Omega-3 Polyunsaturated Fatty Acids: Structural and Functional Effects on the Vascular Wall

Table 2

Studies evaluating n-3 PUFA effects on endothelial function.

(a) Animal studies

First author	Year	Dose	Sample	Duration (w)	Study design	Outcome measure	Results
Nyby [84]	2005	Diet enriched with 60% fructose and 4.4% n-3 PUFA versus diet with 60% fructose or control diet	Hyperinsulinemic rats	8	AES-PG	EDD, oxidative stress	Improve EDD and oxidative stress
Matsumoto [88]	2009	300 mg/kg/day EPA versus control diet	Diabetic rats	4	AES-PC	EDD	Improve EDD
Zhang [83]	2013	Diet enriched with ALA 500 mg/kg/day versus control diet	Type 2 diabetic rats	5	AES-PC	EDD, oxidative stress	Improve EDD and oxidative stress
Gortan Cappellari [82]	2013	800 mg/kg/day by gavage versus control diet	Ovariectomized rats	8	AES-PC	EDD, oxidative stress	Improve EDD and oxidative stress

(b) Human studies

First author	Year	Dose	Sample	Duration (w)	Number	Study design	Outcome measure	Results
Woodman [117]	2003	3800 mg EPA or 3700 mg DHA versus olive oil	Hypertensive type 2 patients	6	30	RCT-PG	EDD, EID	Unchanged EDD and EID
Engler [118]	2004	1200 mg n-3 PUFA versus control diet	Hypercholesterolemic children	10	20	RCT-PC	EDD, oxidative stress, inflammation	Improved EDD, unchanged oxidative stress and inflammation
Ros [119]	2004	1100–1700 mg n-3 PUFA versus Mediterranean diet	Hypercholesterolemic patients	4	20	RCT-PG	EDD, oxidative stress and CRP	Improved EDD, unchanged oxidative stress and inflammation
Keogh [120]	2005	4700 mg mg n-3 PUFA versus isocaloric high carbohydrate, saturated or monounsaturated fat enriched-diet	Healthy subjects	4	40	RCT-PG	EDD, CRP, inflammation	Improved EDD in all groups except in saturated fat enriched diet
Prabodh Shah [121]	2007	500 mg n-3 PUFA versus placebo	Healthy subjects	2	26	RCT-PC	EDD, EID	Improved EDD and EID
Wright [122]	2008	3000 mg n-3 PUFA versus standard therapy	Systemic lupus erythematosus patients	24	56	RCT-PG	EDD, oxidative stress	Improved EDD and oxidative stress
Schiano [123]	2008	1700–2000 mg versus standard therapy	Intermittent claudication patients	13	32	RCT-PG	EDD, inflammation	Improved EDD, inflammation unchanged
Mindrescu [124]	2008	4500 mg n-3 PUFA + rosuvastatin 10 g versus rosuvastatin 10 g	Dyslipidemic patients	4	30	RCT-PG	EDD, EID	Improved EDD and EID
Rizza [125]	2009	1700–2000 mg n-3 PUFA versus placebo	Offspring of type 2 diabetic subjects	12	50	RCT-PC	EDD, inflammation	Improved EDD and inflammation
Wong [99]	2010	4000 mg n-3 PUFA versus control (olive oil)	Type 2 diabetes mellitus	12	97	RCT-PG	EDD, CRP, renal function	Improved renal function; no effect on EDD or CRP
Stirban [100]	2010	2000 mg versus control (olive oil)	Type 2 diabetes mellitus	6	34	RCT-PC	Postprandial EDD	Improved postprandial EDD
Sanders [58]	2011	450–900 or 1800 mg n-3 PUFA versus placebo (refined oil)	Healthy subjects	51	310	RCT-PC	EDD	Unchanged EDD and EID
Skulas-Ray [101]	2011	850 or 3400 mg versus placebo	Moderate hypertriglyceridemia	8	26	RTC-PC	EDD, IL-6, CRP	No effect on EDD, IL-6, or CRP
Moertl [103]	2011	1000 or 4000 mg n-3 PUFA versus placebo	CHF	12	43	RCT-PC	LVEF, EDD, IL-6	Improved LVEF, EDD, and IL-6
Haberka [104]	2011	1000 mg n-3 PUFA versus control (standard diet and therapy)	Previous AMI	12	40	RCT-PG	EDD, EID	Improved EDD; EID unchanged
Din [105]	2013	2000 mg n-3 PUFA versus placebo	Cigarette smokers	6	20	RCT-PC	EDD, P-selectin, CD40L	Improved EDD and P selectin; CD40L unchanged
Din [108]	2013	2000 mg n-3 PUFA versus placebo	Previous AMI	6	20	RCT-PC	EDD, P-selectin, CD40L	No effect

n-3 PUFA, omega-3 polyunsaturated fatty acids; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid; EDD, endothelium dependent dilation; EID: endothelium independent dilation; AMI: acute myocardial infarction; CHF: chronic heart failure; LVEF: left ventricular ejection fraction; IL-6: interleukin-6; CRP: C reactive protein; AES, animal experimental study; RCT, randomized clinical trial; CT, clinical trial; PG, parallel groups; PC, placebo controlled; d, day; w, week.