Table 2.

A few metabolic biomarkers of diagnostic and prognostic significance.

S/N	Disease Condition	Metabolic Biomarkers/Pathway	Analytical Platform	Statistics	References
1	Parkinson’s disease	Long-chain acylcarnitine	CE–TOF/MS	ROC	[42]
		Kynurenic acid, quinolinic acid, ratio of kynurenic acid/kynurenine, ratio of quinolinic acid/kynurenic acid	UPLC–TOF/MS	OPLS-DA	[41]
		3-hydroxykynurenine/kynurenic acid ratio	LC–MS	t-test	[43]
2	Alzheimer’s disease/ dementia	Total plasma tau			[61]
			1H NMR		[20]
3	Diabetic retinopathy	Perturbations in carbohydrate metabolism, lipid contents, biomarkers associated with phosphorylation and amide II group	FTIR spectroscopy	Difference between mean spectra (DBMS), forward feature selection (FFS), and Mann–Whitney U tests	[44]
		Alterations in glucose and purine metabolism; activation of the hexose monophosphate shunt	Untargeted MS		[45]
		Fumarate, uridine, acetic acid, and cytidine	LC–MS	Area under the curve (AUC)	[30]
		Plasma glutamine and glutamate	GC–MS/UPLC–MS	Multivariate analysis	[46]
		Activation of alanine, aspartate, and glutamate metabolic pathways	NMR-based spectroscopy	PCA, heat map analysis, average change analysis	[47]
4	Cardiovascular disease	N6,N6,N6-trimethyl-L-lysine	Stable isotope dilution tandem MS (LC–MS/MS)	Spearman’s correlation analyses	[18]
		Linoleate metabolism, glycosphingolipid metabolism, and carnitine shuttle pathway	Untargeted metabolomics	‘Meet in the middle’ statistics	[48]
		Acetylglycine, threoninyl-glycine, glutarylglycine, and nonanoylcarnitine	UPLS–Q/TOF–MS	ROC with AUC, sensitivity, specificity	[62]
		Phosphatidylserine, C16-sphingosine, N-methyl arachidonic amide, N-(2-methoxyethyl) arachidonic amide, linoleamidoglycerophosphate choline, lyso-PC (C18:2), lyso-PC (C16:0), lyso-PC (C18:1), arachidonic acid, and linoleic acid	UPLS–Q/TOF–MS	PCA, PLS-DA	[49]
		N8-acetylspermidine	LC–FT spectroscopy MS	Student t-test, ANOVA, Mann–Whitney U test, Kruskal–Wallis test, chi-square	[51]
		Acylcarnitine	MS	Paired t-test, generalised estimating equations	[52]
		Urea cycle/amino group, tryptophan, aspartate/asparagine, lysine, tyrosine, and carnitine shuttle pathways	LC–MS	t-test, chi-square	[53]
		Asparagine, tyrosine, xylose, for ischaemic stroke	LC–MS	Wilcoxon test, OPLS-DA	[54]
		Sphingomyelin for incident ischaemic stroke	LC–MS	Paired Wilcoxon rank test	[63]
		Citrate, tyrosine, 2- and 3-hydroxybutyrates for acute heart failure	NMR spectroscopy	Logistic regression analysis	[55]
		23 metabolites, with higher levels of 7 (3-hydroxybutyrate, proline, acetate, creatinine, acetone, formate, mannose) and lower levels of 2 (valine, histidine) as predictors of mortality	NMR spectroscopy	ROC, multivariate regression/PCA, Cox models	[56]
		104 metabolites, with lower levels of 7 (pelargonic acid, glucosamine/galactosamine, thymine, 3-hydroxybutyric acid, creatine, 2-aminoisobutyric acid, hypoxanthine) as correlates for coronary artery disease	CE–TOF/MS	Unsupervised PCA	[57]
		2-Hydroxycaproate, gluconate, and sorbitol for atherosclerosis	UPLC–MS	ROC	[58]
		13 metabolites, 2 of which (phenylalanine and acetate) were significant predictors of heart failure hospitalisation	NMR spectroscopy	t-test, Cox proportional hazard regression	[64]
5	Inborn errors of metabolism	Mannosyl-β1,4-N-acetylglucosamine, the biomarker for β-mannosidase deficiency; correctly diagnosed 90% of IEM cases	UHPLC–Orbitrap–MS	Z-scores	[60]
		Correctly identified 42 out of 46 IEM cases	LC–QTOF–MS	Two-sided t-tests	[59]