Randomised controlled trialindependent cross-checkabstract checked I-DRY-115 standard review

Lactose, not the A1 protein, explained milk symptoms

Tolerance of protein-hydrolyzed lactose-free A1 milk and A2 milk in lactose-tolerant and lactose-intolerant volunteers: A randomized crossover trial with 2 parallel groups.

Overview

Mannila E et al.. J Dairy Sci 2025 · PMID 40614809 · DOI 10.3168/jds.2025-26712

No difference between A2 and A1 milk in lactose-tolerant people; no rise in inflammation markers.

Does the study support the specific claim? No · Methodological quality: moderate

Original publication

Plain-language summary

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

Separate lactose from A1 protein effects.

How was the study done?

Crossover RCT.

How many people, animals or samples were studied?

36 adults.

What was actually found?

Lactose mattered; A1 did not.

How large was the observed effect?

No significant differences.

What do the results mean in everyday life?

Lactose-free milk may help sensitive people.

What are the study's limitations?

Very short and small.

What does it say about Elawady's specific claim?

Contradicts A1-inflammation claim.

Do the results apply to Germany and Europe?

Applicable.

What can explicitly not be concluded from this study?

Cannot rule out long-term effects.

Scientific in-depth review

1. Full reference

Authors
Mannila E et al.
Journal
J Dairy Sci
Year
2025
Identifier
PMID 40614809 DOI 10.3168/jds.2025-26712
Verification
verified – PubMed efetch 2026-10-26
Retracted
no
Corrections
none
Extent checked
abstract only
Conflicts of interest and funding

not stated in abstract

2. Research question

Do A2 milk and hydrolysed lactose-free A1A2 milk differ in gut symptoms and inflammation markers?

3. Study design and population

Study design
Randomised controlled trial – Three-leg, 3-day randomised crossover trial; groups by lactase genotype
Population

Self-reported milk-sensitive volunteers

Country

not stated in abstract

Period

not stated

Sample size

36

Inclusion and exclusion criteria

Self-reported milk sensitivity

4. Methods and endpoints

Exposure / intervention

A2 milk; protein-hydrolysed lactose-free A1A2 milk

Comparator

Each other; milk-free run-in

Endpoints

GI symptoms, faecal calprotectin, plasma hs-CRP and cytokines

Statistical methods

Crossover analysis by genotype group

5. Actual results

Results

No difference in perceived gut symptoms between A2 and hydrolysed A1A2 milk in the lactose-tolerant group; symptoms increased with lactose content in the lactose-intolerant group. Calprotectin and hs-CRP did not increase during any milk period compared with the milk-free run-in. Weak, non-significant cytokine changes.

Absolute risks

not reported

Authors' conclusion

Protein-hydrolysed lactose-free A1A2 milk was as tolerated as A2 milk in lactose-tolerant volunteers and better tolerated by lactose-intolerant volunteers.

6. Strengths

  • Genotype-based lactase status
  • Milk-free baseline
  • Objective inflammation markers

7. Weaknesses

  • Very short (3 days)
  • Small
  • Processed products differ in more than beta-casein

8. Risk of bias

Orienting tool
RoB 2
Type of assessment
simplified assessment (abstract only)
Full formal assessment
no
Overall risk of bias
some concerns
Rationale

Small, short.

9. Assessment of the statistical interpretation

Null for beta-casein type; lactose explains symptoms.

10. Relevance to the specific claim

Suggests lactose, not A1 beta-casein, drives symptoms, and that milk did not raise gut (calprotectin) or systemic (hs-CRP) inflammation markers.

11. Independent contrary findings

A-DRY-10.

12. Transferability to Germany and Europe

Population not described in abstract.

13. Overall methodological judgement

Low-certainty evidence against A1-driven inflammation.

Multidimensional assessment
Multidimensional assessment
Authenticity of the sourceverified
Methodological qualitymoderate
Risk of biassome concerns
Precision of resultslow
Directnessdirect
Reproducibilityunknown
Consistency with the overall evidencemixed
Regional transferabilitymoderate
Adequacy of the interpretation (by the archive)not applicable

14. Open questions

Longer trials.

15. Linked fact checks