Providing Healthy and Safe Foods As We Age: Workshop Summary (2010)

Moderated by Kerry Dearfield of the U.S. Department of Agriculture (USDA), this session comprised four presentations followed by a panel discussion. Steven Gendel of the Food and Drug Administration’s (FDA’s) Center for Food Safety and Applied Nutrition (CFSAN), College Park, Maryland, provided an overview of foodborne pathogens considered the greatest risk to aging populations, emphasizing that susceptibility to infection and severity of symptoms resulting from infection vary with age, depending on the pathogen. Furthermore, the two factors (susceptibility to infection and severity of illness) are not necessarily linked and should be monitored separately. Bernadene Magnuson of Cantox Health Sciences International, Bridgewater, New Jersey, discussed the effects of dietary food contaminants on health during aging. She also discussed surprising findings on the adverse effects of two purportedly beneficial dietary supplements, soy and curcumin, in older adults and emphasized the need to collect more safety data on active ingredients in dietary supplements. Food Forum Chair Michael Doyle of the University of Georgia, Athens, provided an overview of food processing and formulation technologies designed to protect against pathogens and contaminants, emphasizing the potential benefits and market sustainability of some of the newer non-thermal physical processing technologies and chemical treatments. He suggested that there could be niche market opportunities for some of the technologies that are otherwise having a difficult time penetrating the general marketplace (e.g., irradiated food products might be more acceptable and could be marketed to older adults, who are especially at risk of infection from food-borne pathogens). Finally, Aaron Brody of Packaging/Brody, Inc., Duluth,

Georgia, described recent innovations in food packaging, emphasizing that one of the main roles of food packaging is to provide protection against microbiological contamination. To conclude the session, David J. Greenblatt of Tufts University School of Medicine, Boston, Massachusetts, joined the four speakers in a panel session. Greenblatt offered a different perspective than Magnuson’s on the issue of nutrient-drug interactions.

Presenter: Steven Gendel

Gendel began by remarking that he would be exploring in detail which pathogens are considered to be of concern to aging populations and why. He explained that there are two factors to consider when determining whether a pathogen is of concern: (1) the probability that a person will develop an illness, given a certain level of exposure; and (2) the severity of the consequences if an illness does develop. These two factors are not necessarily directly linked and must be considered separately.

Different countries and even different agencies within a country (i.e., in the United States, FDA and the Centers for Disease Control and Prevention [CDC]) list different foodborne pathogens as being of concern to aging populations:

• In the “Bad Bug Book,” FDA’s handbook of foodborne microbes,¹ 19 foodborne pathogens are listed, only 6 of which are identified as being of concern to older adults.

• CDC lists 12 foodborne pathogens, only 4 of which are identified as being of concern.

• The United Kingdom (UK) Health Protection Agency lists 11 foodborne pathogens, only 4 of which are identified as being of concern for aging populations.

• The New Zealand Food Safety Authority (NZFSA) lists 16 foodborne pathogens, only 3 of which are identified as being of concern for aging populations.

Gendel remarked that not only are the numbers of listed pathogens surprisingly low, but there are some remarkable differences among the

agencies with respect to which particular infectious agents are considered to be of concern to older adults. All four agencies list Listeria monocytogenes, Salmonella, and E. coli O157:H7 as being of concern for aging populations, and all four agencies note the possibility of greater severity of disease with Salmonella and E. coli O157:H7 infections in older adults. However, only NZFSA considers Shigella to be of particular concern to aging populations, and only FDA considers Clostridium perfringens and Yersinia entercolitica to be of concern.

The fact that different agencies list different pathogens as being of concern to aging populations raises the question: How are pathogens of concern identified? Gendel explained that epidemiological and surveillance data, such as data from CDC FoodNet,² are the most useful type of data for determining whether a particular foodborne pathogen is more likely to infect or cause more serious illness in older adults. CDC FoodNet is a monitoring system that collects data at sites across the United States. The system covers about 15 percent of the U.S. population, providing a good estimate of total disease burden. Gendel then described several examples of how surveillance data are used to identify pathogens of concern, emphasizing again the importance of distinguishing between susceptibility versus severity of infection:

• Listeria: Again, all four agencies that Gendel examined list Listeria monocytogenes as being of concern to aging populations. CDC FoodNet data show that Listeria infection incidence rates are much higher in aging populations than younger ones. For both females and males, rates dramatically increase after middle age (i.e., at age 50–59). Data from Australia’s OzFoodNet show the same trend of an increased incidence rate at about age 50–59. Similarly, in Canada, data from two different monitoring systems show that incidence rates increase dramatically with age (Clark et al., 2010). In addition to older adults being more susceptible to infection, older adults also experience more severe consequences of infection. Data collected for non-pregnancy associated Listeria severity in England and Wales from 1990–2007 show that the percentage of fatal cases increases with age, from about 10 percent in the 0–9 age group to about 45

percent in the 80-and-over age group.³ See Figure 4-1 for a summary of data on Listeria trends with aging.

• Campylobacteria: In contrast to Listeria, Campylobacteria data from CDC FoodNet show a much higher incidence in the very young and then, with aging, a decreasing and eventually constant rate. In other words, incidence does not increase with aging. Data from Australia’s OzFoodNet demonstrates the same trend. While Campylobacteria is of interest since it is an extremely common foodborne illness, it is not necessarily any more common in older adults than it is in younger populations. Indeed, none of the four agencies that Gendel

examined lists it as being of particular concern to aging populations. He remarked that the difference in incidence rates between Listeria and Campylobacteria is an example of how increased susceptibility to foodborne infectious disease with aging is not a general trend.

• Shigella: Data on Shigella incidence are not as clear-cut as with Listeria and Campylobacteria. Neither CDC FoodNet nor OzFoodNet show an increased incidence with age. Gendel speculated that when advisories are released warning older adults to avoid foods that may be contaminated with Shigella, it may be that older populations are not necessarily more susceptible to infection but are more susceptible to severe consequences of infection (e.g., diarrhea, vomiting).

• Vibrio: CDC FoodNet data show that Vibrio incidence rates by age differ between males and females, with incidence rates in males increasing dramatically with age. This is particularly true of Vibrio vulnificus. While this could indicate that males are more susceptible as they age, in fact susceptibility to Vibrio is affected by several kinds of underlying behavioral and medical conditions. It more likely reflects that fact that men are at a greater risk not because they are men, because they consume more shellfish as well as alcohol, and certain kinds of alcoholic conditions are underlying risk factors for Vibrio infection. The trend in Vibrio incidence is a good example of a trend that is confounded by other risk factors (i.e., eating shellfish).

• Salmonella: As with Shigella, CDC FoodNet data provide no clear indication that susceptibility to Salmonella infection increases with age. However, when outbreak data are examined more closely, it is clear that though incidence rates do not increase with age, severity of illness does. The percentage of people infected with Salmonella who then develop bacteremia increases dramatically with age (Blaser and Feldman, 1981). Likewise, the percentage of people infected with Salmonella that develop bacteriuria increases with age, particularly for females (Sivapalasingam et al., 2004).

• E. coli O157:H7: As with Salmonella, while CDC FoodNet data show low and constant levels of infection with aging, outbreak data from Scotland and China show that the percentage of cases with severe complications increases with age (Dundas et al., 2001; Zhu et al., 2009).

Gendel noted viral gastroenteritis and the lack of concern expressed by any of the four authorities about viruses as age-related problems, with the exception of norovirus. Norovirus is likely to cause diarrhea in older adults, thus the issue is probably that the consequences of the symptoms are what is more severe in older populations, rather than the incidence of disease.

In conclusion, Gendel claimed that susceptibility to foodborne pathogens in aging populations differs among microbes and is not just a matter of the immune system becoming dysfunctional as people age [which Meydani had argued in the previous session]. As he said, “Something about the pathogens themselves and the way that they interact with the body differs for different [pathogens].” Moreover, for many pathogens, the increased probability of severe outcomes is of greater concern than increased susceptibility to infection per se. Sometimes incidence rates increase with aging, sometimes incidence rates remain constant with aging but severity increases, and sometimes both incidence and severity increase with aging. Thus, Glendel suggested the problem is more nuanced than it might seem if one considers only changes in immune system function and general health characteristics.

Presenter: Bernadene Magnuson

Magnuson began by noting the scarcity of data and information available on the effect of dietary contaminants on health during aging. Most of the evidence for the impact of contaminants in aging populations is for non-dietary contaminants, with many of the known associations coming from occupational exposures (e.g., to pesticides); and because occupational exposure is generally greater than dietary exposure, it is difficult to make inferences.

Magnuson identified three ways that exposure (i.e., including non-dietary exposure) to contaminants could play a role during aging:

• Contaminants could promote aging by accelerating degenerative processes. Examples include the association between increased exposure to cigarette smoking and the development of wrinkles (i.e., people who smoke develop more wrinkles), with considerable information available on the actual molecular mechanism for how this occurs; the known association between cognitive decline and the toxic effects of several heavy metals; hypothesized but debated associations between exposure to pesticides, heavy metals, and polychlorinated biphenyls (PCBs) and an increased risk of Parkinson’s disease (i.e., some epidemiological reports support this hypothesis, others do not); and a clear association between contaminants or toxins that inhibit calcium absorption and bone integrity. Again, most of these data are from occupational, not dietary, exposure levels (Cummings, 2007; Bernhard and Laufer, 2008; Peterson et al., 2008). No clear

relationships have been established for dietary levels of contaminants and these various degenerative processes.

• Contaminants could accumulate over time and have adverse effects with advancing age, impacting the overall health status of the aging population. Examples include heavy metals that accumulate in various organs, such as lead in bones, mercury in the brain, and cadmium in the kidney; and organochlorines, such as dichlorodiphenyltrichloroethane (DDT), PCBs, and chlordane that accumulate in adipose tissue. While lead toxicity is usually associated with neurological effects, a recent prospective study on bone lead concentrations and health outcomes in 868 men found that the strongest association was between the accumulation of bone lead and both all-cause and cardiovascular disease mortality (Weisskopf et al., 2009).

• Older adults could be more vulnerable or susceptible to the adverse effects of toxic insult, because of the way body composition changes with aging (i.e., aging is usually associated with a loss of lean muscle mass and increased adipose tissue), impaired cell and tissue function, and altered nutritional status (Ginsberg et al., 2005). Various specific factors play a role in this increased sensitivity with aging, including changes in liver physiology and function, changes in gastrointestinal (GI) function, changes in dietary patterns, increased use of dietary supplements, and increased potential for interactions between supplements and drugs.

With respect to changes in liver function, hepatic metabolic capacity decreases with advancing age, such that clearance (ability of the body to eliminate drugs) decreases and retention (half-life of drugs) increases. Drugs (or contaminants) remain at active levels for a longer time. Also, because of the increase in body fat percentage among older adults, lipophilic clearance decreases as well; and proteinuria results in a decreased plasma protein binding capacity. Both of these changes further impact the ability of the body to eliminate drugs and contaminants.

With respect to GI function, Magnuson noted that, as had been discussed in previous presentations, the function throughout the small and large intestines change little with age. Yet, studies on exposure to toxic substances conducted by her lab and others show that some changes that influence susceptibility to toxins do occur with aging. For example, she and her colleagues have demonstrated a loss of epidermal growth factor receptor-related protein function in an aged colon, which in turn increases the risk of colon cancer (Schmelz et al., 2004). The proteins offer protection against various toxins, and loss of function increases exposure to potential food carcinogens (e.g., those found in cooked meats). Magnuson’s group

has observed dramatic changes in the morphology of the aging colon of rats, with much less structure and fewer epithelial cells, which are likely responsible for changes in function and biological response to acute insult (Kwon and Magnuson, 2007, 2009).

Finally, changes in nutritional status, such as those caused by poor oral health or a loss of taste or smell, can affect susceptibility (Soliman et al., 1999; Hickson, 2006).

For the remainder of her talk, Magnuson discussed the widespread use of dietary supplements, the scarcity of safety data on the active ingredients in many dietary supplements, and the potential risks of dietary supplement-drug interactions.

Over 80 percent of Americans have tried at least one of the some 29,000 supplements on the market, and at least 40 percent of older Americans regularly use some form of herbal or specialty supplement. People, particularly the elderly, try or use supplements for various reasons: maintenance of overall health (most older adults no longer feel quite as invulnerable as they did at the age of 20 and start feeling a sense of their own mortality); increased energy (e.g., as reflected in the proliferation of energy drinks in the marketplace); memory improvement; prevention or treatment of illness; and slowing of the aging process.

Importantly, safety of the active ingredients of many dietary supplements is not tested to nearly the same extent that safety of food ingredients is tested. For example, there is no required testing for differences in susceptibility in older populations. In fact, usually the concern is with pregnant women, children, and infants. Unless there are other subpopulations that are of specific concern, everybody tends to get lumped together for risk assessment purposes. The lack of safety data is of concern given that dietary supplements have been contaminated in the past with heavy metals (lead, mercury, arsenic), organic solvents, pesticide residues, and other substances (e.g., melamine). Magnuson stated that some of these contaminants are “expected” (e.g., lead and mercury), but others like melamine “totally come out of the blue” and have never been considered potential contaminants. Even when recommended maximum levels for specific contaminants exist, those specifications are rarely enforced, leaving consumers little choice but to trust the reputation of the manufacturer. The challenge is even greater for products being imported from countries where quality control ranges from limited to non-existent. For example, a survey of herbal medicines imported from South Asia showed that 20 percent contained heavy metals in large enough quantities such that if a person were to take the recommended amount of oral supplement, he or she would be exceeding the recommended

intake levels (of heavy metal) just from intake of the supplement alone (Saper et al., 2004).

In addition to the risk of contamination, older adults are also at greater risk of dietary supplement-drug interactions because of aging-related decreased metabolic capacity, increased likelihood of liver or kidney disease, and decreased capacity for tissue defense and repair. In a recent survey of older adults on the U.S.-Mexico border, 72.3 percent of adults surveyed reported using multiple medications, including 38.5 percent who took five or more; 16.2 percent reported taking multiple herbs; 26 percent multiple supplements; and 9 percent multiple nutraceuticals (Loya et al., 2009). Forty-six percent of adults surveyed were identified as being at risk for a drug-drug interaction, and 32 percent were identified as being at high risk for a drug-herbal product interaction (Loya et al., 2009).

The problem, Magnuson explained, is that there is not much known about these drug-herbal product interactions, given there are approximately 29,000 herbal products on the market and most of the information collected is based on case reports. Many people do not admit they are taking dietary supplements, unless the supplement becomes popular, as Goji berry juice did in Canada in 2008.

Magnuson’s laboratory has been investigating the issue of age-related changes in drug/toxin-supplement interactions. In particular, they are interested in age-related differences in the efficacy of two dietary supplements commonly used as a form of chemoprotection against cancer: curcumin and soy isoflavones.

• Curcumin is believed to have antioxidant, anti-inflammatory, anti-aging, and anti-cancer (against many forms of cancer) properties. While its chemopreventive capacity is well documented in young animals, Magnuson’s team sought to explore its chemopreventive capacity in older animals by feeding differently aged rats diets supplemented with curcumin (Kwon et al., 2004). Because it is an antioxidant, they expected that the supplement would become even more chemopreventive with aging. However, they found that while curcumin reduced early neoplastic lesions in both young (6 weeks old) and old rats (about 2 years), it had no effect in mature rats (1 year). This unexpected finding was subsequently shown to be likely a result of age-related differences in induction of apoptosis (Kwon and Magnuson, 2009).

• Soy isoflavones are believed to prevent cancer (breast and prostate) and provide relief from post-menopausal symptoms. In another study, Magnuson’s team fed diets supplemented with soy isoflavones to differently aged female rats (Daly et al., 2007). One week

after starting the experimental diet, the rats were treated with a colon carcinogen. They expected that older rats would be less sensitive or responsive because of lower rates of absorption as well as lower estrogen and estrogen receptor levels. However, shockingly, they found immediate evidence of age-related toxicity, with old rats (22 months) rapidly becoming very ill. Half of the rats in the old age group died within the first 96 hours. The young rats showed no signs of toxicity. The soy isoflavone diet had no benefit for any age rat in terms of inhibiting the development of colon cancer lesions. Additionally, older rats that were fed the supplemented diet lost significantly more weight during the course of the experiment than older rats fed the control diet. The soy isoflavone supplement had no effect on weight in younger rats. Also, older rats fed the supplemented diet showed a dramatic increase in serum estradiol with aging, even though older rats were consuming less soy isoflavone per body weight than younger rats were (serum estradiol levels normally decrease with aging, as was the case with rats fed the control diet).

In sum, dietary curcumin was not chemoprotective in mature animals, although it did reduce colon cancer lesions in young and old rats, demonstrating age-dependent mechanisms. Soy isoflavone supplementation also resulted in very different responses among three age groups of rats, with older female rats becoming very ill, suggesting that soy isoflavones augment or trigger age-related toxicity. The soy isoflavone study raises the question: Why? Is this a drug-diet interaction? Because supplementation with soy isoflavones affected estrogen and estrogen-responsive tissues in older rats, might it have adverse effects with other hormone-dependent cancers? Magnuson stated that the adverse effects of soy isoflavones in aged female animals observed in their pilot study needs further examination, because older women are the primary target population for the consumption of soy supplements.

In conclusion, Magnuson reiterated that there is very little information available on the effect of dietary contaminants on health during aging, but that changes in diet and physiology during aging clearly increase the risk for adverse effects. Dietary supplements are an important source of contaminants, given the widespread use of supplements among older adults and the prevalence of contamination in supplements. The high use of both supplements and drugs in older adults also increases the likelihood of supplement-drug interactions. Lack of awareness around patient use of

supplements in older adults makes it difficult to monitor and gather information on possible interactions, and what is known about interactions in the young cannot be used to predict effects in older adults.

Presenter: Michael Doyle

Doyle began by posing the question: What has the industry done and what can be done to develop products that are safe for aging populations? He shared a list of foods of concern, which was almost identical to the list that Sundlof had shown in an earlier session: sprouts (e.g., alfalfa, broccoli), raw meat and poultry, raw fish and seafood, raw milk and milk dairy products, fresh fruits and vegetables, unpasteurized fruit juices, deli meats, frankfurters, and cold smoked seafoods. Foodborne illnesses in aging populations, Doyle observed, are largely associated with consumption of raw and uncooked foods.

The industry has developed several different types of interventions and continues to develop new ways to ensure food safety. Doyle identified four categories of interventions:

• Physical (e.g., heat, ionizing radiation, high pressure, ultraviolet [UV] light)

• Gas (e.g., modified atmospheres)

• Biological (e.g., bacteriophage, competitive exclusion bacteria)

• Chemical (e.g., organic acids, oxidizing agents, bacteriocins)

Thermal processing technologies can be the “easiest” to apply and are the most traditional technologies used to ensure the safety of foods. Steam and hot water approaches have been used for decades for pasteurization and commercial sterilization, and there are also some newer innovative microwave and ohmic heating (liquids/pumpable) technologies. The problem with heat is that although the end result is a safe food, it has a cooked flavor, which Doyle explained is not always considered a desirable quality. Some of the non-thermal physical processing technologies and chemical treatments provide ways around this problem with end products that are not only safe but also taste and look fresh. For the remainder of his talk, Doyle discussed these non-thermal physical and chemical ways of protecting foods from pathogen contamination, their advantages and disadvantages, and their actual and potential applications.

Non-thermal physical processes are those that do not require high temperatures and which therefore can have several advantages from both a taste and nutrition perspective. Not only do non-thermally processed foods not taste cooked, if given a sporicidal treatment, they may not require the addition of preservatives which means that the sodium content could be kept low. Doyle highlighted several types of non-thermal processing technologies.

Many companies utilize this type of technology, which involves applying high-pressure water (e.g., 87,000 pounds per square inch [psi]) to foods. The high pressure precludes the need for high temperatures. Foods can be subject to pressures between 100 and 800 megapascal (MPa) and can be treated at temperatures from 0^°C to above 100^°C. Exposure times range from a few seconds to more than 20 minutes. This technology works best on moist foods that can withstand high-pressure water without being crushed, such as liquids, pastes, and meats. For example, it does not work very well on lettuce but does work well on apple juice.

High hydrostatic pressure technology has several benefits: foods retain their nutritional, flavor, and color characteristics; the process kills vegetative cells of many different pathogens (e.g., Salmonella, Listeria mono-cytogenes); it works for both liquid and solid foods and with or without packaging; it uniformly kills microbes regardless of size, shape, and food composition; and it precludes the need for preservatives, which in turn can reduce sodium content. But it also has its drawbacks: it is not a continuous system (i.e., it is batch or semi-continuous) and therefore cannot be used for beverages that are made on a continuous basis; it does not kill spores reliably at temperatures below about 90^°C; and it is more expensive than canning or freezing.

Commercial applications include apple juice and other fruit juices, smoothies, deli meats, guacamole, oysters, and clams. With oysters and clams, not only does high hydrostatic pressure kill Vibrio without killing the shell organism, it also has added value because of the fact that it enables easier shucking of the shell.

While ionizing radiation, or irradiation, technology is approved for many uses (i.e., spices, fruits, vegetables, wheat, flour, pork, chicken, red meats, shell eggs, seeds for sprouts, mollusks, lettuce, spinach, and food for

the U.S. space program), few products on the market today are protected through it. Doyle argued that ionizing radiation has greater potential and more applications than are currently being realized and there may be niche market opportunities, for example the production of irradiated foods for aging populations at high risk of acquiring severe foodborne illnesses.

There are several benefits of ionizing radiation: it kills pathogens, preserves food, and disinfects; and 50 years of testing and safety studies have deemed it safe when used at dosages that would pasteurize food. But there are also significant drawbacks: its lack of consumer acceptance; it is generally not useful for destroying viruses, toxins, and prions; and it may produce off odors and off flavors in foods (e.g., some people describe it as producing a “wet dog” odor). With respect to consumer acceptance, Doyle mentioned irradiated ground beef and how, after being marketed nationwide but not selling well, irradiated ground beef was taken off the market and the company responsible went bankrupt.

There are several different types of ionizing radiation technologies:

• Gamma irradiation involves the use of radionucleotides (Cobalt 60, Cesium 137, or other photons) as the ionization energy source, whereby the radionucleotides are simply exposed to the food. Unlike the other ionizing radiation technologies, the radionucleotides are always present in the processing plant.

• Electron beam processing involves focusing a beam of electrons onto the food. Unlike gamma irradiation, electron beam processes can be turned on and off and are therefore not always present in the plant. The downside is the technology has a very low penetration and only works for relatively thin layers of food.

• X-ray processing involves using electrons that have been converted into X-rays. Like an electron beam, X-rays can be turned on and off. They also have a high penetration and can therefore be used for thicker foods.

Doyle noted that as Gendel had already discussed, the severity of illness from Listeria infection increases with advancing age, so it is an important threat to consider when formulating new food safety interventions. Ready-to-eat meat products are subject to Listeria contamination primarily during the slicing and packaging process after the meat has been cooked. Listeria can persist and grow at refrigeration temperatures, and most luncheon meats have a refrigeration shelf life of about one to two months. The food industry has developed several different commercial treatments for the

prevention of later Listeria growth at refrigeration temperature, including heat (i.e., submersion of packaged meat into 90^°C water for two minutes, which does not cook the inside meat but does slightly cook the outside meat, which is where Listeria usually grows); high hydrostatic pressure processing (only a few companies are using this technology); and chemical antimicrobials, namely the combined use of potassium lactate and sodium diacetate.

Doyle described a study showing how growth of Listeria in untreated vacuum-packed, sliced, cooked ham increases tremendously over time (from 0 to 40 days at 4^°C), while there is no growth at all in meat treated with a solution of 2.5 percent sodium lactate and 0.25 percent sodium acetate (Blom et al., 1997) (Figure 4-2). When the same product is slightly temperature abused (i.e., stored at 9^°C instead of 4^°C), the chemical treatment no longer totally suppresses growth, although growth is not nearly as rapid as it is without treatment. Taken together, these results suggest that chemical treatment is both time and temperature dependent. The longer the storage

FIGURE 4-2 Growth of Listeria monocytogenes (closed symbols) and lactic acid bacteria (open symbols) in vacuum-packed, sliced, cooked ham stored at two different temperatures: (a) at 4°C and (b) at 9°C, with or without treatment with sodium lactate and sodium acetate.

SOURCE: Blom et al., 1997.

FIGURE 4-3 Growth of Listeria monocytogenes in uncured turkey breast meat stored at 7°C for 12 days, with and without added lactate-diacetate.

SOURCE: Lianou et al., 2007.

time and the warmer the temperature, the less likely it is that growth will be suppressed.

In another study, with vacuum-packaged uncured turkey breast meat stored at 7^°C for up to 12 days, again the chemical treatment (in this case 1.5 percent sodium lactate and 0.05 percent sodium diacetate) suppressed Listeria growth (Lianou et al., 2007). In the untreated package, the Listeria population increased from about 100 cells at day 0 to 10⁸ cells at day 12 (Figure 4-3).

Doyle stated that because lactate-diacetate provides such a high level of public health protection by mitigating the growth of Listeria monocytogenes on high-risk deli meats during in-home and retail use, it is widely used by the food industry today.

Doyle explained how he and his colleagues recently discovered that the use of levulinic acid in combination with a detergent, sodium dodecyl sulfate (SDS), is a highly effective way to kill harmful bacteria on produce and poultry (Zhao et al., 2009). They showed that neither chemical on its own suppresses either Salmonella or E. coli O157:H7 growth on lettuce

with exposure times of 5 minutes or less, but that, together, the combination “is like dynamite.” Treatment with a 0.5 percent levulinic acid and 0.05 percent SDS solution results in a dramatic reduction in Salmonella or E. coli O157:H7 contamination after just five minutes of exposure. Treatment with a 3 percent levulinic acid and 1 percent SDS solution results in complete reduction of all detectable microbes within just one minute. The beauty of this technique, Doyle said, is that levulinic acid does not destroy the integrity of the food being treated, as is the case with lactic acid and other organic acids, which usually cause lettuce leaves (or leafy greens) to turn brown and wilt within a couple days of exposure. As part of the same study, the researchers also found that treatment with 3 percent levulinic acid plus 2 percent SDS killed all detectable Salmonella on poultry wings within two minutes of exposure.

Doyle commented on the many advantages of a levulinic acid plus SDS antimicrobial treatment:

• Studies have shown that, depending on concentrations and exposure time, the chemical combination has strong antimicrobial activity not just against Salmonella and E. coli O157:H7 but also Listeria monocytogenes, Yersinia pestis, Bacillus anthracis, and Norovirus.

• Its antimicrobial activity is not inactivated by the organic load, which is what happens with chlorine (if there is blood or soil in the tanks used to wash poultry, it will inactivate the chlorine).

• It is non-corrosive to stainless steel and non-irritating to skin.

• It removes biofilms.

• It is fast-acting.

• Foods can retain their sensory properties (color, appearance, texture, odor).

In addition to all of these various existing and innovative technologies aimed at protecting against or suppressing microbial growth in foods, many companies have also begun reducing the portion sizes of products in packages. Doyle remarked that this is commendable, given the additional cost of producing these that may not be fully recovered. Hot dogs, for example, are now available in packages of five and not just packages of 10. Many older adults are not likely to go through 10 hot dogs, or even five, in just one sitting. This is an important food safety preventative measure, given that opening a package and then putting the unused resealed hot dogs back in the refrigerator creates the potential for Listeria contamination and growth.

In conclusion, Doyle emphasized the market sustainability of three processes in particular:

• high hydrostatic pressure processing of deli meats, fruit juices, and oysters;

• the formulation of ready-to-eat meats with listeriostatic chemicals (i.e., potassium lactate and sodium diacetate); and

• the packaging of smaller portion sizes.

Challenges to applying some of the other new processing technologies and formulations to mitigate pathogen contamination of foods are largely related to sensory changes (e.g., changes in smell or taste), added costs, and consumer acceptance or willingness to pay more for foods that have been processed or formulated using these technologies. However, perhaps with a growing population of older adults, a niche of sufficient market size will eventually develop such that production of new lines of “pathogen-free” foods created from some of these other technologies (e.g., irradiation) can be sustainable.

Presenter: Aaron Brody

Brody remarked that the goal of his talk would be to describe the key role played by the packaging industry in meeting consumer food and nutrition needs and desires. He stated that the industry is doing this better than it has at any other time in history and at a lower cost and with less environmental impact. Packaging costs fewer than 7 percent of the retail price of food, which itself is at its lowest cost in history; food expenses today amount to fewer than 11 percent of disposable income, even with away-from-home eating.

Brody defined packaging as the separation of a product from the environment. He stated that a package is not merely a piece of material or a structure; it is a holistic system, with its primary purpose being protection “against an always hostile natural environment.” Without packaging, industrialized society would not exist. Not only does packaging enable the

delivery of goods from one place to another, it also enables eating. About 60 percent of all packaging is food packaging.

One of the primary functions of food packaging is protection from the natural environment. Food packaging protects against oxygen, moisture, water, microorganisms, light, dirt, odors, animals, and humans; and without food packaging, food waste would be over 50 percent. Food packaging also allows for delivery to its intended recipient(s); protects foods during distribution (e.g., from the impact, vibration, and compression that occurs during transit); retains the nutritional quality and sensory characteristics of the initial product; allows for an extended commercial shelf life; communicates information; allows for accessing and dispensing of contents (e.g., Brody mentioned the development of easy-open soup packages that eliminate the need for can opener); and serves other functions. Industry “guidelines” for packaging include safety, protection of the contents, consumer convenience (ease of access and use), facilitation of finding products, attractiveness to a diverse customer base, applicability for away-from-home eating (which amounts to about half of all food consumption), and minimal environmental impact.

Brody discussed several recent developments in food packaging, emphasizing that the weight of packaging per unit food is at its lowest in history. The use of heavier-weight glass, metal, and high-caliper paperboard structures is declining, while the use of lightweight plastic and other flexible structures is growing. He showed several pictures of the wide variety of new types of food packaging systems currently being marketed, and he reiterated the important role of packaging in ensuring microbiological safety.

Carbonated beverages were the first beverage or food to be packaged in lightweight, non-breakable polyester bottles instead of glass (in 1977). Today, many different beverages and foods are packaged in plastic bottles, including fruit beverages, jams, tomato sauce, and even beer. For example, instead of all-steel cans, roasted and ground coffee is now being packaged in lighter-weight, more unitizing (larger quantities can be moved at once) plastic containers; and hot-fill high acid fluid foods (e.g., tomato paste) are being packaged in laminated flexible pouches instead of metal cans. Plastics are also being used to design other types of packages, like microwavable, individual unit portion, and liner-less composite paperboard packages. Brody explained that no single plastic material is “magic” and that different materials are often used in combination.

Another recent development is aseptic packaging, which involves sterilizing the product and package separately and then assembling them together in a sterile environment. This reduces the amount of heat used on the product, thereby extending its shelf life, while simultaneously allowing for the use of just about any packaging material (e.g., composite paperboard bricks, barrier plastic cups, lightweight packaging). The use of very carefully temperature-controlled distribution systems extends shelf life even further.

Another recent trend is the use of gas-permeable packaging for fresh-cut vegetables. By giving the vegetables a little bit of oxygen, their shelf life lasts longer (i.e., two weeks in a refrigerated environment).

The industry is seeking new ways to “delight” customers, for example by using differently shaped cans (instead of cylindrical cans), as well as new ways to make products more convenient. Examples of new convenience foods include “no drain” tuna, which is packaged in a reduced liquid retort pouches instead of heavy metal cans, and ready-to-eat fruit bowls.

Brody ended by summarizing current and future trends in food packaging. He mentioned increased use of flexible packaging, which reduces both the product weight and the risk of breakage that would exist if glass were used. He showed products shaped for convenience and portability, such as single-serving packages and heat-and-eat packages, where the package serves as the processing aid and the serving container. He also mentioned that some packaging methods require less heat for sterilization, which boosts the nutritional value of the products, making these types of packaging potentially attractive for new product development.

A panel discussion followed the four presentations. David J. Greenblatt of Tufts University School of Medicine, Boston, Massachusetts, was invited to join the four speakers on stage and provide initial comments.

Presenter: David Greenblatt

To begin the panel discussion, Greenblatt offered some brief thoughts on the interaction between nutrients and prescription medications. He noted that pharmaceuticals have advanced at an incredible pace over the past 20 to 30 years and that one reason the U.S. population is aging so successfully is because of these and other biomedical advances. He said that when talking about the aging population and nutrition, one is automatically talking about people on medication. This raises questions about whether and how medications interact with nutrients. The “prototype” of a nutrient-drug interaction, he said, is “the grapefruit juice story.”

In the early 1990s, pharmacology researcher David Bailey and his team at the University of Western Ontario were the first to report an interaction between grapefruit juice and the calcium channel antagonist felodipine (Edgar et al., 1992). They reported that felodipine in combination with grapefruit juice caused about a five to tenfold increase in plasma felodipine concentration, resulting in adverse effects in many individuals. Knowledge of these adverse effects eventually led to hundreds of scientific studies but also a tremendous amount of inaccurate press and widespread public belief that it was not safe to drink grapefruit juice with any medication. Through a combined effort on the part of both the biomedical and nutritional science communities, researchers eventually learned that the interaction revolved around the enzyme cytochrome P450-3A (CYP3A).

Greenblatt explained that CYP3A intervenes at two points in the drug metabolism process. With an oral dose of the drug, the drug first passes through the mucosa of the small bowel, which Greenblatt described as containing substantial quantities of CYP3A. There, any drugs that are substrates for metabolism by CYP3A maybe metabolized. Whatever drug remains (i.e., has not been metabolized) enters the portal circulation and the liver, where there is more CYP3A, before entering the systemic circulation. Again, in the liver, there is another opportunity for metabolism. So there are two opportunities for first-pass metabolism (i.e., pre-systematic extraction). Since grapefruit juice contains furanocoumarins, which interact with CYP3A in the small bowel, individuals who drink grapefruit juice may be less able to metabolize drugs that serve as substrates for CYP3A in the small bowel, and they may end up with greater amounts of drug in systemic circulation.

Greenblatt emphasized that only a few drugs are of concern and that the interaction is a product only of grapefruit juice, no other fruit product. Only buspirone, felodipine and simvastatin have shown probable interac-

tions (e.g., see Lilja et al., 1998), and only a handful of additional drugs having shown possible interactions (triazolam, midazolam, diazepam, nisoldipine, lovastatin, carbamazepine, cyclosporine) (Greenblatt, 2010). His advice to patients already taking any of these drugs with grapefruit juice and not showing any signs of an adverse effect is to continue what they are doing, as presumably their dose has been adjusted to achieve the proper pharmacologic and clinical effects. However, for patients who are taking any of the three drugs that have shown probable interaction, he advised that grapefruit juice be avoided. With the other drugs that have shown possible interactions, he would advise caution but would not necessarily advise avoiding grapefruit juice. Although pomegranate, cranberry, grape, lime, pomelo, and tangerine juices have all shown interactions with CYP3A in a test tube, the interaction is reversible. With grapefruit juice, the interaction is irreversible: the only way to increase the level of active enzyme is to produce more. This is a property only of grapefruit juice; it does not apply to any other fruit products.

Greenblatt also commented on how both overall endowment values and annual rates of return on investments have fallen dramatically over the past several years, for “probably every university in the nation.” He commented that financial reasons have created a “hugely reduced and less friendly” university environment for biomedical research, which coupled with a decrease in NIH funding over the last 5 to 10 years, stimulus money notwithstanding, raises serious questions about how some of these critical nutrition questions will be answered.

The four presentations and Greenblatt’s remarks prompted many comments and questions from the audience about the evidence for nutrient-drug interactions in older adults, data on foodborne infectious diseases in older adults, the challenges of developing innovative packaging for older adults, the complexity of the issue of consumer acceptance (i.e., of food technologies), and the use of chlorine as a decontaminant.

The first remarks were directed toward Dr. Magnuson. An audience member commented that her soy isoflavone study in rats appeared to involve only 11 animals, then asked whether she or others had ever examined

the impact of standard rat chow, which contains soy isolate, on longevity. First, Magnuson remarked that the data she presented were from a preliminary study. She explained that the study began with 7 animals in each of the three age/treatment groups and that the number in the end was as low because of unanticipated deaths that occurred in the study. Five of the 21 rats fed the soy supplement died before the end of the experiment while all animals on the control diet (n = 21) survived to term. The researchers had not anticipated age-related differences in toxicity. The dose of soy isoflavones they used was lower than the reported NOAEL (no-observable-adverse-effect level) of 120 mg/kg/day determined in a 28-day repeated dose study with genistein in male and female rats, well below doses of up to 500 mg/kg/day that have been used in previous chemoprevention studies. Then, she explained that the treatment involved adding soy isoflavone supplements to a standard AIN-96 diet and that the goal was to examine the effects of a supplemental level of soy isoflavone, not the effects of soy protein isolate.

Magnuson later clarified that she and her group chose to examine curcumin and soy isoflavones because of “the plethora of information on beneficial effects on those.” Their data suggest, however, that there is insufficient information to be making those claims across all age groups. It is unclear why the nutrients have adverse effects in certain situations. She urged that more attention be paid to these types of very dramatic effects.

Later during the panel discussion, Greenblatt was asked if the grapefruit juice story he had told was the “last word” on drug-nutrient interactions. Greenblatt said that grapefruit juice is the “best” and “most dramatic” example. He argued that isolated case reports of interactions are useful for guiding future research but do not by themselves prove cause-and-effect; and that many animal studies may be irrelevant to human health because of enzymatic, hepatic blood flow, GI physiology, and other differences. Based on data from controlled human pharmacokinetic studies in which a drug was examined both before and after exposure to the nutrient in question, “there are precious few [examples] compared to grapefruit juice.”

Gendel was asked why the incidence of some foodborne pathogens is higher in older adults and to what extent the data he discussed reflect the fact that someone with symptoms is more likely to seek help (and therefore be included in a surveillance data set) than someone who is infected but not showing symptoms. Gendel replied that the observed effects are real effects, given that FoodNet and other monitoring systems capture as much

data as they do and make every effort to remove the medical intervention effect (i.e., whether somebody has sought medical treatment or not) from the system. For example, the Canadian Listeria data that he presented were obtained from two independent monitoring systems, and they both showed the same trend.

There were several remarks and questions regarding packaging. Brody was asked whether any of the packaging materials that he described have been tested to determine if any chemical residues might be leaching into food products. He responded that, yes, there have been many such studies. He commented on recent media headlines about bisphenol A (BPA), which is used primarily as a building block for the epoxy polymers in can liners. He said that FDA would be issuing a report on BPA very soon and that, in general, plastics are without question one of the most studied materials in world history with respect to chemical leaching. He said that while nobody can guarantee their absolute safety, evidence to date indicates that today’s packaging materials are safe, especially when compared to what has been used in the past. Later during the discussion, there was another comment about BPA and the need to be very careful when measuring BPA, as BPA has been known to leach out of materials used (e.g., PEEK [polyether ether ketone] tubing) for BPA analytical procedures.

Another audience member commented that, while advances in packaging have made it easier to open certain products, “one of the ways that you are keeping elderly people safe from the food inside is that they still can’t get to all of it.” Often, the questioner said, older adults have difficulties opening some of the newer types of packaging, such as the fruit cups with pull-off lids, because of limited mobility in their fingers. This raises the question, how conscious is the packaging industry of the needs of older adults when designing new ways to package food products? Brody said that the industry shares an “extremely high level of consciousness” about the need to make products more accessible to older adults, as well as the need to keep children from opening packages that they should not be accessing. Brody mentioned ring-top pulls, peelable packaging, and slider zip loc bags as examples of the type of ongoing improvements being made with packaging. Many of these improvements are based on efficacy trials and other tests. However, with some 15,000 new packages introduced into the market every year, not every new package goes through the same testing procedures.

Another audience member mentioned a focus group study currently under way in Manitoba, Canada, with the goal of gaining a better understanding of how to design and develop food products for baby boomers.

While there has been improvement in packaging, some of the baby boomers participating in the study have been commenting on the difficulties with opening some of these new types of packages. For example, older adults with arthritis have reported difficulties opening the supposedly easy-open cans because they can’t lift the lids with their fingers. So they use dull knives to open lids and, if that doesn’t work, they’ll bang cans on counters until the lids pop open. Or, they use scissors to try to pull lids open. Also, with many of the juices with antioxidant properties, the containers are very large and difficult to pour, again making them difficult to use. People who live alone end up not buying those products. So even with the introduction of new packaging, issues remain. Is the industry conducting any tests to determine how baby boomers and older adults open all of these new packages? Brody responded that yes, the industry is involved with focus group and other types of testing. He mentioned packaging industry trade magazines and journals as a source of information on the type of studies being conducted.

A comment that Doyle had made during his presentation about irradiated foods prompted an audience member to comment on the complexity of the issue of consumer acceptance. Consumer acceptance of risk depends on many factors, such as taste and cost. With respect to taste, irradiated beef reportedly tasted like wet dog to some consumers and singed hair to others. With respect to cost, irradiated beef was sold as safer and was therefore sold at a higher price in an attempt to recoup some of the cost, and most consumers probably did a fairly intuitive cost-benefit analysis and concluded that the higher cost was not worth reducing the risk of bacterial contamination. It is important to recognize this complexity and not draw the wrong conclusions. Some people have concluded that the failure of irradiated beef was a result of irresponsible propaganda, when in fact the situation was much more complicated than that. Consumers were making a “complicated, nuanced decision.”

In response to these comments, Brody remarked that the unpleasant taste from irradiation occurs only when the official maximum dose is exceeded. Magnuson agreed with the audience member, stating that the remarks “hit on a very important point” about the complexity of public perception and consumer acceptance. For example, with dietary supplements, cost is not the issue for most consumers. Public perception is that because a supplement is “natural,” it is therefore safe.

Doyle remarked that all new technologies come at a price and that the industry faces a tremendous challenge in terms of developing technologies that can be used to ensure safe food that still looks, smells, and tastes good. The challenge is especially difficult with those foods that are of greatest risk: fresh, uncooked foods. This remark prompted a question about the use of active chlorine to minimize Salmonella and Camplyo-bacter contamination in poultry products. The questioner noted that U.S. poultry plants use active chlorine for food decontamination purposes, but the European Commission does not allow the use of this practice in European plants. He asked the panelists their opinions on the use of a chemical that has toxic properties but that also effectively kills pathogens. The questioner also noted that there have been some claims that active chlorine is not efficacious at killing Salmonella. Doyle remarked that active chlorine is very effective at killing both Campylobacter and Salmonella “as long as the water is clear and clean.” He reiterated that an organic load (e.g., blood, residue) in the chill water tanks or other liquids used to process poultry neutralizes active chlorine and makes it ineffective. Other factors, such as the hardness of the water used in the plant, also play a role. The U.S. industry uses active chlorine because it is relatively inexpensive compared with other disinfectants. There are other products that work better than active chlorine and that work well even in the presence of organic load, but they are more expensive. Companies often use these more expensive products when problems arise but then, when the problem is cleared, they revert to using active chlorine for routine decontamination. He noted that one of the alternatives is peracetic acid, which is not only more expensive than active chlorine but is also corrosive to equipment.

The final query, directed to Gendel, was about the reason for the consistent incidence rate for Campylobacter infections. The audience member questioned whether older consumers’ lack of increased susceptibility to infection, especially compared to the very young, is due to immunity that has built up throughout life. Gendel replied that there is no protective immunity against such pathogens, and said that perhaps children show a higher incidence of infection than older adults because they are more likely to get checked if something is wrong.