Title: Association Between Blood Lead Levels and Constipation in Adults: Insights from
NHANES Data (2005–2010)
Version: 2 Date: 17 Apr 2025
Reviewer:  Xuefeng Jin
Reviewer's report:
This is a well-designed and novel study using high-quality data and advanced analytical
techniques. However, due to concerns around causal overinterpretation, constipation definition,
and confounding adjustment, I recommend minor revision before considering publication.
1. Causal Inference in Discussion
The manuscript at times implies causality (e.g., “lead reduces constipation”), which is not
warranted in a cross-sectional study. Revise to consistently use associative language throughout.
2. Biological Mechanisms Lack Empirical Support
While the authors provide several speculative mechanisms, none are directly tested. Emphasize
their hypothetical nature and avoid overinterpretation.
3. Confounding Bias
Residual confounding remains a concern, especially with lifestyle and medication use. Discuss
the potential impact of unmeasured confounders such as laxative, iron, opioid, or supplement
use.
4. Reverse Causation Possibility
The discussion should include the possibility that individuals with chronic constipation may alter
their lifestyle (diet, supplements, hydration) in ways that affect blood lead levels, contributing
to the observed association.
Title: Association Between Blood Lead Levels and Constipation in Adults: Insights from
NHANES Data (2005–2010)
Version: 2 Date: 17 Apr 2025
Reviewer:  Xuefeng Jin
Reviewer's report:
This is a well-designed and novel study using high-quality data and advanced analytical
techniques. However, due to concerns around causal overinterpretation, constipation definition,
and confounding adjustment, I recommend minor revision before considering publication.
1. Causal Inference in Discussion
The manuscript at times implies causality (e.g., “lead reduces constipation”), which is not
warranted in a cross-sectional study. Revise to consistently use associative language throughout.
2. Biological Mechanisms Lack Empirical Support
While the authors provide several speculative mechanisms, none are directly tested. Emphasize
their hypothetical nature and avoid overinterpretation.
3. Confounding Bias
Residual confounding remains a concern, especially with lifestyle and medication use. Discuss
the potential impact of unmeasured confounders such as laxative, iron, opioid, or supplement
use.
4. Reverse Causation Possibility
The discussion should include the possibility that individuals with chronic constipation may alter
their lifestyle (diet, supplements, hydration) in ways that affect blood lead levels, contributing
to the observed association.
Please review this paper.
user
Title: Association Between Blood Lead Levels and Constipation in Adults: Insights from
NHANES Data (2005–2010)
Version: 2 Date: 17 Apr 2025
Reviewer:  Xuefeng Jin
Reviewer's report:
This is a well-designed and novel study using high-quality data and advanced analytical
techniques. However, due to concerns around causal overinterpretation, constipation definition,
and confounding adjustment, I recommend minor revision before considering publication.
1. Causal Inference in Discussion
The manuscript at times implies causality (e.g., “lead reduces constipation”), which is not
warranted in a cross-sectional study. Revise to consistently use associative language throughout.
2. Biological Mechanisms Lack Empirical Support
While the authors provide several speculative mechanisms, none are directly tested. Emphasize
their hypothetical nature and avoid overinterpretation.
3. Confounding Bias
Residual confounding remains a concern, especially with lifestyle and medication use. Discuss
the potential impact of unmeasured confounders such as laxative, iron, opioid, or supplement
use.
4. Reverse Causation Possibility
The discussion should include the possibility that individuals with chronic constipation may alter
their lifestyle (diet, supplements, hydration) in ways that affect blood lead levels, contributing
to the observed association.
assistant