Randomised controlled trialindependent cross-checkabstract checked★ key study I-INS-119 in-depth review
Low-fat plant diet versus ketogenic animal diet: how much people eat
Effect of a plant-based, low-fat diet versus an animal-based, ketogenic diet on ad libitum energy intake.
Overview
Hall KD et al.. Nat Med 2021 · PMID 33479499 · DOI 10.1038/s41591-020-01209-1
On a high-carbohydrate low-fat diet people ate about 690 fewer calories per day than on a ketogenic diet.
Does the study support the specific claim? No · Methodological quality: moderate
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Test the carbohydrate-insulin model on food intake.
- How was the study done?
Inpatient crossover trial.
- How many people, animals or samples were studied?
20 adults.
- What was actually found?
Low-fat diet: 689 kcal/d less intake.
- How large was the observed effect?
-689 kcal/d.
- What do the results mean in everyday life?
Insulin is not the only factor in weight gain.
- What are the study's limitations?
Short and small.
- What does it say about Elawady's specific claim?
Contradicts 'insulin is the only cause of obesity'.
- Do the results apply to Germany and Europe?
Applicable.
- What can explicitly not be concluded from this study?
Cannot predict long-term weight change.
Scientific in-depth review
1. Full reference
- Authors
- Hall KD et al.
- Journal
- Nat Med
- Year
- 2021
- Identifier
- PMID 33479499 DOI 10.1038/s41591-020-01209-1
- Verification
- verified – PubMed efetch 2026-10-26; Crossref 2026-10-26
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
NIH (record).
2. Research question
Does a low-carbohydrate ketogenic diet reduce ad libitum energy intake compared with a high-carbohydrate low-fat diet, as the carbohydrate-insulin model predicts?
3. Study design and population
- Study design
- Randomised controlled trial – Inpatient randomised crossover trial (2 weeks per diet)
- Population
Adults (BMI 27.8)
- Country
USA (NIH Clinical Center)
- Period
NCT03878108
- Sample size
20
- Inclusion and exclusion criteria
Inpatient volunteers
4. Methods and endpoints
- Exposure / intervention
Animal-based ketogenic diet (10% carbohydrate)
- Comparator
Plant-based low-fat diet (75% carbohydrate)
- Endpoints
Ad libitum energy intake
- Statistical methods
Crossover comparison
5. Actual results
- Results
The low-fat diet led to 689 +/- 73 kcal/d less energy intake over 2 weeks (P<0.0001) and 544 +/- 68 kcal/d less in the final week; one participant withdrew due to hypoglycaemia on the low-carbohydrate diet.
- Absolute risks
not reported
- Authors' conclusion
The predictions of the carbohydrate-insulin model were inconsistent with the observations.
6. Strengths
- Tightly controlled inpatient setting
- Randomised crossover
7. Weaknesses
- Small, short
- Not a test of long-term weight
8. Risk of bias
- Orienting tool
- RoB 2
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- low
- Rationale
Well-controlled but short.
9. Assessment of the statistical interpretation
Large intake difference despite higher insulin on the low-fat diet.
10. Relevance to the specific claim
A high-carbohydrate, higher-insulin diet led to lower energy intake, contrary to insulin as the sole driver of fat gain.
11. Independent contrary findings
12. Transferability to Germany and Europe
Directly applicable; same biology and clinical standards in Europe.
13. Overall methodological judgement
Direct short-term evidence against the 'only cause' wording.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | moderate |
| Risk of bias | low |
| Precision of results | moderate |
| Directness | direct |
| Reproducibility | unknown |
| Consistency with the overall evidence | mixed |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
15. Linked fact checks
- Insulin is the single and only cause of obesity (local or generalised) because it is the only hormone that builds fat and blocks fat breakdown (lipolysis). – Studies contradicting or limiting the claim
- Dietary fat is not the origin of weight accumulation. – Studies with mixed or unclear results
- Calories are not a relevant concept ('there is no such thing as calories'); his system is based on high calorie intake, and people lose weight while eating sugar, juices, fats, potatoes and rice, because with 'zero insulin' no fat is formed (the passage continues: 'even if you drink oil, even if you swallow bags of sugar'). Elsewhere he says he drinks 6 litres of sugar-cane juice and eats baladi ghee, rice and potatoes every day. – Studies contradicting or limiting the claim