Table 7.

Clinical trials assessing the impact of omega-3 fatty acids supplementation in AD patients.

N° Patients	Population Characteristic	Type and Dose Supplementation	Exposure Period	Results	References
204	AD (DSM-IV) MMSE 15–30 OmegAD Study	1720 mg/die DHA+ 600 mg/die EPA Placebo: 4000 mg corn oil Both groups: + 16 mg/die vitamin E	12 months	There was no significant statistical difference after 6- or 12-month treatment between groups in MMSE, ADAS-cog, CDR. A subgroup with very mild cognitive dysfunction showed a reduction in decline rate.	[64]
204	AD (DSM-IV) MMSE 15–30 OmegAD Study	1720 mg/die DHA+ 600 mg/die EPA Placebo: 4000 mg corn oil Both groups: + 16 mg vitamin E	12 months	Supplementation with omega-3 did not result in marked effects on neuropsychiatric symptoms except for possible positive effects on depressive symptoms (assessed by MADRS) in non-APOEε4 carriers and agitation symptoms (assessed by NPI) in APOEε4 carriers.	[65]
46	AD AD (DSM-IV) MMSE 10–26 CDR-score 1–2	720 mg/die DHA+ 1080 mg/die EPA Placebo: Olive oil Both groups: + 1.2 mg hydroquinone + 12 mg tocopherols	6 months	The treated group did not show an improvement in cognitive symptoms measured by MMSE, ADAS-cog, HDR but a relative improvement in CIBIC-plus score. In a subgroup with subjects with mild cognitive impairment (MMSE >27 e CDR 0.5–1) there was an improvement in ADAS-cog.	[66]
402	AD MMSE 14–26 Alzheimer’s Disease Cooperative Study (ADCS) DHA Supplementation Trial USA	2000 mg/die DHA from seaweed Placebo: Corn or soy oil	18 months	Supplementation with DHA compared with placebo did not slow the rate of cognitive and functional decline in patients with mild to moderate Alzheimer’s disease assessed by MMSE, ADAS-cog, CDR, ADS-ADL, NPI.	[67]
225	AD Souvenir I Study	1700 mg/die DHA+ 600 mg/die EPA (Souvenaid) Placebo: Control drink	6 months	Supplementation with omega -3 improved delayed verbal recall. However, ADAS-cog, CIBIC-plus, NPI, ADCS-ADL, ADSC-ADL were unchanged.	[68]
225	AD Souvenir I Study	1700 mg/die DHA+ 600 mg/die EPA (Souvenaid) Placebo: Control drink	6 months	Souvenaid had a positive result on ADAS-cog outcome. A higher intake of Souvenaid was also associated with greater cognitive benefit.	[69]
238	AD Souvenir II Study	1200 mg/die DHA+ 300 mg/die EPA (Souvenaid) Placebo: Control products	6 months	In the active group, the NTB memory domain increased.	[70]
527	AD MMSE 14 – 24 Connect Study	1200 mg/die DHA+ 300 mg/die EPA (Souvenaid) Placebo: Control products	6 months	Cognitive performance, as assessed by ADAS-cog, showed a decline over time in both control and active study groups, with no significant difference between study groups. Add-on intake of Souvenaid did not slow cognitive decline in persons treated for mild-to-moderate AD.	[71]
174	AD mild to moderate OmegAD Study	1720 mg/die DHA+ 600 mg /die EPA Placebo: 4000 mg corn oil	12 months	Plasma transthyretin positively correlated with MMSE and inversely with ADAS-Cog, suggesting a potential mechanism for probable positive effects of omega-3 on cognition.	[72]
39	AD MMSE 15–26 CDR 0.5–1.0 Not depressed (CESD <4.0)	675 mg/die DHA+ 975 mg /die EPA Group omega-3 plus alpha lipoic acid (LA): 675 mg/die DHA+ 975 mg/die EPA+ 600 mg/die LA Placebo: Soy oil	12 months	Active groups were no different from the placebo group in ADAS-cog, ADL. Omega-3 + LA group showed less decline assessed by MMSE. IADL differences between placebo e omega-3 and between placebo e omega-3 + LA groups were observed.	[73]
179	AD mild Souvenir II Study	1700 mg/die DHA+ 6 mg/die EPA (Souvenaid) Placebo: Control drink	6 months	The administration contributed to the maintenance of the organization of brain networks in mild AD patients.	[74]
19	AD MMSE 16–30	625 mg/die DHA+ 600 mg/die EPA Placebo: Olive oil Both groups: + 20 mg mixed tocopherols	4 months	The daily supplementation was associated with none or only negligible benefits on mood and cognition, assessed by MMSE, HVLT-R, BASDEC, BADLS.	[75]
204	AD OmegAD Study	1720 mg/die DHA+ 600 mg/die EPA Placebo: 4000 mg corn oil Both groups: + 16 mg vitamin E	6 months	The daily supplementation stabilized the cognitive performance of AD subjects, assessed by ADAS-cog and MMSE scores.	[76]
204	AD OmegAD Study	1720 mg/die DHA+ 600 mg/die EPA Placebo: 4000 mg corn oil Both groups: + 16 mg vitamin E	6 months	A decrease was observed in RvD1 and LXA4 production from peripheral blood mononuclear cells of AD patients who did not receive omega-3 but not in cells of AD subjects under omega-3 intake.	[77]
201	AD Open label extension study (OLE) Souvenir II MMSE ≥ 20	1200 mg/die DHA+ 300 mg/die EPA (Souvenaid) Placebo: Control drink	6 months	The intake of Souvenaid was well tolerated with a favorable safety profile. The adherence to Souvenaid was very high reflecting its good tolerability and ease of use.	[78]
171	AD OmegAD Study	1720 mg/die DHA+ 600 mg/die EPA Placebo: 1 g corn oil Both groups: + 16 mg vitamin E	6 months	The effect of omega-3 supplementation on MMSE and CDR appeared to be influenced by homocysteine plasma levels.	[79]