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DHA-rich n-3 fatty acid supplementation decreases DNA methylation in blood leukocytes: the OmegAD study
Karolinska Inst, Karolinska Univ Hosp Huddinge, Dept Med & Hematol HERM, Stockholm, Sweden..
Karolinska Inst, Karolinska Univ Hosp Huddinge, Dept Med & Hematol HERM, Stockholm, Sweden..
Karolinska Inst, Karolinska Univ Hosp Huddinge, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
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2017 (English)In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 106, no 4, p. 1157-1165Article in journal (Refereed) Published
Abstract [en]

Background: Dietary fish oils, rich in long-chain n-3 (omega-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'-cytosinephosphate- 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.

Place, publisher, year, edition, pages
AMER SOC NUTRITION-ASN , 2017. Vol. 106, no 4, p. 1157-1165
Keywords [en]
fish oil, DHA, EPA, DNA methylation, LINE-1, Alzheimer disease
National Category
Nutrition and Dietetics
Identifiers
URN: urn:nbn:se:uu:diva-337084DOI: 10.3945/ajcn.117.155648ISI: 000412004300022PubMedID: 28855224OAI: oai:DiVA.org:uu-337084DiVA, id: diva2:1178932
Available from: 2018-01-31 Created: 2018-01-31 Last updated: 2018-02-22Bibliographically approved

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Basun, HansCederholm, T

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