Table 3.

Studies included in this review, which assessed the effect of lipids on the chronic subclinical inflammation.

Reference	Study type	Population	Methods	Results
Kantor et al. [56]	Retrospective cohort	8177 elderly, institutionalized Americans, included in the 1999–2004 cycles of the National Health and Nutrition Examination Survey	BMI classification: eutrophic < 25 kg/m²; overweight ≥ 25 < 30 kg/m²; obese  ≥ 30 kg/m²	Lower SFA intake and utilization of fish oil were associated with ↓ CRP in eutrophic and overweight groups, but not in obese
			24 h recall
Krysiak et al. [69]	Randomized, controlled clinical trial	101 (66 M/35 W) overweight, hypertriglyceridemic Polish adults	Group 1: placebo	Group 2: ↓ IL-2, IFN-γ, and TNF-α and CRP n-3 did not significantly reduce these parameters
			Group 2: bezafibrate (200 mg twice a day)	Bezafibrate was better than n-3 in inhibiting low-grade inflammation
			Group 3: n-3 (1 g, twice a day)
			Duration: 12 weeks
Dewell et al. [70]	Randomized, controlled clinical trial	100 obese American adults, with metabolic syndrome	Group 1: vegetable-derived n-3	↔ sICAM-1, IL-6, and monocyte chemoattractant protein in all three groups
			Subgroup 1: low dose (2.2 g/d of n-3)	No beneficial independent effect of dose or source
			Subgroup 2: high dose (6.6 g/d of n-3)
			Group 2: sea-derived n-3
			Subgroup 1: low dose (1.2 g/d)
			Subgroup 2: high dose (3.6 g/d)
			Group 3: placebo
			Duration: 8 weeks
Malekshahi Moghadam et al. [61]	Double-blind, controlled, randomized clinical trial	84 (42 M/42 W) overweight Iranian adults and elderly with DM for at least 2 years	Group 1: 3 n-3 capsules/day (EPA 1.548 mg; DHA 828 mg; other n-3 338 mg)	Group 1: ↓ IL-2 and TNF-α
			Group 2: 3 placebo capsules (sunflower oil 2100 mg)	↔ CRP
			Duration: 8 weeks
Kratz et al. [67]	Double-blind, controlled, randomized clinical trial	24 (8 M/16 W) overweight, or level-1 obese American adults	Group 1: n-3-rich diet (3.5% of diet energy)	↔ Gene expression of inflammatory mediators by adipose tissue
			Group 2: diet poor in n-3 (0.5% of energy diet)	↔ IL-6, MCP-1, TNF receptors 1 and 2, and CRP
			Duration: 14 weeks (ad libitum by 12)
Rajkumar et al. [62]	Randomized, controlled clinical trial	60 (30 M/30 W) overweight Indian adults	Group 1: placebo	Group 2: ↓ CRP
			Group 2: omega-3 (EPA 180 mg/d, DHA 120 mg/d)	Group 4: more pronounced effect in CRP reduction
			Group 3: probiotic VSL # 3 (112.5 × 109 UFC)
			Group 4: omega-3 (EPA 180 mg/d, DHA 120 mg/d) and probiotic VSL # 3 (112.5 × 109 UFC)
			Duration: 6 weeks
Cipollina et al. [66]	Double-blind, controlled, randomized clinical trial	45 overweight American adults, with EPA + DHA consumption ≤ 300 mg/d	Group 1: capsules containing 1.4 g/d of EPA + DHA	Group 1: ↑ DHA and EPA, no significant modulation in the levels of arachidonic acid metabolites
			Group 2: Placebo (soy oil)
			Duration: 4 months
Nigam et al. [71]	Double-blind, controlled, randomized clinical trial	316 (221 M/105 W) overweight American adults and elderly with symptomatic paroxysmal or persistent FA	Group 1: fish oil (4 g/d)	Group 1 ↔ inflammation or oxidative stress ↓ CRP in a similar degree between the groups, after 6 months (CRP 11% versus 11% for fish oil versus placebo, respectively)
			Group 2: placebo
			Duration: 271 ± 129 days
Ito et al. [63]		125 (64 M/61 W) obese Japanese adults, with (n = 94) or without (n = 31) dyslipidemia	Group 1 (treatment group—dyslipidemic): diet (isocaloric, normoproteic, and normolipidemic), EPA 1.8 g/d	DHA/AA and DGLA/AA ratios were higher in dyslipidemic obese, in comparison with the nondyslipidemic
			Group 2 (control—dyslipidemic): diet (isocaloric, normoproteic, and normolipidemic), no EPA.	Group 1: ↓ CRP, ↓ DLGA/AA ratio
			Group 3 (control—nondyslipidemic): no intervention
			Duration: 3 months
Lee et al. [32]	Double-blind, controlled, randomized clinical trial	14 obese American with metabolic syndrome and 45 adults and elderly type-2 diabetics	Group 1: corn oil (4.02 g/d)	Group 2: ↑ serum ALA
			Group 2: botanical oil (BO) (6.28 g/d)	Group 3: ↑ EPA and DHA; ↓ DGLA and AA
			Group 3: fish oil (FO) (7.64 g/d)	Groups 1 and 2 were associated with increased levels in biomarkers related to type-2 diabetes and metabolic syndrome
			Duration: 8 weeks
Camargo et al. [78]	Randomized, cross-over clinical trial	49 individuals (19 M/30 W) with metabolic syndrome	Group 1: breakfast rich in olive oil with high phenolic content (398 ppm)	Group 1: higher IL-6, IL-1, CXCL reduction
			Group 2: breakfast rich in olive oil with intermediate phenolic content (149 ppm)
			Group 3: breakfast rich in olive oil with low phenolic content (70 ppm)
			Duration: 2-hour postprandial
Ceriello et al. [77]	Randomized, controlled clinical trial	24 diabetics (17 M/7 W)	Group 1: Mediterranean diet (olive oil)	Group 1: ↓ IL-6, sICAM-1, PGF2α
			Group 2: hypolipidemic diet
			Duration: 3 months
Casas et al. [7]	Randomized, controlled clinical trial	164 (77 M/87 W) individuals with cardiovascular risk	Group 1: Mediterranean diet + 50 ml extravirgin olive oil	Groups 1 and 2: ↓ CRP, IL-6, sICAM
			Group 2: Mediterranean diet + 30 g/d of oilseeds
			Group 3: hypolipidemic diet
			Duration: 12 months
Darghosian et al. [72]	Double-blind, controlled, randomized clinical trial	190 (109 M/81 W) overweight American adults and elderly with FAR	Group 1: n-3 (4 g/d)	↔ IL-6, IL-8, IL-10, TNF-α, monocyte chemoattractant protein, and vascular endothelial growing factor
			Group 2: placebo
			Duration: 6 months
Krantz et al. [68]	Double-blind, controlled, randomized clinical trial	72 (22 M/42 W), mainly Latin (71%) obese adults and elderly	Group 1: 3.36 g/d of n-3 (EPA/DHA)	Group 1: nonsignificant CRP reduction
			Group 2: placebo	↔ Inflammation
			Duration: 3 months
Itariu et al. [64]	Randomized, controlled clinical trial	55 (9 M/46 W) level-3 obese American adults and elderly	Group 1: 3.36 g/d of n-3 (EPA/DHA)	Group 1: ↓ gene expression of inflammatory markers in subcutaneous adipose tissue
			Group 2 (placebo): 3.36 g/d of butter	↓ IL-6
			Duration: 8 weeks	↑ anti-inflammatory eicosanoids in visceral adipose tissue
Lesná et al. [57]	Double-blind, controlled, randomized clinical trial	15 overweight or obese adult American women, in postmenopause	2- to 3-week cross-over interventions, with 1-week interval between them	Change from Group 1 to Group 2: ↓ CRP and IL-18 (the latter was not significant)
			Group 1 (animal-derived SFA): 42% of TCV
			Group 2 (vegetable-derived PUFA): 40% of TCV
Silver et al. [59]	Double-blind, controlled, randomized clinical trial	144 level-1 obese adult American women in postmenopause	Women received Group 1 diets during 2 weeks	↓ IL-1α, IL-1β, 1L-12, IL-17, IFN-γ, TNF-α, TNF-β
			Group 1 (DHL): high-fat diet (50% of TCV); 1/3 SFA, 1/3 MUFA, 1/3 PUFA)	Compared to DHL + P, DHL + S had higher effect on the IFN-γ reduction (↓74%) and DHL + L had higher effect on PAI-1 reduction (↓ 31%)
			Hence, they were randomized into the following groups for 14 weeks:	MUFA/PUFA/SFA in the diet changed markers to CVD
			Group 2 (DHL-P): DHL + placebo
			Group 3 (DHL-S): DHL + stearate (9 g/d)
			Group 4 (DHL+O): DHL + oleate (9 g/d)
			Group 5 (DHL+L): DHL + linoleate (9 g/d)
Agh et al. [65]	Double blind, controlled, randomized clinical trial	45 men with coronary artery disease	Group 1: n-3 (720 mg EPA, 480 mg DHA)	Group 1: ↓ CRP
			Group 2: placebo (edible paraffin)
			Duration: 8 weeks	Group 2: ↔ CRP

M: men; W: women; BMI: body mass index; SFA: saturated fatty acids; CRP: C-reactive protein; n-3: omega-3; sICAM-1: soluble intercellular adhesion molecule-1; IL: interleukin; IFN-γ: interferon gamma; TNF-α: tumor necrosis factor alpha; EPA: eicosapentaenoic acid; DHA: docosahexaenoic acid; DM: diabetes mellitus; AA: arachidonic acid; DGLA: dihomo-gamma-linolenic acid; ALA: alpha-linolenic acid; CXCL: chemokine (C-X-C motif) ligand; PGF2α: prostaglandin F2α; PAI-1: plasminogen activator inhibitor-1; CVD: cardiovascular disease; MUFA: monounsaturated fatty acids; PUFA: polyunsaturated fatty acids.