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DHA-rich n-3 fatty acid supplementation decreases DNA methylation in blood leukocytes: the OmegAD study
Department of Medicine and Hematology (HERM), Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Department of Medicine and Hematology (HERM), Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Department of Neurobiology, Care, Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.ORCID-id: 0000-0001-6863-6679
Department of Public Health and Caring Sciences, Division of Geriatrics, Uppsala University Hospital, Uppsala, Sweden.
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2017 (Engelska)Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 106, nr 4, s. 1157-1165Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
HighWire Press , 2017. Vol. 106, nr 4, s. 1157-1165
Nyckelord [en]
Alzheimer disease, DHA, DNA methylation, EPA, LINE-1, fish oil
Nationell ämneskategori
Näringslära Hematologi Neurologi
Identifikatorer
URN: urn:nbn:se:oru:diva-74058DOI: 10.3945/ajcn.117.155648ISI: 000412004300022PubMedID: 28855224Scopus ID: 2-s2.0-85031697359OAI: oai:DiVA.org:oru-74058DiVA, id: diva2:1313970
Forskningsfinansiär
Stockholms läns landstingDemensförbundetStiftelsen Gamla TjänarinnorGun och Bertil Stohnes Stiftelse
Anmärkning

Funding agencies:

Karolinska Institutet

Funds of Capio

Swedish Alzheimer Foundation

Odd Fellows

Swedish Nutrition Foundation

Swedish Society of Physicians

Lion's Sweden

Pronova Biocare A/S

Tillgänglig från: 2019-05-07 Skapad: 2019-05-07 Senast uppdaterad: 2019-06-18Bibliografiskt granskad

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Freund-Levi, Yvonne

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