Bell, Christopher, John M. Carson, Nathaniel W. Motte, and Douglas R. Seals. Ascorbic acid does not affect the age-associated reduction in maximal cardiac output and oxygen consumption in healthy adults. J Appl Physiol 98: [845][846][847][848][849] 2005. First published October 22, 2004; doi:10.1152 doi:10. /japplphysiol.00790.2004 decreases progressively with age, primarily because of a reduction in maximal cardiac output (Q max). This age-associated decline in V O2 max may be partially mediated by the development of oxidative stress that can suppress ␤-adrenergic-receptor responsiveness and, consequently, reduce Q max. To test this hypothesis, V O2 max (indirect calorimetry) and Q max (open-circuit acetylene breathing) were determined in 12 young (23 Ϯ 1 yr, mean Ϯ SE) and 10 older (61 Ϯ 1 yr) adults following systemic infusion of either saline (control) and/or the powerful antioxidant ascorbic acid (acute: bolus 0.06; drip 0.02 g/kg fat-free mass) and following chronic 30-day oral administration of ascorbic acid (500 mg/day). Plasma ascorbic acid concentration was not different between young and older adults and was increased similarly, independent of age [change (⌬) acute ϭ 1,055 Ϯ 117%; ⌬ chronic ϭ 62 Ϯ 19%]. Oxidized low-density lipoprotein concentration was greater (P Ͻ 0.001) in older (57 Ϯ 5 U/l) compared with young (34 Ϯ 3 U/l) adults and was reduced in both groups (P Ͻ 0.02) following acute (⌬ ϭ Ϫ6 Ϯ 2%) but not chronic (P ϭ 0.18) ascorbic acid administration. Control (baseline) V O2 max and Q max were positively related (r ϭ 0.76, P Ͻ 0.001) and were lower (P Ͻ 0.05) in older (34 Ϯ 2 ml⅐ kg Ϫ1 ⅐ min Ϫ1 ; 16.1 Ϯ 1.1 l/min) compared with young (43 Ϯ 3 ml⅐ kg Ϫ1 ⅐ min Ϫ1 ; 20.2 Ϯ 0.9 l/min) adults. Following ascorbic acid administration, neither V O2 max (young acute ϭ 41 Ϯ 2; young chronic ϭ 42 Ϯ 2; older acute ϭ 34 Ϯ 2; older chronic ϭ 34 Ϯ 2 ml⅐ kg Ϫ1 ⅐ min Ϫ1 ) nor Q max (young acute ϭ 20.1 Ϯ 0.9; young chronic ϭ 19.1 Ϯ 0.8; older acute ϭ 16.2 Ϯ 1.1; older chronic ϭ 16.6 Ϯ 1.4 l/min) was changed. These data suggest that ascorbic acid administration does not affect the age-associated reduction in Q max and V O2 max. maximum oxygen uptake; open-circuit acetylene breathing MAXIMAL OXYGEN UPTAKE (V O 2 ; V O 2 max ) is an independent predictor of mortality (32) and functional capacity (1) and decreases progressively with primary or physiological aging (aging in the absence of clinical disease) (4, 35, 39). The decrease in V O 2 max with age is largely due to a reduction in maximal cardiac output (Q max ) (34,38,42). This age-associated decline in Q max is mediated in part by reduced maximal left ventricular contractility and heart rate as a partial consequence of decreased ␤-adrenergic-receptor responsiveness (38).The definitive physiological mechanism responsible for the age-associated reduction in ␤-adrenergic-receptor responsiveness has not been determined, but increased reactive oxygen species (ROS) may be involved. Primary aging in adult humans is associated with increased oxidative stress as a res...