Table 4.
Peak time and amplitude of 52 metabolites that showed significant (P<0.01) circadian rhythm in all 3 participants*
| Peak time-DLMO** | Amplitude¶ | Participants with P- value<2.5×10−5♯ |
|||||
|---|---|---|---|---|---|---|---|
| Metabolite | P1 | P2 | P3 | P1 | P2 | P3 | |
| Amino Acid | |||||||
| hydantoin-5-propionic acid | 1.45 | −4.02 | −4.64 | 0.77 | 1.15 | 1.49 | P1, P2 |
| 3-hydroxy-2-ethylpropionate | 8.2 | 9.53 | 0.44 | 0.50 | 0.43 | 0.15 | |
| isoleucine | 3.95 | −2.01 | −2.94 | 0.53 | 0.30 | 0.52 | P3 |
| valine | 4.7 | −0.36 | −1.03 | 0.24 | 0.32 | 0.31 | |
| 6-oxopiperidine-2-carboxylate | 0.63 | −6.48 | −4.57 | 0.85 | 0.83 | 0.94 | P2 |
| N6,N6,N6-trimethyllysine | 3.52 | 3.31 | −0.24 | 0.32 | 0.28 | 0.73 | P3 |
| dopamine sulfate (2) | −1.24 | −3.51 | −6.04 | 0.69 | 1.93 | 1.79 | P2, P3 |
| phenylalanine | 1.25 | −3.11 | −3.8 | 0.31 | 0.22 | 0.24 | P3 |
| tyramine O-sulfate | 1.64 | −1.66 | −2.52 | 0.68 | 1.39 | 3.03 | P2 |
| acisoga | 12.26 | 10.11 | 7.77 | 0.68 | 0.87 | 0.63 | P2 |
| N-acetylcitrulline | −0.36 | −1.86 | −3.08 | 1.18 | 0.28 | 1.17 | P3 |
| ornithine | 0.55 | −1.7 | −3.74 | 0.26 | 0.24 | 0.35 | |
| pro-hydroxy-pro | 10.91 | 7.6 | 4.3 | 0.41 | 1.11 | 0.52 | P2 |
| Carbohydrate | |||||||
| mannitol/sorbitol | 1.6 | −3.01 | −5.45 | 5.89 | 1.44 | 2.37 | |
| mannose | 6.52 | 7.17 | 4.68 | 0.71 | 0.33 | 0.56 | |
| arabitol/xylitol | −3.45 | −3.48 | −4.62 | 0.46 | 0.34 | 0.34 | P3 |
| Cofactor and Vitamins | |||||||
| bilirubin (Z,Z) | 12.68 | 10.94 | 7.97 | 0.33 | 0.43 | 0.25 | P1, P2 |
| biliverdin | −11.08 | −11.87 | −15.8 | 0.24 | 0.39 | 0.30 | P2 |
| trigonelline (N'-methylnicotinate) | 1.2 | −0.05 | −0.68 | 2.48 | 0.93 | 1.28 | |
| Energy | |||||||
| aconitate [cis or trans] | −3.15 | −5.86 | −8.38 | 1.59 | 0.81 | 0.85 | |
| Lipid | |||||||
| Diacylglycerol | |||||||
| linoleoyl-arachidonoyl-glycerol (18:2/20:4) [2]* | 1.97 | −8.95 | −6.69 | 0.61 | 0.64 | 1.70 | |
| oleoyl-linoleoyl-glycerol (18:1/18:2) [1] | −20.04 | −13.37 | −8.76 | 0.56 | 0.49 | 0.69 | P2, P3 |
| oleoyl-linoleoyl-glycerol (18:1/18:2) [2] | 3.86 | 11.25 | 14.92 | 0.72 | 0.49 | 0.73 | |
| Lysolipid | |||||||
| 1-linolenoyl-GPC (18:3)* | 1.84 | −1.21 | −2.84 | 0.37 | 0.27 | 0.80 | P3 |
| 1-linoleoyl-GPC (18:2) | 1.27 | −1.31 | −2.88 | 0.48 | 0.45 | 0.76 | P2, P3 |
| 1-linoleoyl-GPE (18:2)* | 1.11 | −5.36 | −5.01 | 0.82 | 0.73 | 1.37 | P3 |
| 1-linoleoyl-GPG (18:2)* | −1.07 | −4.35 | −5.2 | 0.85 | 0.59 | 1.00 | P3 |
| 1-oleoyl-GPE (18:1) | 1.64 | −2.91 | −4.79 | 0.80 | 1.22 | 1.59 | P2, P3 |
| Phospholipid | |||||||
| 1-oleoyl-2-linoleoyl-GPE (18:1/18:2)* | 1.25 | −3.27 | −6.14 | 1.19 | 0.63 | 1.15 | P1, P3 |
| 1-palmitoyl-2-oleoyl-GPE (16:0/18:1) | 2.5 | −4.71 | −7.13 | 0.49 | 0.32 | 0.85 | P3 |
| 1-stearoyl-2-linoleoyl-GPE (18:0/18:2)* | 1.12 | −4.1 | −6.65 | 0.78 | 0.64 | 1.04 | P2, P3 |
| 1-stearoyl-2-oleoyl-GPE (18:0/18:1) | 1.54 | −3 | −4.77 | 0.89 | 1.00 | 1.22 | P2, P3 |
| 1-stearoyl-2-oleoyl-GPI (18:0/18:1)* | 1.61 | −1.32 | −2.93 | 0.45 | 0.62 | 0.56 | P3 |
| 1,2-dilinoleoyl-GPC (18:2/18:2) | 3 | 0.77 | −2.35 | 0.26 | 0.21 | 0.42 | P3 |
| 1,2-dilinoleoyl-GPE (18:2/18:2)* | 0.1 | −2.21 | −5.83 | 3.13 | 1.25 | 2.83 | P2, P3 |
| Steroid | |||||||
| 17alpha-hydroxypregnenolone sulfate | 12.37 | 12.42 | 9.48 | 0.85 | 2.04 | 0.76 | P2 |
| 4-androsten-3alpha,17alpha-diol monosulfate (2) | 13.78 | 9.9 | 9.81 | 0.79 | 1.90 | 0.67 | P2 |
| cortisol | 13.84 | 9.83 | 8.52 | 1.61 | 2.71 | 1.42 | P2, P3 |
| cortisone | 12.86 | 9.78 | 11.45 | 1.46 | 1.83 | 0.96 | P2, P3 |
| etiocholanolone glucuronide | 14.1 | 10.72 | 8.07 | 0.89 | 0.85 | 0.35 | P2 |
| pregn steroid monosulfate* | 17.94 | 14.57 | 14.38 | 0.38 | 0.73 | 0.69 | P2 |
| pregnenolone sulfate | 13.46 | 13.85 | 12.81 | 0.88 | 1.51 | 0.84 | P2 |
| Other lipids | |||||||
| glycohyocholate | 0.95 | −6.46 | −1.41 | 0.38 | 0.89 | 1.13 | |
| N-palmitoyl-sphinganine (d18:0/16:0) | 2.02 | −2.18 | −5.17 | 1.12 | 0.76 | 1.26 | P2, P3 |
| Peptide | |||||||
| prolylglycine | 0.82 | −3 | −4.07 | 0.89 | 1.29 | 3.32 | P2, P3 |
| gamma-glutamylisoleucine* | 5.33 | −0.8 | −1.8 | 0.58 | 0.48 | 0.85 | P2, P3 |
| gamma-glutamylleucine | 4.81 | −1.49 | −2.43 | 0.47 | 0.45 | 0.72 | P3 |
| gamma-glutamylphenylalanine | 2.25 | −2.14 | −2.78 | 0.55 | 0.64 | 0.62 | P3 |
| gamma-glutamylvaline | 5.05 | 0.5 | −1.23 | 0.37 | 0.31 | 0.51 | P3 |
| Xenobiotics | |||||||
| 3-hydroxypyridine sulfate | −5.65 | −5.41 | −7.55 | 1.65 | 1.37 | 1.54 | |
| 2,3-dihydroxyisovalerate | −0.03 | −3.37 | −6.89 | 1.08 | 3.24 | 4.26 | P3 |
| erythritol | −2.7 | −4.43 | −3.62 | 0.41 | 0.40 | 0.22 | |
Results were from one- and two-order harmonic models. Amplitude was defined as the difference between the fit highest value and the fit lowest value over a 24-hour period using either the one- or two-harmonic model.
Peak time was defined as the time for the maximum value of the fit metabolite-specific harmonic curve. Peak time-DLMO was defined as the difference between the eastern time zone clock time (Supplementary Table 2) minus the Dim Light Melatonin Onset (DLMO) time of each participant (P1=21:32, P2=20:46 and P3=20:17). Some values additionally added 24, for convenience of comparison.
The amplitude was based on the median normalized concentration of each metabolite
Participants whose p-value for circadian rhythm <2.5×10−5 (0.05/663/3) met the Bonferroni corrected significance level.