Introduction
Literature Search
Fish Oil Intervention Studies and Targeted Gene Expression Studies in PBMCs
Study | Study design | Intervention | Intervention duration (wk) | Subjects a
(n, age) | Genes | Upregulated | Downregulated | No effect |
---|---|---|---|---|---|---|---|---|
Cruz-Teno et al, 2012 | Randomized dietary intervention study | Four diets; High saturated fat (HSFA) or high monounsaturated fatty acids (HMUFA) or low-fat, high complex carbohydrate supplemented with n-3 (LFHCC n-3) or high complex carbohydrate (LFHCC) (placebo) | 12 and 4 h postprandial challenge | 75 subjects with metabolic syndrome | IκB-α, TNFα, MMP9, IL-6, MCP-1, p65, MIF | Fasting: higher IκB-α mRNA after LFHCC n-3 compared with HSFA and HMUFA. Postprandial: 12 wk consumption of HMUFA increased postprandial (fat load; 4 h) gene expression of IκB-α compared with HSFA and LFHCC n-3 groups. | No difference in postprandial PBMC p65, MIF, and MCP-1, mRNA between the 4 diets. | |
Telle-Hansen et al, 2012 | Randomized controlled dietary intervention study | Three groups; 150 g of cod or 150 g salmon, or potato (control) daily | 15 d | 30 Healthy male and female, 20–40 y | SCD-1, FAS | The mRNA level of FAS significantly increased within the salmon group. | No effect on SCD-1 or FAS after intervention with cod or salmon compared with potato. | |
Myhrstad et al, 2011 | Crossover study, fixed-order meals. | Three test meals (chocolate cakes): (1) coconut cake (43 E% from SFA); (2) Linseed cake (14 E% from ALA); and (3) cod liver oil cake (5 E% from ALA, 5 E% from EPA and 3 E% from DHA). Ex vivo PBMC stimulation with ALA and EPA | Postprandial | 14 Healthy young women, 22–25 y (IQR) | IL-8, IL-1β, IL-6, PPARγ and CPT1a | Intake of cod liver oil cake: significant increase in the mRNA level of IL-8 after 6 h compared with fasting. Significant increase in the mRNA level of CPT1A after 6 h compared with 3 h. Ex vivo stimulation: EPA increased gene expression of IL-8 and CPT1A compared with unstimulated cells. | No significant difference in mRNA level of IL-1β, IL-6, and PPARγ compared with fasting or between the different cakes. No difference in mRNA levels of CPT1A between the meals. Ex vivo stimulation: EPA had no effect on IL-1β. | |
Radler et al, 2011 | Placebo-controlled double blind | Two groups: low-fat yogurt (125 g) containing grapeseeds (81 mg polyphenols), fish oil (100 mg n-3 PUFA), phospholipids (400 mg), L-carnitine (1 g) vitamin C (60 mg), and vitamin E (10 mg) (PPC) or low-fat yogurt containing only vitamin C (60 mg) and vitamin E (10 mg) | 12 | 22 moderately hyperlipidemic obese subjects, 53.9 y ± 10.9 and 20 matching participants, 53.8 y ± 10.4 | PPARα, CPT1A, CPT1B, CrAT, OCTN2 | The PPC administration increased mRNA levels of PPARα, CPT1A, CPT1B, CrAT, and OCTN2 . No effect on these genes in control group before and after intervention. | ||
Weaver et al, 2009 | “Crossover”: 4 wk dietary supplements and 2 wk washout. Not randomized | One group: dietary supplement; fish oil (775 mg EPA/d), and Borage oil (831 mg GLA/d) | 4 | 27 healthy volunteers | PI3K, Akt, NFκB, IL-1β, IL-10, IL-23, IL-5, IL-17, TNFα | Significant decrease in PBMC gene expression of PI3Kα, PI3Kγ. Cytokines; IL-10 and IL-23 mRNA were decreased after supplementation. Borderline significant decrease for IL-1β (P = 0.09), IL-5 (P = 0.06), and IL-17 (P = 0.09) after supplementation. | No difference in gene expression of Akt, NFκB, PI3Kδ, and PI3Kβ, IL-12, TNFα, and IL-6 after supplementation. | |
de Mello et al, 2009 | Randomized dietary intervention study | Three groups: fatty or lean fish (4 meals per wk) or control (chicken) | 8 | 27 subjects with myocardial infarction or unstable ischemic attack during the last 3 mo, >70 y | TNF, IL-1β, IL-6, CCL2, CCL5, ICAM1, VCAM1, E-selectin, and P-selectin. | No significant differences in both fish groups were observed. | ||
Baumann et al, 1999 | Randomized controlled study, investigator-blinded | Four groups: fish oil 7 g/d, corn oil 7 d/d or olive oil 7 d/d or no dietary intervention | 4 | 28 healthy volunteers, 20–38 y | IL-10, PDGF-A, PDGF-B, MCP-1, and HB-EGF. | Reduced expression of PDGF-A, PDGF-B, and MCP-1 (25 %, 31 %, and 40 %, respectively), in MNC after fish oil consumption. | No effect of fish oil on mRNA expression of IL-10 and HB-EGF. | |
Kaminski et al, 1993 | Controlled, randomized observer-blinded study | Two groups; fish oil group; 7 g/d fish oil concentrate (54.7 % EPA, 28.7 % DHA, 5.4 % C22:5, n-3; 2.4 % C20:4, n-3; 2.4 % C18:4, n-3; 2.1 % C21:5, n-3; and control group. | 6 | 14 healthy volunteers, 28.9 ± 3.5 y | PDGF-A, PDGF-B | Reduced PBMC gene expression of PDGF-A and PDGF-B after fish oil consumption. | ||
Jendraschak et al, 1993 | Controlled, randomized observer-blinded study | Two groups; fish oil group; 7 g/d fish oil concentrate (54.7 % EPA, 28.7 % DHA, 5.4 % C22:5, n-3; 2.4 % C20:4, n-3; 2.4 % C18:4, n-3; 2.1 % C21:5, n-3 and control group | 6 | 14 healthy volunteers, 28.9 ± 3.5 y | PD-ECGF, TGF-β1, IGF-1A, IGF-1B. | No effect of fish oil on mRNA expression of PD-ECGF, TGF-b1, IGF-1A, IGF-1B. |
Fish Intervention Studies and Targeted Gene Expression Studies in PBMCs
Fish Oil Interventions and Whole Genome Transcriptomics in PBMCs
Study | Study Design | Interventionb
| Intervention duration (wk) | Subjectsa
(n, age) | Microarray platform | Regulated genes | Regulated processes, pathways/networks | Biomarkers related to CVD |
---|---|---|---|---|---|---|---|---|
Myhrstad et al, 2014 | Double-blinded, randomized, placebo-controlled study. | 8 g/d fish oil (1.6 g EPA + DHA/d) or 8 g/d HOSO (control) | 7 | 36 healthy subjects, 18–50 y, M/F | Illumina HumanHT-12 v4 | Between groups: 470 gene transcripts (P < 0.05) | Between groups: biological processes and pathways related to cell cycle, DNA package/chromosome organization, ER stress response, apoptosis, and survival. ↑ | Not included |
Rudkowska et al, 2012 | Intervention study, not placebo-controlled. | 5 g/d fish oil (3 g EPA + DHA/d) | 6 | 29 healthy subject, 12 M (mean age 33.5 y ); 17 F (mean age 34.4 y) | Illumina HumanHT-6 v3 | Pre- to postintervention: M + F: 170 gene transcripts (P < 0.05) M: 610 gene transcripts (P < 0.05) F: 250 gene transcripts (P < 0.05) | Within group: changes in pathways related to NrF2 oxidative stress response, PPARγ activation of gene regulation, HIF signaling, NF-κB signaling. Differences in response between M and F. | M + F: TG ↓ TC, LDL, IL-6, TNFα, CRP ↔ |
Vedin et al, 2012 | Double-blind, randomized placebo-controlled study. | 1.7 g DHA + 0.6 g EPA/d (EPAX 1050TG) or 1 g/d Corn oil with LA (control) | 24 | 16 Alzheimer disease (AD) subjects | Human Genome Focus Array (Affymetrix) | Between groups: 5 gene transcripts (P < 0.05), CD63, RHOB, LOC399491, ZNF24, ANAPC5 Within n-3 group: 19 gene transcripts (FDR <10 %) | Within n-3 group: hanges in gene transcripts related to inflammation, ubiquitination, and neurodegeneration. | Not included |
Rudkowska et al, 2011 | Randomized controlled study, crossover design. | Fish oil: 1.8 g EPA + DHA/d or fish oil + fish gelatin (1.8 g EPA + DHA/d and 25 % of daily protein intake). | 8 | 16 obese, insulin resistant subjects, M and F | Illumina HumanHT-6 v3 | Within FO group: 805 gene transcripts Within FO + FG group: 184 gene transcripts (Fold change <0.8 or >1.2 and P < 0.05) Overlap: 3 genes FADS1, EFAR3, and EDA | Within fish oil and fish oil + fish gelatin group: similar changes in the pathway related to PPARγ. Changes in pathways related to HIF signaling, NF-κB, oxidative stress response via Nrf2 in both groups but to different extent. | TG ↓ TC, HDL, LDL, IL-6, TNFα, CRP ↔ |
Bouwens et al, 2009 | Double-blind, randomized, placebo-controlled study. | 1.8 g/d EPA + DHA or HOSO (control) | 26 | 48 elderly healthy subjects | Human whole-genome NuGO Gene Chip arrays (Affymetrix) | Between groups: not shown within n-3 group: 1040 gene transcripts (P < 0.05). Within HOSO group: 298 | Within n-3 group: pathways related to NF-κB-signaling, eicosanoid synthesis, scavenger receptor activity, adipogenesis, and hypoxia signaling. ↓ Pathways related to cell cycle. ↑ | FFA and TG↓, CRP ↔ c
|