Omega-3 fatty acids for cystic fibrosis

Oliver, Colleen; Watson, Helen

doi:10.1002/14651858.cd002201.pub5

Cited by 29 publications

(20 citation statements)

References 37 publications

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“…Correlations between altered FA levels and genotype, pancreatic status, and respiratory deficiency have been previously reported in CF subjects (Strandvik et al, 2001; Coste et al, 2008; Maqbool et al, 2008; Rise et al, 2010), and evidence has also been provided that a prolonged n-3 FA supplementation may have some positive effects on CF (Oliver and Watson, 2016). In our study, DHA supplementation resulted in a decrease of pro-inflammatory mediators, such as LTB 4 , suggesting that the lower concentrations of DHA observed in CF subjects (Rise et al, 2010) could indeed cause a lack of anti-inflammatory/pro-resolving LMs.…”

Section: Discussionmentioning

confidence: 83%

“…COPD subjects, GOLD stage 2 to 3 under treatment according to the GOLD document (Vogelmeier et al, 2017), were examined at the time of enrolment, whereas CF patients were examined both at enrolment; after 10 weeks of supplementation with Aladin ® 500 mg (Laborest, Italy), two capsules, three times a day; and after an additional 10 weeks of washout. Dosage and duration regimen adopted were those already routinely used by the CF hospital unit, and were based on average values present in the literature (Coste et al, 2007; Oliver and Watson, 2016). Nine CF patients (five female) completed the study.…”

Section: Methodsmentioning

confidence: 99%

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Arachidonic Acid and Docosahexaenoic Acid Metabolites in the Airways of Adults With Cystic Fibrosis: Effect of Docosahexaenoic Acid Supplementation

et al. 2019

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Cystic fibrosis (CF) is an autosomal recessive disorder, caused by genetic mutations in CF transmembrane conductance regulator protein. Several reports have indicated the presence of specific fatty acid alterations in CF patients, most notably decreased levels of plasmatic and tissue docosahexaenoic acid (DHA), the precursor of specialized pro-resolving mediators. We hypothesized that DHA supplementation could restore the production of DHA-derived products and possibly contribute to a better control of the chronic pulmonary inflammation observed in CF subjects. Sputum samples from 15 CF and 10 chronic obstructive pulmonary disease (COPD) subjects were collected and analyzed by LC/MS/MS, and blood fatty acid were profiled by gas chromatography upon lipid extraction and transmethylation. Interestingly, CF subjects showed increased concentrations of leukotriene B 4 (LTB 4 ), prostaglandin E 2 (PGE 2 ), and 15-hydroxyeicosatetraenoic acid (15-HETE), when compared with COPD patients, whereas the concentrations of DHA metabolites did not differ between the two groups. After DHA supplementation, not only DHA/arachidonic acid (AA) ratio and highly unsaturated fatty acid index were significantly increased in the subjects completing the study ( p < 0.05) but also a reduction in LTB 4 and 15-HETE was observed, together with a tendency for a decrease in PGE 2, and an increase in 17-hydroxy-docosahexaenoic acid (17OH-DHA) levels. At the end of the washout period, LTB 4 , PGE 2 , 15-HETE, and 17OH-DHA showed a trend to return to baseline values. In addition, 15-HETE/17OH-DHA ratio in the same sample significantly decreased after DHA supplementation ( p < 0.01) when compared with baseline. In conclusion, our results show here that in CF patients, an impairment in fatty acid metabolism, characterized by increased AA-derived metabolites and decreased DHA-derived metabolites, could be partially corrected by DHA supplementation.

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Section: Discussionmentioning

confidence: 83%

Section: Methodsmentioning

confidence: 99%

Arachidonic Acid and Docosahexaenoic Acid Metabolites in the Airways of Adults With Cystic Fibrosis: Effect of Docosahexaenoic Acid Supplementation

et al. 2019

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“…85 Acid suppressive drugs and broad spectrum antibiotics have been proposed and empirically employed to optimize fat absorption. 85 Despite insufficient evidence to draw firm conclusions, regular administration of omega 3 long-chain fatty acids 86 has also been proposed as beneficial in patients with CF. An approach to inadequate clinical response to PERT is suggested to the reader in Figure 1.…”

Section: Diagnosis Of Pimentioning

confidence: 99%

Cystic fibrosis: An update for clinicians. Part 2: Hepatobiliary and pancreatic manifestations

Ledder

Haller

Couper

et al. 2014

J of Gastro and Hepatol

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This paper, the second in the series, will build on the first and explore the importance of liver and pancreatic manifestations of cystic fibrosis (CF) and the effect on morbidity and mortality of this multifaceted genetic condition. It will also further develop the critical role of the gastroenterologist as part of the multidisciplinary group of clinicians and allied health staff in the effective management of patients with CF.

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“…33 This turned all interest to this fatty acid resulting in many clinical studies supplementing DHA to patients with CF, but the results were mainly disappointing regarding any influence on the symptomatology. 34 Later a long-term study of similar cftrÀ/À mouse strain could not repeat the beneficial effect of DHA supplementation, but showed a protection of liver abnormality. 35 The development of murine models opened a possibility to study organ pathophysiology in CF, but the investigations have shown different results depending on models with null alleles or those with more or less CFTR function related to mutation strategy.…”

Section: Impact Statementmentioning

confidence: 99%

Low linoleic and high docosahexaenoic acids in a severe phenotype of transgenic cystic fibrosis mice

Strandvik

Neal

Ali

et al. 2018

Exp Biol Med (Maywood)

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Low linoleic acid concentration is a common finding in patients with cystic fibrosis and associated with severe clinical phenotype. Low docosahexaenoic and arachidonic acids are more inconsistently found in patients, but arachidonic/docosahexaenoic ratio is usually high. In animal models with cftr mutations or KO animals for the cftr gene, linoleic acid deficiency has not been consistently reported and some report docosahexaenoic deficiency as the major fatty acid abnormality. We hereby describe fatty acid profile in a severe clinical cystic fibrosis phenotype in mice with a duplication of exon 3 generated in the cystic fibrosis gene of C57B1/6J mice ( cftr allele). In 43/50 animals, plasma phospholipid fatty acids were repeatedly analyzed (mean three times/animal) covering ages between 7 and 235 days. Linoleic acid concentrations were significantly lower in cftr-/- mice compared to heterozygotes ( P = 0.03) and wild type mice ( P < 0.001). Females had significantly lower linoleic acid than males, not related to age. Arachidonic acid did not differ but docosahexaenoic acid was higher in cftr-/- than in wild type mice ( P < 0.001). The arachidonic/docosahexaenoic acid ratio did not differ but arachidonic/linoleic acid ratio was higher in cftr-/- mice compared to wild type mice ( P = 0.007). Similar to clinical studies, type of mutation is important for lipid abnormality with low linoleic acid most consistently found in the animals. Rodents differ in metabolism by synthesizing docosahexaenoic acid more efficiently comparing to humans, suggesting greater influence by diet. Precaution seems important when comparing animal and humans. Impact statement In translational research, animal models are important to investigate the effect of genetic mutations in specific diseases and their metabolism. Special attention has to be given to differences in physiology and metabolism between species and humans, which otherwise can hazard the conclusions. Our work illustrates that the different synthesis capacity in mice and humans for DHA would explain different results in different models for cystic fibrosis and different influences of diets. To avoid disappointing clinical results, these facts have to be considered before extensive clinical studies are started based on results from single animal studies.

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Omega-3 fatty acids for cystic fibrosis

Abstract: Analysis 1.5. Comparison 1 Omega-3 fatty acids versus placebo, Outcome 5 Biochemical markers of essential fatty acid status (B4/B5 ratio

Cited by 29 publications

References 37 publications

Arachidonic Acid and Docosahexaenoic Acid Metabolites in the Airways of Adults With Cystic Fibrosis: Effect of Docosahexaenoic Acid Supplementation

Arachidonic Acid and Docosahexaenoic Acid Metabolites in the Airways of Adults With Cystic Fibrosis: Effect of Docosahexaenoic Acid Supplementation

Cystic fibrosis: An update for clinicians. Part 2: Hepatobiliary and pancreatic manifestations

Low linoleic and high docosahexaenoic acids in a severe phenotype of transgenic cystic fibrosis mice

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