IMMUN JUNIOR LITERATURE REPORRT

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Literature Report Summaries of recent studies

Nutritional effects of micronutrients (vitamins, minerals, trace elements, phytonutrients) on the immune system


Introduction The­immune­system­is­a­complex­system­serving­the­body­to­defend­itself­against­pathogens­and­to­ destroy­cells­that­the­immune­system­recognizes­as­being­defective­and­thus­avert­danger. For­maintaining­its­functions,­the­immune­system­needs­an­adequate­supply­of­micronutrients,­such­­ as­vitamins,­trace­elements­and­phytonutrients. Normally­the­diet­will­ensure­that­these­substances­are­supplied­to­the­level­required­by­the­immune­ system,­e.g.­by­a­sufficient­intake­of­micronutrients­which­are­capable­of­influencing­the­immune­ response.­ If­the­immune­system­is­exposed­to­unusual­stress,­such­as­recurrent­infections,­the­body­has­an­in-­ creased­need­for­micronutrients.­Often­the­standard­diet­can­no­longer­cover­that­need,­and­in­order­­ to­ensure­adequate­amounts­of­micronutrients,­the­substances­lacking­can­be­supplied­to­the­body­by­ supplementing­the­standard­diet­with­an­immune-specific­micronutrient­combination. Micronutrients­(vitamins,­trace­elements,­phytonutrients)­play­a­crucial­role­in­a­functioning­immune­ system.­We­know­that­an­increased­intake­of,­e.g.,­vitamins­C­and­E,­phytonutrients­(carotenoids,­bio-­ flavonoids)­as­well­as­zinc­and­selenium­will­support­the­immune­cell­function.­


Antioxidant responses in children with acute pneumonia Oxidative stress and enzymic-non-enzymic antioxidant responses in children with acute pneumonia Cemek M, Caksen H, Bayiroglu F, et al. Cell Biochem Funct 2006;24:269-273.

Study design, patients and method The aim of this retrospective observational study was to investigate the oxidative stress and the enzymatic and non-enzymatic antioxidant status in children with acute pneumonia. 28 children with acute pneumonia, age 2 to 11 (patient group), and 29 healthy children, age 2 to 12 (control group), were included in the study. Whole blood malondialdehyde (MDA) and reduced gluthanione (GSH), serum beta-carotene, retinol, vitamin C, vitamin E, ceruloplasmin (CLP) and total bilirubin, erythrocyte superoxide dismutase (SOD) and gluthanione peroxidase (GPx) were measured. Results The difference between the groups was statistically significant for all parameters. The MDA, CLP and total bilirubin levels were higher in the patient group than they were in the control group. The SOD, GPx, beta-carotene, retinol, vitamin C, vitamin E and GSH levels were lower in the patient group compared to the control group. All activities of the antioxidant vitamins were decreased in the children with acute pneumonia. Conclusion The study has shown that the oxidative stress is increased in children with acute pneumonia. Serum and erythrocyte enzymatic and non-enzymatic antioxidative capacity is significantly reduced, whereas whole blood lipid oxidation products are increased. There is a discussion about the imbalance between oxidants and antioxidants and the role oxidative stress may play in inflammatory processes.


Acute bronchiolitis in infants: serum selenium levels and lipid peroxidation Relationship among serum selenium levels, lipid peroxidation, and acute bronchiolitis in infancy Gurkan F, Atamer, Y, Ece A, et al. Biol Trace Elem Res 2004;100(2):97-104.

Study design, patients and method In this case control study the potential relationship between the serum levels of malondialdehyde (MDA*) and selenium (Se) and the severity of acute bronchiolitis in infants was investigated. Thirtyfour children with acute bronchiolitis (average age 9 months) and, as control group, 25 age-matched healthy children (average age 11.5 months) were included in the study. At the start of the study and after 2 months serum MDA and selenium levels were measured. Results The MDA levels were significantly higher in children with acute bronchiolitis (4.2 ± 2.5 nmol/L) as compared to the postbronchiolitis stage (1.4 ± 0.8 nmol/L) and compared to the control group (0.7 ± 0.2 nmol/L; p<0.001). In the acute stage the patients had lower selenium levels than two months later (31.7 ± 28.9 pg/L vs. 68.4 ± 26.4 pg/L; p<0.05). Both parameters were significantly lower than in the control group (145.0 ± 21.9 pg/L; p<0.001). MDA and selenium levels in the patient group were negatively correlated (p<0.001). Conclusion In summary, the higher MDA levels and the impaired selenium status indicated a potential relationship of these parameters with the pathogenesis of acute bronchiolitis. An antioxidant selenium supplementation may therefore have a beneficial effect on children with bronchiolitis. * MDA: marker of oxidative stress


Antioxidant vitamins and selected trace elements in chronic rhinosinusitis Serum levels of antioxidant vitamins, copper, zinc and magnesium in children with chronic rhinosinusitis Ăœnal M, Tamer L, Pata YS, et al. J Trace Elem Med Biol 2004;18:189-192

Study design, patients and method In this retrospective observational study the serum levels of antioxidant vitamins and mineral substances in 24 children (age 7 – 12; 14 boys and 10 girls) with chronic rhinosinusitis were measured and compared with 20 healthy children matched for age and gender. Blood samples were taken in the morning before breakfast and before any medication. The serum vitamin A, E and C levels were determined by liquid chromatography (HPLC), copper, zinc and magnesium levels by means of atomic absorption spectrometry. Results Vitamin E, vitamin C, copper and zinc levels were significantly lower in the patient group vs. the control group (there were no differences between the groups for vitamin A and magnesium). Conclusion The authors conclude that the levels of antioxidant vitamins and mineral substances may play a role in the pathogenesis and treatment of chronic rhinosinusitis in children.


Meta-analysis: prevention of childhood diarrhoea and respiratory diseases with zinc Role of zinc administration in prevention of childhood diarrhea and respiratory illnesses: A meta-analysis Aggarwal R, Sentz J, Miller MA. Pediatrics 2007;119:1120-1130.

Study design, patients and method This meta-analysis includes the data of 17 studies with a total of 7,659 children who were given either a zinc supplement or placebo. Only randomised, controlled, blinded studies with children under the age of 5 who had taken zinc supplements for at least 3 months were eligible for the analysis. Results Compared to the placebo group, the risk of diarrhoea and respiratory tract infections of the children who had been given zinc supplements was reduced by 14% (rate ratio: 0.86) and 8% (rate ratio: 0.92), respectively, the risk of severe diarrhoea or dysentery by 15% (rate ratio: 0.85), and the risk of persistent diarrhoea by 25% (rate ratio: 0.75). In addition, the risk of developing respiratory tract infections or pneumonia was 20% (rate ratio: 0.80) lower in the supplement group. Moreover, the total number of days with illness due to diarrhoea dropped significantly by 14% (rate ratio: 0.86). Conclusion Zinc supplementation reduces significantly the frequency and severity of respiratory illnesses and diarrhoea as well as the duration of diarrhoeal morbidity.


Otitis media with effusion: role of oxygen radicals The role of free oxygen radicals on the development of otitis media with effusion Yariktas M, Doner F, Dogru H, et al. Int J Pediatr Otorhinolaryngol 2004;68:889-894.

Study design, patients and method The purpose of this retrospective observational study was to determine if free oxygen radicals (FORs) and antioxidant enzyme activities play a role in the pathogenesis of otitis media with effusion (OME) in children with adenoid hyperplasia. Seventy-four subjects, subdivided into three groups, were enrolled in the study: 26 patients who had adenoidectomy with ventilation tube placement due to chronic OME (group 1), 28 age-matched patients who had adenoidectomy without ventilation tube insertion (group 2), and 20 healthy controls (group 3). Erythrocyte malondialdehyde levels (MDA), superoxide dismutase (SOD), catalase (CAT) and gluthanione peroxidase (GHS-Px) enzyme activities were measured in venous blood. Results Erythrocyte MDA levels and GSH-Px enzyme activity in group 1 were significantly higher than in groups 2 and 3 (p<0.05). SOD enzyme activity in group 1 was significantly lower than in group 2 (p<0.05). CAT enzyme activity was significantly lower in group 1 than it was in group 3 (p<0.05). Conclusion Otitis media increases the FOR levels in erythrocytes. FOR levels are normally maintained at a stable level by antioxidant enzymes. When the antioxidant defense level is weakened, the increased FORs may contribute to the development or OME. The authors suggest that the antioxidant vitamins C and E as well as the radical scavenger enzymes, such as CAT, SOD and GSH-Px, may be considered in the treatment of OME.


Antixodiant status in asthmatic children Evaluation of the serum antioxidant status in asthmatic children Liao M-F, Chen C-C, Hsu M-H. Acta Paediatr Tw 2004;45:213-217.

Study design, patients and method In this case control study, serum total antioxidant status (TAS) and antioxidant enzyme activities (SOD - superoxide dismutase, GPx / gluthanione peroxidase) were measured in asthmatic children. Forty-six asthmatic children 5 to 9 years old (patient group) and 52 healthy* children 6 to 9 years old (control group) were enrolled in the study. Results In the asthmatic children, TAS levels were significantly lower than in the control group. GPx levels were markedly lower than they were in the control group. Conclusion The results show that in asthmatic children the oxidative stress is increased and the antioxidant capacities are altered. * healthy meaning free of allergic or hypersensitive diseases / no family history or genetic predisposition


Asthmatic children exposed to high levels of ozone: antioxidant supplementation Antioxidant supplementation and nasal inflammatory responses among young asthmatics exposed to high levels of ozone Sienra-Monge JJ, Ramirez-Aguilar M, Moreno-Macias H, et al. Clin Exp Immunol 2004;138:317-322.

Study design, patients and method In this randomised, placebo-controlled, double-blind study the effects of antioxidant supplementation on the nasal inflammatory response of asthmatic children to ozone exposure was investigated. 117 children with asthma, residents of Mexico City, were given randomly a daily supplement of vitamins (50 mg of vitamin E and 250 mg of vitamin C) or a placebo. During a 4-month follow-up period three nasal lavages were performed and analysed for content of interleukin–6 (IL-6), IL-8, uric acid and glutathione (GSx). Results During the trial, the 8-hour ozone mean values were between 11.1 and 142.5 ppb (average: 66.2 ppb/m³), for PM they were between 16.6 pg/m³ and 180.9 pg/m³ (average: 77.3 pg/m³). IL-6 levels in the nasal lavage after ozone exposure were significantly increased in the placebo group, whereas in the supplement group no increase was observed. The difference in the response to ozone exposure between the two groups was significant (p = 0.02). GSx levels were reduced significantly in both groups, uric acid decreased slightly in the placebo group. Conclusion In the authors’ view the data suggest that vitamin C and E supplementation in children with asthma and low vitamin E intake may provide some protection against acute inflammatory response to ozone.


Air pollution in children with asthma: marker breath malondialdehyde Exhaled breath malondialdehyde as a marker of effect of exposure to air pollution in children with asthma Romieu I, Barraza-Villarreal A, Escamilla-NuĂąez C. J Allergy Clin Immunol 2008;121:903-909.

Study design, patients and method The panel study evaluated the exposure to traffic-related pollution of children with asthma using the exhaled breath condensate (EBC) malondialdehyde as a biomarker. 107 asthmatic children from a hospital for allergic patients living in two densely populated parts of Mexico City with heavy traffic were enrolled in the study. The children’s breath condensate was collected over a period of 8 weeks and spirometry and nasal lavages were performed in the clinic every two weeks. Results Altogether malondialdehyde was found in 480 samples at a median level of 18.7 nmol (interquartile range/IQR: 12.4-28.7). Ambient particulates (PM2) and ozone on the day of sampling were significantly associated with higher malondialdehyde levels. An increase in the 8-hour average for PM2 by 14.2 pg/m³ (IQR) was associated with an increase in malondialdehyde levels by 1.12 nmol, an increase in the 8-hour average for ozone by 15.9 ppb (IQR) was associated with an increase in malondialdehyde levels by 1.16 nmol. The malondialdehyde levels were inversely correlated with forced vital capacity (FVC*) and forced expiratory volume (FEV1**) and positively correlated with IL-8 levels in nasal lavage. Conclusion The authors concluded that exhaled breath malondialdehyde was related to exposure to air pollution and changes in pulmonary function and inflammatory markers. * FVC: Forced vital capacity: the volume of air that can forcibly be blown out after full inspiration ** FEV1: Forced expiratory volume (1 second): the volume of air that can maximally be exhaled in 1 second


Vitamin D in childhood and adolescence Vitamin D in childhood and adolescence Cashman KD. Postgrad Med J 2007;83(978):230-5.

Study design, patients and method This review is a summary of studies made by authors dealing with the prevalence and likely causes of a poor vitamin D status in children and adolescents. Whereas it is well established that prolonged and severe vitamin D deficiency leads to rickets, the effects, especially the non-skeletal effects, of a less severe vitamin D deficiency on health are not entirely clear. Recent studies suggest that a low vitamin D status (serum 25-OH vitamin D levels <50 nmol/l) may contribute to the development of various chronic diseases (including cardiovascular disease, hypertension, diabetes mellitus and certain forms of cancer). Results A number of recent studies have shown that especially adolescents have a high prevalence of low vitamin D status during the winter and a lower prevalence in the summer. The reasons for the high prevalence in adolescents are unclear. Conclusion The author concludes that vitamin D supplementation is an important option with regard to improving the vitamin D status in childhood and adolescence, especially in the winter.


EsKiMo – Selected results EsKiMo Ernährungsstudie als KiGGS*-Modul. Ernährung 2007;1(9):405-9.

Study design, patients and method In this review article selected results of EsKiMo (Nutrition Study as KiGGS Module) are presented. The study covered the eating habits of the 6-17 year old children/adolescents in Germany from January to December 2006. Of the 17,641 children and adolescents interviewed within the scope of KiGGS, 2506 participated in EsKiMo. Together with their parents, the 6-11 year old children kept a nutrition protocol for three days, and a standardised nutrition interview was conducted with the 12–17 year old adolescents. There were 1,234 nutrition protocols (of the 6–11 year old children) and 1,272 interviews (of the 12–17 year old adolescents) available for evaluation. Results All subjects consumed too little food of plant origin (especially vegetables, bread, potatoes). Only very few children and slightly more adolescents reached the amount of fruits and vegetables recommended for the optimised mixed diet. With rising age the consumption of high-fat and high-protein food of animal origin increased. High-fiber food was eaten in rather insufficient and sweets in excessive amounts. The share of carbohydrates and fats in the energy supply complied with the reference levels as a rule, average protein intake was far above the reference levels in all age groups. For girls, folate, vitamin D and iron supply was below the D-A-CH reference levels. Moreover, the median intake of calcium and vitamins A and E of the 6–11 year old children was inadequate. Conclusion In order to improve the nutrient supply of children and adolescents in Germany, the authors of the EsKiMo Study recommend a higher consumption of phytogenic food, especially vegetables, bread and potatoes. Additional measures for the improvement of the folic acid supply are to be taken. Due to the low vitamin D intake with the diet, it is emphasised how important it is to give infants vitamin D preventively and to ensure that children and adolescents spend sufficient time outdoors. Generally, in the diet preference should be given to whole-grain products, low-fat dairy products, sausages and meat with reduced fat content, and as far as fats and oils are concerned to rapeseed oil, if possible. * KiGGS: nationwide representative survey of the health of children and adolescents performed by the Robert Koch Institute and the Paderborn Unviersity. EsKiMo was funded by the Federal Ministry of Food, Agriculture and Consumer Protection.


Antioxidant status in obese children with multimetabolic syndrome Reduced antioxidant status in obese children with multimetabolic syndrome Molnár D, Decsi T, Koletzko B. Int J Obes 2004;28:1197-1202.

Study design, patients and method This retrospective observational study dealt with the question whether decreased levels of antioxidant vitamins and reduced antioxidant capacity were typical of obese children with multimetabolic syndrome (MMS). The levels of fat-soluble antioxidant vitamins and the total antioxidant status (TAS) of altogether 48 children were measured: 16 controls (age: 16.2 ± 1.1 years, BMI: 20.7 ± 1.9 kg/m², body fat (BF) 25.6 ± 5.7%), 15 obese children with MMS (age: 13.4 ± 2.1 years, BMI 34.2 ± 3.1 kg/m², BF: 36.9 ± 5.8%), and 17 obese children without MMS (age: 14.4 ± 2.3 years, BMI 30.4 ± 6.2 kg/m², BF 36.3 ± 5.8 %) were included in the trial. Results The plasma alpha-tocopherol and beta-carotene levels (corrected for the plasma lipids cholesterol and triglycerides) were significantly lower in the obese children with MMS (2.4 pmol/mmol and 12.3 pmol/mmol; p<0.05) than they were in the obese children without MMS (3.7 pmol/mmol and 48.2 pmol/mmol) and in the controls (3.8 pmol/mmol and 86.6 pmol/mmol). The plasma TAS levels of the children with MMS were also significantly reduced (1.2 mmol/I; p<0.05) as compared to the obese children without MMS (1.62 mmol/l) and the control group (1.58 mmol/l). Conclusion The authors conclude that obese children with MMS are prone to oxidative stress. These children may benefit from vitamin E and beta-carotene supplementation.


Low vitamin B12 levels in obese children and adolescents Obese children and adolescents: A risk group for low vitamin B12 concentration Pinhas-Hamiel O, Doron-Panush N, Reichman B, et al. Arch Pediatr Adolesc Med. 2006;160:933-936.

Study design, patients and method In this prospective descriptive study, the vitamin B12 concentrations of 392 children and adolescents were measured. The subjects were subdivided into a normal-weight group (BMI < 95 percentile) and an obese group. Results In the normal-weight children serum vitamin B12 levels were 530 pg/mL and in the obese children they were 400 pg/mL (p<0.001). Low B12 levels were measured in 10.4 % of the obese children but only in 2.2% of the normal-weight children (p<0.01). Vitamin B12 deficiency was observed in 12 children, i.e. in 8 (4.9%) of the obese and 4 (1.8%) of the normal-weight group (p=0.08). After adjustment for age and gender, obesity was associated with a 4.3-fold risk for low serum B12 levels. Conclusion Obesity in children and adolescents was associated with an increased risk of low B12 levels. The authors recommend that the dietary assessment of obese children should include an estimation of the intake of vitamin B12 and other micronutrients.


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