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 three decades researching and 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 Primal/paleo, keto, and Whole30-friendly kitchen staples.

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21 thoughts on “Dear Mark: Do High Protein Diets Cause Colon Cancer?”

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  1. Human beings aren’t rats. I get really tired of researchers running studies on rodents and then inferring that the results apply to people as well. Also, humans do have multiple individual differences due to ancestry, environment, etc. Certainly 45 percent would be excessive for most of us, but some people can and do eat considerably more protein throughout their lives than others without creating health issues for themselves.

    1. What would happen if we gave dogs high carb low protein/fat diets? What would happen if we fed rabbits a high protein low carb diets? What would happen if you fed a tiger nothing but cheese-it’s and KFC every day? Drum roll… They would all probably get cancer and die.

  2. I’ve always equated the primal/paleo diet to a high’ish fat or carb diet with moderate protein. Some people either do high carb primal foods while others stick to high fat. I’ve never seen or heard someone stick to a high protein diet, it’s always moderate based on individual needs.

    But a protein diet fully derived from basically protein powder?? That’s ridiculous, then further to that canola oil and wheat starch.. it kind of puts things into perspective.

    Again, this just falls back on, eating a normal whole foods diet

  3. Today my breakfast micronutrient ratio was this, Fat: 42 grams (23.5 grams saturated) Carbs: 45 grams (6 grams of fiber) Protein: 31 grams. Speaking on the behalf of protein my protein portions will likely decrease for the rest of the day so “high protein” really isn’t my thing anyways. With that being said I don’t think high protein causes colon cancer, I think it has to do with gut flora more then anything. Plus lets face it, we might all love occasional dairy but casein is a pro-inflammatory protein. A little bit in mix with a anti-inflammatory diet (omega 3s, mufa’s, and sfa’s) probably won’t cause any harm. I personally only like grassfed butter and organic heavy cream, to my understanding both of these products are relatively low (or lower) in casein. I do drink full fat goat milk from time to time, but this is filled with A2 casein which is less inflammatory. Goat’s milk is also high in MCTs, which are anti-inflammatory.

  4. It seems that the more you dig into these studies, the more you realize that few of them use real food. I heard of one study that used lard to attempt to prove the dangers of fat, but it was hydrogenated lard. And then these studies are presented to the public, and unfortunately, they buy it. Well, thank heavens for blogs and websites that promote real food. I feel that these sorts of studies need to be discouraged and not funded in the first place. I would like to see the bar raised for protocol.

  5. Thanks Mark for making sense of another ridiculous study. Just eat real food, everyone! And listen to your body…see how you feel. I know I do my best with pretty high fat, moderate protein, and my carbs mostly coming from veggies. Keeps my energy high and good body composition. But everyone is different. And every now and then my body seems to need more carbs, and I listen.

  6. Without monitoring vitamin D levels (particularly in humans) any meat and colon cancer research is pissing in the dark hoping to get more funding.

  7. Could we possibly funnel all this rat-study funding to a more worth while study? Really, does the world need one more rat study with a diet no real person would ever (I hope) eat? I know they’re cheap to do but there are just so many of them!

  8. Thanks for the informative post. So the Atkins Diet is out then? I was on that diet for about three months and lost 25 lbs in that time. I think it was the low carbs that led to the weight loss though. Now I still eat low carbs, lots of veggies, moderate protein.

    1. Atkins diet is high fat and as you know (you did it) you control the carbs until you reach your desired weight.
      Atkins was way ahead of his time, if alive he would be a champion of the Paleo thing. There are videos of Atkins stating that he ate more greens than many vegetarians. And when presented with the question of the high protein he said that his diet was high fat.
      He gets little credit these days, good that Taubes set the record straight in Good Calories and Bad calories.

  9. Sisson, you say “4.Casein may only be carcinogenic in the presence of unsaturated oils”. However, the rats were fed canola oil, which is mostly mono – 63 percent and 7 percent sats. So this isn’t really a valid argument.

    1. But it is unsaturated, so I’m not seeing how that statement is incorrect?

  10. Why do people get concerned over one study? There are tons of different results for similar experiments. High bacon rats have low incidence of polyps versus other meats; calorie restricted high protein have slower aging, more muscle, and more strength, but in other studies low protein have slower aging. It’s important to try and understand why things happen, instead of coming to a new conclusion every time you read something new.

    1. No, why be so sensible?! Here’s what you do instead – read one study or find one plausible dietary concept, become convinced it’s going to solve everything – first for you, then the world – start a blog evangelising about it even though you’ve only done it for 3 days. Presume anyone who doesn’t have the same idea is dumb, or better yet, has a sinister agenda, possibly ruled over by alien lizard lords.

      Spend 6 months eating the very limited palette of foods the diet concept permits, until deficiencies/intolerances occur, have a breakdown, find new method that’s opposed to this (which will rapidly calm symptoms caused by previous insane diet, until it goes on to cause its own problems later on) – rinse and repeat.

      And thus we have an internet filled with nonsense that not only leads people into increasing degrees of neuroticism round food, but also implies that there must be a one single RIGHT way to do things, furthering and spreading the pattern….

      One thing I like about MDA and the whole primal concept is its marked difference from that approach.

  11. Hey mark, I’m surprised you didn’t reference this study..

    “This study provides the first insight into the potential of animal tissues to influence large intestinal fermentation in a strict carnivore, and indicates that animal tissues have potentially similar functions as soluble or insoluble plant fibers in vitro”

    Not sure if i originally found this on caloriesproper or from a link here..

    I know you’ve always been a champion of eating from the rooter to the tooter. Casein as the only dietary protein certainly doesn’t sound paleo.

  12. Mark,
    I was thinking about the formula you suggest for finding a person’s target zone for aerobic training. In the Primal Blueprint 21-Day Total Body Transformation, you use 208 minus (0.7 times age) = Estimated Maximum Heart Rate. I like it because it does give me something to help me guide my workout. However, I am wondering about the age factor. Is that an accurate way to figure the heart rate out? For instance, while someone might be 56 years old chronologically, might they physically be the equal of a 50 year old or even a 46 year old? It just seems like some people could be under training. Maybe I’m just over thinking this too much.

  13. All ihad to read was ” high protein, canola oil and grains included”

    Well duh…of course they got those conclusions.

    Anyone who wants to assure themselves…read jeff volek and stephen phinney’s research. Listen to lectures on youtube.

    Low carb MODERATE protein of healthy sources, and keep your fats real. Butter coconut, olive and clean fed animal and fish protein.

    This study was doomed to fail to provide any good science from the get go.only make lowncarb look bad. I’d like to see what happens if they did it again and removed only canola oil. And again removing only grains..and then again replacing fat with real fats and removing grain totally.otherwise it tells us nothing. Except someone got paid a grant to have a job to go to for a few years and was able to pay their mortgage.