Plasma fatty acid profile in advanced cirrhosis: unsaturation deficit of lipid fractions

Fatty acid (FA) profile of plasma total lipids, phospholipids (PL), cholesteryl esters (CE), and triglycerides (TG) were measured in 101 patients with advanced liver cirrhosis and in 44 age- and sex-matched healthy controls. Plasma levels of lipidic phosphorus, esterified cholesterol, and TG also were measured, and the unsaturation index (UI) was calculated for each fraction. Total plasma concentrations of saturated FA, linoleate, and polyunsaturated FA (PUFA) were lower in cirrhotics than in controls. This profile was also found in plasma levels of PL- and CE-associated FA. No detectable amounts of C20:3n9 were found in cirrhotic patients. Percent FA distribution of lipid fractions showed a lower percentage of linoleate and PUFA and a higher relative amount of saturated and monoenoic FA in cirrhotics than in controls. As a consequence, the UI of PL and CE was diminished in liver cirrhosis. Linoleate and PUFA deficiency was more marked in CE than in PL, as shown by the number of patients with values below the 5th percentile of the control group, suggesting an attempt to maintain the unsaturation of PL as the most important component of cell membranes. Hepatic failure, poor essential FA intake, and malnutrition are some of the possible etiologic factors for PUFA deficiency in cirrhosis. Their relative contribution to plasma FA abnormalities, as well as the clinical and pathophysiological consequences of PUFA deficit in cirrhotic patients, requires further investigation.     

Polyunsaturated Fatty Acid Deficiency in Liver Cirrhosis: Its Relation to Associated Protein-Energy Malnutrition (Preliminary Report)

Plasma fatty acids (FA) from C14:0 to C22:6 omega 3 were measured in five healthy subjects and in 27 patients with liver cirrhosis. According to the assessment of triceps skinfold, mid-arm muscle circumference, and serum albumin concentration, patients were prospectively included in three groups: group A (n = 7) with acceptable nutritional status (including good nutrition and mild malnutrition), group B (n = 10) with moderate malnutrition, and group C (n = 10) with severe malnutrition. Plasma levels of total FA, saturated FA, linoleic acid, and omega 6 greater than 18C and omega 3 greater than 18 polyunsaturated fatty acids (PUFA) were lower in cirrhotics than in controls. Linoleic:arachidonic ratio was increased and delta 5-desaturation precursors:products ratio did not change, suggesting a reduction in delta 6-desaturase and/or C18-C20 elongase activities. In addition, a stepwise fall in plasma levels of all but saturated FA was found as the nutritional status worsened, suggesting that, in cirrhosis, impairment in PUFA biosynthesis is related to the severity of associated malnutrition. Since PUFA have important biological functions as components of cell membranes and precursors of eicosanoids, the results reported here may open new perspectives in the understanding of the cirrhosis-malnutrition relationship.     

Choline may be an essential nutrient in malnourished patients with cirrhosis

Elemental diets designed for nutritional support in protein-calorie malnutrition are often deficient in choline, a nonessential nutrient. Previously, malnourished patients on these diets were found to be at risk of developing plasma choline deficiency. We have now estimated the prevalence of this deficiency by determining fasting plasma levels of choline among cirrhotic and noncirrhotic malnourished male subjects maintained on regular hospital mixed food or elemental parenteral and enteral formulas. Plasma choline concentrations (microM, average +/- SD) were as follows: (i) mixed foods, 11.3 +/- 4.3 for cirrhotic (n = 22) and 9.3 +/- 2.4 for noncirrhotic (n = 12) patients; (ii) parenteral formula, 5.3 +/- 1.6 for cirrhotic (n = 5) and 8.6 +/- 5.2 for noncirrhotic (n = 16) subjects; and (iii) enteral formula, 6.1 +/- 1.2 for cirrhotic (n = 5) and 11.7 +/- 1.9 for noncirrhotic (n = 4) subjects. The level for healthy normal subjects eating mixed foods was 12.0 +/- 2.2. The prevalence of plasma choline deficiency, i.e., plasma levels greater than or equal to 2 SD below the normal average, was as follows: parenteral formula, all cirrhotic and 10 of 16 noncirrhotic subjects; enteral formula, all cirrhotic and none of the noncirrhotic subjects. The reversibility of choline deficiency was examined in a longitudinal study of three phases involving 10 patients--5 with alcoholic cirrhosis (all on enteral formula); 5 noncirrhotic (1 on enteral and 4 on parenteral formula). During phase 1 (3-day equilibration period; ad libitum regular hospital diet), plasma choline levels were within the normal range for all subjects. During phase 2 (2 wk, choline depletion phase, elemental formulas), choline levels were subnormal in all cirrhotic subjects (5.1 +/- 2.0 microM) on enteral formula and all noncirrhotic patients on parenteral formula (5.9 +/- 1.3 microM). During phase 3 (2 wk, choline repletion phase, elemental formula + 6 g choline/day), the levels normalized in all patients (cirrhotic 11.4 +/- 3.1 microM and noncirrhotic 11.9 +/- 3.2 microM). Analyses of abdominal computed tomographic scans and plasma liver chemistries in the cirrhotic subjects during the three phases suggested a correlation between plasma choline deficiency and hepatic steatosis and abnormal liver enzyme levels in some patients. Therefore, choline may be an essential nutrient in malnourished cirrhotic patients and its deficiency may be associated with adverse hepatic effects.     

Total and individual free fatty acid concentrations in liver cirrhosis

The finding of high plasma free fatty acid (FFA) levels in cirrhotic patients has been attributed either to decreased hepatic clearance or to enhanced fat mobilization. To better clarify these hypotheses, total and individual FFA and glycerol levels were determined in 21 cirrhotic patients with different degrees of hepatocellular damage (evaluated by liver function tests), portal hypertension (evaluated by endoscopy and clinical signs), and nutritional status (evaluated by anthropometric and biohumoral parameters) and in 10 age- and sex-matched healthy subjects. Glucose tolerance and insulin and glucagon levels were determined in all individuals. Well-nourished and malnourished patients were identified within the cirrhotic group. Plasma FFA and glycerol concentrations were well correlated (r = 0.47, P less than 0.05), levels being significantly higher in cirrhotic individuals than in controls (746.6 +/- 46.29 SE v 359.22 +/- 40.82 mumol/L, P less than 0.001 for plasma FFA; 150.1 +/- 3.12 v 82.5 +/- 9.2 mumol/L, P less than 0.01 for glycerol). Plasma FFA and glycerol showed no correlation with the liver function test results or portal hypertension parameters. Interestingly, plasma levels of FFA and glycerol were influenced by the nutritional status, significantly higher FFA levels being observed in the well-nourished than in the malnourished patients (842.5 +/- 47.5 v 563.4 +/- 78 mumol/L, P less than 0.005). Furthermore, a positive correlation was found between plasma glycerol level and percentage of triceps skinfold (r = 0.45, P less than 0.05). No correlation was found between plasma levels of FFA or glycerol and glucose tolerance, insulin and glucagon.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oxidative metabolism in cirrhotic patients with and without hepatocellular carcinoma: effects of malnutrition.

Progressive degrees of metabolic alterations are frequent in cirrhosis impairing peripheral tissue and body composition. Hepatocellular carcinoma worsens protein wasting and malnutrition. A normal energy production rate and an abnormal substrate oxidation rate are well-known findings in cirrhosis; however, no data are available on cirrhotic patients with hepatocellular carcinoma. The aim of this study was to measure oxidative metabolism in cirrhotic patients with and without hepatocellular carcinoma and to investigate the correlation between energy production rate, respiratory quotient and nutritional state. Thirteen male cirrhotic patients with hepatocellular carcinoma (8 well-nourished and 5 malnourished) were compared with 17 cirrhotic patients without hepatocellular carcinoma (11 well-nourished and 6 malnourished) and six controls who were age and sex matched. A diagnosis of malnutrition was made if the fat mass percentage was reduced to less than 20% of the patient's body weight. Indirect calorimetry was performed between 8 and 10 AM, after a 12-hr fast, for 30 min (with a 10-min steady-state period), and measured energy production rate was calculated according to Weir's formula. Body composition was assessed by means of the Durnin and Womersley formula. Anthropometry and bioelectric impedance analysis showed no variations in kilograms of fat-free mass in our malnourished patients. Our data show that, when the energy production rate is measured while the patient is at rest and corrected for fat-free mass, the energy requirements of cirrhotic patients and cirrhotic patients with hepatocellular carcinoma matched that of the controls, regardless of nutritional state.(ABSTRACT TRUNCATED AT 250 WORDS)     

Malnutrition and diabetes mellitus are related to hepatic encephalopathy in patients with liver cirrhosis.

BACKGROUND/AIMS: Studies on animal models of hepatic encephalopathy (HE) suggest that poor nutritional status may facilitate the development of HE. Insulin resistance and diabetes mellitus have recently been reported to affect cognition in patients with hepatitis C cirrhosis awaiting liver transplantation. Our aim was to investigate the effects of malnutrition and diabetes mellitus on HE in unselected patients with liver cirrhosis. METHODS: A total of 128 consecutive cirrhotic patients were prospectively evaluated for the presence of HE according to the West-Haven criteria as well as by means of two psychometric tests and fasting plasma ammonium ion concentrations. Nutritional status was assessed by anthropometry and estimation of recent weight change. Fasting plasma glucose was measured, and in a subgroup of 84 patients fasting serum insulin and insulin resistance were also determined. RESULTS: Fifty-one (40%) cirrhotics were malnourished, 33 (26%) had diabetes and 42 (34%) had HE. Patients with vs. without malnutrition had more frequently HE (46 vs. 27%; P=0.031) but did not differ in age, aetiology or severity of liver cirrhosis (P>0.1). Multivariate analysis showed that the time needed to perform number connection test A was independently correlated to age, the Child-Pugh score, diabetes and malnutrition (P<0.05 for all). Plasma ammonium ion levels were related to insulin resistance (r=0.42, P<0.001) and muscle mass (r=0.28, P=0.003). CONCLUSION: Malnutrition and diabetes mellitus seem to be related to HE in patients with liver cirrhosis. Nutritional status and insulin resistance might be implicated in the pathogenesis of HE.     

Sensibility of anthropometric-laboratory markers of protein-energy malnutrition in cirrhotic patients

AIM: The prevalence and severity of protein-energy malnutrition (PEM) were investigated through the anthropometric (body mass index, triceps and subescapular skinfolds and upper arm circumferences) and blood measures in 117 cirrhotic patients. The sensitivity and specificity of single or combined PEM markers were tested among Child A (n=18), Child B (n=42) and Child C (n=57) adults (51+/-13y). RESULTS: Were calculated as z score and considered deficient when z< or =-1.28SD according to local standards. The most deficient markers where albumin (93%), hemoglobin (90%), upper arm circumference (61%), triceps (55%) and subescapular (53%) skinfolds. By combining upper arm circumference with triceps or subescapular skinfolds, PEM were detected in 63% of patients varying from 39-44% (Child A) to 64-68% (Child B or C). CONCLUSION: Thus the pattern of PEM present in cirrhosis is predominantly in their protein compartment and worsened with the severity of hepatocellular insuficiency. Upper arm circumference can be used as sensitive markers of presence and severity of PEM in cirrhotic patients but showing low specificity for discriminate PEM among Child grades (B and C) of hepatocellular dysfunctions.     

Relationship of Insulin Resistance to Protein-Energy Malnutrition in Patients with Alcoholic Liver Cirrhosis: Effect of Short-Term Nutritional Support

Protein-energy malnutrition (PEM) and insulin resistance (IR) are common features of alcoholic liver cirrhosis (ALC). In order to determine a relationship between them, nutritional status and glucose homeostasis were studied in 26 patients with ALC. Nutritional status was assessed through dietary, anthropometric, and biological parameters. An IR index (M/I) was obtained from the euglycemic insulin clamp technique. M/I was significantly correlated with accurate markers of PEM (albumin, transthyretin, and retinol-binding protein) but not with other markers of liver dysfunction. Nine patients were studied before and after nutritional support: M/I was significantly improved as were serum markers of PEM. Other markers of liver dysfunction were also significantly improved. These findings suggest that PEM could be responsible, in part, for IR in patients with ALC who are frequently malnourished. Moreover, nutritional support improved insulin sensitivity in these patients.     

Nutritional status using mini nutritional assessment and subjective global assessment predict mortality in geriatric patients

OBJECTIVES: To evaluate the clinical assessment of nutritional status and mortality in geriatric patients. DESIGN: Prospective follow-up study. SETTING: Acute geriatric inpatient ward. PARTICIPANTS: Eighty-three consecutive acute geriatric patients (mean age +/- standard deviation = 83 +/- 7; 68% women). MEASUREMENTS: Patients were classified as (1) having protein-energy malnutrition (PEM), (2) having moderate PEM or being at risk for PEM, or (3) being well nourished according to Subjective Global Assessment (SGA) and Mini Nutritional Assessment (MNA). Body mass index ((BMI) kg/m2), arm anthropometry, and handgrip strength were determined. In a subgroup of patients (n = 39), body composition was analyzed using dual energy x-ray absorption and bioelectrical impedance. Three-year mortality data were obtained from the Swedish population records. RESULTS: Twenty percent and 26% of the patients were classified as having PEM based on SGA and MNA, respectively, whereas 43% and 56%, respectively, were classified as having moderate PEM or being at risk for PEM. Objective measures, such as BMI, arm anthropometry, handgrip, and body fat were 20% to 50% lower in the malnourished group than in the well-nourished subjects (P <.05). Moreover, mortality was higher in those classified as being malnourished, ranging from 40% after 1 year to 80% after 3 years, compared with 20% after 1 year (P =.03-0.17) and 50% after 3 years (P <.01) in patients classified as being well nourished. CONCLUSION: Fewer than one-third of newly admitted geriatric patients had a normal nutritional status according to SGA and MNA. BMI, arm anthropometry, body fat mass, and handgrip strength were reduced, and 1-, 2-, and 3-year mortality was higher in patients classified as malnourished. The present data justify the use of SGA and MNA for the assessment of nutritional status in geriatric patients.     

Nonalcoholic fatty liver disease: from lipid profile to treatment

Nonalcoholic fatty liver disease (NAFLD) is characterized by excess lipid accumulation in the liver. Although the majority of NAFLD is benign simple steatosis, a subset of NAFLD includes nonalcoholic steatohepatitis (NASH), which can progress to liver cirrhosis and liver cancer. In both simple steatosis and steatohepatitis, triglyceride is well known as the major lipid that accumulates in the liver. However, we have little information on the other lipids that deposit in the liver. Thus, lipid profiling is necessary to understand the pathogenesis of NAFLD. In addition, these data provide further information on early detection of NASH and optimal treatment for NAFLD. Although plasma and hepatic lipid profiles are similar between simple steatosis and steatohepatitis, recent intensive researches demonstrate that free cholesterol, polyunsaturated fatty acid (PUFA), and phospholipid levels are altered in human NAFLD. In experimental models, liver injury is induced by free cholesterol accumulation and compositional changes of n-6/n-3 PUFAs and phospholipids. Therefore, these lipid levels are candidates to predict the progression to NASH. Lipid-lowering agents have potential to normalize these lipid levels. Currently, favorable results are obtained using statins, ezetimibe, and n-3 PUFAs in simple steatosis. But the effects of these agents for NASH are limited. These unsatisfactory results may partially depend on the study design because most studies are relatively short-term and small number of patients. Larger studies are necessary to determine the promising effects of lipid-lowering agents for NASH and its comorbidities.     

TIPS implantation raises leptin levels in patients with liver cirrhosis.

Increased leptin levels in patients with liver cirrhosis are postulated to result in malnutrition and increased energy expenditure. Since cirrhotic patients show improved nutritional status after a transjugular intrahepatic portosystemic stent shunt (TIPS), it was the aim of this study to evaluate plasma leptin levels and their influence on nutritional status prior to and after the TIPS procedure. We evaluated plasma leptin levels, body mass index (BMI), Child-Pugh score and pertinent biochemical parameters in 31 patients (19 men and 12 women) with severe complications of liver cirrhosis (74% ethyltoxic men, 50% ethyltoxic in women), prior to and after TIPS. Nineteen cirrhotic patients without TIPS served as controls. In women ascitic-free BMI significantly increased (from 22.8 +/- 4.6 kg/m2 to 23.9 +/- 4.9; p = 0.004 three months after TIPS), whereas in men only a tendency toward higher values (26.1 +/- 4.7 vs. 26.7 +/- 4.4; p = 0.28) was found. Analysis of peripheral venous leptin concentrations before and three months after TIPS revealed a significant increase in women (11.9 +/- 8.8 ng/ml vs. 18.6 +/- 14.9; p = 0.009) and in men (7.7 +/- 6.2 ng/ml vs. 12.2 +/- 9.0; p = 0.005). In addition, the leptin-BMI ratio increase significantly in women and men three months after TIPS implantation (women 0.49 +/- 0.29 vs. 0.73 +/- 0.52; p = 0.017; men 0.28 +/- 0.22 vs. 0.43 +/- 0.28; p = 0.002). On the other hand, patients without TIPS implantation showed no significant alterations of BMI and peripheral venous leptin concentrations. After TIPS implantation in liver cirrhotic patients, leptin levels were increased and the nutritional status improved. Therefore, our analysis suggests that in patients with predominantly ethyltoxic liver cirrhosis, elevated leptin levels are not a major reason for poorer body composition.     

不同糖耐量人群血浆脂肪酸谱与胰岛素抵抗

目的　研究不同糖耐量人群血浆脂肪酸谱与胰岛素抵抗 (IR)之间的关系。方法　将受试者根据口服葡萄糖耐量试验 (OGTT)结果分为正常糖耐量组 (NGT) ,糖耐量受损组 (IGT )及 2型糖尿病组(DM )。采用毛细血管气相色谱法测定血浆脂肪酸谱 ,用胰岛素敏感指数 (IAI)评估IR。结果　DM组及IGT组血浆软脂酸 (C16:0 )、硬脂酸 (C18:0 )、二十二烷酸 (C2 2 :0 )、二十四烷酸 (C2 4:0 )和饱和脂肪酸浓度较NGT组明显升高 (P <0 .0 5～P <0 .0 1) ;花生四烯酸 (C2 0 :4)分别从NGT、IGT和DM组依次升高 ,差异有显著性 (P <0 .0 5～P <0 .0 1) ;血浆饱和脂肪酸 (SFA)从NGT、IGT、DM亚组依次升高 (P <0 .0 5～P <0 .0 1) ;NGT组的多不饱和脂肪酸 (PUFA)与饱和脂肪酸 (SFA)的比率高于IGT组和DM组 (均P <0 .0 5 ) ;血浆C16:0、C2 0 :4、C2 2 :0、SFA与IAI呈负相关 (P均 <0 .0 1)、PUFA/SFA与IAI呈正相关 (P <0 .0 1)。结论　不同糖耐量者血浆脂肪酸谱不同 ,糖耐量减低与 2型糖尿病患者SFA浓度升高 ,PUFA/SFA下降 ,且与胰岛素抵抗密切相关     

Impaired vitamin E status in patients with parenchymal liver cirrhosis: relationships with lipoprotein compositional alterations, nutritional factors, and oxidative susceptibility of plasma

Vitamin E is a lipid-soluble vitamin and an important antioxidant that protects lipoproteins and cell membranes from lipid peroxidation. The aims of the present study were to investigate, in patients with parenchymal liver cirrhosis, the following: (1) nutritional and vitamin E status in relation to compositional changes in lipoproteins; and (2) the effects of these alterations on the patients' plasma susceptibility to copper-mediated oxidation. Patients (n = 55) with liver cirrhosis and 25 healthy volunteers had vitamin E in serum and in isolated lipoprotein fractions analyzed by high-performance liquid chromatography (HPLC). Plasma susceptibility to peroxidation was measured by incubation with Cu(2+). Nutritional status was assessed by anthropometry. Vitamin E concentration was significantly decreased (P <.001) in the serum and in very-low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) in cirrhotic patients. The decrease was related to the degree of liver impairment. There were significant correlations between cholesterol and vitamin E concentrations in serum and in all the lipoprotein fractions (r between 0.72 and 0.89; P <.001) in cirrhotic patients, but there were no significant relationships between vitamin E and any of the anthropometric indices of nutritional status. The plasma maximal oxidation rate was significantly increased in cirrhotic patients (P <.01) and was inversely related to the serum concentration of vitamin E (P <.05). We conclude that lipoprotein alterations and not nutritional factors should be regarded as major factors explaining serum vitamin E reduction in patients with parenchymal liver cirrhosis, and that vitamin E depletion is associated with an increased plasma susceptibility to oxidation.     

The behavior of lipids in acute viral hepatitis and chronic hepatopathies

The dynamic changes of total lipids, beta-lipoproteids, cholesterol, free fatty acids and triglycerides levels were observed in patients with viral hepatitis B (48 patients), viral hepatitis Non A/Non B (13 patients), chronic persistent hepatic (22 patients) and liver cirrhosis (26 patients) in relation with HBV infection. Total lipids, beta-lipoproteids and cholesterol levels in serum of all patients were not significantly changed. In patients with liver cirrhosis without HBs-antigenemia, the triglycerides levels in serum were lower in exacerbation phase as well as in clinical amelioration phase of illness. The triglycerides levels in serum were not significantly changed in remaining groups of patients. In the patients with viral hepatitis B, viral hepatitis Non A/Non B and liver cirrhosis with HBs-antigenemia the primary increased plasma free fatty acids levels decreased in recovery and clinical amelioration phase of patients with liver cirrhosis.     

The Erythrocyte Membrane Disturbances in Protein-Energy Malnutrition: Nature and Mechanisms

In protein-energy malnutrition (PEM), as observed in Kivu, the RBC have an increased ratio of surface area to volume which is demonstrated by the presence of target cells on light microscopy and cup cells with scanning electron microscopy. The osmotic fragility is decreased. These abnormalities can be attributed to the accumulation of cholesterol and phosphatidylcholine (PC) in the RBC membrane. The molar ratio of cholesterol to phospholipids is moderately increased. Several findings suggest that the cholesterol and PC build-up results from disturbed exchanges in these lipids between the RBC and the plasma lipoproteins. Firstly, the osmotic fragility of a patient's RBC gradually becomes normal when the cells are transfused into a healthy recipient. Secondly, the cholesterol flux between the RBC and the plasma LDL seems to be low. Thirdly, the increase in RBC PC cannot be explained by a diminished fatty acids transport between the deep RBC PC pool and the RBC phosphatidylethanolamine (PE) pool. Finally complex disturbances of the plasma lipoproteins are obvious. It is improbable that the cholesterol and PC build-up accounts for the premature RBC destruction which has been described in Kivu PEM. However, the observation of an increased fatty acid turnover in RBC PC and PE, as well as other data previously obtained in Kivu PEM, lead to the conclusion that membrane peroxidation may be a major cause of the shortened erythrocyte life-span in this syndrome.     

Nutritional state and energy balance in cirrhotic patients with or without hypermetabolism: Multicentre prospective study by the ‘Nutritional Problems in Gastroenterology’ Section of the Italian Society of Gastroenterology (SIGE)

BACKGROUND AND AIMS: A total of 334 stable, compensated cirrhotic patients admitted to 10 Italian Gastroenterology Units were included in a prospective study to evaluate nutritional state and energy balance in liver cirrhosis. MATERIALS AND METHODS: Nutritional state and calorie intake were examined in the total population, while adequacy of calorie intake versus measured total energy expenditure was evaluated in a comparable subpopulation and in 40 matched controls, by computing the energy balance. RESULTS: Our data demonstrated that: (i) malnutrition was present in 25% of the total patients and significantly correlated with the Child's group (A=16%; B=25%; C=44%); (ii) the type of malnutrition is influenced by mBEE: normometabolic patients exhibit a significant (p<0.005) reduction of mid-arm fat area while both hypermetabolic and hypometabolic patients show a significant (p<0.005) decline in kg of free fat mass; (iii) normometabolic and hypometabolic patients have a negative energy balance, due to a high level of physical activity (127+/-14 kJ) in the first group and a reduced energy intake/kg body weight (102+/-12 kJ) in the second; (iv) hypermetabolic patients have a positive energy balance due to decreased daily physical activity/kg body weight (108+/-28 kJ); (v) malnourished and normometabolic patients eat a significantly (p<0.05) reduced percentage of protein whereas malnourished and hypermetabolic patients eat a significantly increased percentage of fat (p<0.05). CONCLUSION: Although multivariate regression analysis confirms that the Child-Pugh's score is a better independent predictor of malnutrition, the measure of REE, TEE, calorie intake and energy balance need to be routinely performed in cirrhotic patients, in order to recognise hypermetabolic and hypometabolic patients (approximately 30%) in whom the nutritional and metabolic parameters are indispensable as a basis for designing and prescribing personalised nutritional strategies that can treat muscle malnutrition and thus improve the morbidity and mortality rates.     

Plasma amino acid levels in patients with colorectal cancers and liver cirrhosis with hepatocellular carcinoma

BACKGROUND/AIMS: A variety of cancer-bearing patients have been shown to have disturbances in carbohydrate, lipid and protein metabolism. The complex of metabolic derangements of protein in cancer patients may be reflected by alteration in the plasma free amino acid profile. In this study, we try to investigate the plasma free amino acid profile in patients with colorectal cancer and liver cirrhosis with hepatocellular carcinoma, which are the most common cancers in Taiwan. METHODOLOGY: Fasting venous blood samples were drawn from sixteen control volunteers and 42 cancer-bearing patients including 14 early stage colorectal cancer patients (Duke A and B), 18 late stage ones (Duke C and D) and 10 liver cirrhotic patients with hepatocellular carcinoma. Seventeen amino acid levels were measured using a Beckman amino acid analyzer. RESULTS: About one third of early or late colorectal cancer patients had body weight loss more than 10% in half a year and were defined as malnourished. For individual amino acids, in early colorectal cancer patients, the plasma level of most essential amino acids and non-essential amino acids decreased (significantly in Tyr, Ala, Met, Phe and Thr). In late stage colorectal cancer patients and patients with liver cirrhosis with hepatocellular carcinoma, plasma levels of most essential amino acids and non-essential amino acids decreased more obviously. For group amino acids, the plasma levels of essential amino acids, non-essential amino acids, gluconeogenic amino acids and branched-chain amino acids were also lower in the cancer patients than those in control volunteers. The difference was also noticeably significant in patients with late stage colorectal cancer and liver cirrhosis with hepatocellular carcinoma. The plasma free amino acid patterns in colorectal cancer patients are quite different from those in patients with non-gastrointestinal cancer and weight loss. The plasma level of essential amino acids and branched-chain amino acids was not kept within normal range in colorectal cancer patients. Elevation of plasma aromatic amino acids and methionine levels usually observed in liver cirrhotic patients without hepatocellular carcinoma was not apparent in our cirrhotic patients with hepatocellular carcinoma. CONCLUSIONS: The plasma free amino acid patterns in our colorectal cancer patients and cirrhotic patients with hepatocellular carcinoma were rather characteristic. The results will offer useful tools for improving diagnosis and therapy.     

A case-control pilot study on n-3 polyunsaturated fatty acid as a negative risk factor for myocardial infarction

The relation between n-3 polyunsaturated fatty acid (PUFA) and nonfatal myocardial infarction is still controversial. A multicenter case-control pilot study on n-3 PUFA as a negative risk factor for myocardial infarction was performed in Niigata prefecture. Seventy-three patients with acute myocardial infarction (AMI) and age and gender matched controls (n = 84) were recruited. Serum leptin levels were significantly higher in patients with AMI than the controls (8.1 +/- 6.7 ng/mL versus 5.8 +/- 3.7 ng/mL, P < 0.01), and serum high-density lipoprotein cholesterol (HDLc) levels were significantly lower in patients with AMI than the controls (46 +/- 10.5 mg/dL versus 60 +/- 15 mg/dL, P < 0.00001). Statistically significant differences were preserved in leptin and HDLc when the data were analyzed separately by gender. Serum levels (%weight) of linolenic acid (C18:3:n3), eicosapentaenoic acid (C20:5:n3), docosapentaenoic acid (C22:5:n3), and total n-3 PUFA were significantly lower in patients with AMI than the control group (P < 0.000001, < 0.05, < 0.05, < 0.05, respectively). The serum n-3 PUFA/saturated fatty acid (SF) ratio and n-3 PUFA/n-9 monounsaturated fatty acid (MUFA) ratio were significantly lower in patients with AMI than the controls (P < 0.05 and < 0.01, respectively). When the subjects were separated into two categories according to an n-3/n-6 PUFA ratio below 0.3 or above 0.3, patients with AMI were more frequently in the former while the controls were more frequently in the latter (P < 0.05). N-3 PUFA may be a negative risk factor for AMI. The results suggest leptin is a risk factor for AMI irrespective of ethnicity and gender.     

Variation in the fatty acid binding protein 2 gene is not associated with markers of metabolic syndrome in patients with coronary heart disease

BACKGROUND AND AIM: It has been suggested that the threonine (Thr) 54 allele of the intestinal fatty acid binding protein 2 (FABP2) gene is associated with insulin resistance and affects the fatty acid composition of serum lipids. Our aim was to investigate the frequency of the alanine (Ala) 54Thr polymorphism of the FABP2 gene in patients with coronary heart disease (CHD), and the association between the polymorphism and the markers of metabolic syndrome, serum lipid levels and the fatty acid profile of serum lipids. METHODS AND RESULTS: A total of 414 CHD patients (mean age 61 years, range 33-74) participated in the cross-sectional EUROASPIRE (European Action on Secondary Prevention through Intervention to Reduce Events) Study. Markers of metabolic syndrome included fasting plasma glucose concentration, serum high-density lipoprotein cholesterol and triglycerides (TG), waist circumference, the waist/hip ratio, body mass index (BMI) and blood pressure (BP). The frequency of the Thr54 allele was similar in the CHD patients (27.2%) and control subjects from two independent studies (27.8% and 28.7%). There were no significant differences in plasma glucose, serum lipids, BP, BMI, waist circumference or waist/hip ratio among the genotypes. Genotype frequency was not associated with the prevalence of diabetes or metabolic syndrome, but metabolic syndrome (as defined by National Cholesterol Education Program criteria) tended to be more frequent in subjects with the Thr/Thr genotype (p = 0.095). There were no differences in the fatty acid profiles of serum cholesteryl esters, TG or phospholipids among the genotypes. CONCLUSIONS: The Ala54Thr polymorphism of the FABP2 gene is not associated with CHD, markers of the metabolic syndrome, or the fatty acid profile of serum lipids in Finnish CHD patients.     

Association of fatty acid profile in plasma lipid fractions with HbA1c in type 2 diabetic patients

The aim of this pilot study has been the comparison of fatty acid profiles of diabetic and healthy subjects in order to evaluate the relationship between fatty acid profiles in plasma lipid fractions and glycated haemoglobin (HbA1c) in type 2 diabetes (T2D) patients. The fatty acid composition of fasting plasma lipid subfractions has been analyzed in patients (n?=?26) diagnosed with T2D and in corresponding control group (n?=?26) of healthy voluntary blood donors. Five subfractions containing phospholipids (PLs), diglycerides (DGs), free fatty acids (FFAs), triglycerides (TGs), and cholesterol esters (CEs) were isolated from plasma samples and separated by thin-layer chromatography. Fatty acid composition of these subfractions was analyzed by GC/FID. Significant changes in fatty acid profiles were found in all lipid fractions from T2D patients in comparison with the control group. HbA1c correlated negatively with delta 9 desaturation (9D) index. Significantly positive correlation of palmitic acid levels and negative correlation of oleic acid levels with HbA1c concentration were found in PL and TG fractions with higher significance in TGs. This pilot study has shown possible associations of HbA1c, common parameter measured in routine laboratories, with lipid metabolism. The strongest correlation was found in plasma TGs, especially in case of palmitic and oleic acids. This is the first report showing that metabolic control assessed by HbA1c is negatively associated with delta 9D index.