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August 15, 2002
Thank you for the opportunity to appear before you today representing the National Institutes of Health (NIH), Division of Nutrition Research Coordination (DNRC). The DNRC is administratively located within the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH. Prior to my current position, I was the Director, Office of Nutrition, National Institute on Aging (NIA), NIH. This testimony includes a brief overview of the federal government's current efforts in aging and nutrition research. These efforts include research on caloric restriction, diet and physical activity and recent research activities in dietary supplementation with regard to aging and nutrition.
Today, approximately 13 percent of Americans are over age 65. By the year 2030, the number of individuals age 65 and older will likely double–reaching 70.3 million or 20 percent of the total population. Of great concern is the explosive increase in numbers anticipated among those most at risk of disease and disability–people age 85 and older. Their ranks are expected to grow from 4.3 million in 2000 to at least 19.4 million in 2050.
In order to understand the aging process, it is important to identify those factors that affect the overall life span of an organism. It is essential to understand the responsible physiological mechanisms and to identify ways to slow down age-related changes. Beyond any gains in life span, studies in this area are aimed more importantly at developing interventions to keep older people healthy and free of disease and/or disability as long as possible. Studies in a number of animal models are providing valuable insights into the mechanisms of longevity, yet important questions still remain. For example, it is likely that heredity, environment, and lifestyle all have complex roles in determining a long and healthy life. But is there a maximum human life span beyond which we cannot live no matter how optimal our environment or favorable our genes? And perhaps, most importantly, how can insights into longevity be used to fight age-related diseases and disabilities to ensure a healthy, active, and independent life well into very old age? With a rapidly aging population, it is critically important to find answers to these questions, which could possibly help us identify ways to maximize the span of good health and thereby improve the quality of life of older people. Nutritional factors hold great promise for realizing this goal.
Federally-Supported Aging and Nutrition Research
The NIA at the NIH is the leader in aging research and research on the role of nutrition in aging. However, the NIA is not alone in this endeavor; other Institutes and Centers, other component agencies within the U.S. Department of Health and Human Services, and other federal agencies such as the U.S. Department of Agriculture (USDA) also support research in these areas.
The federal research efforts in the area of nutrition recognize the need to combine physical activity and diet. The Surgeon General's "Call to Action to Prevent and Decrease Overweight and Obesity," which was released in December 2001, encourages the promotion of healthy eating and adequate physical activity. Aging and nutrition researchers were well ahead of the curve in this line of study. In the early 1990s, scientists at Tufts University, supported by NIA and USDA, conducted a study examining the effect of a nutritional supplement, an exercise regimen or the combination of both, on frailty in the elderly. While nutrition supplementation resulted in a slight decrease in frailty, physical activity provided a better response; however, the best results were obtained with a combination of both nutrition and exercise.
The importance of combining a healthy diet and exercise was again demonstrated in August 2001, when the Diabetes Prevention Program (DPP) clinical trial was halted a year early due to remarkably positive results. The DPP compared three approaches–lifestyle modification, treatment with metformin, and standard medical advice–in 3,234 overweight people with pre-diabetes, a condition in which blood glucose levels are higher than normal but not yet diabetic. About 16 million people in the U.S. have pre-diabetes, which raises the risk of developing type 2 diabetes and cardiovascular disease. Once a person has type 2 diabetes, the risk of heart and blood vessel disease is even greater. It is two to four times that of people without diabetes.
An intervention consisting of diet plus exercise that together produced an average 5 to 7 percent weight loss reduced progression to type 2 diabetes by 58 percent in participants randomized to this lifestyle intervention. Participants in this group exercised at moderate intensity, usually by walking an average of 30 minutes a day five days a week, and lowered their intake of fat and calories. This intervention was most effective in people 60 years and older whose risk of developing diabetes was reduced by 71 percent. Participants randomly assigned to treatment with the diabetes drug metformin had a 31 percent overall lower incidence of type 2 diabetes; however, metformin was most effective in younger individuals. Metformin lowers blood glucose mainly by decreasing the liver's production of glucose.
Changes in diet and physical activity not only prevented the development of diabetes, but also restored normal glucose levels in many people who had impaired glucose tolerance. The DPP, conducted at 27 centers nationwide, is the first major trial to show that lifestyle changes can effectively delay diabetes in a diverse population of overweight American adults with pre-diabetes. The DPP was spearheaded by the NIDDK and co-sponsored by the NIA, the National Institute of Child Health and Human Development, the National Center on Minority Health and Health Disparities, the National Center for Research Resources, the NIH Office of Research on Women's Health, and the NIH Office of Behavioral and Social Science Research, as well as the Centers for Disease Control and Prevention (CDC), the Indian Health Service and the American Diabetes Association.
Caloric Restriction Research
Since the 1930s, investigators have consistently found that laboratory rats and mice live up to 30 percent longer than usual when fed a nutritionally balanced diet that has at least 30 percent fewer calories than they would normally consume. These studies were the first demonstration that the maximum life span of a mammal could be increased.
More recent research has found that these animals also appear to be more resistant to age-related diseases including cancer. Other rodent studies have found that caloric restriction may increase resistance of neurons in the brain to dysfunction and death. In fact, caloric restriction appears to delay normal age-related degeneration of a number of physiological systems in rodents.
Studies on the effects of caloric restriction in higher mammals (monkeys) are ongoing. Preliminary results are promising, including greater resistance to diabetes and heart disease in these animals. Yet, even if caloric restriction is successful in extending primate life span, it is doubtful that it will ever become a practical and acceptable long-term goal for most humans. However, caloric restriction shows that life span can be altered, prompting research into possible mechanisms.
In an effort to further elucidate the role of caloric restriction in extending healthy life span in humans, in March 1999, the NIA and NIDDK co-sponsored a meeting of the Caloric Restriction Clinical Implications Advisory Group. In October 2000, based on the scientific recommendations from this group, the NIA and NIDDK issued a research solicitation for "Exploratory Studies of Sustained Caloric Restriction in Non-Obese Persons: Physiologic Effects and Comparisons/Interactions with Physical Activity."
Subsequently, three sites were awarded a research grant: Tufts University (Boston, MA), Washington University (St Louis, MO) and The Pennington Biomedical Research Center (Baton Rouge, LA). Collectively, the three projects are known as CALERIE (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy). Briefly, the CALERIE projects involve exploratory, controlled human intervention studies on the effects of caloric restriction interventions on physiology, body composition, and risk factors for age-related diseases in non-obese persons. The populations of interest in this study include overweight individuals (Body Mass Index of 25.0 to 29.9), other individuals at risk for becoming overweight or obese, and formerly obese persons at risk for recurrence of obesity. The primary goals of the CALERIE projects are to gain knowledge about the effects in humans of sustained calorie restriction on physiology, metabolism, body composition, risk factors for age-related pathologies, progression of age-related changes, and potential adverse effects; and to gain knowledge of similarities, differences and interactions between the effects of calorie restriction and physical activity on the previous outcomes when employed in interventions to prevent weight gain. The endpoints of the CALERIE studies include energy intake and expenditure, physical activity, body composition, endocrine responses, insulin sensitivity/glucose metabolism, cardiovascular function, bone density, immune function, quality of life, and potential adverse effects of calorie restriction. Study populations in the CALERIE projects are non-obese adults, with a likely age range of 25 to 60 years. The expected duration of the CALERIE projects is seven years. CALERIE is about to begin the Phase I (pilot) portion of the study which is expected to last about two years.
Dietary Supplements and Aging
The use of dietary supplements has increased dramatically as our knowledge has increased about the role of nutrients and other bioactive components of food in health. Although much of the information about the diet and health connection that has driven this trend is related to the reduction of chronic disease risk in adults, belief in the prophylactic use of these substances has been extended to consumers throughout the life cycle. The NIH–along with other government agencies such as the USDA, the Food and Drug Administration (FDA), and the CDC–has had a keen interest in expanding knowledge about: (1) the bioavailability of nutrients and other bioactive components of dietary supplements; (2) the identification of critical gaps in our knowledge about the use of dietary supplements in the elderly; and (3) mechanisms of action whereby dietary supplements might delay aging, facilitate health and prevent the progression of diseases of the elderly.
Dietary supplements encompass a wide range of products. They include vitamins, minerals, amino acids, herbs and other botanicals. They also include dietary substances used to supplement the diet by increasing the total dietary intake. They can be prepared as a concentrate, metabolite, constituent, extract, or combination of any ingredient described previously, and ingested in the form of a capsule, powder, tablet, liquid, or softgel. The amount of scientific data available on the safety and efficacy of dietary supplements varies enormously, ranging from folklore to facts. For some supplements, recommended levels for the elderly have been established through extensive research and published, but for others, serious negative health consequences can occur.
Findings from CDC's third National Health and Nutrition Examination Survey (1988-1994) suggest that 40 percent of Americans use dietary supplements. Approximately 56 percent of middle-aged and older adults consume at least one supplement on a regular basis. Because of this high frequency of use of dietary supplements in the elderly, the General Accounting Office published two reports in September 2001. Reasons for dietary supplement use include maintenance of overall health, increase of energy, improving memory, preventing or treating illness, and slowing the aging process. The number of scientific studies on the safety or efficacy of these products is limited because FDA approval is not required prior to marketing of dietary supplements, as they are not considered to be either a food or a drug. Problems surrounding the use of dietary supplements include adverse events, interactions with prescription drugs and/or over-the-counter medications, interactions with medical conditions, contamination of preparations, mislabeling, and high cost. Of particular concern for the elderly is the issue of interaction of dietary supplements and prescription medications because the elderly take more prescription drugs than other age groups. For example, the effects of anticoagulant medications commonly taken by the elderly may be adversely affected by coenzyme Q10, gingko biloba, garlic, ginseng, glucosamine, and St. John's Wort. Another major issue is the high cost of many dietary supplements; the elderly are often living on modest fixed incomes and paying for unnecessary or potentially harmful supplements may present an economic hardship.
On the other hand there are significant health benefits associated with the use of certain vitamin and mineral supplements. The evidence supporting the benefit of supplemental vitamin B12 for older adults is so strong that, in 1998, the Institute of Medicine advised all adults age 50 and over to obtain their vitamin B12 from dietary supplements or fortified foods due to a decrease in the body's ability to absorb B12 with aging. There is increasing clinical evidence that B vitamins, such as folic acid, vitamins B6 and B12 play a role in preventing blood vessel diseases and in maintaining normal cognitive function. The need is well established for vitamin D and calcium in the prevention of osteoporosis due to bone mineral loss. Older individuals who do not consume vitamin D-fortified milk should consider consuming 400 International Units of vitamin D per day from a supplement. Similarly, the current adequate daily intake for calcium for adults age 50 and over is 1,200 mg, which–in addition to diet–can only be achieved in some individuals through fortified foods and/or consumption of dietary supplements.
Recent exciting work has examined the role of folate supplementation in protecting the brain against Alzheimer's disease, Parkinson's disease, and other neurodegenerative disorders. One recent study concluded that high blood levels of homocysteine in people was correlated with nearly twice the risk of developing Alzheimer's disease. In a new study, the investigators fed one group of mice, which were genetically-engineered (transgenic mice) to develop Alzheimer's-like plaques in their brains, a diet that included normal amounts of folate, while a second group was fed a diet deficient in this vitamin. The investigators found a decreased number of neurons in one region of the hippocampus (brain region critical for learning and memory) in the mice fed the folic acid-deficient diet. In addition, in transgenic mice fed a folate-deficient diet, nerve cells in the hippocampus exhibited damage to their DNA. Such damage was not observed in transgenic mice fed an adequate amount of folate. Subsequent experiments in cell culture have suggested that folic acid deficiency and homocysteine may compromise a neuron's ability to repair its DNA successfully.
Another mouse experiment suggests that folic acid deficiency could increase the brain's susceptibility to Parkinson's disease. Moreover, the scientists discovered that mice with low amounts of dietary folic acid had elevated levels of homocysteine in the brain and blood. It is suspected that increased levels of homocysteine in the brain may exacerbate the cellular damage caused by environmental and other agents to the substantia nigra, an important brain structure that produces dopamine. Loss of dopamine causes the nerve cells to dysfunction, leaving Parkinson's patients unable to direct or control their movement in a normal manner. People who have Alzheimer's disease or Parkinson's disease often have low levels of folic acid in their blood, but it is not clear whether this is a result of the disease or if they are simply malnourished due to their illness.
Based on this recent research, consuming adequate amounts of folic acid–either in the diet or by supplementation–could be beneficial to the aging brain and could help protect it against Alzheimer's disease, Parkinson's disease and possible other neurodegenerative diseases. However, it should be noted that currently available data, although suggestive, do not establish the role of folic acid in susceptibility to neurodegenerative disease. Definitive determination of whether folic acid or homocysteine levels play a role in Alzheimer's or Parkinson's disease will require completion of controlled clinical trials.
In order to further investigate the role of supplements in preventing or delaying age-associated diseases, the NIA, in collaboration with the NIH Office of Dietary Supplements, will convene a two-day conference in January 2003, to present current data and research about dietary supplement use by the elderly in both U.S. and international populations. The goals of the conference are to develop a focused research program in this area. The issues to be explored include:
Mr. Chairman and Members of the Committee, I thank you again for inviting me to review aging and nutrition issues and to highlight some exciting ongoing research. I would be happy to answer questions.
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Last revised: August 19, 2002