Otherindependent cross-checkabstract checked★ key study I-FAST-101 in-depth review

Hormones during weeks of fasting

Glucagon levels and metabolic effects in fasting man.

Overview

Marliss EB et al.. J Clin Invest 1970 · PMID 5480852 · DOI 10.1172/JCI106445

During fasts of up to six weeks, insulin fell to a low plateau by the third day and stayed there; glucagon rose.

Does the study support the specific claim? Partly · Methodological quality: moderate

Original publication

Plain-language summary

Study explained simply
What did the researchers want to find out?

Describe glucagon and insulin in prolonged human fasting.

How was the study done?

Repeated blood measurements during supervised fasts; glucagon infusions.

How many people, animals or samples were studied?

Volunteers on 6-week fasts (number not in abstract).

What was actually found?

Insulin fell to a plateau by day 3; glucagon peaked on day 3.

How large was the observed effect?

Not reported in abstract.

What do the results mean in everyday life?

Fasting lowers insulin, but a low basal level remains.

What are the study's limitations?

Old, small, uncontrolled; abstract only.

What does it say about Elawady's specific claim?

Correct that insulin falls; wrong that it becomes zero.

Do the results apply to Germany and Europe?

Applies; same physiology.

What can explicitly not be concluded from this study?

Exact insulin concentrations; effects in lean people.

Scientific in-depth review

1. Full reference

Authors
Marliss EB et al.
Journal
J Clin Invest
Year
1970
Identifier
PMID 5480852 DOI 10.1172/JCI106445
Verification
verified – PubMed efetch 2026-10-26; Crossref update-to/updated-by check
Retracted
no
Corrections
none
Extent checked
abstract only
Conflicts of interest and funding

not stated in abstract

2. Research question

How do glucagon and insulin change during prolonged (up to 6 weeks) fasting in humans?

3. Study design and population

Study design
Other – Physiological study of hormone levels during 6-week therapeutic fasts plus glucagon infusion experiments
Population

Adults undergoing supervised prolonged fasts (obese volunteers; details not in abstract)

Country

USA (not stated in abstract)

Period

not stated in abstract

Sample size

not stated in abstract

Inclusion and exclusion criteria

not stated in abstract

4. Methods and endpoints

Exposure / intervention

Total fasting up to 6 weeks; glucagon infusions in 4-6-week fasted subjects

Comparator

Post-absorptive state

Endpoints

Plasma glucagon, insulin, amino acids, glucose, ketone metabolism

Statistical methods

Descriptive time courses (abstract)

5. Actual results

Results

Plasma glucagon rose twofold to a peak on day 3 of fasting, then declined to a level at or above post-absorptive; 'Insulin concentration declined to a plateau by the 3rd day.' A persisting altered glucagon/insulin relationship characterised the fasted state.

Absolute risks

not reported

Authors' conclusion

A synergism of low insulin and relatively or absolutely raised glucagon controls hepatic substrate extraction for gluconeogenesis in prolonged fasting.

6. Strengths

  • Direct hormone measurements across very long fasts
  • Classic, frequently replicated physiology

7. Weaknesses

  • Small, old, uncontrolled study; numbers not in abstract
  • Mostly obese subjects under supervision

8. Risk of bias

Orienting tool
none applicable
Type of assessment
simplified assessment (abstract only)
Full formal assessment
no
Overall risk of bias
not assessable
Rationale

Physiological study; no comparator; abstract only.

9. Assessment of the statistical interpretation

Qualitative: insulin falls and then stays at a plateau; it is not reported to disappear.

10. Relevance to the specific claim

Directly tests whether insulin reaches zero during fasting: insulin falls to a plateau (a persisting low level), not to zero.

11. Independent contrary findings

Consistent with modern 72-h fasting reference data (I-FAST-103) and 36-h fasting studies (I-FAST-102).

12. Transferability to Germany and Europe

Universal biology; applies in Europe and Egypt.

13. Overall methodological judgement

Supports the correct kernel (insulin falls) and contradicts 'insulin equals zero'.

Multidimensional assessment
Multidimensional assessment
Authenticity of the sourceverified
Methodological qualitymoderate
Risk of biasnot assessable
Precision of resultsnot applicable
Directnessdirect
Reproducibilityreplicated
Consistency with the overall evidenceconsistent
Regional transferabilityhigh
Adequacy of the interpretation (by the archive)not applicable

14. Open questions

15. Linked fact checks