Do High-Protein Diets Cause Kidney Disease and Cancer? | Chris Kresser
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Do High-Protein Diets Cause Kidney Disease and Cancer?

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protein and kidneys
Do protein sources like this increase the risk for kidney disease? iStock.com/Smitt

It seems like every other week there is a media uproar about the dangers of any number of foods. Lately, the target has been meat – specifically high-protein diets – and its supposed connection to a range of chronic diseases and early death.

I’ve discussed high-protein diets a on my podcast here, but with the recent press surrounding a new study on high-protein diets and cancer risk, there’s been yet another upsurge in concern over their safety.

In this article, we’ll take a look at the research behind three of the most common concerns about high-protein diets: kidney health, cancer, and longevity. By the end of this article, you’ll know what the real danger underlying high meat consumption may be, and how you can easily avoid it by eating a Paleo diet.

Will a high protein diet give you kidney disease and cancer? Find out here! #Paleo #mythbusting

High-Protein Diets Don’t Cause Kidney Disease in Healthy People

Before getting into this, I want to make something clear.

Research does show that high-protein diets can be harmful for people who already have chronic kidney disease, and low-to-moderate protein diets are generally advisable for these patients.

However, just because a low-protein diet can be therapeutic for those with kidney disease, doesn’t mean a high-protein diet causes kidney disease in the first place. (This is the same distinction I made when critiquing Dr. Perlmutter’s broad recommendation for a low-carb diet to prevent neurological disorders.) What I’m addressing here is the notion that high-protein diets cause kidney disease in healthy people—which is not, as you’ll find out, supported by research.

Since one of the main biological roles of the kidney is to metabolize and excrete nitrogen byproducts from protein digestion, many people believe that eating more protein will ‘strain’ the kidneys. This is similar to the argument made against acid-forming diets. There is an upper limit to the body’s ability to metabolize protein (studies suggest that this limit is around 35 percent of total calories), but the brain has specific mechanisms that regulate desire for protein, and these mechanisms are difficult to override through willpower alone. (1)

It’s clear from controlled trials that high-protein diets do induce measurable changes in kidney function. (2, 3, 4) These changes include increases in glomerular filtration rate (GFR) (often referred to as “hyperfiltration”), and an increase in the size and volume of glomeruli, which are the functional filtration units of the kidney. (5) The sticking point seems to be in how these changes are interpreted, because while some researchers view hyperfiltration as a sign of kidney stress and even damage, others view it as the kidneys simply getting better at doing their job.

The best paper I’ve found to explain this issue shows that hyperfiltration is a normal adaptive response to additional protein in the diet, as opposed to a pathological condition that will eventually lead to kidney disease. (6) Pregnancy is discussed as one case where GFR increases significantly, but does not increase the risk for kidney disease.

A more compelling example is that of someone who has donated one of their kidneys, because in these cases, GFR in the remaining kidney increases as an adaptive response and remains elevated. One would expect that if hyperfiltration leads to or indicates kidney disease, increased kidney disease would be found in these patients down the road. However, studies have not found a higher risk for kidney disease in patients with one kidney, even 20 years after donation.

After reviewing all of the published research on high-protein diets and kidney disease, the authors of this paper concluded that while high-protein diets can be harmful for those with kidney disease, they do not harm the kidneys in healthy individuals. Since that paper was published, new studies have tested the effects of high-protein diets on renal function in healthy individuals, and generally, their conclusions are the same. (7, 8, 9)

The Newest “Meat Will Give You Cancer” Study

Now to the primary motivation for this article: the study behind headlines such as “Diets high in meat, eggs and dairy could be as harmful to health as smoking”. In this study, researchers reported a positive association between high protein intake and cancer incidence based on observational evidence from people between the ages of 50 and 65. (10)

However, they found that high-protein diets were actually associated with lower mortality from cancer in people over 65. (In this study, “high protein” was defined as at least 20% of calories from protein.) Importantly, this relationship only existed for animal protein; researchers found no relationship between a high consumption of plant protein and cancer or mortality.

For a thorough critique of this study, I recommend reading Denise Minger’s analysis. As she points out, the oft cited “healthy user bias” is less relevant to this study because protein hasn’t been demonized such that people who eat more protein would be expected to have unhealthy lifestyle habits. In fact, the high-protein participants in the study actually had slightly lower rates of smoking.

The major downside of most observational studies is that they don’t shed light on the mechanisms behind the associations they uncover. On this point, this study is designed better than most. Researchers hypothesized that increased IGF-1 activity due to high protein consumption may lead to a higher instance of cancer and an earlier death, so after observing a positive relationship between these variables, they designed a mouse study to test the mechanism of their hypothesis.

They found that mice eating a higher protein diet (18% of calories) grew larger tumors at a higher rate than mice on a low protein diet (4-7% of calories), and that the high-protein mice had higher levels of circulating IGF-1. (IGF-1 is a hormone that prompts cell growth in almost every tissue of the body.)

This is unsurprising, as earlier animal studies have shown that increasing protein intake (especially from isolated casein, which tends to promote cancer growth more than other sources of protein anyways) increases IGF-1 levels, and it’s well-known that IGF-1 encourages the growth of cancer cells as well as healthy cells. However, as Denise brings up in her analysis, total protein restriction is only one way that researchers have been able to decrease circulating levels of IGF-1 in rodent studies.

Is Protein to Blame—or Is Methionine?

This is also where the issue of longevity comes into play, because increased levels of IGF-1 are thought to contribute to accelerated aging and shorter lifespans. Many early studies found that calorie restriction reduced IGF-1 and increased lifespan in many animal models, in addition to protecting against cancer. (11) Researchers then discovered that restricting total protein—but not total calories—accomplished the same goal, often more effectively than calorie restriction. (12, 13)

Recently, the amino acid methionine was targeted as the primary operator in the protein/IGF relationship, and new animal studies demonstrated that methionine restriction alone was able to reduce IGF levels and extend lifespan. (14, 15, 16) Methionine is an amino acid found primarily in muscle meats and eggs, and I frequently emphasize the importance of maintaining a healthy methionine-to-glycine ratio by consuming glycine-containing foods like bone broth and gelatin.

This evolution of research from calorie restriction to methionine restriction is already fascinating, but here’s the kicker —a study done in 2011 found that supplementing with glycine had the same life-extending, IGF-reducing, health-promoting effects as restricting methionine intake (and restricting protein intake or overall calories)! (17)

Eat the “Odd Bits”!

Granted, this is one study, and it was done in mice. But from an evolutionary perspective, this connection makes perfect sense! Until recently, humans were not getting a majority of their protein from high-methionine foods such as muscle meat and eggs. We just didn’t have the luxury of heading to the nearest grocery store and picking out steak, chicken breasts, and pork tenderloin.

It can be easy to forget when these cuts are all packaged up nicely in the store, but those “prime cuts” used to be attached to bones, cartilage, skin, organs, and all the other odd bits that now usually end up in pet food (so at least Fido is getting his glycine!).

These odd bits (especially liver) also have other nutrients, in addition to glycine, that help the body metabolize methionine, including vitamins B6, B12, folate, betaine, and choline. As is often the case, traditional foods have a range of nutrients that work together synergistically, and whole foods tend to be much healthier when they’re left whole.

So, will a high-protein diet give you kidney disease and cancer? As far as kidney disease goes, the research suggests that the answer is no. But when it comes to cancer and longevity, it depends on the overall context of your diet.

If you’re getting a high percentage of calories from protein, and you eat muscle meats and eggs without glycine-rich foods and organ meats, there is reason to believe you may be at higher risk for cancer. Fortunately, if you’re following the advice I outlined in Your Personal Paleo Code (published as The Paleo Cure in paperback in December 2014) and “eating nose-to-tail”, you need not be concerned about eating a high-protein diet.

How do you feel about the research I presented? Are you planning on making any changes to your diet, or have I simply boosted your confidence that your current diet is appropriate? Let me know in the comments below!

  1. Nutritionfacts.org argues that soy produces the same IGF-1 stimulus as meat, but soy’s methionine to glycine ratio is a theoretically superb: 1.3/4.0, or tofu 1.3/4.6. This could mean there could be another amino acid.

    Glycine can be made from serine, and egg has masses of serine.

    It seems like endless mistakes can be made, trying to beat the diets that we know increase longevity, from older endpoint studies.

  2. As I stand here eating a half cup of raw pecans, I have to say this is what I expected, and I still feel really good about my dietary choices. A friend of mine just had surgery to remove her kidney and a very large, cancerous tumor. She is a smoker and a huge meat eater, but believes she is healthy because she’s interested in natural remedies. She doesn’t want to have chemotherapy, and asked me for some guidance in dealing with her doctor.

    I’m a pescetarian, on a high fat, very low carb, low protein diet, that is high in leafy green vegetables, high fat nuts, avocados, coconuts, and vegetables. When I eat salmon, I eat the whole canned salmon, skin, bones, and all, but I only eat 2 ounces of it.

    What I think would help her is to fast and take advantage of kinase inhibitors as the new “chemotherapy” option. Then adopt the high fat, very low carb diet, and low protein diet that includes the “complete” protein source. Glucose from carbs fuel cancer cells, so very low carb diets and fasting starves them. High protein diets trigger the mTOR pathway, which benefits cancer cells. What you need to do is starve and block them, any way you can. That’s just logical.

    • I dont know if your even going to know I gave you a reply, but eating a high nut diet isn’t necessarily good for you. Nuts like pecans, walnuts and almond have a terrible omega 3:6 ratio and should be eaten in moderation, as to avoid inflammation.

      • You casually toss that in, as though nuts are all I eat. Seriously, my Omega-3/Omega-6 ratio is 50-50, because I carefully select all the fats I include in my high fat, very low carb, high fiber, low protein diet. Between flax oil, krill oil, avocados, goat butter, goat yogurt, coconut oil, my personal supply of free range eggs, the occasional wild caught Alaskan salmon, occasional extra virgin olive oil, and the absence of any other “grain oils”, this diet is so far from the typical modern 1:25 Omega-3/Omega-6 ratio that your comment demonizing the healthy fats of fresh, raw nuts seems to be taking a very narrow view of nutrition. Nuts are much better for you than grains, and grain derived fats. Their carb load is also much lower than grains.

  3. Hi Chris, I SO appreciate you and all you do to help us with health issues that can be so confusing at times. I recently had blood work done and was told today by my Nephorolgist that I have 50% kidney function. In 2009 I donated a kidney and just saw what you wrote here about high protein diets and kidney disease. I think I will reduce my protein intake a bit, but not go crazy. I do love beef and chicken liver, make my own bone broth and consume gelatin.

    Because I have bouts of sugar addiction I wonder what impact that is having on my kidneys.

    I am 66 so I am hoping my one kidney will out-live me!

    Thank you again!

  4. Hi Chris,

    According to Valter Longo, a high animal protein diet is most definitively linked with increased IGF-1 levels in the middle aged population. Don’t you think that the Paleo diet encourages way too much protein consumption? Also, what is the best way to remove phytates and lectins from legumes? I already know that soaking for upto 24 hours and using an acidic medium like apple cider vinegar are helpful. Are there any additional steps that would be helpful?

    Thanks

    • This (from Ray Peat) should make you feel better about glycine”s effect on cancer, Rob: “Glycine … is one of the factors promoting wound healing and tumor inhibition.
      It has a wide range of antitumor actions, including the inhibition of new blood vessel formation (angiogenesis), and it has shown protective activity in liver cancer and melanoma. Since glycine is non-toxic (if the kidneys are working, since any amino acid will contribute to the production of ammonia), this kind of chemotherapy can be pleasant.”

        • It turns out that dietary glycine (as opposed to the glycine made and consumed by cells in the body, including cancer cells) both inhibits cancerous growths and promotes longevity. It is a potent anti-stress nutrient that helps you sleep, too.

    • I can’t answer your question but be aware that Tofu is NOT fermented. The only healthy soy is fermented soy.

  5. Is the paleo diet right if your trying to reduce plaque build up in the Choroid Artery. I am at approx 70% blocked and want to reduce this percentage of blockage. Please respond or send me to the right place to read the answer.

    • Use nattokinase. It is a natural clot buster. It works. I had severe peripheral artery disease and could hardly walk. Nattokinase took away all the symptoms within a month. Been well for last 10 years. There are no side effects and no worry about taking too much. It takes a couple months to remove most of the blockage. Doctor’s Best brand is brand I use.

      Take 4000 FU, 3 times a day on empty stomach for first months and then use when waking and going to sleep. You could also take some serrapeptase with it. Maybe 40,000 IU.

      Long term maintenance is 2000 FU in morning and/or night (before bed is best time to take it).

      If you want to research it further, look up fibrinolytic enzymes. Also look up cholesterol myths.

      My other advice –
      do not take aspirin while taking it.
      do not take vitamin K2 since it is a coagulant while clearing blockage
      do not take blood pressure medications because they can irreparably damage your health.

  6. In the mentioned study of rats on high Lysine diets living longer – the effects is achieved at 8 and 12 % lysine. Assuming a 2000 Kcal diet -this amounts to a minimum of 40g of lysine – this seems to be a very high dose, even if one chooses to supplement?

    • I noticed that too, safe to say it isn’t practical to get that much glycine in your diet. As long as you are consuming as much or more glycine than methionine that should be sufficient to balance out the amino acids and promote clearance of methionine.

  7. chris I think you made a mistake, you said “a study done in 2011 found that supplementing with glycine had the same life-extending, IGF-reducing, health-promoting effects as restricting methionine intake”

    But in the abstract they made no mention of glycine supplementation lowering IGF, rather the health benefits were relating to increasing clearance of methionine.

  8. So do I have to eat my beef and broth at the same meal or can I eat the muscle meat at lunch and the broth for dinner, for example? Thx!

  9. The methionine and glycine content in 3 ounces of fish, meat and chicken are:
    fish 557 mg and 960 mg
    meat 572 mg and 1200 mg
    chicken 586 mg and 1300mg
    source: http://www.wolframalpha.com/input/?i=methionine+content+of+chicken
    you can type in an inquiry for methionine and glycine content there.
    Also see wikipedia methionine article:
    Food sources of Methionine[8]

    Food g/100g
    Egg, white, dried, powder, glucose reduced
    3.204
    Sesame seeds flour (low fat)
    1.656
    Egg, whole, dried
    1.477
    Cheese, Parmesan, shredded
    1.114
    Brazil nuts
    1.008
    Soy protein concentrate
    0.814
    Chicken, broilers or fryers, roasted
    0.801
    Fish, tuna, light, canned in water, drained solids
    0.755
    Beef, cured, dried
    0.749
    Bacon
    0.593
    Beef, ground, 95% lean meat / 5% fat, raw
    0.565
    Pork, ground, 96% lean / 4% fat, raw
    0.564
    Wheat germ
    0.456
    Oat
    0.312
    Peanuts
    0.309
    Chickpea
    0.253
    Corn, yellow
    0.197
    Almonds
    0.151
    Beans, pinto, cooked 0.117
    Lentils, cooked
    0.077
    Rice, brown, medium-grain, cooked

    National Nutrient Database for Standard Reference. U.S. Department of Agriculture. Retrieved 2009-09-07. 0.052
    From Wikipedia

    According to the first source glycine content of fish, meat and chicken > methionine content.

  10. I think that Denise’s analysis is very good, but wonder are a lot of people missing the point; a quick review of the protein study author’s baseline data (not published in the report itself), shows some key elements that make the study conclusions, well, kinda worthless:

    See: http://www.thefatemperor.com/latest-material/

    You need to scroll down to the critique – it’s just below the slides for my latest seminar…

    best regards
    Ivor

  11. So is it established that eating meats and eggs as protein sources will increase risk of cancer and earlier death?

    I’ll strive to eat organ meat or broths once a week.

    I wonder if eating the amino acid mentioned that is more available in other parts of the animals is the only way to offset this.

    If you have a fairly balanced diet, you probably are getting lots of foods and substances that reduce risk of cancer and increase longevity. I wonder if this somehow is enough to offset.

  12. Great article. Thanks. I always have to wonder about how protein studies are done. There seems to be too many uncontrolled variables to really say anything significant based on the findings. Because they are often using proteins isolated from their ‘whole food’ origins it begs the question of whether it’s the isolate or the original food which is damaging to health. Like you say, there’s a synergy between all the many compounds in whole food and by extracting one chemical out are we then really talking about the same thing? There’s also the big question of the source of meat as well. Did the scientists running these studies take efforts to use only grass fed ‘happy’ animals or did they not control for that variable either? The list of questions continues, for sure, and perhaps there are many layers at work here that we are only just beginning to reveal.

  13. Macrobiotic Diet theorized and advocated since their inception in the 30’s, “consumption of whole foods” no matter the location though there emphasis was more cereals, sea vegetables, fish, plant based because of it’s origination in Japan. There argument was to eat all of everything and be healthy whether that be seal in the Aleutians, or fish in the southern Pacific, or algae. Eat local, eat natural, eat fermented, etc. However most people who follow a Paleo diet are unaware how difficult it was to secure and consume large amounts of animal protein throughout our history. Feedlot animals are as foreign to this diet as Fruit Loops. I am a graduate student in Holistic Health at St. Catherine University in St. Paul, Mn studying these issues of alternative nutrition and the impact on our health and society. Cereals are not necessarily the enemy any more than animal protein. Ask the Okinawan’s who have the longest documented and recorded life spans in the world. They eat everything including too much sodium. Nothing consumed is without consequence. Now let’s talk about GMO’s ;0).

  14. Chris- Thanks for the info. The 2011 study (Dietary glycine supplementation mimics lifespan extension by dietary methionine restriction in Fisher 344 rats) is, as far as I can see, a conference publication supplement, and might not even be peer-reviewed. No follow-up work has been done, as far as I gather from a PubMed search — do you know otherwise? Fascinating stuff, though!

    Brian

  15. To complicate the matter, I was just told by my doc that my eGFR numbers now place me in the range of mild kidney failure! But I’m told Medicare tweaked the numbers in order to “try” to detect early and keep people off dialysis as a cost-saving measure. I’ve had the same numbers since at least 2011, but now they show that I’m high risk. I wasn’t eating paleo back then…. but I know my protein intake has increased at least somewhat (but so have veggies!). No idea what to do with that one, so I’ve done the ultrasound recommended (normal) and will do the urinalysis recommended, and then not worry about it! Thoughts?

  16. Could you please consider your article in the context of the mTOR pathway. Nora Gedgaudas in Primal Body, Primal Mind mentions that it is a protein sensor and when protein exceeds our maintenance and growth requirement, the excess levels up regulate the mTOR pathway, which stimulates cellular proliferation, including cancer growth. How is this related to IGF-1? And is there a problem with reducing protein intake to what she suggests at around 25g of protein in a meal (as Dr Rosedale also suggests)? Her dietary approach suggests unlimited above ground vegetables, restricted protein and as much fat as is satiating. Many thanks

    • I was wondering the exact same thing! Have been using Nora Gedgaudas’ PBPM as my main nutritional bible and have reduced my protein to around 25g/meal to keep mTOR from upregulating. Would really appreciate Dr. Kresser’s input.

  17. I was eating bone broth but have had a huge reaction to glutamate so no more bone broth, fermented food or digestive enzymes for me, even eggs now cause me problems – I don’t really know what to do from here. I am not sure if it is worth continuing on with paleo.

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