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;19(3):407-417.
Dietary protein consumption was examined in a US population cohort and links sought to overall and disease specific mortality.
The cohort studied consisted of 6,381 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 subjects consumed 1,823 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 subjects into a high-protein group (20% or more of calories from protein), a moderate-protein group (10–19% of calories from protein), and a low-protein group (less than 10% of calories from protein).
Mortality was followed via the National Death Index until 2006, which provides timing and cause of death. The 18-year follow-up period covered 83,308 total person-years with 40% overall mortality; 10% was due to cancer, 19% cardiovascular disease, and 1% diabetes.
Members of the study cohort aged 50–65 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. There was a 5-fold increase in diabetes mortality across all ages for those consuming high-protein diets. These results suggest that low protein intake during middle age followed by moderate to high protein consumption in older adults may optimize health span and longevity.
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 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 people who did not have diabetes at baseline, and only 1 was from the low-protein group.
Insulin-like growth factor-1 (IGF-1) was significantly lower among those 50–65 years old with low protein intake, while for those 65+ the difference between the effects 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 4 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 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 more slowly 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- 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 high- or low-protein diets have may vary with age.
Mice were also used to test the hypothesis that the growth hormone receptor and insulin like growth factor-1 together promoted cancer progression. Melanoma cells were implanted into growth hormone receptor (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 and 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 in 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 (2007) for example reported no increase in all-cause, heart, or cancer mortality when comparing lower quartiles vs highest quartiles of protein consumption in the NHANES III data.1
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 causes and cancer. Fung et al reported in 2010 that low-carbohydrate diets are associated with increased all-cause mortality.2
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.3
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.4
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 will offer up resistance. A number of common dietary strategies, including the Atkins diet and the Paleolithic diet, along with others, can increase a follower's protein consumption to the degree that, if this study’s conclusions are true, may adversely affect a person’s health, increasing risk of diabetes, cancer, and early mortality.
Anyone advocating high meat diets for people younger 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 high protein may have on long-term survival. This idea that protein consumption should vary with age is a new concept that the public is still unaware of it, and it will take effort to explain. It might be a good idea to print off a copy and read the full paper yourself before attempting to speak to your patients.
- Saydah S, Graubard B, Ballard-barbash R, Berrigan D. Insulin-like growth factors and subsequent risk of mortality in the United States. Am J Epidemiol. 2007;166(5):518-526.
- 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;153(5):289-298.
- 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;169(6):562-571.
- Pan A, Sun Q, Bernstein AM, et al. Red meat consumption and mortality: results from 2 prospective cohort studies. Arch Intern Med. 2012;172(7):555-563.