1.
The hormetic role of dietary antioxidants in free radical-related diseases.
Calabrese, V, Cornelius, C, Trovato, A, Cavallaro, M, Mancuso, C, Di Rienzo, L, Condorelli, D, De Lorenzo, A, Calabrese, EJ
Current pharmaceutical design. 2010;(7):877-83
Abstract
Regular consumption of cruciferous vegetables or spices is associated with a reduced incidence of cancer and reduction of markers for neurodegenerative damage. Furthermore, greater health benefit may be obtained from raw as opposed to cooked vegetables. Nutritional interventions, by increasing dietary intake of fruits and vegetables, can retard and even reverse age-related declines in brain function and cognitive performance. The mechanisms through which dietary supplementation with antioxidants may be useful to prevent free radical-related diseases is related to their ability to counteract toxic production of both reactive oxygen and nitrogen species, along with the up-regulation of vitagenes, such as members of the heat shock protein (Hsp) family heme oxygenase-1 and Hsp70. The most prominent dietary factor that affects the risk of many different chronic diseases is energy intake - excessive calorie intake increases the risk. Reducing energy intake by controlled caloric restriction or intermittent fasting increases lifespan and protects various tissues against diseases, in part, by hormetic mechanisms that increase cellular stress resistance. This biphasic dose-response relationship, referred to here as hormesis, display low-dose stimulation and a high-dose inhibition. Despite the current interest in hormesis by the toxicology community, quantitatively similar U-shaped dose responses have long been recognized by researchers to be involved with factors affecting memory, learning, and performance, as well as nutritional antioxidants and oxidative stress-mediated degenerative reactions. Dietary polyphenols present strong cytoprotective effects, however under uncontrolled nutritional supplementation gene induction effects and the interaction with detoxification responses can have negative consequences through the generation of more reactive and harmful intermediates.
2.
Work at high altitude and oxidative stress: antioxidant nutrients.
Askew, EW
Toxicology. 2002;(2):107-19
Abstract
A significant portion of the world's geography lies above 10,000 feet elevation, an arbitrary designation that separates moderate and high altitude. Although the number of indigenous people living at these elevations is relatively small, many people travel to high altitude for work or recreation, exposing themselves to chronic or intermittent hypoxia and the associated risk of acute mountain sickness (AMS) and less frequently, high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE). The symptoms of AMS (headache, nausea, anorexia, fatigue, lassitude) occur in those who travel too high, too fast. Some investigators have linked the development of these symptoms with the condition of altered blood-brain barrier permeability, possibly related to hypoxia induced free radical formation. The burden of oxidative stress increases during the time spent at altitude and may even persist for some time upon return to sea level. The physiological and medical consequences of increased oxidative stress engendered by altitude is unclear; indeed, hypoxia is believed to be the trigger for the cascade of signaling events that ultimately leads to adaptation to altitude. These signaling events include the generation of reactive oxygen species (ROS) that may elicit important adaptive responses. If produced in excess, however, these ROS may contribute to impaired muscle function and reduced capillary perfusion at altitude or may even play a role in precipitating more serious neurological and pulmonary crisis. Oxidative stress can be observed at altitude without strenuous physical exertion; however, environmental factors other than hypoxia, such as exercise, UV light exposure and cold exposure, can also contribute to the burden. Providing antioxidant nutrients via the diet or supplements to the diet can reduce oxidative stress secondary to altitude exposure. In summary, the significant unanswered question concerning altitude exposure and antioxidant supplementation is when does oxidative stress become potentially damaging enough to merit antioxidant therapy and conversely, what degree of oxidative stress is necessary to foster the adaptive response of altitude exposure?