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Effects of supplementation with omega-3 fatty acids on oxidative stress and inflammation in patients with Alzheimer's disease: the OmegAD study.

Abstract

BACKGROUND

Oxidative stress and inflammation are two key mechanisms suggested to be involved in the pathogenesis of Alzheimer's disease (AD). Omega-3 fatty acids (ω-3 FAs) found in fish and fish oil have several biological properties that may be beneficial in AD. However, they may also auto-oxidize and induce in vivo lipid peroxidation.

OBJECTIVE

The objective of this study was to evaluate systemic oxidative stress and inflammatory biomarkers following oral supplementation of dietary ω-3 FA.

METHODS

Forty patients with moderate AD were randomized to receive 1.7 g DHA (22:6) and 0.6 g EPA (20:5) or placebo for 6 months. Urinary samples were collected before and after supplementation. The levels of the major F2-isoprostane, 8-iso-PGF2α, a consistent in vivo biomarker of oxidative stress, and 15-keto-dihydro-PGF2α, a major metabolite of PGF2α and biomarker of inflammatory response, were measured.

RESULTS

F2-isoprostane in urine increased in the placebo group after 6 months, but there was no clear difference in treatment effect between supplemented and non-supplemented patients on the urinary levels of F2-isoprostanes and 15-keto-dihydro-PGF2α. At baseline, the levels of 15-keto-dihydro-PGF2α showed negative correlative relationships to ω-3 FAs, and a positive correlation to linoleic acid. 8-iso-PGF2α correlated negatively to the ω-6 FA arachidonic acid.

CONCLUSION

The findings indicate that supplementation of ω-3 FAs to patients with AD for 6 months does not have a clear effect on free radical-mediated formation of F2-isoprostane or cyclooxygenase-mediated formation of prostaglandin F2α. The correlative relationships to FAs indicate a potential role of FAs in immunoregulation.

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  • Authors+Show Affiliations

    ,

    Section of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet and Department of Geriatrics Karolinska University Hospital Stockholm, Sweden.

    ,

    Division of Haematology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital at Huddinge, Stockholm, Sweden.

    ,

    Division of Neurodegeneration, Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Stockholm, Sweden.

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    Division of Geriatrics, Uppsala University, Uppsala, Sweden and Chaire d'Excellence Program, Department of Biochemistry, Molecular Biology and Nutrition, Universite d'Auvergne, Clermont-Ferrand, France.

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    Divisions of Clinical Nutrition, Karolinska Institutet, Karolinska University Hospital at Huddinge, Stockholm, Sweden.

    ,

    Division of Neurodegeneration, Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Stockholm, Sweden.

    ,

    Section of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet and Department of Geriatrics Karolinska University Hospital Stockholm, Sweden.

    ,

    Division of Haematology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital at Huddinge, Stockholm, Sweden.

    ,

    Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.

    ,

    Section of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet and Department of Geriatrics Karolinska University Hospital Stockholm, Sweden.

    ,

    Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.

    Division of Oxidative Stress and Inflammation, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden and Chaire d'Excellence Program, Department of Biochemistry, Molecular Biology and Nutrition, Universite d'Auvergne, Clermont-Ferrand, France.

    Source

    MeSH

    Administration, Oral
    Aged
    Alzheimer Disease
    Cognition Disorders
    Cytokines
    Depression
    Dietary Supplements
    Dinoprost
    Docosahexaenoic Acids
    Eicosapentaenoic Acid
    F2-Isoprostanes
    Female
    Humans
    Male
    Neuropsychological Tests
    Oxidative Stress
    Psychiatric Status Rating Scales
    Retrospective Studies

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    24934544

    Citation

    Freund-Levi, Yvonne, et al. "Effects of Supplementation With Omega-3 Fatty Acids On Oxidative Stress and Inflammation in Patients With Alzheimer's Disease: the OmegAD Study." Journal of Alzheimer's Disease : JAD, vol. 42, no. 3, 2014, pp. 823-31.
    Freund-Levi Y, Vedin I, Hjorth E, et al. Effects of supplementation with omega-3 fatty acids on oxidative stress and inflammation in patients with Alzheimer's disease: the OmegAD study. J Alzheimers Dis. 2014;42(3):823-31.
    Freund-Levi, Y., Vedin, I., Hjorth, E., Basun, H., Faxén Irving, G., Schultzberg, M., ... Basu, S. (2014). Effects of supplementation with omega-3 fatty acids on oxidative stress and inflammation in patients with Alzheimer's disease: the OmegAD study. Journal of Alzheimer's Disease : JAD, 42(3), pp. 823-31. doi:10.3233/JAD-132042.
    Freund-Levi Y, et al. Effects of Supplementation With Omega-3 Fatty Acids On Oxidative Stress and Inflammation in Patients With Alzheimer's Disease: the OmegAD Study. J Alzheimers Dis. 2014;42(3):823-31. PubMed PMID: 24934544.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Effects of supplementation with omega-3 fatty acids on oxidative stress and inflammation in patients with Alzheimer's disease: the OmegAD study. AU - Freund-Levi,Yvonne, AU - Vedin,Inger, AU - Hjorth,Erik, AU - Basun,Hans, AU - Faxén Irving,Gerd, AU - Schultzberg,Marianne, AU - Eriksdotter,Maria, AU - Palmblad,Jan, AU - Vessby,Bengt, AU - Wahlund,Lars-Olof, AU - Cederholm,Tommy, AU - Basu,Samar, PY - 2014/6/18/entrez PY - 2014/6/18/pubmed PY - 2015/8/26/medline KW - $F_2$-isoprostane KW - Alzheimer's disease KW - eicosanoids KW - inflammation KW - lipids KW - omega-3 fatty acids KW - oxidative stress KW - prostaglandin $F_{2 \alpha}$ SP - 823 EP - 31 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 42 IS - 3 N2 - BACKGROUND: Oxidative stress and inflammation are two key mechanisms suggested to be involved in the pathogenesis of Alzheimer's disease (AD). Omega-3 fatty acids (ω-3 FAs) found in fish and fish oil have several biological properties that may be beneficial in AD. However, they may also auto-oxidize and induce in vivo lipid peroxidation. OBJECTIVE: The objective of this study was to evaluate systemic oxidative stress and inflammatory biomarkers following oral supplementation of dietary ω-3 FA. METHODS: Forty patients with moderate AD were randomized to receive 1.7 g DHA (22:6) and 0.6 g EPA (20:5) or placebo for 6 months. Urinary samples were collected before and after supplementation. The levels of the major F2-isoprostane, 8-iso-PGF2α, a consistent in vivo biomarker of oxidative stress, and 15-keto-dihydro-PGF2α, a major metabolite of PGF2α and biomarker of inflammatory response, were measured. RESULTS: F2-isoprostane in urine increased in the placebo group after 6 months, but there was no clear difference in treatment effect between supplemented and non-supplemented patients on the urinary levels of F2-isoprostanes and 15-keto-dihydro-PGF2α. At baseline, the levels of 15-keto-dihydro-PGF2α showed negative correlative relationships to ω-3 FAs, and a positive correlation to linoleic acid. 8-iso-PGF2α correlated negatively to the ω-6 FA arachidonic acid. CONCLUSION: The findings indicate that supplementation of ω-3 FAs to patients with AD for 6 months does not have a clear effect on free radical-mediated formation of F2-isoprostane or cyclooxygenase-mediated formation of prostaglandin F2α. The correlative relationships to FAs indicate a potential role of FAs in immunoregulation. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/24934544/Effects_of_supplementation_with_omega_3_fatty_acids_on_oxidative_stress_and_inflammation_in_patients_with_Alzheimer's_disease:_the_OmegAD_study_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-132042 DB - PRIME DP - Unbound Medicine ER -