TABLE 2.
Quantitative synthesis and evidence grading for meta‐analyses of unsaturated fatty acids supplementation interventions for participants with mental disorders1
| Study, year (ref) | Mental disorders | Outcomes | Unsaturated fatty acids supplementation | No. of studies (participants, n) | Original effect metrics | Random-effects summary estimate (95% CI) | Random-effects P | I 2, % | Converted as equivalent OR (95% CI) | 95% Prediction interval | Egger's test> P | Largest study estimate (95% CI) | Significant studies | Grading | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| O/E | P | ||||||||||||||
| Xu et al., 2022 (64) | Schizophrenia | Positive and Negative Syndrome Scale total scores | EPA/DHA/EPA+DHA | 6 (317) | MD | −3.274 (−5.449, −1.098) | 0.003 | 22.2 | 0.326 (0.061, 1.751) | (0.001, 144.492) | 0.22 | 1.11 (0.49, 2.52) | 1/0.33 | 0.29 | Not significant |
| Appleton et al., 2021 (56) | Depression | Depressive symptoms | Total n–3 PUFAs | 33 (1848) | SMD | −0.401 (−0.642, −0.160) | 0.001 | 80.7 | 0.484 (0.313, 0.748) | (0.052, 4.482) | 0.05 | 0.83 (0.59, 1.18) | 10/2.16 | <10−3 | Weak |
| Quality of life | Total n–3 PUFAs | 12 (476) | SMD | −0.376 (−0.816, 0.063) | 0.093 | 78.9 | 0.506 (0.228, 1.121) | (0.029, 8.799) | 0.26 | 1.63 (0.72, 3.68) | 5/1.52 | 0.01 | Not significant | ||
| Adverse events | Total n–3 PUFAs | 24 (1503) | OR | 1.267 (0.977, 1.644) | 0.075 | 5.7 | — | (0.840, 1.912) | 0.48 | 1.26 (0.83, 1.91) | 2/1.70 | 0.69 | Not significant | ||
| de Andrade Wobido et al., 2021 (57) | Autism spectrum disorder | Aberrant Behavior Checklist | Total n–3 and n–6 PUFAs | 5 (183) | SMD | −0.183 (−0.341, −0.025) | 0.023 | 0.0 | 0.718 (0.540, 0.955) | (0.531, 0.970) | 0.80 | 0.79 (0.31, 2.03) | 1/1.46 | — | Weak |
| Social Responsiveness Scale | Total n–3 and n–6 PUFAs | 5 (238) | SMD | −0.059 (−0.239, 0.122) | 0.524 | 46.2 | 0.953 (0.691, 1.314) | (0.337, 2.694) | <0.01 | 1.88 (1.36, 4.83) | 1/4.11 | — | Not significant | ||
| Goh et al., 2021 (58) | Schizophrenia | Positive and Negative Syndrome Scale total scores | Total n–3 PUFAs | 9 (443) | SMD | −0.295 (−0.527, −0.064) | 0.012 | 28.1 | 0.586 (0.386, 0.891) | (0.230, 1.497) | 0.81 | 1.18 (0.55, 2.52) | 3/0.55 | 0.01 | Weak |
| Positive and Negative Syndrome Scale– Positive scale | Total n–3 PUFAs | 6 (266) | SMD | −0.105 (−0.349, 0.139) | 0.400 | 0.0 | 0.827 (0.531, 1.287) | (0.442, 1.547) | 0.86 | 0.82 (0.38, 1.75) | 0/0.38 | — | Not significant | ||
| Positive and Negative Syndrome Scale–Negative scale | Total n–3 PUFAs | 3 (195) | SMD | 1.193 (−0.654, 3.039) | 0.205 | 96.7 | 8.661 (0.306, 245.036) | (<0.001, >1000) | 0.08 | 0.67 (0.31, 1.46) | 1/0.42 | 0.37 | Not significant | ||
| Positive and Negative Syndrome Scale–General Psychopathology scale | Total n–3 PUFAs | 2 (145) | SMD | −0.388 (−1.103, 0.327) | 0.287 | 77.7 | 0.495 (0.136, 1.806) | — | — | 0.93 (0.44, 2.03) | 1/0.10 | 0.10 | Not significant | ||
| Händel et al., 2021 (59)2 | Attention-deficit/hyperactivity disorder | Parent-reported core symptoms | Total n–3 and n–6 PUFAs | 24 (1754) | SMD | −0.167 (−0.318, −0.015) | 0.031 | 60.7 | 0.739 (0.562, 0.972) | (0.245, 2.228) | 0.04 | 1.54 (1.36, 3.24) | 8/1.04 | 0.05 | Weak |
| Teacher-reported core symptoms | Total n–3 and n–6 PUFAs | 10 (640) | SMD | −0.062 (−0.310, 0.186) | 0.626 | 55.0 | 0.894 (0.571, 1.401) | (0.241, 3.324) | 0.26 | 1.14 (0.59, 2.22) | 2/0.58 | 0.11 | Not significant | ||
| Parent-reported behavioral difficulties | Total n–3 and n–6 PUFAs | 7 (682) | SMD | −0.014 (−0.169, 0.141) | 0.859 | 0.0 | 0.975 (0.736, 1.291) | (0.675, 1.409) | 0.73 | 0.74 (0.41, 1.31) | 0/0.89 | — | Not significant | ||
| Teacher-reported behavioral difficulties | Total n–3 and n–6 PUFAs | 5 (377) | SMD | −0.041 (−0.346, 0.264) | 0.791 | 49.1 | 0.928 (0.534, 1.612) | (0.178, 4.824) | 0.38 | 0.96 (0.49, 1.88) | 1/0.25 | 0.23 | Not significant | ||
| Quality of life | Total n–3 and n–6 PUFAs | 2 (191) | SMD | 0.014 (−0.288, 0.316) | 0.929 | 0.0 | 1.025 (0.593, 1.771) | — | — | 0.98 (0.52, 1.88) | 0/0.10 | — | Not significant | ||
| Suradom et al., 2021 (60) | Depression | Prevention of depression severity | Total n–3 and n–6 PUFAs | 10 (1027) | SMD | −0.033 (−0.201, 0.134) | 0.697 | 23.2 | 0.942 (0.695, 1.275) | (0.493, 1.797) | 0.45 | 1.20 (0.71, 2.03) | 1/0.78 | 0.56 | Not significant |
| Treatment of depression severity | Total n-3 and n-6 PUFAs | 4 (209) | SMD | −0.138 (−0.543, 0.268) | 0.506 | 30.7 | 0.780 (0.374, 1.623) | (0.070, 8.640) | 0.31 | 1.54 (0.56, 4.18) | 0/0.55 | — | Not significant | ||
| Xu et al., 2021 (61) | Mild cognitive impairment | Mini-Mental State Examination | Unsaturated fatty acids | 3 (96) | MD | 0.658 (−0.008, 1.325) | 0.053 | 59.8 | 3.293 (0.986, 10.995) | (<0.001, >1000) | 0.44 | 1.10 (0.33, 3.64) | 2/0.16 | 0.01 | Not significant |
| Araya-Quintanilla et al., 2020 (52) | Alzheimer disease | Narcissistic Personality Inventor | Total n–3 PUFAs | 2 (543) | SMD | −0.342 (−1.077, 0.393) | 0.362 | 93.7 | 0.539 (0.142, 2.037) | — | — | 0.28 (0.19, 0.41) | 1/1.99 | — | Not significant |
| Mini-Mental State Examination | Total n–3 PUFAs | 3 (283) | SMD | 0.582 (−0.434, 1.597) | 0.262 | 0.0 | 2.865 (0.456, 18.016) | (<0.001, >1000) | 0.79 | 2.06 (0.19, 22.09) | 0/1.34 | — | Not significant | ||
| Alzheimer's Disease Assessment Scale– Cognitive section | Total n–3 PUFAs | 3 (239) | SMD | 1.096 (−1.031, 3.224) | 0.312 | 96.9 | 7.275 (0.155, 342.043) | (<0.001, >1000) | 0.11 | 216.09 (99.23, 470.60) | 1/2.99 | — | Not significant | ||
| Luo et al., 2020 (53)2 | Depression | Depressive symptoms | Total n–3 and n–6 PUFAs (≥2000 mg/d) | 4 (160) | SMD | −0.941 (−1.581, −0.301) | 0.004 | 66.9 | 0.182 (0.057, 0.580) | (0.001, 22.190) | 0.05 | 0.54 (0.24, 1.18) | 3/0.73 | 0.02 | Weak |
| Depressive symptoms | Total n-3 and n-6 PUFAs (<2000 mg/d) | 7 (985) | SMD | −0.630 (−1.186, −0.075) | 0.026 | 90.8 | 0.319 (0.117, 0.874) | (0.010, 9.976) | 0.13 | 0.82 (0.58, 1.16) | 2/0.68 | 0.14 | Weak | ||
| Mocking et al., 2020 (54) | Perinatal depression | Depressive symptoms | Total n–3 and n–6 PUFAs | 14 (3781) | SMD | −0.072 (−0.188, 0.045) | 0.227 | 19.0 | 0.879 (0.712, 1.084) | (0.571, 1.352) | 0.95 | 0.83 (0.67, 1.04) | 1/1.71 | 0.68 | Not significant |
| Postpartum depression | Depressive symptoms | Total n–3 and n–6 PUFAs | 4 (423) | SMD | −0.656 (−1.690, 0.378) | 0.213 | 92.7 | 0.305 (0.047, 1.982) | (<0.001, >1000) | 0.10 | 0.03 (0.01, 0.06) | 2/3.99 | — | Not significant | |
| Zhang et al., 2020 (55) | Mild cognitive impairment | Mini-Mental State Examination | Total n–3 PUFAs | 7 (434) | WMD | 0.852 (0.039, 1.665) | 0.040 | 52.2 | 1.646 (1.009, 2.685) | (0.424, 6.395) | 0.55 | 0.98 (0.59, 1.62) | 1/0.35 | 0.30 | Weak |
| Devoe et al., 2019 (48) | Psychosis | Attenuated psychotic symptoms | Total n–3 PUFAs | 3 (347) | SMD | −0.309 (−0.878, 0.261) | 0.288 | 81.1 | 0.572 (0.204, 1.604) | (<0.001, >1000) | 0.74 | 0.91 (0.57, 1.46) | 1/0.17 | 0.16 | Not significant |
| Morsy et al., 2019 (49) | Huntington disease | Total motor score | Ethyl-EPA | 2 (285) | MD | −2.720 (−4.763, −0.677) | 0.009 | 0.0 | 0.071 (0.001, 3.786) | — | — | 0.52 (0.35, 0.79 | 2/1.42 | 1.00 | Not significant |
| Total motor score-4 | Ethyl-EPA | 2 (285) | MD | −2.225 (−3.843, −0.607) | 0.007 | 9.7 | 0.025 (0.008, 0.080) | — | — | 0.01 (0.01, 0.03) | 2/1.99 | 1.00 | Weak | ||
| Zhang et al., 2019 (51) | Depression in children | Depressive symptoms | Total n–3 PUFAs | 4 (153) | SMD | −0.119 (−0.533, 0.296) | 0.575 | 30.5 | 0.807 (0.381, 1.709) | (0.069, 9.412) | 0.03 | 1.22 (0.43, 3.49) | 1/0.25 | 0.23 | Not significant |
| Su et al., 2018 (47)2 | Anxiety | Symptoms | Total n–3 PUFAs | 19 (1203) | Hedges' g | −0.374 (−0.666, −0.081) | 0.012 | 89.9 | 0.508 (0.300, 0.863) | (0.049, 5.300) | 0.10 | 1.29 (0.88, 1.87) | 6/2.11 | 0.01 | Weak |
| Rosenblat et al., 2016 (45) | Bipolar depression | Depressive symptoms | Total n–3 PUFAs | 4 (140) | SMD | −0.364 (−0.735, 0.007) | 0.054 | 8.3 | 0.517 (0.265, 1.012) | (0.092, 2.895) | 0.79 | 0.48 (0.20, 1.14) | 0/0.83 | — | Not significant |
| Tan et al., 2016 (46) | Specific learning disorders | Adverse effects | PUFAs | 2 (116) | RR | 1.402 (0.237, 8.281) | 0.710 | 0.0 | 1.402 (0.237, 8.281) | — | — | 2.05 (0.19, 21.7) | 0/0.63 | — | Not significant |
| Cooper et al., 2015 (42)2 | Attention-deficit/hyperactivity disorder | Attention (omission errors) | Total n–3 PUFAs | 6 (387) | SMD | −0.129 (−0.327, 0.069) | 0.200 | 0.0 | 0.792 (0.554, 1.132) | (0.477, 1.314) | 0.82 | 0.76 (0.43, 1.3) | 0/0.54 | — | Not significant |
| IQ | Total n–3 PUFAs | 5 (706) | SMD | 0.139 (−0.07, 0.351) | 0.200 | 23.3 | 1.286 (0.876, 1.888) | (0.513, 3.221) | 0.96 | 1.00 (0.55, 1.82) | 1/0.25 | 0.23 | Not significant | ||
| Inhibition | Total n–3 PUFAs | 12 (951) | SMD | −0.037 (−0.217, 0.143) | 0.687 | 38.9 | 0.935 (0.675, 1.295) | (0.396, 2.208) | 0.49 | 0.74 (0.43, 1.27) | 1/1.36 | — | Not significant | ||
| Mean reaction time | Total n–3 PUFAs | 11 (1107) | SMD | −0.001 (−0.118, 0.117) | 0.997 | 12.8 | 0.999 (0.808, 1.236) | (0.684, 1.460) | 0.86 | 1.29 (0.89, 1.85) | 1/1.16 | — | Not significant | ||
| Reaction time variability | Total n–3 PUFAs | 2 (114) | SMD | 0.290 (−0.709, 1.289) | 0.569 | 82.1 | 1.691 (0.277, 10.319) | — | — | 0.68 (0.25, 1.92) | 1/0.24 | 0.22 | Not significant | ||
| Reading | Total n–3 PUFAs | 8 (1433) | SMD | 0.014 (−0.062, 0.090) | 0.722 | 0.0 | 1.025 (0.894, 1.176) | (0.864, 1.218) | 0.22 | 1.04 (0.79, 1.34) | 0/0.42 | — | Not significant | ||
| Short-term memory | Total n–3 PUFAs | 14 (2188) | SMD | 0.067 (−0.013, 0.147) | 0.101 | 28.5 | 1.129 (0.976, 1.306) | (0.793, 1.608) | 0.41 | 1.00 (0.72, 1.39) | 2/0.70 | 0.15 | Not significant | ||
| Spelling | Total n–3 PUFAs | 6 (974) | SMD | 0.031 (−0.090, 0.153) | 0.614 | 5.1 | 1.058 (0.849, 1.319) | (0.738, 1.517) | 0.90 | 0.95 (0.66, 1.34) | 0/0.32 | — | Not significant | ||
| Working memory | Total n–3 PUFAs | 8 (1410) | SMD | 0.089 (−0.007, 0.185) | 0.068 | 3.6 | 1.175 (0.988, 1.397) | (0.917, 1.505) | 0.02 | 0.96 (0.74, 1.27) | 1/0.42 | 0.35 | Not significant | ||
| Yang et al., 2015 (43)2 | Depression in women | Depressive symptoms | EPA+DHA | 8 (267) | SMD | −0.648 (−1.120, −0.175) | 0.007 | 78.4 | 0.310 (0.132, 0.728) | (0.018, 5.344) | 0.09 | 0.53 (0.24, 1.20) | 6/1.70 | <0.01 | Weak |
1
All summary estimates were recalculated based on a random-effects model using the method of DerSimonian and Laird. The 95% prediction interval and Egger's test were not evaluated if available studies were <3. For excess of significance, the P value was not evaluated if the observed number of studies was smaller than expected. E, expected number of studies with positive finding; MD, mean difference; O, observed number of studies with positive finding; ref, reference; SMD, standardized mean difference; WMD, weighted mean difference.
2
The direction of comparison was normalized to supplementation group versus non-supplementation group.