Table 6 Clinical effects induced by PUFAs.
Intervention (n) Main anti-inflammatory findings Other relevant findings References
Healthy subjects
4-month intervention:➢ 1.5 g fish oil (1042.5 mg EPA and 174 DHA daily)
➢ 2.5 g fish oil (2085 mg EPA and 348 mg DHA daily)
➢ placebo 138 ↓TNF-α and ↓ IL-6 for both low and high dose groups ↓ n-6:n-3 ratio for both low and high dose groups Kiecolt-Glaser et al. (2012)
6-week intervention:➢ 600 mg EPA/day
➢ 1800 mg EPA/day
➢ 600 mg DHA/day
➢ placebo 121 No effect on hsCRP, TNF-α, IL-6, VCAM-1, ICAM-1 and fibrinogen Only High dose EPA ↓ Lp-PLA2;DHA: ↓ TG; ↑ LDLNo effect of low dose EPA Asztalos et al. (2016)
18-week intervention:1000 mg EPA + 400 mg DHA/day vs. placebo 261 No effect on serum CRP and IL-6 – Muldoon et al. (2016)
5-month intervention:➢ 300 mg EPA + DHA/day
➢ 600 mg EPA + DHA/day
➢ 900 mg EPA + DHA/day
➢ 1800 mg EPA + DHA/day
➢ placebo 125 No significant effect on IL-6 or CPR;Marginal effect on TNF-α observed at the highest dose (1800 mg) Higher RBC DHA was associated with lower TNF-α concentrations. Flock et al. (2014)
8-week intervention:2500 mg EPA + DHA/day vs. placebo 35 ↓IL-6, IL-1β and TNFα – Tan et al. (2018)
Obese patients
2-month intervention:➢ 460 mg EPA and 380 mg DHA/day
➢ control (butter fat) 55 ↓IL-6↓ inflammatory gene expression in adipose tissue↑release of anti-inflammatory eicosanoids in adipose tissue ↓TG Itariu et al. (2012)
3-month intervention: 360 mg EPA and 1290 mg DHA/day vs. placebo 59 ↓ VCAM-1; ↓ PECAM-1; ↓ hsCRP No effect on IL-6 ↓ TG; ↓insulin.No effect on TC, HDL, LDL, NEFA, FBG Polus et al. (2016)
10-week intervention:➢ 2700 mg EPA/day
➢ 2700 mg DHA/day
➢ placebo 154 ↓ IL-18 and ↑ adiponectin (DHA > EPA)No difference between EPA and DHA regarding effect on CRP, IL-6, TNFα ↓ TG; ↑ HDL (DHA > EPA)↑ LDL by DHA only in men Allaire et al. (2016)
10-week intervention:➢ 2700 mg EPA/day
➢ 2700 mg DHA/day
➢ control (corn oil) 154 EPA: ↑TRAF3 and PPARα expressionDHA: ↑ PPARα and TNFα expression both ↓CD14 expression No significant difference between EPA and DHA. Vors et al. (2017)
12-week intervention:➢ LSM + 600 mg EPA + DHA/day
➢ LSM
➢ placebo 29 LSM & n-3 PUFA ↑ adiponectin in comparison to LSMNo effect on IL6 No effect on leptin, LIF, follistatin, BDNF, and fasting triacylglycerol Sedláček et al. (2018)
Hypertensive and/or diabetic obese patients
8-week intervention:300 mg EPA + 200 mg DHA/day vs. control 64 ↓CRP ↓ FBG; ↓TG Ellulu et al. (2016)
Impaired glucose metabolism patients
6-month intervention:1800 mg EPA/day vs. placebo 107 ↓ CRP but similar effects in placebo ↑ HDL and ↓fasting TG; No effect on HbA1c and FBG Sawada et al. (2016)
9-month intervention:2388 mg EPA +1530 mg DHA/day vs placebo 36 No effect in IL-1B, IL-6, hsCRP, ICAM and VCAM No effect on FBG, insulin, HOMA-IR. Clark et al. (2016)
Type 2 diabetes mellitus
12-week intervention: 4000 mg (42% EPA + 25%DHA)/day vs. placebo 91 No significant effect on CPR ↓ TG; No effect on LDL, HDL, HbA1c Wong et al. (2010)
12-week intervention: 900 mg EPA/day vs. placebo 24 No effect on CRP, IL-6 and TNFα ↑ HDL and ↑ total cholesterol Mocking et al. (2012)
8-week intervention: 2700 mg EPA + DHA/day 84 ↓ IL-2 and ↓ TNFαNo effect on CRP None tested Malekshahi Moghadam et al. (2012)
12-weeks intervention:➢ 1000 mg EPA/day
➢ 1000 mg DHA/day
➢ placebo 60 No effect on serum CRP and MDA No effect on body weight, BMI or fat mass Azizi-Soleiman et al. (2013)
24-week intervention:➢ 2800 mg EPA + DHA + 15 mg pioglitazone/day
➢ 2800 mg EPA + DHA + placebo/day
➢ 5 mg pioglitazone/day
➢ placebo 60 No effect on SOD, TBARS, GSSG/GSH ↑ HbA1c; ↑FBGNo effect on TG, TC, HDL, LDL, NEFA, Leptin, Adiponectin Veleba et al. (2015)
3-month intervention: 1000 mg EPA + 1000 mg DHA/day vs. placebo 74 No effect on hsCRP, IL-6, TNF-α, ICAM-1, VCAM-1 No effect on insulin, HbA1c, adiponectin, leptin, and lipid levels Poreba et al. (2017)
Metabolic syndrome
90-day intervention:➢ 1800 mg EPA+ 1200 mg DHA + 10 mL extra virgin oil/day
➢ 1800 mg EPA + 1200 mg DHA + placebo/day
➢ 10 mL extra virgin oil/day
➢ placebo 102 No effect on CPR No effect on TG, TC, HDL, LDL, FBG, insulin, HOMA-IR Venturini et al. (2015)
Inflammatory bowel disease
8-week intervention: 3400–3600 mg n-3 PUFA (as salmon)/day 12 ↓ CPR, ↑ anti-inflammatory fatty acid indexNo effect TNF- α, MDA ↑ n-3 PUFAs,↑ n-3/n-6 ratio in plasma and rectal biopsies; No effect on the fecal calprotectine Grimstad et al. (2011)
90-day intervention: 2000 mg EPA/day 20 ↑ IL-10 expression; HES1, SOCS3, and KLF4 ↓ fecal calprotectinePartially redressed microbiota composition Prossomariti et al. (2017)
6-month intervention: 1000 mg EPA/day vs.placebo 60 No effect on CPR ↓ fecal calprotectine Scaioli et al. (2018)
EPA – Eicosapentaenoic Acid; DHA – Docosahexaenoic Acid; PG – Prostaglandins; LTB – Leukotriene; TNF-α – Tumour Necrosis Factor alpha; IL – Interleukin; CRP – C-Reactive Protein; ICAM – Intercellular Adhesion Molecule; VCAM – Vascular Cell Adhesion molecule; hsCRP – high sensitive C reactive protein; IL1RN – interleukin-1 receptor antagonist protein; LSM – lifestyle modification; NF-κB – nuclear factor-kappa B); PPAR – peroxisome proliferator-activated receptor; TRAF3 – TNF Receptor Associated Factor 3; Lp-PLA2 – lipoprotein-associated phospholipase A2; PECAM – platelet and endothelial cell adhesion molecule; COX – cyclooxygenase; LOX – lypoooxigenase; TBARS –thiobarbituric acid substances; SOD – superoxide dismutase; GSH – glutathione peroxidase; MDA – malonyldialdehyde; HOMA-IR – homeostasis model assessment of insulin resistance index; HES1 – transcription factor HES1; SOCCS3 – suppressor of cytokine signaling 3; KLF4 – Kruppel-like factor 4; HbA1c – Glycated haemoglobin; RBC – red blood cell; BDNF – Brain-derived neurotrophic factor; CD14 – cluster of differentiation 14; NEFA – Non-esterified fatty acids; TC – total cholesterol; TG – Triglycerides; LDL – low-density lipoproteins; HDL – high-density lipoproteins; FBG – fasting blood glucose; LIF – leukocyte inhibitory factor.