TABLE 5.
Summary of randomized controlled trials of ω-3 fatty acids in cognitively healthy subjects1
| Subjects, n; age range; mean ± SD age, y; study length; % male | P values | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| RAVLT | ||||||||||
| Authors | Intervention | COWAT | DSST | TMT A | TMT B | RAVLT1 | RAVLT2 | RAVLT3 | RAVLT4 | |
| Külzow et al.2 (29) | n = 44;50–75 y;Age: EPA/DHA: 63 ± 6, Placebo: 61 ± 6;26 wk;45% male | EPA 1320 mg, DHA 880 mg, both with vitamin E 15 mg;Placebo: sunflower oil 406 mg | Words starting with S: 0.25;Fruits: 0.62 | 0.55 | 0.33 | 0.48 | 0.87 | |||
| Howe et al. (36) | n = 38;40–85 y;Age: EPA: 63.2 ± 1.6, Placebo: 64.1 ± 2.3;20 wk;68% Male;Mildly hypertensive | EPA 400 mg, DHA 1600 mg;Placebo: corn oil | P = 0.5 for the sum of TMT A and TMT B | |||||||
| van de Rest et al. (34) | n = 302;≥65 y;Age: EPA/DHA: 1800 mg: 69.9 ± 3.4, EPA/DHA: 400 mg: 69.5 ± 3.2, Placebo: 70.1 ± 4.0;26 wk;55% male | High dose:EPA 1093 mg, DHA 847 mg;Low dose:EPA 226 mg, DHA 174 mg;Placebo: high-oleic sunflower oil | NS | NS | NS | NS | NS | NS | ||
| Dangour et al.3 (35) | n = 867;70–79 y;Age: fish oil: 74.7 ± 2.5, Placebo: 74.6 ± 3.0;24 mo;55% male | EPA 200 mg, DHA 500 mg;Placebo: olive oil | NS | NS | 0.14 | 0.46 | ||||
| Chew et al.4 (37) | n = 3501;50–85 y;Age: 72.7 ± 7.7;5 y;42.5% male | EPA 650 mg, DHA 350 mg;Vs. AREDS formulation: vitamins C, E, β-carotene, and zinc | Animals: 0.34;Letters starting with F, A, and S: 0.78 | |||||||
| Witte et al.5 (28) | n = 65;50–75 y;Age: 63.9 ± 6.6;26 wk;53.9% male | EPA 1320 mg; DHA 880 mg;Placebo: sunflower oil | 0.009 | |||||||
| Mazereeuw et al. (32); CAD subjects | n = 92;Age: 61.7 ± 8.7;12 wk;76% male | DHA 1200 mg/d, EPA 600 mg/d, EPA:DHA ratio 1:2;Other: LC-PUFAs 100 mg/d;Placebo: soybean/corn oil | NS | NS | No benefit on CVLT which is similar to RAVLT | |||||
| Tokuda et al. (31) | n = 113;Age: Placebo: 59.5 ± 0.4, EPA/DHA: 59.8 ± 0.5;1 mo;100% male | DHA 300 mg, EPA 100 mg,ARA 120 mg;Placebo: olive oil | Improvement in P3006 | |||||||
| Geleijnse et al. (33); post-MI patients | n = 2911;Age: men: 68.7 ± 5.5 y, women: 70.3 ± 5.6 y;40 mo | 1) EPA:DHA 400 mg/d, EPA:DHA ratio 3:2; 2) EPA/DHA 400 mg/d, ALA 2 g/d, EPA:DHA ratio 3:2;Placebo: margarine | No change in MMSE | |||||||
| Konagai et al. (30) | n = 45;Age: 67.1 ± 3.4 y;3 mo;100% male | 1) Krill oil: DHA 92 mg/d, EPA 193 mg/d, DHA:EPA ratio 1:2;2) Sardine oil: DHA 251 mg/d, EPA 491 mg/d;Placebo: medium-chain triglyceride | Both krill oil and sardine oil had better P300 6 than placebo | |||||||
ARA, arachidonic acid; AREDS, Age-Related Eye Disease Study; CAD, coronary artery disease; COWAT, Controlled Oral Word Association Test; CVLT, California Verbal Learning Test; DSST, Digit-Symbol Substitution Test; LC-PUFA, long-chain PUFA; MMSE, Mini-Mental Status Examination; NS, nonsignificant; RAVLT, Rey Auditory Verbal Learning Test; RAVLT1, immediate recall as a sum of 4 trials; RAVLT2, short delay recall; RAVLT3, delayed recall; RAVLT4, delayed recognition; TICS-M, Telephone Interview Cognitive Status-Modified; TMT, Trail Making Test.
Külzow et al. (29) used the LOCATO, which examines visual-spatial object location of buildings, and the RAVLT. After adjustment for changes in diet, those on ω-3 fatty acids did better on the LOCATO (P = 0.004). As noted in the table, the RAVLT was not significant.
The CVLT was performed which is similar to the RAVLT.
This is an ancillary study of the AREDS2 randomized clinical trial. A composite score was computed to obtain an overall score for a battery of 8 cognitive function tests and was not significant. The composite score included the scores of the following: TICS-M word list for immediate recall; Verbal fluency with animal category; Verbal fluency with letter category; Verbal fluency alternating between animal and letter categories; Wechsler logical memory I and Wechsler logical memory II which measured immediate and delayed recall of 2 stories, respectively; Digits backward; and TICS-M delayed recall. All test results were converted into z scores which were then added.
Witte et al. (28) calculated a composite executive score which was significant at P = 0.023. The composite executive score was defined as the sum of phonemic fluency and semantic fluency minus TMT (part B − part A)/part A and minus STROOP {[part 3 − (part 1 + part 2)]/2}/4. Preservation of both the integrity of the microstructure of white mass and the volume of gray mass was observed with a dose of 1320 mg EPA plus 880 mg DHA per day for 26 wk.
P300 measures working memory by measuring event-related potentials using an electroencephalograph (31). P300 depicts central nervous system activity involved in the processing of new information when attention is engaged to update memory representation. P300 has 2 components: latency, which reflects cognitive processing speed; and amplitude, which measures attentional resources engaged in task completion (30). Latency is prolonged and amplitude is decreased with aging, a finding suggesting that P300 testing can evaluate cognitive function in healthy elderly adults (31).