Table 1.

Key studies investigating the three most promising metabolic pathways

Study design	Study population	Specimen	Sample size	Findings	References
Cross-sectional (discovery and replication)	Human, British females	Serum	598	BCAA to histidine ratio	Zhai et al. [26]
Cross-sectional (discovery and replication); longitudinal	Human, Canadian and Australian population	Plasma	415	BCAA to histidine ratio; lysoPC to PC ratio	Zhang et al. [27]
Animal OA model	Sheep	Serum	72	BCAAs	Maher et al. [28]
In vitro	Cultured human synovial tissue	OA synovium	22	Collagen, BCAA, energy and tryptophan metabolism	Adams et al. [48]
Cross-sectional (discovery and replication)	Human, Canadian population	Plasma	256	Arginine	Zhang et al. [49]
Cross-sectional	Human, Italian population	Plasma and SF	63	Arginine	Pascale et al. [51]
Animal OA model	Rabbits	Plasma	12	Arginine	Ohnishi et al. [53]
Cross-sectional	Human, German population	SF	57	PC metabolism	Kosinska et al. [54]
Cross-sectional (discovery and replication)	Human, Canadian population	Plasma and SF	227	PC metabolism	Zhang et al. [55]
Cross-sectional	Human, Dutch females	Plasma	59	LysoPC to PC ratio	Castro-Perez et al. [57]

BCAA: branched chain amino acid; lysoPC: lysophosphatidylcholine; PC: phosphatidylcholine.