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The Study

Higher circulating FGF21, lower protein intake, and lower muscle mass: Associations with a higher risk of mortality

In simple terms

This study looked at a bunch of people over many years and noticed that those with higher FGF21 levels tended to eat less protein and have less muscle, and also died more often. But it didn’t change anyone’s diet or give them medicine — it just watched what happened. So it can’t prove that FGF21 or low protein causes death — only that they often happen together.

60%

Analysis score

60/ 72

Maximum 72 for a cohort study.

Where the score came from

Reporting40
Methodology38
Publication100
Statistical77
Study type (basis of the score)
Cohort Study
Level 2b - Individual cohort study
What’s the bottom line?

Your body releases a hormone called FGF21 when you don't eat enough protein. This hormone tells your body you're low on protein, and it's also linked to losing muscle and a higher chance of dying early.

Where does this study sit?

Reviews of RCTs (Meta-analyses)

Max 100

Randomized Trials

Max 90

Reviews of Cohort Studies

Max 85

Cohort Studies

Max 72

Reviews of Case-Control Studies

Max 63

Case-Control Studies

Max 58

Cross-Sectional & Case Series

Max 50

Expert Opinion

Max 5
StrongerWeaker
Cohort Studies
Level 2b
60

60 / 100

Quality score

Groups of people are followed over time to see who develops an outcome. Strong for identifying risk factors and associations, but cannot prove causation as firmly as RCTs.

Cannot establish causation

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Key takeaways

Summary

Based on the study abstract and findings.

  1. 1Yes—eating enough protein helps keep your muscles strong and lowers your risk of dying early, even if you have other health problems.
  2. 2People with higher FGF21 had 48% higher odds of eating less than 0.8g protein per kg of body weight.
  3. 3Those who ate more protein had 33% lower risk of dying over 10 years.
  4. 4People with more muscle had 17% lower risk.
  5. 5FGF21 itself didn't cause death—low protein did.

Score breakdown, methodology, conflicts of interest, evidence analysis & raw study data

Publication

Journal

Journal of Internal Medicine

Year

2025

Authors

A. Post, Wendy A Dam, D. Groothof, C. Franssen, S. J. Bakker, R. Dullaart

Open Access
3 citations
Analysis v5

Related Content

Claims (6)

Assertion

Without enough dietary protein, the body cannot build new muscle and will lose muscle mass over time.

Mechanistic
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Assertion

Adults aged 28–75 who consume more dietary protein have a 33% lower risk of dying from any cause over 10 years, compared to those who consume less, even when accounting for differences in muscle mass, inflammation, and metabolic disease.

Correlational
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Assertion

Adults aged 28–75 with higher muscle mass, measured by creatinine excretion relative to height, have a 17% lower risk of dying from any cause over 10 years, even when accounting for protein intake, inflammation, and metabolic disease.

Correlational
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Assertion

In adults aged 28–75, higher levels of the protein FGF21 in the blood are linked to lower dietary protein intake, and a doubling of FGF21 concentration is associated with a 48% higher likelihood of consuming less than 0.8 grams of protein per kilogram of body weight per day. FGF21 levels are proposed as an indicator of long-term inadequate protein consumption.

Correlational
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Assertion

Higher levels of the protein FGF21 are linked to a greater risk of death from any cause, but this link exists only because low protein intake causes both higher FGF21 levels and higher mortality risk; FGF21 itself does not cause death.

Mechanistic
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Assertion

Higher levels of FGF21 in the blood are linked to lower muscle mass in adults, but this link exists only because people with higher FGF21 tend to consume less protein; when protein intake is accounted for, FGF21 shows no direct relationship with muscle mass.

Mechanistic
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Not medical advice. For informational purposes only. Always consult a qualified healthcare professional before making health decisions.