Induced pluripotent stem cells as suitable sensors for fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome

Table 1 Summary of studies reporting significant differences in the urine composition of myalgic encephalomyelitis/chronic fatigue syndrome patients (P ≤ 0.1)

Ref.	Population studied/study design	Diagnosis criteria	Technique	Metabolites with increased levels				Metabolites with decreased levels
Erasmus et al[19], 2019	31 high CFS (patients) (31 F, 0 M). 39 low CFS (control) (39 F, 0 M). Age range, median and mean age NA	NA	H-NMR	Salicylic acid						P = 0.06
				Glucose
				Acetaminophen						P = 0.08
				Acetaminophen-glucuronide
Zhang et al[10], 2019	105 CFS (65 F, 40 M). 97 DD (56 F, 41 M). 190 HC (69 F, 121 M). Age range 20-49. Median and mean age NA	NA	H-NMR	M: Taurine						P < 0.01
				M: Tyrosine
				M: Leucine
				M: Valine
				M: Isoleucine
				M: Aspartate
				M: Ethylmalonate
				M: Lactate
				M: Threonine
				M: Trans-Aconitate
				M: 2-Aminohippurate
				M: N-Phenylacetylglycine
				M: N-Acetylaspartate
				M: Thymol
				B: Dimethylamine
				B: Histidine
				B: 4-Aminohippurate
				B: Hippurate
				B: Glutamine
				B: Isocitrate						P > 0.05
				B: 1-Methylnicotinamide
				B: N-Acetylglutamine
				B: Creatinine
				F: Isobutyrate
				F: Lysine
				F: Alanine
				F: Hypoxanthine
				F: Fucose
				F: N,N-dimethylglycine
				F: Urea
				F: Carnosine
				F: 3-Hydroxymandelate
				F: Indole-3-lactate
McGregor et al[20], 2019	11 ME/CFS (11F, 0 M) Mean age 30.9. 25 HC (24 F, 1 M). Mean age 33. 6	Canadian criteria	H-NMR	Mannitol	P < 0.001		Acetate			P < 0.001
							Urea
				Methylhistidine	P < 0.01		Pyruvate
Chi et al[21], 2018	98 CFS (77 F, 21 M). Age range 21-69. Median age 43. 99 HC (76 F, 23 M). Age range 19-65 yr. Median age 39 yr. Mean age: NA	United States centers	LC-MS	AE: Methyladenosine	P < 0.05		BE: Indoleacetaldehyde			P < 0.05 or P < 0.01
							BE: Phytosphingosine
							BE: Pyroglutamic acid
							BE: Creatinine
							AE: Acetylcarnitine
							AE Capric acid
							AE: Corticosterone
				AE: Creatinine			AE: Levonorgestrel
							AE: Pantothenic acid
							AE: Pyroglutamic acid
							AE: Xanthosine
							AE: Xanthurenic acid
							AE: Nonanedioic acid
Ruiz-Núñez et al[14], 2018	98 CFS (77 F, 21 M). Age range 21-69 yr. Median age 43 yr. 99 HC (76 F, 23 M). Age range 19-65 yr. Median age 39 yr. Mean age: NA	Fukuda criteria	LC-MS	NA			Nutritional factor		Urinary Iodine	P < 0.001
McGregor et al[11], 1996	20 CFS (16 F, 4 M). Age range 17-58 yr. Mean age 39.4 yr. 45 HC (32 F, 13 M). Age range 12-74 yr. Mean age 37.1 yr. Median age NA	CDC criteria	GC-MS	Aminohydroxy-N-methylpyrrolidine CFSUM1		P < 0.00003	CFSUM2			P < 0.0007
				Tyrosine		P < 0.02	Alanine			P < 0.005
				β-alanine
				Aconitic acid		P < 0.05	Glutamic acid			P < 0.02
				Succinic acid

AE: After exercise; B: Both; BE: Before exercise; F: Female; GC-MS: Gas chromatography-mass spectrometry; H-NMR: Proton nuclear magnetic resonance; HC: Healthy control; LC-MS: Liquid chromatography-mass spectrometry; M: Male; ME: Myalgic encephalomyelitis; NA: Not available.