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Coughlin_IFT_Risk Benefit Talk_July 2010

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  • 1. Beyond Acrylamide: Risk-Benefit Evaluation of Maillard- Browned Foods Containing Animal Carcinogens James R. Coughlin, Ph.D. President, Coughlin & Associates Aliso Viejo, California jrcoughlin@cox.net SYMPOSIUM “Food Processing Toxicants: Risks and Remedies” Institute of Food Technologists Annual Meeting, Chicago July 18, 2010 1
  • 2. Abstract Carcinogens from heated foods have been a significant health concern since the 1970’s, when trace levels of animal carcinogens/mutagens (PAHs) were found in barbecued steaks and other heated foods and N-nitrosamines were found in fried bacon and beer. Heterocyclic amines were also found in grilled meats, and many of these compounds are known to be potent mutagens and animal carcinogens. Many of these compounds are produced by heat in the Maillard Browning Reaction (MBR) between carbohydrates and amino acids and are known as Maillard reaction products (MRPs). Acrylamide and furan have caused widespread concern as animal carcinogens, as have numerous other compounds highlighted by the EU’s HEATOX project. However, an important question in assessing the safety of individual heat- induced food chemicals is why there is still such an intense interest in trace level carcinogens in heated foods, when there is little human epidemiologic evidence linking these foods with the risk of disease, including cancer. One of the reasons may be that the health benefits of a food are often neglected by public health and regulatory authorities when assessing the overall safety of a food. While it is obviously important to evaluate the toxicological risks of heat-induced chemicals, it is equally important to fully evaluate the safety of whole foods using a combination of modern toxicologic and epidemiologic techniques. In fact, numerous health-protective compounds are also produced during heat processing and cooking, so it is critical to evaluate the beneficial health effects of heated foods and then to undertake a thorough risk-benefit evaluation of the whole food. In the case of carcinogens, such an evaluation must carefully consider how best to interpret animal toxicology and cancer bioassay results for individual chemicals, as well as any information that the whole food itself may actually be cancer protective. 2
  • 3. Presentation Outline Assessing the safety of foods containing heat-produced toxicants: Doing it the WRONG WAY for decades, by simply evaluating the risk of individual chemicals one by one But the RIGHT WAY going forward is to evaluate the overall safety of the whole food (compare the risks vs. the benefits) Background: Recent “Risk-Benefit” schemes and evaluations Carcinogens in heated foods vs. beneficial effects of whole foods IFT Expert Report, “Risks of Chemicals in Foods,” July 2009 Case examples: Acrylamide/furan/other Maillard Browning Reaction carcinogens Protective compounds in heated foods (antioxidants, MRPs) The “Coffee/Cancer Paradox”© 3
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  • 6. EU’s “BRAFO” Project “Risk Benefit Analysis of Foods” (www.brafo.org) European Commission financial support; ILSI Europe coordination role; several institutes & universities; September 2007 – December 2010 Framework being developed for defining a common measurement scale to compare risks and benefits quantitatively using 3 test cases: Natural foods (oily fish and soy) Macronutrient replacement agents (sweeteners, fat substitutes) Impact of heat processing on foods (acrylamide, benzo(a)pyrene, heat treatment of milk) Among the Key Questions: What risks and benefits should be considered? How do we handle different/sensitive population groups? Where does risk-benefit assessment end and risk management by governments and health authorities begin? 6
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  • 8. Dietary Nitrite and Nitrate: Roles in Nitric Oxide Biology From the Foreword by Louis J. Ignarro, Nobel Laureate in Physiology/Medicine "The body of work contained in this volume, linking NO to food and nutrition, may have revolutionary implications in terms of developing strategies to combat heart disease and many other contemporary diseases associated with NO deficiency. Proving that a natural and inexpensive regimen of foods rich in nitric oxide activity does restore NO homeostasis can have profound effects on human health…The research presented in this text provides an important expansion of NO work…(and) Dr. Nathan Bryan, the editor…is to be congratulated for…communicating new knowledge and assembling the world's experts in their fields." 8
  • 9. Milkowski A, Garg HK, Coughlin JR and Bryan NS. “Nutritional epidemiology in the context of nitric oxide biology: A risk-benefit evaluation for dietary nitrite and nitrate.” Nitric Oxide: Biol. Chem. 22: 110-119 (2010). Discovery of nitric oxide (NO) pathway in the 1980s was a critical advance in understanding cardiovascular disease; today a number of human diseases are characterized by NO insufficiency Recent research demonstrates that NO can be modulated by consumption of nitrite- and nitrate-rich foods such as fruits, leafy vegetables and cured meats along with antioxidants Some in the public perceive that dietary sources of nitrite and nitrate may be harmful; some epidemiological studies reveal a weak association between foods that contain nitrite and nitrate, namely cured meats, and cancer; however, these data are currently inconclusive We must revisit such risks in the face of new data on the undisputed health benefits of nitrite- and nitrate-enriched diets; any risks are far outweighed by the health benefits of restoring NO homeostasis via dietary nitrite and nitrate. 9
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  • 11. Focus of IFT Expert Report U.S. and international legal and regulatory frameworks - measures governing the safety of the food supply Toxicology and Risk Analysis - how the nature and size of real or potential risks are determined, especially when data are incomplete Assessing consumer dietary exposure Establishing concentration levels in various foods Determining how much of each food is consumed Risk-benefit evaluation of whole foods: Disease prevention vs. health promotion Methyl mercury risks vs. nutritional benefits of seafood Maillard Browning Reaction (acrylamide, coffee) 11
  • 12. Key “Risk-Benefit” Controversies Interpretation of rodent cancer bioassays of extreme chemical doses has been shown to be overly conservative Assessing individual food chemicals has been our focus in the past, but we now need to consider the risks and benefits of whole foods using a “Holistic Approach” Failure to give proper weight to epidemiology studies showing little or no increased risk Failure to consider the POSITIVE health benefits of foods containing only trace levels of carcinogens & toxicants Comprehensive risk-benefit assessment is going to be complex, data-demanding and expensive. 12
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  • 15. Risk-Benefit Assessment HEATOX Program concluded in 2007: “Current knowledge does not allow for a risk-benefit assessment of cooking with respect to acrylamide or other heat-induced toxicants.” “Risk-benefit assessments should be performed. There is a special need for establishing agreed protocols including weighting factors for risk-benefit assessments.” In light of the HEATOX “Iceberg” it’s time to move forward with this approach - Health-protective compounds are also produced by heating foods Health benefits of the heated foods themselves These protective health effects must be factored into the risk-benefit evaluation process. 15
  • 16. General Scheme of Maillard Browning Reaction Ammonia Melanoidins Alkyl amines (pigments) Amine Amino acids Proteins HEAT Phospholipids Amino-Carbonyl Volatile Compounds Interaction (aroma chemicals) (Amadori Products) Aldehydes Ketones Carbonyls Carbonyl Sugars Esters Furans Oxazoles Amides (Acrylamide) Carbohydrates Pyrroles Imidazoles Lipids Thiophenes Pyridines Heterocyclic Compounds Thiazoles Pyrazines 16
  • 17. “Maillard Reaction Products” (MRPs) - Possible Beneficial Health Effects While flavors, aromas, colors and texture of browned foods depend on the MBR, animal carcinogens are also formed But Antioxidants are also produced by the MBR, and they may protect against diseases linked to oxidative damage (cancer, diabetes, atherosclerosis, arthritis, inflammation, etc.) The brown melanoidin polymers and some heterocyclic compounds (furan) have been shown to have antioxidant properties Some MRPs can also induce protective detoxification enzymes, including ones that detoxify acrylamide. 17
  • 18. J. Agric. Food Chem. 54: 853 (2006)
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  • 20. “Risk-Benefit Considerations of Mitigation Measures on Acrylamide Content of Foods – A Case Study on Potatoes, Cereals and Coffee.” Seal et al., Br. J. Nutr. 99 [Suppl 2]: S1-S46 (2008). Expert Report commissioned by the ILSI Europe Process Related Compounds Task Force (12 institutes, universities and companies) 1. To summarize and evaluate the impact of pre-harvest, post-harvest and processing conditions on acrylamide formation in potatoes, cereals and coffee. 2. To consider the nutritional value and beneficial health impact of consuming these commodities. 3. To calculate the impact of mitigation using probabilistic risk-benefit modeling to demonstrate the principle of this approach. 20
  • 21. The “Coffee / Cancer Paradox”© Coffee contains ~ 2,000 identified compounds, including trace levels of many animal carcinogens (including acrylamide & furan) But global health authorities now agree that coffee drinking is NOT causing any increased risk of human cancer In fact, epidemiological studies show significant risk reductions for liver, colorectal and endometrial cancers in spite of the presence of these animal carcinogens How can this be? Naturally occurring antioxidants (chlorogenic acids) Heat-formed antioxidants (the brown melanoidin polymers) Inducers of detoxification enzymes Other mechanisms are being studied 21
  • 22. “Epidemiologic Evidence on Coffee and Cancer.” Lenore Arab (UCLA). Nutrition and Cancer 62: 271–283 (2010). “For most cancer sites, there is a significant amount of evidence showing no detrimental effect of consumption of up to 6 cups of coffee/day in relation to cancer occurrence. In fact, some of the evidence…suggests that coffee might prevent some cancers.” [based on over 500 publications] Hepatocellular and endometrial cancers - a strong and consistent protective association Colorectal cancer - the association is borderline protective Breast, pancreatic, kidney, ovarian, prostate, gastric cancer - no association Bladder cancer - very weak increase in risk is associated with heavy coffee consumption in some populations and among men Childhood leukemia - ambiguous risk with mother’s consumption of coffee at high levels of daily consumption. 22
  • 23. Key Questions about Coffee’s Antioxidants Fundamental question: What do oxidants and antioxidants (AOX) do in human health & disease? What kinds and amounts of AOX are in coffee compared to other well-known dietary AOX sources (wine, tea, chocolate, fruits, vegetables)? Are coffee’s AOX “bioavailable”? Are coffee’s AOX actually protecting us from diseases, including cancer? 23
  • 24. mg AOX/day B C la 0 100 200 300 400 500 600 700 800 of ck f Te ee a B (b ee ag r( ) La W ge in r) e O (R ra ed G ng ) ra e pe Ju Ju ic ic e e (R A ed G pp le ) ra Ju pe fr ic C ui e ra tJ nb ui er ce Pi r ne y J ap ui pl ce e Ju ic e 24
  • 25. Possible Mechanisms of Coffee’s Protective Effects Antioxidant effects of chlorogenic acids and melanoidins Many studies have shown ready bioavailability in animals and humans “MRPs aid detoxification by enhancing the expression of protective glutathione-S-transferase (GST) enzymes.” Faist et al., Intl. Congress Ser. 1245: 313-320 (2002) While the MBR does produce carcinogens, it also enhances protective enzymes, possibly resulting in increased detoxification of some of the carcinogens (including acrylamide) “Identification of a chemopreventive compound in coffee beverage using in vitro and in vivo techniques.” Somoza et al., J. Agric. Food Chem. 51: 6861-6869 (2003) Coffee beverage and N-methylpyridinium ions increased GST and UDP-GT activities in rat feeding experiments and also elevated plasma total AOX capacity. 25
  • 26. My Conclusions on Coffee’s Benefits Outweighing Risks Ongoing global interest in determining whether and how coffee and its compounds may be influencing human cancer risk While trace levels of many animal carcinogens are found in brewed coffee, it also contains many compounds that may reduce cancer risk Some of these protective compounds occur naturally in unroasted coffee beans (chlorogenic acids), while others are formed during roasting via the MBR (melanoidins, volatile AOX, others) To determine the overall cancer risk to humans, we must: Continue to study the health effects of coffee’s naturally occurring and heat-produced compounds, both “bad” and “good” Recognize that some of these compounds may be health- protective and outweigh the effects of trace level carcinogens. 26
  • 27. Conclusions on “Risk–Benefit Evaluation” The beneficial health effects of specific whole foods, such as coffee, may outweigh the effects of trace levels of animal carcinogens and other toxicants found in these foods We must expand on the preliminary efforts to develop improved methods for the qualitative and quantitative assessment of the benefits of whole foods We must press health and regulatory authorities globally to: Use improved toxicology and risk assessment methodologies Consider the health benefits of protective compounds produced by heating Assess the safety of the whole food, not just individual food carcinogens/toxicants one at a time Keep the major focus on nutritional and microbial risks. 27