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
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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.
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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”©
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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?
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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."
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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.
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10. 10

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)
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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.
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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.
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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
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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.
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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.
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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
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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.
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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?
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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.
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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.
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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.
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