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; ↑ LDL No 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 expression DHA: ↑ 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 LSM No 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 ↓ TNFα No 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; ↑FBG No 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 index No 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 calprotectine Partially 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.