5
Nutrition Concerns for Aging Populations

Moderated by Johanna Dwyer of the National Institutes of Health (NIH) and the Jean Mayer U.S. Department of Agriculture (USDA) Human Nutrition Research Center on Aging (HNRCA) at Tufts University, Boston, Massachusetts, this session included four presentations. Katherine Tucker, also of the Jean Mayer USDA HNRCA at Tufts University, spoke about diet quality issues in aging populations. Stephen Barnes of the University of Alabama, Birmingham, discussed functional foods (i.e., foods with health benefits beyond what their traditional nutrients provide) and the challenge of bioavailability. He emphasized that not all functional foods, like soy, are necessarily alike with respect to their health-promoting benefits, depending on how they are processed. Luigi Fontana of Washington University, St. Louis, Missouri, and the Italian National Institute of Health, Rome, Italy, discussed recent research on caloric restriction and is effects on longevity and age-associated diseases. Both Fontana and Tucker also addressed the issue of protein intake in older adults. Finally, Jim Kirkwood of General Mills discussed the importance of combining science with consumer desires when considering how to formulate foods that older consumers will actually purchase and eat. He emphasized the importance of understanding “what really matters to consumers” when developing and marketing food products, a theme that was revisited at length in the session on communication (see Chapter 6). The session ended with a panel discussion.



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5 Nutrition Concerns for Aging Populations M oderated by Johanna Dwyer of the National Institutes of Health (NIH) and the Jean Mayer U.S. Department of Agriculture (USDA) Human Nutrition Research Center on Aging (HNRCA) at Tufts University, Boston, Massachusetts, this session included four pre- sentations. Katherine Tucker, also of the Jean Mayer USDA HNRCA at Tufts University, spoke about diet quality issues in aging populations. Stephen Barnes of the University of Alabama, Birmingham, discussed func- tional foods (i.e., foods with health benefits beyond what their traditional nutrients provide) and the challenge of bioavailability. He emphasized that not all functional foods, like soy, are necessarily alike with respect to their health-promoting benefits, depending on how they are processed. Luigi Fontana of Washington University, St. Louis, Missouri, and the Ital- ian National Institute of Health, Rome, Italy, discussed recent research on caloric restriction and is effects on longevity and age-associated diseases. Both Fontana and Tucker also addressed the issue of protein intake in older adults. Finally, Jim Kirkwood of General Mills discussed the importance of combining science with consumer desires when considering how to formulate foods that older consumers will actually purchase and eat. He emphasized the importance of understanding “what really matters to con- sumers” when developing and marketing food products, a theme that was revisited at length in the session on communication (see Chapter 6). The session ended with a panel discussion. 

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 PRoVIdIng HEAltHy And SAFE FoodS AS WE AgE DIET QUALITY ISSUES FOR AgINg POPULATIONS Presenter: Katherine tucker Tucker remarked that the focus of her talk would be on how dietary needs change with aging, which nutrients in particular are important for ag- ing populations, and the challenge of achieving access to and consumption of a high quality diet given the obstacles already discussed by other speakers (e.g., loss of appetite, oral health decline, mobility constraints). How Dietary Needs Change with Aging Dietary needs change with aging in several ways: • People become less active, their metabolism slows, their energy re- quirement decreases, all of which mean that they need to eat less. • Recent research demonstrates that because older adults’ abilities to absorb and utilize many nutrients become less efficient, their nutri- ent requirements (particularly as a function of body mass) actually increase. Tucker mentioned that the last set of nutrition recommen- dations issued by the Institute of Medicine (IOM) include separate recommendations for people age 70 and above for this reason (IOM, 2006). • Tucker noted that as some of the previous speakers had discussed, chronic conditions and medications can affect nutrition require - ments. For example, in addition to drug-nutrient interactions af- fecting drug metabolism, some drug-nutrient interactions are also nutrient wasting. This is especially true of the B vitamins. Maintaining a nutrient-dense diet is critically important for older adults because of the impact of food intake on health. Years of research have dem- onstrated that diet quality has a huge effect on physical condition, cogni- tive condition, bone health, eye health, vascular function, and the immune system. Yet, this can be challenging to achieve for several reasons: • As Pelchat discussed, aging is often accompanied by a loss of ap- petite and changes in taste and smell, all of which can lead to more limited food choices and lower intake of healthful foods. • As Jensen discussed, aging is also often accompanied by general oral health decline and a reduced ability to swallow, which can affect food choice and intake. • Many older adults experience mobility constraints, which make it difficult to shop for food, lift heavy jars, open containers, etc.

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 nUtRItIon ConCERnS FoR AgIng PoPUlAtIonS • As both Wellman and Kinsella mentioned, low income is prevalent in aging populations, making it difficult for many older adults to access high quality foods (i.e., because those foods tend to be more expensive). A Modified Food guide Pyramid for older Adults Because of the changing dietary needs of older adults, Tucker’s col- leagues at the Jean Meyer USDA HRNCA developed what they termed the Modified Food Pyramid for older adults (Russell et al., 1999) (Figure 5-1). Key modifications to the original USDA Food Guide Pyramid include place- ment of water at the bottom of the pyramid because many older adults do not drink enough water to stay hydrated, and placement of a flag at the top of the pyramid indicating the need for calcium, vitamin D, and vitamin B12 supplements because many older adults do not get enough of these nutrients in a standard diet. After an update to the Food Guide Pyramid took place for the general population, Tucker’s colleagues also created a new Modified MyPyramid for older adults with illustrated examples of healthful foods in each food group (Lichtenstein et al., 2008) (Figure 5-2). Key modifications to the original MyPyramid include the addition of examples of physical FIgURE 5-1 The original Food Guide Pyramid and the modified Food Guide Pyra- mid for adults more than 70 years of age. SOURCE: Russell et al., 1999. Figure 5-1, fixed

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0 PRoVIdIng HEAltHy And SAFE FoodS AS WE AgE FIgURE 5-2 A modified MyPyramid for adults more than 70 years of age. SOURCE: Lichtenstein et al., 2008. activity at the bottom of the pyramid. Greater physical activity allows for intake of larger quantities of food, which in turn increases the likelihood that all of the necessary nutrients will be consumed. Also, physical activity Figure 5-2, fixed helps maintain muscle mass with aging. Dietary Patterns of Older Adults Of course, not all older adults follow the guidelines of the modified MyPyramid. Tucker discussed the variety of ways that older adults eat. She and her colleagues have been examining dietary patterns in older adults as part of the Baltimore Longitudinal Study on Aging.1 They identified 1The Baltimore Longitudinal Study on Aging is a National Institute on Aging (NIA) project. For more information, visit the website http://www.grc.nia.nih.gov/branches/blsa/blsa.htm.

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 nUtRItIon ConCERnS FoR AgIng PoPUlAtIonS five eating patterns: “white bread” (people that obtain considerably more energy intake from white bread [16 percent, on average] relative to other patterns), “healthy” (higher energy intake from fruit, high fiber cereal, and whole grain bread), “meat” (higher energy intake from meat and potatoes), “alcohol” (higher energy intake from alcohol), and “sweets” (higher energy intake from baked sweets) (Newby et al., 2003). As just one example of how diet affects health, she showed data on waist circumference. Gener- ally, as people age, their weight increases with the rate of increase slow- ing down over time; most of the gained weight is deposited in the central area of the body. Tucker and her colleagues found that older adults in the “white bread” group experienced a significantly greater increase in weight circumference than older adults in the other eating groups. The “healthy” group showed the least gain in weight circumference. Protein Intake Tucker spent much of the remainder of her talk focusing on specific components of the diet, beginning with protein intake. The issue of protein intake in older adults is controversial. She explained that while some experts warn that higher protein intake could be harmful because it could increase the risk of toxicity or impaired renal function, recent research suggests that moderately high protein intake is necessary for maintaining nitrogen balance and offsetting age-related lower energy intake, decreased protein synthetic efficiency, and impaired insulin action. Current recommendations (IOM, 2005) actually call for the same protein intake in both older and younger adults. Even so, according to 2003–2004 data from the National Health and Nutrition Examination Survey (NHANES), about 6 percent of men at the age of 71 and above and about 4 to 6 percent of women above the age of 50 are not meeting the recommended intake levels. As an example of recent evidence implicating the importance of protein intake, Houston et al. (2008) show that among men and women with sarcope- nia2 and between the ages of 70 and 79, individuals with the highest protein in- take lost the least amount of lean muscle mass over a three-year period. Tucker explained that the greater the proportional loss of lean muscle mass, the greater the proportion of fat mass, and the greater the risk of metabolic imbalances and related chronic conditions. Also, loss of lean muscle mass increases the likelihood of falling. She stated that maintaining muscle mass in older adults is one of the most important preventative health steps that can be taken. In another study, contrary to expectations, Tucker and colleagues found that higher protein intake was associated with lower bone loss (Hannan et 2 Sarcopenia is the degenerative loss of muscle mass and strength that occurs with aging; muscle mass as a proportion of total body mass decreases.

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 PRoVIdIng HEAltHy And SAFE FoodS AS WE AgE al., 2000). In the past, based on results from short-term clinical studies, it was generally believed that higher protein intake leads to calcium loss in the urine, which in turn contributes to bone loss. other Macronutrients Tucker briefly described the role of other macronutrients, namely omega-3 fatty acids and fiber, in maintaining health during aging. Dietary fiber is known to be important for maintaining intestinal health and pro- tecting against heart disease and other metabolic conditions. With lipids, the concern with older adults is not too much total fat or too much satu- rated fat, as it is with younger adults, rather too few omega-3 fatty acids. Epidemiological studies have found that higher intakes of omega-3 fatty acids provide greater protection against many conditions, including car- diovascular events (e.g. arrhythmias, cardiac death, recurrent myocardial infarction), diabetes, and cognitive decline. The problem is that omega-3 fatty acids are very limited in the standard diet, with the main sources being fatty fish, flax seeds, and walnuts. Moreover, the omega-3 fatty acid obtained from flax seeds and walnuts is different than what can be obtained from fatty fish and may not be as beneficial. The health effects associated with this group of fatty acids are an important area of current investigation. Tucker stated that it is unclear whether supplements can provide the same benefits. Both of these macronutrients are far from adequate in the diets of most older adults. For example, an ongoing study of older Puerto Rican adults in the Boston area has shown that about 40 percent of adults between the ages of 51 and 70 and about 70 percent of adults age 71 and older have omega-3 fatty acid intakes above the Adequate Intake (AI)3 for n-3 polyunsaturated fatty acids.4 About 10 percent of 51–70 year-olds and 40 percent of adults 71 and older have dietary intake levels above the AI for fiber. The AIs were established by the Institute of Medicine (IOM, 2005). 3 An Adequate Intake (AI) was developed because of inadequate scientific evidence to deter- mine an Estimated Average Requirement (EAR). The AI is a recommended average daily nutri- ent intake level based on observed or experimentally determined approximations or estimates of nutrient intake by a group (or groups) of apparently healthy people that are assumed to be adequate. Mean usual intake greater than the AI implies a low prevalence of inadequate intakes, especially when the AI is based on the mean intake of a healthy group. 4 Omega-3 fatty acids do not specifically have an AI and are instead included in the AI for n-3 polyunsaturated fatty acids. The omega-3 fatty acids DHA and EPA contribute approxi- mately 10 percent of the total n-3 fatty acid intake (IOM, 2005).

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 nUtRItIon ConCERnS FoR AgIng PoPUlAtIonS Micronutrients In almost every dietary survey conducted over the past few decades, older adults have inadequate intakes of some essential micronutrients. Moreover, subsets of older adults are often at greater risk of certain micronutrient defi- ciencies. For example, Non-Hispanic black and low-income older adults typi- cally experience micronutrient intake levels lower than the 1989 Recommended Dietary Allowances (RDA)5 compared to other groups (Weimer, 1997). According to 2005–2006 NHANES data, 92 percent of adults over the age of 51 years are below the Estimated Average Requirement (EAR)6 for vitamin E; 67 percent are below the magnesium EAR; 46 percent are below the vitamin C EAR; 33 percent are below the zinc EAR; and 32 percent are below the vitamin B6 EAR. Only 14.6 percent are above the AI for calcium (1,200 mg), which Tucker stated is high and controversial. She described in more detail three of these nutrients: vitamin E, vitamin B6, and magnesium. Vitamin E. Tucker mentioned Meydani’s earlier discussion about vitamin E and the important role that it plays as an antioxidant and in maintaining immune function. She stated that the only straightforward way to meet the currently very high RDA of 15 mg of α-tocopherol is to include nuts and seeds, like almonds or sunflower seeds, in the diet and that there are other important tocopherols in other foods that are being overlooked. Partially because of the difficulties in obtaining sufficient levels of vitamin E through diet, many people are taking vitamin E supplements. Data from the Jack- son Heart Study show, however, that concentrations of certain tocopherols are actually lower in people taking supplements (Talegawkar et al., 2007). In particular, γ -tocopherol concentrations in people taking α-tocopherol supplements were half of what they were in people not taking supplements, because the two forms compete with each other. It is not clear what the implications of this exchange are, although some experts believe that loss of γ -tocopherol may somehow contribute to DNA damage. Tucker empha- sized that the larger problem is that negative consequences can occur when supplements are used as a substitute for food. Vitamin B6. Tucker explained that vitamin B6 is important for numerous metabolic reactions in the body, with inadequacies sometimes leading to 5 The Recommended Dietary Allowance (RDA) is an estimate of the daily average dietary intake that meets the nutrient needs of nearly all (97–98 percent) healthy members of a par- ticular life stage and gender group. 6 The Estimated Average Requirement (EAR) is the average daily nutrient intake level esti- mated to meet the requirement of half of the healthy individuals in a particular life stage and gender group. It is used to examine the prevalence of nutrient inadequacy in groups.

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4 PRoVIdIng HEAltHy And SAFE FoodS AS WE AgE high homocysteine concentrations and impaired immune function. Vitamin B6 deficiencies have also been associated with cognitive function decline and depression, both of which are common problems in older adults. Data from the Massachusetts Hispanic Elderly Study show a high prevalence of low vitamin B6 blood concentrations among both Hispanic and non-Hispanic whites, with 30 percent of Hispanics and 28 percent of non-Hispanic whites having blood concentrations less than 30 nmol/L, and 16 percent of Hispan- ics and 11 percent of non-Hispanic whites having blood concentrations less than 20 nmol/L (Merete et al., 2008). Data from the Normative Aging Study show that individuals in the lowest tertile of vitamin B6 concentration have significant loss in cognitive ability over five years, while individuals with the highest vitamin B6 concentrations showed no loss (Tucker et al., 2005). Magnesium. Tucker noted only that data from the Framingham Study show that magnesium and potassium are also very important (along with calcium) for maintaining bone health. This means that fruits and vegetables, which people have not associated with bone health in the past (as Tucker said, “it was all about dairy”), are in fact important. Vitamin B12. The same 2005–2006 NHANES data indicate that very few people age 51 and older (16 percent) are below the EAR for vitamin B12, although there are some subsets of the older population whose intake levels are lower than others (Kwan et al., 2002). Importantly, even though most older adults consume enough vitamin B12, it nonetheless remains a serious problem in the aging population because it is so poorly absorbed due to decreased stomach acidity. Many widely prescribed and over-the-counter acid blocking drugs also block the ability to absorb vitamin B12. Data from the Framingham Offspring Study (Tucker et al., 2000) showed that 8 percent of vitamin B12 supplement users still had low concentrations of B12 in their blood (0.250 µmol/L), and 20 percent of non-supplement users had low concentrations. Low vitamin B12 concentrations in older adults create a serious problem, as deficiencies can lead to a variety of serious nerve-related effects, including peripheral neuropathy, balance disturbances, cognitive disturbances, and ultimately physical disability (e.g., see Healton et al., 1991). Inadequate concentrations of vitamin B12 also lead to high homocysteine concentrations and a greater risk of heart disease. New find- ings also show an association between lower vitamin B12 concentrations and greater loss of bone density (Tucker et al., 2005). Other studies suggest additional vulnerabilities to compromised nutri- ent status among older adults (e.g., Lichtenstein et al., 2008). Lichtenstein and colleagues (2008) also showed that folate and sodium, on the other hand, are overconsumed by older adults. While overconsumption of sodium

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 nUtRItIon ConCERnS FoR AgIng PoPUlAtIonS among older adults has been well known for a long time Tucker remarked folate overconsumption is an interesting story. Folate. Folic acid was added to the food supply as a way to protect against neural tube defects, with the goal of reaching women at childbearing age before they get pregnant. However, researchers have since identified several possible adverse effects of high folic acid in the food supply, including accel- erated effects of vitamin B12 deficiency (while folate masks B12 deficiency by covering up the anemia, it also drives pathways that make the B12 deficiency worse), an increased risk of some cancers (while folic acid from food can be protective against cancer, large amounts of folic acid from supplements or fortified foods can accumulate in the blood), and an increased risk of cogni- tive decline (again, folic acid from food can protect against cognitive decline because of its important role in DNA methylation, but large amounts of folic acid may be detrimental). Vitamin D. Tucker explained that older adults are at high risk of vitamin D inadequacy because of limited sources of vitamin D in the diet (fortified milk, fatty fishes), less exposure to sunlight, a decreased capacity to synthesize vita- min D in the skin even when exposure to sunlight is plentiful, and a decreased capacity of the kidneys to convert vitamin D into its active form. In the past, the focus with vitamin D was on calcium absorption and metabolism and bone health. Now, vitamin D has been proposed to be associated with many neurological and other chronic conditions. Tucker shared data from an ongo- ing study of an older Puerto Rican population near Boston showing that only 18 percent of adults between 51 and 70 years old have intakes above the AI and just 8 percent of adults age 71 and older have intakes above the AI. In a study of homebound elders, Buell et al. (2009) found that more than 60 percent of their study population had insufficient vitamin D concentrations in their blood (less than 20 ng/mL), and more than 50 percent had less than 400 international units (IU) intake per day. When the data were examined by race, the researchers found that about 69 percent of non-black elders had vitamin D deficiency (defined in this study as less than 10 ng/mL), compared to about 80 percent of black elders. Buell and colleagues (2009) also identi- fied associations between vitamin D deficiency and several different measures of cognitive function with the interesting exception of memory. Dietary Variety In conclusion, Tucker said that “one of the most important things we can do for the aging population” is ensure good dietary intake. Important risk nutrients include protein; omega-3 fatty acids; dietary fiber; vitamins B6, B12, and E; calcium; magnesium; and potassium. Many older adults

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 PRoVIdIng HEAltHy And SAFE FoodS AS WE AgE are not getting enough of these nutrients. On the other hand, too many older adults are getting too much folate and sodium. She remarked the best way to ensure good dietary intake is by increasing intake of whole grains, fruits and vegetables, fish, nuts, lean protein sources, and low-fat dairy and decreasing intake of refined grains and highly processed foods. Tucker emphasized the importance of complexity in the diet and referred to a study suggesting higher dietary variety is associated with overall better nutritional status and better health outcomes in frail elderly people (Bernstein et al., 2002). The challenge is getting good quality foods to this population. FUNCTIONAL FOODS AND AgINg POPULATIONS Presenter: Stephen Barnes Barnes began by remarking that he would be talking about functional foods and some of the challenges around bioavailability of active com- pounds in functional foods. What Is a Functional Food? Barnes explained that functional foods were not specifically defined in the Federal Food, Drug, and Cosmetic (FDC) Act of 1938. Instead, he referred to a 1994 IOM definition of functional food: a “food or food ingredient that may provide a health benefit beyond the traditional nutrients it contains” (IOM, 1994). Many functional foods are conventional foods, that is, foods that were foods even before the concept of a functional food was generated; often they contain specific GRAS (Generally Recognized as Safe) components with known benefits. However, anytime a health-promoting claim is made about an item that is not related to the item’s “nutritive” value, the item is considered a supplement and thereby falls under the provisions of the Dietary Supplement Health and Education Act (DSHEA). If a claim is made that re- lates to disease treatment or prevention, the item is considered a drug. Barnes’s interest in functional foods stemmed from his interest in soy and the fact that the chemistry of isoflavones varies among different types of soy foods. In Asia, soy is consumed largely in the form of miso, which is a fermented form of soybean; and soymilk and tofu, which are extracted from heated soybean. In the United States, on the other hand, soy is con- sumed largely in the form of textured vegetable protein, which is processed differently than the common Asian soy foods and therefore has a differ- ent composition (i.e., it is processed through dry heat, not fermentation or hot water extraction). In fermented and hot water extracted products, the soy isoflavones are not only converted into readily absorbable forms of genistein (i.e., 6-hydroxy and 8-hydroxy genistein), they also contain

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 nUtRItIon ConCERnS FoR AgIng PoPUlAtIonS added chemical groups that make them more bioactive. With dry heat, on the other hand, the isoflavones are converted into an acetyl glucoside form of genistein that is not absorbed very well until it reaches the lower gut. Barnes questioned whether the benefits of fermented or hot water extracted soy functional foods exist with these other dry heat products. In addition to isoflavonoids in soy (and also kudzu), some of the other most common bioactive components of functional foods include fiber (in whole grains), carotenoids (in carrots, tomatoes and green vegetables), alli- cin (in garlic), flavonoids (in fruits and green tea), sulforaphane (in broccoli sprouts), and omega-3 fatty acids (in wild fish). Functional Foods for Aging Populations Barnes stated that these and other bioactive compounds could be used to create functional foods for older adults that improve or maintain taste and smell, digestion, brain health, the immune system, bone and joint health, cardiovascular health, gut flora (i.e., probiotic foods), and eye health. A recent survey indicates that many older adults are in fact eating more fruits and vegetables as they age because of these and other potential health-promoting (i.e., functional) benefits (Shatenstein et al., 2003). As for dietary supplements, the top 20 sellers in 2008 are listed in Table 5-1. Barnes emphasized the importance of considering whether foods are in a form that older adults can actually digest. Not only do many older adults not have adequate teeth, they could be experiencing problems related to impaired acid production (e.g., due to medications that interfere with acid production), or other physiological changes such as those discussed in Chapter 3. TABLE 5-1 Top-Selling Dietary Supplements in 2008 Dietary Supplement Cranberry Green tea Soy Evening primrose Garlic Valerian Saw palmetto Horny goat weed Gingko Grape seed Echinacea Elderberry Milk thistle Bilberry St. John’s Wort Ginger Ginseng Horse chestnut seed Black cohosh Yohimbe SOURCE: Cavaliere et al., 2009.

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 PRoVIdIng HEAltHy And SAFE FoodS AS WE AgE Bioavailability: Absorption, Distribution, Metabolism, and Excretion (ADME) in Older Adults Barnes recalled how once, as a student, he had entered a pub late in the evening and observed a group of “little old ladies” knitting and drink- ing stout. He realized later that the women were probably not drinking the stout to drink stout, but rather because stout is very nutritious for older adults. A pint of stout has only 200 calories, is low in sodium, and is rich in vitamin B6, iron, and flavonoids. He described stout as a “very good soup.” Moreover, it is easy to digest. Stout is a great example of how physical form matters. He stated that foods are generally much better than dietary supplements in terms of bioavailability, because the bioactives are gener- ally much more dispersed among the food particles and therefore more likely to be absorbed by the body. Bioavailability of purified compounds (i.e., a dietary supplement) is very dependent on the physical properties of those compounds, and many dietary supplements are simply not very well absorbed. He used flavonoids in foods to illustrate how bioavailability is impacted by the physiology of the gastrointestinal (GI) tract, beginning in the oral cavity where pre-hydrolysis (i.e., pre-digestion) dissolves some fats and sends signals to the rest of the GI system that “food is coming.” Then, in the stomach, there may be some hydrolysis, although Barnes is unsure to what extent. Small intestine metabolism, however, is definitely very im- portant, with lactase and other intestinal enzymes preparing (hydrolyzing) the flavonoid glycosides7 for enterohepatic circulation (i.e., the compound passes through either the small intestine or large intestine wall, enters the liver where other metabolic processes occur, and then reenters the small intestine). Flavonoids not absorbed in the small intestine are metabolized by microflora in the colon, where they undergo considerable structural modi- fications. In the colon, bioavailability is impacted by transit time and bac- terial composition, with a faster transit time leading to less enterohepatic circulation (and therefore less metabolism and absorption) and the presence of certain bacterial populations also affecting metabolism. Changes in any of these organs, as well as changes in kidney or renal function, can impact bioavailability. Importantly, drug interactions could occur at any point along this pathway, also impacting bioavailability. 7 All flavonoids, except flavanols, are found in glycosylated forms in foods. This is a key factor influencing bioavailability because in these native forms, most flavonoids cannot be absorbed (D’Archivio et al., 2010).

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 nUtRItIon ConCERnS FoR AgIng PoPUlAtIonS Conclusion In conclusion, Barnes echoed what other speakers had emphasized: Op- timizing nutrition is important. In fact, that is the rationale for functional foods. However, depending on what type of processing methods are used to make the functional food, some of the potential health benefits may not be as great as they are in other, differently processed foods because of reduced bioavailability. In other words, not all soy products are necessarily alike with respect to their health-promoting benefits, because of how different processing technologies alter bioavailability of the compounds that confer those benefits. Moreover, the fact that aging alters the properties of all of various organs that handle bioactive compounds in food creates another major challenge to formulating and providing health-promoting functional foods to older adults. With respect to drug-food interactions, which could occur at any point along the GI pathway and impact bioavailability, Barnes said that is “something we don’t know enough about.” NUTRITIONAL MODULATION OF AgINg AND AgE-ASSOCIATED DISEASES BY CALORIC RESTRICTION Presenter: luigi Fontana Fontana began by defining aging as “the progressive accumulation of cell/tissue/organ damage with time.” He emphasized that aging is a lifetime process and not something “kicking in when you are 65,” which means that how people behave (e.g., eat) when they are young and middle-aged matters. The accumulation of damage is due to failure of maintenance and repair mechanisms to completely protect against damage, leading to pro- gressive decline in function and structure and eventually death. Importantly, chronic diseases accelerate the accumulation of damage. Is Aging Preventable? While aging is not preventable, there are interventions that can slow it. The best characterized of these is caloric restriction (CR) without mal- nutrition. Fontana said hundreds of studies in yeast, worms, and mice and rats have shown that CR can slow aging, with about 10 percent CR increasing maximal life span by as much as 50 percent. As an example, Fontana showed data from Weindruch and Walford (1982) and Weindruch and Sohal (1997) indicating the impact of CR on the lifespan of rodents (Figure 5-3).

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00 PRoVIdIng HEAltHy And SAFE FoodS AS WE AgE Initiated at Initiated at 12-mos of age 1-mo of age FIgURE 5-3 Survival of rodents placed on ad libitum versus calorie restricted diets. This evidence suggests that long term caloric restriction without malnutrition may extend healthspan and maximal lifespan in rodents. SOURCES: Weindruch and Walford, 1982; Weindruch and Sohal, 1997. Murine models of longevity include 5-3, fixed Figure • Ames and Snell dwarf mice, • growth hormone receptor knock-out (KO) mice, • insulin-like growth factor-1 (IGF-1) receptor deficient mice, • klotho overexpressing mice, • fat insulin receptor KO mice, • insulin receptor substrate 1 KO mice, • brain insulin receptor substrate 2 KO mice, • ribosomal S6 protein kinase 1 KO mice, • p66shc KO mice, • type 5 adenylyl cyclase KO mice, and • Ang II type 1 KO mice. Are Chronic Diseases Associated with Aging Preventable? Despite the current “epidemic of obesity” in the United States and as- sociations between excessive adiposity and cardiovascular disease mortality (Calle et al., 1999), cancer mortality (Hu et al., 2004) and other conditions (Willet et al., 1999), Fontana said that his interest in CR is not weight loss. Rather, he is interested in what a 20 or 30 year old man or woman who wants to live a longer and, more importantly, healthier life, can do. He defined healthy aging as the ability of human beings to remain physically and mentally healthy, happy and creative, empowered, active, contributing,

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0 nUtRItIon ConCERnS FoR AgIng PoPUlAtIonS and independent for as long as possible. His questions are (1) What inter- ventions, even among lean individuals, promote healthy aging?, and (2)Are chronic diseases associated with aging preventable? Data from CR in animals suggest that not only do calorie restricted animals live longer lives, they also are more likely to die without any pa- thologies. In one study, none of the CR animals showed any signs of patho- logical lesions upon autopsy, whereas only six percent of the animals on a typical diet (i.e., non-CR diet) showed no signs of pathology (Shimokawa et al. 1993). Subsequently, Colman et al. (2009) suggested that CR “works” not only in mice and rats but also in primates. Rhesus monkeys fed a 30 percent CR diet starting in middle age demonstrated a 50 percent reduction in cardiovascular disease mortality and a 50 percent reduction in cancer mortality. Fontana said that the implications of this study are “huge,” be- cause both the CR and control animals were fed a very healthful diet. As far as extension in maximal life span goes, the researchers will not know for another 10 years if CR animals live longer. He mentioned another study demonstrating even among lean animals with the same body weight, only those fed a CR diet had an extended maximal life span (Holloszy, 1997). Exercise did not increase maximal life span; it only increased average life span, presumably by preventing excessive adiposity and the type of metabolic alterations that typically ac- company excessive adiposity (e.g., type 2 diabetes). Only CR slowed down “intrinsic aging.” Then he discussed a study that he has been involved with for the past two years, where he and his colleagues are examining the effects of CR without malnutrition in a group of healthy volunteers between the ages of 35 and 82. The CR participants (n = 32) are eating 100 percent of their Reference Daily Intake (RDI) for each nutrient and approximately 1800 calories daily. They have been doing this for eight years, on average. The first control group (n = 32) is a group of age and sex-matched U.S. athletes that are equally lean because they are running about 50 miles a week and eating about 2,000 calories daily. The second control group (n = 32) is a group of matched sedentary individuals eating a typical American diet. The researchers are examining the effects of these three different diets (i.e., CR participants, exercisers, and sedentary participants) on body mass index, body fat, hormone levels, glucose tolerance and insulin action, cardio- metabolic risk factors, carotid artery thickness, and arterial elasticity. Only published data are presented here. Fontana et al. (2004) found that CR practitioners had significantly lower serum concentrations of several risk factors, including lower total and low-density lipoprotein (LDL) choles- terol, fasting glucose, C-reactive protein, and blood pressure. Fontana et al. (2009) found that both CR and exercisers had signifi- cantly lower fasting glucose and insulin levels than the sedentary group.

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0 PRoVIdIng HEAltHy And SAFE FoodS AS WE AgE Insulin is a risk factor for cardiovascular disease and cancer, and it has been implicated in aging. However, when challenged with a glucose load, the athletes did much better than the CR individuals, suggesting that exercise is much more powerful than CR in preventing type 2 diabetes. Fontana remarked that clearly hormones and growth factors play a major role in modulating aging in humans. The same changes that have been observed in humans (i.e., reduction in inflammation, insulin, and to- tal testosterone) also occur in mice, rats, and primates, with one important difference. In rats, long-term CR reduces serum IGF-1 concentration by 40 percent (Breece et al., 1991). In humans, however, long-term CR does not reduce serum IGF-1 concentrations (Fontana et al., 2008). IGF-1 is a risk factor for premenopausal breast cancer, prostate cancer, and colon cancer, so the higher the IGF-1 concentration, the greater the risk of developing these cancers (Chan et al., 1998; Hankinson et al., 1998). Not only is IGF- 1 a major player in cancer, Fontana said that it is also probably important in the aging process itself. The Importance of Protein While CR may not reduce serum IGF-1 concentration in humans, moderate protein restriction does. Fontana and his colleagues realized this when they observed that a group of strict vegans in the study described in Fontana et al. (2008) had significantly lower IGF-1 than either controls or people on a CR diet. The average American obtains about 15 to 16 percent of calories from protein. People on the CR diet had a very high protein diet, obtaining about 24 percent of calories from protein. The vegans obtained only about 10 percent of calories from protein. During the course of the study, Fontana asked some of the CR individuals to go on reduced protein diet, after which their IGF-1 serum levels dropped 25 percent, suggesting that protein restriction is more important than calories in reducing IGF-1. Noting that the Recommended Dietary Allowance (RDA) for protein is 0.83 g/kg per day and that many people are consuming much more than this (Rand et al., 2003), Fontana challenged workshop participants to con- sider that while nitrogen balance data may be suggesting that older adults need more protein, not less, IGF-1 data suggest otherwise. Fontana and colleagues are currently studying protein restriction (not just CR) in both animals and humans. Conclusion In conclusion, Fontana stated that other factors besides CR, and pos- sibly protein restriction, also affect aging. For example, exercise is very

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0 nUtRItIon ConCERnS FoR AgIng PoPUlAtIonS important. Likewise, phytochemical intake may impact antiaging pathways independent of CR and other interventions. Moreover, CR is not necessar- ily always beneficial. Too much restriction can have detrimental effects and may even lead to death. Plus, various factors such as age, sex, and genetic predisposition might also make a difference. For example, Fontana said that starting a CR diet at the age of 65 is probably not a good idea. CR should be started at an earlier age to control body weight and avoid increased abdominal fat, though Fontana did not specify an age range. FORMULATINg FOR AgINg BOOMER CONSUMERS Presenter: Jim Kirkwood Kirkwood began by describing his role at General Mills as somebody who connects the science with something that people actually want to eat. He asks the question: Since consumers don’t understand much of the science around nutrition and food safety (i.e., the science that is being discussed during this workshop), what drives their decision-making? He remarked that most of his talk would revolve around efforts that General Mills food developers and creators are making to understand what drives aging boomer consumers’ food choices. General Mills is the world’s sixth largest food company, with products marketed in more than 100 countries. Aging consumers are very important to General Mills because of the fast rate of growth in the aging population. Kirkwood said that 65 percent of the estimated future growth for General Mills will come from aging boomer consumers.8 Kirkwood posed the question, “Who are these aging boomer consum- ers?” He asked the audience to raise their hands if they thought that old age “starts” at 45. Several people raised their hands. When asked if old age starts at 55, a few more people raised their hands. When asked if it starts at 65, many more people raised their hands. At 75, everybody had their hands raised. He said that if General Mills were to build food products for aging consumers, nobody would buy them, because nobody is aging in his or her own mind. In a survey of 2,969 adults conducted by the Pew Research Center, 65 percent of respondents 75 and older did not consider themselves “old.” When asked at what age one becomes old, on average, 18–29 year- olds said 60, 30–49 year-olds said 69, and 50–64 year-olds said 72. Kirkwood then posed the question, “What do aging consumers care about?” He emphasized that while scientific evidence is very important from a food development perspective, consumers are driven by other fac- 8 Kirkwood cited Nielson Scantrack and HomeScan, BCS Analysis, as the source of these facts.

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04 PRoVIdIng HEAltHy And SAFE FoodS AS WE AgE tors. He and his team have identified five key areas of concern among aging boomer consumers: (1) physical vitality; (2) mental acuity; (3) legacy (i.e., what people are going to leave for their families and in the world, how they will be remembered); (4) financial security; and (5) community (e.g., many people fear being alone as they get older). Of these, mental acuity is the biggest consumer worry. People assume that medicines would be available for physical health problems and that family and other sources would be available for financial assistance, if necessary, but it would be very difficult to deal with loss of mental acuity. Kirkwood asked, “What do these questions have to do with food?” He explained, “Food is only an enabler for the things that really matter to consumers. . . . If we can tie food to what matters, then we will be able to inject good things into their lives.” If food developers do not relate their products to what is important for consumers, then consumers will not use those products. For boomers in particular, compromise is not an option. He said, “Boomers do not want to give up anything. They want it all.” In order to relate products to those factors that are important to consum- ers, companies must do two things according to Kirkwood: (1) comprehen- sively understand aging consumers’ needs, and (2) translate that understanding into food solutions that consumers want, need, and can afford. Kirkwood then showed a short film, Project goldie, describing the results of ethnography studies that General Mills has conducted as a way to understand baby boomer consumer values. The video demonstrated that while food is important, there are many other factors besides food that are also important to people’s lives. In particular, there are six key needs of aging consumers: (1) health and wellness, (2) care for others, (3) grandchil- dren, (4) connections, (5) life experiences, and (6) small households. Product Development Product development—that is, translating aging consumers’ needs into products on the shelf—is a very complex, time-consuming process. It in- volves everything from “culinary creation” (i.e., making a food that tastes good) to ensuring microbiological stability and regulatory compliance. Kirkwood said that everything that goes into product development can be broken down into four essential “elements”: • Form (i.e., channel, product form, and package configuration). Form is a key element of the decision-making that goes on around how a product is going to be formulated. For example, will the product be refrigerated, frozen, or shelf stable? Is it something that consum- ers will want to carry with them? Is it something that people will enjoy preparing for their grandchildren? With respect to package

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0 nUtRItIon ConCERnS FoR AgIng PoPUlAtIonS configuration, will the product be single-serve? For aging boomer consumers, ease of use and legibility of preparation instructions are additional considerations (e.g., Kirkwood referred to Brody’s description of the packaging industry’s efforts to develop new types of easy-to-open packages). • Function (i.e., safety, benefit delivery, and nutritional delivery). Func- tion is another key consideration, with the primary goal being to ensure that a product is safe regardless of consumer need. With re- spect to benefit delivery, if a product is designed to deliver a specific benefit, that benefit must be validated by science and the necessary ingredient(s) put into the product in a way that ensures bioavailability and that the product is delivering what the package/company claims that it is delivering. For older adults, this means that the health benefit is validated with the targeted age group and that the products actually deliver those benefits specifically to older adults. Nutritional delivery refers to the fact that benefits aside, foods deliver nutrients; therefore, the product in question should be delivering the nutrients it is sup- posed to be delivering, particularly those nutrients with intake levels that are of greatest concern among older adults. • Appeal (i.e., taste, texture, and appearance). If a product does not taste or look good, people will not eat it, regardless of its contents. Product development involves extensive sensory work to ensure that the intended benefits are delivered. For aging boomer consumers, additional considerations include vibrancy, potency, and consistency. Vibrancy is the way a food is experienced, for example, its appear- ance or mouthfeel. Potency refers to a taste profile that hits the “sweet spot” for older adults, especially given that the sense of taste changes with aging. Consistency refers to the texture of a food and the need to develop foods that are not, for example, too crunchy or too hard. • Affordability (i.e., raw materials, manufacturability, distribution). This is a huge concern, especially in today’s economic climate and especially for aging boomer consumers. Product developers must de- termine an acceptable price point for the target audience and then de- sign development so that the product can meet that price point. They do this by optimizing raw material usage, working with suppliers to ensure a cost-effective supply chain, and minimizing manufacturing and distribution costs. Also, unit size is important. As people age, they tend to cook only for themselves (i.e., two-people households). the Fiber one Bar: An Example of a Product that Works Kirkwood used the Fiber One bar as an example of a product devel- oped for aging boomer consumers. The Fiber One bar is designed to meet

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0 PRoVIdIng HEAltHy And SAFE FoodS AS WE AgE the Health and Wellness need category (i.e., one of the six need categories identified in the film Project goldie). Nine out of ten Americans do not get the recommended amount of whole grains and fiber, and consumers know this. They know they need to eat more fiber in order to feel better, but they also want to get that fiber in a way that suits their lifestyles. It can’t be something that does not taste good, and it has to be something that they know is “working.” Kirkwood described how he and his team at General Mills considered all four key elements of product development (form, function, appeal, and affordability) as they made decisions regarding the concept and development plan for the Fiber One bar: • Form: They developed a product that was shelf stable, in easy-to-eat bar form, and in a single serve pouch, because they knew that people wanted to be able to carry the product with them. • Function: They developed a product that delivered 35 percent of the daily fiber recommendation to the target population (i.e., older boomer consumers), had a healthful nutrient profile (e.g., low salt, low fat), and had simple ingredients (i.e., ingredients that consumers recognize, like nuts and wheat). • Appeal: They developed a product with “unexpected great taste,” a soft chewy texture, and a natural appearance. • Affordability: They developed a product with a novel fiber that lowered the cost of the bar from $10 to an affordable price, and formulated it to fit existing factory systems to minimize manufactur- ing costs. In conclusion, Kirkwood remarked that the end result is a product that, since launch, has provided nearly 10 billion grams of fiber to the American diet. The Fiber One bar is an example of a product that has “clearly inter- vened in Americans’ lives.” PANEL DISCUSSION ON IMPLICATIONS FOR REgULATORS, EDUCATORS, AND THE FOOD INDUSTRY The four presentations prompted questions about recommended maxi- mum daily nutrient intakes, the importance of protein in older adults’ diets, hypothesized mechanisms that might explain the effect of caloric restriction (CR) on aging, and drug-nutrient interactions. Recommended Maximum Daily Intakes An audience member asked whether there was any sort of “fudge fac- tor” in Dietary Reference Intakes (DRI) to compensate for variation in

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0 nUtRItIon ConCERnS FoR AgIng PoPUlAtIonS sensitivity. The questioner expressed concern about communicating some of the statistics about nutrient intake. For example, if 92 percent of the population has a less than adequate intake of a particular nutrient, how can that information be communicated in such a way that people will not automatically think that they are probably among that 92 percent and therefore are probably going to suffer the consequences? Tucker explained that the RDA is designed to meet the estimated requirement for almost all healthy individuals, which means that many people do not need to meet the RDA. DRI values also contain an Estimated Average Requirement (EAR) which can be used to assess prevalence of inadequacy. She suggested that when 70 percent or more of a group has values below the EAR that there may be reason for concern. The Importance of Protein in Older Adults’ Diets Another audience member asked Tucker if she was aware of any stud- ies on associations between amino acids, specifically branched-chain amino acids, and sarcopenia. Tucker replied that most of her work was with whole foods and that she was unaware of any studies on specific amino acids. Barnes remarked that he had recently attended a session on food peptides at a World Food Congress and that, while largely ignored in the United States, many Asian scientists are studying bioactivity of specific amino acids and peptides in foods. The Mechanism of the Effect of Caloric Restriction on Longevity Fontana was asked about his thoughts on the mechanism of CR’s ef- fect on improved health and life expectancy. Fontana replied that there is a great deal of research focused on identifying and understanding which mechanisms are mediating the antiaging effects of CR without malnutrition. While data from genetic animal model studies on longevity are filling some gaps in knowledge, he stated that the major mechanisms are unknown. So far, six different animal models for longevity suggest that the IGF-1 path- way is important. Animals with low IGF-1 live longer, healthier lives than animals with high IGF-1, causing Fontana to call IGF-1 “the new frontier.” But other animal models of longevity indicate that there are other factors at play, such as catecholamine signaling and angiotensin activity. Drug-Nutrient Interactions Finally, Barnes was asked to elaborate on a parenthetical comment he had made before he began his presentation about disagreeing with Greenblatt’s view on drug-nutrient interactions. Barnes said that he believes

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0 PRoVIdIng HEAltHy And SAFE FoodS AS WE AgE there is much more to drug activity than metabolism and the interaction be- tween a drug and a single metabolizing enzyme. By examining only the way that a drug interacts with “your favorite enzyme” and not, for example, how that drug is transported through the body, results in a “rather narrow viewpoint.” Moreover, he emphasized the importance of examining drug- nutrient interactions under the type of stressful physiological conditions that many older adults typically experience.