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A recent paper is making a few waves and going to upset some people, such as advocates of certain high-protein diets. The research is also going to bother those companies selling supplements that promise to raise IGF-1 levels. Here's the quick story.
In early 2014, the journal Cell Metabolism published a paper on how high-protein diets affect lifespan.
Researchers compared dietary protein consumption in a US population cohort and looked for associations to overall and disease-specific mortality. The cohort studied consisted of 6381 adults aged 50 and over from the NHANES III, a nationally representative, cross-sectional study. Mean age was 65 years and was representative of the US population in ethnicity, education, and health characteristics.
The participants consumed 1823 calories on average per day, of which the majority came from carbohydrates (51%), followed by fat (33%) and protein (16%), with most of it (11%) derived from animal protein. The percent of calorie intake from protein was used to categorize particpants into a high-protein (20% or more of calories from protein), moderate-protein (10%–19% of calories from protein), and low-protein group (less than 10% of calories from protein).
Mortality was followed via the National Death Index until 2006, which provide timing and cause of death. The 18 year follow-up period covered 83,308 total person-years with 40% overall mortality, 10% due to cancer, 19% cardiovascular disease, and 1% diabetes.
Members of the study cohort aged 50 to 65 reporting high protein intake had a 75% increase in overall mortality and a 4-fold increase in cancer death risk during the following 18 years. These associations were either abolished or attenuated if the proteins were plant derived. Conversely, high protein intake was associated with reduced cancer and overall mortality in respondents over 65, but a 5-fold increase in diabetes mortality across all ages.
These results suggest that low protein intake during middle age followed by moderate to high protein consumption in old adults may optimize health span and longevity.1
These data suggest that people should shift their dietary patterns in two key ways. First, patients younger than 65 should be discouraged from eating high-protein diets, especially diets high in animal protein. They should be encouraged to shift toward vegetable protein. Second, patients over 65 should be encouraged to consume more protein, as it reduces overall and cancer mortality unless the person is at high risk for diabetes.
The increased risk for diabetes seen in the middle-aged population on high-protein diets was striking: subjects with no diabetes at baseline had a 73-fold increase, while those in the moderate protein group had a 23-fold increase in risk of diabetes mortality. These increased hazard ratios may be somewhat inaccurate due to the small sample size; there were only 21 diabetes deaths among persons who did not have diabetes at baseline, only 1 from the low-protein group.
Insulin-like growth factor-1 (IGF-1) was significantly lower among those 50 to 65 years old with low protein intake, while for those 65-plus the difference between the effects that high- and low-protein diets had on IGF-1 were insignificant.
The differences in mortality reported in this study are not small. The researchers found that eating a diet rich in animal proteins during middle age makes you four times more likely to die of cancer than someone with a low-protein diet; this is a an increased risk comparable to smoking.
The study was actually more complex than reported in the summary above. It also involved separate cell studies using yeast and animal studies using mice to examine these same questions. The impact that high-protein diets have on cancer progression was confirmed in mice implanted with melanoma cells. The tumors in the low-protein diet mice grew significantly slower and remained significantly smaller as the experiment progressed.
To test the hypothesis that older subjects on a low-protein diet become malnourished because they have difficulty absorbing amino acids, an experiment was run in which both young and old mice were fed either high-protein or low-protein diets. Old mice fed a high-protein diet for 30 days gained weight. Old mice but not young mice fed a low-protein diet lost 10% of their weight by day 15, confirming the conclusion that the impact of high- or low-protein diets may vary with age.
Mice were also used to test the hypothesis that the growth hormone receptor and insulin-like growth factor-1 (IGF-1) together promoted cancer progression, melanoma cells were implanted into GHR and IGF-1 deficient mice along with normal controls. Tumor growth was far slower in the mice that did not have GHR or were lacking in IGF-1.
Protein intake was also tested on mice implanted with breast cancer. By day 18 after implantation, differences were already seen. Tumor incidence was 100% in the mice on the high-protein diet while only 70% in the low-protein-diet mice. By the end of the experiment at day 53, tumors in the low-protein-diet mice were 45% smaller.
Yeast were used to test the hypothesis that began to form after reviewing the human data, which suggests that the level of amino acids is linked to lifespan. Yeast were grown in media with differing amino acid concentrations. By day 5 of the experiment, the yeast exposed to high amino acids had a 3- to 4-fold higher mutation rate. By day 8, yeast grown in high concentrations of amino acids had a 10-fold decrease in surviving cells.
The strong association between protein consumption, IGF-1, disease, and mortality seen in this study has not been seen in some earlier reports; perhaps the age effect was not considered. Saydah for example reported no increase in all-cause, heart, or cancer mortality when comparing lower quartiles with highest quartiles of protein consumption in the NHANES III data.2
That the amount of animal proteins accounted for a significant proportion of the association between overall protein intake and all-cause and cancer mortality is in agreement with other recent reports on the association between red meat consumption and death from all-cause and cancer. Fung et al. reported in 2010 that low-carbohydrate diets are associated with increased all-cause mortality.3
In 2009, Sinha et al. used data from the National Institutes of Health Diet and Health Study cohort of half a million people aged 50 to 71 and reported that red and processed meat intake was associated with increased total mortality, cancer mortality, and cardiovascular disease mortality.4
Pan et al. reached this same conclusion in 2012 after analyzing data from 37,698 men in the Health Professionals Follow-up Study and 83,644 women in the Nurses' Health Study. They reported that red meat consumption was associated with an increased risk of total, CVD, and cancer mortality. After documenting 23,926 deaths during 2.96 million person-years of follow-up, Pan et al. calculated that for every 1 serving per day of unprocessed red meat eaten, the risk of total mortality increased by 13%. For processed red meat, 1 serving per day increased total risk by 20%. These researchers estimated that substitutions of 1 serving per day of other foods (including fish, poultry, nuts, legumes, low-fat dairy, and whole grains) for 1 serving per day of red meat were associated with a 7% to 19% lower mortality risk.5
The idea that a high-red-meat diet is associated with mortality is not new.
Although these new dietary suggestions are straightforward, it will not surprise us if proponents of various popular dietary regimes offer up resistance. A number of common dietary strategies, including Atkins, the paleo diet, and the ketogenic diet, can increase a follower's protein consumption to the degree that, if this study's conclusions are true, they may adversely effect the person's health, increasing risk of diabetes, cancer, and early mortality.
Anyone advocating high-protein diets for people less than 65 years old should be ethically bound to either find some fault in this paper or find an overriding justification for such a diet that outweighs the impact that high protein may have on long-term survival. The same caution should apply to using dietary supplements for the purpose of increasing IGF-1 levels. Any benefit of increasing IGF-1 needs to be justified in light of these data that suggest an increased risk of cancer, diabetes, and bottom line, dying when IGF-1 levels are high.
This idea that protein consumption should vary with age is a new concept that the public is still unaware of. It will take effort to explain this idea. It might be a good idea to print off a copy and read the full paper yourself before attempting to speak to your patients. The full text is available online for free: http://www.cell.com/cell-metabolism/pdf/S1550-4131(14)00062-X.pdf.
Notes
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 Metab. 2014 Mar 4;19(3):407–417. doi:10.1016/j.cmet.2014.02.006.
2. Saydah S1, Graubard B, Ballard-Barbash R, Berrigan D. Insulin-like growth factors and subsequent risk of mortality in the United States. Am J Epidemiol. 2007 Sep 1;166(5):518–526. Epub 2007 Jun 29.
3. Fung TT, van Dam RM, Hankinson SE, Stampfer M, Willett WC, Hu FB. Low-carbohydrate diets and all-cause and cause-specific mortality: two cohort studies. Ann Intern Med. 2010 Sep 7;153(5):289–298.
4. Sinha R, Cross AJ, Graubard BI, Leitzmann MF, Schatzkin A. Meat intake and mortality: a prospective study of over half a million people. Arch Intern Med. 2009 Mar 23;169(6):562–571.
5. Pan A, Sun Q, Bernstein AM, et al. Red meat consumption and mortality: results from 2 prospective cohort studies. Arch Intern Med. 2012 Apr 9;172(7):555–563.
 Jacob Schor, ND, FABNO, has practiced as a naturopathic physician in Denver, Colorado, with his wife, Rena Bloom, ND, since they graduated from National College of Naturopathic Medicine in 1991. He was humbled in 2008 when presented with the Vis Award by the American Association of Naturopathic Physicians (AANP). He has had the honor of serving the members of the Oncology Association of Naturopathic Physicians as a board member and currently as president. Dr. Schor began a term on the AANP's board of directors in January 2012. He is a frequent contributor to, and associate editor of, the Natural Medicine Journal.
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