Table 3.

Literature review of metabolite changes in PD patients compared to control, including (A) metabolites of the kynurenine pathway, (B) proteinogenic amino acids and (C) metabolites of the polyamine pathway.

No	Study	Research focus	Biomaterial	Cohort size (n)	Screening technique	Metabolites						Metabolite ratios
						Trp	KYN	3-HK	AA	KYNA	QUIN	3-HK/ KYNA	KYN/Trp	KYN/3-HK	KYN/KYNA	KYNA/QUIN
(A) Kynurenine pathway metabolites
0	This study	PD vs. CN/AD	Serum	231	LC-MS		↓	↑					↓	↓
1	Widner et al., 200293	PD vs. CN	Serum + CSF	33	HPLC	↓	↓						↑
2	Schulte et al., 201623	PD vs. RLS/CN	Serum	1449	LC-MS + GC-MS	⟷	⟷
3	Hatano et al., 201631	PD vs. CN	Serum	50	LC-MS + GC-MS	↓
4	Han et al., 201722	PD vs. CN	Serum	85	LC-MS	↓	↓	↑
5	Sorgdrager et al., 2019112	PD vs. AD/CN	Serum & CSF	105	LC-MS	↓		↓		↓			⟷			↓
6	Oxenkrug et al., 201724	PD vs. AD/CN	Plasma	62	LC-MS	↓	↑		↑	↑			↑
7	LeWitt et al., 201319	PD vs. CN	CSF	105	LC-MS + GC-MS			↑				↑
8	Iwaoka et al., 2020113	PD vs. CN	CSF	33	HPLC ECD		↑	↑
9	Havelund et al., 201768	PD vs. CN	Plasma & CSF	40	LC-MS				↓			↑		↓
10	Hartai et al., 200583	PD vs. CN	Plasma & RBC	36	HPLC					↓ plasma ↑ RBC
11	Ogawa et al., 199217	PD vs. CN	Brain regions	−85	HPLC ECD		↓	↑		↓			⟷	↓	⟷
12	Luan et al., 201547	PD vs. CN	Urine	157	LC-MS + GC-MS	↑	↑						↑

No	Study	Research focus	Biomaterial	Cohort size (n)	Screening technique	Arg	His	Lys	Asp	Glu	Ser	Thr	Asn	Gln	Cys	Sec	Gly	Pro	Ala	Val	Ile	Leu	Met	Phe	Tyr	Trp
(B) Amino acids
0	This study	PD vs. CN/AD	Serum	231	LC-MS				↑	↑															↑
1	Hirayama M. et al., 201653	PD vs. CN	Serum & sweat	58 & 107	LC-MS + HPLC fluorescence																			↑	↓
2	Schulte et al., 201623	PD vs. CN/RLS	Serum	1449	LC-MS + GC-MS	↓			↓	↓	↓	↑	↑	↑	↑		↑					↓		↓	↑	⟷
3	Fiandaca M. S. et al., 2018114	PD vs. CN/TBI	Serum	155	LC-MS					↓
4	Figura M. et al., 201852	ePD, lPD + /− LID (no CN)	Serum	73	HPLC fluorescence	↓						↑							↓					↓
5	Sorgdrager et al., 2019112	PD vs. CN/AD	Serum & CSF	105	LC-MS															↓		↓		↓	↓	↓
6	Iwasaki Y. et al., 199225	PD vs. CN	Plasma	40	Ion exchange				↑	↑							↑
7	Mueller T. et al., 201273	l-Dopa & PD (no CN)	Plasma	13	HPLC ECD										↓
8	Kuiper M.A. et al., 200050	PD vs. CN/AD/MSA	CSF	156	HPLC fluorescence	↑
9	Engelborghs S. et al., 2003115	PD vs. CN	CSF	54	HPLC ECD	- No significant changes detected (Asn,Cys, Sec, Pro and Trp not included) -
10	Oehman A. et al., 201520	PD vs. CN	CSF	20	1H-NMR spectr.														↓					↓
11	Jimenez-Jimenez F. J. et al., 199669	PD vs. CN	CSF & plasma	76	Ion exchange				↓				↑	↑			↑
12	Molina J.A. et al., 1997116	PD vs. CN	CSF & plasma	76	Ion exchange							↑								↓		↓	↑		↑	↓
13	Trupp et al., 201443	PD vs. CN	CSF & plasma	40	GC-MS						↑								↑				↑			↓
14	Wuolikainen et al., 201651	PD vs. CN/ALS	CSF & plasma	72	LC-MS + GC-MS		↑					↑		↑					↑		↑	↑
15	Mally J., et al., 1997117	PD vs. CN	CSF & serum	20	HPLC fluorescence					↓				↑
16	Luan et al., 201547	PD vs. CN	Urine	157	LC-MS + GC-MS			↑									↑	↑	↑		↑	↑		↑	↑	↑
17	Sertbas et al., 2014118	PD vs. CN	/	/	Stoichiometric model						(+)						(+)		(+)	(+)	(+)	(+)	(+)
18	Kori M. et al., 2016119	PD vs. AD/ALS	/	/	Pathway enrichment	(+)			(+)	(+)				(+)				(+)	(+)

No	Study	Research focus	Biomaterial	Cohort Size (n)	Screening technique	Cad	Put	Spd	Spm
(C) Polyamines
0	This study	PD vs. CN/AD	Serum	231	LC-MS
1	Saiki et al., 2019120	PD vs. CN/AD	Plasma	467	LC-MS + CE-MS			↑	↓
2	Paik M-J. et al., 201021	PD vs. CN/MSA	CSF	42	GC-MS	↑	↑	↓
3	Gomes-Trolin C. et al., 200227	PD vs. CN/ALS	RBC	60	HPLC fluorescence		↓	↑	↑
4	Betancourt L. et al., 2018102	PD vs. CN	RBC	24	LC-MS		↑
5	Vivo M. et al., 200118	PD vs. CN/HD/PSP	Brain	48	HPLC fluorescence		no difference to CN

The following parameters are shown: Study origin, research focus, source of biomaterial, total cohort size, screening technique, metabolite changes (↓ decrease, ↑ increase, ⟷ no change) and metabolite-ratio changes. The gaps in the table refer to non-analyzed or nonsignificantly changed metabolites.