Chronic fatigue, aging, mitochondrial function and nutritional supplements

Townsend Letter for Doctors and Patients, July, 2003 by Garth L. Nicolson

In animal studies the effects of reducing ROS have been dramatic in aging and disease models. For example, in rodents there are age-dependent losses in antioxidants, such as vitamins C and as well as reductions in reduced glutathione and the levels of antioxidant enzymes. (16, 17) Using aged rats the effects of alpha-lipoic acid and other dietary antioxidants on the levels of cellular antioxidants, such as reduced glutathione and vitamins C and E, levels of mitochondrial membrane lipid peroxidation and activities of mitochondrial electron transport and accessory enzymes were investigated. (18) Supplementation with antioxidants reduced mitochondrial lipid peroxidation, decreased levels of ROS and increased amounts or activities of certain electron transport enzymes. These authors found that dietary antioxidant supplementation reversed the age-related declines in cellular antioxidants and mitochondrial enzyme activities and prevented mitochondria from age-associated functional decline.

In another study rats were fed diets supplemented with coenzyme Q10, alphalipoic acid, melatonin or alpha-tocopherol for a six-month period. They found that antioxidants could inhibit the progression of certain age-associated changes in cerebral mitochondrial electron transport chain enzyme activities. (19) Similar results in rats using dietary coenzyme Q10 and other antioxidants were found in Japan. (20) Thus animal studies have shown -that antioxidants can prevent the aging-associated changes in mitochondrial structure and function.

In addition to the aging-associated oxidative changes in mitochondrial enzymes and lipids, mitochondrial DNA also accumulates oxidative damage during the aging process. (12,13,21) To prevent this antioxidants have also been useful, such as vitamins C and E, coenzyme Q10, sulfur-containing antioxidants and plant antioxidant extracts. (22,23) Age-associated damage to mitochondrial DNA may affect their ability to function due to a loss in the ability to synthesize and replace critical mitochondrial enzymes.

Antioxidants may also affect the pathogenic processes of certain diseases. In a mouse model for Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig's Disease, a neurodegenerative disease that results in brain motorneuron death, dietary coenzyme Q10 significantly increased lifespan and provided some neuroprotective effects, including decreased loss of nerve mitochondria. (24) The experimental dietary use of antioxidants can prevent age-associated mitochondrial dysfunction and damage, inhibit the age-associated decline in immune function and prolong the lifespan of laboratory animals. (25)

Clinical Studies on Antioxidants

There are few clinical studies, unfortunately, that have used the information from animal research to investigate the role of multiple dietary antioxidants in human aging and disease. Of course, one of the problems facing researchers who conduct clinical trials is the widespread use of vitamins and antioxidants by the general population that could affect such trials. Although the results obtained from controlled animal studies are backed up by studies in vitro using cultured human cells, (26) there have been only a few clinical trials that directly address the role of antioxidants in preventing mitochondrial damage during aging and disease. Major problems in designing and conducting such trials are that it is extremely unlikely that a single or even a few antioxidants can produce significant effects and prevent aging-associated changes or affect pathogenic processes and the problem that each individual may have optimum levels of antioxidants that could be suboptimal for others. Also, the number of various di fferent antioxidant combinations and concentrations that could be used in controlled clinical trials is daunting.