Dear Mark: Do High Protein Diets Cause Colon Cancer?

High Protein FinalFor today’s edition of Dear Mark, I’m talking about a new rodent study has just been released that seems to identify the general low-carbish, Primal-ish way of eating as bad for GI tract health. I know, I know. It seems odd, especially since so many people get relief from digestive disorders, inflammatory bowels, and irritable guts after ditching grains and eating more animals and plants. I’ve certainly benefited from going Primal, having spent decades of my life being ruled by IBS to enjoying pristine bowel health the last decade and counting. But what do I and millions of others know?

Let’s dig into it.


Have you seen this latest study? A high protein diet gave rats colon cancer. At first glance, it seem pretty scary and damning of a high protein eating style. Can you take a look at it?



You didn’t make this mistake, Carl, but others have asked me about this paper, and before I get started I want to reiterate that it’s not actually testing a low-carb, high-fat diet. It’s an explicitly high-protein diet.

Researchers placed rats on one of two diets: a high-protein (45% of calories), moderate carb (30% of calories) diet or a normal protein (20% of calories), normal carb (56% of calories) diet. Fat was lowish across the board, at around 25%. Rats who ate high-protein ended up with a ton of bad stuff happening in their guts:

  • Lower markers of immune function.
  • Activation of genes involved with tumor creation and promotion.
  • Increased cadaverine (can you think of a more ominous-sounding gut metabolite?), sulfide, and spermine.
  • Reduced butyrate, the gut-protective bacterial metabolite and energy source for colon cells.
  • Lower levels of beneficial bacteria.

They didn’t actually get cancer, but the high-protein diet did increase many of the traditional colon cancer risk factors. It didn’t look good for them. How does it look for you?

Where’d the macros come from? Let’s go through them one by one.

Protein was entirely casein.

Carbs came from a mix of wheat starch, sucrose, and amylodextrin (basically glucose).

Fat came from canola oil.

Fiber came from cellulose.

The rest of the diet came from isolated vitamins, minerals, and amino acids. All in all, this was a highly refined diet. Normally, that’d be an issue as refined diets beget bad results, but both diets were equally refined. So what’s going on here?

Five issues jump out at me.

  1. Previous papers have found that compared to other protein sources, heat-treated (thermolyzed) casein promotes colonic fermentation and creates seemingly harmful metabolic byproducts like ammonia to a greater degree without actually promoting colon cancer. This week’s study also produced deleterious changes that indicated an increase in cancer risk, but no actual cancer developed. Maybe if it were allowed to play out longer, the rats would develop colon cancer. I wouldn’t be surprised. Those gut profiles didn’t look good. But it’s not proof. Not yet.
  2. Casein usually accompanies calcium—think cheese, yogurt, and milk—which has a protective effect against colon cancer. Many animal studies indicate that calcium protects against heme-induced colon cancer. In fact, it’s often only by removing the calcium that researchers can get colon cancer to progress. I found one study that seems to bear this out. Researchers gave cooked Swiss cheese (which they called “heat treated casein”) to rats. Not only did the cheese not cause colon cancer, it protected against it.
  3. 45% of calories from casein is a different beast than 20% of calories from casein. It may be that a 45% protein diet based on casein is too much for the gut to handle.
  4. Casein may only be carcinogenic in the presence of unsaturated oils. In the recent paper, the fat used in both rat diets was highly unsaturated canola oil. In the 1995 paper which found no increase in colon cancer from casein, the fat used was beef tallow (high MUFA, high SFA). I’ve shown in previous posts that colon cancer “triggers” are only triggers in the presence of high-PUFA diets, while diets higher in MUFA and SFA seem to be protective against those same colon cancer triggers. In one study, feeding heme iron to rats promoted colon cancer only when fed alongside high-PUFA safflower oil. Feeding MUFA-rich and far more oxidatively-stable olive oil alongside the heme prevented the colon carcinogenesis. Another recent study had similar results comparing PUFA to saturated coconut oil—heme led to more carcinogenicity on PUFA, none on SFA.
  5. There weren’t any fermentable fiber sources for the gut bacteria to turn into protective butyrate (cellulose is a poorly fermented fiber that produces little to no butyrate). It’s true that the control rat diet didn’t have any either, but they weren’t dealing with 45% of calories from casein. I suspect adding some resistant starch and inulin and other prebiotic fibers to the rat casein diet would have improved the gut profile, if not normalized it.

So, is casein all bad?

No. Eaten in food form as part of an overall healthy diet, casein should be fine.

There’s the Swiss cheese protecting rats from colon cancer.

There’s the fermentation of casein by lactobacillus bacteria (as seen in yogurt and cheese-making) imbuing it with antiproliferative properties in human colon cancer cells.

There’s the latest meta-analysis which found no relationship between cheese consumption (the richest source of casein) and colon cancer, as well as a protective effect of non-fermented dairy. Earlier studies say the same thing.

If you’re obtaining all your protein from isolated casein, stop doing that. Also, don’t only eat cheese. Cheese is amazing stuff, I know.

Eat some fermentable fiber. Feed your gut.

Don’t eat a refined diet. Eat food.

Don’t eat a 45% protein diet, regardless of the source. The occasional day where you binge on steak? Sure. But eating like that for perpetuity is probably a bad idea.

Be sensible.

Thanks for reading, everyone. I hope today’s post helped.


About the Author

Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending more than three decades educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates flavorful and delicious kitchen staples crafted with premium ingredients like avocado oil. With over 70 condiments, sauces, oils, and dressings in their lineup, Primal Kitchen makes it easy to prep mouthwatering meals that fit into your lifestyle.

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