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. 2020 Feb 13;150(5):1272–1283. doi: 10.1093/jn/nxaa021

TABLE 3.

Least-squares adjusted means (SE) of log-transformed circulating metabolite values across increasing quartiles of dairy intake in the Framingham Heart Study Third Generation cohort, total sample (n = 866)1

Quartile category of dairy intake
Metabolite Unannotated m/z2 n Q1 Q2 Q3 Q4 P-trend Sig.3 In Offspring4
Number per quartile category 216 217 217 216
Total dairy (quartile median, servings/wk) 4.5 8.5 12.5 23.4
 Hippurate 865 −0.73 ± 0.19 −0.86 ± 0.18 −0.77 ± 0.19 −0.83 ± 0.19 0.48 N P = 0.19
 Kynurenic acid 865 −0.23 ± 0.10 −0.24 ± 0.10 −0.22 ± 0.10 −0.28 ± 0.10 0.25 N P = 0.18
 Oxalate 860 −0.52 ± 0.10 −0.50 ± 0.10 −0.45 ± 0.10 −0.40 ± 0.10 0.004 Y P = 0.58
 X1840 431.3395 864 8.50 ± 0.24 8.22 ± 0.24 8.31 ± 0.24 8.03 ± 0.24 0.0003 Y n/a
 X1852 496.4205 855 10.10 ± 0.28 10.08 ± 0.28 10.00 ± 0.28 10.14 ± 0.28 0.68 N n/a
 X203 244.1905 846 8.85 ± 0.16 8.83 ± 0.16 8.83 ± 0.16 8.90 ± 0.16 0.70 N n/a
 X2204 431.3388 863 9.34 ± 0.27 9.21 ± 0.27 9.35 ± 0.27 9.18 ± 0.27 0.23 N n/a
 X291 214.1787 833 5.80 ± 0.25 5.79 ± 0.24 5.85 ± 0.25 5.77 ± 0.25 0.65 N n/a
 X3341 197.0669 838 10.67 ± 0.31 10.58 ± 0.31 10.64 ± 0.31 10.10 ± 0.32 0.0002 Y n/a
 X3517 213.0981 814 10.37 ± 0.35 10.24 ± 0.34 10.38 ± 0.35 9.62 ± 0.35 0.00002 Y n/a
 X3726 207.1742 828 7.47 ± 0.22 7.39 ± 0.22 7.45 ± 0.22 7.44 ± 0.22 0.79 N n/a
 X4778 96.0449 841 9.93 ± 0.42 9.78 ± 0.41 9.67 ± 0.42 9.27 ± 0.42 0.0006 Y n/a
 X6385 94.0657 849 8.63 ± 0.47 8.49 ± 0.47 8.31 ± 0.47 7.95 ± 0.48 0.006 N n/a
 X942 402.2634 862 10.33 ± 0.13 10.50 ± 0.13 10.62 ± 0.13 10.74 ± 0.13 <0.0001 Y n/a
Milk (quartile median, servings/wk) 0.0 3.0 5.5 17.5
 α-Hydroxybutyrate 865 0.00 ± 0.15 0.06 ± 0.15 0.01 ± 0.15 −0.15 ± 0.15 0.04 N P = 0.99
 Hippurate 865 −0.87 ± 0.18 −0.77 ± 0.18 −0.68 ± 0.18 −0.89 ± 0.19 0.40 N P = 0.47
 Kynurenic acid 865 −0.23 ± 0.10 −0.24 ± 0.10 −0.24 ± 0.10 −0.28 ± 0.10 0.19 N P = 0.21
 Maleate 865 −0.14 ± 0.11 −0.11 ± 0.10 −0.25 ± 0.11 −0.24 ± 0.11 0.03 N n/a
 Quinolinate 865 −0.28 ± 0.07 −0.23 ± 0.07 −0.25 ± 0.07 −0.27 ± 0.07 0.75 N P = 0.70
 X1866 308.2218 861 9.21 ± 0.14 9.06 ± 0.13 9.13 ± 0.14 9.20 ± 0.14 0.25 N n/a
 X2920 427.3531 863 10.02 ± 0.16 9.96 ± 0.16 9.89 ± 0.16 9.88 ± 0.17 0.22 N n/a
 X3878 184.071 751 5.23 ± 0.45 5.20 ± 0.45 5.53 ± 0.46 5.10 ± 0.47 0.82 N n/a
Cream/butter (quartile median, servings/wk) 0.5 2.9 7.0 18.0
 Indole-3-carboxyl 865 −0.12 ± 0.16 −0.20 ± 0.16 −0.22 ± 0.17 −0.20 ± 0.16 0.38 N n/a
 Pantothenate 865 −0.15 ± 0.11 −0.20 ± 0.11 −0.26 ± 0.11 −0.29 ± 0.11 0.01 N P = 0.035
 Taurine 865 0.03 ± 0.23 0.14 ± 0.23 0.04 ± 0.23 0.00 ± 0.23 0.47 N P = 0.21
 X5942 510.3926 864 11.63 ± 0.10 11.70 ± 0.10 11.70 ± 0.10 11.82 ± 0.10 0.0002 Y n/a
 X1427 445.2948 766 8.16 ± 0.45 7.63 ± 0.46 7.74 ± 0.46 7.40 ± 0.46 0.001 Y n/a
 X250 96.045 704 7.79 ± 0.45 7.76 ± 0.46 7.60 ± 0.46 8.38 ± 0.45 0.001 Y n/a
 X2979 210.1488 864 10.28 ± 0.19 10.22 ± 0.19 10.41 ± 0.19 10.86 ± 0.19 <0.0001 Y n/a
 X3632 144.1019 864 9.46 ± 0.11 9.45 ± 0.11 9.47 ± 0.12 9.72 ± 0.11 <0.0001 Y n/a
 X4249 221.0643 842 10.17 ± 0.26 10.20 ± 0.27 10.58 ± 0.27 10.96 ± 0.26 <0.0001 Y n/a
 X4259 181.0719 834 9.12 ± 0.27 9.19 ± 0.28 9.45 ± 0.28 9.93 ± 0.27 <0.0001 Y n/a
 X4778 96.0449 841 9.30 ± 0.40 9.17 ± 0.40 9.64 ± 0.41 10.53 ± 0.40 <0.0001 Y n/a
 X5033 797.622 864 12.51 ± 0.04 12.55 ± 0.04 12.55 ± 0.04 12.60 ± 0.04 <0.0001 Y n/a
 X5146 692.5573 864 11.86 ± 0.09 11.99 ± 0.09 12.02 ± 0.09 12.11 ± 0.09 <0.0001 Y n/a
 X6385 94.0657 849 7.95 ± 0.45 7.71 ± 0.46 8.15 ± 0.46 9.44 ± 0.45 <0.0001 Y n/a
Cheese (quartile median, servings/wk) 0.9 3.0 3.5 7.5
 X2459 165.1257 850 6.29 ± 0.41 6.36 ± 0.41 6.36 ± 0.41 6.55 ± 0.41 0.18 N n/a
Yogurt (quartile median, servings/wk) 0.0 0.0 1.0 3.0
 X678 624.5547 865 11.72 ± 0.09 11.69 ± 0.09 11.62 ± 0.09 11.52 ± 0.09 0.00001 Y n/a
 X580 625.5589 865 10.59 ± 0.12 10.56 ± 0.12 10.48 ± 0.12 10.36 ± 0.12 0.00002 Y n/a
 X597 598.5389 864 10.63 ± 0.12 10.58 ± 0.12 10.49 ± 0.12 10.39 ± 0.12 0.00003 Y n/a
 X596 596.524 865 11.60 ± 0.10 11.55 ± 0.10 11.50 ± 0.10 11.39 ± 0.10 0.00004 Y n/a
 X671 581.511 865 12.32 ± 0.11 12.24 ± 0.11 12.19 ± 0.12 12.08 ± 0.12 0.00004 Y n/a
 X608 570.5088 864 10.37 ± 0.12 10.35 ± 0.12 10.28 ± 0.12 10.15 ± 0.12 0.00007 Y n/a
 X843 565.4456 865 11.56 ± 0.11 11.45 ± 0.12 11.43 ± 0.12 11.31 ± 0.12 0.0001 Y n/a
 X717 235.2418 865 10.01 ± 0.12 9.98 ± 0.12 9.91 ± 0.12 9.81 ± 0.12 0.0003 Y n/a
 X634 603.496 862 9.66 ± 0.16 9.55 ± 0.17 9.48 ± 0.17 9.34 ± 0.17 0.0005 Y n/a
 X889 197.19 865 9.99 ± 0.11 9.91 ± 0.11 9.87 ± 0.11 9.79 ± 0.11 0.0005 Y n/a
 X938 425.3626 865 11.18 ± 0.10 11.13 ± 0.10 11.06 ± 0.10 11.01 ± 0.10 0.0007 Y n/a
 X749 409.3675 864 10.08 ± 0.12 10.02 ± 0.12 10.04 ± 0.12 9.89 ± 0.12 0.0007 Y n/a
 X795 225.1848 865 12.64 ± 0.09 12.57 ± 0.09 12.51 ± 0.09 12.46 ± 0.09 0.0007 Y n/a
 X633 535.472 864 10.23 ± 0.14 10.15 ± 0.15 10.13 ± 0.15 9.98 ± 0.15 0.0007 N n/a
 X705 419.388 865 10.63 ± 0.11 10.58 ± 0.11 10.55 ± 0.11 10.44 ± 0.11 0.0007 N n/a
 X741 614.5347 865 12.56 ± 0.12 12.51 ± 0.12 12.44 ± 0.12 12.36 ± 0.12 0.0008 N n/a
 X695 235.2055 865 11.11 ± 0.09 11.06 ± 0.09 11.02 ± 0.09 10.95 ± 0.09 0.0008 N n/a
 X1030 553.4108 865 10.95 ± 0.12 10.87 ± 0.13 10.83 ± 0.13 10.73 ± 0.13 0.0008 N n/a
 X904 243.1954 864 10.00 ± 0.13 9.92 ± 0.13 9.88 ± 0.13 9.77 ± 0.13 0.001 N n/a
 X673 563.5005 865 11.29 ± 0.11 11.24 ± 0.11 11.17 ± 0.11 11.10 ± 0.11 0.001 N n/a
 X1063 345.2784 863 9.20 ± 0.12 9.15 ± 0.12 9.10 ± 0.12 9.00 ± 0.12 0.001 N n/a
 X899 393.3726 865 10.57 ± 0.12 10.49 ± 0.12 10.49 ± 0.12 10.37 ± 0.12 0.001 N n/a
 X802 533.4567 865 12.66 ± 0.09 12.60 ± 0.09 12.56 ± 0.09 12.50 ± 0.09 0.001 N n/a
 X1074 524.3946 865 10.93 ± 0.12 10.90 ± 0.12 10.85 ± 0.12 10.75 ± 0.12 0.002 N n/a
 X650 309.2786 862 8.59 ± 0.16 8.54 ± 0.16 8.48 ± 0.16 8.34 ± 0.16 0.002 N n/a
 X712 567.4624 865 11.22 ± 0.10 11.14 ± 0.10 11.10 ± 0.10 11.04 ± 0.10 0.002 N n/a
 X698 255.2317 865 10.70 ± 0.09 10.65 ± 0.09 10.62 ± 0.09 10.56 ± 0.09 0.002 N n/a
 X709 551.467 865 12.75 ± 0.10 12.67 ± 0.10 12.62 ± 0.10 12.58 ± 0.10 0.002 N n/a
 X1069 526.4104 865 12.19 ± 0.09 12.14 ± 0.09 12.11 ± 0.09 12.04 ± 0.09 0.003 N n/a
 X855 541.4474 865 11.74 ± 0.10 11.66 ± 0.10 11.63 ± 0.10 11.56 ± 0.10 0.003 N n/a
 X477 680.58 853 9.73 ± 0.31 9.43 ± 0.31 9.53 ± 0.32 9.17 ± 0.32 0.003 N n/a
 X1012 321.2786 865 9.86 ± 0.13 9.78 ± 0.13 9.74 ± 0.13 9.65 ± 0.13 0.003 N n/a
 X701 237.2209 865 10.14 ± 0.10 10.11 ± 0.10 10.08 ± 0.10 10.00 ± 0.10 0.004 N n/a
 X807 453.3566 865 12.00 ± 0.08 11.93 ± 0.08 11.93 ± 0.08 11.87 ± 0.08 0.004 N n/a
 X3096 347.2214 830 9.43 ± 0.49 9.24 ± 0.50 9.61 ± 0.50 9.99 ± 0.51 0.005 N n/a
 X811 377.3411 865 10.76 ± 0.09 10.71 ± 0.09 10.70 ± 0.09 10.63 ± 0.09 0.005 N n/a
 X431 786.6593 830 9.90 ± 0.33 9.62 ± 0.34 9.72 ± 0.34 9.34 ± 0.34 0.005 N n/a
 X516 654.5658 859 9.96 ± 0.29 9.70 ± 0.29 9.76 ± 0.30 9.50 ± 0.30 0.006 N n/a
 X732 153.1273 865 11.57 ± 0.09 11.53 ± 0.09 11.48 ± 0.09 11.44 ± 0.09 0.006 N n/a
 X1156 549.377 864 11.24 ± 0.12 11.17 ± 0.12 11.12 ± 0.13 11.06 ± 0.13 0.006 N n/a
 X454 714.6187 865 11.72 ± 0.16 11.85 ± 0.16 11.90 ± 0.16 11.96 ± 0.16 0.007 N n/a
 X1005 363.289 864 9.82 ± 0.11 9.74 ± 0.11 9.75 ± 0.11 9.65 ± 0.11 0.008 N n/a
 X1054 486.4156 865 10.92 ± 0.11 10.89 ± 0.12 10.80 ± 0.12 10.77 ± 0.12 0.008 N n/a
 X3616 433.3165 843 8.43 ± 0.43 8.29 ± 0.43 8.35 ± 0.44 7.93 ± 0.44 0.009 N n/a
 X1427 445.2948 766 7.58 ± 0.45 7.56 ± 0.46 8.01 ± 0.46 8.11 ± 0.46 0.009 N n/a
 X1194 547.3607 863 10.80 ± 0.13 10.73 ± 0.13 10.67 ± 0.13 10.62 ± 0.13 0.01 N n/a
 X1017 485.3844 865 11.75 ± 0.09 11.67 ± 0.09 11.64 ± 0.09 11.61 ± 0.09 0.01 N n/a
 X690 517.4612 860 9.76 ± 0.14 9.71 ± 0.15 9.66 ± 0.15 9.59 ± 0.15 0.01 N n/a
 X1028 479.3357 865 12.01 ± 0.08 11.97 ± 0.08 11.94 ± 0.08 11.90 ± 0.08 0.01 N n/a
 X579 584.5247 862 10.51 ± 0.22 10.47 ± 0.23 10.36 ± 0.23 10.24 ± 0.23 0.01 N n/a
 X956 517.461 856 9.24 ± 0.18 9.24 ± 0.18 9.18 ± 0.18 9.06 ± 0.18 0.01 N n/a
 X1137 551.3942 865 10.84 ± 0.14 10.76 ± 0.14 10.72 ± 0.14 10.65 ± 0.14 0.01 N n/a
 X1135 263.1641 864 9.89 ± 0.11 9.89 ± 0.12 9.81 ± 0.12 9.77 ± 0.12 0.02 N n/a
 X573 589.4816 864 10.36 ± 0.18 10.33 ± 0.18 10.35 ± 0.18 10.17 ± 0.18 0.02 N n/a
 X1146 267.1953 865 11.16 ± 0.08 11.10 ± 0.08 11.07 ± 0.08 11.05 ± 0.08 0.02 N n/a
 X1174 545.3449 861 10.08 ± 0.13 9.99 ± 0.13 9.99 ± 0.14 9.91 ± 0.14 0.02 N n/a
 X414 760.6424 797 10.04 ± 0.37 9.75 ± 0.37 9.85 ± 0.38 9.54 ± 0.38 0.03 N n/a
 X1181 517.3137 792 8.29 ± 0.22 8.24 ± 0.23 8.08 ± 0.23 8.07 ± 0.23 0.03 N n/a
 X1255 521.345 864 10.80 ± 0.12 10.74 ± 0.12 10.71 ± 0.13 10.66 ± 0.13 0.03 N n/a
 X886 498.3789 865 12.07 ± 0.09 12.01 ± 0.09 11.98 ± 0.09 11.96 ± 0.09 0.04 N n/a
 X1131 695.5724 791 9.17 ± 0.30 9.49 ± 0.30 9.47 ± 0.30 9.55 ± 0.30 0.04 N n/a
 X3995 605.55 772 9.86 ± 0.27 9.82 ± 0.27 9.82 ± 0.27 9.62 ± 0.27 0.046 N n/a
 X1222 523.3613 860 10.46 ± 0.14 10.40 ± 0.14 10.38 ± 0.14 10.32 ± 0.14 0.05 N n/a
 X1133 249.1848 865 12.67 ± 0.09 12.62 ± 0.09 12.56 ± 0.09 12.56 ± 0.09 0.05 N n/a
 X440 734.6276 828 10.05 ± 0.42 9.76 ± 0.42 9.93 ± 0.42 9.57 ± 0.43 0.05 N n/a
 X1158 475.3034 864 10.37 ± 0.13 10.32 ± 0.13 10.26 ± 0.13 10.24 ± 0.14 0.07 N n/a
 X1271 519.3294 852 9.86 ± 0.16 9.75 ± 0.16 9.74 ± 0.16 9.68 ± 0.16 0.08 N n/a
 X423 774.6596 799 9.04 ± 0.41 8.69 ± 0.42 8.64 ± 0.42 8.58 ± 0.42 0.21 N n/a
 X1272 231.1741 858 8.87 ± 0.16 8.81 ± 0.16 8.69 ± 0.16 8.75 ± 0.16 0.26 N n/a
1

Metabolite values are log-transformed. Model adjusted for age, sex, BMI, smoking status, history of diabetes, history of cardiovascular disease, intake of other dairy (except in total dairy; i.e., for milk, the model included cheese, cream/butter, and yogurt), and intake of fish, fruit, vegetables, meat, and nuts, as well as batch or plate (as applicable). Conversion of standard serving sizes to grams for dairy is as follows: skim milk, 245 g; whole milk, 245 g; cream, 15 g; sour cream, 12 g; sherbet/ice milk, 96 g; ice cream, 66 g; yogurt, 227 g; cottage/ricotta cheese, 105 g; cream cheese, 28 g; other cheese, 28 g; butter, 5 g. Gen3, Framingham Heart Study Third Generation cohort; n/a, not available; Q, quartile.

2

Unannotated/unknown metabolites were searched by m/z ratio in the Human Metabolome Database and/or METLIN (41). The m/z ratio and putative identities are provided in Supplemental Table 8. Identities have not been verified.

3

Significant after Bonferroni correction: P < 0.05/14 (0.004) for total dairy; <0.05/8 (0.006) for milk; <0.05/14 (0.004) for cream/butter; <0.05/69 (0.0007) for yogurt.

4

Tested in identical models in the Offspring total sample, where metabolite value was measured and annotated.

5

Association in the Offspring was directionally consistent with that in Gen3.