title: Predictive 5-year survivorship model of cystic fibrosis. Oral DHA supplementation in DeltaF508 homozygous cystic fibrosis patients. Effect of linoleic acid intake on growth of infants with cystic fibrosis. Improved antioxidant and fatty acid status of patients with cystic fibrosis after antioxidant supplementation is linked to improved lung function. The Method Quality of Cross-Over Studies Involved in Cochrane Systematic Reviews Effect of an organized lipid matrix on lipid absorption and clinical outcomes in patients with cystic fibrosis. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials Zinc Supplementation for One Year Among Children with Cystic Fibrosis Does Not Decrease Pulmonary Infection Oral magnesium supplementation in children with cystic fibrosis improves clinical and functional variables: a double-blind, randomized, placebo-controlled crossover trial. Effect of Oral Lipid Matrix Supplement on Fat Absorption in Cystic Fibrosis: A Randomized Placebo-Controlled Trial Bioavailability and safety of a high dose of docosahexaenoic acid triacylglycerol of algal origin in cystic fibrosis patients: a randomized, controlled study. Dietary supplementation with multiple micronutrients: no beneficial effects in pediatric cystic fibrosis patients. Eicosapentaenoic acid in cystic fibrosis: evidence of a pathogenetic role for leukotriene B4 The absorption and effect of dietary supplementation with omega-3 fatty acids on serum leukotriene B4 in patients with cystic fibrosis. Effects of an Antioxidant‐enriched Multivitamin in Cystic Fibrosis. A Randomized, Controlled, Multicenter Clinical Trial A randomized placebo-controlled study on high-dose oral algal docosahexaenoic acid supplementation in children with cystic fibrosis. Energy Supplements Rich in Linoleic Acid Improve Body Weight and Essential Fatty Acid Status of Cystic Fibrosis Patients Biological effects of a dietary omega-3 polyunsaturated fatty acids supplementation in cystic fibrosis patients: a randomized, crossover placebo-controlled trial. Abnormal intracellular lipid processing contributes to fat malabsorption in cystic fibrosis patients. The clinical benefits of long-term supplementation with omega-3 fatty acids in cystic fibrosis patients - A pilot study. Fatty acids composition of plasma phospholipids and triglycerides in children with cystic fibrosis. The effect of dietary supplementation with an olive and soybean oils mixture. Oral absorption of omega-3 fatty acids in patients with cystic fibrosis who have pancreatic insufficiency and in healthy control subjects. Effects of β-carotene supplementation for six months on clinical and laboratory parameters in patients with cystic fibrosis Supplementation With Fatty Acids Influences the Airway Nitric Oxide and Inflammatory Markers in Patients With Cystic Fibrosis
abstract: The objective of this study was to create a 5-year survivorship model to identify key clinical features of cystic fibrosis . Such a model could help research ers and clinicians to evaluate therapies , improve the design of prospect i ve studies , monitor practice patterns , counsel individual patients , and determine the best c and i date s for lung transplantation . The authors used information from the Cystic Fibrosis Foundation Patient Registry ( CFFPR ) , which has collected longitudinal data on approximately 90 % of cystic fibrosis patients diagnosed in the United States since 1986 . They developed multivariate logistic regression models by using data on 5,820 patients r and omly selected from 11,630 in the CFFPR in 1993 . Models were tested for goodness of fit and were vali date d for the remaining 5,810 patients for 1993 . The vali date d 5-year survivorship model included age , forced expiratory volume in 1 second as a percentage of predicted normal , gender , weight-for-age z score , pancreatic sufficiency , diabetes mellitus , Staphylococcus aureus infection , Burkerholderia cepacia infection , and annual number of acute pulmonary exacerbations . The model provides insights into the complex nature of cystic fibrosis and supplies a rigorous tool for clinical practice and research AIM The aim of this study was to evaluate whether the previously observed changes in the fatty acid profile , as a result of DHA supplementation , could be maintained during longer study trials and to observe its effect on the clinical outcome of cystic fibrosis ( CF ) patients . METHOD A year-long double-blind placebo-controlled study was performed in DeltaF508 homozygous CF patients above the age of 6 . Clinical data , including pulmonary function and number of infections , were collected . Blood for the determination of the fatty acid ( FA ) composition of serum phospholipid , vitamin E , liver enzymes , immunoglobulins , erythrocyte sedimentation rate and coagulation was drawn at the beginning and then every 6 months after the start of the study . RESULTS Seventeen patients were included ; one dropped out . The treatment group was supplemented with an algal DHA-rich oil and the control group with sunflower seed oil . There was no difference between the control and treatment groups for W/H% , caloric intake , FEV1 % and FVC% at the start of the study and after 1 year of supplements . The phospholipid FA composition did not change in the control group . The treatment group had a significant increase in DHA and eicosapentaenoic acid ( EPA ) concentration . A concomitant decrease of dihomo-gammalinolenic acid , arachidonic acid , 22:5 n-6 and Mead acid was observed . The laboratory results showed no changes in vitamin E level , liver enzymes , albumin , erythrocyte sedimentation rate and IgG concentration in either the placebo or the intervention group . CONCLUSION Although DHA-rich oil shifted the serum phospholipid FAs to a less pro-inflammatory profile , no conclusive clinical improvement could be observed so far Essential fatty acid deficiency as a result of inadequate linoleic acid impairs growth in healthy infants and is common in infants with malabsorption due to cystic fibrosis ( CF ) . We investigated the effect of dietary linoleic acid intake on the growth of infants with CF . In this study , predigested formula preparations A and B , with linoleic acid contents of 12 % and 7 % of energy , respectively , were fed before and after 1989 to infants enrolled in the evaluation and treatment protocol of the Wisconsin CF Neonatal Screening Project . Outcome was assessed from height-for-age ( HAZ ) and weight-for-age ( WAZ ) Z scores on follow-up exams during the first year . Baseline characteristics did not differ significantly between groups A ( n = 43 ) and B ( n = 33 ) . At diagnosis , 53 % of the enrolled infants ( n = 76 ) showed low plasma linoleic acid concentrations and 22 % had a high ratio of triene to tetraene . After correcting for the effect of potentially confounding variables , we found that HAZ ( by .27 , P < 0.05 ) and WAZ ( by 0.26 , P = 0.081 ) were higher in group A than in group B. This occurred despite a significantly higher energy intake in group B. This difference was most pronounced between 6 and 9 mo of age . Our results suggest that a high linoleic acid content in formula benefits infants with CF because it optimizes nutrition , growth , and feeding efficiency BACKGROUND Oxidative stress , as measured by 8-iso-prostagl and in F(2)(alpha ) ( 8-iso-PGF(2)(alpha ) ) , and depleted antioxidant defenses were shown in stable cystic fibrosis ( CF ) patients . The plasma fatty acid status of CF patients was linked to oxidative stress after respiratory exacerbations . OBJECTIVE We examined changes in plasma 8-iso-PGF(2)(alpha ) , antioxidant defenses , plasma fatty acid status , and clinical markers result ing from short-term antioxidant supplementation . DESIGN Forty-six CF patients were r and omly assigned to either group A [ low dose of supplement ( 10 mg vitamin E and 500 micro g vitamin A ) ] or group B [ high dose of supplement ( 200 mg vitamin E , 300 mg vitamin C , 25 mg beta-carotene , 90 micro g Se , and 500 micro g vitamin A ) ] . Plasma concentrations of 8-iso-PGF(2)(alpha ) , vitamins E and C , beta-carotene , zinc , selenium , and copper ; plasma fatty acid composition ; erythrocyte glutathione peroxidase ( EC 1.11.1.9 ) and superoxide dismutase ( EC 1.15.1.1 ) activities ; lung function ; and dietary intake were measured before and after 8 wk of supplementation . RESULTS Antioxidant defenses in group B improved , whereas those in group A did not : in groups B and A , the mean ( + /- SEM ) changes ( Delta ) in vitamin E were 10.6 + /- 1.5 and -1.9 + /- 0.9 micro mol/L , respectively ( P < 0.001 ) , (Delta)beta-carotene were 0.1 + /- 0.04 and -0.01 + /- 0.02 micro mol/L , respectively ( P = 0.007 ) , (Delta)selenium were 0.51 + /- 0.10 and -0.09 + /- 0.04 micro mol/L , respectively ( P < 0.001 ) , and (Delta)glutathione peroxidase activity were 1.3 + /- 0.3 and -0.3 + /- 0.6 U/g hemoglobin , respectively ( P = 0.016 ) . There were no significant differences between the groups in Delta8-iso-PGF(2)(alpha ) , (Delta)vitamin C , (Delta)fatty acid composition , (Delta)superoxide dismutase activity , (Delta)lung function , or (Delta)white cell count . Within group B , (Delta)beta-carotene correlated with (Delta)percentage of forced vital capacity ( r = 0.586 , P = 0.005 ) , (Delta)selenium correlated with (Delta)percentage of forced expiratory volume in 1 s ( r = 0.440 , P = 0.046 ) , and (Delta)plasma fatty acid concentrations correlated with (Delta)percentage of forced expiratory volume in 1 s ( r = 0.583 , P = 0.006 ) and Delta8-iso-PGF(2)(alpha ) ( r = 0.538 , P = 0.010 ) . CONCLUSIONS Whereas increased beta-carotene , selenium , and fatty acid concentrations are linked to improved lung function , increased plasma fatty acid concentrations are linked to oxidative stress . If oxidative stress is deemed to be important to the clinical outcome of CF patients , means of reducing oxidative stress while maintaining a high-fat , high-energy diet must be investigated Background It is possible that cross-over studies included in current systematic review s are being inadequately assessed , because the current risk of bias tools do not consider possible biases specific to cross-over design . We performed this study to evaluate whether this was being done in  cross-over studies included in Cochrane  Systematic Review s ( CSRs ) . Methods We search ed the Cochrane Library ( up to 2013 issue 5 ) for CSRs that included at least one cross-over trial . Two authors independently undertook the study selection and data extraction . A r and om sample of the CSRs was selected and we evaluated whether the cross-over trials in these CSRs were assessed according to criteria suggested by the Cochrane h and book . In addition we reassessed the risk of bias of these cross-over trials by a checklist developed form the Cochrane h and book . Results We identified 688 CSRs that included one or more cross-over studies . We chose a r and om sample of 60 CSRs and these included 139 cross-over studies . None of these CSRs undertook a risk of bias assessment specific for cross-over studies . In fact items specific for cross-over studies were seldom considered anywhere in quality assessment of these CSRs . When we reassessed the risk of bias , including the 3 items specific to cross-over trials , of these 139 studies , a low risk of bias was judged for appropriate cross-over design in 110(79 % ) , carry-over effects in 48(34 % ) and for reporting data in all stages of the trial in 114(82 % ) . Assessment of biases in cross-over trials could affect the GRADE assessment of a review ’s findings . Conclusion The current Cochrane risk of bias tool is not adequate to assess cross-over studies . Items specific to cross-over trials leading to potential risk of bias are generally neglected in CSRs . A proposed check list for the evaluation of cross-over trials is provided OBJECTIVES To compare the absorption of a lysophosphatidylcholine , monoglyceride , and fatty acid matrix ( organized lipid matrix , OLM ) with that of a triacylglycerol (TG)-based fat meal in patients with cystic fibrosis ( CF ) . STUDY DESIGN Five adolescents with CF and 3 control patients were given fat meals supplemented with retinyl palmitate of either OLM or TG at a 2-week interval . In a clinical trial , 73 patients with CF were r and omly assigned to nutritional supplements containing either OLM or TG for a 1-year double-blind trial followed by a 6-month observation period . RESULTS The peak increases and areas under the curve for TG and retinyl palmitate after the fat meal were 10-fold higher after OLM than after the TG fat load and did not differ from values obtained in control patients . OLM led to better clinical outcomes in terms of energy intake from the diet , weight-for-age Z score , essential fatty acid status , vitamin E , and retinol binding protein . Height-for-age Z score and FEV(1 ) only reached statistical significance at the end of the 6-month observation period . CONCLUSIONS These results suggest that OLM is a readily absorbable source of fat and energy in CF and is an effective nutritional supplement Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND : Children with cystic fibrosis may have a deficiency of micronutrients , including zinc , which may affect their susceptibility to infections . There is a paucity of data on zinc supplementation among children with cystic fibrosis . We hypothesized that a pharmacologic dose of zinc administered daily for 12 months would reduce the need for antibiotics by 50 % . METHODS : This double-blind r and omized placebo-controlled trial was conducted among children with cystic fibrosis to assess the effect of zinc supplementation on the need for antibiotics and pulmonary function tests .  The children , age 5–15 y , of either sex , received either 30-mg zinc tablets or similar looking placebo tablets daily in addition to st and ard care . They were followed up every month for a period of 12 months and whenever they had pulmonary exacerbations . Their serum zinc was estimated at baseline and at 12 months of enrollment . During each visit , the children underwent a pulmonary function test and sputum culture . RESULTS : Of a total of 43 children screened , 40 were enrolled , and of them , 37 completed the study . The median ( interquartile range ) number of days of the administration of antibiotics over 12 months of follow-up among the children receiving zinc was 42 ( 14–97 ) d. In the placebo group , it was 38 ( 15–70 ) d ( P = .79 ) . There were no significant differences in the percent-of-predicted FEV1 or change in FEV1 values at 12 months ( P = .44 ) . The number of children in whose respiratory specimens Pseudomonas was isolated was similar for the 2 groups at different time intervals . The adverse events reported were similar in the 2 groups . CONCLUSION : We did not find any significant difference in the need for antibiotics , pulmonary function tests , hospitalization , colonization with Pseudomonas , or the need for antibiotics for children with cystic fibrosis receiving zinc supplementation of 30 mg/d BACKGROUND Magnesium is one of the most important minerals in the body . Although some studies reported that patients with cystic fibrosis ( CF ) lack magnesium , no international study has assessed the importance of oral magnesium supplementation in CF patients . OBJECTIVE We prospect ively investigated the long-term effect of oral magnesium supplementation on respiratory muscle strength by using manuvacuometry and the Shwachman-Kulczycki ( SK ) score among children and adolescents with CF . DESIGN This double-blind , r and omized , placebo-controlled crossover study included 44 CF patients ( aged 7 - 19 y ; 20 males ) who were r and omly assigned to receive magnesium ( n = 22 ; 300 mg/d ) or placebo ( n = 22 ) for 8 wk with a 4-wk washout period between trials . All patients were undergoing conventional treatment of CF . The experimental protocol included clinical evaluation , assessment of urinary concentration of magnesium , and manuvacuometric measurements [ maximal inspiratory pressure ( MIP ) and maximal expiratory pressure ( MEP ) ] . MIP was the primary outcome . RESULTS Urinary magnesium increased after the administration of magnesium ( change : 36.38 mg/d after magnesium compared with 0.72 mg/d after placebo ; P < 0.001 ) . Moreover , MIP and MEP significantly improved only after magnesium administration ( change in MIP : 11 % predicted after magnesium compared with 0.5 % predicted after placebo ; change in MEP : 11.9 % predicted after magnesium compared with 0.8 % predicted after placebo ; P < 0.001 for both ) . Magnesium administration had a beneficial effect on clinical variables assessed by the SK score ( change : 4.48 points after magnesium compared with -1.30 points after placebo ; P < 0.001 ) . CONCLUSION Oral magnesium supplementation helped improve both the SK score and respiratory muscle strength in pediatric patients with CF ABSTRACT Pancreatic enzyme therapy does not normalize dietary fat absorption in patients with cystic fibrosis and pancreatic insufficiency . Efficacy of LYM-X-SORB ( LXS ) , an easily absorbable lipid matrix that enhances fat absorption , was evaluated in a 12-month r and omized , double-blinded , placebo-controlled trial with plasma fatty acids ( FA ) and coefficient of fat absorption ( CFA ) outcomes . A total of 110 subjects ( age 10.4 ± 3.0 years ) were r and omized . Total FA increased with LXS at 3 and 12 months ( + 1.58 , + 1.14 mmol/L ) and not with placebo ( P = 0.046 ) . With LXS  , linoleic acid ( LA ) increased at 3 and 12 months ( + 298 , + 175 nmol/mL , P ⩽ 0.046 ) , with a 6 % increase in CFA ( P < 0.01 ) . LA increase was significant in LXS versus placebo ( 445 vs 42 nmol/mL , P = 0.038 ) . Increased FA and LA predicted increased body mass index Z scores . In summary , the LXS  treatment improved dietary fat absorption compared with placebo as indicated by plasma FA and LA and was associated with better growth status OBJECTIVE Several studies have reported omega-3 and omega-6 fatty acid imbalances in patients with cystic fibrosis ( CF ) . Whether these imbalances contribute to or are manifestations of the pathophysiology of CF is unknown . The study objective was to determine bioavailability , tissue accretion , and safety of a large dose of an algal source of docosahexaenoic acid ( DHA ) triacylglycerol and to observe effects on lung function in patients with CF . METHODS Twenty subjects with CF ( 8 to 20 y of age ) were r and omly assigned to receive algal oil providing 50 mg of DHA per kilogram per day ( 1 to 4.2 g of DHA per subject per day ) or placebo for 6 mo . Fatty acids , liver enzymes , and lipid soluble antioxidants were measured in blood at baseline and at 1 , 3 , and 6 mo . Rectal biopsy specimens were collected at baseline and at 3 mo for fatty acid analysis . Lung function , anthropometrics , and adverse experiences were monitored throughout the study . RESULTS Compared with placebo , DHA supplementation increased plasma , erythrocyte , and rectal DHA levels four- to five-fold ( P < 0.001 ) with concomitant decreases in blood arachidonic acid levels and the ratio of arachidonic acid to DHA . Supplementation was well tolerated , with no treatment-related changes in liver enzymes , growth , or antioxidant status . DHA supplementation had no detectable effect on lung function during the course of this study . CONCLUSIONS Algal DHA triacylglycerol oil is readily absorbed , well tolerated , and increases blood and tissue DHA levels in patients with CF . No adverse developments were associated with this large dose of DHA oil . Larger studies of longer duration are needed to determine whether DHA supplementation results in any clinical ly significant benefits in patients with CF BACKGROUND Cystic fibrosis ( CF ) patients are subjected to increased oxidative stress due to chronic pulmonary inflammation and recurrent infections . Additionally , these patients have diminished skeletal muscle performance and exercise capacity . We hypothesize that a mixture of multiple micronutrients could have beneficial effects on pulmonary function and muscle performance . METHODS A double-blind , r and omized , placebo controlled , cross-over trial with a mixture of multiple micronutrients ( ML1 ) was performed in 22 CF patients ( 12.9+/-2.5 yrs ) with predominantly mild lung disease .  Anthropometric measures , pulmonary function , exercise performance by bicycle ergometry , muscular strength and vitamins A and E were determined . RESULTS Analysis was performed using the paired Student t-test comparing the change in each parameter during ML1 and placebo . Plasma vitamin E and A levels increased during ML1 when compared to placebo . However , no significant difference between the effect of the ML1 or placebo was observed neither for FEV1 , FVC , anthropometry , nor for the parameters for muscle performance . CONCLUSIONS The micronutrient mixture was not superior to placebo with respect to changes in pulmonary function or muscle performance in pediatric CF patients , despite a significant increase in plasma vitamin E concentrations Much of the lung damage that limits the life of young adults with cystic fibrosis is due to proteases and oxygen metabolites generated by neutrophils , which are recruited into the airway by the interaction between Pseudomonas aeruginosa and pulmonary macrophages . Leukotriene B4 ( LTB4 ) has been proposed as a local mediator of this process ; its production is susceptible to specific modulation with dietary eicosapentaenoic acid ( EPA ) . We carried out a placebo-controlled trial of EPA ( 2.7 g daily for 6 weeks ) to assess its effects on markers of clinical state , peripheral neutrophil function , and lung inflammation in sixteen patients with cystic fibrosis colonised with P aeruginosa .  EPA was well tolerated and result ed in a significant reduction in sputum volume ( median change with EPA -10 mL/day , placebo 0 ; p = 0.015 ) , and improvements in Schwachman score ( EPA 5 % , placebo 0 ; p = 0.034 ) , forced expiratory volume in 1 s ( EPA 0.25 L , placebo -0.1 L ; p = 0.006 ) , and vital capacity ( EPA 0.6 L , placebo 0 ; p = 0.011 ) . Relative chemotaxis of circulating neutrophils to LTB4 increased from a subnormal baseline of 4 ( median ; range 0 - 10 ) microns/30 min before treatment , to a near normal value of 11 ( 5 - 18 ) microns/30 min after EPA . Relative chemotaxis to LTB4 of patients taking placebo did not change : the difference in response was highly significant ( p = 0.001 ) . Specific reduction of neutrophil chemotaxis to LTB4 is a sensitive assay of chronic in-vivo exposure to LTB4 . Our results suggest that LTB4 has a pathogenetic role in the lung damage of cystic fibrosis . Longer-term clinical trials of EPA are warranted in a larger number of cystic fibrosis patients The substitution of omega-3 ( n-3 ) fatty acids for omega-6 ( n-6 ) fatty acids generates eicosanoids with diminished inflammatory effects . As the lungs of patients with cystic fibrosis ( CF ) are in a state of chronic inflammation in which increased amounts of eicosanoids are found , n-3 supplementation may reduce this level of inflammation and result in clinical improvement . The absorption and clinical effects of n-3 vs. n-6 fatty acids in CF were measured in a prospect i ve , r and omized , double-blind , crossover study in which 14 patients with CF ( age : 6 - 16 years , mean 10.5 years ; baseline Shwachman-Brasfield scores : 41 - 88 , mean 76.7 ) received 6 weeks of n-3 ethyl ester concentrate from menhaden oil ( 100 - 131 mg/kg/day , mean 112.8 ) or n-6 fatty acids from safflower oil ( 102 - 132 mg/kg/day , mean 113.3 ) , followed by a washout period of 6 weeks , and then 6 weeks of the other supplement . Analysis by gas chromatography showed that n-3 supplementation result ed in increased eicosapentaenoic acid ( 20:5n-3 ) in platelet phospholipids , from 0.14 to 2.16 % , P < 0.05 and in increased docosahexaenoic acid ( 22:6n-3 ) , from 1.33 to 3.72 % , P < 0.05 . Clinical effects were evaluated at weeks 0 , 6 , 12 , and 18 , and analyzed for differences among the n-3 , n-6 , and washout periods . No adverse effects were reported or observed . No statistically significant differences were found ( ANOVA , P > 0.05 ) in Shwachman-Brasfield scores , sweat test , weight change , or forced expiratory volume and flow ( FEV1 , FEF25 - 75 % , and FVC ) percentiles . Tumor necrosis factor was not measurable in any serum sample . Serum leukotriene B4 ( LTB4 ) levels were significantly reduced by n-3 fatty acids , mean reduction ( -177 pg/mL ) compared to n-6 fatty acids ( + 63 pg/mL ) P < 0.05 . These results show that both n-3 fatty acids are absorbed and incorporated into platelet phospholipids in patients with CF and reduced serum LTB4 . No significant clinical differences or adverse effects were found Rationale : Cystic fibrosis ( CF ) is characterized by dietary antioxidant deficiencies , which may contribute to an oxidant‐antioxidant imbalance and oxidative stress . Objectives : Evaluate the effects of an oral antioxidant‐enriched multivitamin supplement on antioxidant concentrations , markers of inflammation and oxidative stress , and clinical outcomes . Methods : In this investigator‐initiated , multicenter , r and omized , double‐blind , controlled trial , 73 pancreatic‐insufficient subjects with CF 10 years of age and older with an FEV1 between 40 % and 100 % predicted were r and omized to 16 weeks of an antioxidant‐enriched multivitamin or control multivitamin without antioxidant enrichment . Endpoints included systemic antioxidant concentrations , markers of inflammation and oxidative stress , clinical outcomes ( pulmonary exacerbations , anthropometric measures , pulmonary function ) , safety , and tolerability . Measurements and Main Results : Change in sputum myeloperoxidase concentration over 16 weeks , the primary efficacy endpoint , was not significantly different between the treated and control groups . Systemic antioxidant ( & bgr;‐carotene , coenzyme Q10 , & ggr;‐tocopherol , and lutein ) concentrations significantly increased in the antioxidant‐treated group ( P < 0.001 for each ) , whereas circulating calprotectin and myeloperoxidase decreased in the treated group compared with the control group at Week 4 . The treated group had a lower risk of first pulmonary exacerbation requiring antibiotics than the control group ( adjusted hazard ratio , 0.50 ; P = 0.04 ) . Lung function and growth endpoints did not differ between groups . Adverse events and tolerability were similar between groups . Conclusions : Antioxidant supplementation was safe and well tolerated , result ing in increased systemic antioxidant concentrations and modest reductions in systemic inflammation after 4 weeks . Antioxidant treatment was also associated with a lower risk of first pulmonary exacerbation . Clinical trial registered with www . clinical trials.gov ( NCT01859390 ) Low plasma concentrations of docosahexaenoic acid ( DHA ) are reported in unsupplemented cystic fibrosis ( CF ) patients . Forty-one CF patients aged from 6 to 12 years were r and omized to receive high-dose DHA ( 100 mg/kg/day in the first month and 1 g per day thereafter through a 12-month supplementation ) or placebo ( germ oil ) . Primary outcome was percentage change in plasma AA : DHA ratio . Secondary outcomes were changes in the number of pulmonary exacerbations compared to previous year , lung function , BMI , skinfold thicknesses , and body composition assessed by DXA and in serum concentrations of C-reactive protein , cytokines and vitamin ( α-tocopherol and retinol ) . Compared to the control group plasma AA : DHA ratio decreased in the intervention group after 6 months ( median percentage changes : -73 % in the intervention group vs. -10 % in the control group , P=0.001 ) . No differences were detected between groups for secondary outcomes . Despite a decrease of the AA/DHA ratio  , DHA supplementation for one year did not induce any significant biochemical and clinical improvement in CF patients Background Patients with cystic fibrosis who have steatorrhea frequently are underweight and have essential fatty acid ( EFA ) depletion , which is associated with a poor clinical course . It has been stated that poor EFA status is difficult to correct in patients with cystic fibrosis , and an impaired EFA metabolism with reduced synthesis of long-chain polyunsaturated fatty acids has been proposed . In this study , the effects of an oral energy supplement rich in linoleic acid were investigated in patients with cystic fibrosis who had a body weight below 95 % of normal for height . Methods Thirty-six patients ( 16 girls ) more than 4 years of age were r and omized either to a control group ( n = 20 , age 13.3 ± 3.8 years , mean ± SD ) receiving intensive dietary counseling only , or an intervention group ( n = 16 , age , 10.4 ± 4.3 years ) treated for 3 months with dietary counseling plus 628 ± 254 mL ( = kcal ) per day of an energy supplement rich in fat ( 31 % of energy ) and linoleic acid ( 16 % of energy ) . Results In contrast to the control group , the patients with supplemented diets achieved significant increases of energy intake ( 2189 ± 731 kcal/day vs. 2733 ± 762 kcal/day ) , weight for height ( 82.8 % ± 8.6 % vs. 84.8 % ± 9.6 % of normal ) , and body fat ( 5.1 ± 1.7 kg vs. 5.8 ± 2.2 kg ) as well as the initially low values of plasma phospholipid linoleic acid ( 11.8 % ± 1.1 % vs. 17.6 % ± 1.6 % of total phospholipid fatty acids ) and its main metabolite arachidonic acid ( 4.4 % ± 0.4 % vs. 5.9 % ± 0.3 % ) . Conclusions Patients with cystic fibrosis with low body weight and poor EFA status benefit from EFA-rich energy supplements and can synthesize arachidonic acid from the precursor linoleic acid BACKGROUND AND AIMS Various anti-inflammatory therapies , including dietary omega-3 polyunsaturated fatty acids ( PUFA ) supplementation , have been investigated in cystic fibrosis ( CF ) patients . To further explore this nutritional approach , biological effects of an omega-3 PUFA oral liquid supplementation were measured in 17 CF patients in a double-blind , r and omized , crossover without a washout period and placebo-controlled study . METHODS CF patients ( age : 18+/-9 year ; weight : 43+/-13 kg ) received a liquid dietary supplementation either enriched or not in omega-3 PUFA ( 390 - 1170 mg/day according to patient weight ) during two 6-month periods . RESULTS Increase in eicosapentaenoic acid was observed in neutrophil membrane following omega-3 PUFA dietary supplementation ( from 0.7+/-0.6 to 1.6+/-0.6 micromol% , P<0.01 ) . The leukotriene B(4 ) ( LTB(4))/leukotriene B(5 ) ( LTB(5 ) ) ratio was decreased ( from 72+/-27 to 24+/-7 , P<0.001 ) in CF patients taking omega-3 PUFA supplements . In contrast , omega-3 PUFA supplementation affected neither internalization of IL-8 receptors following IL-8 exposure , nor IL-8-induced neutrophil chemotaxis . CONCLUSION Our results show that omega-3 PUFA are incorporated in neutrophil membranes . The subsequent decrease in LTB(4)/LTB(5 ) ratio suggests that , in such conditions , neutrophils may produce less pro-inflammatory mediators from the acid arachidonic pathway . These data indicate that omega-3 PUFA intake may have anti-inflammatory effect that still need to be assessed by long-term studies following large groups of patients A common feature of cystic fibrosis ( CF ) is the functional derangement of the exocrine pancreas , which affects output of pancreatic lipase . This condition results in severe dietary malabsorption due to the poor hydrolysis of triacylglycerol ( TG ) in the lumen of the small intestine . Despite the benefits of pancreatic enzyme supplements , patients with CF present with persistent intestinal fat malabsorption . The aim of the present investigation was to determine whether defects in the intracellular phase of lipid transport occur in this pathophysiology in addition to the known disturbed digestive processes . Our hypothesis was tested by incubating  intestinal biopsies  from six CF and six healthy subjects with radiolabeled lipid and protein precursors .  Lipid esterification and secretion were markedly decreased by 22 - 31 % and 38 - 42 % , respectively , in CF sample s , as noted by the low incorporation of [(14)C]palmitic acid into TGs , phospholipids , and cholesteryl esters in patients ' duodenal explants and culture media compared with controls ( 100 % ) . Accordingly , the output of TG-rich lipoproteins was substantially reduced ( P < 0.05 ) , and a similar trend was observed for high-density lipoproteins . Because intestinal lipoprotein assembly/secretion shows an absolute requirement for apolipoprotein ( apo ) B-48 , radioactive labeling experiments were performed ; these experiments demonstrated a significantly ( P < 0.05 ) diminished synthesis of apoB-48 ( 40 % ) and apoA-I ( 30 % ) . Given the critical role of microsomal triglyceride transfer protein in the formation of apoB-containing lipoproteins , its activity was determined and not found to be altered in CF intestinal tissue . Together , these results suggest that CF malabsorption may also be caused by defects in mucosal mechanisms leading to abnormal lipoprotein delivery into the blood circulation Effectiveness of omega-3 supplementation in cystic fibrosis ( CF ) remains controversial . This study sought to evaluate clinical status , exercise tolerance , inflammatory parameters , and erythrocyte fatty acid profile after 1 year of oral omega-3 supplementation in CF patients . Fifteen ΔF508-homozygous patients undergoing chronic azithromycin  were r and omized to receive omega-3 fish oil supplementation at a dose of 60mg/Kg/day or placebo . In comparison with the previous year , in the supplemented group , the number of pulmonary exacerbations decreased at 12 months ( 1.7 vs. 3.0 , p<0.01 ) , as did the duration of antibiotic therapy ( 26.5 days vs. 60.0 days , p<0.025 ) . Supplementation significantly increased the levels of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) as early as <3 months of administration , with concomitant decreases in arachidonic acid ( AA ) levels . This pilot study suggests that long-term omega-3 supplementation offers several clinical benefits as to the number of exacerbations and duration of antibiotic therapy in CF patients Cystic fibrosis ( CF ) is characterized by abnormal levels of essential fatty acids ( EFA ) in plasma phospholipids . The reduced availability of EFA has been reported to alter patterns of circulating and tissue esterified acids and may determine profound changes in membrane fluidity and cell signaling mechanisms . In the current study , the results of a new strategy aim ed at the realization of a practical , low cost integrator , for daily use in the dietary management of FC subjects , are reported . We investigated the plasma phospholipids and triglycerides fatty acids composition of CF patients subjected to a dietary supplement constituted of a mixture of 50 % extra virgin olive oil and 50 % soybean oil  and studied the clinical effects of this supplementation . The study included fourteen young subjects , aged between 6 and 15 years , affected by cystic fibrosis , with pancreatic insufficiency and heterozygotes or homozygotes for the delta F508 mutation . The subjects were matched by age and r and omly assigned to either an oil mixture supplemented ( OM ) group ( n = 7 ) , or to a control ( C ) group ( n = 7 ) . In contrast to the control group , the patients with supplemented diet achieved significant increases of the relative amount of C18:1 in the triglycerides as well as a significant decrease in saturated fatty acids ( C 16:0 , C 17:0 , C 18:0 , C 22:0 ) . Moreover , the ratio between LA acid and AA significantly increased in the triglycerides of the OM group . In the phospholipids of the OM group , the relative amount of C 18:1 and of palmitic acid increased significantly whereas the relative amount of the most important polyunsaturated fatty acids ( PUFA ) decreased . These results show that oleic acid can be absorbed and incorporated into the plasma triglycerides of CF patients receiving pancreatic enzymes , whereas poor incorporation of LA occurs . Despite the reduction in the relative amounts of phospholipid PUFA , the supplemented subjects did not reported adverse effects There were no significant differences between groups in the clinical indexes recorded ( height , weight , BMI , Schwachman-Kulczycki score and FEV 1s ) . The results of this study showed that the supplementation with a mixture of extravirgin olive and soybean oil was safe in seven CF patients treated during a 2-months period and no negative clinical effects were evident . However , further clinical trials will be necessary in order to better evaluate the consequence of the observed changes in plasma fatty acids composition in a longer testing period Dietary supplementation with fish oils high in the omega-3 fatty acids , eicosapentaenoic acid and docosahexaenoic acid , may have an antiinflammatory effect . We determined whether patients with cystic fibrosis ( CF ) could incorporate omega-3 fatty acids into their plasma and cell membrane phospholipids without adverse effects . In this double-blind study , 12 patients with pancreatic insufficiency who have CF ( mean age , 12.2 + /- 5.4 ( SD ) years ) and 13 subjects without CF ( mean age , 13.4 + /- 6.3 ( SD ) years ) were r and omly assigned to ingest 8 gm daily of either encapsulated fish oil ( 3.2 gm of eicosapentaenoic acid and 2.2 gm of docosahexaenoic acid daily ) or olive oil ethyl esters for 6 weeks . Two of seven and two of five patients with CF who received fish and olive oils , respectively , and one of eight and none of five subjects without CF discontinued taking the capsules before 6 weeks because of eructation or diarrhea . Significant incorporation of omega-3 fatty acids into plasma and erythrocyte membrane phospholipids was observed in subjects with and those without CF r and omly assigned to the fish oil treatment . For example , in subjects r and omly assigned to receive fish oil , the eicosapentaenoic acid/arachidonic acid ratio in plasma increased 9.8-fold , from 0.04 + /- 0.02 ( mean + /- SEM ) to 0.39 + /- 0.11 ( p = 0.02 ) , in the patients with CF ( n = 7 ) and 23.0-fold , from 0.04 + /- 0.01 to 0.92 + /- 0.17 ( p = 0.001 ) , in the subjects without CF ( n = 8) who received fish oil ( p = 0.02 , patients with CF vs subjects without CF at 6 weeks ) . No clinical ly or statistically significant changes from baseline were observed in platelet aggregation or levels of vitamin E or A in subjects who received fish oil . Future studies are indicated to determine whether omega-3 fatty acid enrichment provides a clinical ly beneficial antiinflammatory effect in patients with CF BACKGROUND Patients with cystic fibrosis ( CF ) have significantly decreased plasma concentrations of nutrient antioxidant vitamins , especially of β-carotene , which is thought to result from fat malabsorption and chronic pulmonary inflammation . The aim of this double blind , placebo controlled study was to investigate the effect of oral β-carotene supplementation for six months on clinical parameters . METHODS Twenty four patients with CF were r and omised to receive β-carotene 1 mg/kg/day ( maximum 50 mg/day ) for three months ( high dose supplementation ) and 10 mg/day for a further three months ( low dose supplementation ) or placebo . At monthly follow up visits the plasma β-carotene concentration , total antioxidant capacity , malondialdehyde ( MDA ) as a marker of lipid peroxidation , and clinical parameters ( Shwachmann-Kulczycki score , body mass index ( BMI ) , height , and lung function ( FEV1 ) ) were assessed . The number of pulmonary exacerbations requiring antibiotic treatment ( in days ) three months before and during the study were evaluated . RESULTS The plasma concentration of β-carotene increased significantly to the normal range during the three months of high dose supplementation ( baseline 0.08 ( 0.04 ) μmol/l to 0.56 ( 0.38 ) μmol/l ; p<0.001 ) but decreased to 0.32 ( 0.19 ) μmol/l in the period of low dose supplementation . Initially raised plasma levels of MDA fell to normal levels and the total antioxidant capacity showed a non-significant trend towards improvement during high dose supplementation . Antibiotic treatment decreased significantly in the supplementation group from 14.5 ( 14.9 ) days/patient during the three months before the study to 9.8 ( 10.3 ) days/patient during high dose supplementation ( p=0.0368 ) and to 10.5 ( 9.9 ) days/patient during low dose supplementation , but increased in the placebo group . The Shwachmann-Kulczycki score , lung function , and BMI did not show any changes in either of the treatment groups . No adverse events were observed during the study period . CONCLUSION Oral β-carotene supplementation in a dose of 1 mg/kg/day only was effective in normalising the plasma concentration of β-carotene and result ed in a decrease in pulmonary exacerbations . These data suggest that patients with CF may benefit clinical ly from supplementation with β-carotene and further studies are warranted Objectives : To obtain a balance in the fatty acid ( FA ) metabolism is important for the inflammatory response and of special importance in cystic fibrosis ( CF ) , which is characterized by impaired FA metabolism , chronic inflammation , and infection in the airways . Nitric oxide ( NO ) has antimicrobial properties and low nasal ( nNO ) and exhaled NO ( FENO ) , commonly reported in CF that may affect bacterial status . The present study investigates the effect of different FA blends on nNO and FENO and immunological markers in patients with CF . Patients and Methods : Forty-three patients with CF and “ severe ” mutations were consecutively enrolled in a r and omized double-blind placebo-controlled study with 3 FA blends containing mainly n-3 or n-6 FA or saturated FA acting as placebo .  FENO , nNO , serum phospholipid concentrations of FA , and biomarkers of inflammation were measured before and after 3 months of supplementation . Results : Thirty-five patients in clinical ly stable condition completed the study . The serum phospholipid FA pattern changed significantly in all 3 groups . An increase of the n-6 FA , arachidonic acid , was associated with a decrease of FENO and nNO . The inflammatory biomarkers , erythrocyte sedimentation rate , and interleukin-8 decreased after supplementation with n-3 FA and erythrocyte sedimentation rate increased after supplementation with n-6 FA . Conclusions : This small pilot study indicated that the composition of dietary n-3 and n-6 FA influenced the inflammatory markers in CF . FENO and nNO were influenced by changes in the arachidonic acid concentration , supporting previous studies suggesting that both the lipid abnormality and the colonization with Pseudomonas influenced NO in the airways
target: The benefits of antioxidants or DHA/EPA supplementation for CF , although observed in some studies , are not consistent enough to recommend routine use of these supplements .
background: Antioxidant micronutrients and essential fatty acids supplementation intake appears to have a protective effect in some diseases such as cardiovascular disease , cancer , and asthma .
  The aim of this study was to perform a systematic review to evaluate the effects of these nutrients on nutritional and clinical outcomes of patients with cystic fibrosis ( CF ) .
  This is a systematic review of r and omized clinical trials ( RCTs ) in CF .