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. Author manuscript; available in PMC: 2021 May 1.
Published in final edited form as: Clin Nutr. 2019 Jun 17;39(5):1478–1490. doi: 10.1016/j.clnu.2019.06.010

Table 6.

Metabolite discovery among overweight or obese women (n=1289), and an evaluation of the associations with C-reactive protein1,2,3,4,5

Association with EDIP score Association with CRP
Metabolite Category and metabolic pathway HMDB # Beta estimate (95%CI) FDR adjusted P-value Beta estimate (95%CI) FDR adjusted P-value
Trigonelline Alkaloids and derivatives HMDB0000875 −1.38 (−1.63, −1.13) 1.44 E-24 −0.04 (−0.07, −00009) 0.049
1,7−dimethyluric acid Alkaloids and derivatives HMDB0011103 −0.68 (−0.94, −0.42) 2.59 E-05 0.02 (−0.02, 0.06) 0.346
7−methylxanthine Alkaloids and derivatives HMDB0001991 −0.63 (−0.88, −0.37) 1.08 E-04 −0.02 (−0.06, 0.01) 0.202
3−methylxanthine Alkaloids and derivatives HMDB0001886 −0.62 (−0.87, −0.36) 1.08 E-04 −0.01 (−0.05, 0.03) 0.612
Caffeine Alkaloids and derivatives HMDB0001847 −0.54 (−0.79, −0.29) 7.33 E-04 0.02 (−0.01, 0.06) 0.199
Piperine Alkaloids and derivatives HMDB0029377 0.33 (0.08, 0.58) 0.034 0.01 (−0.02, 0.05) 0.482
C18:1 CE Cholesterol esters HMDB0000918 −0.43 (−0.70, 0.17) 0.010 −0.06 (−0.09, −0.02) 0.006
C18:2 CE Cholesterol esters HMDB0000610 −0.45 (−0.75, −0.19) 0.007 −0.05 (−0.09, −0.01) 0.009
C18:3 CE Cholesterol esters HMDB0010370 −0.52 (−0.78, −0.25) 0.002 −0.04 (−0.07, 0.002) 0.064
C20:2 CE Cholesterol esters HMDB0006734 −0.39 (−0.64, −0.13) 0.015 −0.05 (−0.09, −0.02) 0.006
C20:3 CE Cholesterol esters HMDB0006736 −0.34 (−0.61, −0.07) 0.043 0.02 (−0.02, 0.05) 0.394
C20:4 CE Cholesterol esters HMDB0006726 −0.33 (−0.59, −0.06) 0.047 −0.01 (−0.04, 0.03) 0.741
C22:4 CE Cholesterol esters HMDB0006729 −0.40 (−0.67, −0.14) 0.016 −0.04 (−0.08, −0.002) 0.040
C15:0 LPC Lysophosphatidylcholines HMDB0010381 −0.33 (−0.60, −0.06) 0.047 −0.12 (−0.15, −0.08) 2.16 E-08
C18:2 LPC Lysophosphatidylcholines HMDB0010386 −0.40, −0.67, −0.14) 0.014 −0.15 (−0.19, −0.12) 1.31 E-14
C18:3 LPC Lysophosphatidylcholines HMDB0010387 −0.44 (−0.72, −0.17) 0.011 −0.10 (−0.14, −0.06) 1.75 E-06
C20:1 LPC Lysophosphatidylcholines HMDB0010391 −0.51 (−0.79, −0.24) 0.003 −0.09 (−0.13, −0.05) 3.89 E-05
C20:5 LPC Lysophosphatidylcholines HMDB0010397 −0.40 (−0.66, −0.14) 0.015 −0.15 (−0.19, −0.11) 6.29 E-14
C24:0 LPC Lysophosphatidylcholines HMDB0008038 −0.44 (−0.70, −0.18) 0.007 −0.12 (−0.16, −0.08) 2.72 E-09
C36:0 PC Phosphatidylcholines HMDB0008036 −0.33 (−0.60, −0.06) 0.048 −0.03 (−0.07, 0.01) 0.111
C40:11 PC plasmalogen Phosphatidylcholine plasmalogens NA −0.34 (−0.59, −0.08) 0.038 0.01 (−0.03, 0.05) 0.653
C18:1 LPE Lysophosphatidylethanolamines HMDB0011506 −0.33 (−0.60, −0.06) 0.047 −0.07 (−0.11, −0.04) 5.37 E-04
C14:0 SM Sphingomyelins HMDB0012097 −0.45 (−0.72, −0.19) 0.007 0.01 (−0.03, 0.05) 0.633
C20:0 SM Sphingomyelins HMDB0012102 −0.34 (−0.61, −0.07) 0.043 0.01 (−0.02, 0.05) 0.471
C22:0 SM Sphingomyelins HMDB0012103 −0.33 (−0.61, −0.06) 0.047 0.03 (−0.01, 0.07) 0.109
C22:1 SM Sphingomyelins HMDB0012104 −0.32 (−0.59, −0.05) 0.050 −0.01 (−0.05, 0.03) 0.634
C24:0 SM Sphingomyelins HMDB0011697 −0.41 (−0.68, −0.14) 0.015 −0.01 (−0.04, 0.03) 0.764
C24:1 SM Sphingomyelins HMDB0012107 −0.34 (−0.60, −0.07) 0.043 0.05 (0.01, 0.09) 0.016
5−acetylamino−6−amino−3−methyluracil Amino acids HMDB0004400 −0.84 (−1.09, −0.58) 1.70 E-08 −0.01 (−0.04, 0.03 0.723
Phenylalanine−d8 Amino acids Internal Standard −0.44 (−0.72, −0.17) 0.012 0.003 (−0.04, 0.04) 0.887
Glycine Amino acids HMDB0000123 −0.40 (−0.65, −0.15) 0.013 −0.14 (−0.18, −0.11) 3.12 E-13
Asparagine Amino acids HMDB0000168 −0.36 (−0.61, −0.11) 0.022 −0.10 (−0.13, −0.06) 1.27 E-06
Taurine Amino acids HMDB0000251 −0.36 (−0.63, −0.09) 0.032 0.005 (−0.03, 0.04) 0.817
Proline betaine Amino acids HMDB0004827 −0.35 (−0.60, −0.09) 0.034 −0.02 (−0.06, 0.02) 0.311
ADMA Amino acids HMDB0001539 −0.34 (−0.61, −0.07) 0.043 −0.05 (−0.09, −0.01) 0.016
Serine Amino acids HMDB0000187 −0.33 (−0.60, −0.06) 0.048 −0.12 (−0.16, −0.08) 2.96 E-08
N−methylproline Amino acids NA −0.31 (−0.57, −0.05) 0.050 −0.03 (−0.06, 0.01) 0.174
Isoleucine Amino acids HMDB0000172 0.31 (0.07, 0.56) 0.043 0.07 (0.03, 0.10) 4.45 E-04
Uracil Purines and pyrimedines NA −0.47 (−0.74, −0.21) 0.005 −0.03 (−0.07, 0.01) 0.130
Uridine Purines and pyrimedines NA −0.38 (−0.64, −0.13) 0.016 −0.04 (−0.07, 0.001) 0.060
AMP Purines and pyrimedines NA −0.33 (−0.60, −0.06) 0.046 0.03 (−0.01, 0.07) 0.110
GMP Purines and pyrimedines NA −0.33 (−0.60, −0.06) 0.047 0.01 (−0.03, 0.05) 0.495
Indole−3−propionate Indoles and derivatives NA −0.31 (−0.57, −0.06) 0.047 −0.05 (−0.09, −0.01) 0.010
Cortisol Steroids HMDB0000063 −0.46 (−0.73, −0.20) 0.006 −0.01 (−0.05, 0.03) 0.605
Pantothenate Vitamins and minerals HMDB0000210 −0.37 (−0.63, −0.11) 0.022 0.01 (−0.03, 0.05) 0.555
Hexose−monophosphate NA NA −0.31 (−0.58, −0.05) 0.050 0.02 (−0.02, 0.06) 0.320
Eicosapentaenoate Fatty acids HMDB0001999 −0.46 (−0.71, −0.21) 0.004 −0.09 (−0.12, −0.05) 1.19 E-05
2−hydroxyhexadecanoate Fatty acids HMDB0031057 0.33 (0.06, 0.59) 0.047 0.02 (−0.02, 0.06) 0.302
C32:0 DAG Diacylglycerols HMDB0007098 0.49 (0.23, 0.75) 0.003 0.07 (0.03, 0.11) 6.73 E-04
C32:1 DAG Diacylglycerols HMDB0007099 0.40 (0.14, 0.66) 0.014 0.04 (0.01, 0.08) 0.022
C34:0 DAG Diacylglycerols HMDB0007100 0.49 (0.22, 0.76) 0.004 0.04 (0.002, 0.08) 0.037
C34:1 DAG Diacylglycerols HMDB0007102 0.53 (0.27, 0.79) 0.001 0.06 (0.03, 0.10) 0.001
C34:2 DAG Diacylglycerols HMDB0007103 0.51 (0.25, 0.77) 0.002 0.05 (0.01, 0.09) 0.008
C34:3 DAG Diacylglycerols HMDB0007132 0.40 (0.14, 0.66) 0.014 0.02 (−0.01, 0.06) 0.193
C36:1 DAG Diacylglycerols HMDB0007216 0.50 (0.24, 0.76) 0.002 0.05 (0.01, 0.08) 0.018
C36:0 DAG Diacylglycerols HMDB0007158 0.36 (0.10, 0.61) 0.028 0.002 (−0.03, 0.04) 0.918
C36:2 DAG Diacylglycerols HMDB0007218 0.47 (0.20, 0.73) 0.005 0.03 (−0.01, 0.07 0.108
C36:3 DAG Diacylglycerols HMDB0007219 0.44 (0.17, 0.71) 0.010 0.01 (−0.03, 0.05) 0.664
C36:4 DAG−A Diacylglycerols HMDB0007248 0.34 (0.07, 0.60) 0.042 −0.01 (−0.03, 0.04) 0.739
C36:4 DAG−B Diacylglycerols HMDB0007248 0.36 (0.11, 0.61) 0.022 0.04 (0.003, 0.07) 0.034
C38:3 DAG Diacylglycerols HMDB0007168 0.41 (0.14, 0.68) 0.014 0.02 (−0.02, 0.06) 0.291
C48:0 TAG Triacylglycerols HMDB0005356 0.39 (0.09, 0.61) 0.035 0.07 (0.03, 0.11) 5.37 E-04
C48:1 TAG Triacylglycerols HMDB0005359 0.38 (0.12, 0.64) 0.021 0.05 (0.01, 0.09) 0.012
C50:0 TAG Triacylglycerols HMDB0005357 0.36 (0.10, 0.62) 0.028 0.06 (0.02, 0.09)) 0.005
C50:1 TAG Triacylglycerols HMDB0044109 0.54 (0.29, 0.80) 7.33 E-04 0.08 (0.04, 0.12) 8.94 E-05
C50:2 TAG Triacylglycerols HMDB0005377 0.50 (0.24, 0.75) 0.002 0.07 (0.04, 0.11) 4.02 E-04
C50:3 TAG Triacylglycerols HMDB0005433 0.39 (0.13, 0.65) 0.015 0.04 (0.002, 0.08) 0.040
C51:1 TAG Triacylglycerols HMDB0042104 0.36 (0.11, 0.62) 0.024 0.04 (0.01, 0.08) 0.024
C51:2 TAG Triacylglycerols HMDB0049721 0.30 (0.05, 0.56) 0.050 0.03 (−0.01, 0.07) 0.106
C51:3 TAG Triacylglycerols NA 0.36 (0.10, 0.62) 0.028 0 (−0.04, 0.04) 0.990
C52:0 TAG Triacylglycerols HMDB0005365 0.34 (0.08, 0.61) 0.039 0.03 (−0.01, 0.07) 0.103
C52:1 TAG Triacylglycerols HMDB0005367 0.47 (0.22, 0.73) 0.004 0.08 (0.04, 0.12) 0.002
C52:2 TAG Triacylglycerols HMDB0005369 0.56 (0.31, 0.82) 5.77 E-04 0.06 (0.03, 0.10) 0.002
C52:3 TAG Triacylglycerols HMDB0005384 0.56 (0.30, 0.82) 7.33 E-04 0.05 (0.01, 0.08) 0.018
C52:4 TAG Triacylglycerols HMDB0005363 0.41 (0.15, 0.68) 0.014 0.01 (−0.03, 0.05) 0.590
C54:1 TAG Triacylglycerols HMDB0005395 0.36 (0.10, 0.62) 0.028 0.04 (−0.001, 0.07) 0.057
C54:2 TAG Triacylglycerols HMDB0005403 0.47 (0.21, 0.73) 0.004 0.04 (0.01, 0.08) 0.020
C54:3 TAG Triacylglycerols HMDB0005405 0.43 (0.17, 0.70) 0.010 0.02 (−0.02, 0.05) 0.397
C56:8 TAG Triacylglycerols HMDB0005392 0.43 (0.16, 0.70) 0.013 0.03 (−0.01, 0.06) 0.197
Glycolithocholate Bile acids HMDB0000698 0.32 (0.08, 0.56) 0.036 −0.03 (−0.06, 0.01) 0.120
Deoxycholate isomer−G Bile acids NA 0.30 (0.05, 0.55) 0.050 −0.04 (−0.07, −0.001) 0.044
C6 carnitine Acylcarnitines HMDB0000705 0.32 (0.05, 0.59) 0.047 0.04 (0.01, 0.08) 0.022
1

All values are beta estimates obtained from multivariable-adjusted linear regression modeling 5-SD increments in EDIP score or 5-unit increments in CRP levels as the main predictor of interest and metabolite as the main response variable of interest.

2

Metabolites in bold font are 9 of the 10 replicated metabolites or metabolites (n=40 metabolites) also significantly associated with CRP.

3

Models were adjusted for body mass index (continuous) age, physical activity, educational level, race/ethnicity, aspirin/NSAIDs use, smoking status, WHI Hormone Therapy trial arm, CHD case-control status.

4

Statistical significance was defined as false-discovery rate adjusted p<0.05.

5

In the multivariable models, 110 metabolites were significantly associated with the EDIP score and 83 remained significant after additionally adjusting for BMI. In multivariable-adjusted models, 196 metabolites were significantly associated with CRP and 178 remained significant with additional adjustment for continuous BMI. Of the 83 metabolites associated with EDIP, 40 (48%) were also associated with CRP.