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Long-term docosahexaenoic acid (DHA) supplementation in cystic fibrosis patients: a randomized, multi-center, double-blind, placebo-controlled trial

  • Alejandro López-Neyra
    Correspondence
    Corresponding author: Alejandro López-Neyra. Unidad de Fibrosis Quística. Servicio de Pediatría. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS). Hospital Universitario Ramón y Cajal, Cª Colmenar Km 9,1. 28034-Madrid, Spain, Telephone: +34-91 3368092
    Affiliations
    Unidad de Fibrosis Quística. Servicio de Pediatría. Hospital Universitario Ramón y Cajal. Cª Colmenar Km. 9,1. 28034-Madrid. Spain

    Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS). Cª Colmenar Km. 9,1. 28034-Madrid. Spain
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  • Lucrecia Suárez
    Affiliations
    Unidad de Fibrosis Quística. Servicio de Pediatría. Hospital Universitario Ramón y Cajal. Cª Colmenar Km. 9,1. 28034-Madrid. Spain

    Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS). Cª Colmenar Km. 9,1. 28034-Madrid. Spain
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  • Marta Muñoz
    Affiliations
    Unidad de Fibrosis Quística. Servicio de Pediatría. Hospital Universitario Ramón y Cajal. Cª Colmenar Km. 9,1. 28034-Madrid. Spain
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  • Ana de Blas
    Affiliations
    Unidad de Fibrosis Quística. Servicio de Pediatría. Hospital Universitario Ramón y Cajal. Cª Colmenar Km. 9,1. 28034-Madrid. Spain
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  • Marta Ruiz de Valbuena
    Affiliations
    Unidad de Fibrosis Quística. Servicio de Pediatría. Hospital Universitario Ramón y Cajal. Cª Colmenar Km. 9,1. 28034-Madrid. Spain
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  • María Garriga
    Affiliations
    Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS). Cª Colmenar Km. 9,1. 28034-Madrid. Spain

    Unidad de Fibrosis Quística. Servicio de Endocrinología. Hospital Universitario Ramón y Cajal. Cª Colmenar Km. 9,1. 28034-Madrid. Spain
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  • Joaquim Calvo
    Affiliations
    Unidad de Fibrosis Quística. Servicio de Pediatría. Hospital Universitario La Fe. Avinguda de Fernando Abril Martorell, 106. 46026-Valencia. Spain
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  • Carmen Ribes
    Affiliations
    Unidad de Fibrosis Quística. Servicio de Pediatría. Hospital Universitario La Fe. Avinguda de Fernando Abril Martorell, 106. 46026-Valencia. Spain
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  • Rosa Girón Moreno
    Affiliations
    Unidad de Fibrosis Quística. Servicio de Neumología. Hospital Universitario La Princesa. Instituto de Investigación Sanitaria La Princesa. Calle de Diego de León, 62. 28006-Madrid. Spain
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  • Luis Máiz
    Affiliations
    Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS). Cª Colmenar Km. 9,1. 28034-Madrid. Spain

    Unidad de Fibrosis Quística. Servicio de Neumología. Hospital Universitario Ramón y Cajal. Cª Colmenar Km. 9,1. 28034-Madrid. Spain
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  • David González
    Affiliations
    Unidad de Fibrosis Quística. Servicio de Pediatría. Hospital Universitario Central de Asturias. Av. Roma. 33011-Oviedo. Spain
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  • Carlos Bousoño
    Affiliations
    Unidad de Fibrosis Quística. Servicio de Pediatría. Hospital Universitario Central de Asturias. Av. Roma. 33011-Oviedo. Spain
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  • Javier Manzanares
    Affiliations
    Unidad de Fibrosis Quística. Servicio de Pediatría. Hospital Universitario Doce de Octubre. Avda. de Córdoba. 28041-Madrid. Spain
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  • Óscar Pastor
    Affiliations
    Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS). Cª Colmenar Km. 9,1. 28034-Madrid. Spain

    Servicio de Bioquímica Clínica, UCA-CCM. Hospital Universitario Ramón y Cajal. Cª Colmenar Km. 9,1. 28034-Madrid. Spain

    CIBER Fisiopatología Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III. Av. Monforte de Lemos, 3-5. 28029-Madrid. Spain
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  • Javier Martínez-Botas
    Affiliations
    Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS). Cª Colmenar Km. 9,1. 28034-Madrid. Spain

    CIBER Fisiopatología Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III. Av. Monforte de Lemos, 3-5. 28029-Madrid. Spain

    Servicio de Bioquímica-Investigación. Hospital Universitario Ramón y Cajal. Cª Colmenar Km. 9,1. 28034-Madrid. Spain
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  • Rosa del Campo
    Affiliations
    Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS). Cª Colmenar Km. 9,1. 28034-Madrid. Spain

    Servicio de Microbiología, Hospital Universitario Ramón y Cajal. Cª Colmenar Km. 9,1. 28034-Madrid. Spain
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  • Rafael Cantón
    Affiliations
    Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS). Cª Colmenar Km. 9,1. 28034-Madrid. Spain

    Servicio de Microbiología, Hospital Universitario Ramón y Cajal. Cª Colmenar Km. 9,1. 28034-Madrid. Spain
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  • Garbiñe Roy
    Affiliations
    Servicio de Inmunología, Hospital Universitario Ramón y Cajal. Cª Colmenar Km. 9,1. 28034-Madrid. Spain
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  • Miriam Menacho
    Affiliations
    Servicio de Bioquímica Clínica, Hospital Universitario Ramón y Cajal. Cª Colmenar Km. 9,1. 28034-Madrid. Spain.
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  • David Arroyo
    Affiliations
    Unidad de Bioestadística Clínica, Hospital Universitario Ramón y Cajal. Cª Colmenar Km. 9,1. 28034-Madrid. Spain

    CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III. Av. Monforte de Lemos, 3-5. 28029-Madrid. Spain
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  • Javier Zamora
    Affiliations
    Unidad de Bioestadística Clínica, Hospital Universitario Ramón y Cajal. Cª Colmenar Km. 9,1. 28034-Madrid. Spain

    CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III. Av. Monforte de Lemos, 3-5. 28029-Madrid. Spain
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  • Joan B Soriano
    Affiliations
    Hospital Universitario La Princesa. Universidad Autónoma de Madrid. Calle de Diego de León, 62. 28006-Madrid. Spain

    Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III. Av. Monforte de Lemos, 3-5. 28029-Madrid. Spain
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  • Adelaida Lamas
    Affiliations
    Unidad de Fibrosis Quística. Servicio de Pediatría. Hospital Universitario Ramón y Cajal. Cª Colmenar Km. 9,1. 28034-Madrid. Spain

    Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS). Cª Colmenar Km. 9,1. 28034-Madrid. Spain
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Published:October 01, 2020DOI:https://doi.org/10.1016/j.plefa.2020.102186

      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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