Table 3.
Peak height values of serum primary metabolites at baseline and after EPA and DHA supplementation (alphabetic order)1.
| Baseline | EPA | ∆EPA from baseline2 | DHA | ∆DHA from baseline2 | FDR ∆EPA vs. ∆DHA3 | |
|---|---|---|---|---|---|---|
| -Ketoglutarate | 1572 (1374, 2098) | 1344 (820, 1699) | − 546 (− 848, 156)** | 1011 (814, 1303) | − 574 (− 1095, − 25)*** | 0.70 |
| -Tocopherol | 17,567 (15,450, 21,920) | 21,166 (17,377, 24,927) | 3599 (244, 4918)* | 21,490 (15,673, 23,604) | 3495 (− 430, 5599) | 0.042 |
| Citric acid | 67,091 (58,034, 76,758) | 63,059 (55,048, 74,021) | − 5585 (− 12,624, 8242) | 60,541 (46,556, 65,524) | − 10,005 (− 21,349, − 845)*** | 0.05 |
| Cysteine | 30,308 (28,004, 40,007) | 31,598 (25,512, 38,123) | − 1645 (− 6057, 10,161) | 28,160 (25,635, 30,844) | − 2545 (− 11,847, 3008)* | 0.47 |
| Docosahexaenoic acid | 1324 (1002, 1617) | 1833 (1384, 2472) | 493 (272, 1180)*** | 1611 (1214, 1840) | 278 (− 32, 572) | 0.51 |
| Deoxytetronic acid | 1323 (681, 1690) | 1235 (635, 1666) | − 88 (− 504, 273) | 1485 (1306, 1948) | 274 (− 66, 835)* | 0.0342 |
| Fumaric acid4 | 5539 (3793, 6117) | 4073 (3408, 5116) | − 871 (− 2260, − 14)*** | 4216 (3605, 5460) | − 104 (− 1516, 754)** | 0.0042 |
| Gluconic acid | 1288 (1105, 1608) | 1269 (1055, 1558) | 161 (− 164, 247) | 1217 (1042, 1649) | − 45 (− 119, 145)* | 0.23 |
| Glucuronic acid | 1856 (1481, 2717) | 2782 (2254, 3370) | 654 (101, 1153)* | 2697 (2145, 3088) | 580 (− 49, 1371)* | 0.56 |
| Heptadecanoic acid | 7790 (6494, 8727) | 7017 (6143, 8826) | − 560 (− 2055, 458) | 6604 (5490, 7788) | − 697 (− 2400, 344)** | 0.19 |
| Isocitric aicd | 1094 (1001, 1341) | 1146 (948, 1281) | − 94 (− 241, 138) | 979 (808, 1117) | − 152 (− 390, 24)* | 0.23 |
| Isothreitol | 2072 (1580, 2886) | 2418 (1580, 2972) | 85 (− 318, 735) | 1654 (1088, 2221) | − 330 (− 1013, 101)* | 0.41 |
| Ketoisocaproic acid | 50,177 (42,537, 57,751) | 48,120 (36,122, 50,704) | − 6050 (− 10,576, − 1164)** | 41,822 (33,509, 50,332) | − 5555 (− 16,107, 100)*** | 0.92 |
| Malic acid | 1350 (1233, 1731) | 1598 (1261, 1852) | − 94 (− 352, 427) | 1386 (1040, 1600) | − 253 (− 444, 111)* | 0.89 |
| Myristic acid | 7063 (5741, 7953) | 6388 (4678, 7191) | − 769 (− 1620, 583) | 6069 (5771, 8255) | − 798 (− 2198, 1192)* | 0.73 |
| P-tolyl glucuronide | 232 (164, 364) | 294 (197, 569) | 67 (− 64, 350)* | 248 (187, 408) | 19 (− 64, 120) | 0.0381 |
| Palmitic acid | 143,747 (130,251, 170,438) | 134,008 (103,508, 143,473) | − 20,098 (− 31,503, − 4319)*** | 135,581 (118,709, 161,108) | − 13,121 (− 29,561, 12,833)** | 0.13 |
| Parabanic acid | 4087 (2895, 4648) | 3369 (2586, 4401) | − 718 (− 1379, − 6)** | 3576 (2957, 4704) | 322 (− 849, 845) | 0.11 |
| Phenylacetic acid | 803 (612, 1223) | 874 (671, 996) | − 29 (− 205, 348) | 973 (762, 1241) | 190 (9, 464) | 0.0276 |
| Phenylethylamine | 374 (294, 513) | 586 (317, 724) | 130 (− 117, 379) | 358 (221, 549) | − 22 (− 152, 76) | 0.0011 |
| Pyruvic acid | 39,697 (20,995, 49,411) | 27,746 (17,769, 39,011) | − 9691 (− 21,665, − 363) | 14,831 (9284, 25,225) | − 15,509 (− 24,309, 1969)** | 0.83 |
| Serotonin | 1845 (1009, 2652) | 1864 (994, 2670) | − 96 (− 616, 678) | 2204 (1543, 3054) | − 158 (− 341, 739) | 0.99 |
| Stearic acid | 448,176 (414,026, 561,336) | 460,347 (352,958, 512,616) | − 48,364 (− 97,126, − 6545)** | 430,408 (409,245, 499,584) | 474 (− 124,502, 51,301)** | 0.86 |
| Succinic acid | 3303 (2833, 3744) | 3440 (3037, 3823) | 505 (− 233, 1029) | 3560 (3328, 4422) | 579 (3, 1716)* | 0.93 |
| UDP-glucuronic acid | 797 (611, 1103) | 1111 (935, 1578) | 389 (14, 587)** | 1107 (576, 1382) | 320 (− 286, 643) | 0.54 |
| Valine | 1,248,470 (1,134,926, 1,308,718) | 1,234,454 (1,088,759, 1,356,740) | 2072 (− 90,478, 102,381) | 1,134,770 (1,095,117, 1,297,538) | − 11,483 (− 151,936, 71,861)* | 0.68 |
1Values are unadjusted and reported as median (25th, 75th). To correct for skewed distribution, generalized log-transformation and auto-scaling were applied before analysis.
2Comparison of changes from baseline to EPA or DHA was assessed using a liner mixed-effects model. FDR-adjusted P value: * < 0.05, ** < 0.01, *** < 0.001.
3Pairwise comparison between EPA and DHA (changes form baseline) were conducted using the lsmeansLT function from the lmerTest package for the linear mixed effect model.
4Fumaric acid showed significant sequence effect (p = 0.0073). When there was a sequence effect, data from the first period is extracted to run ANCOVA analysis, with baseline value and age as covariates. EPA supplementation reduced level of fumaric acid (p = 0.0107) when sequence effect was taken into account.