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” “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 A Revelation Rats Fed Diets Low in Protein Could Die For Number and Percentage of Rats That Spontaneously Died Percentage of Rats 50 10/22 40 30 20 10 0/34 0 High Protein Low Protein 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? Quotes From Campbell in 1972 “The effect of protein deficiency in male weanling “A deficiency of dietary protein rats onshown the activity of the the was to increase hepatic toxicitymicrosomal of aflatoxin enzyme for rats.” system was studied.” 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? How Accurate Is This Dose Vs. Protein Simplification After All? This Chart Is a Little Closer to the Truth But Still Pretty Far… Percent of Liver Volume Ocupied by Precancerous Lesions Campbell Showed That Dose Does Matter After All… 8 At Least 200 µg/day Is Needed to Produce a Meaningful Response 6 4 2 0 0 100 200 300 400 500 Aflatoxin Dose (mg/kg/day on 10 days) The Higher Doses Campbell Used Were Highly Lethal How Much Aflatoxin Does It Take to Kill a Rat? Percentage of Rats Surviving 100 80 60 40 20 0 0 100 200 300 400 500 Aflatoxin Dose (mg/kg/day for ten days) Highly Carcinogenic Doses of Aflatoxin Are Highly Lethal 100 5 80 4 60 3 40 2 20 1 0 0 0 100 200 300 400 500 Aflatoxin Dose (mg/kg/day on 10 days) Percent of Liver Volume Ocupied by Precancerous Lesions Percentage of Rats Surviving All Animals Fed 20 Percent Casein Aflatoxin Detoxification Depends on Protein and Glutathione Depleting Glutathione Pharmacologically Makes Aflatoxin Much More Carcinogenic to Rats Volume of Precancerous Foci (mm3/liver) 150 125 Depleting Glutathione with a Single Dose of BSO Makes Aflatoxin More Carcinogenic to Rats 69% Control Aflatoxin Aflatoxin + BSO 100 75 50 25 12.6fold 2.8fold 0 3 Weeks 10 Weeks 48 Weeks 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 gelatincontaining 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.