Perhaps you’ve seen the headlines:

“High protein diets as bad as smoking for middle-aged people”

“High protein diet raises cancer risk as much as smoking”

“Study says high-protein diets in midlife liked to high risk of premature death”

All these media outlets are reporting on the same study recently published in the Journal of Cell Metabolism. Let’s take a look at the study.

The researchers administered a 24-hour dietary recall and measured nutrient intake (protein, carbohydrates, fats, and calories) to 6,000 participants. The participants were categorized into three groups based upon their protein consumption (low, med, high) on the first day. They then followed up with the participants 18 years later and measured cause of death (all-cause mortality, cardiovascular mortality, cancer mortality, and diabetes mortality).

As a potential mechanism of action the researchers hypothesized that eating protein increases insulin like growth factor (IGF-1) and examined if it would increase the rate of growth of already present tumors in mice. Additionally, 2,200 people were sampled for IGF-1 levels, although when and under what conditions were not reported.

Here were their reported findings:

“high and moderate protein consumption were positively associated with diabetes-related mortality, but not associated with all-cause, CVD, or cancer mortality”

“Among subjects with no diabetes at baseline, those in the high protein group had a 73-fold increase in risk, while those in the moderate protein category had an almost 23-fold increase in the risk of diabetes mortality.”

“Among those ages 50–65, higher protein levels were linked to significantly increased risks of all-cause and cancer mortality. In this age range, subjects in the high protein group had a 74% increase in their relative risk of all-cause mortality and were more than four times as likely to die of cancer when compared to those in the low protein group.”

“…when the percent calories from animal protein was controlled for, the association between total protein and all-cause or cancer mortality was eliminated or significantly reduced, respectively, suggesting animal proteins are responsible for a significant portion of these relationships.” This is to be expected, as the majority of protein consumed was from meat. If we remove all the protein we remove the relationship.

“ Results showed that for every 10 ng/ml increase in IGF-1, the mortality risk of cancer among subjects ages 50–65 increases for the high protein versus the low protein group by an additional 9%”

In mice “A 45% smaller mean tumor size was also observed in the low protein group compared to the high protein group at the end of the experiment at day 53”.

“Although there was a [extremely low!] trend for an effect of substituting the same level of animal protein with plant protein on IGF-1 andIGFBP-1, the differences were not significant”

This was a study of observational epidemiology. What this means is we look for relationships between two or more phenomena. As researchers, we can then comment on the relationship; however, we cannot prove causation. As an example, we might look at the relationship between socioeconomic status and race. According to the American Psychological Society there are more African Americans living in poverty than Caucasians. It would be both irresponsible and ignorant of us to assume that there is something inherent to Caucasian genes that predisposes them to a greater percentage of success in the US when we know that not only is this not true, but that there are a myriad of other factors such as past and ongoing discrimination and segregation responsible for this.

Unfortunately, claiming causation based off of correlation is exactly what the researchers did. Let’s take a look at their conclusions:

Overall, our human and animal studies indicate that a low protein diet during middle age is likely to be beneficial for the prevention of cancer, overall mortality, and possibly diabetes through a process that may involve, at least in part, regulation of circulating IGF-1 and possibly insulin levels.

Our findings suggest that a diet in which plant-based nutrients represent the majority of the food intake is likely to maximize health benefits in all age groups.

We also propose that at older ages, it may be important to avoid low protein intake and gradually adopt a moderate to high protein, preferably mostly plant-based consumption to allow the maintenance of a healthy weight and protection from frailty.

What we have here is the classic bias of compliance. In short, those who eat more meat are (unlike many of my readers) not living healthy life styles. They do not “listen to their doctors”: they are inactive, consume less fruits/veggies, smoke, rely heavily on caffeine, consume high amounts of added sugar, etc. – They live the typical western life. Despite the ability to control statistically for these factors in an equation, you cannot control physiologically for the interactions, and you certainly cannot pick one factor out of the myriad and claim it is the main causative factor. As another example, we could look at TV consumption and its relationship to metabolic disease, cardiovascular disease, and cancers. A number of studies has shown a positive result between TV consumption, obesity and diabetes. Is it the fact that people who watch a lot if TV are less active and living less healthy lifestyles? Or is it something about the TV device itself (radiation, frequency, etc.) that causes these diseases?

In addition, the authors claim a benefit of increasing the consumption of plant proteins; however, the results from the mice studies where animal protein was actually replaced with plant proteins do not support these statements. There was no effect on tumor growth regardless of type of protein consumption. Take a look at Graph J: high protein from casein or soy equally accelerated tumor growth. And, we should note that mice, unlike humans, do not consume very much of the natural diets from protein sources (they are predominantly herbivores, not omnivores).

Next, if we look at the raw facts provided in the supplemental data we see that the authors committed sensationalism of statistics, check out Table S1 and look at the absolute percentages:

In the low protein cohort 9.8% died of cancer. In the moderate and high protein diet 10.1% and 9.0% died of cancer, respectively. Hardly a significant difference!

The authors then provided the rates of cancer for the 50-65 age group and 65+ age group following questions regarding the arrival at their conclusions and we see:

Low: 18.07%

Mod: 20.28%

High: 26.15% Age 50-65 All-cause Mortality Age 50-65 Cancer Mortality Low: 2.58%

Mod: 7.89%

High 9.89% Age 66+ All-cause Mortality Low: 70.97%

Mod: 63.73%

High: 64.04% Age 66+ Cancer Mortality Low: 18.03%

Mod: 12.94%

High 7.96% This may seem dramatic; however, if we dip further into the data we see that there was a large difference between the number of participants in each group such that for the 50-65 age group there were 219, 2,227, and 543, respectively. Taken a step further (and credit to Zoe Harcombe for doing so) we can calculate the total person years per group and then the cancer rate per 1,000 person years. If we do so the numbers are no longer dramatic: 2.18%, 5.95%, and 7.84%, respectively. In other words, the risk of eating a high protein diet with relation to cancer death is about 5.5% higher per 1,000 person years versus a low protein diet. Another concern not discussed was if the 24 hour recall reflects the way people the majority of their adult lives, then why the sudden change around the age of 65? This was not an intervention trial – the older group did not eat a low protein diet early in life and then change to a higher protein diet upon retiring at 65. Quite the opposite, the older group ate a high protein diet their entire lives. Why then the discrepancy between cancer mortality at young vs. old age? We may interpret this discrepancy as there are other factors involved, such as: dietary quality of food (increased consumption of processed foods in modern life), environmental decay, stress, lower activity levels, and everything else associated with the reduced health outcomes seen in the baby boomer generation. So is it protein that is actually causing the cancer (when no mechanism of cause has yet been identified), or just accelerating the growth (in rodents)? If the latter, then from the data we might actually conclude that protein intake plays a protective role in human health (alongside an active lifestyle rich in unprocessed foods). In which case, if Longo et al. are wrong regarding protein actually leading to the development of cancer (and not the acceleration of cancerous growths) then the .36 g./lb protein recommendation suggest by the author may lead many people into later life with a lower chance for survival. But this is all just speculation, we will never know either way until a controlled intervention trial is conducted. And until a controlled intervention trial is conducted, Longo et al. should not be making ridiculous claims based upon association.

Next the authors claim that protein consumption increases the release of insulin and IGF-1 which expedites the growth of [already present] cancer cells. It does not cause the development of cancer. If IGF-1 and insulin caused the development of cancer then we should all avoid exercising (as exercise is a powerful stimulator of IGF-1 release) and eating as every time we eat (especially carbohydrates) insulin is released to maintain normal blood glucose levels.

Despite these unanswered questions, the media firestorm ensued.

Now the real kicker. For those who are not involved in academia and research science, when we look at a list of the authors it is generally the first author who did most of the grunt work and the final author who supervised (and often designed) the study. The final and corresponding author of this study is Victor D. Longo (VDL). If we look at the related info we see that:

VDL designed the study and obtained funding from the Nation Institutes of Health (NIH)

The NIH had no role in study design, data collection and analysis, or the writing or and publishing of the manuscript

VDL has an equity interest in L-Nutra, a company that develops medical food.

What exactly is L-Nutra and “medical foods”?

L-Nutra’s products are a “formulation of natural nutrients with the ability to provide nourishment and allow subjects to enjoy a combination of good and mostly organically grown and plant-based food.” L-Nutra’s major product ProLon is “an all-natural plant-based 5 five-day Fasting Mimicking & Enhancing™ Diet (FMED) program.”

Since none of us were present in the design or execution of the study we may only speculate that the interpretation/discussion of the results the suggestions to increase plant-based protein intake to prevent cancer despite any evidence in the study to back up this claim in conjunction with the lead authors affiliation (he is actually the founder!) are…well…suspicious to say the least!

Jason Cholewa, Ph.D., CSCS

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