Association of Animal and Plant Protein Intake With All-Cause and Cause-Specific Mortality | Cardiology | JAMA Internal Medicine | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 18.207.129.82. Please contact the publisher to request reinstatement.
1.
Simpson  SJ, Raubenheimer  D.  Perspective: tricks of the trade.  Nature. 2014;508(7496):S66.PubMedGoogle ScholarCrossref
2.
Solon-Biet  SM, McMahon  AC, Ballard  JW,  et al.  The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice.  Cell Metab. 2014;19(3):418-430.PubMedGoogle ScholarCrossref
3.
Wycherley  TP, Moran  LJ, Clifton  PM, Noakes  M, Brinkworth  GD.  Effects of energy-restricted high-protein, low-fat compared with standard-protein, low-fat diets: a meta-analysis of randomized controlled trials.  Am J Clin Nutr. 2012;96(6):1281-1298.PubMedGoogle ScholarCrossref
4.
Santesso  N, Akl  EA, Bianchi  M,  et al.  Effects of higher- versus lower-protein diets on health outcomes: a systematic review and meta-analysis.  Eur J Clin Nutr. 2012;66(7):780-788.PubMedGoogle ScholarCrossref
5.
Tielemans  SM, Altorf-van der Kuil  W, Engberink  MF,  et al.  Intake of total protein, plant protein and animal protein in relation to blood pressure: a meta-analysis of observational and intervention studies.  J Hum Hypertens. 2013;27(9):564-571.PubMedGoogle ScholarCrossref
6.
Westerterp-Plantenga  MS, Nieuwenhuizen  A, Tomé  D, Soenen  S, Westerterp  KR.  Dietary protein, weight loss, and weight maintenance.  Annu Rev Nutr. 2009;29:21-41.PubMedGoogle ScholarCrossref
7.
Rutherfurd-Markwick  KJ.  Food proteins as a source of bioactive peptides with diverse functions.  Br J Nutr. 2012;108(suppl 2):S149-S157.PubMedGoogle ScholarCrossref
8.
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.PubMedGoogle ScholarCrossref
9.
Kelemen  LE, Kushi  LH, Jacobs  DR  Jr, Cerhan  JR.  Associations of dietary protein with disease and mortality in a prospective study of postmenopausal women.  Am J Epidemiol. 2005;161(3):239-249.PubMedGoogle ScholarCrossref
10.
Colditz  GA, Manson  JE, Hankinson  SE.  The Nurses’ Health Study: 20-year contribution to the understanding of health among women.  J Womens Health. 1997;6(1):49-62.PubMedGoogle ScholarCrossref
11.
Rimm  EB, Giovannucci  EL, Willett  WC,  et al.  Prospective study of alcohol consumption and risk of coronary disease in men.  Lancet. 1991;338(8765):464-468.PubMedGoogle ScholarCrossref
12.
Yuan  C, Spiegelman  D, Rimm  EB,  et al.  Validity of a dietary questionnaire assessed by comparison with multiple weighed dietary records or 24-hour recalls.  Am J Epidemiol. In press.Google Scholar
13.
Stampfer  MJ, Willett  WC, Speizer  FE,  et al.  Test of the National Death Index.  Am J Epidemiol. 1984;119(5):837-839.PubMedGoogle Scholar
14.
Hu  FB, Stampfer  MJ, Rimm  E,  et al.  Dietary fat and coronary heart disease: a comparison of approaches for adjusting for total energy intake and modeling repeated dietary measurements.  Am J Epidemiol. 1999;149(6):531-540.PubMedGoogle ScholarCrossref
15.
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.PubMedGoogle ScholarCrossref
16.
Willett  WC.  Implications of Total Energy Intake for Epidemiologic Analyses: Nutritional Epidemiology. 3rd ed. New York, NY: Oxford University Press; 2013.
17.
Rosenbaum  PR, Rubin  DB.  The central role of the propensity score in observational studies for causal effects.  Biometrika. 1983;70(1):41-55.Google ScholarCrossref
18.
Physical Activity Guidelines Advisory Committee.  Physical Activity Guidelines Advisory Committee Report, 2008. Washington, DC: US Dept of Health and Human Services; 2008.
19.
Kipnis  V, Freedman  LS, Brown  CC, Hartman  A, Schatzkin  A, Wacholder  S.  Interpretation of energy adjustment models for nutritional epidemiology.  Am J Epidemiol. 1993;137(12):1376-1380.PubMedGoogle Scholar
20.
Layman  DK, Clifton  P, Gannon  MC, Krauss  RM, Nuttall  FQ.  Protein in optimal health: heart disease and type 2 diabetes.  Am J Clin Nutr. 2008;87(5):1571S-1575S.PubMedGoogle Scholar
21.
Hession  M, Rolland  C, Kulkarni  U, Wise  A, Broom  J.  Systematic review of randomized controlled trials of low-carbohydrate vs low-fat/low-calorie diets in the management of obesity and its comorbidities.  Obes Rev. 2009;10(1):36-50.PubMedGoogle ScholarCrossref
22.
Eisenstein  J, Roberts  SB, Dallal  G, Saltzman  E.  High-protein weight-loss diets: are they safe and do they work? a review of the experimental and epidemiologic data.  Nutr Rev. 2002;60(7, pt 1):189-200.PubMedGoogle ScholarCrossref
23.
Lagiou  P, Sandin  S, Weiderpass  E,  et al.  Low carbohydrate–high protein diet and mortality in a cohort of Swedish women.  J Intern Med. 2007;261(4):366-374.PubMedGoogle ScholarCrossref
24.
Nilsson  LM, Winkvist  A, Eliasson  M,  et al.  Low-carbohydrate, high-protein score and mortality in a northern Swedish population-based cohort.  Eur J Clin Nutr. 2012;66(6):694-700.PubMedGoogle ScholarCrossref
25.
Trichopoulou  A, Psaltopoulou  T, Orfanos  P, Hsieh  CC, Trichopoulos  D.  Low-carbohydrate–high-protein diet and long-term survival in a general population cohort.  Eur J Clin Nutr. 2007;61(5):575-581.PubMedGoogle Scholar
26.
Sacks  FM, Bray  GA, Carey  VJ,  et al.  Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates.  N Engl J Med. 2009;360(9):859-873.PubMedGoogle ScholarCrossref
27.
Willett  WC.  Low-carbohydrate diets: a place in health promotion?  J Intern Med. 2007;261(4):363-365.PubMedGoogle ScholarCrossref
28.
Holmes  MD, Pollak  MN, Willett  WC, Hankinson  SE.  Dietary correlates of plasma insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations.  Cancer Epidemiol Biomarkers Prev. 2002;11(9):852-861.PubMedGoogle Scholar
29.
Allen  NE, Appleby  PN, Davey  GK, Kaaks  R, Rinaldi  S, Key  TJ.  The associations of diet with serum insulin-like growth factor I and its main binding proteins in 292 women meat-eaters, vegetarians, and vegans.  Cancer Epidemiol Biomarkers Prev. 2002;11(11):1441-1448.PubMedGoogle Scholar
30.
Elliott  P, Stamler  J, Dyer  AR,  et al.  Association between protein intake and blood pressure: the INTERMAP Study.  Arch Intern Med. 2006;166(1):79-87.PubMedGoogle ScholarCrossref
31.
He  J, Gu  D, Wu  X,  et al.  Effect of soybean protein on blood pressure: a randomized, controlled trial.  Ann Intern Med. 2005;143(1):1-9.PubMedGoogle ScholarCrossref
32.
Appel  LJ, Sacks  FM, Carey  VJ,  et al; OmniHeart Collaborative Research Group.  Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial.  JAMA. 2005;294(19):2455-2464.PubMedGoogle ScholarCrossref
33.
Lamarche  B, Desroches  S, Jenkins  DJ,  et al.  Combined effects of a dietary portfolio of plant sterols, vegetable protein, viscous fibre and almonds on LDL particle size.  Br J Nutr. 2004;92(4):657-663.PubMedGoogle ScholarCrossref
34.
Anderson  JW, Johnstone  BM, Cook-Newell  ME.  Meta-analysis of the effects of soy protein intake on serum lipids.  N Engl J Med. 1995;333(5):276-282.PubMedGoogle ScholarCrossref
35.
Tremblay  F, Lavigne  C, Jacques  H, Marette  A.  Role of dietary proteins and amino acids in the pathogenesis of insulin resistance.  Annu Rev Nutr. 2007;27:293-310.PubMedGoogle ScholarCrossref
36.
Preis  SR, Stampfer  MJ, Spiegelman  D, Willett  WC, Rimm  EB.  Dietary protein and risk of ischemic heart disease in middle-aged men.  Am J Clin Nutr. 2010;92(5):1265-1272.PubMedGoogle ScholarCrossref
37.
Bernstein  AM, Sun  Q, Hu  FB, Stampfer  MJ, Manson  JE, Willett  WC.  Major dietary protein sources and risk of coronary heart disease in women.  Circulation. 2010;122(9):876-883.PubMedGoogle ScholarCrossref
38.
Lagiou  P, Sandin  S, Lof  M, Trichopoulos  D, Adami  H-O, Weiderpass  E.  Low carbohydrate-high protein diet and incidence of cardiovascular diseases in Swedish women: prospective cohort study.  BMJ. 2012;344:e4026.PubMedGoogle ScholarCrossref
39.
Halton  TL, Willett  WC, Liu  S,  et al.  Low-carbohydrate-diet score and the risk of coronary heart disease in women.  N Engl J Med. 2006;355(19):1991-2002.PubMedGoogle ScholarCrossref
40.
Halton  TL, Liu  S, Manson  JE, Hu  FB.  Low-carbohydrate-diet score and risk of type 2 diabetes in women.  Am J Clin Nutr. 2008;87(2):339-346.PubMedGoogle Scholar
41.
de Koning  L, Fung  TT, Liao  X,  et al.  Low-carbohydrate diet scores and risk of type 2 diabetes in men.  Am J Clin Nutr. 2011;93(4):844-850.PubMedGoogle ScholarCrossref
42.
Malik  VS, Li  Y, Tobias  DK, Pan  A, Hu  FB.  Dietary protein intake and risk of type 2 diabetes in US men and women.  Am J Epidemiol. 2016;183(8):715-728.PubMedGoogle ScholarCrossref
43.
Abete  I, Romaguera  D, Vieira  AR, Lopez de Munain  A, Norat  T.  Association between total, processed, red and white meat consumption and all-cause, CVD and IHD mortality: a meta-analysis of cohort studies.  Br J Nutr. 2014;112(5):762-775.PubMedGoogle ScholarCrossref
44.
Luo  C, Zhang  Y, Ding  Y,  et al.  Nut consumption and risk of type 2 diabetes, cardiovascular disease, and all-cause mortality: a systematic review and meta-analysis.  Am J Clin Nutr. 2014;100(1):256-269.PubMedGoogle ScholarCrossref
45.
Bibbins-Domingo  K, Chertow  GM, Coxson  PG,  et al.  Projected effect of dietary salt reductions on future cardiovascular disease.  N Engl J Med. 2010;362(7):590-599.PubMedGoogle ScholarCrossref
46.
Walker  R.  Nitrates, nitrites and N-nitrosocompounds: a review of the occurrence in food and diet and the toxicological implications.  Food Addit Contam. 1990;7(6):717-768.PubMedGoogle ScholarCrossref
47.
Lavigne  C, Tremblay  F, Asselin  G, Jacques  H, Marette  A.  Prevention of skeletal muscle insulin resistance by dietary cod protein in high fat-fed rats.  Am J Physiol Endocrinol Metab. 2001;281(1):E62-E71.PubMedGoogle Scholar
48.
Tremblay  F, Lavigne  C, Jacques  H, Marette  A.  Dietary cod protein restores insulin-induced activation of phosphatidylinositol 3-kinase/Akt and GLUT4 translocation to the T-tubules in skeletal muscle of high-fat–fed obese rats.  Diabetes. 2003;52(1):29-37.PubMedGoogle ScholarCrossref
49.
Yancy  WS  Jr, Wang  CC, Maciejewski  ML.  Trends in energy and macronutrient intakes by weight status over four decades.  Public Health Nutr. 2014;17(2):256-265.PubMedGoogle ScholarCrossref
50.
Ford  ES, Dietz  WH.  Trends in energy intake among adults in the United States: findings from NHANES.  Am J Clin Nutr. 2013;97(4):848-853.PubMedGoogle ScholarCrossref
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    6 Comments for this article
    EXPAND ALL
    How come India has lot of CAD?
    Anant Rao | None
    Hello,<br/><br/>As a life-long vegetarian, this is good news to me (and those who take it up now thanks to this article), I'd like to share an interesting contradictory information.<br/><br/>Being from India, I know that millions of families, including mine, are vegetarian for generations. However, India has some of the highest cases of diabetes (DM) and coronary artery disease (CAD).<br/><br/>Agreed there're environmental factors like pollution, lack of exercise. Still, I feel if some peoples are genetically predisposed to certain diseases in spite of being consuming a plant-based diet.<br/>
    CONFLICT OF INTEREST: None Reported
    Need for an edit in the abstract's conclusion section?
    John Well | None
    In the abstract section, the conclusion ends with \"Substitution of plant protein for animal protein, especially that from processed red meat, was associated with lower mortality, suggesting the importance of protein source.\"<br/><br/>After reading the rest of the article, I imagine that there might have been an error in that sentence and that its proper edit should likely be \"Substitution of animal protein, especially that from processed red meat, for plant protein was associated with lower mortality, suggesting the importance of protein source.\"<br/><br/>Best regards.
    CONFLICT OF INTEREST: None Reported
    Clarifications on Statistical information
    MN Nicolosi | none
    Hello,
    I've combed through your statistical methods section and I would like to inquire about the following:

    With such a large sample, you probably have too much power, hence the results of your research might be blown out of proportion. Why haven't you reported your effect sizes?

    Also, medical sciences usually work with more stringent p-values, .001, specifically. Why have you chosen this cut-off value (i.e. .05)?

    Finally, your confidence intervals for cause of death by protein illustrate, at best, marginally significant values for consumers of unprocessed meats, poultry, eggs and dairy products and no significant relationship with cancer, even for processed meats:

    (1) Why
    haven't you added the CIs for plant protein as well;
    (2) Don't you think your conclusions were somewhat stretched? There's really nothing new here. It has been known that processed meats are highly associated with CVD. That seems t be the only major finding I see here.
    CONFLICT OF INTEREST: None Reported
    READ MORE
    RE: Clarifications on Statistical information
    Mingyang Song | Massachusetts General Hospital
    I thank MN Nicolosi for the comments, and would like to provide some response.

    First, we have reported the hazard ratio as effect size throughout the manuscript.

    Second, our use of p<0.05 as the threshold for statistical significance is consistent with the standard of the epidemiologic literature.

    Third, it is true that some of the confidence intervals are marginally significant. But as the reader pointed out, statistical significance should be interpreted in the context of the effect size. Also, we did report the confidence intervals for plant protein throughout the manuscript.

    Finally, our conclusions were drawn based on our findings, which I believe go
    well beyond the well-known relationship between processed red meat and CVD.
    CONFLICT OF INTEREST: None Reported
    READ MORE
    Something is missing
    Zoltan Sandor | Research Centre for Natural Sciences, Hungarian Academy of Sciences
    As John Well, I find a strange contradiction, and something is missing or wrong.

    On the end of the abstract (in Conclusions and relevance:) I see:
    \"Substitution of plant protein for animal protein, especially that from processed red meat, was associated with lower mortality, suggesting the importance of protein source.\"

    And in the article:
    \"These results UNDERSCORE THE IMPORTANCE of protein sources FOR RISK ASSESSMENT AND SUGGEST THAT OTHER COMPONENTS in protein-rich foods (eg, SODIUM [45], NITRATES, and NITRITES [46] in processed red meat), in addition to protein per se, MAY HAVE A CRITICAL HEALTH EFFECT.\"

    And in the press release of
    the Massachusetts General Hospital:
    http://www.massgeneral.org/about/pressrelease.aspx?id=1968
    And on scientific media - for example:
    https://www.sciencedaily.com/releases/2016/08/160801113654.htm
    And also on a Hungarian (a little country in Europe) news portal:
    http://www.origo.hu/egeszseg/20160802-novenyi-feherje-allati-feherje-halalozas-riziko.html

    Nothing about the critical health effect of added sodium (NaCl), nitrates and nitrites. Why? Since, the real conclusion is that not the protein source (animal or plant) is important and have health risks, but the added sodium salts have health risks (critical health effect). That is not public? The danger of the sodium-induced disorder is a taboo?

    Some important references:
    Sodium-Induced Disorder Syndrome. Where have all the sciences gone?
    BMJ Online (13 April 2016)
    http://www.bmj.com/content/351/bmj.h4962/rr-45
    https://www.researchgate.net/publication/301297340

    Re: The scientific report guiding the US dietary guidelines: is it scientific?
    BMJ Online (25 September 2015)
    http://www.bmj.com/content/351/bmj.h4962/rr-5
    https://www.researchgate.net/publication/282672806

    Entropy and sodium intakes, the wicked problems of health sciences
    Science 2.0 (9. 9. 2013.)
    http://www.science20.com/entropy_and_sodium_intakes_wicked_problems_health_sciences-120016

    Sincerely: Zoltan Sandor
    Research Centre for Natural Sciences,
    Hungarian Academy of Sciences
    CONFLICT OF INTEREST: None Reported
    READ MORE
    Is it necessary to choose between 2 protein sources?
    George Henderson | Human Potential Centre AUT
    The highest quintile of plant protein intake only has median intake of 6.6% of energy, which is probably not enough to sustain life. The mortality HR for animal protein is minimal and non-significant at the highest quintile. The substitution analysis uses a mere 3%E of plant protein.
    Given the benefits noted from high protein, low carbohydrate diets, is there any reason from this data not to add some plant protein to a diet high in animal protein? For example, the \"paleo\" diet supplements high quality animal protein from various sources with plant protein from nuts and seeds. Low carbohydrate high fat
    and Mediterranean diets are similar, with dairy and legumes as possible additional protein sources.
    If the HRs for highest quintiles of animal and plant protein combined were presented, this might be of use to those considering higher protein diets. Health conscious people today eat protein from a variety of sources, but may not consciously limit meat.
    It is notable that processed meats such as sausage meats of the frankfurter type can be a source of plant protein, and I wonder whether this was factored into the analysis.
    CONFLICT OF INTEREST: None Reported
    READ MORE
    Original Investigation
    October 2016

    Association of Animal and Plant Protein Intake With All-Cause and Cause-Specific Mortality

    Author Affiliations
    • 1Clinical and Translational Epidemiology Unit, Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston
    • 2Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
    • 3Department of Nutrition, Simmons College, Boston, Massachusetts
    • 4Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
    • 5Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
    • 6Longevity Institute, School of Gerontology, Department of Biological Sciences, University of Southern California, Los Angeles
    • 7FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milano, Italy
    • 8Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge
    JAMA Intern Med. 2016;176(10):1453-1463. doi:10.1001/jamainternmed.2016.4182
    Abstract

    Importance  Defining what represents a macronutritionally balanced diet remains an open question and a high priority in nutrition research. Although the amount of protein may have specific effects, from a broader dietary perspective, the choice of protein sources will inevitably influence other components of diet and may be a critical determinant for the health outcome.

    Objective  To examine the associations of animal and plant protein intake with the risk for mortality.

    Design, Setting, and Participants  This prospective cohort study of US health care professionals included 131 342 participants from the Nurses’ Health Study (1980 to end of follow-up on June 1, 2012) and Health Professionals Follow-up Study (1986 to end of follow-up on January 31, 2012). Animal and plant protein intake was assessed by regularly updated validated food frequency questionnaires. Data were analyzed from June 20, 2014, to January 18, 2016.

    Main Outcomes and Measures  Hazard ratios (HRs) for all-cause and cause-specific mortality.

    Results  Of the 131 342 participants, 85 013 were women (64.7%) and 46 329 were men (35.3%) (mean [SD] age, 49 [9] years). The median protein intake, as assessed by percentage of energy, was 14% for animal protein (5th-95th percentile, 9%-22%) and 4% for plant protein (5th-95th percentile, 2%-6%). After adjusting for major lifestyle and dietary risk factors, animal protein intake was not associated with all-cause mortality (HR, 1.02 per 10% energy increment; 95% CI, 0.98-1.05; P for trend = .33) but was associated with higher cardiovascular mortality (HR, 1.08 per 10% energy increment; 95% CI, 1.01-1.16; P for trend = .04). Plant protein was associated with lower all-cause mortality (HR, 0.90 per 3% energy increment; 95% CI, 0.86-0.95; P for trend < .001) and cardiovascular mortality (HR, 0.88 per 3% energy increment; 95% CI, 0.80-0.97; P for trend = .007). These associations were confined to participants with at least 1 unhealthy lifestyle factor based on smoking, heavy alcohol intake, overweight or obesity, and physical inactivity, but not evident among those without any of these risk factors. Replacing animal protein of various origins with plant protein was associated with lower mortality. In particular, the HRs for all-cause mortality were 0.66 (95% CI, 0.59-0.75) when 3% of energy from plant protein was substituted for an equivalent amount of protein from processed red meat, 0.88 (95% CI, 0.84-0.92) from unprocessed red meat, and 0.81 (95% CI, 0.75-0.88) from egg.

    Conclusions and Relevance  High animal protein intake was positively associated with cardiovascular mortality and high plant protein intake was inversely associated with all-cause and cardiovascular mortality, especially among individuals with at least 1 lifestyle risk factor. Substitution of plant protein for animal protein, especially that from processed red meat, was associated with lower mortality, suggesting the importance of protein source.

    ×