Table 1.
Overview of the study characteristics.
| Authors and Year | Country | Dose and Method | Sample | Treatment Duration | Results | Outcome | Type/Genres |
|---|---|---|---|---|---|---|---|
| Freund-Levi et al., 2008 [29] | Sweden | Dose: 1.7 g DHA and 0.6 g EPA daily. Method: Randomized, double-blind, placebo-controlled. Patients received either omega-3 supplements or placebo. |
Size: 204 patients enrolled, 174 completed the study. Characteristics: Patients with Alzheimer’s disease, living in their own homes, stable dose of acetylcholine esterase inhibitors. Mean age: 74 years. Gender distribution: 51% female. |
12 months (6 months randomized to omega-3 or placebo, followed by 6 months of omega-3 for all). | No significant overall treatment effects on neuropsychiatric symptoms, daily living activities, or caregiver’s burden. Some significant effects observed in specific domains (NPI agitation domain in APOEv4 carriers, MADRS scores in non-APOEv4 carriers). |
MADRS | |
| Freund-Levi et al., 2014 [30] * | Sweden | Dose: 430 mg DHA and 150 mg EPA per capsule, total of four capsules daily. Additional Components: 4 mg vitamin E per capsule. Placebo: Corn oil with 0.6 g linoleic acid per capsule. Method: Randomized, double-blind, placebo-controlled. Patients received either omega-3 supplements or placebo oil. |
Size: 41 patients enrolled, 37 completed the study. 17 omega-3 fatty acid (ω-3 FA) group. 20 placebo group. Characteristics: Patients diagnosed with Alzheimer’s disease according to the DSM-IV criteria, having an MMSE score between 15 and 30. Mean age: 70 years. Gender distribution: 40.5% female. |
6 months. | No significant difference in treatment effect between supplemented and non-supplemented patients. | - | |
| Giudici et al., 2020 [31] * | Netherlands | Dose: 400 mg DHA and ≤112.5 mg EPA per capsule, two capsules daily. Method: Randomized assignment into one of four groups: 1. Multidomain intervention plus omega-3 supplementation; 2. Multidomain intervention plus placebo; 3. Omega-3 supplementation only; 4. Placebo. Multidomain intervention components: Cognitive stimulation, physical activity, and nutritional counseling. |
Size: 1445 participants. Characteristics: Participants must have self-reported memory loss and inability to carry out an instrumental activity of daily living. Mean age: 75.3 years. Gender distribution: 64.2% female. |
36 months. | No significant between-group differences were observed in the decrease in intrinsic capacity (IC) Z-score among all groups after 3 years when comparing each intervention group with participants taking placebo. Additionally, no long-term effects were noted in the omega-3 supplementation groups compared to placebo. | - | |
| Hashimoto et al., 2017 [32] | Japan | Dose: 860 mg DHA and 203 mg EPA daily for the intervention group; 53 mg DHA and 15 mg EPA daily for the control group. Method: Double-blind study. Participants received daily cooked meals including fish sausages, with differing DHA and EPA contents. Participants were blinded to the food products. |
Size: 75 participants enrolled, 66 completed the study. Characteristics: Patients with Alzheimer’s disease, elderly individuals from care facilities and a nursing home in Shimane prefecture, Japan, including 10 men and 65 women. Mean age: 88.5 years. Gender distribution: 86.67% female. |
12 months. | Significant increases in the levels of EPA and DHA, as well as in the DHA/AA and EPA/AA ratios, were observed in the active group compared to the control group after 12 months. Furthermore, certain aspects of cognitive functions, measured by MMSE and HDS-R scores, demonstrated significant improvements, suggesting benefits against age-related cognitive decline. | SDS | |
| Lin et al., 2022 [21] | Taiwan | Dose: Pure EPA group: 1.6 gm daily; Pure DHA group: 0.7 gm daily; Combination group: 0.8 gm EPA and 0.35 gm DHA daily. Method: Participants were divided into three groups, each receiving two 0.5 gm capsules twice a day. The placebo group received soybean oil capsules. |
Size: 163 participants. Characteristics: Condition distribution: 93 with MCI, 70 with mild to moderate Alzheimer’s disease. Source: Mainly elderly individuals from veteran retirement centers. Mean age: 77.9 years. Gender distribution: 33.75% female. |
24 months. | No significant differences were observed among treatment groups and placebo regarding cognitive, functional ability, and mood status outcomes after 24 months. This suggests that n-3 PUFA supplementation might not have significant effects on the disease progression rate in MCI and AD patients. | GDS | |
| Maltais et al., 2019 [33] * | France | Dose: Two soft capsules daily, each containing 400 mg DHA and up to 112.5 mg EPA. Method: Participants were assigned to one of four groups for a duration of 3 years: 1. Multidomain intervention plus omega-3; 2. Omega-3 only; 3. Multidomain intervention only; 4. Placebo. Multidomain intervention components: Nutritional and physical activity counseling, and cognitive training. |
Size: 1680 participants. Characteristics: Participants must have self-reported memory loss, and slow gait speed. Demographics: Community-dwelling men and women aged 70 years or older. Mean age: 75.2 years. Gender distribution: 64.73% female. |
36 months. | No significant effect of any intervention (multidomain, omega-3, or their combination) was found on the progression of depressive symptoms. The incidences of developing minimum clinically meaningful, moderate, and severe depressive symptoms were not significantly different across the four groups. | - | |
| Rondanelli et al., 2012 [34] | Italy | Dose: Two capsules daily, each containing DHA 720 mg, EPA 286 mg, vitamin E 16 mg, soy phospholipids 160 mg, tryptophan 95 mg, and melatonin 5 mg, taken 1 h before bedtime. Method: Randomized, double-blind, placebo-controlled. Participants received either the described capsules or placebo capsules containing non-fish oils without omega-3 or omega-6 fatty acids. |
Size: 25 participants: 11 supplement group; 14 placebo group. Characteristics: Participants with MCI. Mean age: 86 years. Gender distribution: 80.20% female. |
12 weeks. | Not statistically significant, the trend of improvement in depressive symptoms as evaluated with GDS was observed in the supplement group after 12 weeks of treatment with the dietary supplement. | GDS | |
| Sinn et al., 2012 [35] | Australia | Dose: EPA-rich fish oil group: 1.67 g EPA and 0.16 g DHA; DHA-rich fish oil group: 1.55 g DHA and 0.40 g EPA; Control group: Safflower oil with 2.72 g linoleic acid (LA). Method: Randomized allocation into one of three groups. |
Size: 50 volunteers recruited, 40 completed assessments. Characteristics: Participants must have self-reported memory loss. Mean age: 74.03 years. Gender distribution: 33% female. |
6 months. | Significant improvement in depression (GDS) scores was observed in the EPA and DHA groups compared with the control group after 6 months. However, no significant treatment effects were found on the physical or mental quality of life outcomes. In the DHA treatment group, initial letter fluency scores significantly improved compared with the control group. | GDS | |
| van de Rest et al., 2009 [36] * | Netherlands | Dose: High dose group: 1800 mg per day of EPA-DHA; Low dose group: 400 mg per day of EPA-DHA; Placebo group. Method: Randomized, double-blind, placebo-controlled. Participants received either 1800 mg, 400 mg of EPA-DHA, or a placebo. |
Size: 302 participants. Characteristics: Participants were aged 65 years and older. A score of more than 21 on the MMSE. Mean age: 69.8 years. Gender distribution: 55% male. |
26 weeks. | No significant differences were observed in the quality of life scores among the three groups after 13 and 26 weeks of intervention. | - | |
Abbreviations: DHA (docosahexaenoic acid), EPA (eicosapentaenoic acid), LA (linoleic acid), MCI (mild cognitive impairment), SDS (Zung Self-Rating Depression Scale), GDS (Geriatric Depression Scale), * (Review only).