Untold Nutrition

Abstract

Nutrition is generally investigated, and findings interpreted, in reference to the activities of individual nutrients. Nutrient composition of foods, food labeling, food fortification, and nutrient recommendations are mostly founded on this assumption, a practice commonly known as reductionism. While such information on specifics is important and occasionally useful in practice, it ignores the coordinated, integrated and virtually symphonic nutrient activity (wholism) that occurs in vivo. With reductionism providing the framework, public confusion abounds and huge monetary and social costs are incurred. Two examples are briefly presented to illustrate, the long time misunderstandings (1) about saturated and total fat as causes of cancer and heart disease and (2) the emergence of the nutrient supplement industry. A new definition of the science of nutrition is urgently needed.

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Untold Nutrition
T. Colin Campbella
a Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA
Published online: 18 Jul 2014.
To cite this article: T. Colin Campbell (2014) Untold Nutrition, Nutrition and Cancer, 66:6, 1077-1082, DOI:
10.1080/01635581.2014.927687
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COMMENTARY
Untold Nutrition
T. Colin Campbell
Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA
Nutrition is generally investigated, and findings interpreted,
in reference to the activities of individual nutrients. Nutrient
composition of foods, food labeling, food fortification, and
nutrient recommendations are mostly founded on this assumption,
a practice commonly known as reductionism. While such
information on specifics is important and occasionally useful in
practice, it ignores the coordinated, integrated and virtually
symphonic nutrient activity (wholism) that occurs in vivo.
With reductionism providing the framework, public confusion
abounds and huge monetary and social costs are incurred. Two
examples are briefly presented to illustrate, the long time
misunderstandings (1) about saturated and total fat as causes of
cancer and heart disease and (2) the emergence of the nutrient
supplement industry. A new definition of the science of nutrition
is urgently needed.
Nutrition has long been viewed through the lens of reduc-
tionism, which focuses on parts instead of the whole. The vast
majority of experimental studies have focused on individual
nutrients, their structural identities, their mechanisms of action
and their effects on specific outcomes. This strategy has served
the purpose of sharpening the message about functions of indi-
vidual nutrients but, far too often, these findings are not syn-
thesized into a whole food context.
The activities of individual nutrientsoften determined in
laboratory (in vitro) experimentsare substantially modified
upon consumption. Nutrients interact with each other and with
other chemicals in food, both during intestinal digestion and
absorption and after, during their metabolism and tissue distri-
bution. Nutrient functions also vary with nutrient dose and
these relationships, however defined they may be under static
conditions, can readily change within microminutes of time.
The proportion of nutrients digested, absorbed, transported,
metabolized, and stored or excreted during these stages con-
stantly changes. Collectively, these varying activities affect
ultimate function that makes it virtually impossible to know
how much of a nutrient in food, itself only an estimate, is
needed at the functional site.
Even though estimates of dose-response behaviors for indi-
vidual nutrients may be useful under many circumstances,
they are limited to the conditions of the observational period,
especially when nutrients are evaluated in isolation. In spite of
these limitations, we still conduct experimental research and
inform ourselves about nutrition by assuming activities of
individual nutrients. The nutrient composition of foods is
described and displayed as the amounts of individual nutrients
and health claims often focus on the kind, amount, and pre-
sumed functions of individual nutrients, as in food labeling,
food fortification, and health claims. This myopic focus on
individual nutrients rather than food, which may be called
reductionism, is costly, both in dollars spent and in lives lost. I
will cite two prominent examples of reductionism (among
many) to illustrate the problem created by assuming that single
nutrients, upon consumption, act independently.
The first is the vitamin supplement industry, now running at
$32 billion annually, according to a 2011 industry report (1).
Its modern day history started in the mid-1980s after it got a
marketing boost in 1976 with the Proxmire Amendment of the
food and drug regulations. This legislation permitted food
companies to sell vitamins and minerals without a doctor’s
prescription (2). The industry also got a scientific boost from
the publication of the 1982 National Academy of Science
(NAS) report on Diet, Nutrition and Cancer (3) that set goals
of using a lower fat diet (<30%) and the consumption of more
fruits, vegetables, and grains based on their nutrient contents.
Although this NAS expert committee based their goals in ref-
erence to the nutrient contents of foods, they explicitly cau-
tioned that these goals applied to whole foods, not to the
individual nutrients contained therein, as in nutrient supple-
ments. Still, the emerging vitamin supplement industry at that
time ignored the warning and claimed otherwise, landing them
in a 3-year administrative court hearing before the U.S. Fed-
eral Trade Commission. Being a witness on behalf of the NAS
to those hearings, I saw firsthand the intense, well-funded
effort by the industry to argue that the NAS goals referred to
individual nutrients, thus supporting their efforts to develop
nutrient supplements for the marketplace (4). Now, 20–
30 years later, a large number of randomized clinical trials
Submitted 20 May 2014; accepted in final form 21 May 2014.
Address correspondence to T. Colin Campbell, Jacob Gould
Schurman Professor Emeritus of Nutritional Biochemistry, Division
of Nutritional Sciences, Cornell University, Ithaca, NY 14850.
Phone: 607-533-9156. E-mail: tcc1@cornell.edu
1077
Nutrition and Cancer, 66(6), 1077–1082
Copyright Ó2014, Taylor & Francis Group, LLC
ISSN: 0163-5581 print / 1532-7914 online
DOI: 10.1080/01635581.2014.927687
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have been undertaken to test the efficacy of these supplements
and the results have been found wanting (5–9)
Summaries, which mostly represent meta-analyses of more
than 100 trials and hundreds of thousands of experimental sub-
jects, overwhelmingly show no long-term benefit for vitamin
supplements, along with worrisome findings that certain vita-
mins may even increase disease occurrence for diabetes (5, 9),
heart disease (6, 7), and cancer (7). Supplementation with
omega-3 fats also was said to have no long-term benefits, even
posing increased risk for diabetes (8, 9). More worrisome is
the fact that these findings, first appearing more than 10 years
ago, have had no discernible effect on their market. The public
desire for quick fixes through pills (i.e., reductionism) is over-
whelming, especially when money can be made. The activities
of individual nutrients observed in carefully controlled
research conditions will not necessarily be the same, at least
quantitatively, when these nutrients are consumed in the form
of whole food.
A second example of nutritional reductionism has a lifetime
of many decades. Total dietary fat (as well as dietary choles-
terol and saturated fat) has long been considered a major cause
of cardiovascular disease (10, 11) and some cancers (12–14),
culminating in major policy recommendations to reduce its
intake (3, 15, 16). This conviction has had major implications
far beyond what may be known to the casual observer. This
story began about a century ago with experimental animal
studies that mistakenly and mysteriously concluded that fat
was a primary cause of these diseases. Some, but not all, of
this early research, conducted by German and Russian scien-
tists, certainly indicated that dietary fat elevated serum choles-
terol and arteriosclerotic lesions [as reviewed by Kritchevsky
(17)], but these findings were somewhat equivocal and incon-
sistent until the 1920s when it was shown that protein was a
much more important cause of atherosclerosis than dietary fat
(18–20). These 1920s studies also showed that serum cholesterol
was not the cause of heart disease and, further, that dietary
cholesterol had little or no effect on serum cholesterol (19).
Somewhat later, additional insight emerged when it was
animal-protein [especially casein (21, 22) but also lactalbumin
(23)] not plant-based protein that increased serum cholesterol
and enhanced development of early heart disease. This casein
effect was substantial, being about 5 times greater than the
soy protein effect (21, 22). A substantial cholesterol-lowering
effect of soy protein also was shown in human studies (24),
and subsequently in still more human studies, as reviewed by
a soy industry consultant (25). Eventually, this cholesterol-
lowering effect of soy was judged to be an acceptable claim
by the FDA in 1999 (26).
When it was shown that soy protein decreased serum
cholesterol in rabbits by 70-80% (21, 22) [as reported by
Kritchevsky (23)] and in humans by as much as 30–40% (27),
it was called a cholesterol-lowering (hypocholesterolemic)
effect by soy, a marketable idea. But this observation also
could just as easily have been said to be a cholesterol-
increasing (hypercholesterolemic) effect of animal protein
(especially casein). In doing so, the soy protein effect would
have been considered an indication of a natural, healthy condi-
tion promoted by plant proteins in general, whereas the casein
effect would have indicated an unnatural, unhealthy condition.
Therefore, during that history, it is animal protein that should
have been labeled as the main cause of increased serum cho-
lesterol and heart disease, not total fat, animal fat, and/or
cholesterol.
A very similar story can be told for the association of die-
tary fat with cancer, especially cancers of the breast (28) and
colon (29). Dietary fat as a cause of cancer became a leading
hypothesis at a conference in Miami, Florida, and published in
the November 1975 issue of Cancer Research. Also, the previ-
ously mentioned NAS 1982 report on diet, nutrition and cancer
(3) suggested as their first-listed goal a reduction of dietary fat
to 30% of total calories. Thereafter, several other public policy
reports also made similar recommendations to decrease fat
consumption (15, 30–32).
The association of fat with breast cancer in population-
based studies was especially impressive (Fig. 1) (33). How-
ever, this oft-cited paper (33) also showed that this association
of total dietary fat with breast cancer (Fig. 1A) was explained
by the consumption of saturated fat (Fig. 1B) (typically found
in animal-based foods), not polyunsaturated fat (Fig. 1C) (typ-
ically found in plant-based foods). Essentially the same dietary
fat associations exist for colon and prostate cancers as well
(34).
I find these opposing associations of animal and plant fat
diets with breast cancer (Fig. 1A–1C) to be especially reveal-
ing. Animal fatthus also total fatis highly correlated with
animal protein (rD0.94), according to a large database on
food and health for different countries (35). This impressive
association therefore suggests that dietary animal protein
could be an equally important cause of cancer, similar to the
conclusion drawn for the association of animal protein with
heart disease discussed above. And because chronic degenera-
tive diseases typically common to Western industrially devel-
oped countries are substantially correlated with each other
(29, 36, 37), this interpretation is likely to apply to these other
diseases as well. An association of protein with cancer is con-
sistent with experimental animal reports from the 1940s and
1950s showing animal protein to promote development of can-
cers of various sites (38–40).
Similarly, in a long series of laboratory animal experiments
in my laboratory, the animal-based protein, casein, proved to
be a powerful promoter of primary liver cancer initiated either
by a powerful chemical carcinogen (41–48) or by a viral car-
cinogen (49, 50). Increasing dietary casein above recom-
mended protein levels (»10% of diet calories) dramatically
promotes tumor formation (»100% of experimental animals)
(41), whereas switching to diets containing low dietary protein
(»10% of diet calories) reverses cancer development (»0% of
experimental animals) (42, 48). A series of many experiments
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FIG. 1. Correlations of age-adjusted breast cancer mortality with total dietary fat (A), saturated fat (B) and polyunsaturated fat (C). Regressions are eyeball,
based on authors findings that total fat (A) and saturated fat (B) were significantly correlated with breast cancer mortality while polyunsaturated fat (C) was not
correlated. This figure is reprinted from Carroll et al. (33). From Carroll KK, Braden LM, Bell JA, and Kalamegham R: Fat and cancer. Cancer 58, 1818–1825,
1986. Copyright Ó2006 by John Wiley Sons, Inc. Reprinted by permission of John Wiley & Sons, Inc. (Continued)
UNTOLD NUTRITION 1079
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on this protein effect illustrated a multimechanistic and highly
integrated network of metabolic reactions converging to pro-
duce the outcome (42, 44, 51–59). This evidence is more than
sufficient to qualify casein, when fed in excess of the recom-
mended level of protein (i.e., the RDA equivalent) as the most
significant chemical carcinogen ever identifiedeither this is
the conclusion or the expensive, highly reductionist govern-
ment-sponsored bioassay program for determining chemical
carcinogens (60) as important causes of human cancer should
be abandoned.
In short, an important role for animal-based protein in can-
cer causation has long been overshadowed in favor of the false
hypothesis that it was total fat and especially animal-based fat
(mostly saturated fat) that causes these diseases (28, 33).
Searching for specific nutrients as independent causes of
heart disease, cancer, and related diseases has been a routine
assumption and practice of long standing, which causes more
confusion than clarity. First, it is the combined, integrated
effects of all nutrients that is far more relevant than the inde-
pendent effects of individual nutrients. Second, in the exam-
ples cited here, although it is acceptable to choose a few
nutrients as indicators of a total diet (as with antioxidants or
dietary fiber indicating plant-based foods or saturated fat
favoring animal-based foods), choosing saturated fat either as
a primary causal factor or as an indicator of a high risk dietary
pattern has proven to be very misleading.
It is not that fat or protein or other individual nutrients do
not have independent and direct-acting properties that could
contribute to increased or decreased disease risk. This is
important information provided by reductionist research. But
this information should not be used out of its context. It should
be used to help explain the larger environment of which it is a
part and to which it contributes.
Early during the history of heart disease, a choice was
made in favor of fat instead of protein as a (or “the”) principle
cause of this disease. This choice has survived for almost an
entire century, becoming embedded in our collective con-
sciousness. The correct choice should have been animal-based
protein, not as a single nutrient causing heart disease or cancer
but, more importantly, as a marker of a diet that causes these
diseases.
This is a highly significant and relevant observation
because diets ever richer in animal protein-based foods also
are ever more deficient in plant-based foods. This exchange
assumes, of course, that total food or calorie consumption is
mostly a zero-sum game. Plant-based foods in the whole food
form are far, far richer in antioxidants, complex (natural) car-
bohydrates, and vitamins while also having lower and more
appropriate concentrations of protein and fat. This dietary pat-
tern sets up a broad and worthy hypothesis involving very
complex causes (e.g., plant-based foods) and outcomes that
offer a frame of reference for interpreting detailed and
FIG. 1. (Continued)
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mechanistic findings of reductionist research. These detailed
findings inform us of the biochemical properties of the partic-
ipating nutrient parts, which either support or deny such a
broad hypothesis, thus helping us to understand the healthful
properties arising from the wholeness of food and dietary
lifestyles.
I believe that focusing on the properties of isolated nutrients
beyond their whole food context is more akin to pharmacol-
ogy; considering whole foods containing countless nutrient-
like substances that act within a natural context describes
nutrition; and limiting our thinking to out-of-context parts
considers only the threads of a tapestry, not the tapestry itself.
Trying to understand nutrition from a perspective of
its parts as if they were acting independently explains why
nutrition is so confusing for so many people, professionals
included. Within this scenario, choosing which specific
nutrients or nutrient combinations are responsible for hypo-
thetical cause-effect relationships offers a long list of choices
whose interpretive analyses are likely to be much more subjec-
tive. Without a biologically plausible context, we risk becom-
ing entrapped in trying to understand the meaning of nutrient
parts instead of the whole diet, or even the whole dietary life-
style. Nutrition, if and when it is understood as a wholistic
(spelling intended) phenomenon, only then can its real mean-
ing be understood and applied.
REFERENCES
1. Lariviere D: Nutritional supplements flexing muscles as growth industry.
Forbes, 2013 Apr 18. Available from: http://www.forbes.com/sites/
davidlariviere/2013/04/18/nutritional-supplements-flexing-their-muscles-
as-growth-industry/.
2. Anonymous: CODEX and Dietary Supplements. Frequently Asked Ques-
tions. (2010).
3. Committee on Diet Nutrition and Cancer: Diet, Nutrition and Cancer.
National Academy Press, Washington, DC, 1982.
4. United States Federal Trade Commission: Complaint Counsel’s Proposed
Findings of Fact, Conclusions of Law and Proposed Order (Docket No.
9175). Report No. 9175 Washington, DC: United States Federal Trade
Commission, 1985.
5. Hooper L, Thompson RL, Harrison RA, Summerbell CD, Ness AR,
et al.: Risks and benefits of omega 3 fats for mortality, cardiovascular
disease, and cancer:systematic review. Brit Med Journ 332, 752–760,
2006.
6. Morris CD and Carson S: Routine vitamin supplementation to prevent
cardiovascular disease: a summary of the evidence for the U.S. Preventive
Services Task Force. Ann Internal Med 139, 56–70, 2003.
7. U.S. Preventive Services Task Force: Routine vitamin supplementation to
prevent cancer and cardiovascular disease: recommendations and ratio-
nale. Ann Internal Med 139, 51–55, 2003.
8. Kaushik SV, Mozaffarian D, Spiegelman D, Manson JE, and Willett W:
Long-chain omega-3 fatty acids, fish intake, and the risk of type 2 diabe-
tes mellitus. Am J Clin Nutr 90, 613–620, 2009.
9. Djousse L, Gaziano JM, Buring JE, and Lee I-M: Dietary omega-3 fatty
acids and fish consumption and risk of type 2 diabetes. Am J Clin Nutr
93, 143–150, 2011.
10. Keys A: Coronary heart disease in seven countries. Circulation 41
(Suppl.), I1–I211, 1970.
11. Keys A: The diet/heart controversy. Lancet, 844–845, 1979 Oct 20.
12. Carroll KK: Experimental evidence of dietary factors and hormone-
dependent cancers. Cancer Res 35, 3374–3383, 1975.
13. Higginson J: Present trends in cancer epidemiology. Proc Can Cancer
Conf 8, 40–75, 1969.
14. Wynder EL and Shigematsu T: Environmental factors of cancer of the
colon and rectum. Cancer 20, 1520–1561, 1967.
15. National Research Council & Committee on Diet and Health: Diet and
Health: Implications for Reducing Chronic Disease Risk. National Acad-
emy Press, Washington, DC, 1989.
16. Select Committee on Nutrition and Human Needs, U.S. Senate: Dietary
Goals for the United States, 2nd ed. Washington, DC: U.S. Government
Printing Office, 1977.
17. Kritchevsky D and Czarnecki SK: Dietary protein and experimental
atherosclerosis: early history. In Animal and Vegetable Proteins in Lipid
Metabolism and Atherosclerosis: Vol. 8. Current Topics in Nutrition and
Disease, Gibney MJ and Kritchevsky D (eds.). Alan R. Liss, Inc., New
York, NY, 1983, pp. 1–7.
18. Newburgh LH and Clarkson S: Production of athersclerosis in rabbits by
diet rich in animal protein. JAMA 79, 1106–1108, 1922.
19. Newburgh LH and Clarkson S: The production of arteriosclerosis in
rabbits by feeding diets rich in meat. Arch Intern Med 31, 653–676,
1923.
20. Clarkson S and Newburgh LH: The relation between athreosclerosis and
ingested cholesterol in the rabbit. J Exp Med 43, 595–612, 1926.
21. Meeker DR and Kesten HD: Experimental atherosclerosis and high pro-
tein diets. Proc Soc Exp Biol Med 45, 543–545, 1940.
22. Meeker DR and Kesten HD: Effect of high protein diets on experimental
atherosclerosis of rabbits. Arch Pathology 31, 147–162, 1941.
23. Kritchevsky D, Tepper SA, Czarnecki SK, Klurfeld DM, and Story
JA: Effects of animal and vegetable protein in experimental athero-
sclerosis. In Current Topics in Nutrition and Disease: Vol. 8. Animal
and Vegetable Proteins in Lipid Metabolism and Atherosclerosis,
Kritchevsky D and Gibney MJ (eds.). Alan R. Liss, Inc., New York,
NY, 1983, pp. 85–100.
24. Sirtori CR, Noseda G, and Descovich GC: Studies on the use of a soybean
protein diet for the management of human hyperlipoproteinemias. In
Current Topics in Nutrition and Disease: Vol. 8. Animal and Vegetable
Proteins in Lipid Metabolism and Atherosclerosis. Kritchevsky D
and Gibney MJ (eds.). Alan R. Liss, Inc., New York, NY, 1983,
pp. 135–148.
25. Messina M and Messina V: The role of soy in vegetarian diets. Nutrients
2, 855–888, 2010.
26. U.S. Food and Drug Administration: Soy Protein and Coronary Heart
Disease. Washington, DC: Food and Drug Administration, Health &
Human Services, 1999.
27. Sirtori CR, Agradi E, Conti F, Mantero O, and Gatti E: Soybean-protein
diet in the treatment of type II hyperlipoproteinemia. Lancet 1, 275–277,
1977.
28. Carroll KK, Gammal EB, and Plunkett ER: Dietary fat and mammary
cancer. Can Med Assoc Journ 98, 590–594, 1968.
29. Wynder EL: The epidemiogy of large bowel cancer. Cancer Res 35,
3388–3394, 1975.
30. United States Department of Health and Human Services: The Surgeon
General’s Report on Nutrition and Health. Superintendent of Documents,
U.S. Government Printing Office, Washington, DC, 1988.
31. World Cancer Research Fund/American Institute for Cancer Research:
Food, Nutrition, and the Prevention of Cancer: A Global Perspective.
American Institute of Cancer Research, Washington, DC, 1997.
32. World Health Organization: Diet, Nutrition and the Prevention of chronic
Diseases: Report of a Joint WHO/FAO Expert Consultation. Geneva,
Switzerland: World Health Organization, 2003.
33. Carroll KK, Braden LM, Bell JA, and Kalamegham R: Fat and cancer.
Cancer 58, 1818–1825, 1986.
UNTOLD NUTRITION 1081
Downloaded by [Cornell University Library] at 19:51 18 January 2015

34. Rose DP, Boyar AP, and Wynder EL: International comparisons of
mortality rates for cancer of the breast, ovary, prostate, and colon, and per
capita food consumption. Cancer 58, 2363–2371, 1986.
35. Armstrong D and Doll R: Environmental factors and cancer incidence and
mortality in different countries, with special reference to dietary practices.
Int J Cancer 15, 617–631, 1975.
36. Campbell TC, Chen J, Brun T, Parpia B, Qu Y, et al.: China: from dis-
eases of poverty to diseases of affluence. Policy implications of the epide-
miological transition. Ecol Food Nutr 27, 133–144, 1992.
37. Rose DP: Dietary factors and breast cancer. Cancer Surveys 3, 671–687,
1986.
38. Hawrylewicz EJ: Fat-protein interaction, defined 2-generation studies. In
Dietary Fat and Cancer, Ip C, Birt DF, Rogers AE, and Metlin C (eds.).
Alan R. Liss, Inc., New York, NY, 1986, pp. 403–434.
39. Hawrylewicz EJ, Huang HH, Kissane JQ, and Drab EA: Enhancement of
the 7,12-dimethylbenz(a)anthracene (DMBA) mammary tumorigenesis
by high dietary protein in rats. Nutr Reps Int 26, 793–806, 1982.
40. Hawrylewicz EJ, Huang HH, and Liu J: Dietary protein enhancement
of N-nitroso-methylurea-induced mammary carcinogenesis, and their
effect on hormone regulation in rats. Cancer Res 46, 4395–4399,
1986.
41. Madhavan TV and Gopalan C: The effect of dietary protein on carcino-
genesis of aflatoxin. Arch Path 85, 133–137, 1968.
42. Appleton BS and Campbell TC: Effect of high and low dietary protein on
the dosing and postdosing periods of aflatoxin B1-induced hepatic pre-
neoplastic lesion development in the rat. Cancer Res 43, 2150–2154,
1983.
43. Appleton BS and Campbell TC: Dietary protein intervention during the
post-dosing phase of aflatoxin B1-induced hepatic preneoplastic lesion
development. J Natl Cancer Inst 70, 547–549, 1983.
44. Dunaif GE and Campbell TC: Relative contribution of dietary protein
level and Aflatoxin B
1
dose in generation of presumptive preneoplastic
foci in rat liver. J Natl Cancer Inst 78, 365–369, 1987.
45. Schulsinger DA, Root MM, and Campbell TC: Effect of dietary protein
quality on development of aflatoxin B1-induced hepatic preneoplastic
lesions. J Natl Cancer Inst 81, 1241–1245, 1989.
46. Youngman LD: Recall, memory, persistence, and the sequential modula-
tion of preneoplastic lesion development by dietary protein. M.S. Thesis,
Cornell University, Ithaca, NY, 1987.
47. Youngman LD: The sustained development of preneoplastic lesions
depends on high protein diets. Nutr Cancer 18, 131–142, 1992.
48. Youngman LD and Campbell TC: Inhibition of aflatoxin B1-
induced gamma-glutamyl transpeptidase positive (GGTC) hepatic preneo-
plastic foci and tumors by low protein diets: evidence that altered GGTC
foci indicate neoplastic potential. Carcinogenesis 13, 1607–1613, 1992.
49. Cheng Z, Hu J, King J, Jay G, and Campbell TC: Inhibition of hepatocel-
lular carcinoma development in hepatitis B virus transfected mice by low
dietary casein. Hepatology 26, 1351–1354, 1997.
50. Hu J, Cheng Z, Chisari FV, Vu TH, Hoffman AR, et al.: Repression of
hepatitis B virus (HBV) transgene and HBV-induced liver injury by low
protein diet. Oncogene 15, 2795–2801, 1997.
51. Adekunle AA, Hayes JR, and Campbell TC: Interrelationships of dietary
protein level, aflatoxin B
1
metabolism, and hepatic microsomal epoxide
hydrase activity. Life Sci 21, 1785–1792, 1977.
52. Bell RC, Golemboski KA, Dietert RR, and Campbell TC: Long-term
intake of a low-casein diet is associated with higher relative NK cell cyto-
toxic activity in F344 rats. Nutr Cancer 22, 151–162, 1994.
53. Bell RC, Levitsky DA, and Campbell TC: Enhanced thermogenesis and
reduced growth rates do not inhibit GGTChepatic preneoplastic foci
development. FASEB J 6, 1395, 1992.
54. Hayes JR, Mgbodile MUK, Merrill AH Jr, Nerurkar LS, and Campbell
TC: The effect of dietary protein depletion and repletion on rat hepatic
mixed function oxidase activities. J Nutr 108, 1788–1797, 1978.
55. Horio F, Youngman LD, Bell RC, and Campbell TC: Thermogenesis,
low-protein diets, and decreased development of AFB1-induced preneo-
plastic foci in rat liver. Nutr Cancer 16, 31–41, 1991.
56. Mgbodile MUK and Campbell TC: Effect of protein deprivation of male
weanling rats on the kinetics of hepatic microsomal enzyme activity.
J Nutr 102, 53–60, 1972.
57. Nerurkar LS, Hayes JR, and Campbell TC: The reconstitution of
hepatic microsomal mixed function oxidase activity with fractions
derived from weanling rats fed different levels of protein. JNutr108,
678–686, 1978.
58. Preston RS, Hayes JR, and Campbell TC: The effect of protein deficiency
on the in vivo binding of aflatoxin B
1
to rat liver macromolecules. Life
Sci 19, 1191–1198, 1976.
59. Youngman LD and Campbell TC: High protein intake promotes the growth
of preneoplastic foci in Fischer #344 rats: evidence that early reemodeled
foci retain the potential forfuture growth. J Nutr 121, 1454–1461, 1991.
60. National Toxicology Program: Report on Carcinogens, 12th ed. US
Department of Health and Human Services, Public Health Service,
National Toxicology Program, Research Triangle Park, NC, 2011.
1082 T. COLIN CAMPBELL
Downloaded by [Cornell University Library] at 19:51 18 January 2015