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DHA-rich n-3 fatty acid supplementation decreases DNA methylation in blood leukocytes: the OmegAD study.

Abstract

Background:

Dietary fish oils, rich in long-chain n-3 (ω-3) fatty acids (FAs) [e.g., docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3)], modulate inflammatory reactions through various mechanisms, including gene expression, which is measured as messenger RNA concentration. However, the effects of long-term treatment of humans with DHA and EPA on various epigenetic factors-such as DNA methylation, which controls messenger RNA generation-are poorly described.

Objective:

We wanted to determine the effects of 6 mo of dietary supplementation with an n-3 FA preparation rich in DHA on global DNA methylation of peripheral blood leukocytes (PBLs) and the relation to plasma EPA and DHA concentrations in Alzheimer disease (AD) patients.

Design:

In the present study, DNA methylation in four 5'-cytosine-phosphate-guanine-3' (CpG) sites of long interspersed nuclear element-1 repetitive sequences was assessed in a group of 63 patients (30 given the n-3 FA preparation and 33 given placebo) as an estimation of the global DNA methylation in blood cells. Patients originated from the randomized, double-blind, placebo-controlled OmegAD study, in which 174 AD patients received either 1.7 g DHA and 0.6 g EPA (the n-3 FA group) or placebo daily for 6 mo.

Results:

At 6 mo, the n-3 FA group displayed marked increases in DHA and EPA plasma concentrations (2.6- and 3.5-fold), as well as decreased methylation in 2 out of 4 CpG sites (P < 0.05 for all), respectively. This hypomethylation in CpG2 and CpG4 sites showed a reverse correlation to changes in plasma EPA concentration (r = -0.25, P = 0.045; and r = -0.26, P = 0.041, respectively), but not to changes in plasma DHA concentration, and were not related to apolipoprotein E-4 allele frequency.

Conclusion:

Supplementation with n-3 FA for 6 mo was associated with global DNA hypomethylation in PBLs. Our data may be of importance in measuring various effects of marine oils, including gene expression, in patients with AD and in other patients taking n-3 FA supplements. This trial was registered at clinicaltrials.gov as NCT00211159.

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  • Authors+Show Affiliations

    ,

    Departments of Medicine and Hematology (HERM) and.

    ,

    Departments of Medicine and Hematology (HERM) and.

    ,

    Neurobiology, Care, Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; and Departments of.

    ,

    Public Health and Caring Sciences, Division of Geriatrics, and.

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    Neurobiology, Care, Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; and Departments of.

    ,

    Neurobiology, Care, Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; and Departments of.

    ,

    Neurobiology, Care, Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; and Departments of.

    ,

    Neurobiology, Care, Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; and Departments of.

    ,

    Neurobiology, Care, Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; and Departments of.

    ,

    Clinical Nutrition and Metabolism, Uppsala University Hospital, Uppsala, Sweden.

    Departments of Medicine and Hematology (HERM) and jan.palmblad@ki.se.

    Source

    The American journal of clinical nutrition 106:4 2017 Oct pg 1157-1165

    MeSH

    Aged
    Aged, 80 and over
    Alzheimer Disease
    Apolipoprotein E4
    CpG Islands
    DNA Methylation
    Dietary Supplements
    Docosahexaenoic Acids
    Double-Blind Method
    Eicosapentaenoic Acid
    Fatty Acids
    Female
    Fish Oils
    Humans
    Inflammation
    Leukocytes, Mononuclear
    Long Interspersed Nucleotide Elements
    Male
    Time Factors

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial

    Language

    eng

    PubMed ID

    28855224

    Citation

    Karimi, Mohsen, et al. "DHA-rich N-3 Fatty Acid Supplementation Decreases DNA Methylation in Blood Leukocytes: the OmegAD Study." The American Journal of Clinical Nutrition, vol. 106, no. 4, 2017, pp. 1157-1165.
    Karimi M, Vedin I, Freund Levi Y, et al. DHA-rich n-3 fatty acid supplementation decreases DNA methylation in blood leukocytes: the OmegAD study. Am J Clin Nutr. 2017;106(4):1157-1165.
    Karimi, M., Vedin, I., Freund Levi, Y., Basun, H., Faxén Irving, G., Eriksdotter, M., ... Palmblad, J. (2017). DHA-rich n-3 fatty acid supplementation decreases DNA methylation in blood leukocytes: the OmegAD study. The American Journal of Clinical Nutrition, 106(4), pp. 1157-1165. doi:10.3945/ajcn.117.155648.
    Karimi M, et al. DHA-rich N-3 Fatty Acid Supplementation Decreases DNA Methylation in Blood Leukocytes: the OmegAD Study. Am J Clin Nutr. 2017;106(4):1157-1165. PubMed PMID: 28855224.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - DHA-rich n-3 fatty acid supplementation decreases DNA methylation in blood leukocytes: the OmegAD study. AU - Karimi,Mohsen, AU - Vedin,Inger, AU - Freund Levi,Yvonne, AU - Basun,Hans, AU - Faxén Irving,Gerd, AU - Eriksdotter,Maria, AU - Wahlund,Lars-Olof, AU - Schultzberg,Marianne, AU - Hjorth,Erik, AU - Cederholm,Tommy, AU - Palmblad,Jan, Y1 - 2017/08/30/ PY - 2017/03/03/received PY - 2017/08/04/accepted PY - 2017/9/1/pubmed PY - 2017/10/14/medline PY - 2017/9/1/entrez KW - Alzheimer disease KW - DHA KW - DNA methylation KW - EPA KW - LINE-1 KW - fish oil SP - 1157 EP - 1165 JF - The American journal of clinical nutrition JO - Am. J. Clin. Nutr. VL - 106 IS - 4 N2 - Background: Dietary fish oils, rich in long-chain n-3 (ω-3) fatty acids (FAs) [e.g., docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3)], modulate inflammatory reactions through various mechanisms, including gene expression, which is measured as messenger RNA concentration. However, the effects of long-term treatment of humans with DHA and EPA on various epigenetic factors-such as DNA methylation, which controls messenger RNA generation-are poorly described.Objective: We wanted to determine the effects of 6 mo of dietary supplementation with an n-3 FA preparation rich in DHA on global DNA methylation of peripheral blood leukocytes (PBLs) and the relation to plasma EPA and DHA concentrations in Alzheimer disease (AD) patients.Design: In the present study, DNA methylation in four 5'-cytosine-phosphate-guanine-3' (CpG) sites of long interspersed nuclear element-1 repetitive sequences was assessed in a group of 63 patients (30 given the n-3 FA preparation and 33 given placebo) as an estimation of the global DNA methylation in blood cells. Patients originated from the randomized, double-blind, placebo-controlled OmegAD study, in which 174 AD patients received either 1.7 g DHA and 0.6 g EPA (the n-3 FA group) or placebo daily for 6 mo.Results: At 6 mo, the n-3 FA group displayed marked increases in DHA and EPA plasma concentrations (2.6- and 3.5-fold), as well as decreased methylation in 2 out of 4 CpG sites (P < 0.05 for all), respectively. This hypomethylation in CpG2 and CpG4 sites showed a reverse correlation to changes in plasma EPA concentration (r = -0.25, P = 0.045; and r = -0.26, P = 0.041, respectively), but not to changes in plasma DHA concentration, and were not related to apolipoprotein E-4 allele frequency.Conclusion: Supplementation with n-3 FA for 6 mo was associated with global DNA hypomethylation in PBLs. Our data may be of importance in measuring various effects of marine oils, including gene expression, in patients with AD and in other patients taking n-3 FA supplements. This trial was registered at clinicaltrials.gov as NCT00211159. SN - 1938-3207 UR - https://www.unboundmedicine.com/medline/citation/28855224/DHA_rich_n_3_fatty_acid_supplementation_decreases_DNA_methylation_in_blood_leukocytes:_the_OmegAD_study_ L2 - https://academic.oup.com/ajcn/article-lookup/doi/10.3945/ajcn.117.155648 DB - PRIME DP - Unbound Medicine ER -