Title: Association between dietary flavonoids intake and metabolic dysfunction-associated
steatotic liver disease especially in non-smokers: A cross-sectional study in US adults
Version: 0 Date: 21 Apr 2025
Reviewer's report:
This study reveals a U-shaped association between dietary flavonoid intake and MAFLD/
MASLD, mediated by low-grade inflammation. Anthocyanidins and flavanones offer the most
protection. Non-smokers exhibited stronger benefits, with smoking status influencing effects.
Using NHANES data, Gao et al., emphasize the importance of flavonoid-rich diets and smoking
cessation for managing MAFLD/MASLD.
I have a few comments:
1. It should be noted that reliance on FLI/USFLI indices without imaging or biopsy may
misclassify cases and introduce outcome bias, which will affect the diagnostic validity of
MAFLD/MASLD.
2. A single 24-hour recall may not accurately reflect habitual intake, which risks
misclassification of exposure.
3. U-shaped inflection thresholds lack validation; the mechanistic rationale for nonlinearity is
underexplored.
4. Biological pathways linking smoking to reduced flavonoid efficacy remain speculative and
require experimental validation. Additionally, authors should clarify their choice of smoke as a
subgroup analysis instead of other lifestyle factors.
5. Additive effects of flavonoid subclasses may oversimplify interactions that are synergistic
or antagonistic.
6. The differential bioavailability of flavonoid subclasses (e.g., isoflavones vs. anthocyanidins)
is overlooked.
7. The recommendation for a "flavonoid-rich diet" lacks practical guidance, such as food sources
and dosages.
8. Abstract highlights smoking interactions, but results emphasize non-smokers; reframe for
consistency.
9. Some citations (e.g., global prevalence of MAFLD/MASLD) are outdated; please include
more updated literature.
10. Considering the difference in flavonoid association between MASLD and MAFLD, a further
subgroup analysis of MASLD-only and MAFLD-only is suggested. And the difference should
be discussed.
Title: Association between dietary flavonoids intake and metabolic dysfunction-associated
steatotic liver disease especially in non-smokers: A cross-sectional study in US adults
Version: 0 Date: 21 Apr 2025
Reviewer's report:
This study reveals a U-shaped association between dietary flavonoid intake and MAFLD/
MASLD, mediated by low-grade inflammation. Anthocyanidins and flavanones offer the most
protection. Non-smokers exhibited stronger benefits, with smoking status influencing effects.
Using NHANES data, Gao et al., emphasize the importance of flavonoid-rich diets and smoking
cessation for managing MAFLD/MASLD.
I have a few comments:
1. It should be noted that reliance on FLI/USFLI indices without imaging or biopsy may
misclassify cases and introduce outcome bias, which will affect the diagnostic validity of
MAFLD/MASLD.
2. A single 24-hour recall may not accurately reflect habitual intake, which risks
misclassification of exposure.
3. U-shaped inflection thresholds lack validation; the mechanistic rationale for nonlinearity is
underexplored.
4. Biological pathways linking smoking to reduced flavonoid efficacy remain speculative and
require experimental validation. Additionally, authors should clarify their choice of smoke as a
subgroup analysis instead of other lifestyle factors.
5. Additive effects of flavonoid subclasses may oversimplify interactions that are synergistic
or antagonistic.
6. The differential bioavailability of flavonoid subclasses (e.g., isoflavones vs. anthocyanidins)
is overlooked.
7. The recommendation for a "flavonoid-rich diet" lacks practical guidance, such as food sources
and dosages.
8. Abstract highlights smoking interactions, but results emphasize non-smokers; reframe for
consistency.
9. Some citations (e.g., global prevalence of MAFLD/MASLD) are outdated; please include
more updated literature.
10. Considering the difference in flavonoid association between MASLD and MAFLD, a further
subgroup analysis of MASLD-only and MAFLD-only is suggested. And the difference should
be discussed.
Please review this paper.
user
Title: Association between dietary flavonoids intake and metabolic dysfunction-associated
steatotic liver disease especially in non-smokers: A cross-sectional study in US adults
Version: 0 Date: 21 Apr 2025
Reviewer's report:
This study reveals a U-shaped association between dietary flavonoid intake and MAFLD/
MASLD, mediated by low-grade inflammation. Anthocyanidins and flavanones offer the most
protection. Non-smokers exhibited stronger benefits, with smoking status influencing effects.
Using NHANES data, Gao et al., emphasize the importance of flavonoid-rich diets and smoking
cessation for managing MAFLD/MASLD.
I have a few comments:
1. It should be noted that reliance on FLI/USFLI indices without imaging or biopsy may
misclassify cases and introduce outcome bias, which will affect the diagnostic validity of
MAFLD/MASLD.
2. A single 24-hour recall may not accurately reflect habitual intake, which risks
misclassification of exposure.
3. U-shaped inflection thresholds lack validation; the mechanistic rationale for nonlinearity is
underexplored.
4. Biological pathways linking smoking to reduced flavonoid efficacy remain speculative and
require experimental validation. Additionally, authors should clarify their choice of smoke as a
subgroup analysis instead of other lifestyle factors.
5. Additive effects of flavonoid subclasses may oversimplify interactions that are synergistic
or antagonistic.
6. The differential bioavailability of flavonoid subclasses (e.g., isoflavones vs. anthocyanidins)
is overlooked.
7. The recommendation for a "flavonoid-rich diet" lacks practical guidance, such as food sources
and dosages.
8. Abstract highlights smoking interactions, but results emphasize non-smokers; reframe for
consistency.
9. Some citations (e.g., global prevalence of MAFLD/MASLD) are outdated; please include
more updated literature.
10. Considering the difference in flavonoid association between MASLD and MAFLD, a further
subgroup analysis of MASLD-only and MAFLD-only is suggested. And the difference should
be discussed.
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