Inside Dr. Campbell’s Lab
What happens when rats eat animal protein, and does it make a difference for us?
Welcome to Part 2 (of 7) of our special series about holistic nutrition and some of the research behind the Whole Food Plant Based Diet. To learn more about the series, check out the Introduction here, where I explain how this project is something very different than yet another polemic for or against veganism!
These posts are much longer and far more complex than what I usually post at The Healthy Jew. You might find them boring – or the most interesting thing you’ve read in months. (To keep things simpler, I’ve taken out the sources from the online post - you can find them in the PDF version at the end.)
If this isn’t your cup of tea, we’ll be back soon with concise, practical guides for Jewish wellness and the Land of Israel.
In the meantime, check out this week’s Mishpacha Magazine feature about my work here at Healthy Jew. Their super-talented team really made it come alive!
And of course don’t forget to check out my new book, Land of Health: Israel’s War for Wellness, to learn in detail how Israel is the healthy body of the Jewish people, together with practical strategies for living well during challenging times.
By the way, the ebook is now also available for a crazy cheap introductory sale price of $1.99!
Now let’s get to business…
In the late 1960’s, Dr. T Colin Campbell was hard at work in the Philippines, looking for nutrition solutions for malnourished children.
But lack of food wasn’t his only problem: liver cancer rates were skyrocketing because staple foods, such as peanut butter, were heavily contaminated with the potent carcinogen aflatoxin.
Yet when Dr. Campbell discussed the issue with a local doctor, he was surprised to learn that liver cancer was predominant in the wealthiest families, those who “ate what we thought were the healthiest diets… like our own meaty American diets.” Assuming everyone was consuming similar amounts of tainted foods, why would the ones eating the most protein get the most cancer?
This finding, anecdotal as it was, was very strange. It flew in the face of the fact that worldwide liver cancer rates were highest in the countries that eat the least protein, a fact which had even caused researchers to think that protein deficiency is the cause of the disease. Why in the Philippines were the most robust, well-fed, children falling prey to a cancer that usually strikes only adults?
The Indian Study
Then an Indian group published a fascinating study about rats who were fed the same amount of aflatoxin – but different amounts of protein. The ones who ate 20% protein all got liver cancer (or its precursors), while not a single animal on a 5% diet had any sign of the disease.
A proper laboratory experiment was pointing the finger at protein as a possible culprit of carcinogenesis, right in line with what the Filipino doctor reported from his clinical experience with the same risk factor.
Dr. Campbell was very intrigued. Today everyone knows the research showing the dangers of nitrites, a common preservative for meats. How do we know that those chemicals are deadly? Part of the evidence is that 35% of animals given a low dose of nitrites died from throat cancer – but that low dose is the equivalent of a person eating 270,000 bologna sandwiches a day for thirty years. Imagine if a chemical would give 100% of animals cancer, and its absence would reduce rates to zero. That’s exactly what the Indian study had found with protein!
Like any good scientist, Dr. Campbell didn’t jump to conclusions from a single laboratory experiment and his anecdotal experience in the Philippines. Perhaps the experiment’s result was unique to rats. Maybe other nutrients were skewing the data.
Although The China Study doesn’t mention any specific reservations about what the author observed in the Philippines, it’s worth noting that there are several other obvious explanations for what he saw. Perhaps those wealthy families with a more American diet had become Westernized in other ways known to be risk factors for disease, such as less exercise and eating more processed foods. Maybe they simply were able to afford more aflatoxin-laced peanut butter. So while it’s indeed an interesting observation, I don’t know why at this early stage Dr. Campbell even thought to point specifically at protein.
For whatever reason, Campbell decided that his experiences suggested that the Indian researcher’s results must be investigated – in both animals and humans, and with a variety of test models. And investigated they were. Dr. Campbell and his team spent the next two years conducting NIH-funded laboratory tests on protein’s link with cancer and then led a landmark study on humans in China.
Before we examine these next two stages of Campbell’s research, I’ll note that despite Dr. Campbell’s own caution at this point, Chris Masterjohn, one of The China Study’s first critics, is already crying foul. He dug up the Indian research and found a quite different narrative than reported in The China Study.
In his article on this stage of the WFPB diet’s development, The Curious Case of Campbell’s Rats, Masterjohn reports that the low-casein rats too suffered an early demise – just not as much from liver cancer. He analyzed at length another paper from the same group that showed the low-casein rats to have much more non-cancer liver damage due to the direct toxicity of the aflatoxin. In fact, they stopped giving the low-protein animals aflatoxin a quarter of the way into the experiment simply because half of the animals had died from aflatoxin poisoning.
Cancer Initiation and Growth with Casein
Dr. Campbell’s own initial experiments with rats showed that decreasing their protein intake (from 20% to 5%) reduced the aflatoxin-caused initiation of cancer on the cellular level. This was observed to be happening in several biological mechanisms, suggesting that the body has multiple systems of defense against cancer initiation – which are all strengthened by eating less protein.
Dr. Campbell then turned to look at protein’s effect on cancer growth by observing “foci,” clusters of cancerous cells that eventually develop into tumors. His experiments showed that the levels of foci closely corresponded to protein intake, regardless of carcinogen exposure. Even highly exposed rats had fewer foci than less exposed ones who had received higher doses of protein. They even found that foci growth can be turned on and off by alternating between higher doses and lower doses of protein.
Perhaps the most striking finding was the large amounts of foci found in animals who had received low protein immediately after aflatoxin exposure and only later got the higher protein dose. This suggests that the body “remembered” the earlier exposure, and waited around until there was enough protein to then develop cancer.
Until this point, Dr. Campbell and this team had experimented by switching between two fixed amounts of protein, 5% and 20%. They then checked what would happen with other protein doses, ranging from 4%-24%. They found that no foci developed until around 10% or 12%, the amount necessary to sustain their appropriate body growth rate, but after that, their levels increased dramatically as protein was added. This is very relevant for humans because we too are recommended to get 10% protein - but instead in America consume 15-16%. Such animal studies suggest that our high protein intake puts us at risk for cancer.
But do all proteins promote cancer equally? Dr. Campbell tested gluten (wheat protein) or soy instead of milk-derived casein. These plant proteins didn’t cause any foci in the aflatoxin-exposed animals.
Finally, they experimented over two years with full-fledged tumors. As with the earlier experiments, the exposed rats were fed with different amounts of casein (either 5% or 20%), and some of the protein amounts were switched in the middle. Again, the levels of cancer directly corresponded with protein intake.
From Casein to Milk, And From Milk to Animal Foods
So far, all of Dr. Campbell’s experiments with animal protein were with the primary protein of milk, casein. For them to be relevant for humans regarding general protein intake, we must accept two assumptions: that all animal proteins are like casein, and that whole animal foods act in the body in the same way as one of their isolated proteins. We haven’t seen any evidence for either claim.
And to his credit, at this point in the story, Dr. Campbell mostly sticks to describing what he directly observed about casein and liver cancer. He hasn’t yet indicted all animal foods for all cancers.
The China Study itself tacitly acknowledges the limitations of these studies:
Even though I became convinced that increasing dietary casein promotes cancer, I still had to be wary of generalizing too much… I wanted to broaden my evidence still more. Perhaps these findings were a seed that might expose a far greater truth. What effect did other nutrients have on cancer, and how did they interact with different carcinogens and different organs? Might the effects of other nutrients, carcinogens, or organs cancel each other, or might there be consistency of effect for nutrients within certain types of foods?
We’ll return soon to Campbell’s attempts to expand this observation to animal protein in general. For now, we’re still contemplating the “seed” from which the other experiments germinated: can these two assumptions possibly be correct?
The China Study’s critics already claim that the data suggest that both are probably wrong.
Recent research has shown that whey (another milk protein) protects from cancer in situations like those that indicate casein. This finding, argues Denise Minger, demonstrates the fallacy of inferring from casein to all animal foods: not only aren’t all animal proteins created equal, but even within milk some proteins act differently than others. The whole food called milk is a particularly poignant example, for the whey and casein inside it may work together in synergy, the former cancelling out the latter’s cancer-promoting properties.
Besides lacking all sorts of other nutrients contained in milk, the casein used in experiments is a heavily processed product, quite a different thing than its natural form. Who knows how its chemical structure might be altered by low-temperature dehydration, high-temperature spray-drying, and more?
Perhaps the most disturbing implication of the jump from casein is breastfeeding, for human breast milk also contains lots of casein (although less then cow’s milk). Must we put all of our children on soy formula? As Minger put it, “does nature really muck it up that much?” If casein is so dangerous, all mammals are in deep trouble.
Denise Minger adroitly observes how these problems point to a larger, more disturbing flaw: Dr. Campbell’s premise is made of the very reductionism that he so strongly wishes to repudiate. As we saw earlier, his philosophy of nutrition is built around the principle of “wholism,” the belief that complete foods contain much more than the individual molecules that we might observe inside them. We’ll see later how he even wrote that evaluating individual chemicals instead of whole foods is simply “idiocy.” So why should casein – an isolated nutrient – incriminate all animal foods?
An Alternative Explanation
The critics aren’t only bothered by the proof’s weakness. Both Denise Minger and the nutrition reviewers at Red Pen Reviews have another explanation for Dr. Campbell’s findings, which according to his own line of reasoning would expand the group of guilty foods to include many whole plant meals.
In both situations where low protein dosage was shown to protect from cancer, the animals were fed protein-deficient diets. The low-casein rats ate a high-quality protein in insufficient quantity, and the gluten rats had a protein that was missing one of the essential amino acids, lysine. What does this show? That cancer can be prevented by starving animals from a macronutrient that is critical for their growth and metabolism, perhaps because rapidly-dividing cancer cells need large reserves of high-quality protein in order to proliferate.
In a chart that shows how the rates of cancer skyrocketed exactly when the rats reached the threshold of their protein requirements, The China Study itself seems to support this alternative explanation: not just any reduction was protective, but only when it was less than needed to maximize growth rate. Moreover, Minger dug up a study in which Campbell himself found that when the wheat protein when completed into a full protein (by adding lysine) it promoted cancer just like casein. (The China Study mentions that soy – a high-quality plant protein – also protected from cancer, which would suggest that whole plant proteins are indeed protective. But there is no reference provided, and the Red Pen reviewers weren’t able to locate such a study.)
This explanation would render these experiments irrelevant in the real world where people consume a variety of foods. Even people who eat no animal products will get the full spectrum of amino acids by complementing plant proteins. And if there is something healthful about the act of eating an incomplete protein, meat eaters can also get that benefit by including some plant protein in their diet.
(Masterjohn suggested a third, more speculative, interpretation for Campbell’s animal studies.)
What Happened to the Low Casein Rats?
One might still argue that these experiments indeed show the danger of eating significant amounts of any full protein, no matter what its source. Perhaps we will all remain cancer free if only we’d limit our protein intake to what’s found in tiny amounts of animal foods and larger quantities of uncomplemented plant foods. You can have bread or beans, but not both!
In other words, maybe Dr. Campbell’s studies ought to challenge nutritionists to reevaluate our understanding of protein requirements.
Obviously, the first thing to look at is the health of the supposedly protein-deficient rats: if they had less cancer but starved to death, it’s not much of a tradeoff. But Dr. Campbell reports that the low-casein rats were healthier in every way; they lived longer, were skinnier, and had healthier hair coats. Perhaps most significantly, they exercised on their spinning wheels twice as much as the high-protein ones.
Yet Chris Masterjohn isn’t convinced. He analyzed Dr. Campbell’s academic papers about these and other animal experiments and found quite a different story. In his first paper on the subject, published in 1972, Dr. Campbell’s primary subject of research was how protein deficiency affects aflatoxin toxicity, not cancer promotion. He found that the 5% protein rats hardly grew at all, developed fatty livers, and were indeed much more susceptible to poisoning from aflatoxin and other toxins. He published similar findings throughout the 1970’s.
Why does The China Study’s portray the low-protein animals as a picture of perfect wellness? Because Dr. Campbell later switched the strain of rats to one that’s more immune to fatty liver. This is quite disturbing when considering the relevance of these studies: if rats differ from one strain to another in their protein requirements, who says we can extrapolate anything from them to humans?
(As an aside, Dr. Campbell observes how people too indeed feel sluggish after a high protein meal, indicating that this might be another reason to eliminate animal foods. And in his discussion on the topic of obesity, Dr. Campbell returns to this observation in rats as proof that a plant-based diet lowers weight since those animals exercised. But I wonder if, to the contrary, this all might dig yet another wrench into his conclusions: maybe the high-protein rats got more cancer and were fatter because they were sedentary? Real people living in the real world can choose to exercise despite eating protein-dense meals, saving themselves from cancer and obesity.)
Sandwiches by the Million
Masterjohn and Minger still aren’t finished with challenging these experiments’ relevance to human nutrition. They took a close look at the dosage of aflatoxin that Campbell gave his rats and found it was equal to a person eating 1,125,000 contaminated peanut butter sandwiches within four days. With this huge amount of cancer initiator, protein intake was found to affect cancer promotion. Since humans aren’t usually exposed to such use amounts of carcinogens, who says that our dietary protein affects cancer rates at all?
In fact, the Indian researchers had also done studies with much lower aflatoxin exposure, and the results were the opposite: the low-protein group was the one with the tumors! They suggested a complex biochemical explanation of this anomaly which is way beyond our purview. But the basic idea remains that at practical levels of aflatoxin contamination, there’s no evidence that protein promotes cancer – if anything, it protects from it.
This all is quite strange of Dr. Campbell. As we saw, he’s cynical of people that make a big deal of nitrites that only at an insanely high amount gave rats cancer, implying that we ought to shift our phobia from salami’s preservatives to the salami itself. But he too only found that casein promotes cancer that was initiated by unrealistic amounts of aflatoxin!
In fairness to Dr. Campbell, I’ll note that he also experimented with another, more practical initiator of liver cancer, the hepatitis B virus. Here too he found that the animals who received more casein had more cancer. Although The China Study only mentions this experiment to show that other carcinogens also act like aflatoxin vis-à-vis protein, it also suggests that whatever protective affect low-casein diets have towards liver cancer can apply to real-life situations.
Other Cancers and Nutrients
As we saw earlier, Dr. Campbell was cautious not to draw conclusions about all animal foods from casein alone, instead using them as a “seed” from which further investigation can sprout. Therefore, although The China Study focuses on casein’s effect on liver cancer promotion, the book also tells about other experiments involving more diseases and nutrients.
After what seen about the “seed’s” dubious quality, those additional experiments are ever more crucial. If they show how various animal foods promote various cancers at all sorts of levels, while various plant proteins are widely protective, Dr. Campbell might still be noticing a genuine pattern that can’t be easily explained away by protein deficiency or the isolation of nutrients from their natural contexts.
Dr. Campbell first reports that another research group found that increasing casein promoted breast cancer in rats that had received two experimental carcinogens.
That finding, together with his own earlier experiments, led him to observe the following:
An impressively consistent pattern was beginning to emerge. For two organs [liver and breast], four carcinogens [aflatoxin and HBV in liver, two in breast], and two species [rats and mice], casein promotes cancer growth while using a highly integrated system of mechanisms. It is a powerful, convincing, and consistent effect.
I’m not too impressed by this purported pattern. While there is some variety of organs and cancer initiators, they all point at casein as the promoter, an argument which we’ve seen is riddled with holes. And for all their differences, rats and mice are fairly similar critters.
But now comes Dr. Campbell’s clincher. Because of his reservations about overgeneralizing from casein, he indeed studied how other nutrients affect cancer growth. Yet The China Study devotes less than a page to these critical studies, which is a bit unfortunate considering the numerous weaknesses of the earlier experiments. But we’ll have to deal with what we’ve got.
We’re told that Dr. Campbell and his team conducted studies with “fish protein, dietary fats, and the antioxidants known as carotenoids.” All of them showed that nutrition is a much stronger indicator of cancer promotion than the amount of the initial carcinogen. In a consistent pattern, “nutrients from animal-based foods increased tumor development while nutrients from plant-based foods decreased tumor development.”
This is an important claim, particularly the fish protein one. That’s really the only other animal protein that was tested; the fats and antioxidants were both plant-based and didn’t involve protein. (Whatever cancer-inhibiting properties Dr. Campbell found in plant extracts are interesting, but don’t support the claim against all animal-based protein, because it’s possible to eat protein from both animal and plant sources.) What does that fish study show? Is this finally the proof that the casein studies indeed tell about the dangers of all animal foods?
Not quite. In fact, that study didn’t compare high fish protein with low fish protein at all. Instead, it compared the following three groups: casein with corn oil, fish protein with corn oil, and fish protein with fish oil. The first two groups had similar amounts of tumors, although we can’t really know if the promoter was the fish protein or the corn oil (which has been shown to promote cancer). In fact, there might not have been any dietary factor that promoted cancer; maybe it was the carcinogen alone that did them in. We also don’t know if adding or reducing these animal protein doses would have changed the results, because all the groups had the same amount of protein and fat (20% respectively). And we certainly don’t know anything about plant proteins, because there weren’t any.
The study’s interesting finding was in the third group: they had significantly less cancer than the others, which the researchers attributed to a protective effect of the fish oil. Denise Minger added that this might be more than the fish oil itself; perhaps it neutralizes whatever cancer-promoting capabilities that fish protein really might have, similarly to what she suggested earlier about casein and whey. Considering that fish protein and fish oil are much closer to the whole food call fish, that’s not such a radical proposal. So if this study shows anything about animal protein and cancer promotion, it is that proteins aren’t healthy when removed from their natural context. It would be very interesting to see what would happen to rats that are fed casein together with milk fat.
Whatever the story with the fish oil, this study proves nothing about the dangers of animal foods. The cancer levels might have had nothing to do with animal protein; even if they do, we might as well conclude that it’s better to eat animal foods in their natural form.
In Conclusion…
What should we take away from Dr. Campbell’s laboratory experiments? Do they provide sufficient evidence for us to consider dropping all animal foods from our diets?
I’d conclude that even if only half of the critics’ arguments are well-founded, Dr. Campbell’s “pattern” seems terribly overextended.
Here’s how Masterjohn summed things up:
Before we can make any dietary conclusions from these studies, we need to understand the mechanism. Is the effect of protein the intrinsic property of any complete protein, or does it depend on other nutrients? None of us consume 20 percent of our diet as casein, wheat gluten, freeze-dried cod protein, or any of the other proteins Campbell tested. Many of us drink milk, or eat meat, fish, bread, legumes, fruits, vegetables, and other whole foods. What are the effects of these whole foods on cancer? This is a question that cannot be answered from Campbell’s rat studies… Campbell’s research is in fact fascinating, but without answering these deeper questions, it is difficult to interpret. One thing is certain: low-protein diets depressed normal growth, increased the susceptibility to many toxins, killed toxin-exposed animals earlier, induced fatty liver, and increased the development of pre-cancerous lesions when fed during the initiation period of chemical carcinogenesis…”
But The China Study’s author has a different view of his critics. In the book’s second edition, he notes how his million-plus readers have reacted in very different ways to this chapter. Two groups of people said “that’s it!” – one by changing their diet and the second by stopping to read. He believes the difference between them isn’t because they evaluated the evidence differently. Instead, for the first group “the thought that their most revered nutrient, when consumed in excess, enhanced development of their most feared disease, was enough to alter their eating, no further explanation needed.” But the second one was too “deeply embedded in cultural dietary practices,” so they went “on a tirade of questioning why this research was ever done in the first place.”
All that being said, Dr. Campbell knew that he needed more proof. Since all the evidence was obtained from animal studies, questions remain about the “quantitative relevance” for people: do these conclusions apply to all humans in all situations, or only to a few people in unique situations? Does animal foods promote a thousand cancers a year, or millions? To study this, Dr. Campbell needed to observe large cohorts of people with similar lifestyles and genetic backgrounds but different disease occurrences.
Here’s a PDF version of this post along with all the footnotes:
