Redox‐regulation of haemostasis in hypoxic exercising humans: a randomised double‐blind placebo‐controlled antioxidant study

• Published in: The Journal of physiology 2018-10, Vol.596 (20), p.4879-4891
• Main Authors: Fall, Lewis, Brugniaux, Julien V., Davis, Danielle, Marley, Christopher J., Davies, Bruce, New, Karl J., McEneny, Jane, Young, Ian S., Bailey, Damian M.
• Format: Article
• Language: English
• Subjects: Acetic acid; activated coagulation; Antioxidants; Antithrombin; Ascorbic acid; Blood coagulation; Cellulose; Dietary supplements; Double-blind studies; Exercise; Free radicals; haemostasis; Hypoxia; Olfaction; Oxidative stress; Prophylaxis; Research Paper; Thrombin; Vitamin E
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/JP276414

Key points In vitro evidence has identified that coagulation is activated by increased oxidative stress, though the link and underlying mechanism in humans have yet to be established. We conducted the first randomised controlled trial in healthy participants to examine if oral antioxidant prophylaxis alters the haemostatic responses to hypoxia and exercise given their synergistic capacity to promote free radical formation. Systemic free radical formation was shown to increase during hypoxia and was further compounded by exercise, responses that were attenuated by antioxidant prophylaxis. In contrast, antioxidant prophylaxis increased thrombin generation at rest in normoxia, and this was normalised only in the face of prevailing oxidation. Collectively, these findings suggest that human free radical formation is an adaptive phenomenon that serves to maintain vascular haemostasis. In vitro evidence suggests that blood coagulation is activated by increased oxidative stress although the link and underlying mechanism in humans have yet to be established. We conducted the first randomised controlled trial to examine if oral antioxidant prophylaxis alters the haemostatic responses to hypoxia and exercise. Healthy males were randomly assigned double‐blind to either an antioxidant (n = 20) or placebo group (n = 16). The antioxidant group ingested two capsules/day that each contained 500 mg of l‐ascorbic acid and 450 international units (IU) of dl‐α‐tocopherol acetate for 8 weeks. The placebo group ingested capsules of identical external appearance, taste and smell (cellulose). Both groups were subsequently exposed to acute hypoxia and maximal physical exercise with venous blood sampled pre‐supplementation (normoxia), post‐supplementation at rest (normoxia and hypoxia) and following maximal exercise (hypoxia). Systemic free radical formation (electron paramagnetic resonance spectroscopic detection of the ascorbate radical (A•−)) increased during hypoxia (15,152 ± 1193 AU vs. 14,076 ± 810 AU at rest, P