Introduction & background

Early last March a provocative study published by Levine et al. [1] in the prestigious Cell Metabolism has really shaken up the nutritional science world ever since one of the authors of the study suggested that eating a diet higher in protein is potentially more harmful than smoking cigarettes. Talk about rustling some jimmies!

Now, before we go any farther, let’s keep one thing in mind: this was not a randomized controlled trial wherein participants were randomly assigned to either high or low protein groups and followed for a period of time at which point various health outcomes could be tallied and assessed. No, instead this study was part epidemiological and part rodent research, each of which has their own serious limitations when extrapolating to health policy and human physiology. That being said, Levine et al. reported that in people aged 50-years and over, moderate and high protein intakes were associated with increased type 2 diabetes mortality, but not cardiovascular disease (CVD), cancer, or all-cause mortality. However, when the study population was split into persons aged 50-65 and those 66 and over, high and moderate protein intakes were associated with increased mortality from cancer and all-causes in the 50-65 age group, but not the latter. In addition, when animal protein was accounted for, the harmful associations between protein intake and mortality risks disappeared, suggesting that animal proteins, and not plant-based proteins, are potentially harmful at higher intakes during middle-age. With respect to those over 65, it appears that higher protein intake had a protective effect and was not associated with increased disease mortality risk, save type 2 diabetes. But wait, there’s more!

In subsequent analysis the investigators looked at insulin-like growth factor-1 (IGF-1) and its association with protein intake and mortality risks. In recent years insulin and IGF-1 have been suggested to contribute to the pathogenesis of cancer, due to their similar intracellular signaling pathways and downstream effects on various targets that favor cell survival rather than death [2]. Therefore, cells which should probably die are instead salvaged and are at an increased likelihood of becoming cancerous through various metabolic “reprogramming” mechanisms. This has prompted a recent interest in examining the potential therapeutic effects of low-carbohydrate and/or ketogenic diets in treating cancer due to their ability to drastically reduce serum levels of glucose and insulin [3] – two factors that are predictive of future cancer risk and cancer-related mortality [4-6]. The current study, however, chose to focus only on protein and IGF-1. So, what did the researchers find?

They found that IGF-1 levels were positively associated with protein intakes and that for every 10ng/mL increase in IGF-1 for those ages 50-65, mortality risk of cancer increased by about 9%. No association was observed in those over 65. But that’s not all!

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