Premature loss of muscle mass and function in type 2 diabetes.

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 60years 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 10years 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 60years old, independent of length of disease, metabolic control, vitamin D status and presence of microvascular complications and pain.

Skeletal muscle ceramide species in men with abdominal obesity.

BACKGROUND: 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. AIM: 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. METHODOLOGY: 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). RESULTS: Body mass index (BMI) of twenty six individuals was > 25 k/m2, while BMI of 7 was > 30 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 p < 0.05). 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). CONCLUSIONS: 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.

Effect of weight maintenance or gain in a 10 years period over telomere length, sirtuin 1 and 6 expression and carotid intima media thickness.

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.

Dietary intake increases serum levels of carboxymethil-lysine (CML) in diabetic patients.

INTRODUCTION: Advanced glycation end products are produced endogenously, in association with hyperglycemia and oxidative stress. They can also be generated during cooking or food processing and, once absorbed, alter protein function and promote inflammation. METHODS: We selected 40 healthy male subjects, 17 patients with type 2 diabetes of both sexes and 15 patients with type 1 diabetes of both sexes. Each participant underwent both a food frequency questionnaire (FFQ) and 24-hour dietary recall specially adapted for measuring CML intake, anthropometry, measurement of blood pressure and biochemical parameters in blood and urine. RESULTS: Serum CML levels were significantly higher in patients with diabetes compared to healthy subjects (p 0.04), showing a direct relationship between dietary intake and serum levels of CML in T2D patients (r 0.53 p 0.03). sCML levels correlated positively with length of diabetes mellitus, and inversely with body mass index (BMI). The most important dietary factor contributing to raise CML levels in these patients with diabetes was the consumption of milk powder. CONCLUSION: Serum levels of CML were found to be higher among diabetic subjects, associated to length of diabetes as expected, but also with the ingestion of foods containing higher amounts of ML. The consumption of milk powder in this group is a major determinant of increased serum levels.

Dietary intake increases serum levels of carboxymethil-lysine (CML) in diabetic patients / La ingesta dietaria de carboximetil-lisina (CML) aumenta los niveles plasmáticos de este compuesto en pacientes diabéticos

Introduction: Advanced glycation end products are produced endogenously, in association with hyperglycemia and oxidative stress. They can also be generated during cooking or food processing and, once absorbed, alter protein function and promote inflammation. Methods: We selected 40 healthy male subjects, 17 patients with type 2 diabetes of both sexes and 15 patients with type 1 diabetes of both sexes. Each participant underwent both a food frequency questionnaire (FFQ) and 24-hour dietary recall specially adapted for measuring CML intake, anthropometry, measurement of blood pressure and biochemical parameters in blood and urine. Results: Serum CML levels were significantly higher in patients with diabetes compared to healthy subjects (p 0.04), showing a direct relationship between dietary intake and serum levels of CML in T2D patients (r 0.53 p 0.03). sCML levels correlated positively with length of diabetes mellitus, and inversely with body mass index (BMI). The most important dietary factor contributing to raise CML levels in these patients with diabetes was the consumption of milk powder. Conclusion: Serum levels of CML were found to be higher among diabetic subjects, associated to length of diabetes as expected, but also with the ingestion of foods containing higher amounts of ML. The consumption of milk powder in this group is a major determinant of increased serum levels (AU)

Introducción: Los productos avanzados de la glicación se producen de forma endógena en relación con la hiperglucemia y el estrés oxidativo. También pueden generarse durante el cocinado o el procesamiento de los alimentos; una vez absorbidos, alteran la función proteica y favorecen la inflamación. Métodos: Seleccionamos a 40 hombres sanos, 17 pacientes con diabetes tipo 2 de ambos sexos y 15 pacientes con diabetes tipo 1 de ambos sexos. A cada participante se le realizó un cuestionario de frecuencia de consumo de alimentos (CFA) y un recordatorio de 24 horas especialmente adaptado para medir el consumo de CML, antropometría, medición de la presión sanguínea y parámetros bioquímicos en la sangre y la orina. Resultados: Las concentraciones séricas de CML fueron significativamente mayores en pacientes con diabetes en comparación con los individuos sanos (p = 0,04). Se encontró una relación directa entre el consumo dietético y las concentraciones séricas de CML en los pacientes con diabetes tipo 2 (r = 0,53; p = 0,03). Las concentraciones séricas de CML se correlacionan positivamente con la duración de la diabetes mellitus e inversamente con el índice de masa corporal (IMC). El alimento que más contribuye al aumento de las concentraciones plasmáticas de CML en estos pacientes fue el consumo de leche en polvo. Conclusión: Se encontró que las concentraciones séricas de CML eran mayores en los sujetos diabéticos, asociado con la duración de la diabetes, como era de esperar, pero también con la ingestión de alimentos que contienen mayores cantidades de CML. El consumo de leche en polvo en este grupo es un factor determinante en el aumento de las concentraciones séricas de CML (AU)

Proliferation and differentiation of human adipocyte precursor cells: differences between the preperitoneal and subcutaneous compartments.

Human adipocyte precursor cells (APC) have been characterized in their proliferation and differentiation potential from subcutaneous, omental, and mesenteric depots, mostly from morbidly obese patients. Cells from the preperitoneal adipose compartment have not been characterized yet, least of all when obtained from normal weight subjects. The aim was to compare proliferation and differentiation of subcutaneous (SC) and preperitoneal (PP) APC derived from adipose tissue in healthy subjects with different body mass. SC and PP adipose tissue was obtained during surgery of inguinal hernias in five healthy non-obese subjects and three obese otherwise healthy men. APC, obtained by collagenase digestion, were cultured. Proliferation was assayed by cell counting and differentiation by oil red O staining and flow cytometry using Nile Red staining. Proliferation of SC was higher than PP APC. Such differences between both compartments were even higher in APC obtained from obese patients. Conversely PP APC differentiated earlier in vitro compared with SC cells. These results agree with published data on fat cell proliferation. However regarding differentiation, our data show that APC from deeper depots (in this case PP) differentiate earlier than subcutaneous APC. This is different to previous studies performed in mesenteric or omental adipose tissue.

Fluorescent serum and urinary advanced glycoxidation end-products in non- diabetic subjects.

INTRODUCTION: Advanced glycoxidation end-products (AGEs) are involved in age-related conditions and diabetic complications. Diet intake contributes to their circulating concentrations. AIM: To measure serum and urinary AGEs in non-diabetic volunteers and relate their concentration to body composition, blood chemistry and dietary ingestion. METHODS: We studied 41 adult men (31 middle-aged adults and 10 elderly). A nutritional assessment including a dietary recall designed for detection of AGE ingestion (specifically carboxymethyl-lysine(CML)), and anthropometric measurements were performed. Also serum lipoproteins, insulin, glucose, leptin and C reactive protein (CRP). AGEs were measured in serum and urine samples using size exclusion chromatography and flow injection assay (FIA); the technical procedures were first employed in 11 heterogeneous diabetics, as positive controls for this methodology. RESULTS: Serum and urinary chromatograms indicated that areas under the curve were not different in younger compared with elderly adults. AGEs did not correlate with dietary intake, body composition, nor metabolic parameters, however they correlated significantly with renal function and CRP concentration. DISCUSSION: In these non-diabetic volunteers, with low CML intake, serum and urinary concentration of AGEs were not related to dietary intake. AGEs were related to renal function and CRP, but not to body composition, lipoproteins, insulin and glucose.

Fluorescent serum and urinary advanced glycoxidation end-products in non- diabetic subjects

Introduction: Advanced glycoxidation end-products (AGEs) are involved in age-related conditions and diabetic complications. Diet intake contributes to their circulating concentrations. Aim: To measure serum and urinary AGEs in non-diabetic volunteers and relate their concentration to body composition, blood chemistry and dietary ingesti¢n. Methods: We studied 41 adult men (31 middle-aged adults and 10 elderly). A nutritional assessment including a dietary recall designed for detection of AGE ingesti¢n (specifically carboxymethyl-lysine(CML)), and anthropometric measurements were performed. Also serum lipoproteins, insulin, glucose, leptin and C reactive protein (CRP). AGEs were measured in serum and urine samples using size exclusion chromatography and flow injection assay (FIA); the technical procedures were first employed in 11 heterogeneous diabetics, as positive controls for this methodology. Results: Serum and urinary chromatograms indicated that areas under the curve were not different in younger compared with elderly adults. AGEs did not correlate with dietary intake, body composition, nor metabolic parameters, however they correlated significantly with renal function and CRP concentration. Discussion: In these non-diabetic volunteers, with low CML intake, serum and urinary concentration of AGEs were not related to dietary intake. AGEs were related to renal function and CRP, but not to body composition, lipoproteins, insulin and glucose.

Lean and fat mass as determinants of muscle strength and insulin sensitivity in Chilean elderly subjects.

PURPOSE: To report the association of lean body mass with nutritional, social and economic factors and its functional consequences in free living healthy elderly subjects. MATERIAL AND METHODS: Healthy elderly subjects of low socioeconomic level were studied. Monthly income, marital status, anthropometric measures and fall risk were assessed. Mini Nutritional Assessment score was calculated. Body composition and bone mineral density were measured by double beam X ray absorptiomentry. Fasting serum lipids, fasting and postprandial insulin and glucose levels were measured. Hand grip, quadriceps and biceps strengths and maximal inspiratory and expiratory pressures were measured. RESULTS: One hundred and nine subjects (56 women), aged 75 +/- 4 years old were studied. Lean body mass was 34.1 +/- 4 and 49.2 +/- 5.4 kg in women and men respectively (p < 0.001), fat mass was 22.8 +/- 7.1 and 20.7 +/- 6.4 kg in women and men respectively (p= NS). Lean body mass correlated with hand grip, quadriceps and biceps muscle strengths in men and with quadriceps and biceps strength in women. Men that exercised regularly had higher quadriceps strength and maximal expiratory pressure. Total body fat correlated positively with fasting and postprandial serum insulin levels. CONCLUSIONS: In this sample, lean body mass is directly related to muscle strength mostly in men. On the other hand, total fat mass is related to serum insulin levels.

The impact of nutritional supplementation and resistance training on the health functioning of free-living Chilean elders: results of 18 months of follow-up.

Body composition changes and loss of functionality in the elderly are related to substandard diets and progressive sedentariness. The aim of this study was to assess the impact of an 18-mo nutritional supplementation and resistance training program on health functioning of elders. Healthy elders aged > or = 70 y were studied. Half of the subjects received a nutritional supplement. Half of the supplemented and nonsupplemented subjects were randomly assigned to a resistance exercise training program. Every 6 mo, a full assessment was performed. A total of 149 subjects were considered eligible for the study and 98 (31 supplemented and trained, 26 supplemented, 16 trained and 25 without supplementation or training) completed 18 mo of follow-up. Compliance with the supplement was 48%, and trained subjects attended 56% of programmed sessions. Activities of daily living remained constant in the supplemented subjects and decreased in the other groups. Body weight and fat-free mass did not change. Fat mass increased from 22.2 +/- 7.6 to 24.1 +/- 7.7 kg in all groups. Bone mineral density decreased less in both supplemented groups than in the nonsupplemented groups (ANOVA, P < 0.01). Serum cholesterol remained constant in both supplemented groups and in the trained groups, but it increased in the control group (ANOVA, P < 0.05). Upper and lower limb strength, walking capacity and maximal inspiratory pressure increased in trained subjects. In conclusion, patients who were receiving nutritional supplementation and resistance training maintained functionality, bone mineral density and serum cholesterol levels and improved their muscle strength.

Acute nutritional and intestinal changes after pelvic radiation.

OBJECTIVE: Pelvic radiotherapy induces acute small bowel injury but its effects on nutritional status are unknown. The objective of this study was to prospectively evaluate nutritional, functional and morphologic intestinal changes, after radiotherapy. METHODS: Fifteen patients were studied before and after pelvic irradiation. A clinical, nutritional and routine clinical laboratory assessment was performed. Nutritional parameters included dietary recall, subjective global assessment, anthropometric measurements (body mass index, skinfold thickness at four sites and circumferences of arm, waist and hip), hand grip strength, indirect calorimetry and Dual Energy X-ray absortiometry (DEXA). Intestinal parameters included permeabilty to sugars (assessed by lactulose and mannitol urinary excretion), intestinal transit time (measured by hydrogen breath test after ingestion of lactulose) and jejunal biopsies. RESULTS: Thirteen patients presented diarrhea during radiation therapy. After five weeks, intestinal permeability increased, while intestinal transit time decreased. The second biopsy showed hypertrophy of villae and crypts. Simultaneously, patients lost weight at the expense of fat free mass. Resting energy expenditure was elevated prior to treatment and declined after five weeks. Changes in caloric ingestion were not significant. CONCLUSIONS: Our results indicate that pelvic radiation induces a loss of fat free mass along with intestinal morphologic and functional changes.

Therapeutic potential of vitamin E in heart disease.

Low density lipoprotein (LDL) oxidation is considered an important step in the atherogenic process. Oxidatively modified particles induce the expression of adhesion molecules, stimulate the production of inflammatory cytokines and impair endothelial function. The measurement of oxidised LDLs in vivo is very difficult, therefore most investigators rely on the measurement of in vitro oxidability of these particles to evaluate their deleterious effects. Supplementation with water and lipid soluble anti-oxidant vitamins, especially vitamin C and E, significantly increase the resistance to LDL oxidation. Vitamin E supplementation also improves endothelium-dependent vasodilation in hypercholesterolaemic and subjects who smoke cigarettes. Epidemiological studies have not consistently demonstrated a protective effect of vitamin E consumption as food or supplements on coronary events or stroke. Likewise, only one of five large prospective trials has shown a beneficial effect of vitamin E supplementation on cardiovascular events or mortality. One report showed that supplemented haemodialysed patients had a lower incidence of cardiovascular events. Thus, presently, there is not enough evidence to widely recommend the use of vitamin E supplements for vascular protection.

[Prevention of cardiovascular diseases: should the same criteria be applied in Latin America and Europe and North America?]. / Prevención de enfermedades cardiovasculares: deben aplicarse los mismos criterios en América Latina que en Europa y Norteamérica?

The prevention of cardiovascular diseases is based on the management of known cardiovascular risk factors by pharmacological means or by modifying lifestyles. A reduction in cholesterol levels is associated with a lower incidence of cardiovascular events and mortality, in both primary or secondary prevention trials. A reduction in blood pressure also leads to a decrease in acute myocardial infarction and the incidence of stroke. Regular exercise is associated with better disease free survival and the effects of smoking cessation are well known. High homocysteine levels are also associated with cardiovascular disease. However, there are no prospective clinical trials showing a beneficial effect of homocysteine reduction on cardiovascular mortality. A change in the type of dietary fat should also be beneficial, but this has not been proven in prospective clinical trials. In Chile, cardiovascular diseases are the leading cause of death among adults and the prevalence of cardiovascular risk factors, including hyperhomocysteinemia is similar to that of European or North American populations. Successful primary and secondary prevention programs to manage these risk factors have been developed in Chile. Therefore, the criteria applied in North America and Europe for the prevention of cardiovascular diseases, should be applied with slight modifications, in Latin American Countries.

Changes in microsomal activity in alcoholism and obesity.

BACKGROUND: Liver damage is more prevalent among obese alcoholics, and cytochrome P-4502E1(CYP2E1) induction is involved in its pathogenesis. OBJECTIVES: The study was undertaken to assess microsomal function, in alcoholic and nonalcoholic male subjects with different body compositions, through pharmacokinetics of chlorzoxazone (CLZ). We also intended to study the relationship between CLZ hydroxylation and urinary levels of 8-hydroxydiguanosine, and between CLZ levels and liver histology. METHODS: Serial measurements of CLZ serum concentration, after a 750 mg dose, were performed in 17 alcoholics (9 normal weight and 8 obese) and 21 nonalcoholic subjects (10 normal weight and 11 obese). Concentration of 6-hydroxy-chlorzoxazone (6-OH-CLZ) was determined at the second hour. Anthropometry, clinical laboratory tests, and urinary 8-hydroxydiguanosine concentrations were measured. Liver biopsies were performed in alcoholics. RESULTS: Five biopsies revealed severe lesions, one in normal-weight and four in obese patients (p = NS). Area under the curve (AUC) of CLZ was higher in normal-weight controls compared with the rest of the groups (ANOVA p = 0.001). This parameter correlated negatively with adiposity in nonalcoholic subjects and did not correlate with liver histology. 6-OH-CLZ/CLZ ratio was lower in normal-weight controls, compared with obese subjects and normal-weight alcoholics (p = 0.02). Both alcoholism and obesity were included as predictors of CLZ AUC in a multiple regression analysis. The two-factor ANOVA showed an additive effect of centripetal body fat distribution and alcoholism. Urinary 8-hydroxydiguanosine levels were extremely variable. CONCLUSIONS: Centripetal adiposity and alcoholism are associated with induction of CYP2E1. This may explain the higher prevalence of liver damage among obese alcoholics and also nonalcoholic steatohepatitis.

Low serum folate but normal homocysteine levels in patients with atherosclerotic vascular disease and matched healthy controls.

Mild hyperhomocysteinemia has been considered a cardiovascular risk factor. However, recent prospective studies have not demonstrated that hyperhomocysteinemia or the underlying genetic defect on methylentetrahydrofolate reductase is associated with a higher risk of coronary or peripheral artery disease. We compared serum homocysteine, folate, and vitamin B(12) levels of patients with coronary and peripheral vascular disease with those of age- and sex-matched healthy individuals. Subjects taking multivitamins, with diabetes mellitus, or serum creatinine levels over 1.5 mg/dL were excluded from the study. Homocysteine was measured by fluorimetric high-performance liquid chromatography. Serum folate and vitamin B(12) levels were measured by an ion-capture method. We studied 32 patients with peripheral vascular disease (10 female), aged 69.6 +/- 11 y, 24 age- and sex-matched control subjects, 52 patients with coronary artery disease (7 female), aged 59.5 +/- 10.4 y, and 42 age- and sex-matched control subjects. Serum homocysteine levels were 11.7 +/- 7.4 and 9.3 +/- 4.5 micromol/L in vascular patients and in the control counterparts, respectively (not significant). The levels for coronary patients and the control counterparts were 9.0 +/- 3.9 and 8.6 +/- 3.6 micromol/L, respectively (not significant). Folate levels were 4.48 +/- 2.42 and 7.14 +/- 4.04 ng/mL in vascular patients and control subjects, respectively (P < 0.02); the levels in coronary patients and control counterparts were 5.15 +/- 1.9 and 6.59 +/- 2.49 ng/mL, respectively (P < 0.01). No differences in vitamin B(12) or tocopherol levels were observed between patients and control subjects. There were no differences in homocysteine levels, but lower serum folate levels were observed when comparing patients with atherosclerotic vascular disease and healthy control subjects.

Effects of supplementation with folic acid and antioxidant vitamins on homocysteine levels and LDL oxidation in coronary patients.

Hyperhomocysteinemia is an important cardiovascular risk factor. Serum homocysteine levels are specially dependent on folate nutritional status. In addition, the oxidative modification of low-density lipoproteins (LDLs) in the endothelial microenvironment is a damaging factor that can be modified with fat-soluble antioxidant vitamins. The present study was done to assess the effect of a supplementation of folic acid and antioxidant vitamins on homocysteine levels and in vitro LDL oxidation in patients with coronary artery disease. Twenty-three patients with angiographically proven coronary artery disease were given supplements for 15 d consisting of one capsule twice a day of a multivitamin preparation containing 0.65 mg folic acid, 150 mg alpha-tocopherol, 150 mg ascorbic acid, 12.5 mg beta-carotene, and 0.4 microgram vitamin B12. Serum lipids, vitamin and homocysteine levels, and in vitro LDL oxidation were measured before and after the supplementation period. During the supplementation period, serum folate levels increased from 5.0 +/- 1.5 to 10.8 +/- 3.8 ng/mL (P < 0.001), vitamin B12 increased from 317.4 +/- 130.4 to 334.5 +/- 123.8 pg/mL (P < 0.05), and alpha-tocopherol increased from 8.2 +/- 5.1 to 13.7 +/- 7.9 mg/L (P < 0.001). Serum homocysteine levels decreased from 8.7 +/- 4.3 to 6.3 +/- 2.2 mumol/L (P < 0.001). In vitro LDL oxidation decreased from 2.6 +/- 1.1 to 1.6 +/- 1.1 nmol malondialdehyde/mg protein (P < 0.001). In comparing patients with healthy controls, basal levels of folate were lower in the patients, whereas vitamin B12, alpha-tocopherol, and homocysteine levels were similar. No changes in serum lipid levels or body weight were observed. In conclusion, a short-term supplementation with folic acid and antioxidant vitamins can reduce serum homocysteine levels and in vitro LDL oxidation in patients with coronary artery disease.

Nutritional support in alcoholic cirrhotic patients improves host defenses.

BACKGROUND: Malnutrition is usual in patients with alcoholic liver disease and is associated with a poor outcome. Nutritional support decreases nutrition-associated complications. AIM: To demonstrate that nutritional support in ambulatory alcoholic cirrhotic patients improves host defenses. METHODS: Thirty-one male outpatients with alcoholic cirrhosis CHILD-PUGH B or C were included. Twenty-five subjects completed six months consuming daily a nutritional supplement (Ensure, 1000 Kcal and 35 g protein), in addition to their regular diet. At entrance and every three months, a clinical assessment, nutritional evaluation and indirect calorimetry were performed. Liver function tests and LPS-induced monocyte production of cytokines, salivary secretory IgA, lactulose/mannitol ratio and breath hydrogen tests were also measured in these intervals. Delayed cutaneous hypersensitivity and IgG and IgM antibody response to endotoxin were assessed at entrance and at the end of the study. RESULTS: Patients drank 85% of the provided supplement as an average. REE, total body fat and serum albumin increased, basal breath hydrogen decreased and cellular immunity improved significantly during the follow up period (p< or =0.03). All the other parameters remained unchanged throughout the study. Six patients (16.2%) died during the study, five due to upper gastrointestinal bleeding. CONCLUSION: Nutritional support in alcoholic cirrhotic patients improves nutritional status and cell mediated immunity.