TABLE 2.
Full list of known metabolites significantly associated with healthy dietary patterns1
| HEI (n = 60) | AHEI (n = 78) | DASH (n = 77) | aMED (n = 51) | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Method2 | Metabolite | β | P value | β | P value | β | P value | β | P value |
| HILIC-neg | 2-hydroxy-3-methylbutyrate/hydroxyisovalerate | — | — | — | — | −0.0207 | 6.68 × 10−6 | — | — |
| HILIC-neg | 2-hydroxy-3-methylpentanoate/hydroxyisocaproate | — | — | −0.0073 | 1.16 × 10−5 | −0.0198 | 1.34 × 10−6 | — | — |
| HILIC-pos | 3-methylxanthine | −0.0259 | 1.50 × 10−5 | — | — | — | — | — | — |
| HILIC-neg | 4-pyridoxate | — | — | 0.0189 | 7.12 × 10−6 | 0.0567 | 4.99 × 10−8 | — | — |
| HILIC-pos | 4-pyridoxate | — | — | 0.0185 | 4.39 × 10−6 | 0.0539 | 4.99 × 10−8 | — | — |
| HILIC-neg | α-keto-β-methylvalerate/α-ketoisocaproate | — | — | −0.0066 | 4.58 × 10−6 | — | — | — | — |
| C8-pos | C16:0 CE | — | — | 0.0032 | 3.50 × 10−6 | 0.0079 | 2.94 × 10−6 | — | — |
| C8-pos | C18:2 CE | — | — | 0.0034 | 5.72 × 10−6 | 0.0079 | 2.16 × 10−5 | — | — |
| C8-pos | C20:5 CE | — | — | 0.0085 | 2.39 × 10−6 | 0.0201 | 6.10 × 10−6 | — | — |
| C8-pos | C22:6 CE | 0.0119 | 6.47 × 10−8 | 0.0132 | 1.65 × 10−10 | 0.0289 | 1.68 × 10−8 | 0.0604 | 3.67 × 10−6 |
| C8-pos | C16:0 Ceramide (d18:1) | — | — | — | — | −0.0142 | 2.82 × 10−6 | −0.0325 | 2.44 × 10−5 |
| C8-pos | C22:0 Ceramide (d18:1) | — | — | — | — | −0.0163 | 5.14 × 10−6 | — | — |
| C8-pos | C24:1 Ceramide (d18:1) | — | — | −0.0064 | 4.58 × 10−6 | −0.0177 | 3.17 × 10−7 | −0.0391 | 8.23 × 10−6 |
| C8-pos | C32:0 DAG | — | — | −0.0117 | 4.99 × 10−6 | −0.0305 | 1.07 × 10−6 | — | — |
| C8-pos | C32:1 DAG | — | — | −0.0134 | 1.42 × 10−7 | −0.0278 | 1.03 × 10−5 | — | — |
| C8-pos | C34:0 DAG | −0.0136 | 6.04 × 10−7 | −0.0142 | 4.58 × 10−8 | −0.0373 | 4.84 × 10−9 | −0.0795 | 1.14 × 10−6 |
| C8-pos | C34:0 DAG + NH4 | −0.0140 | 7.06 × 10−7 | −0.0143 | 9.05 × 10−8 | −0.0383 | 5.44 × 10−9 | −0.0820 | 1.11 × 10−6 |
| C8-pos | C34:1 DAG | — | — | −0.0087 | 1.34 × 10−6 | — | — | — | — |
| HILIC-pos | C34:1 DAG or TAG fragment | −0.0137 | 8.66 × 10−6 | −0.0154 | 1.25 × 10−7 | −0.0342 | 2.08 × 10−6 | −0.0938 | 2.95 × 10−7 |
| C8-pos | C36:0 DAG | −0.0095 | 3.30 × 10−7 | −0.0084 | 1.98 × 10−6 | −0.0247 | 1.19 × 10−8 | −0.0502 | 5.75 × 10−6 |
| C8-pos | C36:1 DAG | −0.0113 | 9.30 × 10−6 | −0.0138 | 8.16 × 10−9 | −0.0327 | 3.10 × 10−8 | −0.0720 | 1.74 × 10−6 |
| HILIC-pos | C16:1 LPC | — | — | −0.0074 | 3.01 × 10−8 | — | — | — | — |
| C8-pos | C16:1 LPC | — | — | −0.0083 | 2.56 × 10−8 | — | — | — | — |
| HILIC-pos | C22:4 LPC | −0.0110 | 1.33 × 10−7 | −0.0140 | 8.56 × 10−13 | — | — | −0.0639 | 2.17 × 10−7 |
| HILIC-pos | C22:5 LPC | — | — | −0.0067 | 1.46 × 10−5 | −0.0257 | 1.29 × 10−7 | — | — |
| HILIC-pos | C24:0 LPC | 0.0095 | 7.26 × 10−10 | 0.0089 | 1.08 × 10−9 | 0.0213 | 3.49 × 10−9 | 0.0531 | 6.50 × 10−9 |
| HILIC-pos | C20:1 LPE | — | — | −0.0086 | 5.93 × 10−10 | — | — | −0.0427 | 1.15 × 10−6 |
| C8-pos | C20:4 LPE | — | — | −0.0059 | 1.53 × 10−5 | — | — | — | — |
| HILIC-pos | C20:4 LPE | — | — | −0.0055 | 2.17 × 10−5 | — | — | — | — |
| C8-pos | C30:1 PC | — | — | −0.0141 | 2.43 × 10−5 | — | — | — | — |
| C8-pos | C36:1 PC | — | — | −0.0066 | 4.16 × 10−7 | — | — | −0.0384 | 2.69 × 10−6 |
| C8-pos | C38:3 PC | — | — | −0.0075 | 4.36 × 10−7 | — | — | — | — |
| C8-pos | C38:6 PC | 0.0067 | 2.31 × 10−6 | — | — | — | — | — | — |
| C8-pos | C40:9 PC | 0.0050 | 4.94 × 10−7 | — | — | — | — | — | — |
| C8-pos | C34:5 PC plasmalogen | — | — | — | — | −0.0264 | 1.59 × 10−6 | — | — |
| C8-pos | C36:4 PC plasmalogen | — | — | –0.0046 | 2.12 × 10−6 | −0.0146 | 1.37 × 10−9 | — | — |
| C8-pos | C36:5 PC plasmalogen-B | — | — | — | — | −0.0117 | 1.03 × 10−5 | — | — |
| C8-pos | C38:4 PC plasmalogen | −0.0071 | 7.63 × 10−9 | −0.0069 | 2.55 × 10−9 | −0.0183 | 1.98 × 10−10 | −0.0426 | 5.06 × 10−9 |
| HILIC-pos | C38:7 PC plasmalogen | 0.0073 | 4.21 × 10−7 | 0.0065 | 2.23 × 10−6 | — | — | — | — |
| C8-pos | C36:0 PE | — | — | −0.0063 | 2.05 × 10−5 | — | — | −0.0475 | 3.35 × 10−7 |
| HILIC-pos | C38:6 PE | 0.0076 | 2.63 × 10−6 | — | — | — | — | — | — |
| C8-pos | C36:2 PE plasmalogen | — | — | — | — | −0.0183 | 3.13 × 10−7 | — | — |
| C8-pos | C36:5 PE plasmalogen | — | — | — | — | −0.0180 | 7.79 × 10−6 | — | — |
| C8-pos | C38:3 PE plasmalogen | — | — | — | — | −0.0217 | 7.63 × 10−6 | −0.0560 | 5.12 × 10−6 |
| HILIC-pos | C38:5 PE plasmalogen | — | — | −0.0045 | 1.65 × 10−6 | −0.0138 | 2.21 × 10−9 | −0.0249 | 2.22 × 10−5 |
| C8-pos | C38:5 PE plasmalogen | — | — | — | — | −0.0211 | 1.73 × 10−9 | — | — |
| C8-pos | C38:6 PE plasmalogen | — | — | — | — | −0.0155 | 3.72 × 10−6 | — | — |
| HILIC-pos | C38:7 PE plasmalogen | 0.0054 | 1.73 × 10−6 | 0.0053 | 7.64 × 10−7 | — | — | 0.0305 | 5.37 × 10−6 |
| C8-pos | C18:1 SM | — | — | — | — | — | — | −0.0320 | 2.10 × 10–5 |
| C8-pos | C44:0 TAG | −0.0198 | 1.06 × 10−5 | — | — | −0.0448 | 1.95 × 10−5 | — | — |
| C8-pos | C44:1 TAG | −0.0196 | 1.49 × 10−5 | −0.0187 | 1.24 × 10−5 | −0.0449 | 2.03 × 10−5 | — | — |
| C8-pos | C44:2 TAG | −0.0199 | 9.45 × 10−6 | −0.0181 | 2.08 × 10−5 | −0.0449 | 1.87 × 10−5 | — | — |
| C8-pos | C45:1 TAG | −0.0182 | 5.30 × 10−6 | — | — | — | — | −0.1014 | 2.03 × 10−5 |
| C8-pos | C46:1 TAG | −0.0186 | 6.79 × 10−7 | −0.0195 | 3.66 × 10−8 | −0.0433 | 7.48 × 10−7 | −0.1075 | 1.40 × 10−6 |
| C8-pos | C46:2 TAG | −0.0166 | 2.73 × 10−6 | −0.0175 | 1.79 × 10−7 | −0.0378 | 4.84 × 10−6 | −0.0895 | 2.13 × 10−5 |
| C8-pos | C46:3 TAG | −0.0155 | 8.35 × 10−6 | −0.0160 | 1.25 × 10−6 | −0.0353 | 1.46 × 10−5 | — | — |
| C8-pos | C47:0 TAG + NH4 | −0.0163 | 1.76 × 10−5 | — | — | −0.0385 | 1.43 × 10−5 | — | — |
| C8-pos | C47:1 TAG | −0.0212 | 9.48 × 10−7 | −0.0198 | 1.27 × 10−6 | −0.0446 | 1.03 × 10−5 | −0.1326 | 2.30 × 10−7 |
| C8-pos | C47:2 TAG | −0.0139 | 1.12 × 10−6 | −0.0139 | 2.49 × 10−7 | −0.0307 | 4.38 × 10−6 | −0.0848 | 5.48 × 10−7 |
| C8-pos | C48:0 TAG | −0.0192 | 6.91 × 10−6 | −0.0185 | 5.62 × 10−6 | −0.0494 | 7.23 × 10−7 | −0.1163 | 5.64 × 10−6 |
| C8-pos | C48:1 TAG | −0.0148 | 2.14 × 10−5 | −0.0162 | 9.11 × 10−7 | −0.0367 | 6.21 × 10−6 | −0.0875 | 2.39 × 10−5 |
| C8-pos | C48:2 TAG | −0.0130 | 7.88 × 10−8 | −0.0151 | 4.33 × 10−11 | −0.0302 | 9.97 × 10−8 | −0.0785 | 5.09 × 10−8 |
| C8-pos | C48:3 TAG | −0.0105 | 2.12 × 10−5 | −0.0129 | 2.71 × 10−8 | −0.0246 | 1.95 × 10−5 | −0.0975 | 8.40 × 10−8 |
| C8-pos | C49:0 TAG + NH4 | −0.0195 | 7.60 × 10−7 | −0.0195 | 1.78 × 10−7 | −0.0497 | 5.87 × 10−8 | −0.1191 | 3.67 × 10−7 |
| C8-pos | C49:1 TAG + NH4 | −0.0154 | 1.58 × 10−6 | −0.0172 | 1.30 × 10−8 | −0.0377 | 4.68 × 10−7 | −0.1010 | 1.06 × 10−7 |
| C8-pos | C49:2 TAG | −0.0147 | 1.88 × 10−6 | −0.0148 | 3.60 × 10−7 | — | — | −0.0975 | 8.40 × 10−8 |
| C8-pos | C49:3 TAG | −0.0094 | 1.18 × 10−6 | −0.0116 | 2.37 × 10−10 | −0.0211 | 3.24 × 10−6 | −0.0653 | 1.24 × 10−8 |
| C8-pos | C50:0 TAG | −0.0149 | 1.00 × 10−6 | −0.0145 | 6.18 × 10−7 | −0.0382 | 7.28 × 10−8 | −0.0886 | 1.29 × 10−6 |
| C8-pos | C50:1 TAG | −0.0085 | 2.65 × 10−6 | −0.0096 | 1.79 × 10−8 | −0.0227 | 6.77 × 10−8 | — | — |
| C8-pos | C50:2 TAG | — | — | −0.0079 | 7.93 × 10−8 | –0.0158 | 1.47 × 10−5 | — | — |
| C8-pos | C50:3 TAG | — | — | −0.0066 | 1.13 × 10−9 | –0.0117 | 1.22 × 10−5 | –0.0289 | 2.07 × 10−5 |
| C8-pos | C50:4 TAG | — | — | −0.0062 | 1.43 × 10−5 | — | — | — | — |
| C8-pos | C51:0 TAG | — | — | −0.0122 | 2.74 × 10−6 | −0.0297 | 3.34 × 10−6 | −0.0719 | 1.00 × 10−5 |
| C8-pos | C51:1 TAG | −0.0110 | 7.59 × 10−7 | −0.0127 | 1.47 × 10–9 | −0.0304 | 4.52 × 10−9 | −0.0753 | 1.12 × 10−8 |
| C8-pos | C52:0 TAG | −0.0181 | 1.10 × 10−7 | −0.0180 | 2.82 × 10−8 | −0.0471 | 3.17 × 10−9 | −0.1067 | 1.65 × 10−7 |
| C8-pos | C52:1 TAG | −0.0086 | 8.69 × 10−7 | −0.0101 | 1.26 × 10−9 | −0.0237 | 6.02 × 10−9 | −0.0574 | 3.60 × 10−8 |
| C8-pos | C52:2 TAG | — | — | −0.0047 | 2.58 × 10−6 | — | — | — | — |
| C8-pos | C53:2 TAG | — | — | −0.0069 | 2.28 × 10−7 | — | — | — | — |
| C8-pos | C54:1 TAG | −0.0148 | 1.90 × 10−7 | −0.0148 | 3.28 × 10−8 | −0.0379 | 9.48 × 10−9 | −0.0868 | 2.58 × 10−7 |
| C8-pos | C54:2 TAG | — | — | −0.0061 | 4.49 × 10−6 | — | — | — | — |
| C8-pos | C55:2 TAG | — | — | −0.0106 | 2.87 × 10−7 | −0.0254 | 5.70 × 10−7 | −0.0597 | 3.87 × 10−6 |
| C8-pos | C56:7 TAG | 0.0068 | 2.37 × 10−7 | 0.0057 | 4.75 × 10−6 | — | — | 0.0385 | 7.15 × 10−7 |
| C8-pos | C56:8 TAG | 0.0095 | 6.10 × 10−10 | 0.0090 | 6.17 × 10−10 | 0.0166 | 4.08 × 10−6 | 0.0535 | 4.15 × 10−9 |
| C8-pos | C56:9 TAG | 0.0108 | 1.24 × 10−6 | 0.0089 | 2.14 × 10−5 | — | — | 0.0591 | 6.71 × 10−6 |
| C8-pos | C58:9 TAG | 0.0167 | 1.66 × 10−10 | 0.0158 | 1.68 × 10−10 | 0.0313 | 3.34 × 10−7 | 0.0868 | 2.28 × 10−8 |
| C8-pos | C58:10 TAG | 0.0136 | 1.35 × 10−8 | 0.0132 | 4.41 × 10−9 | 0.0243 | 1.46 × 10−5 | 0.0736 | 2.06 × 10−7 |
| C8-pos | C58:11 TAG | 0.0181 | 1.06 × 10−6 | 0.0171 | 9.14 × 10−7 | — | — | 0.0971 | 9.46 × 10−6 |
| C8-pos | C60:12 TAG | 0.0278 | 2.37 × 10−9 | 0.0281 | 1.58 × 10−10 | 0.0530 | 1.15 × 10−6 | 0.1367 | 7.59 × 10−7 |
| HILIC-pos | Cinnamoylglycine | — | — | 0.0227 | 1.57 × 10−5 | 0.0637 | 9.14 × 10−7 | — | — |
| HILIC-pos | Citrulline | 0.0052 | 1.12 × 10−5 | — | — | — | — | 0.1647 | 2.11 × 10−7 |
| HILIC-neg | CMPF | 0.0284 | 1.07 × 10−7 | 0.0317 | 3.12 × 10−10 | 0.0541 | 1.55 × 10−5 | — | — |
| HILIC-neg | Glycerate | 0.0094 | 7.95 × 10−9 | — | — | 0.0190 | 5.71 × 10−7 | — | — |
| HILIC-neg | Hippurate | — | — | 0.0168 | 4.54 × 10−6 | 0.0479 | 1.08 × 10−7 | — | — |
| HILIC-pos | Hippurate | 0.0132 | 1.23 × 10−5 | 0.0133 | 2.70 × 10−6 | 0.0368 | 1.57 × 10−7 | — | — |
| HILIC-neg | Indole-3-propionate | 0.0209 | 2.42 × 10−6 | — | — | 0.0511 | 7.77 × 10−7 | — | — |
| HILIC-neg | Inositol | 0.0072 | 8.09 × 10−7 | — | — | — | — | — | — |
| HILIC-neg | Malondialdehyde (MDA) | 0.0096 | 5.27 × 10−8 | — | — | 0.0225 | 4.41 × 10−8 | — | — |
| HILIC-pos | N-acetylornithine | 0.0148 | 5.43 × 10−9 | 0.0133 | 2.73 × 10−8 | 0.0339 | 9.93 × 10−9 | 0.0828 | 3.62 × 10−8 |
| HILIC-pos | N1-methyl-2-pyridone-5-carboxamide | — | — | — | — | 0.0300 | 1.18 × 10−6 | — | — |
| HILIC-pos | N-methylproline | 0.0291 | 5.07 × 10−8 | — | — | — | — | — | — |
| HILIC-pos | N-methylmalonamic acid (NMMA) | 0.0047 | 1.80 × 10−6 | 0.0057 | 4.59 × 10−10 | 0.0102 | 7.47 × 10−6 | — | — |
| HILIC-neg | Oxalate | 0.0138 | 2.80 × 10−6 | — | — | 0.0300 | 1.25 × 10−5 | — | — |
| HILIC-neg | Pantothenate | — | — | — | — | 0.0338 | 1.48 × 10−7 | — | — |
| HILIC-pos | Pantothenate | 0.0118 | 1.95 × 10−5 | 0.0121 | 3.10 × 10−6 | 0.0362 | 1.55 × 10−8 | — | — |
| HILIC-pos | Proline-betaine | 0.0384 | 6.94 × 10−13 | — | — | 0.0535 | 2.17 × 10−5 | 0.1527 | 1.69 × 10−6 |
| HILIC-neg | Quinate | — | — | — | — | 0.1364 | 2.27 × 10−7 | — | — |
| HILIC-pos | Thiamine | — | — | — | — | 0.0564 | 4.80 × 10−8 | — | — |
| HILIC-neg | Uracil | 0.0063 | 4.00 × 10−8 | 0.0054 | 6.34 × 10−7 | 0.0118 | 1.14 × 10−5 | 0.0334 | 8.38 × 10−7 |
| HILIC-neg | Uridine | 0.0065 | 2.14 × 10−7 | 0.0057 | 1.81 × 10−6 | — | — | 0.0340 | 5.24 × 10−6 |
1
β and P values were calculated from multivariable linear regression models which adjusted for sociodemographic characteristics (age, race/ethnicity, sex, clinical center, education, income), health behaviors (physical activity, smoking status), clinical factors (BMI, estimated glomerular filtration rate, proteinuria, HDL cholesterol, diabetes status, history of cardiovascular disease, hypertension status), and total energy intake. For HEI-2015 and DASH dietary patterns, models also adjusted for drinking status because alcohol consumption was not part of the scores. P values were considered to be statistically significant at a Bonferroni-adjusted level of 2.57 × 10−5 [0.05/(486 metabolites × 4 dietary patterns)] for dietary patterns. AHEI-2010, Alternative Healthy Eating Index; aMED, alternate Mediterranean diet; CE, cholesterol esters; CMPF, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid; DAG, diacylglycerols; DASH, Dietary Approaches to Stop Hypertension; HEI-2015, Healthy Eating Index; LPC, lysophosphatidylcholines; LPE, lysophosphatidylethanolamines; PC, phosphatidylcholines; PE, phosphatidylethanolamines; SM, sphingomyelins; TAG, triacylglycerols.
2
HILIC-pos indicates hydrophilic interaction liquid chromatography (HILIC) analyses of positively charged polar analytes in the positive ionization mode. HILIC-neg indicates HILIC analyses of negatively charged polar analytes in the negative ionization mode. C8-pos indicates that lipids were analyzed using positive ion mode (C8-pos). Details on these methods can be found in a prior publication (21).
— indicates that the association was not statistically significant at the Bonferroni threshold for the specific metabolite and dietary pattern.