The aim of this systematic review and meta-analysis [International Prospective Register of Systematic Reviews (PROSPERO) CRD42017055619] was to assess the effects of strict prolonged bed rest (without countermeasures) on maximal oxygen uptake (<(V) over dot>o(2max)) and to explore sources of variation therein. Since 1949, 80 studies with a total of 949 participants (> 90% men) have been published with data on strict bed rest and <(V) over dot>o(2max). The studies were conducted mainly in young participants [median age (interquartile range) 24.5 (22.4 -34.0) yr]. The duration of bed rest ranged from 1 to 90 days. <(V) over dot>o(2max) declined linearly across bed rest duration. No statistical difference in the decline among studies reporting <(V) over dot>o(2max) as l/min (-0.3% per day) compared with studies reporting <(V) over dot>o(2max) normalized to body weight (ml.kg(-1).min(-1); -0.43% per day) was observed. Although both total body weight and lean body mass declined in response to bed rest, we did not see any associations with the decline in <(V) over dot>o(2max). However, 15-26% of the variation in the decline in<(V) over dot>o(2max) was explained by the pre-bed-rest <(V) over dot>o(2max) levels, independent of the duration of bed rest (i. e., higher pre-bed-rest <(V) over dot>o(2max) levels were associated with larger declines in <(V) over dot>o(2max)). Furthermore, the systematic review revealed a gap in the knowledge about the cardiovascular response to extreme physical inactivity, particularly in older subjects and women of any age group. In addition to its relevance to spaceflight, this lack of data has significant translational implications because younger women sometimes undergo prolonged periods of bed rest associated with the complications of pregnancy and the incidence of hospitalization including prolonged periods of bed rest increases with age. NEW & NOTEWORTHY Large interindividual responses of maximal oxygen uptake (<(V) over dot>o(2max)) to aerobic exercise training exist. However, less is known about the variability in the response of <(V) over dot>o(2max) to prolonged bed rest. This systematic review and meta-analysis showed that pre-bed-rest <(V) over dot>o(2max) values were inversely associated with the change in<(V) over dot>o(2max) independent of the duration of bed rest. Moreover, we identified a large knowledge gap about the causes of decline in <(V) over dot>o(2max), particularly in postmenopausal women, which may have clinical implications.
