The objective of the study was to test the hypothesis that serum levels of cartilage oligomeric 2 matrix protein (COMP) would decrease and serum levels of tumor-necrosis factor alpha 3 (TNF-α) and selected matrix metalloproteinases (MMPs) would increase in response to bed 4 rest (BR) and that these changes are unaffected by the intake of potassium bicarbonate or 5 whey protein. Seven and 9 healthy male subjects participated in two 21-day 6° head down tilt 6 crossover BR-studies with nutrition interventions. Serum samples were taken before, during, 7and after BR and biomarker concentrations were measured using commercial enzyme-linked 8 immunosorbent assays. MMP-3 during BR was significantly lower than at baseline (reduction 9 greater 20%; P<0.001). MMP-3 increased significantly from 14 to 21 days of BR (+7%; 10 P=0.049). COMP during BR was significantly lower than at baseline (reduction greater 20%; 11 P<0.001). MMP-3 and COMP returned to baseline within one day after BR. MMP-9 on day 3 12 of BR was significantly lower than at baseline (-31%; P<0.033) and on days 3, 5 and 14 of 13