HIGHLIGTHS
- •Inflammation has a key role in cystic fibrosis pathophysiology
- •Benefits of docosahexaenoic acid (DHA) in cystic fibrosis inflammation are controversial
- •Long-term supplementation with DHA in CF did not improve inflammatory biomarkers
- •Long-term supplementation with DHA in CF did not improve clinical outcomes
ABSTRACT
Background
Cystic fibrosis (CF) patients have an alteration in fatty acid (FA) metabolism, associated
with increased omega-6 and low omega-3 FA. Previous studies on supplementation with
omega-3 FA in CF had contradictory results, and to date there is no evidence to recommend
routine use of omega-3 supplements in CF patients. We hypothesized that long-term
supplementation with docosahexaenoic acid (DHA) will have beneficial effects in these
patients, by reducing pulmonary, systemic and intestinal inflammation.
Methods
This was a randomized, double-blind, parallel, placebo-controlled trial. CF patients
(age >2 months) were randomized to receive a seaweed DHA oil solution (50 mg/Kg/day)
or matching placebo for 48 weeks. Primary outcomes were pulmonary (interleukin [IL]-8),
systemic (IL-8) and intestinal (calprotectin) inflammatory biomarkers. Secondary outcomes
included other pulmonary (IL-1β, IL-6, neutrophil elastase, lactate and calprotectin)
and systemic (serum-IL-1β, IL-6) inflammatory biomarkers, as well as clinical outcomes
(FEV1, pulmonary exacerbations, antibiotic use, nutritional status and quality of life).
Results
Ninety six CF patients, 44 female, age 14.6±11.9 years (48 DHA and 48 placebo) were
included. At trial completion, there were no differences in all primary outcomes [serum-IL-8
(p=0.909), respiratory-IL-8 (p=0.384) or fecal calprotectin (p=0.948)], all secondary
inflammatory biomarkers, or in any of the clinical outcomes evaluated. There were
few adverse events, with similar incidence in both study groups.
Conclusion
In this study, long-term DHA supplementation in CF patients was safe, but did not
offer any benefit on inflammatory biomarkers, or in clinical outcomes compared with
placebo.
(NCT01783613)
Keywords
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Article info
Publication history
Published online: October 01, 2020
Accepted:
September 29,
2020
Received in revised form:
September 25,
2020
Received:
February 23,
2020
Footnotes
Declaration of interest: none
Funding
This study has been supported by the Spanish Clinical Research Network (SCReN), funded by the Instituto de Salud Carlos III, Subdirección General de Evaluación y Fomento de la Investigación, grant PT13/0002/0007 integrated in the Plan Estatal de I+D+I 2013-2016, and cofinanced by the European Regional Development Fund.
This study was funded by:
a. Ministry of Health (Orden SAS/2377/2010 de ayudas para la investigación clínica independiente).
b. Consorcio de Apoyo a la Investigación Biomédica en Red (CAIBER): reference code: 1392-I-036.
c. CAIBER 2012 grant for Marta Muñoz as clinical researcher.
d. Sira Carrasco grant, awarded by Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátrica (SEGHNP) 2011.
e. “Ayuda a la Fibrosis Quística” grant, awarded by Pablo Motos Foundation 2011.
f. “Ayuda a la Fibrosis Quística” grant, awarded by Sira Carrasco Foundation 2011.
g. “Ayuda a la Fibrosis Quística” grant, awarded by Sira Carrasco Foundation 2014.
h. Project OBN18PI03, Instituto de Salud Carlos III
Sponsor had not any role in study design, in collection, analysis or interpretation of data, in the writing of the report or in the decision to submit the article for publication.
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