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Nutrition and Aging: GUEST EDITORIAL |
1 Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts.
2 Department of Rheumatology and Institute of Physical Medicine, University Hospital Zurich, Switzerland.
3 Department of Geriatrics, University Hospital Basel, Switzerland.
Address correspondence to Walter Willett, MD, DrPH, Department of Nutrition, Harvard School of Public Health, 655 Huntington Ave., Boston, MA 02115. Email: wwillett{at}hsph.harvard.edu
THE concept of frailty is complex and multidimensional based on the interplay of physical, psychological, social, and environmental factors (1,2). According to Fries and colleagues, frail elderly persons typically have low muscle strength, exhaustion, reduced physical activity, and unintentional weight loss (3). How nutrition contributes to this loss of reserves (energy, physical ability, cognition, health) is unclear, and little direct evidence exists on diet and frailty. Thus, in this editorial, the authors concentrate on evidence on diet and chronic age-related diseases that may contribute to the construct of frailty, and on adverse outcomes that have been linked to frailty, such as falls, fractures, and loss of independence (4–6). Chronic age-related diseases discussed in this editorial include coronary heart disease (CHD), stroke, osteoporosis, and dementia. Because the relation of diet to some of these conditions has been studied extensively, findings from this research may help to reduce the burdens associated with frailty and suggest directions to investigate the prevention of frailty more directly.
DIET IN THE PREVENTION OF CARDIOVASCULAR DISEASE, TYPE 2 DIABETES, AND FRACTURE: STRONG EVIDENCE
During the 1990s, the focus of most dietary recommendations was to reduce total fat intake and increase consumption of carbohydrates. However, controlled feeding studies, randomized trials, and epidemiologic evidence all indicate that the type of fatty acids, rather than the total percentage of calories from fat, is important. In a meta-analysis of feeding studies, replacing carbohydrate with saturated fat does not appreciably affect the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol, which strongly predicts risk of CHD (7). However, replacing carbohydrate with either monounsaturated or polyunsaturated fat reduces this lipid ratio, and thus would be expected to reduce the risk of heart disease. Trans fat has by far the worst effect on blood lipids. Findings from the 14-year follow-up of the Nurses' Health Study were qualitatively consistent with the controlled feeding studies (8). No association was observed between total fat intake and risk of CHD but, compared to a similar percent of calories from carbohydrate, trans fat was strongly related to higher risk and intakes of monounsaturated and polyunsaturated fats were associated with reduced risk. There was a 42% lower risk associated with replacing 5% of energy from saturated fat by unsaturated fat, and a 53% lower risk associated with replacing 2% of energy from trans fat by unsaturated fat.
In epidemiologic studies, the benefit of polyunsaturated fatty acids on risk of CHD appears to be stronger than predicted by their benefits on the lipid profile alone. This is probably due to additional effects of polyunsaturated fatty acids, including improvement of insulin sensitivity (9), reduction in platelet aggregation (10), decreases in inflammatory factors (11), and suppression of ventricular arrhythmias (12,13). Foods rich in n-3 polyunsaturated fatty acids are fish, flaxseed oil, soy oil, canola oil, and walnuts. Foods rich in n-6 polyunsaturated fatty acids are sunflower and other vegetable oils. In addition to their uniquely adverse effects on HDL and low-density lipoprotein (LDL), trans fatty acids from partially hydrogenated oils increase triglyceride levels, and adversely affect biomarkers of inflammation (such as C-reactive protein and soluble cell adhesion molecules) leading to impaired endothelial function 914). Trans fats are found in stick margarines, many baked goods, and deep-fried foods.
As with coronary heart disease, the type of dietary fat appears important in relation to risk of type 2 diabetes, itself a major risk factor for CHD. In the most extensive study of type of fat and risk of type 2 diabetes (15), a highly significant positive association was seen for trans fat intake. In contrast, risk was lower with higher intake of polyunsaturated fat, consistent with evidence that this reduces insulin resistance (16). The importance of the type of fat, rather than the percentage of energy from fat, has been emphasized in the 2005 U.S. Dietary Guidelines (http://www.healthierus.gov/dietaryguidelines), which include the recommendation that trans fat intake should be below 1% of energy.
While dietary fats have been at the center of efforts to reduce heart disease by nutritional means, many other aspects of diet also appear to be important. High consumption of rapidly absorbed carbohydrates, for example, from refined flour, sugar, sodas, and potatoes, has been associated with increased risk of CHD (17), hemorrhagic stroke (18), and type 2 diabetes (19). In contrast, higher intakes of fruits, vegetables, and whole grains have been associated with lower risks in many studies (20). Although much ongoing work is being directed at the identification of the responsible constituents, practical interventions can be based on overall dietary patterns. A dietary pattern typified by higher intakes of red and processed meats, refined grains, sweets, and desserts (Western diet) was associated with an increased risk of stroke and type 2 diabetes in a large cohort of United States nurses. If the highest quintile was compared to the lowest quintile within the Western diet, the increase in risk was 58% for total stroke and 49% for type 2 diabetes (21,22). In the Lyon Heart Study, the whole-diet approach was tested in a randomized trial among patients who had already experienced a myocardial infarction (23). In this study, a "Mediterranean-type diet" rich in fruits and vegetables and enriched in alphalinoleic acid (n-3 polyunsaturated fatty acid) in the form of canola oil was compared to a typical reduced-fat diet. Those on the Mediterranean-type diet experienced a 73% reduction in coronary events and a 70% reduction in total mortality after a 27-month follow-up. The rapid and large reduction in risk of CHD among patients with existing coronary disease highlights the potential for benefits from improved nutrition even late in the disease process.
Strong evidence also indicates that many or most adults in the United States and Europe would benefit from vitamin D supplements. Vitamin D modulates fracture risk in two ways: by decreasing falls and increasing bone density. In a cross-sectional analysis on the National Health and Nutrition Examination Survey (NHANES) data, blood levels of 25-OH vitamin D were positively associated with bone mineral density (24). A positive gradient was seen across the whole "normal" range of vitamin D levels, suggesting that the large majority of the United States population has suboptimal levels. In this same data set, vitamin D levels were inversely related to measures of muscle strength. In a recent report, Benedetta and colleagues found that low vitamin D intake predicted more than two-fold greater odds of becoming frail. Many lines of evidence also suggest that low vitamin D status increases the risk of colon and possibly other cancers (25–27).
The effects of vitamin D on falls and fractures have been summarized in two recent meta-analyses of double-blind, randomized controlled trials. For fall prevention, vitamin D reduced the odds ratio (OR) of falling by 22% (pooled OR = 0.78; 95% confidence interval [CI], 0.64–0.92) (28). The number needed to treat (NNT) was 15 (95% CI, 8–53), or equivalently 15 patients would need to be treated with vitamin D to prevent 1 person from falling. The benefit on falls was most pronounced for 800 IU vitamin D per day (pooled OR = 0.65 [95% CI, 0.40–1.00]), while 400 IU per day did not reduce the odds of falling. In a separate meta-analysis, vitamin D doses of 700 to 800 IU/d reduced the risk of hip fracture by 26% (29). Similar to falls, no significant benefit was observed for randomized controlled trials that used 400 IU/d vitamin D. The NNTs for hip fracture prevention was 45 and 27 for any nonvertebral fracture. A recent pragmatic trial from the United Kingdom did not achieve fracture prevention with 800 IU vitamin D per day, while mean 25-hydroxyvitamin D levels increased from 38 to only 62 nmol/l (30). This is consistent with a suggested fracture efficacy level at 80–100 nmol/l 25-hydroxyvitamin D as proposed in a recent meta-analysis and studies of bone density and lower extremity function (24,29,31).
Older persons are more dependent on dietary sources of vitamin D because previtamin D produced through sunlight exposure of the skin is reduced up to four-fold with age (32). Other risk factors for suboptimal levels include obesity, darker skin, living at a Northern latitude, and residing in an institution, although low blood levels are also common in healthy community-dwelling individuals (31,32). Vitamin D supplements are inexpensive and effective in increasing serum 25-hydroxyvitamin D levels in older individuals, but more than 800 IU of vitamin D per day will often be needed to reach serum 25-hydroxyvitamin D levels of 80 nmol/l or above (33).
A healthy body composition is important in the prevention of frailty. The relation between body weight, energy intake, and frailty is complex because loss of muscle mass and reduced activity are features of the syndrome, which in turn reduce physical activity and energy intake. Although low energy intake will tend to be associated with frailty, as seen in the InCHIANTI study by Bartali and colleagues in this issue (60), simply increasing energy intake may not be beneficial for many elderly people. Increases in energy intake without increases in physical activity can result in greater adiposity, which in turn contributes risk for several chronic diseases associated with frailty, such as cardiovascular disease and diabetes (34,35). Regular physical activity, including resistance training, to increase muscle mass and function accompanied by adequate energy intake will have many benefits (20,36).
PROMISING AREAS OF RESEARCH: ANTIOXIDANT, HOMOCYSTEINE LOWERING, AND ANTIINFLAMMATORY NUTRIENTS
Reasonable hypotheses exist relating these aspects of diet to cognition, dementia, and eye health, but more research is needed to accumulate strong evidence. The importance of preventing these conditions will continue to grow as we become more successful in reducing the incidence of cancer and cardiovascular disease. In several observational studies, antioxidant micronutrients, such as vitamin C and E (37), appeared to reduce cognitive impairment and dementia, especially Alzheimer's disease (38). Supporting a possible role of oxidative stress in the development and progression of dementia, in vivo markers of lipid peroxidation are increased in individuals with cognitive impairment, and their levels correlate with measures of cognitive impairment and the number of apolipoprotein E epsilon-4 alleles (39). In a preliminary report from the Physicians' Health Study randomized trial, men assigned to long term use of beta-carotene supplements had improved cognitive function (40). Peifeng and colleagues recently found that antioxidants, and especially beta-carotene, may reduce cognitive decline among older individuals at increased risk due to the presence of one or two apolipoprotein E epsilon-4 alleles. This finding needs replication, but has great potential importance, as it might eventually justify screening to identify these high-risk individuals.
Elevated blood levels of homocysteine are associated with both CHD (41,42), stroke (43,44), and lower cognitive function (45), and folic acid, vitamin B6, vitamin B12, and riboflavin (41,43) can reduce hyperhomocysteinemia. Although folic acid supplementation (5 mg/day) has reduced brachial pulse pressure, a measure of artery stiffness (46), the effects of reducing homocysteine levels on risk of cardiovascular disease and cognitive decline remain unsettled. Although benefits of homocysteine lowering have not been seen in secondary prevention trials of relatively short duration (47,48), this may be too late in the course of disease to have a measurable effect. Notably, in a randomized trial in China, a multivitamin/multimineral supplement significant reduced the incidence of stroke (49,50).
Intakes of long-chain omega-3 fatty acids and fish, the primary source of these fatty acids, have been associated with lower risk of dementia and Alzheimer's disease in some studies (39,51). A recent review (52) concluded that data to support a favorable effect of omega-3 fatty acids on the incidence and improvement of cognitive function are limited. The strong evidence for benefit of omega-3 fatty acid in reducing CHD lends plausibility to findings for dementia and suggests the need for further research.
The development of cataracts is tightly related to aging, and in one large prospective study, cataract extraction was associated with a nearly two-fold higher risk of CHD (53). Because cataracts represent the accumulation of oxidized and glycosolated proteins, they may serve as one of most directly observable indicators of tissue aging. In two prospective studies, intake of lutein, mainly obtained from green leafy vegetables and the primary carotenoid found in the lens, was associated with lower risk of cataract (54,55). Some evidence suggests that lutein may also reduce the risk of age-related macular degeneration (56), and, in a recent trial among patients with existing macular degeneration, a combination of antioxidants and zinc supplements reduced progression of this disease (57–59).
Summary
Although there is limited direct evidence on the relationship between diet and frailty, indirect evidence suggests that optimal nutrition may contribute to the prevention of frailty by decreasing the incidence of CHD, stroke, and type 2 diabetes. Greater intake of vitamin D will reduce risks of falls and fractures among elderly individuals, and other benefits are possible. Higher intakes of B vitamins, dietary carotenoids , and omega-three fatty acids may be important for the prevention of frailty among older persons, but further research is needed. A reasonable diet for most persons would emphasize monounsaturated and polyunsaturated fats, whole grains, and an abundant intake of fruits and vegetables, and would minimize consumption of saturated and trans fatty acids, sugar, and refined starches. A vitamin D supplement that contains 800 to 1000 IU daily would be generally desirable. Relatively few persons consume such a diet, which presents a challenge for researchers and those who care for elderly patients.
F
Decision Editor: Luigi Ferrucci, MD, PhD
Received June 10, 2005
Accepted April 2, 2006
References
60 y. Am J Clin Nutr. 2004;80:752-758.
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