Effect of an organized lipid matrix on lipid absorption and clinical outcomes in patients with cystic fibrosis. Physical exercise training for cystic fibrosis. 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. Bioavailability and safety of a high dose of docosahexaenoic acid triacylglycerol of algal origin in cystic fibrosis patients: a randomized, controlled study. Nutritional Intervention as a Preventive Approach for Cognitive-Related Outcomes in Cognitively Healthy Older Adults: A Systematic Review. 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. Biological effects of a dietary omega-3 polyunsaturated fatty acids supplementation in cystic fibrosis patients: a randomized, crossover placebo-controlled trial. Oral DHA supplementation in DeltaF508 homozygous cystic fibrosis patients. Ursodeoxycholic acid for liver disease associated with cystic fibrosis: a double-blind multicenter trial. The Italian Group for the Study of Ursodeoxycholic Acid in Cystic Fibrosis. Fatty acid supplements improve respiratory, inflammatory and nutritional parameters in adults with cystic fibrosis. Effects of Autogenic Drainage on Sputum Recovery and Pulmonary Function in People with Cystic Fibrosis: A Systematic Review Relationships among nutritional status and skeletal and respiratory muscle function in cystic fibrosis: does early dietary supplementation make a difference? Dietary supplementation with multiple micronutrients: no beneficial effects in pediatric cystic fibrosis patients. The clinical benefits of long-term supplementation with omega-3 fatty acids in cystic fibrosis patients - A pilot study. [Antioxidant micronutrients and chronic degenerative pathology: the role of complementary nutritional doses]. Concordance of randomized and nonrandomized studies was unrelated to translational patterns of two nutrient-disease associations. A randomized controlled trial of a new behavioral home-based nutrition education program, "Eat Well with CF," in adults with cystic fibrosis. Routine Vitamin Supplementation To Prevent Cancer and Cardiovascular Disease: Recommendations and Rationale Bioavailability of a Novel, Water-Soluble Vitamin E Formulation in Malabsorbing Patients Oral absorption of omega-3 fatty acids in patients with cystic fibrosis who have pancreatic insufficiency and in healthy control subjects. The absorption and effect of dietary supplementation with omega-3 fatty acids on serum leukotriene B4 in patients with cystic fibrosis. Effect of a Medium Dose of Ursodeoxycholic Acid with or without Taurine Supplementation on the Nutritional Status of Patients with Cystic Fibrosis: A Randomized, Placebo‐Controlled, Crossover Trial
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 Cystic fibrosis ( CF ) is the most common life-shortening autosomal recessively inherited disease in Caucasian population s [ 2 ] . Progressive respiratory disease in CF results in an abnormal ventilatory response to exercise which contributes to dyspnea and is a major limiting factor to exercise tolerance [ 3 ] . In addition , a sedentary lifestyle contributes to the progression of physical and functional impairment in CF [ 4 ] , likely with the consequence of a reduced life expectancy as exercise capacity is linked to survival [ 5 ] . Exercise has received growing recognition among research ers and clinicians as treatment for chronic disease including CF lung disease [ 6,7 ] . In CF , exercise has the potential to improve airway clearance through a combination of hyperventilation , mechanical vibration , and improved sputum viscoelasticity thereby leading to facilitated and increased sputum expectoration [ 8,9 ] . Regular physical exercise  improves exercise tolerance and slows progressive pulmonary function decline [ 4,10 ] . Until today , much of the knowledge on the effects of physical conditioning in CF originates predominantly from observational or small non-r and omized and non-controlled studies . Therefore , a systematic review of evidence from r and omised controlled trials ( RCTs ) on the effects of regular physical exercise training was required to critically evaluate potential beneficial effects on patient-relevant outcomes in CF 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 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 The link diet-cognitive function/dementia has been largely investigated in observational studies ; however , there was a lack of evidence from r and omized clinical trials ( RCTs ) on the prevention of late-life cognitive disorders though dietary intervention in cognitively healthy older adults . In the present article , we systematic ally review ed RCTs published in the last four years ( 2014 - 2017 ) exploring nutritional intervention efficacy in preventing the onset of late-life cognitive disorders and dementia in cognitively healthy subjects aged 60 years and older using different levels of investigation ( i.e. , dietary pattern changes/medical food/nutraceutical supplementation/multidomain approach and dietary macro- and micronutrient approaches ) as well as possible underlying mechanisms of nutritional prevention . From the 35 included RCTs , there was moderate evidence that intervention through dietary pattern changes , medical food/nutraceutical supplementation , and multidomain approach improved specific cognitive domains or cognitive-related blood biomarkers . There was high evidence that protein supplementation improved specific cognitive domains or functional status in prefrail older adults without effect on cognitive function . For fatty acid supplementation , mainly long-chain polyunsaturated fatty acids , there was emerging evidence suggesting an impact of this approach in improving specific cognitive domains , magnetic resonance imaging ( MRI ) findings , and /or cognitive-related biomarkers also in selected subgroups of older subjects , although some results were conflicting . There was convincing evidence of an impact of non-flavonoid polyphenol and flavonoid supplementations in improving specific cognitive domains and /or MRI findings . Finally , there was only low evidence suggesting efficacy of intervention with homocysteine-related and antioxidant vitamins in improving cognitive functions , dementia incidence , or cognitive-related biomarkers in cognitively healthy older subjects 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 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 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 Liver disease is increasingly recognized as a major cause of morbidity in cystic fibrosis ( CF ) . Preliminary data suggest that ursodeoxycholic acid ( UDCA ) may be beneficial for treatment of this manifestation . We performed a double-blind , multicenter trial in these patients to establish efficacy and safety of UDCA in terms of the improvement of clinical and nutritional indicators besides st and ard liver function tests . We also intended to establish whether taurine supplementation has a beneficial effect in patients receiving UDCA . From June to December 1990 , we enrolled in 12 centers 55 CF patients with liver disease ( 39 male subjects ; median age , 13.8 years ) . They were r and omly assigned to receive for 1 year one of the following treatments : UDCA ( 15 mg/kg body weight daily ) plus taurine ( 30 mg/kg body weight daily ) , UDCA plus placebo , placebo plus taurine , or double placebo .  Clinical and laboratory evaluations were performed every 3 months . After 1 year , deterioration of overall clinical conditions , as indicated by the Shwachman-Kulczycki score ( SKS ) , occurred in patients who received placebo but not in those who received UDCA ( P = .025 ) . Patients treated with UDCA also showed an improvement in gamma-glutamyl transpeptidase ( GGT ) ( P = .004 ) and 5'-nucleotidase ( P = .006 ) levels . Treatment with taurine was followed by a significant increase in serum prealbumin levels ( P = .053 ) , a trend toward a reduction in fat malabsorption , and no effect on the biochemical profile . No severe side effects occurred with any treatment . Thus , we concluded that UDCA administration improves clinical and biochemical parameters in CF patients with liver disease .  Taurine supplementation may be indicated in patients with severe pancreatic insufficiency and poor nutritional status INTRODUCTION AND AIMS Chronic inflammation plays a major role in lung deterioration in cystic fibrosis ( CF ) patients and anti-inflammatory strategies have beneficial effects . To study the changes seen after a one-year course of low-dose dietary supplements with a mixture of fatty acids in adult patients with CF in chronic inflammation , pulmonary status ( lung function , respiratory exacerbations and antibiotic consumption ) , quality of life and anthropometric parameters . PATIENTS AND METHOD Seventeen adult subjects with CF received 324 mg of eicosapentaenoic , 216 mg of docosahexaenoic , 480 mg of linoleic and 258 mg of gammalinolenic acid daily . We assessed inflammation markers , spirometry parameters , number and severity of respiratory exacerbations , antibiotic consumption , quality of life ( St George 's QoL ) , anthropometric parameters and serum phospholipid fatty acid composition . RESULTS At the end of the treatment period TNF alpha levels fell significantly and its soluble receptors ( 60 and 80 ) rose significantly . Levels of IgG and IgM anti-oxidized LDL antibodies fell significantly . Spirometry improved significantly . Annual respiratory exacerbations and days of antibiotic treatment fell significantly . The improvement in QoL was not significant . Serum levels of docosahexaenoic , total omega-3 and linoleic acid rose significantly and more favourable profiles were seen in monoenoic acids , arachidonic acid and the arachidonic/docosahexaenoic ratio . The fat-free mass and h and grip dynamometry improved significantly . CONCLUSIONS Low-dose supplements of n-3 and gammalinolenic fatty acids over a long period ( one year ) appears to improve pulmonary status ( lung function , respiratory exacerbations and antibiotic consumption ) , inflammatory and anthropometric parameters in adults with CF ABSTRACT Purpose : To determine the effects of short- and long-term use of autogenic drainage ( AD ) on pulmonary function and sputum recovery in people with cystic fibrosis ( CF ) . Methods : The authors conducted a systematic review of r and omized and quasi-r and omized clinical trials in which participants were people with CF who use AD as their sole airway clearance technique . Results : Search es in 4 data bases and secondary sources using 5 key terms yielded 735 articles , of which 58 contained the terms autogenic drainage and cystic fibrosis . Ultimately , 4 studies , 2 of which were long term , were included . All measured forced expiratory volume in 1 second ( FEV1 ) and found no change . The long-term studies were underpowered to detect change in FEV1 ; however , the short-term studies found a clinical ly significant sputum yield ( ≥4 g ) . Conclusion : AD has been shown to produce clinical ly significant sputum yields in a limited number of investigations . The effect of AD on the function of the pulmonary system remains uncertain , and questions have emerged regarding the appropriateness of FEV1 as a valid measure of airway clearance from peripheral lung regions . Further consideration should be given to the use of FEV1 as a primary measure of the effect of AD Relationships among nutritional status and skeletal and respiratory muscle function were examined in 16 children with cystic fibrosis ( CF ) and mild lung disease ( FEV1 95 + /- 16 % predicted ) . Subjects were r and omly assigned to receive ( or not ) noninvasive nutritional supplementation at 25 % of normal energy recommendations for 6 mo . Skeletal muscle strength and power were similar to those of healthy children as were respiratory muscle strength and endurance . Stepwise-regression analysis indicated that changes in skeletal muscle strength and energy intake correlated significantly with growth [ weight ( kg ) = 1.90 - 0.60 ( Tanner Stage ) + 0.49 ( maximum voluntary strength ( Nm ) + 0.03 ( energy intake , % RNI ) , r = 0.76 , P < 0.05 ] , though body composition , protein biochemistry , muscle power , respiratory muscle strength , and use of dietary supplements did not . Thus , changes in skeletal muscle strength may be a functional index of changes in nutritional status in CF . Dietary supplementation per se was not associated with functional improvement 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 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 Many epidemiologic studies based on an observational approach indicate that a high dietary intake or high blood concentrations of some antioxidant micronutrients are associated with a reduced risk of cardiovascular diseases and cancer at several common sites . Inconsistent results of intervention trials suggest that low risk of pathologies may be related to multiple nutrients consumed , at nutritional doses , and in combination . This hypothesis was the rationale of the SU.VI.MAX . study , a r and omized double-blind , placebo-controlled , primary -prevention trial design ed to test the efficacy of a daily supplementation with antioxidant vitamins and minerals at nutritional doses in reducing the major health problems in industrialized countries , and especially the main causes of premature death ( cancers and cardiovascular diseases ) OBJECTIVE There are several examples in nutrition of discordance between the results of observational studies and r and omized controlled trials ( RCTs ) . We hypothesized that this discordance is attributable to differences in the translational paths of nutrient-disease associations . Translational paths can be assessed using citation analysis . STUDY DESIGN AND SETTING We compared the characteristics of citation networks using examples , where RCTs and observational studies agreed ( long-chain n-3 polyunsaturated fatty acids [ n-3 PUFA ] ) or disagreed ( vitamin E ) . We performed systematic review s in each example , constructed citation networks , and compared them with respect to the number of articles and citation relationships between them , as well as the distribution of articles ' hub and authority scores . RESULTS For n-3 PUFA , meta-analyses of 14 RCTs and 10 observational studies both suggested that higher intake was associated with lower cardiovascular mortality . For vitamin E , the meta- analysis of 14 RCTs excluded a clinical ly significant effect , whereas 14 observational studies reported a significant inverse association . The respective citation networks consisted of 392 ( n-3 PUFA ) and 351 ( vitamin E ) articles . No differences between the characteristics of the two networks were identified . There was no evidence that the observational studies pre date d RCTs in the translational process in either example . CONCLUSION In the two examples , citation network characteristics do not predict concordance in the results of observational studies and RCTs Cystic fibrosis ( CF ) remains the most common genetically inherited disease in the white population and its prognosis is affected by nutritional status . Adults with the disease are now surviving longer and new strategies are required to ensure that they maintain optimal nutrition . This article reports preliminary data from a r and omized controlled trial of a 10-week home-based behavioral nutrition intervention , " Eat Well with CF . " Outcome measures of weight change over 6 and 12 months and changes in CF-specific nutrition knowledge score , self-efficacy score , reported dietary fat intake and health-related quality -of-life score were compared between the  intervention group ( n=34 ) and a st and ard care control group ( n=34 ) . The hypotheses to be tested were that adults with CF completing " Eat Well with CF " would have an improved nutritional status , improvement in specific nutrition knowledge , and an improvement in self-efficacy regarding their ability to cope with a special diet , compared to those receiving st and ard care . There were substantial improvements in the intervention group 's specific CF nutrition knowledge score , self-efficacy score , and reported fat intake compared to control , but no substantial change in body mass index or health-related quality of life over time . Home-based nutrition education incorporating behavioral strategies can be an effective way to support adults with CF , enabling improvement in self-management skills in relation to diet and pancreatic enzyme replacement therapy . This study revealed gaps in basic nutrition knowledge and skills , inadequate knowledge of diet-disease links and pancreatic enzyme replacement therapy . These need to be identified when subjects progress from pediatric to adult care , and programs such as " Eat Well with CF " are a useful adjunct for registered dietitians trying to manage this diverse but growing population Summary of the Recommendations The U.S. Preventive Services Task Force ( USPSTF ) concludes that the evidence is insufficient to recommend for or against the use of supplements of vitamins A , C , or E ; multivitamins with folic acid ; or antioxidant combinations for the prevention of cancer or cardiovascular disease . This is a grade I recommendation . ( See Appendix Table 1 for a description of the USPSTF classification of recommendations . ) The USPSTF found poor evidence to determine whether supplementation with these vitamins reduces the risk for cardiovascular disease or cancer . ( See Appendix Table 2 for a description of the USPSTF classification of levels of evidence . ) The available evidence from r and omized trials is either inadequate or conflicting , and the influence of confounding variables on observed outcomes in observational studies can not be determined . As a result , the USPSTF could not determine the balance of benefits and harms of routine use of supplements of vitamins A , C , or E ; multivitamins with folic acid ; or antioxidant combinations for the prevention of cancer or cardiovascular disease . The USPSTF recommends against the use of beta-carotene supplements , either alone or in combination , for the prevention of cancer or cardiovascular disease . This is a grade D recommendation . The USPSTF found good evidence that -carotene supplementation provides no benefit in the prevention of cancer or cardiovascular disease in middle-aged and older adults . In two trials restricted to heavy smokers , -carotene supplementation was associated with higher incidence of lung cancer and higher all-cause mortality . The USPSTF concludes that -carotene supplements are unlikely to provide important benefits and might cause harm in some groups . Clinical Considerations The USPSTF did not review evidence regarding vitamin supplementation for patients with known or potential nutritional deficiencies , including pregnant and lactating women , children , elderly persons , and people with chronic illnesses .  Dietary supplements may be appropriate for people whose diet does not provide the recommended dietary intake of specific vitamins . Individuals may wish to consult a health care provider to discuss whether dietary supplements are appropriate . With the exception of vitamins for which there is compelling evidence of net harm ( for example , beta-carotene supplementation in smokers ) , there is little reason to discourage people from taking vitamin supplements . Patients should be reminded that taking vitamins does not replace the need to eat a healthy diet . All patients should receive information about the benefits of a diet high in fruits and vegetables , as well as information on other foods and nutrients that should be emphasized or avoided in their diet ( see the 2002 USPSTF recommendations on counseling to promote a healthy diet [ 1 ] ) . Patients who choose to take vitamins  should be encouraged to adhere to the dosages recommended in the Dietary Reference Intakes of the Institute of Medicine . Some vitamins , such as A and D , may be harmful in higher doses ; therefore , doses greatly exceeding the Recommended Dietary Allowance or Adequate Intake should be taken with care while considering whether potential harms outweigh potential benefits . Vitamins and minerals sold in the United States are classified as dietary supplements , and there is a degree of quality control over content if they have a U.S. Pharmacopeia seal ( 2 ) . Nevertheless , imprecision in the content and concentration of ingredients could pose a theoretical risk not reflected in clinical trials using calibrated compounds . The adverse effects of beta-carotene on smokers have been observed primarily in those taking large supplemental doses . There is no evidence to suggest that beta-carotene is harmful to smokers at levels occurring naturally in foods . The USPSTF did not review evidence supporting folic acid supplementation among pregnant women to reduce neural tube defects . In 1996 , the USPSTF recommended folic acid for all women who are planning , or capable of , pregnancy ( see the 1996 USPSTF chapter on screening for neural tube defects [ 3 ] ) . Clinicians and patients should discuss the possible need for vitamin supplementation when taking certain medications ( for example , folic acid supplementation for patients taking methotrexate ) . Scientific Evidence The USPSTF review s ( 4 - 6 ) focused on the quality of the evidence regarding the effect of routine supplementation with certain vitamins on primary prevention of cancer and cardiovascular disease . These review s were undertaken because of the growing epidemiologic evidence that dietary factors may play a role in the etiology of these diseases ( 7 - 9 ) . The review s focused on prospect i ve trials of vitamin supplementation and observational studies of associations between the use of specific supplements and the risk for cancer or cardiovascular disease . The value of vitamins naturally occurring in food , the use of vitamin supplements for the prevention of other conditions ( for example , neural tube defects ) , and the use of vitamin supplements for the secondary prevention of complications in patients with existing disease were outside the scope of these review s. Vitamin A No prospect i ve trials have examined the effect of vitamin A supplements alone on the risk for cancer . Observational studies provide no evidence that such supplements prevent cancer in men . In women , observational studies have reported a statistically significant inverse association between use of vitamin A supplements and risk for colon and breast cancer ( 10 , 11 ) . Despite efforts to adjust for confounding variables , the observational , nonr and om design of these studies makes it difficult to assess the extent to which the reduced cancer risk is attributable to vitamin A or to other characteristics of women who take vitamin A supplements .  No evidence from prospect i ve trials is available regarding the benefits of vitamin A alone in preventing cardiovascular disease . One good- quality cohort study found no effect of vitamin A supplementation in reducing cardiovascular disease mortality ( 12 ) . Vitamin C No primary prevention trial of the effect of vitamin C supplementation alone on cancer or cardiovascular disease has been reported . Observational studies have generally shown no statistically significant associations between use of vitamin C supplements and risk for cancer of the breast , prostate , colon , or lung ( 12 - 14 ) . The observational cohort studies examining the effects of vitamin C on cardiovascular disease have produced inconsistent results ( 12 , 15 , 16 ) . Vitamin E Only a few trials have examined the effects of vitamin E on the primary prevention of cancer or cardiovascular disease . A r and omized , controlled trial ( RCT ) involving Finnish male smokers found that vitamin E supplementation is not protective against lung cancer but may have a beneficial impact on prostate cancer ( 14 ) . Because prostate cancer was not a primary end point of the trial and the trial had other limitations , further evidence is needed to confirm this finding . Observational studies have shown no statistically significant association between use of vitamin E supplements and risk for prostate , lung , or breast cancer ( 5 ) . One study suggested that vitamin E protects against colon cancer , but the influence of confounding variables can not be fully excluded ( 17 ) . Among primary prevention trials , two good- quality trials ( 14 , 18 ) and one fair- quality trial ( 19 ) found no statistically significant benefit of vitamin E supplementation in preventing cardiovascular disease ( 20 ) . Only one of seven trials of vitamin E supplementation for secondary prevention demonstrated a statistically significant reduction in cardiac events ( 4 ) . Some prospect i ve cohort studies have suggested a significant benefit , but the results are mixed and the influence of confounding variables can not be excluded ( 4 ) . -Carotene A consistent body of evidence from clinical trials suggests that beta-carotene supplementation does not decrease the risk for lung , prostate , colon , breast , or nonmelanoma skin cancer ( 14 , 21 - 25 ) . -Carotene supplements were associated with an increased risk for lung cancer among smokers , especially heavy smokers , in two RCTs ( 14 , 25 ) . Results from four RCTs demonstrated no reduced risk for cardiovascular events or death after beta-carotene supplementation ( 14 , 21 , 22 , 26 - 28 ) . Antioxidant Vitamin Combinations Studies of the effects of antioxidant vitamin combinations to prevent cancer have yielded mixed results . A recent RCT reported no statistically significant effect of daily supplementation with a combination of antioxidants : vitamin E , vitamin C , and beta-carotene ( 29 ) . Some studies have suggested an adverse effect of antioxidant combinations on cancer , but the results may have been confounded by the inclusion of beta-carotene ( 5 ) . Some observational studies of antioxidant vitamin combinations have suggested a benefit in preventing cardiovascular disease ( 13 , 30 , 31 ) , but other studies , including well- design ed RCTs , have shown no benefit ( 29 , 32 , 33 ) . One secondary prevention trial showed an increase in all-cause mortality among women taking antioxidant supplements  ( 34 ) . Multiple Vitamin Combinations The incremental benefit of taking supplemental doses of folic acid and B vitamins has been examined by comparing the outcomes of observational studies while controlling for the total intake of antioxidant vitamin supplements ( 35 ) . In these analyses , folic acid supplementation was associated with significantly decreased risk for colon cancer , but the protective effect requires confirmation in prospect i ve trials . There is conflicting evidence regarding the use of multivitamins and the risk for cardiovascular disease . Among cohort studies , one good- quality study reported a statistically significant reduction in coronary events ( 36 ) , two good- quality studies reported no statistically significant effect on mortality ( 16 , 37 ) , and one In cystic fibrosis ( CF ) , pancreatic insufficiency and a diminished bile acid pool cause malabsorption of important nutrients and dietary components leading to deficiency , poor nutritional status , and oxidative stress . Of particular significance is the malabsorption of fat-soluble nutrients and antioxidants , which are important for normal immune and neurologic function . Patients with CF often are deficient in these compounds despite supplementation with the current st and ard of care therapy . The objective was to compare the pharmacokinetic profile of this water-soluble vitamin E formulation ( Aqua-E ) with an oil-based softgel formulation in a malabsorbing patient population . Patients with CF who had documented malabsorption were recruited for participation in this pharmacokinetic study . Patients who met inclusion and exclusion criteria discontinued vitamin E supplementation , except for that in a multivitamin , for 7 to 21 days before the day of dosing . Patients were r and omized to a single dose of 20 ml of Aqua-E or three oil-based softgels , which contained equivalent amounts of tocopherols . Blood was drawn from patients at time 0 , 2 , 4 , 8 , 24 , 48 , and 168 hr and analyzed for tocopherols . Eight patients were enrolled in the study and r and omized to Aqua-E or softgels . The primary outcome , the absorption of γ-tocopherol in Aqua-E ( AUC=115 μg/ml*hr ) , was significantly greater than that of oil-based softgels ( AUC=25.3 μg/ml*hr ; P=0.013 ) . Total-tocopherols ( α+γ+δ ) in Aqua-E ( AUC=294 μg/ml*hr ) showed a strong trend toward increased absorption compared with that of oil-based softgels ( AUC=117 μg/ml*hr ; P=0.09 ) . In conclusion , this novel , water-soluble formulation showed a marked and statistically significant increase in absorption of γ-tocopherol in malabsorbing patients with CF compared with an oil-based formulation 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 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 Ursodeoxycholic acid administration has been reported to improve cholestasis and inflammatory activity in primary biliary cirrhosis and , in an uncontrolled study , also in young adults with cystic fibrosis ( CF ) and chronic cholestasis . As an improvement in nutritional status was also observed in these young adult patients , we investigated whether the administration of a medium dose of ursodeoxycholic acid ameliorates the nutritional status of malnourished young adult CF patients with chronic liver disease . The study included 51 patients ( 27 male patients and 24 female patients ; age range , 8–32 years ; median , 14 ) with body mass percentiles < 90 % . Patients were r and omly assigned to receive either ursodeoxycholic acid ( 10–12 mg/kg/day ) alone or with taurine ( 18–22 mg/kg/day ) . Patients were followed in a crossover fashion within each group ; 6 months of treatment was r and omly alternated with 6 months of placebo .  Nine patients dropped out before concluding the study .  Liver function tests , nutritional status , and coefficients of fat absorption were determined at entry and after each 6 months of placebo or treatment .  Nutritional status and fat absorption were not significantly modified by either treatment . Liver function tests improved after ursodeoxycholic acid administration only in patients with concomitant chronic liver disease . Our findings indicate that 6 months of therapy with a medium dose of ursodeoxycholic acid , either alone or with taurine , does not improve the nutritional status of young malnourished CF patients . Higher doses given for longer periods might be worth investigating
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 .
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 .