Table 3:

Sleep Wake Time, Midpoint and Associated Metabolites by Pathway¹

Metabolite	Wake Time				Sleep Midpoint
	Relative change2	95% CI3	P-value	Q-value4	Relative Change2	95% CI3	P-value	Q-value4
Gamma-glutamyl amino acid
Gamma-glutamylisoleucine	1.11	1.05–1.16	0.00014	0.036	1.14	1.06–1.21	0.0002	0.035
Gamma-glutamylphenylalanine	1.04	1.02–1.07	0.00038	0.036	1.06	1.03–1.09	0.0003	0.035
Gamma-glutamylleucine	1.08	1.04–1.13	0.00037	0.036	1.10	1.05–1.17	0.0004	0.036
Gamma-glutamylvaline	1.10	1.04–1.15	0.00054	0.040	1.13	1.06–1.20	0.0005	0.038
Gamma-glutamylalanine	1.06	1.01–1.11	0.012	0.159	1.09	1.03–1.16	0.0053	0.078
Gamma-glutamyltyrosine	1.03	1.01–1.05	0.0083	0.122	1.04	1.01–1.07	0.0057	0.078
Gamma-glutamylglutamate	1.17	1.05–1.29	0.0041	0.099	1.19	1.04–1.36	0.0137	0.108
Phenylalanine and tyrosine metabolism
N-acetyltyrosine	1.02	1.00–1.03	0.010	0.132	1.03	1.01–1.05	0.003	0.075
N-acetylphenylalanine	1.02	1.01–1.03	0.005	0.100	1.02	1.01–1.04	0.006	0.078
3-[3-(sulfooxy)phenyl]propanoic acid	1.10	1.03–1.17	0.004	0.099	1.12	1.03–1.22	0.009	0.095
3-methoxytyramine sulfate	1.02	0.98–1.06	0.314	0.540	1.07	1.01–1.12	0.016	0.117
Thyroxine	0.94	0.89–0.99	0.013	0.168	0.93	0.87–0.99	0.022	0.134
4-hydroxyphenylpyruvate	0.94	0.88–1.00	0.056	0.314	0.91	0.83–0.99	0.027	0.152
P-cresol sulfate	1.03	1.00–1.06	0.081	0.333	1.04	1.00–1.08	0.046	0.194
Glutamate metabolism
Glutamine	0.97	0.95–0.99	0.002	0.092	0.96	0.94–0.99	0.008	0.088
Glutamate	1.05	1.02–1.09	0.003	0.092	1.06	1.02–1.11	0.009	0.100
Dipeptide group
N-acetylcarnosine	1.02	1.00–1.05	0.021	0.213	1.04	1.01–1.07	0.004	0.075
Isoleucylglycine	1.03	1.01–1.06	0.006	0.101	1.04	1.01–1.07	0.009	0.100
Valylleucine	1.04	0.99–1.10	0.092	0.342	1.07	1.00–1.14	0.039	0.183
Valylglycine	1.05	0.99–1.10	0.096	0.344	1.07	1.00–1.14	0.051	0.200
Pyrimidine metabolism
5-methyluridine (ribothymidine)	1.01	1.00–1.03	0.016	0.187	1.02	1.01–1.04	0.003	0.075
Orotidine	1.02	1.01–1.04	0.006	0.101	1.03	1.01–1.05	0.006	0.078
Pseudouridine	1.01	1.00–1.02	0.068	0.319	1.02	1.00–1.03	0.013	0.108
2’-deoxyuridine	1.02	1.00–1.05	0.068	0.319	1.03	1.00–1.07	0.050	0.200
Krebs cycle / TCA cycle
Succinate	1.03	1.01–1.05	0.002	0.092	1.04	1.02–1.07	0.002	0.071
Citrate	0.95	0.89–1.01	0.117	0.379	0.92	0.84–0.99	0.036	0.175
Alpha-ketoglutarate	0.96	0.92–1.00	0.044	0.280	0.95	0.90–1.00	0.050	0.200
Methionine, cysteine, SAM, and taurine metabolism group
Methionine sulfoxide	1.10	1.04–1.16	0.001	0.043	1.12	1.04–1.20	0.002	0.070
Methionine sulfone	1.02	1.00–1.04	0.052	0.302	1.03	1.01–1.06	0.007	0.081
N-acetyltaurine	1.03	1.01–1.05	0.003	0.099	1.03	1.01–1.06	0.011	0.105
Glycolysis, gluconeogenesis, pyruvate metabolism group
1,5-anhydroglucitol (1,5-ag)	1.02	1.01–1.03	0.001	0.060	1.02	1.01–1.04	0.004	0.075
Glucuronate	1.03	1.01–1.05	0.017	0.192	1.04	1.01–1.07	0.005	0.075
Lysolipid
1-stearoylglycerophosphoinositol	1.06	1.03–1.09	0.001	0.043	1.08	1.03–1.12	0.001	0.040
1-oleoylglycerophosphoinositol*	1.04	1.00–1.08	0.063	0.318	1.07	1.02–1.13	0.012	0.108
1-palmitoylplasmenylethanolamine*	1.04	1.01–1.07	0.019	0.201	1.05	1.01–1.09	0.013	0.108
1-palmitoylglycerophosphoinositol*	1.07	1.02–1.13	0.005	0.101	1.08	1.02–1.15	0.015	0.115
1-oleoylplasmenylethanolamine*	1.05	1.01–1.09	0.022	0.213	1.06	1.01–1.11	0.021	0.133
1-stearoylglycerophosphoethanolamine	1.02	1.00–1.04	0.101	0.352	1.03	1.00–1.06	0.035	0.175
1-stearoylplasmenylethanolamine*	1.03	1.00–1.06	0.049	0.294	1.04	1.00–1.08	0.036	0.175
1-arachidonoylglycerophosphoinositol*	1.01	0.99–1.03	0.191	0.456	1.02	1.00–1.05	0.048	0.198
Other
Erythrulose (Advance glycation end-product)	0.96	0.94–0.99	0.004	0.099	0.94	0.91–0.97	0.0002	0.035
HWESASXX (Polypeptide)	1.08	1.02–1.14	0.007	0.113	1.13	1.05–1.21	0.001	0.049
5-Hete (Eicosanoid)	1.06	1.02–1.10	0.003	0.099	1.08	1.03–1.13	0.002	0.075
Leukotriene B4 (Eicosanoid)	1.20	1.04–1.39	0.014	0.175	1.32	1.09–1.59	0.005	0.075
Prostaglandin E2 (Eicosanoid)	1.13	1.03–1.24	0.008	0.122	1.16	1.03–1.31	0.013	0.108
Erythronate (Aminosugar metabolism) *	1.02	1.01–1.03	0.003	0.099	1.02	1.00–1.03	0.015	0.115
Tartronate (hydroxymalonate) (Bacterial/fungal)	1.06	1.00–1.12	0.042	0.274	1.09	1.01–1.17	0.023	0.141
Myo-inositol (Inositol metabolism)	1.01	1.00–1.03	0.030	0.248	1.02	1.00–1.04	0.043	0.189
4-guanidinobutanoate (Guanidino and acetamido metabolism)	1.08	0.99–1.17	0.075	0.327	1.12	1.00–1.24	0.049	0.200
Bradykinin, Des-Arg(9)(Polypeptide)	1.08	0.96–1.22	0.222	0.482	1.17	1.00–1.37	0.051	0.200
Tocopherol metabolism
Delta-tocopherol	1.04	1.00–1.09	0.072	0.323	1.09	1.03–1.15	0.005	0.078
Tryptophan metabolism
Indole-3-carboxylic acid	1.03	1.00–1.06	0.034	0.250	1.05	1.01–1.09	0.007	0.081
Kynurenine	1.01	1.00–1.02	0.032	0.248	1.01	1.00–1.02	0.016	0.118
Leucine, isoleucine and valine metabolism
Isovalerate5	1.12	1.06–1.19	0.0002	0.036	1.15	1.06–1.24	0.001	0.047
N-acetylvaline	1.01	1.00–1.02	0.023	0.214	1.01	1.00–1.03	0.013	0.108
3-methyl-2-oxobutyrate	0.95	0.91–0.99	0.018	0.196	0.94	0.89–0.99	0.014	0.108
Isoleucine	1.01	1.00–1.01	0.042	0.274	1.01	1.00–1.02	0.041	0.184
N-acetylisoleucine	1.02	1.00–1.03	0.064	0.318	1.02	1.00–1.04	0.041	0.184
Fatty acid metabolism group
Butyrylcarnitine	0.96	0.93–0.99	0.017	0.196	0.95	0.91–0.99	0.013	0.108
Palmitoylcarnitine (C16)	0.96	0.93–0.99	0.018	0.196	0.96	0.92–1.01	0.114	0.266
Alanine and aspartate metabolism
N-acetylalanine	1.01	1.00–1.02	0.006	0.103	1.01	1.00–1.02	0.006	0.078
Fatty acid, monohydroxy
13-Hode + 9-Hode	1.10	1.03–1.18	0.004	0.099	1.14	1.05–1.24	0.004	0.075
Drug
4-acetylphenol sulfate	1.05	1.00–1.10	0.035	0.250	1.08	1.01–1.14	0.023	0.141
2-acetamidophenol sulfate	1.06	0.99–1.13	0.089	0.342	1.09	1.01–1.19	0.040	0.184
Benzoate metabolism
4-ethylphenylsulfate	1.05	1.02–1.09	0.006	0.101	1.06	1.01–1.11	0.021	0.133
Catechol sulfate	1.03	1.00–1.07	0.048	0.294	1.05	1.01–1.09	0.027	0.154
O-methylcatechol sulfate	1.03	1.00–1.07	0.085	0.339	1.05	1.00–1.10	0.045	0.192
Lysine metabolism
N6-acetyllysine	1.01	1.00–1.02	0.056	0.314	1.02	1.00–1.03	0.021	0.133
Glutarylcarnitine (C5)	0.99	0.99–1.00	0.166	0.429	0.99	0.98–1.00	0.045	0.192
Monoacylglycerol
1-myristoylglycerol (1-monomyristin)	1.03	1.00–1.06	0.024	0.217	1.05	1.02–1.09	0.005	0.075
Pentose metabolism group
Ribitol	1.02	1.01–1.03	0.002	0.092	1.03	1.01–1.04	0.003	0.075
Purine metabolism group
N6-succinyladenosine	1.02	1.00–1.03	0.006	0.101	1.02	1.00–1.03	0.029	0.156
7-methylguanine	1.01	1.00–1.02	0.078	0.331	1.02	1.00–1.03	0.010	0.104
N2,N2-dimethylguanosine	1.01	1.00–1.02	0.036	0.250	1.02	1.00–1.03	0.013	0.108
Food component/plant
Saccharin	0.93	0.86–1.01	0.106	0.360	0.88	0.78–0.98	0.025	0.145
2-oxindole-3-acetate	1.05	0.99–1.11	0.104	0.357	1.09	1.01–1.17	0.028	0.156
Ergothioneine	0.93	0.88–0.98	0.014	0.171	0.94	0.87–1.01	0.073	0.231
Glycine, serine and threonine metabolism
N-acetylthreonine	1.01	1.00–1.03	0.090	0.342	1.02	1.00–1.05	0.037	0.180
N-acetylserine	.	.	.	.	1.01	1.00–1.02	0.045	0.192
Long chain fatty acid
Cis-vaccenate (18:1n7)	0.98	0.97–1.00	0.062	0.318	0.97	0.95–0.99	0.015	0.113
Myristoleate (14:1N5)	0.98	0.96–1.00	0.063	0.318	0.97	0.94–1.00	0.029	0.156
Xanthine metabolism
3,7-dimethylurate	1.04	0.98–1.11	0.193	0.456	1.10	1.02–1.19	0.020	0.133
Chemical
4-Hydroxychlorothalonil	1.01	1.00–1.02	0.094	0.342	1.02	1.00–1.03	0.018	0.128
Fatty acid, dicarboxylate
3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF)	1.04	1.02–1.07	0.0003	0.036	1.06	1.03–1.09	0.0004	0.035
Sphingolipid metabolism
Oleoyl sphingomyelin	1.01	1.00–1.02	0.094	0.342	1.02	1.00–1.03	0.035	0.175

¹The relative change and its associated 95% confidence interval, P -value and Q-value were calculated using linear random effect models adjusted for age, sex, race, sodium level, dietary pattern and visit. The table is ranked by p-value of pathway analysis.

²The relative change has been exponentiated. The relative change in metabolite per 1-hour increase in sleep variable.

³Lower and upper 95% confidence intervals.

⁴Metabolites with a Q-value of ≥ 0.2 for either wake time or sleep mid-point are included.

^.Result not available.

⁵Isovalerate is classified as both a short chain fatty acid and amino acid