High protein diets may lead to higher levels of diabetes, cancer and all-cause mortality

Healthy diet plan / Category / Emile Du Toit / May 9th 2014

In the on-going feud (let’s face it that is what it is) between low carb and low fat diets protein has been largely neglected. Well, in a way most have seen protein intake as a positive, muscle building, fat reducing thing that is either positive or benign. Certainly high protein consumption appears to be one of the factors that leads to weight loss, irrespective of carbohydrate or fat intake. The caution has always rather been around whether there was large amount of saturated fat attached to the protein!

New research shows that protein may not be that safe

It now appears though that protein – in the amounts that we tend to ingest it – might not be that safe after all. Certainly not for people under 65!

If this is the case it would place a very large spanner in the spokes of the low carb diet bicycle!

The basic theory around why high protein consumption leads to higher mortality and chronic illness

It has been reported that high protein consumption might contribute to disturbance of glucose metabolism through higher insulin, higher BCAA’s, mTOR activation, poorer cell mitochondrial energy and higher IGF-1 values. Now this may appear to go against much of what was reported in the article tracing research on low carbohydrate diets and diabetes, as it needs to be remembered that calories have to come from somewhere so low carb generally means high fat and high protein!

However, the difference is that most of that research was short term. This theory considers the longer term ramifications of a high protein diet. Most of the research in this area is recent and very much cutting-edge.

Earlier research

A study in 2010 examined 38,094 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-NL study, and compared protein intake to incidence of diabetes. During the 10-year follow-up period cases of diabetes were reported and diabetes risk assessed. Mean protein intake was 75.7 g/day; animal protein accounted for the majority. The main contributors to protein intake were meat (39%), milk products (29%), and cheese (1 8%) for animal protein, and bread (43%), fruit and vegetables (1 4%), and potatoes (9%) for vegetable protein.

It was found that diabetes risk significantly increased with protein consumption, as well as with animal protein consumption! There was also a positive, but non-significant trend with diabetes risk and vegetable protein.

Increasing general protein intake by 5% at the expense of 5% carbohydrates increased risk of diabetes by a very significant 30%!

This was actually quite a powerful, prospective study with good methodology, good sample size and a long follow-up period. Several studies in the past had found significant correlations between red meat intake and diabetes risk, but had not examined animal protein consumption in general.

The 2014 mouse study examining higher dietary protein and diabetes risk

This study examined 858 mice on 25 diets with differing ratios of protein to carbohydrates (fat stayed constant). Those that ate higher protein ratios were leaner but didn’t live as long. In fact median lifespan increased by about 30% from 95 – 125 weeks as the protein-to-carbohydrate ratio decreased. On the other hand amount of calories consumed had no effect on lifespan.

Insulin production was influenced by both protein and carbohydrate consumption and was lowest when protein consumed was also lowest. Branch chain amino acid (BCAA) levels correlated positively with protein intake, whilst most other amino acids correlated negatively. This may imply that BCAA’s aid in amino acid absorption. The activation of mTOR was positively correlated with protein intake, with the actual correlation being significant but quite small. Low protein intake was also correlated with higher mitochondrial activity in the liver and higher levels of free radicals.

Diets low in protein and high in carbohydrate were also associated with lower blood pressure, improved glucose tolerance, higher levels of high density lipoprotein (HDL), lower levels of low density lipoprotein (LDL), and lower triglycerides – all markers of improved health. They were also associated with a few potentially poorer health outcome measures such as higher body fat, lower body lean muscle and fatty liver.

Without getting too technical (well okay it is a little technical), it appears the mechanism for high protein reducing lifespan is theorized to be the following: As the protein/carbohydrate ratio increased, there were concomitant increases in hepatic (liver) mTOR activation, which appear linked with the combination of elevated circulating BCAAs and elevated insulin (which results in low blood glucose). Many studies have already shown that activation of mTOR is pro-aging (i.e. shorter lifespan). Chronic exposure to high-protein, low-carbohydrate diets resulted in the lowest food intakes, but elevated both mTOR and insulin, with reduced lifespan.

The 2014 human study examining higher dietary protein and diabetes risk

This 18-year human study also compared protein intake with risk of mortality, tracking 6381 adults aged 50 and over. What was discovered was that consumption of low protein diets promoted longer lifespans in persons under 65, whilst this reversed in those over 65.

Amongst those in the 50-65 (also 45-65) age group higher protein intake was correlated with 4X the mortality rate from cancer and a 74% increase in all-cause mortality. Those people consuming plant protein had 3X the mortality rate from cancer, but no increase in risk of all-cause mortality.

By controlling for protein levels they were able to show that animal protein intake promotes mortality, with vegetable protein being a neutral rather than protective factor.

By the way for those of you out there thinking that high protein consumption means ingesting masses of the stuff and therefore doesn’t include you, this is not necessarily the case. In fact the high protein group in this study was made up of people getting 20% or more of their calories from protein. Those consuming moderate levels of protein consumed anything from 10% but less than 20%, and had a 3X higher mortality rate from cancer.

It is interesting to note that - only for those in the group with high protein consumption – they had even higher levels of cancer and all-cause mortality if they also happened to have high levels of human growth hormone (IGF-1).

Now the cancer protective effect of a low protein diet makes a lot of sense if we consider that in the mouse study the changes caused by reduced protein levels had a potent protective effect against tumors. In fact, this protective effect was potent enough to prevent the establishment of tumors in 10%–30% of the mice (depending on duration), even when 20 000 melanoma cells were implanted at a subcutaneous site. Not only did some mice not develop tumors (all the mice on a high protein diet did), but the tumors in the low protein mice grew significantly slower.


It can be concluded from these studies that higher levels of protein consumption may lead to higher levels of insulin-like growth factor 1 (IGF-1), higher insulin levels, higher levels of BCAA and other factors, and these in turn activate the mTOR signaling pathway. Over-activation of the mTOR signaling pathway leads to insulin resistance and therefore diabetes, as well as cancer and other diseases. Therefore, higher protein consumption may well place one at significantly higher risk of a reduced lifespan.


  1. Levine ME, Suarez JA, Brandhorst S, et al. Low Protein Intake Is Associated with a Major Reduction in IGF-1, Cancer, and Overall Mortality in the 65 and Younger but Not Older Population. Cell Metabolism. Published online March 4 2014. http://dx.doi.org/10.1016/j.cmet.2014.02.006
  2. Sluijs I, Beulens JW, van der A DL, Spijkerman AM, Grobbee DE, van der Schouw YT. Dietary intake of total, animal and vegetable protein and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-NL study. Diabetes Care. 2010 Jan; 33 (1): 43-48. Epub 2009 Oct 13.
  3. Solon-Biet, Samantha M. et al. (2006). The Ratio of Macronutrients, Not Caloric Intake, Dictates Cardiometabolic Health, Aging, and Longevity in Ad Libitum-Fed Mice. Cell Metabolism, Volume 19, Issue 3, 418 - 430

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