized to four tablets of AGE (300 mg/tablet) plus CoQ10 (30 mg/tablet) or placebo. The participants underwent quarterly visits and 1-year follow-up. PWV and DTM were measured at baseline and at the 1-year follow-up.
There were no significant differences in age, cardiovascular risk factors, PWV, and DTM between the AGE/CoQ10 and placebo groups at baseline (P > 0.5). At 1-y, PWV and DTM significantly improved in the AGE/CoQ10 compared with the placebo group (P < 0.05). After an adjustment for cardiovascular risk factors and statin therapy, the mean decrease in vascular stiffness (PWV) was 1.21 m/s in the AGE/CoQ10 compared with the placebo group (P = 0.005). Similarly, the mean increase in the area under the temperature curve, the DTM index of endothelial function, was 31.3 in the AGE/CoQ10 compared with the placebo group (P = 0.01).
The combination of AGE and CoQ10 was independently associated with significant beneficial effects on vascular elasticity and endothelial function in firefighters with high occupational stress, highlighting the important role of AGE and CoQ10 in atherosclerotic prevention of such individuals.
PMCID: PMC4277702  PMID: 22858191
Atherosclerosis; Coronary artery disease; Vascular elasticity; Endothelial function; Pulse-wave velocity; Digital thermal monitoring; Aged garlic extract; Coenzyme Q10
2.  Mineral status of non-anemic Peruvian infants taking an iron and copper syrup with or without zinc from 6 to 18 months of age: a randomized controlled trial 
To evaluate changes in iron, zinc and copper status of non-anemic Peruvian infants receiving daily supplements with 10 mg iron, 0.5 mg copper with or without 10 mg zinc from 6 to 18 months of age.
Overall, 251 infants were randomized to one of two daily supplements. Venous blood draws at 6, 12, and 18 months were taken to characterize hemoglobin, plasma ferritin, zinc and copper concentrations. Urinary excretion of zinc was also measured at each time point. Repeated measures ANOVA was used to evaluate changes over time and by supplement type.
Both hemoglobin and copper concentrations increased significantly, while plasma ferritin decreased from 6 to 12 months of age (P < 0.05). Mean plasma zinc concentrations in the zinc treatment group were maintained over time, while that in the control group declined; differences by treatment were found at 12 and 18 months (P < 0.05). Urinary zinc concentration was increased in the zinc group at 12 months only. There was evidence that zinc treatment improved hemoglobin at 18 months of age (P = 0.09). Compliance with supplementation was high, with 81% of the intended dose consumed over the 12-month period.
Daily mineral supplementation over one year appears feasible and acceptable in this population, and a combined supplement can improve iron, zinc and copper status of infants at the same time.
PMCID: PMC3794366  PMID: 24103510
Zinc; iron; copper; supplements; infancy
3.  Estimated dietary intake and major food sources of polyphenols in the Polish arm of the HAPIEE study☆ 
The aim of this study was to estimate the intake of known individual polyphenols and their major dietary sources in the Polish arm of the HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe) study.
A total of 10,477 random sample (45–69 y) of urban population of Krakow, Poland, completed a validated 148-item food frequency questionnaire. Polyphenol intake was calculated by matching food consumption data with the recently developed Phenol-Explorer database.
The mean intake of polyphenols was 1756.5 ± 695.8 mg/d (median = 1662.5 mg/d). The main polyphenol groups were flavonoids (897 mg/d) and phenolic acids (800 mg/d). A total of 347 polyphenols from 19 polyphenol subclasses were found. The individual compounds with the highest intakes were isomers of chlorogenic acid (i.e., 5-caffeoylquinic acid and 4-caffeoylquinic acid) among hydroxycinnamic acids (average intake 150 mg/d), that largely originated from coffee, and compounds belonging to the catechin chemical family (i.e., [+]-gallocatechin, [-]-epigallocatechin 3-O-gallate, and [-]-epicatechin) among flavanols (average intake 50 mg/d), that mostly originated from tea and cocoa products.
The current study provides the most updated data for individual polyphenols intake in the diet of a well-established nutritional cohort. These findings will be useful to assess potential beneficial role on health of specific foods with high polyphenol content and characterize the effects of individual phenolic compounds.
PMCID: PMC4192147  PMID: 25280419
Polyphenols; Intake; General population; Food sources; Polish adults
4.  A high-fat diet supplemented with fish oil improves metabolic features associated with type 2 diabetes 
The objective for this study was to investigate the effects of a high-fat diet supplemented with fish oil or olive oil on metabolic features associated with type 2 diabetes fed to C57BL/6J mice for an extended period.
Mice were fed one of four diets: a low-fat diet, a high-fat diet supplemented with lard, a high-fat diet supplemented with fish oil, or a high-fat diet supplemented with olive oil for 30 wk. Phenotypic and metabolic analysis were determined at 15 and 25–30 wk, thereby providing comparative analysis for weight gain, energy consumption, fat distribution, glucose and insulin tolerance, and hepatic/plasma lipid analysis.
Mice fed a high-fat diet supplemented with fish oil had improved glucose tolerance after an extended period compared to mice fed a high-fat diet supplemented with lard. Moreover, mice fed a high-fat diet supplemented with fish oil diet had significantly decreased concentrations of liver cholesterol, cholesteryl ester, and triacylglycerol compared to mice fed a high-fat diet supplemented with either lard or olive oil.
Mice fed a high-fat diet supplemented with fish oil improved metabolic features associated with type 2 diabetes such as impaired glucose tolerance and hepatic steatosis.
PMCID: PMC3740005  PMID: 23756282
adipose; diabetes; inflammation; lipogenesis; mouse model; obesity
5.  Zinc and iron supplementation on motor and language milestone scores of infants and toddlers 
To assess the effects of zinc and iron-folic acid supplementation on motor and language milestones in Nepali children.
A total of 544 children 4–17 months old residing in Ishwarpur, Nepal were randomized to receive placebo, iron-folic acid, zinc and zinc plus iron-folic acid daily. Data were collected at baseline and at three month intervals for one year. Main effects of zinc and iron folic-acid supplementation were estimated for motor and language milestones. We modeled crude and adjusted mean cumulative changes in scores between visits 1 and 5, and adjusted rates-of-change.
Adjusted differences in motor milestone scores between visits 1 and 5 and rates-of-change were not significantly different for zinc and non-zinc groups (adj. β=−0.7, 95% CI: −1.4, 0.01; adj. β=−0.1, 95% CI:−0.5, 0.3, respectively). Motor milestones in children receiving and not receiving iron supplements were not significantly different (adj. β=0.1, 95% CI:−0.7, 0.8 from visit 1 to 5; adj. β=0.1, 95% CI:−0.3, 0.5 for rate-of-change). Children receiving zinc had a 0.8 lower mean crude change in language score between visits 1 and 5 compared to children not receiving zinc (95% CI −1.3,−0.3), but significance was lost after adjustment (adj. β=−0.2, 95% CI:−0.6, 0.2, comparing visits 1 to 5; β=−0.1, 95% CI:−0.3, 0.2 for rate-of-change). We observed no significant difference in motor or language milestone scores due to iron supplementation..
After one year, neither zinc nor iron-folic acid supplementation in Nepali children improved attainment of motor or language milestones.
PMCID: PMC3761420  PMID: 23298972
micronutrients; iron; zinc; psychomotor performance; language development; children; Nepal
6.  Obesity, systemic inflammation, and increased risk for cardiovascular disease and diabetes among adolescents: A need for screening tools to target interventions 
Cardiovascular disease (CVD) and type 2 diabetes mellitus have their roots in childhood, particularly in obese children and adolescents, raising important opportunities for early lifestyle intervention in at-risk individuals. However, not all obese individuals are at the same risk for disease progression. Accurate screening of obese adolescents may identify those in greatest need for intensive intervention to prevent or delay future disease. One potential screening target is obesity-related inflammation, which contributes to insulin resistance, metabolic syndrome, and CVD. In adults, the inflammatory marker high-sensitivity C-reactive protein (hsCRP) has utility for risk stratification and treatment initiation in individuals of intermediate CVD risk. In adolescents, hsCRP shares many of the associations of hsCRP in adults regarding the degree of insulin resistance, metabolic syndrome, and carotid artery media thickness. However, long-term data linking increased hsCRP levels—and increased insulin or decreased adiponectin—in childhood to adult disease outcomes are lacking at this time. Future efforts continue to be needed to identify childhood clinical and laboratory characteristics that could be used as screening tests to predict adult disease progression. Such tests may have utility in motivating physicians and patients' families toward lifestyle changes, ultimately improving prevention efforts.
PMCID: PMC3578702  PMID: 23022122
Obesity; Metabolic syndrome; Insulin resistance; Risk; Adolescents; Inflammation; High-sensitivity C-reactive protein; Adiponectin
7.  Characterization of Post-Hospital Infections in Adults Requiring Home Parenteral Nutrition 
Limited data are available on the incidence and risk factors for infection among patients requiring home parenteral nutrition (HPN).
Retrospective study of 101 consecutive adults (63 female, 38 male) discharged on HPN from Emory University Hospital, Atlanta, GA. New bloodstream infections (BSI) requiring re-hospitalization and other infections were evaluated.
Most infections (75%) developed during the initial 6 months after hospital discharge; rates of BSI were particularly high during the first four months. A total of 56 patients (55.4%) developed a total of 102 BSIs (11.5 BSI/1000 catheter-days). Most BSIs were attributed to Gram positive organisms (46%) including coagulase-negative staphylococcus, staphylococcus aureus, enterococcus species, and others, followed by Candida species (20%) and Gram negative organisms (13%). Twenty-one percent of BSIs were polymicrobial. The BSI incidence rate ratio (IRR) was significantly increased for patients with mean pre-hospital discharge blood glucose (BG) concentrations in the highest quartile versus the lowest quartile; IRR 2.4; P = 0.017). Patients with a peripherally inserted central catheter (PICC) versus non-PICC central venous catheters had significantly higher rates of BSI (p = 0.018). Thirty-nine (38.6%) patients developed 81 non-BSI infections, including pneumonia, urinary tract infections, and surgical site infections. Post-discharge PN dextrose, lipid, and total calorie doses were unrelated to BSI but variably related to the rate of non-BSI.
Adult HPN patients exhibit a very high incidence of post-hospital infections. Higher mean BG levels during pre-discharge hospitalization and use of PICCs at discharge are associated with an increased risk of BSI in the post-discharge home setting.
PMCID: PMC3505808  PMID: 22858199
Bloodstream infection; post-hospital infection; parenteral nutrition; risk factors
8.  Increased Plasma Availability of L-arginine in the Postprandial Period Decreases the Postprandial Lipemia in Older Adults 
Older adults have exaggerated postprandial lipemia (PPL), which increases their risk for cardiovascular disease. We sought to determine the effects of increased plasma L-arginine availability on the oxidation of ingested fat (enriched with [1,1,1-13C]-triolein) and plasma triglyceride (TG) concentrations during the postprandial period in older subjects.
On one day, eight healthy subjects (67.8 ± 1.3 years old) received an intravenous infusion of L-arginine during the first hour of the postprandial period (L-ARG), while on a separate day they received saline (control trial; CON).
The 8-h area under the curve (AUC0–8h) describing the postprandial plasma TG concentrations was considerably lower in the L-ARG trial than the CON trial (−4 ± 21 vs 104 ± 21 mg·dL−1·h; P < 0.01). The rate of the postprandial oxidation of the ingested lipid was not different between the trials, but the average contribution of ingested-oleate to the oleate of TG of the plasma small TG-rich lipoproteins (TRL; Sf = 20–400) was lower in the L-ARG trial (11 ± 1 vs 18 ± 2%; P < 0.01). L-arginine infusion decreased also the AUC0–8h of the plasma free fatty acid concentrations derived from the ingested fat when compared to the saline infusion (0.77±0.09 vs 1.11 ± 0.08; mmol·L−1·h; P < 0.01).
Increasing the plasma L-arginine availability during the postprandial period decreases the PPL in older adults, in association with a decrease in the postprandial contribution of ingested lipid into TG of the plasma small TRL.
PMCID: PMC3519962  PMID: 22959634
Elderly; Fatty acids; Triglycerides; Stable isotope tracers; Fat meal
9.  No effects of low and high consumption of dairy products and calcium supplements on body composition and serum lipids in Puerto Rican obese adults 
Nutrition (Burbank, Los Angeles County, Calif.)  2010;27(5):10.1016/j.nut.2010.02.011.
Epidemiologic studies have shown that a high calcium intake is related to lower body weight, fat, and serum lipids in obese individuals. However, clinical studies have shown inconclusive results. The present study was conducted to determine if dairy or calcium supplementation alters body composition or serum lipids in Puerto Rican obese adults without dietary energy restriction or exercise.
A 21-wk randomized clinical trial was conducted in 30 obese adults, aged 21–50 y, with usual calcium intakes <700 mg/d. Subjects were randomly assigned to the following: high dairy (~1300 mg/d of calcium from dairy products by substituting foods); high calcium (~1300 mg/d of calcium; ~700 mg/d from diet and 600 mg/d from a supplement); or placebo. Subjects were asked to continue their established dietary intake (except for the high dairy group) and their physical activity during the study. Body weight was measured monthly; body fat, bone, and serum lipids (total cholesterol, high-density lipoprotein, low-density lipoprotein, and triacylglycerol) were measured at baseline and at 21 wk. Pairwise differences in study endpoints among the groups were assessed using ANOVA and post-hoc analysis.
Grand mean calcium intake was 1200 ± 370 (median 1187) mg/d in the high dairy group, 1171 ± 265 (median 1165) mg/d in the high calcium group, and 668 ± 273 (median 691) mg/d in the control group, which was significantly lower compared to the two treatment groups (P < 0.001). There were no significant group effects in any of the outcome variables.
A high dairy or calcium diet alone did not alter body composition or serum lipids profile in a sample of Puerto Rican obese adults.
PMCID: PMC3827628  PMID: 20579848
High calcium; Low calcium; Dairy products; Body fat; Cholesterol; Triacylglycerol
10.  Dairy protein and leucine alter GLP-1 release and mRNA of genes involved in intestinal lipid metabolism in vitro 
Nutrition (Burbank, Los Angeles County, Calif.)  2008;25(3):10.1016/j.nut.2008.08.012.
A growing body of evidence supports an antiobesity effect of dairy products; however, the mechanisms remain unclear. The objective of this study was to explore possible intestinal mechanisms by which dairy delivers an antiobesity effect. The human intestinal cell line, NCI-H716, was used to test the hypothesis that branched-chain amino acids and dairy proteins regulate satiety hormone secretion and modulate genes involved in fatty acid and cholesterol metabolism.
In dose–response (0.5%, 1.0%, 2.0%, and 3.0%) studies, the effect of leucine, isoleucine, valine, skim milk, casein, and whey on glucagon-like peptide-1 release and the expression of selected genes were tested.
Leucine, isoleucine, skim milk, and casein stimulated glucagon-like peptide-1 release (P < 0.05). Isoleucine and whey downregulated the expression of intestinal-type fatty acid binding protein (i-FABP), fatty acid transport protein 4 (FATP4), Niemann-Pick C-1–like-1 protein (NPC1L1), acetyl-coenzyme A carboxylase (ACC), fatty acid synthase (FAS), sterol regulatory element-binding protein-2 (SREBP-2), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR; P < 0.05). Leucine and valine downregulated the expression of NPC1L1, ACC, FAS, SREBP-2, and HMGCR (P < 0.05). Casein downregulated the expression of i-FABP, FATP4, ACC, FAS, SREBP-2, and HMGCR (P < 0.05). Skim milk downregulated the expression of ACC, FAS, and SREBP-2, but not i-FABP, FATP4, and NPC1L1.
This work suggests that the antiobesity effect of dairy may be mediated, at least in part, by integration of events that promote glucagon-like peptide-1 secretion and inhibit expression of genes involved in intestinal fatty acid and cholesterol absorption and synthesis.
PMCID: PMC3827015  PMID: 19036562 CAMSID: cams3658
Milk protein; Branched-chain amino acids; Lipid metabolism; Gene expression; Fatty acid transport
11.  Sugar free, cancer free? 
PMCID: PMC3746332  PMID: 22925542
12.  Circulating selenium and carboxymethyl-lysine, an advanced glycation end product, are independent predictors of anemia in older community-dwelling adults 
To assess whether selenium and carboxymethyl-lysine (CML), two biomarkers of oxidative stress, are independent predictors of anemia in older, community-dwelling adults.
Plasma selenium, CML, folate, vitamin B12, testosterone, and markers of iron status and inflammation were measured at baseline in 1,036 adults, ≥65 years, in the InCHIANTI Study, a population-based cohort study of aging in Tuscany, Italy, and examined in relationship to prevalent anemia and incident anemia over 6 years of follow-up.
At enrollment, 11.6% of participants were anemic. Of 472 participants who were non-anemic at enrollment 72 (15.3%) developed anemia within 6 years of follow-up. At enrollment, plasma CML in the highest quartile (>425 ng/mL) and plasma selenium in the lowest quartile (<66.6 μg/L) predicted incident anemia (Hazards Ratio [H.R.] 1.67, 95% Confidence Interval [C.I.] 1.07–2.59, P = 0.02; H.R. 1.55, 95% C.I.1.01–2.38, P = 0.05, respectively) in a multivariate Cox proportional hazards model that adjusted for age, education, body mass index, cognition, inflammation, red cell distribution width, ferritin, vitamin B12, testosterone, and chronic diseases.
Elevated plasma carboxymethyl-lysine and low plasma selenium are long-term independent predictors of anemia among older community-dwelling adults. These findings support the idea that oxidative stress contributes to the development of anemia.
PMCID: PMC3377823  PMID: 22325035
advanced glycation end products; aging; anemia; carboxymethyl-lysine; oxidative stress; selenium
13.  Arginine reduces Cryptosporidium parvum infection in undernourished suckling mice involving both nitric oxide synthase and arginase 
This study investigated the role of L-arginine supplementation to undernourished and Cryptosporidium parvum-infected suckling mice.
The following regimens were initiated on the 4th day of life and given subcutaneously daily: either 200mM of L-arginine or PBS for the C. parvum-infected controls. L-arginine-treated mice were grouped to receive either 20mM of NG-nitroarginine-methyl-ester (L-NAME) or PBS. Infected mice received orally 106 excysted-C. parvum oocysts on day 6 and were euthanized on day 14th at the infection peak.
L-arginine improved weight gain compared to the untreated infected controls. L-NAME profoundly impaired body weight gain as compared to all other groups. Cryptosporidiosis was associated with ileal crypt hyperplasia, villus blunting, and inflammation. L-arginine improved mucosal histology following infection. L-NAME abrogated these arginine-induced improvements. Infected control mice showed an intense arginase expression, which was even greater with L-NAME. L-arginine reduced parasite burden, an effect that was reversed by L-NAME. C. parvum infection increased urine NO3-/NO2- concentration when compared to uninfected controls, which was increased by L-arginine supplementation, an effect that was also reversed by L-NAME.
These findings show a protective role of L-arginine during C. parvum infection in undernourished mice with involvement of arginase I and nitric oxide synthase enzymatic actions.
PMCID: PMC3351544  PMID: 22261576
Cryptosporidium parvum; diarrhea; malnutrition; arginine; growing mice
14.  High Sugar Intake Does Not Exacerbate Metabolic Abnormalities or Cardiac Dysfunction in Genetic Cardiomyopathy 
High sugar intake increases heart disease risk in humans. In animals, sugar intake accelerates heart failure development via increased reactive oxygen species (ROS). Glucose 6-phosphate dehydrogenase (G6PD) can fuel ROS production by providing NADPH for superoxide generation by NADPH oxidase. On the other hand, G6PD also facilitates ROS scavenging via the glutathione pathway. We hypothesized that high sugar intake would increase flux through G6PD to increase myocardial [NADPH] and ROS, and accelerate cardiac dysfunction and death.
Research Methods & Procedures
Six-week old TO-2 hamsters, a nonhypertensive model of genetic cardiomyopathy caused by a δ-sarcoglycan mutation, were fed a long-term diet of either high starch or high sugar (57% of energy from sucrose+fructose).
After 24 weeks, δ-sarcoglycan deficient animals displayed expected decreases in survival and cardiac function associated with cardiomyopathy (ejection fraction: control=68.7±4.5%; TO-2 starch=46.1±3.7, p<0.05 TO-2 starch vs control; TO-2 sugar=58.0±4.2%, N.S. vs TO-2 starch or control; median survival: TO-2 starch=278 days, TO-2 sugar=318 days, P=0.133). Although we expected high sugar intake to exacerbate cardiomyopathy, surprisingly there was no further decrease in ejection fraction or survival with high sugar compared to starch in cardiomyopathic animals. Cardiomyopathic animals had systemic and cardiac metabolic abnormalities (elevated serum lipids and glucose, and decreased myocardial oxidative enzymes) which were unaffected by diet. High sugar intake increased myocardial superoxide, but [NADPH] and lipid peroxidation were unaffected.
A sugar enriched diet did not exacerbate ventricular function, metabolic abnormalities, or survival in heart failure despite an increase in NADPH and superoxide production.
PMCID: PMC3327887  PMID: 22304857
heart failure; reactive oxygen species; δ-sarcoglycan; diet; sugar; fructose; sucrose
15.  What is dynapenia? 
Dynapenia (pronounced dahy-nuh-pē-nē-a, Greek translation for poverty of strength, power, or force) is the age-associated loss of muscle strength that is not caused by neurologic or muscular diseases. Dynapenia predisposes older adults to an increased risk for functional limitations and mortality. For the past several decades, the literature has largely focused on muscle size as the primary cause of dynapenia; however, recent findings have clearly demonstrated that muscle size plays a relatively minor role. Conversely, subclinical deficits in the structure and function of the nervous system and/or impairments in the intrinsic force-generating properties of skeletal muscle are potential antecedents to dynapenia. This review highlights in the contributors to dynapenia and the etiology and risk factors that predispose individuals to dynapenia. In addition, we address the role of nutrition in the muscular and neurologic systems for the preservation of muscle strength throughout the life span.
PMCID: PMC3571692  PMID: 22469110
Aging; Strength; Weakness; Function; Muscle; Disability; Sarcopenia; Dynapenia
We previously reported an association between prenatal exposure to airborne PAH and lower birth weight, birth length and head circumference. The main goal of the present analysis was to assess the possible impact of co-exposure to PAH-containing of barbecued meat consumed during pregnancy on birth outcomes.
The birth cohort consisted of 432 pregnant women who gave birth at term (>36 weeks of gestation). Only non-smoking women with singleton pregnancies, 18-35 years of age, and who were free from chronic diseases such as diabetes and hypertension were included in the study. Detailed information on diet over pregnancy was collected through interviews and the measurement of exposure to airborne PAHs was carried out by personal air monitoring during the second trimester of pregnancy. The effect of barbecued meat consumption on birth outcomes (birthweight, length and head circumference at birth) was adjusted in multiple linear regression models for potential confounding factors such as prenatal exposure to airborne PAHs, child’s sex, gestational age, parity, size of mother (maternal prepregnancy weight, weight gain in pregnancy) and prenatal environmental tobacco smoke (ETS).
The multivariable regression model showed a significant deficit in birthweight associated with barbecued meat consumption in pregnancy (coeff = −106.0 g; 95%CI: −293.3, −35.8); The effect of exposure to airborne PAHs was about the same magnitude order (coeff. = −164.6 g; 95%CI: −172.3, − 34.7). Combined effect of both sources of exposure amounted to birth weight deficit of 214.3 g (95%CI: −419.0, − 9.6). Regression models performed for birth length and head circumference showed similar trends but the estimated effects were of borderline significance level. As the intake of barbecued meat did not affect the duration of pregnancy, the reduced birthweight could not have been mediated by shortened gestation period.
In conclusion, the study results provided epidemiologic evidence that prenatal PAH exposure from diet including grilled meat might be hazardous for fetal development.
PMCID: PMC3288524  PMID: 22079395
barbecued meat; pregnancy; birth weight; birth cohort study
17.  Effects of Sunlight and Diet on Vitamin D Status of Pulmonary Tuberculosis Patients in Tbilisi, Georgia 
Vitamin D deficiency is common in tuberculosis (TB) and this may modulate immune responses.
To determine vitamin D status in patients with TB and examine sources of vitamin D in Tbilisi, Georgia.
Research Methods and Procedures
We measured plasma 25-hydroxyvitamin D (25(OH)D) and dietary vitamin D intake in pulmonary TB patients (n=85) in Tbilisi, Georgia. To determine the impact of season on vitamin D status, we tested in vitro conversion of 7-dehydrocholesterol (7-DHC) to previtamin D3 after sunlight exposure.
In TB subjects, mean plasma 25(OH)D concentrations were 14.5 ± 7.0 ng/mL, and vitamin D insufficiency (25(OH)D < 30 ng/mL) occurred in 97% of subjects. Dietary sources of vitamin D were mainly fish, eggs, and butter. Daily intake was well below recommended daily intakes in TB subjects (172 IU + 196 IU). The conversion of 7-DHC to previtamin D3 was undetectable between October to March, and highest in June and July between 11:00 and 14:00 h.
Insufficient vitamin D dietary intake and limited production of vitamin D from sunlight during the majority of the year, may explain the high prevalence of vitamin D insufficiency TB patients in Tbilisi.
PMCID: PMC3303957  PMID: 22304856
cholecalciferol; 7-dehydrocholesterol; dietary intake
18.  25(OH)D deficiency is associated with fatal stroke among whites but not blacks: The NHANES-III linked mortality files 
Deficient 25-hydroxyvitamin D [25(OH)D] levels are associated with cardiovascular disease (CVD) events and mortality. Both 25(OH)D deficiency and stroke are more prevalent among blacks. We examined whether low 25(OH)D contributes to the excess risk of fatal stroke in blacks compared to whites.
Research Methods and Procedures
The Third National Health and Nutrition Examination Survey, a probability sample of US civilians, measured 25(OH)D levels and CVD risk factors between 1988–1994. Vital status through December 2006 was obtained via linkage with the National Death Index. Among white and black adults without CVD reported at baseline (n=7981), Cox regression models were fit to estimate hazard ratios (HR) for fatal stroke by 25(OH)D status and race.
During a median of 14.1 years, there were 116 and 60 fatal strokes among whites and blacks respectively. The risk of fatal stroke was greater in blacks compared to whites in models adjusted for socio-economic status and CVD risk factors, [HR 1.60 (95% CI 1.01–2.53)]. Mean baseline 25(OH)D levels were significantly lower in blacks compared to whites (19.4 vs 30.8 ng/mL, respectively). In multivariable-adjusted models, deficient 25(OH)D levels <15 ng/mL were associated with fatal stroke among whites [HR 2.13 (1.01–4.50)] but not blacks [HR 0.93 (0.49–1.80)].
Vitamin D deficiency was associated with increased risk of stroke death in whites but not blacks. Although blacks had a higher rate of fatal stroke compared to whites, the low 25(OH)D levels in blacks were unrelated to stroke incidence and therefore 25(OH)D levels did not explain this excess risk.
PMCID: PMC3304002  PMID: 22261577
vitamin D; stroke; racial differences
19.  Further Developments in the Neurobiology of Food and Addiction: Update on the State of the Science 
Over the past three decades obesity has become a major public health crisis in the United States. The prevalence of obesity in the United States and in other parts of the World has led to the new word, globesity, now being used to describe the problem. As a result of this increased emphasis on understanding the causes and consequences of obesity, novel theories have stimulated new research aimed to prevent, intervene with, and ameliorate the effects and reduce the incidence and medical consequences of globesity. One theory that has gained popularity in recent years, which we described and analyzed in our previous paper Neurobiology of Food Addiction, is based on the idea that excessive intake of highly-palatable foods shares similarities with the effects on brain and behavior that are seen with some drugs of abuse. While this theory is not new, empirically-based translational research has only recently provided strong support for this hypothesis. In this article, we review the present state of the science in this area and describe a variety of newer clinical and preclinical works that shed light on innovative and interesting overlaps between excessive palatable food intake and drug use.
PMCID: PMC3304017  PMID: 22305533
Addiction; Dopamine; Food intake; Obesity; Overeating
20.  Sulfur amino acid-free diet results in increased glutamate in human midbrain: A pilot magnetic resonance spectroscopy study 
This pilot study was designed to determine if metabolic effects in different brain regions (left and right parietal lobes, midbrain) due to 3 days of food consumption without methionine or cysteine could be detected by proton magnetic resonance spectroscopy (MRS).
Research Methods & Procedures
Healthy individuals aged 18-36 y (n=8) were studied by MRS after receiving diet with adequate sulfur amino acids (SAA) or with zero SAA for 3 days. Pulse sequences were used to selectively measure glutathione (GSH) and linear combination modeling (LCM) of spectra was used to measure other high abundance brain metabolites, and expressed relative to creatine (Cr).
Although dietary SAA are required to maintain glutathione (GSH), the 3-d SAA insufficiency resulted in no significant change in GSH/Cr in the three brain regions. Principal component analysis of 16 metabolites measured by LCM showed that the metabolic pattern in the midbrain, but not the parietal lobes, was distinguished according to the dietary SAA. Multivariate statistical analysis showed that the major discriminating factors were signals of glutamate/Cr, (glutamate+glutamine)/Cr, and myo-inositiol/Cr. Correlation analyses between midbrain metabolites and GSH-related metabolites in plasma showed that midbrain glutamate/Cr had an inverse correlation with plasma cystine.
The data show that MRS is a non-invasive tool suitable for nutritional assessment and suggest that nutritional imbalance caused by 3-d of sulfur amino acid-free food more selectively affects midbrain than the parietal lobes.
PMCID: PMC3273631  PMID: 21917421
Brain metabolism; oxidative stress; amino acid metabolism; nutritional assessment; protein malnutrition; glutathione
Roux-en-Y gastric bypass (RYGB) surgery is the most common surgical intervention for long-term weight loss in morbidly obese patients. By reducing obesity-associated hyperfiltration, diabetes, and hypertension, RYGB is touted to stabilize if not prevent progression of chronic renal disease. To test this, we compare renal histology of diet-induced obese rats that have undergone RYGB surgery to pair-fed and sham obese controls.
Research Methods and Procedures
Sprague-Dawley rats, fed a high fat, low-oxalate diet to induce gross obesity, were randomized to RYGB (n=6), GI-intact sham-operated obese controls (Sham, n=4), or GI-intact sham-operated obese pair-fed rats (Fed, n=8). Daily body weight and food intake were recorded. On post-operative day 42, renal histology and immunohistochemistry was examined. Renal pathology was assessed by a categorical glomerular lesion score and a quantitative glomerular/tubular scoring system by experienced veterinary pathologists. Osteopontin (OPN) and ED-1 (monocyte/macrophage cell) staining were estimated on percentage of stained area and number of counted cells/high power field respectively.
Compared to sham and fed controls, RYGB rats had significant reductions in body weight (p<0.001), more glomerular lesions (p=0.02), and received higher glomerular and tubular lesion scores (p<0.01). RYGB rodents had significantly stronger staining for OPN within the inner medullary region (p<0.005) and ED-1 within the outer medullary region (P<0.02) compared to sham and fed controls.
In this diet-induced obese rat model, RYGB is associated with chronic glomerulosclerosis and tubulointerstitial nephritis, confirmed by histology and immunohistochemistry. Prospective studies to better define the injurious mechanisms in this model are planned.
PMCID: PMC3197873  PMID: 21723091
morbid obesity; interstitial nephritis; gastric bypass; oxalate
Lower brain glucose metabolism is present before the onset of clinically-measurable cognitive decline in two groups of people at risk of Alzheimer’s disease (AD) - carriers of apoE4, and in those with a maternal family history of AD. Supported by emerging evidence from in vitro and animal studies, these reports suggest that brain hypometabolism may precede and contribute to the neuropathological cascade leading cognitive decline in AD. The reason for brain hypometabolism is unclear but may include defects in glucose transport at the blood-brain barrier, glycolysis, and/or mitochondrial function. Methodological issues presently preclude knowing with certainty whether or not aging in the absence of cognitive impairment is necessarily associated with lower brain glucose metabolism. Nevertheless, aging appears to increase the risk of deteriorating systemic control of glucose utilization which, in turn, may increase the risk of declining brain glucose uptake, at least in some regions. A contributing role of deteriorating glucose availability to or metabolism by the brain in AD does not exclude the opposite effect, i.e. that neurodegenerative processes in AD further decrease brain glucose metabolism because of reduced synaptic functionality and, hence, reduced energy needs, thereby completing a vicious cycle. Strategies to reduce the risk of AD by breaking this cycle should aim to – (i) improve insulin sensitivity by improving systemic glucose utilization, or (ii) bypass deteriorating brain glucose metabolism using approaches that safely induce mild, sustainable ketonemia.
PMCID: PMC3478067  PMID: 21035308
Glucose; ketones; brain; aging; Alzheimer’s disease; PET; insulin; cognition; mitochondria
We recently identified an inverse relationship between systolic blood pressure (SBP) and serum 16α-hydroxyestrone, a metabolite of 17β-estradiol, in postmenopausal women. Formation of 16α-hydroxyestrone is catalyzed primarily by CYP1A2, a cytochrome P450 enzyme. The objective of this study was to evaluate the relationships between known modifiers of CYP1A2 activity and serum 16α-hydroxyestrone in postmenopausal women. We hypothesized that fruits, vegetables, and grains, which contain more soluble fiber (a known inducer of CYP1A2) as a proportion of total fiber, would be more positively associated with serum 16α-hydroxyestrone than legumes, which contain less soluble fiber as a proportion of total fiber.
Materials and Methods
Serum from a population-based sample of 42 postmenopausal women aged 55–69 living in Cook County, Illinois, was assayed for 16α-hydroxyestrone using mass spectrometry. Ordinal logistic regression was used to evaluate the cross-sectional relationship between dietary fiber and serum 16α-hydroxyestrone after adjusting for multiple covariates.
Relative to dietary fiber from legumes, dietary fiber from fruits and vegetables was associated with a greater log odds (B = 0.201, p = 0.036) of having higher serum concentrations of 16α-hydroxyestrone. The log odds of having higher serum concentrations of 16α-hydroxyestrone was also lower among African-American women (B = −2.300, p = .030) compared to white women.
These results are consistent with previous studies demonstrating a negative relationship between SBP and dietary fruits and vegetables and a positive relationship between African-American race and SBP. Further research is needed regarding dietary factors that may influence the serum concentration of 16α-hydroxyestrone.
PMCID: PMC3116971  PMID: 21035306
nutrition; fiber; fruits; vegetables; estrogen; metabolism; blood pressure
24.  Mediterranean diet and cardioprotection: the role of nitrite, polyunsaturated fatty acids and polyphenols 
The continually increasing rate of myocardial infarction (MI) in the Western world at least partly can be explained by a poor diet lacking in green vegetables, fruits, and fish, and enriched in food that contains saturated fat. In contrast, a number of epidemiological studies provide strong evidence highlighting the cardioprotective benefits of the Mediterranean diet enriched in green vegetables, fruits, fish and grape wine. Regular consumption of these products leads to an accumulation of nitrate/nitrite/NO•, polyunsaturated fatty acids (PUFA), and polyphenolic compounds, such as resveratrol, in the human body. Studies have confirmed that these constituents are bioactive exogenous mediators, which induce strong protection against MI. The aim of this review is to provide a critical, in-depth analysis of the cardioprotective pathways mediated by nitrite/NO•, PUFA, and phenolic compounds of grape wines discovered in the recent years, including cross-talk between different mechanisms and compounds. Overall, these findings may facilitate the design and synthesis of novel therapeutic tools for the treatment of MI.
PMCID: PMC3117983  PMID: 21454053
25.  A higher degree of LINE-1 methylation in peripheral blood mononuclear cells, a one-carbon nutrient related epigenetic alteration, is associated with a lower risk of developing cervical intraepithelial neoplasia 
The objective of the study was to evaluate LINE-1 methylation as an intermediate biomarker for the effect of folate and vitamin B12 on the occurrence of higher grades of cervical intraepithelial neoplasia (CIN 2+).
Study included 376 women who tested positive for HR-HPVs and were diagnosed with CIN 2+ (cases) or ≤ CIN 1 (non-cases). CIN 2+ (yes/no) was the dependent variable in logistic regression models that specified the degree of LINE-1 methylation of peripheral blood mononuclear cells (PBMCs) and of exfoliated cervical cells (CCs) as the independent predictors of primary interest. In analyses restricted to non-cases, PBMC LINE-1 methylation (≥70% vs. <70%) and CC LINE-1 methylation (≥54% vs. <54%) were the dependent variables in logistic regression models that specified the circulating concentrations of folate and vitamin B12 as the primary independent predictors.
Women in the highest tertile of PBMC LINE-1 methylation had 56% lower odds of being diagnosed with CIN 2+ (OR = 0.44; 95% CI, 0.24-0.83; P = 0.011) while there was no significant association between degree of CC LINE-1 methylation and CIN 2+ (OR = 0.86; 95% CI, 0.51-1.46; P = 0.578). Among non-cases, women with supra-physiologic concentrations of folate (>19.8 ng/mL) and sufficient concentrations of plasma vitamin B12 (≥ 200.6 ng/mL) were significantly more likely to have highly methylated PBMCs compared to women with lower folate and lower vitamin B12 (OR = 3.92; 95% CI, 1.06-14.52; P = 0.041). None of the variables including folate and vitamin B12 were significantly associated with CC LINE-1 methylation.
These results suggest that a higher degree of LINE-1 methylation in peripheral blood mononuclear cells, a one-carbon nutrient related epigenetic alteration, is associated with a lower risk of developing cervical intraepithelial neoplasia.
PMCID: PMC3070926  PMID: 21463750
methylation; cervical; neoplasia

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