Antioxidants and Nutrition

Free Radical Theory and History

This is a review article on the history of the free radical theory of ageing. Ageing is the major cause of death after the age of 28. In 1954, the free radical theory of ageing was first described stating that a "single common process, modifiable by genetic and environmental factors, was responsible for ageing and death of all living things." Ageing is caused by free radical reactions, which may be caused by the environment, from disease and from intrinsic eraction within the ageing process. The free radical theory of ageing is supported by: 1. Studies on the origin of life and evolution. 2. Studies on the effect of ionizing radiation on living things. 3. Dietary manipulations of endogenous free radical reactions. 4. The reasonable explanation that the free radical theory provides for ageing, and 5. The increasing number of studies which show that free radical reactions are involved in the pathogenesis of specific diseases. The author feels that further study of the role of free radical reactions and biological systems will result in significant increases in healthy, useful lives and life span. The main references supporting this view point are from the author himself. 17562

"Free Radical Theory of Aging: History", Harman, Denham, Free Radicals and Ageing, Emerit, I. and Chance, B., Birkhauser Verlag Basel/Switzerland, 1992;1-10. (Address: Denham Harman, University of Nebraska College of Medicine, Omaha, Nebraska 68198-4635, U.S.A.)

Glutathione Levels

This study evaluated 39 healthy men and 130 healthy women, between 20 and 94 years of age, for glutathione levels. Glutathione levels for the 20 to 39 year old subjects were approximately 547 ug/1010 erythrocytes for 40 individuals, with a reference range of 440 to 654. Based on this data, low blood glutathione content in older subjects increased significantly, particularly in the 60 to 79 year old group. Their glutathione levels were 452 ug/1010 erythrocytes, 17% lower than the reference group. An increased incidence of low glutathione levels in apparently healthy subjects might suggest a decreased capacity to maintain metabolic and detoxification reactions that are stimulated by glutathione. The authors feel that glutathione status, physical health, and longevity are closely related. This is the first time that health-associated reference values for glutathione levels have been determined in a sample of healthy young men and women between 20 and 39 years old. 17623

"Low Blood Glutathione Levels in Healthy Ageing Adults", Lang, Calvin A., et al, The Journal of Laboratory and Clinical Science, November 1992;120(5):720-725. (Address: Calvin A. Lang, ScD, Department of Biochemistry, MDR 412, University of Louisville School of Medicine, Louisville, KY 40292, U.S.A.)

Melatonin and Free Radicals

Melatonin is a very potent and efficient endogenous free radical scavenger. Pineal indolamine reacts with toxic hydroxyl radicals and can provide an immediate protection against oxidative damage to biomolecules within every cellular compartment. Melatonin acts as a primary non-enzymatic antioxidative defense against the destruction caused by hydroxyl free radicals. Melatonin and structurally related tryptophan metabolites are principally involved in the prevention of oxidative stress in a diverse range of organisms. Melatonin or treatments preserving the endogenous rythm of melatonin formation can retard the rate of ageing and the time of onset of age-related diseases. The activation of central excitatory amino acid receptors can suppress melatonin synthesis and is accompanied by a reduced detoxification rate of hydroxyl radicals. Aged animals and humans are melatonin-deficient and more sensitive to oxidative stress. New therapies investigating the effect of endogenous excitatory amino acid antagonists and stimulants of melatonin synthesis such as magnesium, may lead to therapeutic approaches for the prevention of diseases related to premature ageing. 18645

"Melatonin, Hydroxyl Radical-Mediated Oxidative Damage, and Ageing: A Hypothesis", Poeggeler, B., et al, Journal of Pineal Research, 1993;14:151-168. (Address: Russel J. Reiter, Department of Cellular and Structural Biology, The University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78284-7762, U.S.A.)

Minerals, Zinc, Magnesium and Phosphorus

This article argues the elderly are at a greater risk of developing mineral deficiencies. Special attention is given to the nutrients phosphorus, magnesium and zinc. The effect of hypochlorhydria on intestinal mineral absorption is also reviewed. Risk factors for developing mineral deficiency in the elderly include decreased food intake because of decreased activity, decreased lean body mass, decreased energy needs, increased prevalence of illness, altered taste and smell, oral health problems and avoidance of certain foods. Altered mineral bioavailability includes changes in dietary patterns and mineral imbalances. Drug mineral interactions are affected by polypharmacy, diuretics, laxatives and antacids. Decreased adaptive ability, reduced gastric acid secretion, decreased intestinal absorption efficiency and decreased renal function can all alter mineral balance in the elderly. Intestinal absorption of magnesium and zinc are reduced as well in the elderly. Renal reabsorption of phosphorus is controlled by hormonal levels of parathyroid hormone. This is critical in maintaining body phosphorus stores. Much less is known about the kidney control of urinary magnesium excretion. A summary of future research needs regarding magnesium phosphorus and zinc requirements in the elderly include improvement of assessment methods of minerals, studies of habitual mineral intake, nutritional status in the elderly, the assessment of the impact of increases in dietary fiber, phytate, calcium, decreases in consumption of foods high in saturated fat and cholesterol and age associated hypochlorhydria. It is important to study the effects of ageing on adaptive responses to decreased mineral intake or alterations in mineral bioavailability. Also, investigations regarding the effects of different body exchangeable pool sizes of minerals on physiologic function. 18319

"Mineral Needs of the Elderly: Developing a Research Agenda for the 1990s", Wood, Richard J., Age, 1991;14:120-128. (Address: Richard J. Wood, Chief, Mineral Bioavailability Laboratory, USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, U.S.A.)

Oxidative Stress, Fish Oil and Vitamin E

This general review article notes that as individuals age, there tend to be more free radical reactions in the body that are involved in the ageing process and degenerative diseases. Fish oil may benefit certain inflammatory conditions that are associated with ageing. With increased consumption of fish oil there is an increased need for vitamin E, especially when oxidative stress is increased. The risk to oxidative stress in elderly subjects may be increased when there are conditions in which highly unsaturated fatty acids are increased in cell membranes. Fish oil supplementation in older women for a period of 3 months showed a greater increase in plasma polyunsaturated fatty acids when compared to young subjects. With the substitution of potentially unstable omega-3 fatty acids, these older subjects are at a greater risk of oxidative stress than the younger subjects. It has been shown, with exercise-induced oxidative stress in older individuals consuming 800 I.U. of vitamin E per day or a placebo for 48 days, that there were significantly lower levels of lipid peroxides in the urine of those receiving the vitamin E compared to placebo. The author concludes by stating that increased levels of dietary antioxidants can significantly reduce tissue levels of lipid peroxides in both humans and animals. Low intake and/or low plasma antioxidant levels have been shown in older adults. Reduced antioxidant protection in conjunction with pro- oxidant toxicants, pollutants, drugs, high intakes of specific nutrients such as iron and copper, and long term fish oil intake along with unaccustomed exercise may increase the likelihood of cellular and tissue lipid peroxidation and damage. These processes may contribute to the ageing process and age-associated degenerative disorders. The author suggests that higher-than-recommended levels of dietary antioxidants, such as vitamin E, may be beneficial in older adults. 17661

"Vitamin E Requirement in Relation to Dietary Fish Oil and Oxidative Stress in Elderly", Meydani, Mohsen, et al, Free Radicals and Ageing, Emerit, I. and Chance, B., Birkhauser Verlag Basel/ Switzerland, 1992;411-418. (Address: Mohsen Meydani, Antioxidant Research Laboratory, USDA-Human Nutrition Research Center on Ageing at Tufts University, 711 Washington Street, Boston, MA 02111, U.S.A.)