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An inexpensive and simple method to determine non-alcoholic fatty liver disease (NAFLD) is the abdominal ultrasound, but there are still doubts about its accuracy. We assessed the precision of a semi-quantitative ultrasound method to determine liver fat infiltration, using magnetic resonance spectroscopy (MRS) as the reference. The study was conducted in youths from an ongoing cohort study. Clinical validation was performed, using receiver operating characteristic analysis, in n = 60 participants (22.6y; 50% males). Abdominal ultrasound was carried out with liver brightness (score 0–3), diaphragm attenuation (0–2) and liver vessel blurring (0–1) scored by two observers. Liver fat was estimated using MRS. Then, analytical validation was conducted in the remaining participants (n = 555; 22.7y; 51% males) using effects size estimates. An ultrasound score ≥4.0 had the highest sensitivity (78%) and specificity (85%) for NAFLD diagnosis. An area under the curve of 86% denotes a good diagnostic performance of the test, whereas a Kappa of 0.63 suggests substantial agreement of ultrasound vs. MRS. The analytical validation showed that participants having NAFLD according to ultrasound had an unhealthier cardiometabolic profile than participants without the condition. Abdominal ultrasound, combined with a semi-quantitative score system, is a reliable method to determine liver fat infiltration in young adults and should be encouraged whenever MRS is unavailable.

Objectives International cutoff points for the diagnosis of sarcopenia are not applicable to the Chilean population due to previous evidence of a lower lean mass and strength in this population. Dual-energy x-ray absorptiometry is used to establish fat-free mass cutoff points to define sarcopenia in the Chilean population and analyze its association with handgrip strength in older adults. Methods Appendicular fat-free mass (AFFM) was calculated from 4062 dual-energy x-ray absorptiometries of healthy Chileans, ages 18 to 99 y. Possible cutoff points for sarcopenia were obtained using four methods: A) Normative, –2 standard deviation (SD) below mean AFFM/height2 (AFFMI) of adults age Results Using the normative method, sarcopenia was defined as an AFFMI Conclusions The AFFM of young Chileans is lower than that reported in Western countries but similar to Latin American data; therefore, the use of the traditional normative method would not be appropriate with –2 SD to establish cutoff points, and using –1 DS resulted in values that are higher than Baumgartner's. Stratification is advantageous because this method throws expected values of AFFM for each population; however, overdiagnosis of sarcopenia is a possibility and thus the method requires a representative sample. The percentage method is simple and showed the expected decrease of muscle mass with age, and also correlated well with handgrip strength in elderly women. Thus, this method represented our method of choice to detect sarcopenia.

Background/Aims Chronic intestinal pseudo-obstruction (CIPO) is a rare syndrome characterized by a failure of the propulsion of intraluminal contents and recurrent symptoms of partial bowel obstruction in the absence of mechanical obstruction. Regional variations of the intestinal compromise have been described. Intestinal manometry can indicate the pathophysiology and prognosis. Our objective is to establish the demographic and clinical characteristics of group Chilean patients and analyze the motility of the small intestine and its prognostic value. Methods Patients with symptoms of intestinal pseudo-obstruction with dilated bowel loops were included, in all of whom a manometry of the small intestine was performed using perfused catheters. Results Of the 64 patients included, 51 women (average age 41.5 ± 17.6 years), 54 primary and 10 secondary CIPO were included. Dilatation of the small intestine was the only finding in 38 patients; in the remaining, the compromise was associated with other segments, primarily the colon. Forty-nine patients underwent 65 surgeries, mainly exploratory laparotomies and colectomies. Intestinal manometry was performed on all patients; 4 “patterns” were observed: neuropathic (n = 26), myopathic (n = 3), mixed (n = 24), and a group without motor activity (n = 11). The most relevant findings were the complex migrating motor disorders and decreased frequency and propagation of contractions. The 9 patients who died had a severe myopathic compromise. Conclusions In our series, isolated small bowel compromise was the most common disorder. Neuropathic motor compromise was observed in most of the patients. Mortality was associated with severe myopathic compromise. (J Neurogastroenterol Motil 2017;23:273-280)

Summary Problem Up to 35% of hospitalized patients may experience functional decline during or after hospitalization. Subjective Global Assessment (SGA) and handgrip strength at admission, have been proposed as simple and accessible tools to predict functional decline, but there are few studies in hospitalized patients to confirm these findings. Objective To assess the predictive value of handgrip strength at hospital admission, on functional decline after 30 days. Methods 125 non-critical patients hospitalized for medical and surgical conditions, were studied in El Pino hospital in Santiago, Chile. Upon admission, nutritional status was assessed by SGA, functional status through the Karnofsky index (KI), and handgrip strength by dynamometry. Change in functionality was assessed by the difference between KI at admission and 30 days later. Multivariate logistic regression models were used to establish associations between the variables at hospital admission, and subsequent functional decline. Results Thirty days post-hospital admission, 28.8% of the sample showed functional decline. In a multivariate analysis, only handgrip strength was associated with this decline (β = −0.025, OR = 0.974 (CI 0.956–0.992), p = 0.007). Conclusions Handgrip strength upon hospital admission can be a useful independent and early method to predict deterioration of functional status during hospitalization.

Objective Omega-3 fatty acids may reduce albuminuria and cardiovascular risk factors in patients with chronic kidney disease (CKD). We aimed to assess the effects of omega-3 fatty acid supplementation on albuminuria, blood pressure, pulse wave velocity, and inflammatory markers in patients with CKD. Methods Patients with CKD and a urine albumin excretion of at least 30 mg/g creatinine were supplemented for 3 months with 3,666 mg/day of docosahexaenoic and eicosapentaenoic acids or a corn oil supplement. The study was double blind. At baseline, 6 weeks, and 12 weeks, fasting blood and morning spot urine samples were obtained. Blood pressure, carotid intima media thickness, and pulse wave velocity were measured. The main outcome measure was a reduction of ≥20% in urine albumin. Results One hundred patients were randomized (50 received omega-3 fatty acids and 50 received corn oil). Four patients who received omega-3 fatty acids and 5 who received vegetable oil were lost to follow-up. In patients receiving omega-3 fatty acids, the omega-3 index increased from 3.08 (2.32-3.81) to 5.48 (3.045-7.04) percent. A 20% reduction in urine albumin excretion was observed in 13 participants of the control group and 19 participants of omega-3 group (Fisher's exact P = .274). However, the supplement had a significant and positive effect on pulse wave velocity and triglyceride level. Conclusion An omega-3 fatty acid supplement of 3,666 mg/day did not modify urine albumin excretion in patients with CKD but did improve pulse wave velocity and serum triglyceride levels.

espanolIntroduccion: la restriccion proteica es fundamental en el manejo de la enfermedad renal cronica. Objetivo: evaluamos la utilidad de la medicion de nitrogeno ureico urinario como marcador de restriccion proteica. Metodos: participantes jovenes sanos fueron divididos aleatoriamente en dos grupos. Un grupo recibio una dieta con 30 kcal/dia/kg peso corporal y 1 g/proteina/dia/kg peso corporal y el otro recibio una dieta con la misma cantidad de calorias pero con 0,6 g/kg peso corporal de proteina. Al inicio, a los siete y a los 14 dias, los participantes respondieron una encuesta dietaria de recordatorio de 24 horas. Ademas, recolectaron orina de 24 horas y se les tomo una muestra aislada de orina al comienzo y a los 14 dias de la intervencion para medir creatinina y nitrogeno ureico. Resultados: cuarenta y un participantes de 29 ± 5 anos completaron el estudio. El grupo que consumio 0,6 g/kg de proteinas redujo su ingesta proteica de 0,88 ± 0,06 a 0,59 ± 0,05 g/kg/dia durante la intervencion. En este grupo se observo una reduccion significativa en la excrecion urinaria de nitrogeno ureico en 24 horas. No se observo tal reduccion en el grupo que consumio 1 g/kg de proteinas. La tasa de probabilidad de detectar una reduccion en la ingesta proteica en las encuestas dietarias, cuando se observaba una disminucion en la excrecion urinaria de nitrogeno ureico/mg creatinina de 24 horas, fue de 5,75 (intervalos de confianza de 95% = 1,29-25,55, p = 0,02). No hubo cambios significativos en la excrecion de nitrogeno ureico en las muestras aisladas de orina. Conclusion: las mediciones repetidas de nitrogeno ureico urinario en 24 horas son un marcador de restriccion dietaria de proteinas. EnglishBackground: protein restriction is the mainstay of dietary management of chronic kidney disease. Aim: to assess the usefulness of urine urea nitrogen measurement as a marker of protein restriction. Methods: healthy young participants were randomly divided in two groups. During 14 days, one group received a diet containing 30 kcal/kg body weight and 1 g protein/kg body weight and the other group received a diet with the same amount of calories and 0.6 g/kg of proteins. At baseline, seven days and 14 days, 24 h dietary recalls were answered by the participants. They collected 24 hour urine and provided spot urine samples at baseline and at the end of the intervention, to measure creatinine and urea nitrogen. Results: forty-one participants aged 29 ± 5 years completed the follow-up. According to 24h dietary recalls, the group receiving 0.6 g/kg protein reduced significantly the protein intake during the intervention from 0.88 ± 0.06 to 0.59 ± 0.05 g/kg/day. A significant reduction in 24 h urea nitrogen excretion was also observed in this group. In the group receiving 1 g/kg of protein, no significant changes in 24 h urea nitrogen excretion were observed. Among all participants, the odds ratio of observing a reduction in protein intake in the dietary survey was 5.75 (95% confidence intervals 1.29-25.55, p = 0.02), when a reduction in 24 h urea nitrogen excretion corrected by creatinine was observed. No changes were observed in urea nitrogen excretion in spot urine samples. Conclusions: repeated urea nitrogen excretion measured in 24 h urine samples can be a reliable indicator of dietary protein restriction.

Introduction Muscle mass and function are among the most relevant factors that contribute to an optimal quality of life, and are strong predictors of mortality in the elderly. Loss of lean tissues and deterioration of muscle function have been described as one of the many complications of type 2 diabetes mellitus (DM2), but most studies do not isolate age as an intervening factor. Aim To study whether adult DM2 patients up to 60 years of age have decreased muscle mass and function compared with healthy non-diabetic (ND) subjects of similar age. Methodology Appendicular fat-free mass (ApFFM) by dual X-ray absorptiometry (DEXA), handgrip strength (HS), quadriceps strength (QS), 12 min walking capacity (12MW) and the Timed Up and Go test (TUG) were measured in 100 DM2 patients and 39 ND controls. Muscle quality, or the ratio between lean mass and muscle strength of upper and lower limbs, and the functional limitations associated with pain and stiffness assessed according to the Western Ontario and McMaster Universities Arthrosis Index (WOMAC) were also recorded. Specific tests were performed to rule out microvascular diabetic complications (retinal and peripheral nerves), metabolic control, kidney function and vitamin D status and examine their association with ApFFM and function. Results ApFFM was significantly higher among DM2 female patients and lower among diabetic men. However opposite results were obtained when individual values were corrected for body mass index (BMI), specifically among women, who were more likely to be obese. As for muscle strength and global functionality tests, significantly better performances in TUG, 12MW, QS and HS were observed among ND subjects of both sexes. These differences prevailed even after excluding diabetic patients with microvascular complications as well as those with more than 10 years of diabetes. Muscle quality was also significantly better among ND women. Higher scores of pain and stiffness in the WOMAC scale correlated with 12MW and TUG in both groups but did not correlate with ApFFM. Conclusions We found a clear deterioration of lean mass and muscle functions among adult DM2 patients of up to 60 years old, independent of length of disease, metabolic control, vitamin D status and presence of microvascular complications and pain.

Background Sedentariness may be an important risk factor for sarcopenia. The aim of this work was to assess the association between muscle mass and strength and markers of usual physical activity such as activity energy expenditure and peak oxygen uptake. Methods Young and old participants were assessed measuring body composition by DEXA (double beam X ray absorptiometry), handgrip strength, peak oxygen consumption and workload during an exercise calorimetry in a braked cycle ergometer and a 72 h activity energy expenditure using Actiheart actigraphs. A heart rate/energy expenditure curve derived from the exercise calorimetry was used to calibrate each actigraph. Sarcopenia was defined as having an appendicular fat free mass index below 7.5 kg/m2 and 5.6 kg/m2 in men and women respectively, or a handgrip strength z score below 1, using local normal data or having both parameters below the cutoff points. Results We analyzed data from 192 assessments performed in participants aged 22 to 88 years (106 women). Sarcopenic participants (as determined by muscle mass, strength or both) had a significantly lower peak oxygen uptake and work load and a significantly lower activity energy expenditure. When analyzing lean mass and strength as continuous variables, peak oxygen consumption was a significant predictor of fat free mass in men. Among women, the association was observed only when percentage of muscle mass was expressed as a z score. Conclusions Activity energy expenditure and peak oxygen consumption are associated with a lower muscle mass and the presence of sarcopenia and should be considered as risk factors for this condition.

Background: the prognostic value of maximal inspiratory and expiratory pressures on functional capacity and mortality of hospitalized patients are not well established. Aim: to evaluate the prognostic value of respiratory pressures in hospitalized patients. Methods: patients admitted to a general hospital in Santiago-Chile were prospectively studied. Within 48 hours of admission, handgrip strength and inspiratory and expiratory pressures were measured. Subjective global assessment of nutritional status (SGA) was determined and Apache II score was calculated. Functional status was assessed using the Karnofski index. Patients were followed for a period of 30 days. Mortality and decline in functional capacity, defined as a reduction in at least two stages of the Karnofski index were determined. Normal values for handgrip strength and respiratory pressures were obtained in 366 healthy subjects aged 20 to 89 years, thus the results obtained in patients were expressed as age and sex matched z-scores. Results: one hundred and eight patients were recruited and 18 had to be excluded. Thus, 90 patients aged 58 ± 16 years (46 females) were studied. During the observation period, six patients died and nine experienced a decline in functional status. Patients who died had significantly lower maximal inspiratory and expiratory pressures, hand grip strength and worse SGA. Logistic regression analysis only accepted maximal expiratory pressure expressed as z-score as a predictor of mortality. In addition, it was the only significant predictor of death or functional decline. Conclusions: maximal expiratory pressure on admission was a predictor of death or functional decline at 30 days.

OBJECTIVETo determine whether probiotic prophylaxes reduce the odds ofClostridium difficileinfection (CDI) in adults and children.DESIGNIndividual participant data (IPD) meta-analysis of randomized controlled trials (RCTs), adjusting for risk factors.METHODSWe searched 6 databases and 11 grey literature sources from inception to April 2016. We identified 32 RCTs (n=8,713); among them, 18 RCTs provided IPD (n=6,851 participants) comparing probiotic prophylaxis to placebo or no treatment (standard care). One reviewer prepared the IPD, and 2 reviewers extracted data, rated study quality, and graded evidence quality.RESULTSProbiotics reduced CDI odds in the unadjusted model (n=6,645; odds ratio [OR] 0.37; 95% confidence interval [CI], 0.25–0.55) and the adjusted model (n=5,074; OR, 0.35; 95% CI, 0.23–0.55). Using 2 or more antibiotics increased the odds of CDI (OR, 2.20; 95% CI, 1.11–4.37), whereas age, sex, hospitalization status, and high-risk antibiotic exposure did not. Adjusted subgroup analyses suggested that, compared to no probiotics, multispecies probiotics were more beneficial than single-species probiotics, as was using probiotics in clinical settings where the CDI risk is ≥5%. Of 18 studies, 14 reported adverse events. In 11 of these 14 studies, the adverse events were retained in the adjusted model. Odds for serious adverse events were similar for both groups in the unadjusted analyses (n=4,990; OR, 1.06; 95% CI, 0.89–1.26) and adjusted analyses (n=4,718; OR, 1.06; 95% CI, 0.89–1.28). Missing outcome data for CDI ranged from 0% to 25.8%. Our analyses were robust to a sensitivity analysis for missingness.CONCLUSIONSModerate quality (ie, certainty) evidence suggests that probiotic prophylaxis may be a useful and safe CDI prevention strategy, particularly among participants taking 2 or more antibiotics and in hospital settings where the risk of CDI is ≥5%.TRIAL REGISTRATIONPROSPERO 2015 identifier: CRD42015015701Infect Control Hosp Epidemiol2018;771–781

Chronic renal disease (CRD) in its pre-dialysis stage is an important risk factor for mortality among adults. The aim of this study was to assess the effects of CRD on mortality among consultants in Chilean public primary care clinics. We obtained information about serum creatinine, urinary albumin excretion (UAE), blood pressure, and body mass index of 5224 consultants [3379 females aged 67 (59-75) years and 1845 males aged 68 (59-75) years] in three clinics of Metropolitan Santiago. Kaplan-Meier curves and Cox proportional hazard regression models were used to determine risk factors for mortality, determined 41 months after obtaining the blood samples. During the follow-up period, 262 patients died (33% due to circulatory causes and 29% due to tumors). Kaplan-Meier curves showed that there was a significant association between survival, estimated glomerular filtration rate, and UAE. Cox models showed that serum creatinine, UAE, a lower body mass index, and a history of diabetes were significant mortality predictors. A sensitivity analysis performed eliminating extreme ages (less than 50 and more than 80 years), included high diastolic pressure as a predictor of survival. We conclude that among patients with CRD in its pre-dialysis stage, UAE is an important predictor of survival, along with serum creatinine. A low body mass index was associated with a higher mortality.

Introduction: Non-caloric artificial sweeteners (NAS) consumption may not be safe for health. Several cohort studies have found a positive association between consumption of artificially sweetened beverages (ASB) with weight gain chronic non-communicable diseases. Therefore, it is of interest to study the effect of the consumption of NAS on glucose and insulin response in different conditions.Aim: To determine the effect of acute NAS consumption on blood glucose and insulin curves in healthy people.Methods: A randomized double-blind clinical trial was conducted in 9 apparently healthy subjects who were randomly assigned to drink one can of ASB and one can of sugar sweetened beverages (SSB) and repeated under identical conditions for 3 times each beverage. Blood glucose and insulin levels were measured in the fasted state and during 180 min after the ingestion of the beverage. Areas Under the Curve (AUC) for glucose and insulin were calculated for the values above baseline for the 3 hour period following the drink intake. Within and between coefficients of variation were calculated.Results: The ASB beverage induced a significantly lower area under the curve (AUC) for plasma glucose (87 ± 182 mg* min/dl) and plasma insulin (36 ± 50 μ UI * min/ml) compared with the SSB drink (glucose 954 ± 669 mg * min/dl and insulin 1738 ± 887 μ UI * min/ml) p

Henriquez, S, Monsalves-Alvarez, M, Jimenez, T, Barrera, G, Hirsch, S, de la Maza, MP, Leiva, L, Rodriguez, JM, Silva, C, and Bunout, D. Effects of two training modalities on body fat and insulin resistance in postmenopausal women. J Strength Cond Res 31(11): 2955-2964, 2017-Our objective was to compare the effects of a low-load circuit resistance training protocol and usual aerobic training in postmenopausal women. Postmenopausal women with at least 1 feature of the metabolic syndrome were randomly allocated to a low-load circuit resistance training protocol or traditional aerobic training in a braked cycle ergometer. The intervention consisted in supervised sessions lasting 40 minutes, 3 times per week, during 6 months. At baseline and at the end of the intervention, fasting serum lipid levels, serum interleukin 6, C-reactive protein, 8 isoprostanes, and insulin resistance (assessed through QUICKI and HOMA-IR) were measured. Body fat was measured by double-beam X-ray absorptiometry and by computed tomography densitometric quantification at lumbar 3 vertebral level. Twenty-one women aged 58 (54-59) years were allocated to aerobic training and 21 women aged 55 (52-61) years were allocated to the low-load circuit resistance training protocol. Eighteen and 16 women in each group completed the 6 months training period. Women in both groups experienced significant reductions in blood pressure, total body, subcutaneous, and intraabdominal body fat. Reductions in total cholesterol and triacylglycerol levels were also observed. No changes in insulin resistance indexes, 8 isoprostanes, C-reactive protein, or interleukin 6 were observed in either group. No significant differences between treatment groups were observed in any of the measured parameters. We conclude that low-load circuit resistance training and aerobic training resulted in the same reductions in body fat and serum lipid levels.

El aporte de folatos durante el embarazo es esencial para un desarrollo fetal y placentario adecuados y para la salud del individuo a largo plazo. Su deficiencia puede inducir alteraciones y patologías fetales como bajo peso al nacer, recién nacidos de pre término y defectos del tubo neural (DTN). Por ello, varios países han decidido implementar políticas públicas de fortificación de alimentos con ácido fólico (AF). Chile inició la fortificación de la harina de trigo con AF en el año 2000, logrando reducir en un 43% la prevalencia de DTN. Sin embargo, además de la elevada ingesta de pan de nuestra población (principal alimento fortificado con AF), muchas mujeres embarazadas consumen suplementos de AF, lo que podría estar superando las concentraciones máximas de AF recomendadas. Adicionalmente, si la dieta materna es reducida en vitamina B12 (vit B12), se alteraría la razón óptima folatos/vit B12 lo que modificaría la metilación de genes específicos y otras vías metabólicas pudiendo afectar el desarrollo fetal y la salud de los recién nacidos a largo plazo. Creemos que, transcurridos 17 años del inicio de la fortificación de la harina de trigo con AF, es necesario evaluar los posibles efectos secundarios de un alto consumo de AF, no solo durante el embarazo, sino también en la población general. Presentamos antecedentes acerca del mecanismo de acción de folatos y vit B12 a nivel celular, y conceptos actuales sobre las posibles consecuencias de un aporte materno elevado de AF sobre la descendencia.

Background: The Chilean Ministry of Health developed a healthy lifestyles intervention directed to adults with overweight and cardiovascular risk factors, called "Program on Healthy Eating and Physical Activity" (PASAF). Aim: To evaluate the impact of PASAF on nutritional status and metabolic parameters. Patients and Methods: We analyzed databases from three primary care centers belonging to a municipality of Metropolitan Santiago. We selected adults enrolled in the PASAF during three years (2007-2009). The program lasted four months and included an assessment of anthropometric and metabolic parameters at baseline and at the end, eight workshops with a nutritionist, seven with a psychologist and 32 sessions of physical activity. Result: We evaluated 526 subjects aged ≥ 18 years (93% females), of whom 85.6% attended the last appointment for assessment. Analyzing available data, attendance to workshops was < 50% of the scheduled sessions. Weight, body mass index and waist circumference decreased significantly (median: -1.4 kg, -0.6 kg/m² and -3 cm, respectively). The median weight loss was 1.8% of initial weight and 17.1% of participants experienced a decrease ≥ 5% of their initial weight. There were significant improvements in lipid levels and blood pressure among participants with lower initial excess weight. A reduction in fasting blood glucose was observed only among subjects who lost ≥ 5% of their initial weight. Conclusions: The PASAF modestly reduced nutritional parameters. Correction of metabolic parameters was especially effective in less obese subjects. The attendance to workshops was low.

Background Lack of weight gain throughout adult life could mimic the beneficial effects of energy restriction in humans. The present study aimed to assess the effects of weight stability or gain, over a period of 10 years, on telomere length, sirtuin 1 and 6 expression, and carotid intima media thickness. Methods We studied 148 healthy adults (age range 20–59 years; 101 females) who had an objective record of their weight 10 years before. They were classified as weight losers, weight maintainers, weight gainers and extreme weight gainers. A fasting blood sample was obtained for routine laboratory and isolation of peripheral blood mononuclear cells, to extract DNA and RNA, and to measure telomere length and sirtuin 1 and 6 expression, respectively. Carotid intima media thickness was measured by ultrasound. Body composition was measured by Dual-energy X-ray absorptiometry. Results In the 10-year period, 24 participants lost weight (17 females), 65 maintained weight (41 females), 25 gained weight (15 females) and 34 were extreme weight gainers (28 females). Female weight gainers had a higher body mass index, waist circumference, total body fat and homeostatic model assessment insulin resistance. Male weight gainers had a higher hip circumference and total body fat. No differences in telomere length, sirtuin 1 expression and carotid intima media thickness were observed between weight gainers and maintainers. Conclusions No effect of weight maintenance or gain was observed on metabolic and vascular markers of ageing.

Aim To explore the usefulness of carotid ultrasound examination as a marker of aging and predictor of disability among older people. Methods Carotid ultrasound, measuring carotid intima media thickness (CIMT) and recording the presence of plaques, was carried out in 152 adults aged 29–59 years (47 women) and in 107 older adults aged 61–88 years (86 women). In all, clinical routine laboratory parameters and lymphocyte telomere length as T/S ratio were measured. Among older adults, 12-min walk, timed up and go, hand grip and quadriceps strength were determined. Results CIMT was significantly higher among older people and T/S ratio was significantly higher in young women. Carotid plaques were found in one adult and 17 older people. A multiple regression analysis accepted age, systolic blood pressure and T/S ratios as independent predictors of CIMT (R2 = 0.51). Among older people, a logistic regression accepted age and the presence of carotid plaques as significant predictors of a 12-min walk speed below 1 m/s. Conclusions An abnormal 12-min walk as an indicator of functional decline among older people is associated with the presence of carotid artery plaques. CIMT is independently associated with age. Geriatr Gerontol Int 2014; 14: 710–715.

Purpose: To determine if irisin plasma levels are associated with regular physical activity, body composition and metabolic parameters in women subjected to calorie restriction. Subjects and methods: We studied 42 women aged 34 ± 13 years with a body mass index of 27.7 ± 1.8 kg/m2, who were subjected to a calorie restriction for three months. At baseline and at the end of the study, weight, waist and hip circumference, laboratory parameters, body composition by DEXA, resting and activity energy expenditure by indirect calorimetry and 72 hours actigraphy were measured. Fasting serum irisin was quantified using an ELISA kit. Results: After the intervention period, participants lost 1.5 (0.4-3.4) kg and irisin levels did not change. Irisin baseline levels were positively but weakly correlated with the level of physical activity. This association was lost at the end of the intervention. No association was found between irisin levels and body composition or insulin sensitivity or their changes after calorie restriction. No association between serum irisin levels and PGC-1α expression in peripheral blood mononuclear cells and serum irisin was observed. Conclusions: Fasting serum irisin was weakly associated with usual physical activity and did not change after calorie restriction.

Summary Background & aims During the past few years, consumption of high amounts of folic acid and high serum levels of folate have been associated with cancer risk. Several mechanisms have been proposed to explain this association. One of them is that supraphysiological levels of folate may diminish natural killer (NK) cell cytotoxic activity and its action as an antitumoral barrier. To demonstrate this hypothesis, we studied the effect of serum folate levels on NK cell cytotoxic activity in healthy subjects. Methods We recruited 227 healthy subjects of both sexes and measured serum folate levels and NK cell cytotoxic activity. Serum folate was adjusted for sex, age and body mass index to look for an association between its levels and cytotoxic activity of NK cell. Results We found supraphysiological serum folate levels in 24% of studied subjects. NK cell cytotoxic activity was not associated with serum folate levels. There was no relation between NK cell activity and other variables such as age, sex and BMI. Conclusions In this study, NK cell cytotoxic activity was not associated with serum folate levels. It is necessary to search for other hypothesis in order to explain the observed association between folic acid and cancer.

BACKGROUND: Advanced glycation end-products (AGEs) are one of the mechanisms related to diabetic vascular complications. However, since AGEs are multiple and heterogeneous moieties, there is no universally accepted method to measure them for clinical purposes. The aim of this work was to study the utility of a simple fluorimetric assay as predictor of complications. METHODS: Blood samples from 102 type 2 diabetic patients were obtained to assess glucose, glycosylated haemoglobin, creatinine, lipoproteins and C Reactive Protein (CRP), fluorescent AGES by spectrophotofluorimetry and non-fluorescent AGEs by measurement of N(e)-carboxymethyl-Lysine (CML) using an ELISA kit in a subsample of 82 patients. Urinary fluorescent AGEs, albumin and creatinine were also measured in a morning urine sample. Microvascular complications were studied by ophthalmologic examination, albuminuria and peripheral nerve conduction velocity. RESULTS: Patients without microvascular complications had significantly lower levels of both serum and urinary AGEs. CML was associated with retinopathy. Multiple regression analysis confirmed that AGEs, length of diabetes and glycosylated haemoglobin were all variables associated with diabetic complications, in this sample. CONCLUSIONS: A simple fluorimetric assay to measure low molecular weight fluorescent AGEs, and CML could be employed as screening tools to predict diabetic complications, at a primary care setting. AGEs should probably be considered as another therapeutic target in diabetes management.

Background Exercise training during the dialytical procedure may have positive cardiovascular effects and prevent or revert muscle wasting in patients undergoing chronic hemodialysis. Aim To evaluate the effects of an exercise training program in patients undergoing chronic hemodialysis. Material and methods Fifteen patients on chronic hemodialysis aged 21 to 69 years (three females) were included in the study. Nine of these were included in an exercise training program. During 16 weeks, exercise sessions were carried out during each dialytical procedure that included a warm-up period, aerobic exercises done using standing cycles, and resistance exercises, performed using Thera-Band(®) elastic bands and loops. Borg scale was used to control the intensity of training. At baseline and at the end of the study, a blood sample prior and after the dialytical procedure was obtained to measure C reactive protein, tumor necrosis factor α and interleukin 6. Quadriceps muscle strength, six minutes' walk and quality of life using the SF-36 questionnaire, were also measured. Results Four experimental subjects did not complete the study period, two that withdrew before starting, one due to problems with the venous access and one that decided to withdraw after 1 month of training. Among the five patients that finished the training period, significant improvements in the six minutes' walk and quadriceps strength were observed in the experimental group. No significant changes were observed among controls. No changes were observed in either group in C reactive protein, tumor necrosis factor and interleukin 6 levels or quality of life. Conclusions Among patients undergoing chronic hemodialysis exercise training improves endurance and muscle strength.

Aim: To evaluate the association between loss of fat-free mass and mortality among older people. Methods: Information of healthy Chilean older people evaluated by dual energy X-ray absorptiometry was used, identifying those who died in a period of 12 years. A Cox proportional hazards model was used to identify mortality predictors. Life tables were constructed calculating survival using predictive variables. Results: Information from 1413 participants aged 74.3 ± 5.6 years (1001 women), was obtained. During the follow-up (median 1594 days), 221 participants died. The Cox model identified age and appendicular fat-free mass as predictors of death (hazard ratios 1.08 and 0.85, respectively). According to life tables, participants in the lower sex-specific quartile for appendicular fat-free mass/height had significantly higher mortality. This association was significant among participants aged over 73 years. Conclusion: A low fat-free mass was predictive of mortality in older people.

Introduction. The inhibition of angiotensin-converting enzyme could be useful to avoid sarcopenia in the elderly. Materials and methods. We compared in a prospective double blind trial, the effects of treatment with enalapril or nifedipine on muscle performance in hypertensive elderly subjects. Patients were followed for nine months, and at baseline, 4.5 months and the end of follow-up, quadriceps and hand grip muscle strength, walking capacity, timed up and go and the short physical performance test were measured. Results. During follow-up, more subjects on nifedipine than on enalapril discontinued the medication due to side-effects. No differences in the evolution of muscle strength, walking capacity or functional measures were observed. At nine months, plasma angiotensin-converting enzyme activity decreased by 6.0±2.5 U/L among patients on enalapril and increased by 8.5±4.2 U/L (p Conclusion. In this group of elderly subjects, enalapril was not superior to nifedipine with regard to the age-related decline of muscle performance.

A blood sample and muscle biopsies were obtained from 54 elderly subjects. Twenty-seven subjects aged 77+/-3 years, had experienced a change in fat free mass (FFM) of +194+/-282g/year (lean body mass maintainers) and 27 subjects aged 78+/-3 years, had a change in FFM of -487+/-209g/year (lean body mass losers). Muscle biopsies were also obtained from 10 healthy subjects aged 34+/-4 years. In muscle, the ratio of mitochondrial DNA (mtDNA) to nuclear DNA (nDNA) and telomere length were assessed and deposition of 4-hydroxy-2-nonenal adducts (4HNE) was visualized by electron microscopy. In FFM maintainers, losers and young controls, the ratio of mtDNA to nDNA was 2.1 (95% confidence intervals (CI), 0.1-31.7), 1.5 (95% CI, 0.2-15.7) and 18.6 (95% CI, 2.8-46.2), respectively. 4HNE deposition was 5.9 (95% CI, 1.5-28), 4.9 (95% CI, 0.9-13) and 3.4 (95% CI, 1.1-4.6) gold particles/microm(2), respectively. Telomere length, expressed as T/S ratio, was 0.06 (95% CI, 0.01-0.16), 0.06 (95% CI, 0.03-0.27) and 0.34 (95% CI, 0.1-1.34), respectively (p

Background Folate depletion is associated with anincreased risk of colorectal carcinogenesis. A temporalassociation between folic acid fortification of enrichedcereal grains and an increase in the incidence of colorectalcancer in the United States and Canada has, however, beenreported recently.Aim To compare the rates of hospital discharges owing tocolon cancer in Chile before and after the start of themandatory flour fortification program with 220lgofsynthetic folic acid/100g of wheat flour.Methods Cancer and cardiovascular hospital dischargerates were compared using rate ratios between two studyperiods, 1992–1996, before folic acid fortification and2001–2004, after the flour fortification with folic acid wasestablished in the country. Standard errors of the log rateratio to derive confidence intervals, and to test the nullhypothesis of no difference, were calculated.Results The highest rate ratio between the two periodswas for colon cancer in the group aged 45–64 years (rateratio: 2.6, confidence interval: 99% 2.93–2.58) andin the 65–79 years (rate ratio: 2.9, confidence interval: 99%3.25–2.86).Conclusion Our data provide new evidence that afolate fortification program could be associated with anadditional risk of colon cancer. Eur J Gastroenterol Hepatol00:000–000

Tissue accumulation of advanced glycation end products (AGEs) is associated with ageing, both in diabetics and nondiabetic subjects.The purpose of this study was to assess immunostaining for AGEs, specifically carboxymethyl-lysine (CML) and receptor for AGEs (RAGE), in muscle tissue of healthy male subjects differing in age and weight stability.Muscle tissue was obtained during hernia surgery in middle-aged men reporting weight maintenance (WM, n = 10) or weight gain (WG, n = 7), and also in 4 elderly men. Tissue inmunostaining for CML and RAGE was performed.Intensity of CML and RAGE staining were highly correlated (r = 0.84) and also significantly associated with weight change and age. Muscle AGEs accretion was statistically associated with muscle expression of oxidative injury (8-hydroxy-deoxyguanosine and 4-hydroxy-2-nonenal) and inflammatory markers (tumor necrosis factor-alpha).The increase of skeletal muscle AGEs/RAGE and markers of inflammation and oxidative injury in association with weight gain and old age suggest a pathogenic role of AGEs in weight gain and in sarcopenia of aging.

Objective We assessed the value of height reduction, calculated using knee height measurement, as a risk factor or predictive sign for osteoporosis in healthy elderly women. Methods In 181 healthy women 76 ± 5 y of age, height, weight, and knee height were evaluated. Femoral and spine bone mineral densities and body compositions were measured using dual-energy X-ray absorptiometry. In 76 young women 27 ± 4 y of age, a regression equation to predict height, based on knee height, was derived. Using this equation, maximum attained height and height loss were calculated in elderly women, which was correlated to bone mineral density. Results The equation to predict height was height (cm) = knee height (cm) × 2.22 + 50.54. The calculated height loss in elderly women was −6.1 ± 3.8 cm or −0.08 ± 0.05 cm/y of age. Height loss and hip circumference were significant predictors of spine bone mineral density. In the case of femoral bone mineral density, to the same predictors, a negative effect of waist circumference was added. Women in the highest quintile of height reduction (>0.199 cm/y) had an odds ratio of 4.5 (95% confidence interval 1.56–13.3, P Conclusion Knee height can be used as an accurate measurement of height loss in the elderly, which is a significant predictor of femur and spine bone mineral densities, in addition to hip circumference.

Obesity is a risk factor for diabetes and its consequences, including accelerated ageing and mortality. The underlying factor could be accumulation of certain lipid moieties, such as ceramides (CER) and diacylgycerol (DAG) within muscle tissue, which are known to promote insulin resistance (IR), induce inflammation and oxidative injury, ultimately altering muscle function.First, to study the relationship between body composition and age (independent variables) with skeletal muscle accumulation of lipid species, oxidative injury and strength. Second, to analyze the relationship between muscle tissue metabolites and insulin resistance, inflammation and lymphocyte telomere length, the latter as an indicator of ageing.The sample included 56 healthy sedentary males, scheduled for inguinal hernia surgery, aged 27 to 80 y. Each individual was subject to anthropometric measurements, body composition assessment through radiologic densitometry (DEXA), measurement of handgrip and quadriceps strength, serum biochemical parameters (lipoproteins, creatinine, high sensitivity C reactive protein [hsCRP], fasting and post glucose insulin and glucose concentrations for calculation of IR through the Matsuda and HOMA-IR indexes), and extraction of peripheral leukocytes for measurement of telomere length. During the surgical procedure, a sample of muscle tissue was obtained (anterior abdominal oblique) in order to measure CER and DAG (and sub species according to chain length and saturation) by mass spectrometry, 4 hydroxy-2-nonenal adducts (4-HNE) using electron microscopy immunohistochemistry, and carboxymethyl-lisine (CML) by immunohistochemistry, the latter as indicators of oxidative stress (OS).Body mass index (BMI) of twenty six individuals was25 k/m2, while BMI of 7 was30 k/m2. Overweight/obese individuals, did not exhibit differences in skeletal muscle lipid metabolites, however total CER and specific long chain CER sub-species (20 and 22 carbon) increased significantly among individuals with a central fat distribution (n = 14) as well as in glucose intolerant subjects (n =23). A negative association was found between mononuclear leukocyte telomere length and 20 and 22 carbon CER (rho = - 0.4 and -0.5 0 p0.05). Muscle strength was not associated with any of the measured muscle metabolites or markers of OS. A multiple regression analysis accepted central abdominal fat and telomere length as significant predictors of CER (R2 = 0.28).An association was found between accumulation of specific ceramide species in muscle tissue and abdominal obesity, glucose intolerance and shortening of leukocyte telomeres, although not with muscle oxidative injury or dysfunction.

Summary Background and aims Weight maintenance within normal standards is recommended for prevention of conditions associated with oxidative injury. To compare oxidative damage in a post mitotic tissue, between adults differing in long-term energy balance. Methods During hernia surgery, a sample of skeletal muscle was obtained in 17 non-obese adults. Subjects were divided into two groups according to their self-reported weight change: weight maintainers (WM) reported 5 kg increment. Muscle immunohistochemistry for 8-hydroxy-deoxyguanosine (8OHdG), 4-Hydroxy-2-nonenal (4HNE), and TNF-α, as markers of oxidative injury and inflammation, were performed. As known positive controls for oxidative injury, we included 10 elderly subjects (66–101 yr). Anthropometric measures and blood samples for clinical laboratory and serum cytokines (TNF-α and IL-6) were obtained. Results 8OHdG was higher in WG compared with WM (149.1±16.2 versus 117.8±29.5, P = 0.03 ), and was associated with anthropometric indicators of fat accumulation. 4HNE was similar in WG compared with WM (10.9±7.6 versus 9.8±6.3) but noticeably higher in elderly subjects (21.5±15.3, P = 0.059 ). TNF-α protein in WG was higher compared with WM (114.0±41.7 versus 70.1±23.3, P = 0.025 ), and was associated with weight increase. Conclusions Moderate self-reported weight increase, and body fat accumulation, suggesting long-term positive energy balance is associated with muscle DNA oxidative injury and inflammation.

The aim was to assess the effects of resistance training and vitamin D supplementation on physical performance of healthy elderly subjects. Ninety-six subjects, aged 70 years or more with 25 OH vitamin D levels of 16 ng/ml or less, were randomized to a resistance training or control group. Trained and control groups were further randomized to receive in a double blind fashion, vitamin D 400 IU plus 800 mg of calcium per day or calcium alone. Subjects were followed for nine months. Serum 25 OH vitamin D increased from 12.4 ± 2.2 to 25.8 ± 6.5 ng/ml among subjects supplemented with vitamin D. Trained subjects had significant improvements in quadriceps muscle strength, the short physical performance test and timed up and go. The latter improved more in trained subjects supplemented with vitamin D. At the end of the follow up, gait speed was higher among subjects supplemented with vitamin (whether trained or not) than in non-supplemented subjects (838 ± 147 and 768 ± 127 m/12 min, respectively, p = 0.02). Romberg ratio was lower among supplemented controls than non-supplemented trained subjects (128 ± 40% and 144 ± 37%, respectively, p = 0.05). In conclusion, vitamin D supplementation improved gait speed and body sway, and training improved muscle strength.

Vitamin B-12 deficiency is prevalent among the elderly population but it is often unrecognized because the clinical manifestations are not present. Objective: To evaluate the effects of a nutritional supplement fortified with vitamin B-12 on well nourished, free-living elderly subjects. Patients and methods: Healthy elderly subjects attending two of four clinics were allocated to receive, over six months’ duration, a nutritional supplement with 3.8 µg of vitamin B-12. Subjects attending the other two clinics served as controls. Serum vitamin B-12 levels were measured at baseline and 6 months after the supplementation was started. Results: After 6 months of consuming the supplement fortified with vitamin B-12, serum B-12 concentration increased from 350.1 ± 166.5 pmol/L to 409.0 ± 166.1 and decreased in the control group from 319.4 ± 129.1 to 290.1 ± 135.7 (ANOVA, p < 0.005). Conclusion: A supplementation with 3.8 µg /day of vitamin B-12 led to significant improvements in the serum concentrations of vitamin B-12 in older persons.

Prebiotics increase intestinal levels of health-promoting bacteria implicated in decreasing pathogen colonization, stimulating immune functions and stabilizing gut barrier functions, parameters which are altered in burn patients. We propose that regular intake of a prebiotic, oligofructose (OF), might help to improve the altered gastrointestinal (GI) permeability observed in burn patients. A randomized, double-blind, controlled clinical trial was carried out in 41 burn patients (mean burn surface area=17.1+/-8.2%) who ingested daily 6 g of oligofructose (OF group) or sucrose as placebo (Control group) during 15 days. Gastrointestinal permeability to sucrose and lactulose/mannitol (L/M) was evaluated on days 1 (before treatment) 3, 7, 14 and 21. A permeability test was also performed in 18 healthy subjects as controls. Thirty-one patients completed the protocol (dropout rate=24.4%). Healthy subjects had a basal sucrose excretion of 21.3 mg (14.0-32.5 mg) and a basal L/M ratio of 0.017% (0.009-0.022%). Sucrose excretion increased 5-fold and L/M ratio 4.4-fold in burn patients on day 1 and these high levels of marker excretion decreased significantly throughout the study (p=0.016 and 0.000001, respectively). No differences between the OF and Control groups were observed for sucrose excretion or L/M ratio. In conclusion, the normalization of gastrointestinal permeability is not accelerated by prebiotic intake.

Objective Folate depletion and hyperhomocysteinemia increase the risk for hepatic alcoholic damage and promote oxidative stress in animals. In addition, some investigators have reported an inverse association between serum folate and body mass index and a positive correlation between total homocysteine and fat mass. We investigated whether there is an association between serum folate and total homocysteine concentrations with the presence of non-alcoholic fatty liver disease (NAFLD) in obese subjects. Methods Forty-three obese (body mass index ≥35 kg/m 2 ) patients who underwent bariatric surgery and hepatic biopsy were included. Serum total homocyteine, folate and vitamin B12 concentrations and hepatic enzymes were measured. Liver biopsies were graded for the presence of fat, inflammation, and fibrosis on a scale from 0 to 3. A total histologic score was calculated based on the sum of partial scores. Severe NAFLD was defined as a total score of at least 4 or severe steatosis (partial score for fat = 3). Results Severe NAFLD was present in 17 patients. Serum folate concentration was significantly lower in obese patients with NAFLD than in those with normal liver or minimal alterations (9.3 ± 3.5 versus 12.2 ± 3.1 ng/mL, P = 0.005). Serum total homocysteine and vitamin B12 concentrations were similar in both groups. An inverse correlation between serum folate concentration and body mass index was observed ( r = −0.31, P = 0.046). Conclusions In this study, severe NAFLD in obese subjects was associated with lower serum folate concentrations and serum homocysteine and vitamin B12 concentrations were not associated with liver damage in obese subjects.

Immune response is impaired in the elderly. Our aim was to study the effects of a special nutritional formula on the immune response and response to influenza and pneumococcal vaccination in elderly subjects.Sixty healthy subjects agedor = 70 years, with a Mini Mental scoreor = 22 were studied. Half of the subjects received a special nutritional formula (in addition to the regular diet) providing, among other nutrients, 480 kcal, 31 g proteins, 120 IU vitamin E, 3.8 microg vitamin B12, 400 microg folic acid, 10(9) cfu Lactobacillus paracasei (NCC 2461), and 6 g of fructo-oligosaccharides. At 4 months of follow-up, subjects were vaccinated against influenza and pneumococcus. Lymphokine production by mononuclear cells (PBMC), lymphocyte subpopulations, and natural killer cell (NK) activity were measured at baseline and 4 months of follow-up (before vaccination). Antibodies against influenza and pneumococcal antigens and flu-stimulated production of interferon gamma and interleukin-2 by PBMC were measured at 4 and 6 months. Skin response to 7 recall antigens and body composition were assessed at baseline and at 4 and 12 months. All infections occurring during the study period were recorded.NK activity increased in supplemented subjects and decreased in nonsupplemented individuals. Interleukin-2 production by PBMC and the proportion of T cells with NK activity decreased in controls and did not change in supplemented subjects. Supplemented subjects reported less infections than nonsupplemented individuals (in 13% and 22% of scheduled visits, respectively; p = .02).This nutritional supplement increased innate immunity and protection against infections in elderly people.

The mechanism by which homocysteine (Hcy) causes endothelial dysfunction is probably mediated by oxidative stress. The aim of this study was to evaluate the effect of oxidative stress on endothelial function in young and elderly hyperhomocysteinemic (HHcy) men. A total of 35 HHcy (Hcy > 15 micro mol/L), young (n = 15; 20-40 y) and elderly men (n = 20; > 65 y) and 33 normohomocysteinemic (NHcy; controls) young (n = 14) and elderly (n = 19) men (Hcy < 13 micro mol/L), without classic cardiovascular risk factors were recruited. Serum Hcy, folate, and vitamin B-12, whole-blood glutathione, plasma total antioxidants status, TBARS, and 8-F(2alpha) isoprostanes were determined. Noninvasive ultrasound measurements of endothelium-dependent (EDVR) and -independent dilatation (EIVR) were performed. EDVR, EIVR, and markers of oxidative stress did not differ among the groups. Folate concentrations were higher in elderly than in young men (P < 0.001), independent of Hcy concentrations. Vitamin B-12 concentrations were lower in HHcy than in NHcy elderly men (P < 0.045). EDVR was correlated with folate concentrations in young men (r = 0.40, P = 0.04) and negatively with BMI in elderly men (r = -0.52, P = 0.002). In the present study, HHcy with normal serum folate concentrations was not associated with poor EDVR or oxidative stress in healthy young and elderly men.

To study long-term changes in nutritional status and gastrointestinal (GI) functions of 15 women previously treated with radiotherapy for gynecological cancer. Two years prior to this research, these patients had been assessed twice: before external radiotherapy and 5 weeks later, at the completion of the external dose (45-50 Gy).Each patient was given complete clinical evaluation, consisting of dietary, physical activity and digestive symptoms questionnaires. Blood was drawn for routine clinical laboratory tests (hemoglobin, white blood cell count, creatinine, lipoproteins, glucose, total proteins, albumin, and C reactive protein). Body composition was assessed by classical anthropometric indicators and double beam X-ray absorptiometry (DEXA), while muscle strength was measured through a hand dynamometer. Resting energy expenditure (REE), obtained by indirect calorimetry, was subtracted from energy ingestion, derived from dietary records, to calculate energy balance.This third evaluation included fifteen patients. A significant increase in body mass index (BMI), % body fat and waist circumference were observed in comparison to earlier evaluations. The lean compartment decreased significantly, and REE descended in parallel. Meanwhile, total energy, fat and protein intake increased, compared to previous measurements. The changes in bowel habits observed during radiotherapy persisted at this third evaluation, with the exception of diarrhea, which was less reported. Abdominal bloating and rectal symptoms were the most prevalent complaints.After radiation treatment for gynecological cancer, patients gained more body fat than expected in Chilean women around menopause. In spite of high protein ingestion, the loss of fat-free mass observed during radiation treatment was not recovered along with weight increase. This is probably associated with infrequent physical activity, both during and after treatment, and hyperphagia.

Objective There is a seasonal variation in the incidence of diabetes mellitus and cardiovascular diseases. However, there is very little information about the seasonal variation in insulin sensitivity. We report the seasonal variation in insulin sensitivity in a group of elderly subjects followed for 1 y. Methods Healthy elderly (≥70 y) subjects living independently were included. Fifty percent of subjects received a daily nutritional supplement that provided 400 kcal, 15 g of protein, and 50% of vitamin daily reference values (DRVs). Those receiving and not receiving supplements were randomly assigned to a resistance exercise training program. Every 6 mo (winter, summer, and winter), body composition was measured by dual-energy x-ray absorptiometry and blood samples were used to measure serum lipids, fasting and postprandial glucose, and insulin levels. Results One hundred eight subjects (31 supplemented and trained, 28 supplemented, 16 trained, and 33 without supplementation or training) completed the follow up. Higher homeostasis assessment of insulin sensitivity, postprandial insulin, and fasting triacylglycerol levels were observed during the summer than during the winter. Body fat increased steadily during the study period, and fat-free mass did not change. Serum low-density lipoprotein cholesterol decreased significantly in the supplemented and trained group and increased in the non-intervention group. Conclusions In this group of elderly subjects, insulin resistance and triacylglycerol levels were higher during the summer. Nutritional supplementation and training had a positive effect on serum low-density lipoprotein cholesterol.

Background L-methionine, the principal sulfur-containing amino acid in proteins, plays critical roles in cell physiology as an antioxidant and in the breakdown of fats and heavy metals. Previous studies suggesting the use of L-methionine as a treatment for depression and other diseases indicate that it might also improve memory and propose a role in brain function. However, some evidence indicates that an excess of methionine can be harmful and can increase the risk of developing Type-2 diabetes, heart diseases, certain types of cancer, brain alterations such as schizophrenia, and memory impairment. Results Here, we report the effects of an L-methionine-enriched diet in wild-type mice and emphasize changes in brain structure and function. The animals in our studypresented 1) higher levels of phosphorylated tau protein, 2) increased levels of amyloid-β (Aβ)-peptides, including the formation of Aβ oligomers, 3) increased levels of inflammatory response,4) increased oxidative stress, 5) decreased level of synaptic proteins, and 6) memory impairment and loss. We also observed dysfunction of the Wnt signaling pathway. Conclusion Taken together, the results of our study indicate that an L-methionine-enriched diet causes neurotoxic effects in vivo and might contribute to the appearance of Alzheimer’s-like neurodegeneration. Electronic supplementary material The online version of this article (doi:10.1186/s13024-015-0057-0) contains supplementary material, which is available to authorized users.

Background: The relationship between hyperhomocysteinemia and cardiovascular disease has not been totally elucidated. Hypothesis: The study aimed to verify the association between hyperhomocysteinemia and endothelial dysfunction before and after modification of total homocysteine (tHcy) serum levels with vitamin supplementation in young male subjects devoid of any other cardiovascular risk factor. Methods: Twenty hyperhomocysteinemic (tHcy gt; 15 μmol/1) male volunteers (≤ 40 years) and 20 age-matched subjects with normal tHcy levels (tHcy < 13 μmol/1) were included. Exclusion criteria were smoking, hypertension, diabetes, vitamin ingestion, obesity, hypercholesterolemia, renal failure, and positive antiphospholipid antibodies. Serum tHcy, folate, vitamin B12 levels, activated protein C and S, protein C resistance, fibrinogen, prothrombin, thrombin, antithrombin III, and in vitro oxidation of low-density lipoprotein (LDL) particles were measured. Noninvasive ultrasound measurements of endothelium-dependent (EDD) and -independent dilatation (EID) of the brachial artery were performed. Each pair was then randomly assigned to receive a vitamin capsule (0.6 mg folic acid, 0.8 mg B12, and 2.0 mg B6) or an identical placebo during 8 weeks, in a double-blind study design. After the treatment phase, blood samples and vascular reactivity were repeated. Results: Nine pairs of volunteers received vitamins and 11 received placebo. Hyperhomocysteinemic subjects had lower baseline serum levels of vitamin B12. Serum folate levels, antithrombotic function, in vitro LDL oxidation, and EDD were similar in all groups. After the vitamin supplementation, serum folic acid levels increased significantly both in normo-and hyperhomocysteinemic subjects, unlike vitamin B12, which increased only in the hyperhomocysteinemic individuals. Plasma tHcy decreased significantly in the supplemented groups. Treatment with vitamins was not associated with improvement in EDD or antithrombotic function. Conclusions: Mild hyperhomocysteinemia is not associated with endothelial dysfunction in young male subjects with no additional cardiovascular risk factors, and reduction of tHcy by vitamin supplementation does not modify EDD in this age group. In this sample, tHcy was more related to vitamin B12 than to folic acid status.

Prebiotics stimulate the growth of bifidogenic bacteria in the gut. The aim of this work was to assess the effects of a prebiotic mixture on the immune response in healthy elderly people.Healthy free-living elderly people (age,or = 70 years), receiving a nutritional supplement that provided 1.6 MJ, 15 g of protein, and 50% of vitamin daily reference values per day, were randomly assigned to receive a prebiotic mixture (6 g/d of a 70% raftilose and 30% raftiline mixture) or placebo (6 g of maltodextrin powder) for 28 weeks. At week 2 of the study, all subjects were vaccinated with influenza and pneumococcal vaccines. At weeks 0, 2, and 8 of the study, serum total proteins, albumin, immunoglobulins, saliva secretory immunoglobulin A (IgA), and serum titers of influenza A and B and pneumococcal antibodies were measured. At week 8, cultured peripheral monocyte cell secretion of interleukin-4, interferon-gamma, and lymphocyte proliferation, stimulated with phytohemagglutinin and influenza antigen, were measured.Sixty-six subjects were considered eligible for the study, and 43 (20 receiving prebiotics and 23 receiving placebo) were considered for final analyses on a per protocol basis. No changes in serum proteins, albumin, immunoglobulins, and secretory IgA were observed. Antibodies against influenza B and pneumococcus increased significantly from weeks 0 to 8, with no significant differences between groups. Antibodies against influenza A did not increase. No effects of prebiotics on interleukin-4 and interferon-gamma secretion by cultured monocytes were observed.No immunological effects of prebiotics were observed in this study.

OBJECTIVES: To compare endothelium-dependent vasomotor response in healthy younger and older subjects without classic cardiovascular risk factors, with high and normal fasting homocysteine (tHcy) levels. DESIGN: We compared endothelium-dependent vasodilatation, using ultrasound, in healthy younger (aged 18–40) and older (≥70) people with normal ( 15 μmol/L) tHcy levels. Exclusion criteria were smoking, personal history of cardiovascular disease, hypertension, chronic diseases, vitamin intake, obesity, abnormal serum lipids levels, and creatinine higher than 130 μmol/L. SETTING: Research laboratory. MEASUREMENTS: In addition to tHcy levels, serum folate and vitamin B12 levels were measured. RESULTS: We studied 17 younger and 12 older hyperhomocysteinemic subjects and respective aged-matched normohocysteinemic subjects. Endothelium-dependent vasodilatation was lower in the hyperhomocysteinemic older people (P < .01) than in all younger subjects and in normohomocysteinemic older people. Serum vitamin B12 levels were higher in younger and older normal controls. Folic acid levels were higher in younger controls and in both older groups. CONCLUSIONS: This study shows an effect of high circulating tHcy on vascular reactivity in older people. Because serum levels of tHcy are associated with nutritional status of vitamin B12 and folic acid, prospective studies are necessary to demonstrate the effects of a long-term nutritional supplementation with vitamins on vascular function and global cardiovascular risk.

Background Simple and reliable methods to evaluate muscle mass in older people are lacking. Aim To evaluate ultrasound as a measure of RF muscle mass and quality in healthy subjects of different ages and gender, assessing its concordance with dual energy X-ray densitometry (DEXA) and association with muscle strength and walking capacity. Methods We selected 54 adults of both genders, aged 20–55 years and 51 adults older than 60 years. Ultrasound images of the RF were obtained at the mid-thigh to measure its thickness and ultrasonographic density using a GE Logiq e equipment. Body composition was assessed by DEXA. Quadriceps isometric strength and 12 minutes’ walk were also measured and gender specific t scores for older adults were calculated using the values obtained in adults. Results RF ultrasound measurements correlated significantly with lean body mass assessed by DEXA (Double energy X-ray absorptiometry). The concordance between both measures was also adequate. Older people had lower muscle mass and worse ultrasound parameters than adults. Older males with a t score for quadriceps strength of −2 or less, had a significantly higher RF grayscale density. Older males with a 12 minutes’ walk t score of −2 or less and old males and females with a walking speed of 1 m/s or less had a lower RF thickness. Discussion There is a good concordance between RF ultrasound and DEXA. Conclusions Assessment of RF using ultrasound appears to be a reliable and accurate method to evaluate muscle mass in older people.

The role of cytokines in the etiology of liver injury and their contribution to the systemic manifestations that occur in patients with liver disease, are not clearly understood. Aim: To study if serum levels and in vitro blood mononuclear cell (BMC) production of IL-Iβ and TNFα are related to the severity of alcoholic liver cirrhosis, and identify potential factors that can modify cytokine production in these patients. Serum levels, spontaneous and in vitro LPS stimulated BMC production of Interleukin-Iβ (IL-Iβ) and Tumor Necrosis Factor α (TNFα), were measured in 38 patients with alcoholic cirrhosis Child B or C, and nine normal volunteers. Serum levels and spontaneous in vitro production of IL-Iβ and TNFα were below detection limits. There were no differences between normal controls and Child B or C patients in LPS-stimulated production of IL-Iβ or TNFα. However eight patients with alcoholic hepatitis or infections superimposed on cirrhosis, had higher levels on LPS-stimulated BMC production of IL-Iβ (12.9 ± 5.8 ng/ml) and TNFα (4.9 ± 2.3 ng/ml) than the rest of cirrhotic patients (5.3 ± 3.5 and 1.8 ± 0.9 ng/ml). There was no association between IL-Iβ and TNFα BMC production and parameters of liver function or recent alcohol ingestion. Increased levels of IL-Iβ and TNFα production by stimulated BMC are associated with acute inflammatory events in cirrhotic alcoholic patients and not with the severity of liver disease.

Excessive ethanol ingestion induces hypoandrogenism in male subjects. To confirm its presence and to study its relationship with the degree of liver damage and alcohol abstinence, plasma sex hormones were measured in alcoholic patients without liver failure, after two different abstinence periods. Patients were 30 male chronic alcoholics admitted to the Alcoholism Ward for treatment of their addiction. On admission, we measured: testosterone (T), estradiol (E), follicle stimulating hormone (FSH), luteinizing hormone (LH) and sex-hormone binding globulin (SHBG). A liver biopsy was also performed. These measurements were repeated at discharge and were also done in 15 normal volunteers. On admission (mean abstinence 1.9 +/- 1.7 days) total T was similar to controls, FSH was lower (p0.02) and high levels of SHBG were found (3.5 fold increase, as compared to controls). Histologically, 9 patients had normal liver; 14 had moderate alterations and 7 showed marked alterations. Hormonal values were not different in these 3 groups. At discharge, 11.1 +/- 4.7 days after admission, T, E and FSH did not show significant changes but LH decreased (8.2 +/- 5.2 mIU/ml vs 12.9 +/- 4.1, p0.001); SHBG also decreased (65.4 +/- 21.6 nmol/l vs 117.2 +/- 33.3, p0.001) to values that still were twice those of controls. It is concluded that alcoholic patients without clinical signs of liver failure have normal plasma testosterone levels, irrespective of their histologic liver alterations and high plasma SHBG levels that decreased significantly after a short abstinence. The concomitant LH decrease suggests that hypoandrogenism is likely in these patients. Fast changes in SHBG levels rise the possibility that this protein is candidate marker of alcoholism.

Alcohol ingestion promotes lipoperoxidation and alters cellular antioxidant mechanisms. Alpha-tocopherol levels decrease in alcoholics as severity of liver damage increases. The aim of this protocol was to study the effects of a long-term oral 500 mg vitamin E daily supplementation in decompensated ambulatory alcoholic cirrhotics.67 subjects were included in this double blind trial; 33 patients received vitamin E and 34 patients received placebo tablets of identical appearance during 1 year. Each month, the patients were seen by a nurse practitioner who was in charge of detecting alcohol ingestion and checking adherence to treatment. Every 3 months, the patients underwent a medical examination, and blood samples were taken for clinical laboratory analysis and serum vitamin E measurement.Alpha-tocopherol levels were significantly lower in patients with more severe liver disease. This difference was not significant when vitamin E levels were corrected by cholesterol. Oral supplementation significantly increased serum vitamin E levels in the experimental group. Alcohol ingestion and hospitalization rates were similar in both groups. Life table analysis did not show significant differences in mortality between the two groups.Vitamin E supplementation with adequate doses of an alpha-tocopheryl acetate formulation during 1 year did not influence hepatic laboratory parameters, mortality or hospitalization rates of decompensated alcoholic cirrhotics, although serum levels of the vitamin significantly increased.

Sarcopenia is defined as the loss of muscle mass that occurs during normal aging and is associated with functional impairment. This is a dynamic concept that should consider the reduction of muscle mass over time but, for practical purposes, we must rely on cross-sectional measures to determine the presence of a significant loss of muscle mass. Double energy X ray absorptiometry is a reasonably accurate and inexpensive method to determine body composition. Knowing the body composition of a representative sample of older subjects in a specific community, regression equations to predict muscle mass can be derived to determine which individuals are sarcopenic using the residuals method. Functional measures should also be incorporated in the assessment of sarcopenia. The most popular assessments include walking capacity, the ability to rise from a chair and the measurement of muscle strength using dynamometers. A lower muscle mass and function in older subjects are risk factors for mortality and disability. Physical training is the only intervention capable of reverting the adverse consequences of sarcopenia.

Thirteen asymptomatic chronic alcoholic patients were studied to investigate the early stages of portal hypertension in alcoholic liver disease and the effects of withdrawal and ethanol on hepatic function and hemodynamic variables. None of the patients presented clinical signs of decompensated liver disease, and their liver biopsies showed normal liver or moderate alterations only. In basal conditions and after an intravenous ethanol infusion (1 g/kg body weight), hepatic venous pressure gradient and hepatic blood flow using indocyanine green were measured through hepatic vein catheterization. Hepatic sinusoidal vascular resistance and indocyanine green intrinsic clearance were also calculated. Portal blood flow measurements were obtained by Doppler ultrasound. No correlation was observed between hepatic venous pressure gradient and histologic features, (steatosis, necrosis, fibrosis, inflammation and hepatocyte surface area). In basal conditions, portal hypertension was not found in any case. After ethanol, portal pressure increased significantly (p0.001); in four cases it rose to or above 5 mmHg. Portal blood flow, hepatic blood flow and hepatic vascular resistance also increased significantly. Intrinsic indocyanine green clearance decreased slightly but significantly. No significant correlations were found between portal pressure, hepatic resistance and the histologic parameters. It was concluded that alcoholic patients, without clinical or laboratory evidence of liver failure and with minimal or moderate histologic alterations, have normal portal pressures. After an intravenous ethanol load, however, four out of 13 patients (31%) reached levels of 5 mmHg or more, irrespective of their liver histology.

Publisher Summary Colorectal cancer (CRC) is the fourth most common cancer in men and the third most common cancer in women worldwide. Folate is a water-soluble B vitamin that participates in one-carbon metabolism, which has a critical function in methylation reactions and in DNA synthesis and repair. The association between dietary folate intake including natural and synthetic folic acid (FA) and risk of CRC has been evaluated in numerous epidemiologic studies. Whereas some studies have reported inverse associations, other studies have observed null and positive associations. Folate has a critical function in methylation reactions and in DNA synthesis and repair, and may accelerate tumor cell growth. In the mandatory era of FA fortification, approximately 40% of the population has supraphysiologic levels of serum or plasma folate. Low and high folate intake or plasma concentration are related with the risk of CRC. The upper limit for FA intake as well as the safe upper folate concentration needs to be determined to prevent adverse effects.

A preoperative nutritional assessment including anthropometry, biochemical indices and global subjective assessment was performed for 127 patients admitted for elective gastrointestinal surgery. Of these, 24 were subjected to minor surgery, 65 to intermediate surgery and 38 to major procedures. Patients were followed postoperatively, recording complications or mortality. Intermediate and major surgery patients had lower triceps skinfold thickness and mid-arm circumference and greater weight loss than did minor surgery patients. Thirty-six percent of the patients suffered complications. No association was found between preoperative nutritional status and incidence of postoperative complications. Six patients died and they showed greater preoperative weight loss (21 +/- 6.5 vs 12 +/- 1.4%) and lower serum albumin levels (25 +/- 4 vs 35 +/- 1 g/l) than patients who survived complications. Global subjective assessment classified 43% of survivors as malnourished, compared to 100% of patients who died.