Antioxidant defense and oxidative damage vary widely among high-altitude residents.

OBJECTIVES People living at high altitude experience unavoidable low oxygen levels (hypoxia). While acute hypoxia causes an increase in oxidative stress and damage despite higher antioxidant activity, the consequences of chronic hypoxia are poorly understood. The aim of the present study is to assess antioxidant activity and oxidative damage in high-altitude natives and upward migrants. METHODS Individuals from two indigenous high-altitude populations (Amhara, n = 39), (Sherpa, n = 34), one multigenerational high-altitude population (Oromo, n = 42), one upward migrant population (Nepali, n = 12), and two low-altitude reference populations (Amhara, n = 29; Oromo, n = 18) provided plasma for measurement of superoxide dismutase (SOD) activity as a marker of antioxidant capacity, and urine for measurement of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a marker of DNA oxidative damage. RESULTS High-altitude Amhara and Sherpa had the highest SOD activity, while highland Oromo and Nepalis had the lowest among high-altitude populations. High-altitude Amhara had the lowest DNA damage, Sherpa intermediate levels, and high-altitude Oromo had the highest. CONCLUSIONS High-altitude residence alone does not associate with high antioxidant defenses; residence length appears to be influential. The single-generation upward migrant sample had the lowest defense and nearly the highest DNA damage. The two high-altitude resident samples with millennia of residence had higher defenses than the two with multiple or single generations of residence.