The Curious Case of Campbell’s Rats Zeroing In on the Myths Purveyed in Chapter 3 of The China Study Chris Masterjohn, PhD Portland Regional Wise Traditions, September, 2013

“A Revelation to Die For” Campbell tells the story like this.  In 1965, he took a faculty position at Virginia Tech, then still an advocate of animal protein as good, nourishing American fare.  In 1967, he accepted an invitation from a department head at that university to travel to the Phillipines with the task of alleviating childhood malnutrition and making sure peanuts could provide good protein without the potential harms of aflatoxin, a carcinogenic mold toxin with which peanuts are often contaminated.  A shocking revelation then came in two-fold form: first an epidemiological study suggested that liver cancer was rampant among Filipino children and that the “best-fed” rather than the malnourished children were the ones most ravaged by the disease; then, in 1968, ”a research paper from India surfaced in an obscure medical journal” showing that aflatoxin only produced liver cancer in rats when they were fed high levels of casein, a milk protein.  Campbell was surprised and skeptical, but he attempted to replicate these findings, and thus was born his two-decade research program showing that animal protein, but not plant protein, was the single most important trigger that turns cancer “on” like a light switch.

“A Revelation to Die For”

“Turning Off Cancer” With Diets Low in Protein, as Depicted in The China Study

Campbell’s Research Showing “Dairy” Protein Promoting Cancer as Depicted in Forks Over Knives

The China Study: Dietary Protein, Not Carcinogens, Promote Cancer

The China Study: Low Dietary Protein “Turns Off” the Dose Response Between Carcinogens and Cancer

Campbell Mocks the Unrealistic Doses of Carcinogens Used in Cancer Experiments

Campbell Mocks the Unrealistic Doses of Carcinogens Used in Cancer Experiments

Campbell Mocks the Unrealistic Doses of Carcinogens Used in Cancer Experiments

The China Study: Milk Protien (Casein), But Not Wheat Protein (Gluten), Promoted Cancer

The China Study: “Plant Protein” Does Not Promote Cancer

The China Study: Plant-Based Nutrients Protect Against Cancer, Animal-Based Nutrients Promote Cancer

Revisiting the “Revelation to Die For”

A Toxic Revelation: Rats Fed Low Protein More Vulnerable to Aflatoxin Toxicity

A Revelation Rats Fed Diets Low in Protein Could Die For In the very paper (2) that Campbell cites as “a revelation to die for,” showing that a high-protein diet turns the cancer switch to the “on” position, the low-protein diet proved lethal to the animals.  The investigators gave rats a small dose of aflatoxin every day for six months and fed them either a 5 percent casein or 20 percent casein diet.  The experiment carried on for two years, in fact, but they stopped adminstering aflatoxin at six months for the simple reason that half the animals on the low-protein diet had died.  They had typical symptoms of aflatoxin toxicity including liver necrosis (cell death), proliferation of bile duct tissue, and fatty liver.  All the animals receiving 20 percent casein, on the other hand, were still alive at that point.  For the remainder of the two years, the rats receiving 20 percent casein continued to live longer, but many of them developed liver cancer or pre-cancerous changes, while none of the rats fed 5 percent casein developed liver cancer.

A Revelation Rats Fed Diets Low in Protein Could Die For

The China Study: The MFO Drug-Detoxifying Enzyme Turns Aflatoxin Into a Carcinogen

The China Study: Low Protein Decreases the Activity of the Dangerous Drug-Detoxfying MFO Enzyme

Does “Protein Deficiency” Protect Against Cancer Does “Protein Deficiency” Protect Against Cancer? Quotes From Campbell in 1972 “The effect of protein deficiency in male weanling rats on the activity of the hepatic microsomal enzyme system was studied.” “A deficiency of dietary protein was shown to increase the toxicity of aflatoxin for rats.”

Campbell’s Low-Protein Rats Ate Less Food

Campbell’s Rats Should Have Grown From 50 to 100 Grams

Campbell’s Low-Protein Rats Had Very Low Body Weight

Campbell’s Low-Protein Rats Hardly Grew at All

Campbell’s Low-Protein Rats Were Malnourished and Had Fatty Liver – Quotes From Campbell, 1972 “First, the reduced DNA content could be indicative of a lower cell number per gram of liver and would accordingly imply larger cells in the protein-deprived group. These cells could be larger in response to lipid infiltration since the livers of the low protein group were observed to be very fatty. Consequently, the normal rate of cell proliferation would have been decreased during protein deprivation, which is similar to the retardation of brain cell growth of young malnourished animals described by Winick and Rosso.”

A Toxic Revelation – Quotes From Campbell, 1983 Some degree of bile duct proliferation was observed in all animals dosed with [aflatoxin]. However, the groups fed the 5% casein diet during the dosing period had relatively severe bile duct proliferation and cholangiofibrosis [fibrosis of the bile duct]. In these groups, the architecture of the liver was often distorted by fibrous septa. Groups fed the 20% casein diet during the dosing period had mild bile duct proliferation and no cholangiofibrosis.

Protein Deficiency Disappears Down the Memory Hole – Quotes From Campbell, 1991 “Although a 5% casein diet is not generally considered nutritionally adequate (i.e., it does not support maximal growth), for every health index we have thus far measured, the 5% casein diet supports better health in rats than does the 20% casein diet.”

But Don’t We Want Low Protein to Avoid Making Aflatoxin Toxic?

Aflatoxin Detoxification Depends on Protein and Glutathione

Campbell’s Low-Protein Rats Had 40-71% Lower Glutathione

The China Study: Dietary Protein, Not Carcinogens, Promote Cancer

The Protein vs. Aflatoxin Dose Study Was Much More Complex Than Presented in The China Study

How Different Are the High-Protein Low-Aflatoxin and the Low-Aflatoxin High-Protein Groups? Note the Y axis begins at 0.2, minimizing the 0.3% volume of liver occupied by precancerous lesions.

How Accurate Is This Dose Vs. Protein Simplification After All? 9-fold difference!

This Chart Is a Little Closer to the Truth But Still Pretty Far… 3-fold difference! No numbers on y axis. Some how 20/16/12/8/4 turned into all 5%.

Campbell Showed That Dose Does Matter After All…

The Higher Doses Campbell Used Were Highly Lethal

Highly Carcinogenic Doses of Aflatoxin Are Highly Lethal Campbell’s experiments are, of course, much more realistic than this scenario.  If your friend offered you peanut butter sandwiches with 100 grams worth of peanut butter contaminated with the maximum amount of aflatoxin allowed by the FDA, you’d only have to eat 270,000 peanut butter sandwiches for four days to obtain the dose of aflatoxin that produced a “barely detectable response” in Campbell’s study.  Still, 1,125,000 peanut butter sandwiches is an awful lot of peanut butter sandwiches and you’d better have one heck of a toothbrush.  Clearly, exposure to carcinogens is important.

Aflatoxin Detoxification Depends on Protein and Glutathione

Depleting Glutathione Pharmacologically Makes Aflatoxin Much More Carcinogenic to Rats

What Percentage Protein Is Used for the Initiation Period?

High Protein During Initiation to Complete the Detoxification of Aflatoxin

Protein Promotes the Growth of Cancer Already Formed, But Prevents Its Initiation

Chronic Dosing in Monkeys: Protein Protects Against Toxicity at High Doses and Cancer at Low Doses

As in Rats, in Monkeys Fed Chronic Doses of Aflatoxin, Protein Is Protective

This Graph is Missing Something… Lysine supplementation of wheat gluten during the postinitiation period enhanced the gamma-glutamyltransferase-positive response to a level comparable with that of the high-quality protein. These results suggest that one can inhibit the development of foci either by decreasing the quantity of protein intake and holding the quality of the protein constant or by decreasing the quality and holding the quantity constant.

It’s a General Effect of Protein, Not Animal Protein – Quotes From Campbell, 1989 [I]n 1945 Larsen and Heston found that the incidence of spontaneous pulmonary tumors was doubled in strain A mice fed low-casein diets supplemented with cystine (the most limiting amino acid). Silverstone and Tannenbaum (14) showed that the development of spontaneous hepatomas was enhanced in C3H mice fed a gelatin-containing diet when methionine and cystine were added.

It’s a General Effect of Protein, Not Animal Protein – Quotes From Campbell, 1989 A review of the somewhat limited data from these and earlier studies (1) indicated that inhibition of tumor development as a result of marginal intakes of various proteins could be abolished by supplementation with the respective limiting amino acid for each protein. . . .

It’s a General Effect of Protein, Not Animal Protein – Quotes From Campbell, 1989 [O]ur results suggest that the enhancement of focus development by lysine supplementation of gluten is due to a general improvement in dietary protein quality and not to any particular metabolic effect peculiar to lysine. This conclusion is supported by previous work (1, 12-14) showing that various low-quality proteins are better able to enhance tumor development when they are supplemented with the amino acid in greatest deficit.

Campbell’s Curious Rats – Conclusions Adequate protein is necessary for detoxification and other roles of glutathione such as antioxidant defense. Protein protects against cancer in the experiments most closely resembling contexts experienced naturally. There may be a role for restricting protein in someone who already has cancer. There is no qualitative difference between animal and plant protein except that animal protein is more abundant and of higher biological quality.