Table 5.
Association between omega-3 PUFA supplementation and cognitive function.
| Study | Design | Mean Follow-Up | Country | Sample Size | Average Age (Year) | Sex Male/Female (%) |
Intervention | Main Results |
|---|---|---|---|---|---|---|---|---|
| Lin PY et al. [108] | RCT | 24 months | Taiwan | 163 | 77.8 ± 8.4 | 66.2/33.8 | 163 patients were randomly assigned to DHA (0.7 g/day), EPA (1.6 g/day), or EPA (0.8 g/day) + DHA (0.35 g/day) group for 24 months. | A statistically significant difference in cognitive, functional, and mood status scores, biochemical profiles, and inflammatory cytokines levels was not determined between the placebo and treatment groups. |
| Nolan JM et al. [103] | RCT | 12 months | Ireland | 50 + 27 | ≥65 | 53/47 | Patients consumed 1 g fish oil (of which 500 mg DHA, 150 mg EPA), 22 mg carotenoids (10 mg lutein, 10 mg meso-zeaxanthin, 2 mg zeaxanthin), and 15 mg vitamin E daily. | The active group performed better in objective measures of AD severity (i.e., memory and mood), with a statistically significant difference in the clinical collateral for memory (p < 0.001). |
| Giudici KV et al. [109] | RCT | 3 years | France | 1445 | 75.3 ± 4.4 | 35.8/64.2 | ω-3 (800 mg DHA and 225 mg EPA/day) | No effect. |
| Arellanes IC et al. [113] | RCT | 6 months | USA | 33 | 68 (58–90) | 18.2/81.8 | 33 individuals were provided with a vitamin B complex (1 mg of vitamin B12, 100 mg of vitamin B6 and 800 mcg of folic acid per day) and randomized to 2152 mg of DHA per day or placebo over 6 months. | No effect. |
| Rasmussen J. [107] | RCT | 24 months | Finland, Germany, Netherlands, Sweden | 311 | >65 | 45/55 | Patients were given a combination of DHA, EPA, uridine monophosphate, choline, phospholipids, selenium, folic acid, and vitamins B12 and E (>200% the recommended daily intake). | This intervention had the potential to improve the progression of Alzheimer’s disease (attention, memory, executive function p < 0.05). |
| Stavrinou PS et al. [104] | RCT | 6 months | Cyprus | 36 | 78.8 ± 7.3 | 38.8/61.2 | 20 mL dose of a formula containing a mixture of omega-3 (810 mg EPA and 4140 mg DHA) and omega-6 FA (1800 mg gamma-LA and 3150 mg LA) (1:1 w/w), with 0.6 mg of vitamin A, vitamin E (22 mg) plus pure γ-tocopherol (760 mg). | A significant interaction between supplementation and time was found on cognitive function (MMSE, ACE-R, STROOP) functional capacity (6 min walk test; p = 0.028) fatigue (p < 0.001), physical health (p = 0.007), and daily sleepiness (p = 0.007). |
| Mengelberg A et al. [110] | RCT | 12 months | New Zealand | 30 + 30 | 72.3 ± 6.1 | 69.8/30.2 | 1491 mg of DHA + 351 mg of EPA per day. | No effect. |
| Atmadja T et al. [105] | RCT | 90 days | Indonesia | 29 | 66.1 ± 5.3 | 20.6/79.4 | Subjects were divided into three groups: SO, CFO, and CO with omega-3 (catfish oil enriched with omega-3). The intervention involved 1000 mg of oil/day. | Significant effects on oxidative stress and cognitive function (p < 0.05), and significantly increased MMSE score (p < 0.05). |
| Leckie RL et al. [111] | RCT | 18 weeks | USA | 271 | 30–54 | 43.5/56.5 | Fish oil capsules (1400 mg/day of EPA and DHA). | No effect. |
| Kuszewski JC et al. [114] | RCT | 16 weeks | Australia | 64 | 65.8 ± 1.4 | 44/56 | Randomly assigned to either fish oil (2000 mg/d of DHA + 400 mg/d of EPA), curcumin (160 mg/d), or a combination. | Fish oil improved CVR to a processing speed test (4.4% ± 1.9% vs. −2.2% ± 2.1%; p = 0.023) and processing speed in males only (Z-score: 0.6 ± 0.2 vs. 0.1 ± 0.2; p = 0.043). |
| Patan MJ et al. [106] | RCT | 26 h | UK | 310 | 25–49 | 35/65 | Participants consumed either 900 mg of DHA/d and 270 mg of EPA/d (DHA-rich oil), 360 mg of DHA/d and 900 mg of EPA/d (EPA-rich oil), or 3000 mg/d of refined olive oil (placebo). | EPA supplementation improved global cognitive function, superior to oil enriched with DHA; improved memory accuracy compared with DHA (p = 0.034) |
| Sueyasu T et al. [112] | RCT | 24 weeks | Japan | 71 | 65.7 ± 1.0 | 45.1/54.9 | PUFA in Combination with LZ (containing 120 mg ARA, 300 mg DHA, and 100 mg EPA per day) combined with LZ (containing 10 mg lutein and 2 mg zeaxanthin per day). | LCPUFAs + LZ supplementation did not significantly affect memory function. |
ACE-R: Addenbrooke’s Cognitive Examination–Revised; CFO: commercial fish oil; CO: catfish oil; CVR: cerebrovascular responsiveness; DHA: docosahexaenoic acid; DHA: docosahexaenoic acid; EPA: Eicosapentaenoic acid; FA: fatty acid; LA: linolenic acid; LCPUFAs + LZ: Long-Chain Polyunsaturated Fatty Acids in Combination with Lutein and Zeaxanthin; MMSE: Mini-Mental State Examination; PUFA: Polyunsaturated Fatty Acid; SO: soybean oil; STROOP: Stroop Color and Word Test.