European Journal of Nutrition (v.49, #4)

Glutamine as indispensable nutrient in oncology: experimental and clinical evidence by Katharina S. Kuhn; Maurizio Muscaritoli; Paul Wischmeyer; Peter Stehle (197-210).
In hypermetabolic situations, glutamine is intensively used by rapidly dividing cells such as enterocytes, lymphocytes, and fibroblasts as nitrogen source and/or alternative energy fuel. It is hypothesized that in cancer patients the increased glutamine demands of the host increase the capacity of endogenous production resulting in a strong glutamine deprivation with detrimental effects on organ functions. In long-term periods of cancer cachexia, an adequate nutrition support including glutamine can essentially contribute to cover glutamine needs and, thus, to spare energy reserves of the host and to retard severe complications such as multi-organ failure. Due to the early in vitro knowledge that cancer cells preferably consume glutamine, oncologists often refuse to supply glutamine to the tumor-bearing host to avoid any potential risk. An objective evaluation whether supplemental glutamine supports tumor growth in vivo is, however, still lacking.The present review evaluates in vivo experimental and clinical data with respect to potential effects of glutamine administration in tumor-bearing hosts and draws conclusions for the use of glutamine supplements in clinical oncology.Experimental and clinical intervention studies were identified in a systematic review of MEDLINE Database (last entry: June 2008) using key search terms and review articles. These studies were supplemented with reports identified through manual searches and other studies previously known by the authors.Numerous experimental studies (rat/mouse model) show that oral/enteral or intravenous glutamine supports metabolism of the tumor-bearing host and can ameliorate gastrointestinal toxicity of therapeutical measures. Within the last two decades, 36 (24 oral/enteral, 12 parenteral) clinical studies evaluating the tolerance, safety and effects of glutamine in various patient groups have been published. In the great majority of these clinical studies, glutamine supplementation in cancer patients improves host metabolism and clinical situation without increasing tumor growth. Potential mechanisms of glutamine effects include maintenance of mucosal integrity, improved immune competence, inhibition of cell proliferation, increased apoptosis rate, increased synthesis of glutathione, induction of heat shock protein synthesis, and increased synthesis of glucagons-like peptides.In various clinical situations, appropriate exogenous glutamine supply is safe and can beneficially contribute to diminish risks of high-dose chemotherapy and radiation. In addition, there is some evidence that adequate glutamine availability can beneficially affect outcome, especially in patients undergoing bone marrow transplantation.
Keywords: Glutamine; Oncology; Experimental studies; Clinical studies; Cellular mechanisms

Alcohol consumption and the risk of coronary heart disease in postmenopausal women with diabetes: Women’s Health Initiative Observational Study by Swapnil N. Rajpathak; Mathew S. Freiberg; Cuiling Wang; Judith Wylie-Rosett; Rachel P. Wildman; Thomas E. Rohan; Jennifer G. Robinson; Simin Liu; Sylvia Wassertheil-Smoller (211-218).
Although several observational studies have consistently reported an inverse association between moderate alcohol consumption and risk of coronary heart disease (CHD), it is yet not well established if this association also exists among people with type 2 diabetes. The aim of this study is to evaluate the association between the frequency and quantity of alcohol intake and the risk of developing CHD among postmenopausal women with diabetes.We conducted a prospective cohort study, which included 3,198 women with self-reported diabetes and without any history of cardiovascular disease at baseline, in the Women’s Health Initiative Observational Study. Alcohol intake was assessed by a semiquantitative food frequency questionnaire. The primary outcome of this study was CHD, which was validated by medical record review. Cox proportional hazards regression was used to estimate the hazard ratio (HR) for the association of alcohol intake and risk of incident CHD while adjusting for several potential confounders.During the 22,546 person-years of follow-up, there were 336 incident cases of CHD. Both frequency and quantity of alcohol intake were inversely associated with the risk of developing CHD. Compared to nondrinkers, the multivariable HRs across categories of frequency of alcohol consumption (≤0.5, 0.5–2 and ≥2 drinks/week) were 0.89 (95% confidence intervals [CI]: 0.63, 1.26), 0.84 (95% CI: 0.56, 1.25) and 0.65 (95% CI: 0.43, 0.99), respectively (p for trend: 0.04). This association did not appear to differ based on the type of the alcoholic beverage consumed.Moderate alcohol consumption of postmenopausal women with type 2 diabetes may have a benefit on CHD similar to that seen in postmenopausal nondiabetic women. The potential risks of alcohol on noncardiac outcomes may need consideration when recommending alcohol to women with diabetes.
Keywords: Alcohol; Cardiovascular; Women; Diabetes

Decreased high-density lipoprotein cholesterol and insulin resistance were the most common criteria in 12- to 19-year-old adolescents by Nurten Budak; Ahmet Öztürk; Mümtaz Mazicioglu; Cevad Yazici; Fahri Bayram; Selim Kurtoglu (219-225).
Metabolic syndrome (MetS) is characterized by a group of metabolic risk factors leading to an increase in diabetes mellitus and cardiovascular diseases. It is known that the pathologic processes such as hyperinsulinemia and atherogenic risk profile associated with the development of MetS begin during childhood and adolescence.To determine the prevalence of MetS and assess the association between MetS and certain demographic and lifestyle factors in a representative adolescent population.The study was carried out in central and ten districts located around Kayseri Province, Central Anatolia. A total of 790 adolescents aged from 12 to 19 years were selected systematically from the schools. Criteria of MetS were modified from Adult Treatment Panel III: (1) waist circumference > 90th percentile (aged between 12 and 17 years) and >102 cm in male, >88 cm in female (for aged 18 and 19 years), (2) serum triglycerides [≥136 mg/dl (aged between 12 and 16 years) and ≥150 mg/dl (for 17 and 19 years)], (3) high-density lipoprotein cholesterol [≤40 mg/dl (males) and ≤50 mg/dl (females)], (4) systolic blood pressure ≥ 95th percentile for gender, age and height, (5) insulin resistance HOMA index < 3.16. Multivariate regression model was performed to search for the association between MetS and demographic and lifestyle factors including gender, age, body mass index, settlement, socioeconomic class, smoking habit, physical activity and family history for diseases (cardiovascular diseases and diabetes mellitus).The overall prevalence of MetS was found as 10.8%. The prevalence was significantly higher in males than in females (13.5 and 8.6%, respectively). Low high-density lipoprotein cholesterol and insulin resistance were the most common criteria of the syndrome. According to the analysis, only gender and high socioeconomic class were weak-positive related factors with MetS.High prevalence of MetS especially among overweight and obese adolescents is a serious health problem. Early identification of the syndrome would contribute greatly to the prevention of diabetes and cardiovascular diseases in youth.
Keywords: Metabolic syndrome; Insulin resistance; High-density lipoprotein cholesterol; Adolescents

Prevention of oxidative DNA damage in inner organs and lymphocytes of rats by green tea extract by Nina Kager; Franziska Ferk; Michael Kundi; Karl-Heinz Wagner; Miroslav Mišík; Siegfried Knasmüller (227-234).
Consumption of green tea (GT) is associated with decreased incidences of specific forms of cancer in humans and it was postulated that its antioxidant (AO) properties may account for these effects. The evidence for AO effects of GT is mainly based on the results from in vitro experiments and on animal studies in which protection against chemically induced damage was monitored.The goal of the study was the investigation of the prevention of strand breaks and DNA migration attributable to endogenous oxidation of bases by GT extract (GTE) in inner organs and lymphocytes of untreated rats. In addition, immunological parameters and biochemical markers were monitored.DNA migration was measured in hepatocytes, colonocytes and lymphocytes after consumption of a low (1.3 mg/kg bw per day, 5 days) and a high dose (6.5 mg/kg bw per day, 5 days) of GTE in COMET assays (n = 5 animals per group). In addition, immunological parameters (TNF-α, IFN-γ, IL-4 and IL-10), the total AO capacity and oxidized low-density lipoproteins were determined in plasma.No evidence for reduction in DNA damage was found with a lower dose, whereas with the higher dose, reduction in DNA migration attributable to formamidopyrimidine-DNA-glycosylase sensitive lesions (oxidized purines) and endonuclease III-sensitive sites (oxidized pyrimidines) (58 and 73%) was observed in lymphocytes; also, in colonocytes (reduction in FPG-sensitive sites by 46%) and hepatocytes (decrease in Endo III-sensitive sites by 74%) protective effects were found, while none of the other parameters was altered.Our results show that a dose of GTE, which is equivalent to consumption of 500 ml GT/p/day in humans protects lymphocytes and to a lesser extent inner organs against oxidative DNA damage, while no effect was seen with a lower dose corresponding to an uptake of 100 ml/p/day.
Keywords: Green tea; Single-cell gel electrophoresis assay; Oxidative DNA damage; Biochemical parameters; Immunological parameters

Long chain saturated fatty acids increase haptoglobin gene expression in C57BL/6J mice adipose tissue and 3T3-L1 cells by Allain Amador Bueno; Lila Missae Oyama; Caio Sussumu de Macedo Motoyama; Carolina Rodrigues da Silva Biz; Vera Lucia Silveira; Eliane Beraldi Ribeiro; Cláudia Maria Oller do Nascimento (235-241).
Dietary lipids are directly related to the composition of adipose tissue, aetiology of obesity and arousal of obesity-related pathologies, like chronic inflammation states. Haptoglobin is an acute phase protein secreted by the liver and white adipose tissue, and its blood levels vary according to the volume of fat in the body.To investigate the effect of diets enriched with large amounts of dietary fats, which differ in their fatty acid composition, on the haptoglobin gene expression by visceral and subcutaneous adipose tissue of mice fed for 2 days or 8 weeks. 3T3-L1 cells were treated with fatty acids that are found in those types of dietary fats.Mice were treated acutely (for 2 days) or chronically (for 8 weeks) with diets enriched with soybean oil, fish oil, coconut oil or lard. 3T3-L1 cells were treated with six different fatty acids. Haptoglobin gene expression was quantified by northern blotting.Both chronic and acute treatment with lard, which is rich in long chain saturated fatty acids, increased the haptoglobin mRNA expression in the retroperitoneal and epidydimal white adipose tissues. Chronic treatment with coconut oil, which is rich in medium chain saturated fatty acids, increased the haptoglobin expression in the epidydimal and subcutaneous depots. In 3T3-L1, palmitic acid increased the haptoglobin gene expression.The type of lipids in the diet can differently modulate the white adipose tissue gene expression of haptoglobin, and saturated fatty acids play a major role in promoting a pro-inflammatory environment. This response is fat pad specific and dependant on the duration of treatment.
Keywords: White adipose tissue; Haptoglobin; High fat diet; Palmitic acid; Lauric acid

Suppressive effects of the marine carotenoids, fucoxanthin and fucoxanthinol on triglyceride absorption in lymph duct-cannulated rats by Megumi Matsumoto; Masashi Hosokawa; Noriko Matsukawa; Masahito Hagio; Aki Shinoki; Megumi Nishimukai; Kazuo Miyashita; Takaji Yajima; Hiroshi Hara (243-249).
Fucoxanthin isolated from edible seaweeds and its metabolite fucoxanthinol have been recently found to have anti-obesity effects, but the mechanism is not fully understood.We investigated the effects of these carotenoids on the absorption of triglycerides in conscious rats implanted with cannulae into a lymph duct and the portal or jugular vein.A duodenal infusion of 1 ml of test oil emulsion with or without 2 mg of fucoxanthin or fucoxanthinol was administered in the lymph duct and the portal (Experiment 1) or the jugular vein (Experiment 2) cannulated rats. The test oil contained 10% soybean oil (Experiment 1) and pre-digested 10% soybean oil (Experiment 2). The inhibitory activities of these carotenoids on pancreatic lipase activity were measured in vitro.Increases in lymphatic and blood triglyceride levels were much lower in the two carotenoid-treated groups than in the carotenoid-free group, indicating that these carotenoids inhibit triglyceride absorption. The total amounts of triglycerides released into the lymph after 4 h in the carotenoid-free, fucoxanthin and fucoxanthinol groups were 113.5, 59.4 and 53.1 μmol, respectively. The inhibitory effects of carotenoids were completely abolished after an infusion of pre-digested soybean oil containing carotenoids. Furthermore, these carotenoids inhibited pancreatic lipase activity in vitro. Regarding absorptive route, we found that fucoxanthinol, but not fucoxanthin, appeared in lymph fluid, whereas neither carotenoid was detected in portal blood.These results show that these two marine carotenoids inhibit lipase activity in the gastrointestinal lumen and suppress triglyceride absorption, and fucoxanthin was converted to fucoxanthinol in the intestine and released into the lymph.
Keywords: Fucoxanthin; Fucoxanthinol; Lipase; Lymph cannulation; Triglyceride

Two prolamin peptides from durum wheat preclude celiac disease-specific T cell activation by gluten proteins by Massimo De Vincenzi; Olimpia Vincentini; Giovanni Di Nardo; Monica Boirivant; Laura Gazza; Norberto Pogna (251-255).
Celiac disease (CD) is a permanent intolerance to wheat prolamins and related proteins displayed by genetically susceptible individuals. Blocking or modulation of CD-specific T cell response by altered prolamin peptides are currently considered as a potential alternative to the only effective therapy of CD based on a life-long gluten-free diet. Two prolamin peptides, the 9-mer ASRVAPGQQ and the 10-mer GTVGVAPGQQ sequences, were identified by mass spectrometry in the peptic/tryptic digest of prolamins (PTP) from durum wheat (Triticum turgidum ssp. durum) cv. Adamello, and investigated for their ability to preclude the stimulation of CD-specific mucosal T cells by gluten proteins.Gluten-specific polyclonal intestinal T cell lines from five CD children (mean age 5 years) were exposed to 50 μg/ml of a deamidated PTP from whole flour of common wheat (T. aestivum) cv. San Pastore, and tested for proliferation and production of interferon-γ (INF-γ) and interleukin 10 (IL-10). The same experiment was performed in the presence of 20 μg/ml of the 9-mer or the 10-mer peptide.T cells exposed to PTP showed a threefold increase in proliferation and INF-γ production, and a significant (P ≤ 0.05) reduction in IL-10 secretion as compared with control cells incubated with the culture medium. Addition of either the 9-mer or the 10-mer peptide to PTP downregulated T cell proliferation and INF-γ production, and caused a significant (P ≤ 0.05) increase in IL-10 secretion.The T cell reactivity elicited by PTP is precluded by both the 9-mer and the 10-mer sequence, suggesting that over-expression of these proteolytically stable peptides may result in a wheat flour with reduced toxicity for CD patients.
Keywords: Celiac disease; Durum wheat; Peptides; Prolamins; T cells