This document outlines James Coughlin's career journey as a food toxicologist. Some key points include: - He studied nitrite/nitrate in processed meats and their potential risks/benefits related to cancer and nitric oxide production. - He also researched coffee/caffeine and found that initial concerns about health risks were often unfounded, and coffee may provide health benefits. - Throughout his career, he advocated for a "benefit-risk" approach to evaluating foods and ingredients based on the totality of their components and effects, rather than focusing only on potential risks of individual constituents.

1. Turning Toxicants into Nutrients:
A Food Toxicologist’s Journey
James R. Coughlin, M.S. Ph.D. CFS
President, Coughlin & Associates
Aliso Viejo, California
jrcoughlin@cox.net
www.linkedin.com/in/jamescoughlin
University of California Davis
Food Science & Technology Department
Virtual Department Seminar Series
February 9, 2022

2. Presentation Outline
 A Disclaimer: All Toxicants Can’t be Turned into Nutrients! 
 Food and Food Ingredient Safety Evaluation Must Take Both Risks and
Benefits Into Consideration
 Key Takeaway & My Major Career Focus: Benefit-Risk Evaluation
 Required Learning Nutrition, Epidemiology & Clinical Medicine
 Two of the Key Focal Points of My Career in Food Toxicology –
 Nitrite/Nitrate/Nitric Oxide & Processed Meats [1974- ]
 Coffee/Caffeine and Health [1981- ]
 My Passion for Risk Communication
 Future Considerations on Dietary Bioactives for Chronic Disease
Prevention
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3. Where Did My Long Journey
Start?
 Long family history in foods and toxicology…
 Daniel Flinn was a grain/feed merchant in Ireland
who emigrated to Albany NY in 1820 and founded
Flinn’s Grain & Feed Store, which my great-
grandfather Peter and grandfather Fabian ran until
1957
 My Uncle Peter Flinn ran his own rabbit farm and
sold the rabbits for tox testing [skin & eye]
 So of course…I had to become a Food Toxicologist!
 Chemistry was my major in college; Biochemistry &
Medicine became my passion for 5 college summers
working in a Biochem lab at Albany Medical College
 Started my PhD in Biochemistry at Case Western
Reserve Medical School, but this got interrupted after
one semester by serving 3+ years as an Army Medical
Service Corp officer in Korea and San Francisco
 From the Presidio of SF in 1972, I discovered Food
Science at UC Davis [MS & PhD], then stayed for
postdoctoral training in Environmental Toxicology
before heading off to the food industry in 1979.
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4. Remembering My “Roots” at the University of
California, Davis

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11. Benefit - Risk Evaluation
of Foods and Ingredients
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17. Nitrite / Nitrate / Nitric Oxide
& Processed Meats [1974- ]
UC Davis, Armour Foods, Oscar Mayer Foods,
American Meat Institute
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18. N-Nitrosamine Carcinogenicity Concerns
Began with Rodents in 1956
~
My PhD/Post-doc research on N-Nitrosamines in the
“Maillard Browning Reaction” began in 1974 at
UC Davis
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20. Nitric Oxide-Myoglobin [NO-Mb]
[The Cured Meat Pink Pigment]
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23. Ammonia
Alkyl amines
Amino acids
Proteins
Phospholipids
Aldehydes
Ketones
Sugars
Carbohydrates
Lipids
Carbonyls
Esters
Amides (Acrylamide)
Heterocyclic Compounds
Amine
Carbonyl
Amino-Carbonyl
Interaction
(Amadori Products)
HEAT
HEAT
Furans Oxazoles
Pyrroles Imidazoles
Thiophenes Pyridines
Thiazoles Pyrazines
Melanoidins
(pigments)
Volatile Compounds
(aroma chemicals)
General Scheme of Maillard Browning Reaction
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24. N-NO-Fructose glycine
[One N-Nitroso-Amadori Compound]
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25. Presentations of My PhD Research
 “Synthesis, mutagenicity and human health implications of N-nitroso
Amadori compounds from Maillard browning reactions in the
presence of nitrite."
American Chemical Society Congress, Honolulu, April 1979.
 "Mutagenic N-nitroso Amadori compounds formed from model
Maillard nonenzymatic browning products in the presence of nitrite."
Society of Toxicology, New Orleans, March 1979.
 1979 - U.S. National Cancer Institute “Diet and Cancer” Project
Proposal based on my studies was unfortunately not funded [$2
million requested]; this proposed effort involved 15 researchers in 4
UC Davis departments
* this changed my career direction away from academics and
into 12 years in the food industry [Armour Foods, General
Foods, Kraft General Foods] before starting consulting 30 years
ago.
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26. Safety and Regulatory History of Nitrite / Nitrate –
Animal Carcinogens and Cancer
N-nitroso compounds discovered as animal carcinogens (1956), later found
at low ppb levels in processed meats; Nitrite itself as a possible rat
carcinogen (Newberne, MIT 1979), faced carcinogen ban under the FD&C
Delaney Clause.
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28. International Agency for Research on Cancer (IARC)
Evaluation of Meat and Cancer, October 2015
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30. IARC: Red & Processed Meat Decisions (Oct. 2015)
 22 invited scientists on Working Group; 8 global meat industry Observers were
silenced; 8 days of deliberations; global written submissions were not shared with
WG; conclusions published two weeks later in Lancet Oncology (Oct. 2015)
 RED MEAT:
 Group 2A, “Probable Human Carcinogen”
 “Limited Evidence” in humans, colorectal cancer only
 “Inadequate Evidence” in animals
 Mechanistic considerations made classification go from Group 3 to Group 2A
 PROCESSED MEAT:
 Group 1, “Human Carcinogen”
 “Sufficient Evidence” in humans for colorectal cancer only;
Relative Risk =1.18; barely statistically significant, translates to 18% increase
in risk; fuller published meta-analysis showed no increased risk; IARC
excluded some epi studies demonstrating less risk
 “Inadequate Evidence” in animals
 Mechanistic considerations made classification go from Group 2B to Group 1.
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31. Summary on Potential Risks
 Potential hazards of Nitrite and Nitrate exposure have been
extensively evaluated by many regulatory agencies and public
health bodies for decades
 Nitrate is not a carcinogen and is associated with an overall low
level of toxicity…it’s been Nitrite that has gotten all the attention
 Nitrite per se is not a carcinogen in animals [NTP Bioassay] or man
 Yes, nitrite does react to form carcinogenic N-nitroso compounds in
foods and in the human body, but at ppb levels much to low to
induce human cancer risk
 Processed meats have been tortured with barely-statistical human
epidemiologic findings [for colorectal cancer only] and unproven
mechanistic hypotheses linking them to cancer.
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32. Using a “Benefit-Risk” Approach for
Nitrite-Processed Meats…
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38. Foreword by Nobelist
Dr. Louis Ignarro
“This book brings the NO-story full
circle and presents novel thought on
the future treatment for many of the
country’s most pressing health
issues.”
“This text effectively overviews the
important role nitrite and nitrate play
in biological systems and NO
homeostasis.”
“The broader context of research
regarding nitrate, nitrite and nitric
oxide suggests these simple nitrogen
oxides serve as a critical dietary
component for protection against
various chronic diseases.”
“The future use of nitrite/nitrate in
dietary considerations will likely have
a significant impact on current public
health policy.”
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39. Coffee/Caffeine and Health [1981- ]
General Foods, Kraft General Foods, Consulting for
Coffee Companies and Trade Associations
“Association for Science and Information on Coffee”
Professional Society in Paris
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40. THE Health Beverage!!!

41. My 40-Year Perspective on Coffee & Health
 Studies on Rats, Mice & Humans, and on almost Every Disease
 “Well Conducted” and “Poorly Conducted” Scientific Research
 Good and Bad Health Policy & Regulatory Decisions and Very
Extensive Media Coverage
 First 15-20 Years: Much Bad News! Coffee & Caffeine were
linked to so many animal toxicities and human diseases!
 But since 2000 or so, the “GOOD NEWS” is that almost all of the
earlier bad news about coffee & caffeine was WRONG!
 Medical and scientific evidence has been building strongly that
coffee & caffeine may actually be GOOD FOR US!!!

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43. Coffee’s “Maligning” Started in the 1970’s and
Ballooned in the 1980’s & Early 1990’s
 Coffee and heart attacks…was it the caffeine?
 Caffeine and birth defects/other reproductive risks in
rats force-fed massive doses (U.S. FDA studies, 1978);
hundreds of subsequent studies have been conducted
in humans
 Coffee and cancer risk? [bladder & pancreas]
 Caffeine and osteoporosis risk? [from loss of calcium &
bone]
 Caffeine and the central nervous system [CNS]?
[stimulant effects, anxiety, sleep disturbance,
“addiction”]

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45. Using a “Benefit-Risk”
Approach for Coffee…
“Holistic Approach”
&
“Coffee - Cancer
Paradox”

46. “Benefit-Risk” Evaluation of Coffee Consumption
 Coffee has > 2,000 chemical components, mostly flavor/aroma
compounds, produced by roasting in the “Maillard Browning
Reaction”
 Coffee also contains many health-protective chemicals,
including polyphenolic Antioxidants, both naturally occurring
(chlorogenic acids) and heat-produced (brown polymeric
melanoidins, the “color”)
 My “mantra” for decades: Public health & regulatory authorities
should weigh the health effects of all coffee components when
deciding about safe daily consumption levels
 Coffee’s “benefit-risk” evaluation process requires using the
“Holistic Approach” - looking at coffee as a whole food!

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48. Coffee and Cancer Risk
 Coffee contains trace ppb levels of numerous animal
carcinogens produced by heat in the “Maillard Browning
Reaction” (acrylamide, furan, furfuryl alcohol, caffeic acid)
 Most health authorities across the globe, including IARC,
now agree that coffee drinking (and caffeine) is NOT a
human cancer risk, and in fact coffee actually reduces the
risk of numerous types of human cancer
 I have termed this the “Coffee-Cancer Paradox” – and it
results from doing a “Benefit-Risk” evaluation using the
“Holistic Approach” (coffee as a whole food).

49. U.S. Congress & FDA Concerns
over Caffeine in Energy Drinks
[2013 - ]
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51. U.S. Senate Report Released April 2013
 Report by Offices of Rep.
Markey (D-MA), Sen. Durbin
(D-IL) and Sen. Blumenthal
(D-CT), April 10, 2013:
 Inconsistent
representation and
claims
 Inadequate labeling
 Unsubstantiated claims
of benefits
 Targeting children
 Effects of other
constituents unknown

52. U.S. Senate Report Released January 2015
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56. Dietary Bioactives for Chronic
Disease Prevention
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60. Conclusion: Essential Nutrients vs. Dietary Bioactives
 Essential Nutrients:
 It will be very difficult to ever get new vitamins and minerals officially
recognized by global health authorities
 Essential nutrients were historically recognized because inadequate intakes
were proven to cause deficiency diseases, so that current RDAs cover how to
prevent such deficiencies
 But we don’t yet consider compounds that prevent chronic diseases to be
essential nutrients
 Dietary Bioactives:
 There is a great push globally to establish a scientific and regulatory framework
for deciding intake recommendations for dietary components that can be shown
to assist in preventing chronic diseases…
 Nitrate/nitrite, coffee antioxidants, marine oils [EPA/DHA], lutein…
 Such intake recommendations must come along with recommended upper safe
intake levels determined by toxicologists.
The New Goal might become –
“Turning Toxicants into Health-Protective
Dietary Bioactives!”
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61. Thank You!
~
Questions?
James R. Coughlin, MS PhD CFS
jrcoughlin@cox.net
949-632-4453

62. Additional References
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