Roger B. McDonald

Use of Antioxidant Nutrients in the Prevention and Treatment of Type 2 Diabetes

Type 2 diabetes, or non-insulin dependent diabetes mellitus (NIDDM), is increasingly common throughout the world. The World Health Organization has predicted that between 1997 and 2025, the number of diabetics will double from 143 million to about 300 million. The incidence of NIDDM is highest in economically developed nations, particularly the U.S., where approximately 6.5% of the population (17 million people) have either diagnosed or undiagnosed diabetes. The two most important factors contributing to the development of NIDDM are obesity and physical inactivity. The leading cause of mortality and morbidity in people with NIDDM is cardiovascular disease caused by macro- and microvascular degeneration. Current therapies for NIDDM focus primarily on weight reduction. Indeed, several investigations indicate that 65% to 75% of cases of diabetes in Caucasians could be avoided if individuals in this subgroup did not exceed their ideal weight. The success of this approach has been, at best, modest. An alternate approach to the control of Type 2 diabetes is to arrest the progress of the pathology until a cure has been found. To this end, some investigators suggest that dietary antioxidants may be of value. Several studies in humans and laboratory animals with NIDDM indicate that vitamin E and lipoic acid supplements lessen the impact of oxidative damage caused by dysregulation of glucose metabolism. In this brief review, we discuss the incidence, etiology, and current therapies for NIDDM and further explore the usefulness of dietary antioxidants in treating this disorder.

Dietary Acculturation among Latinos of Mexican Descent

The current Mexican diet, high in complex carbohydrates, is being abandoned as first and second generation Americans of Mexican descent adopt a more typical mainstream American diet. Some changes—more milk, fruit and vegetables—can be considered “healthy,” but many others may be considered potentially deletrious.

Iron, zinc and magnesium nutrition and athletic performance.

SummaryDuring the last decade there has been considerable interest in the idea that dietary trace element supplementation can result in an improvement in athletic performance. The current paper discusses this idea as it relates to 3 elements: iron, zinc and magnesium. Emphasis has been placed on examining the implicit assumptions underlying the idea that mineral supplements help the athlete. These assumptions include the beliefs that the athlete has a higher than normal requirement for minerals; that the athlete consumes a diet inadequate in these minerals; and that a marginal deficiency of these elements has a direct effect on athletic performance.Evidence is presented that both iron deficiency and magnesium deficiency can result in a significant reduction in exercise performance; however, the biochemical lesions under-lying the reductions in exercise performance have not been identified. There is evidence that dietary magnesium intake may be suboptimal in some individuals, thus dietary supplementation of this element may be useful in some population groups. Excessive magnesium supplementation is not thought to be a serious health problem. Similar to magnesium, dietary iron supplements can improve athletic performance in individuals severely deficient in this element. However, few studies have documented a need for iron supplements in healthy athletes. If iron supplements are used, it is important that the level of supplementation is not excessive, as excess iron in the diet can result in an induced zinc deficiency.In marked contrast to iron and magnesium, there is little evidence for the idea that zinc deficiency influences exercise performance in humans. Despite this fact, zinc supplements have been widely advocated for the athlete, as it is known that intense exercise can result in changes in zinc metabolism. If zinc supplements are used, it is important that they are not excessive, as excess zinc in the diet can result in a secondary copper deficiency.

Complex I-associated hydrogen peroxide production is decreased and electron transport chain enzyme activities are altered in n-3 enriched fat-1 mice.

The polyunsaturated nature of n-3 fatty acids makes them prone to oxidative damage. However, it is not clear if n-3 fatty acids are simply a passive site for oxidative attack or if they also modulate mitochondrial reactive oxygen species (ROS) production. The present study used fat-1 transgenic mice, that are capable of synthesizing n-3 fatty acids, to investigate the influence of increases in n-3 fatty acids and resultant decreases in the n-6∶n-3 ratio on liver mitochondrial H2O2 production and electron transport chain (ETC) activity. There was an increase in n-3 fatty acids and a decrease in the n-6∶n-3 ratio in liver mitochondria from the fat-1 compared to control mice. This change was largely due to alterations in the fatty acid composition of phosphatidylcholine and phosphatidylethanolamine, with only a small percentage of fatty acids in cardiolipin being altered in the fat-1 animals. The lipid changes in the fat-1 mice were associated with a decrease (p<0.05) in the activity of ETC complex I and increases (p<0.05) in the activities of complexes III and IV. Mitochondrial H2O2 production with either succinate or succinate/glutamate/malate substrates was also decreased (p<0.05) in the fat-1 mice. This change in H2O2 production was due to a decrease in ROS production from ETC complex I in the fat-1 animals. These results indicate that the fatty acid changes in fat-1 liver mitochondria may at least partially oppose oxidative stress by limiting ROS production from ETC complex I.

Brown Adipose Tissue Thermogenesis During Aging and Senescence

We have found that cold- and norepinephrine-induced brown adipose tissue (BAT) nonshiveringthermogenesis (NST) is significantly lower in old male Fischer 344 rats and is associatedwith the decreased ability of these animals to maintain homeothermy. This decline in BATthermogenesis is not as great in females. Although the mechanism(s) underlying this genderdifference in the age-related decrease in brown fat NST are not completely elucidated, theydo not appear to reflect decreased sympathetic neural activity of BAT in the older males vs.females. Rather, our investigations, strongly suggest that the blunted cold-induced heatproduction of BAT reflects less functional BAT. The fact that the older animals have less functionalBAT than do their younger counterparts may predispose them to the accumulation of excessbody fat. Our studies have also found that near the end of the natural life of these rats, theyenter a state of senescence that can be identified by spontaneous rapid body weight loss,resulting from decreased food intake. In this state, the rats are considerably more susceptibleto cold than are comparably aged presenescent (body weight stable) rats of the samechronological age. The greater hypothermia exhibited by the senescent vs. presenescent rats during coldexposure is associated with a significant reduction in the amount of functional brown fat andin the amount of heat each brown fat cell can generate. It is the intent of this review to discussthe findings of these investigations.

Alterations in endogenous circadian rhythm of core temperature in senescent Fischer 344 rats

We assessed whether alterations in endogenous circadian rhythm of core temperature (CRT) in aging rats are associated with chronological time or with a biological marker of senescence, i.e., spontaneous rapid body weight loss. CRT was measured in male Fischer 344 (F344) rats beginning at age 689 days and then continuously until death. Young rats were also monitored. The rats were housed under constant dim red light at 24-26°C, and core temperature was recorded every 10 min via biotelemetry. The CRT amplitude of the body weight-stable (presenescent) old rats was significantly less than that of young rats at all analysis periods. At the onset of spontaneous rapid weight loss (senescence), all measures of endogenous CRT differed significantly from those in the presenescent period. The suprachiasmatic nucleus (a circadian pacemaker) of the senescent rats maintained its light responsiveness as determined by an increase in c- fos expression after a brief light exposure. These data demonstrate that some characteristics of the CRT are altered slowly with chronological aging, whereas others occur rapidly with the onset of senescence.

Influence of dietary sucrose on biological aging

The segment of the population aged > 65 y is the fastest growing age segment in most developed countries. The increasing numbers of individuals living into their eighth and ninth decades of life have shifted the focus of biomedical research from seeking mechanisms for extending life to finding ways to improve health and to reduce age-related morbidity. One area of research that has shown considerable promise for improving the health of elderly people is nutrition. I review recent literature pertinent to the influences of nutrition on biological aging by discussing the effects of dietary sucrose and other carbohydrates on glucose homeostasis, age-related disorders and pathology, and life span. Although critical gaps remain in our understanding of how dietary sucrose can affect biological aging, evidence exits that the type and amount of dietary carbohydrate can significantly affect the health and life span of elderly people.

Effect of Participation in Congregate-Site Meal Programs on Nutritional Status of The Healthy Elderly

OBJECTIVE This study was designed to evaluate whether participation in a congregate-site meal program influenced the nutritional status of a group of healthy elderly. DESIGN Nutritional status, as defined by dietary intake and biochemical indexes, was assessed in free-living persons (aged 60 to 89 years) who either did (n = 70) or did not (n = 65) participate in the meal program. Three-day mean intakes of 17 nutrients and serum levels of 13 indexes of nutritional status were measured. STATISTICAL ANALYSES Multifactorial analysis of variance was used to determine differences in nutrient intake data and biochemical indexes between the groups. By means of correlation analysis, relationships between income and main outcome measures were examined. chi 2 Analysis was used to determine differences in response to categorical variables of the questionnaire. RESULTS In general, dietary intakes of participants did not differ significantly from those of nonparticipants, nor did the meal provided at the site significantly affect the overall dietary intake of participants. Mean biochemical indexes of nutritional status were within normal ranges for participants and nonparticipants, except for iron. However, 26% of the population consumed diets that may place them at risk for nutritional inadequacy. CONCLUSIONS Mean dietary intake data and biochemical indexes of nutritional status suggest that the congregate-site meal program did not significantly affect the nutritional status of the population surveyed. Additional studies focusing on the nutritional intake and status of low-income, ethnic minority, and socially isolated participants in the congregate-site meal program are needed to assess which populations are at risk for nutritional deficiencies.

Effect of aging, caloric restriction, and uncoupling protein 3 (UCP3) on mitochondrial proton leak in mice

Mitochondrial proton leak may modulate reactive oxygen species (ROS) production and play a role in aging. The purpose of this study was to determine proton leak across the life span in skeletal mitochondria from calorie-restricted and UCP2/3 overexpressing mice. Proton leak in isolated mitochondria and markers of oxidative stress in whole tissue were measured in female C57BL/6J mice fed ad-libitum (WT-Control) or a 30% calorie-restricted (WT-CR) diet, and in mice overexpressing UCP2 and UCP3 (Positive-TG), their non-overexpressing littermates (Negative-TG) and UCP3 knockout mice (UCP3KO). Proton leak in WT-CR mice was lower than that of control mice at 8 and 26 months of age. The Positive-TG mice had greater proton leak than the Negative-TG and UCP3KO mice at 8 months of age, but this difference disappeared by 19 and 26 months. Lipid peroxidation was generally lower in WT-CR vs. WT-Control mice and UCP3KO mice had greater concentrations of T-BARS (thiobarbituric acid reactive substances, a measure of lipid peroxidation) than did Positive-TG and Negative-TG. The results of this study indicate that sustained increases in muscle mitochondrial proton leak are not responsible for alterations in life span with calorie restriction or UCP3 overexpression in mice. However, UCP3 may contribute to the actions of CR through mechanisms distinct from increasing basal proton leak.

A diet high in fat stimulates adipocyte proliferation in older (22 month) rats

The effect of a high fat diet in stimulating adipocyte proliferation, as measured by the incorporation of [3H]-thymidine into fat cell DNA, was studied in 22-month-old female Sprague-Dawley rats. Rats were fed a low fat (n = 10) or a high fat diet (n = 9) for a total of six days. On days 4 and 5 of dietary manipulation, rats were injected with 80 microCi/100 g body weight of [3H]-thymidine. Rats were continued on their respective diets for one more day, starved for 72 h and then refed a stock diet for three weeks in order to increase turnover of stroma cells, thus diluting the specific activity of stromal DNA with minimal effect on specific activity of fat cell DNA. The diet groups did not differ significantly with respect to body masses, food intake, parametrial (PARA) and retroperitoneal (RP) depot masses, cell number or cell size. The specific activity of DNA in both PARA and RP depots was greater in the adipocyte than in the stromavascular fraction. Specific activity of fat cells was significantly greater from rats fed the high fat than the low fat diet in both PARA and RP depots. Radioautography of adipose tissue confirmed that there was a greater percentage of adipocyte nuclei labeled in the rats fed the high fat diet. Also, there were few labeled nuclei found in stroma cells. In conclusion, older female rats increased adipocyte proliferation when fed a high fat diet.