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Cited by 910Dietary Effects on HealthGenetics, Aging, and Longevity in Model OrganismsGrowth Hormone and Insulin-like Growth Factors

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

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Levine, Morgan E., Suarez, Jorge A., Brandhorst, Sebastian, Balasubramanian, Priya, Cheng, Chia-Wei, Madia, Federica, Fontana, Luigi, Mirisola, Mario G. +8 more·2014·Cell Metabolism
DOI 10.1016/j.cmet.2014.02.006PMC PMC3988204
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Abstract

Summary Mice and humans with Growth Hormone Receptor/IGF-1 deficiencies display major reductions in age-related diseases. Because protein restriction reduces GHR-IGF-1 activity, we examined links between protein intake and mortality. Respondents (n=6,381) aged 50–65 reporting high protein intake had a 75% increase in overall mortality and a 4-fold increase in cancer and diabetes mortality during an 18 year follow up period. These associations were either abolished or attenuated if the source of proteins was plant-based. Conversely, in respondents over age 65, high protein intake was associated with reduced cancer and overall mortality. Mouse studies confirmed the effect of high protein intake and the GHR-IGF-1 axis on the incidence and progression of breast and melanoma tumors, and also the detrimental effects of a low protein diet in the very old. These results suggest that low protein intake during middle age followed by moderate protein consumption in old subjects may optimize healthspan and longevity.

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Crossref · 10.1016/j.cmet.2014.02.006

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  • High protein intake could have adverse effects on metabolic function.

    “and could have adverse effects on metabolic function”

    From Preserving Healthy Muscle during Weight Loss (2017) · cites this paper as [125]

    The Results (Association between Protein and Mortality; page not provided) associate higher protein intake with increased diabetes-related mortality, which supports concern about a possible adverse metabolic effect. The paper does not show that high protein intake impairs metabolic function itself, and its Discussion notes that the effects of protein intake differ by age. (LLM, conf=0.82)

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  • In an epidemiological study, individuals aged 50-65 years with the highest protein intake, more than 20% of calories from protein, had a 75% increase in total mortality and a fourfold increase in cancer mortality.

    “In a recent epidemiological study, individuals aged 50–65 years with the highest protein intake (more than 20% of calories from protein) had a 75% increase in total mortality and a fourfold increase in cancer mortality.”

    From Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms (2018) · cites this paper as [75]

  • The associations between high protein intake and increased total and cancer mortality were either eliminated or diminished if people were consuming plant-based proteins.

    “These associations were either eliminated or diminished if people were consuming plant-based proteins (75).”

    From Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms (2018) · cites this paper as [75]

  • In NHANES III, higher total protein intake was linked to significantly increased all-cause mortality among participants younger than 65 years.

    “In another report from the NHANES III study, 15 although higher total protein intake levels were linked with significantly increased risks of all-cause mortality (among participants younger than 65 years), this association was significantly attenuated when animal protein was controlled for, a finding that was also replicated in our study (eTable 6 in the Supplement), implicating the role of animal”

    From Association of Animal and Plant Protein Intake With All-Cause and Cause-Specific Mortality in a Japanese Cohort (2019) · cites this paper as [15]

  • A NHANES analysis found that greater protein intake was tied to a significantly higher risk of death from all causes.

    “An analysis using the US National Health and Nutrition Examination Survey (NHANES) reported a significant increase in the risk of death due to all causes associated with higher protein intake.15”

    From Association of Animal and Plant Protein Intake With All-Cause and Cause-Specific Mortality in a Japanese Cohort (2019) · cites this paper as [15]

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Authors
Levine, M. E., Suarez, J. A., Brandhorst, S., Balasubramanian, P., Cheng, C.-W., Madia, F., Fontana, L., Mirisola, M. G., Guevara-Aguirre, J., Wan, J., Passarino, G., Kennedy, B. K., Wei, M., Cohen, P., Crimmins, E. M., & Longo, V. D.
Affiliations
  • University of Southern California (US)
  • Washington University in St. Louis (US)
  • University of Calabria (IT)
  • Buck Institute for Research on Aging (US)
Corresponding author
Longo, Valter D.
ORCID
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2014-03
Volume
19
Issue
3
Pages
407-417
ISSN
1550-4131 (ISSN-L)
DOI
10.1016/j.cmet.2014.02.006
PMC
PMC3988204
OpenAlex
W2150665743
Semantic Scholar
2b0d7bbcb29edccce90eb6798d644a79c53a982a
Cited by
910
References
80
Citations by year
2026: 32 · 2025: 71 · 2024: 67 · 2023: 90 · 2022: 93 · 2021: 96 · 2020: 84 · 2019: 76 · 2018: 80 · 2017: 63 · 2016: 63 · 2015: 58 · 2014: 34 · 2013: 1
FWCI
47.87
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
  • Archive of Doctoral Theses and Digital Collections (University of Calabria) (submittedVersion)
  • Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion)
Funders
  • U.S. Department of Health and Human Services
  • National Institute on Aging (P01AG034906, AG20642, R01AG020642, AG034906, AG025135, R01AG025135, P30AG017265, T32AG000037)
Topics
  • Health Sciences › Medicine › Physiology › Dietary Effects on Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords
protein intake, insulin-like growth factor I, growth hormone receptor, mortality, cancer mortality, diabetes mortality, plant proteins, aging, healthspan, longevity, breast cancer, melanoma, middle age (human life stage), older adults
MeSH terms
Aged, Animals, Breast Neoplasms, Carrier Proteins, Cross-Sectional Studies, Diabetes Mellitus, Female, Follow-Up Studies, Humans, Insulin-Like Growth Factor I, Longevity, Male, Melanoma, Mice, Inbred BALB C, Mice, Inbred C57BL, Middle Aged, Neoplasms, Signal Transduction, Proportional Hazards Models, Mice, Knockout, Diet, Protein-Restricted, Mice

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