# Associations between magnesium depletion score and depression among individuals aged 20 to 60 years
Researcher: Ge Zhang
Chinese name: 张格
ORCID identity anchor: https://orcid.org/0000-0002-3116-3246
Canonical researcher: https://drgezhang.com/#person
Journal: Journal of Trace Elements in Medicine and Biology
Year: 2024
Type: Article
DOI: 10.1016/j.jtemb.2024.127543
Canonical page: https://drgezhang.com/papers/doi-10-1016-j-jtemb-2024-127543.html
Markdown record: https://drgezhang.com/papers/doi-10-1016-j-jtemb-2024-127543.md
## Full Authors
1. Zongao Cai
2. Jiachen She
3. Xiaozhu Liu
4. Ruihui Li
5. Shuang Guo
6. Zeyang Han
7. Jiyang Zhou
8. Hairong Zhang
9. Yudi Xu
10. Ge Zhang
11. Zhaokai Zhou
12. Xueli Guo
13. Shiyong Wu
## Research & review context
### Research fields
- Nutritional epidemiology
- Population mental-health research
### Review topics
- Magnesium depletion proxies and depressive symptoms
- Medication and renal-function components in cross-sectional nutritional scores
### Scientific role
A survey-weighted secondary analysis relating a four-domain proxy score to concurrent PHQ-9 classification in US adults aged 20–60.
### Evidence position
Observational prevalence-odds evidence, with questionnaire-defined symptoms and no biochemical magnesium validation or intervention.
### Related concepts
- Proxy exposure measurement
- PHQ-9 outcome definition
- Cross-sectional confounding
### Possible citation contexts
- Evidence synthesis on MDS and depressive symptoms, specifying the PHQ-9 threshold, sample exclusions and adjusted odds rather than incident disease risk.
- Methods discussion of composite exposure scores and survey weighting; not evidence for a validated depression screening tool.
Possible literature-review contexts, not evidence of existing citations. Read the findings and Evidence Scope before citing the original article.
## Evidence Snapshot
**Associations between magnesium depletion score and depression among individuals aged 20 to 60 years**
A cross-sectional NHANES analysis examined a medication, renal-function and alcohol-based magnesium depletion score in relation to PHQ-9-defined depressive symptoms. The adjusted associations describe the surveyed analytic sample; they do not validate a depression diagnostic tool or demonstrate benefit from magnesium supplementation.
| Evidence | Value |
| --- | --- |
| Unique total | n=18,247 |
| Pooled NHANES 2005–2018 analytic sample | n=18,247 |
## Research Question
Among NHANES 2005–2018 adults aged 20–60 years, how was magnesium depletion score associated with a PHQ-9 score of at least 10 after survey-weighted covariate adjustment?
## Author Evidence Summary
The study pooled public survey data and compared concurrent MDS and PHQ-9 classifications. The main regression table supports a modest adjusted per-point association and higher odds in the MDS 2 and at least 3 categories. MDS is a proxy score, the outcome is questionnaire-defined, and reverse causation and residual confounding remain possible.
## Key Findings
### KF1: The pooled NHANES 2005–2018 cross-sectional analysis included 18,247 adults aged 20–60 years; 1,753 met the study's PHQ-9 threshold of at least 10.
Context: These are unweighted participant counts after the stated exclusions. PHQ-9 reflects self-reported symptoms in the preceding two weeks; the threshold classification is not an independently confirmed clinical diagnosis or incident depression outcome.
| Evidence | Value |
| --- | --- |
| analytic participants | 18,247 |
| PHQ-9 at least 10 | 1,753 |
| PHQ-9 below 10 | 16,494 |
| survey years | 2005–2018 |
Source locator: Publisher PDF p. 2, Methods 2.1–2.2 and Fig. 1; pp. 3–4, Table 1.
### KF2: MDS was a 0–5 score assembled from diuretic use, proton pump inhibitor use, reduced estimated glomerular filtration rate and heavy drinking.
Context: The score is an operational proxy assembled from medication, renal-function and alcohol variables. This study did not measure or validate whole-body magnesium deficiency against serum magnesium. A higher score must not be described as a directly measured magnesium concentration.
| Evidence | Value |
| --- | --- |
| score range | 0–5 |
| diuretic use | 1 point |
| proton pump inhibitor use | 1 point |
| renal component | 1 point for eGFR between 60 and 90; 2 points below 60 mL/min/1.73 m² |
| heavy drinking component | 1 point; more than 1 drink/day for women or 2 drinks/day for men |
Source locator: Publisher PDF p. 2, Methods 2.3; p. 5, Discussion limitations.
### KF3: In survey-weighted Model 3, each one-point higher MDS was associated with higher odds of PHQ-9-defined depression: OR 1.15, 95% CI 1.04–1.26, P=0.0100.
Context: Model 3 adjusted for age, sex, race/ethnicity, education, marital status, BMI, smoking, diabetes and dietary energy, calcium and magnesium intake. This adjusted prevalence-odds association is neither a prospective risk estimate nor an effect of changing magnesium status.
| Evidence | Value |
| --- | --- |
| model | Survey-weighted Model 3 |
| comparison | Per 1 MDS point |
| OR | 1.15 |
| 95% CI | 1.04–1.26 |
| P | 0.0100 |
Source locator: Publisher PDF p. 3, Methods 2.5; p. 4, Results 3.2 and Table 2, continuous MDS row and footnote a.
### KF4: Relative to MDS 0, Model 3 ORs were 1.03 (95% CI 0.87–1.21) for MDS 1, 1.41 (1.12–1.78) for MDS 2, and 1.58 (1.06–2.35) for MDS at least 3.
Context: MDS 1 did not show a statistically significant association. The highest category contained only 368 participants, including 71 with PHQ-9 at least 10; sparse high scores limit precision and do not define a clinical screening or treatment threshold.
| Evidence | Value |
| --- | --- |
| MDS 1 versus 0 | OR 1.03; 95% CI 0.87–1.21; P=0.7600 |
| MDS 2 versus 0 | OR 1.41; 95% CI 1.12–1.78; P=0.0040 |
| MDS at least 3 versus 0 | OR 1.58; 95% CI 1.06–2.35; P=0.0300 |
| highest-category participants | 368 |
| highest-category PHQ-9 at least 10 | 71 |
Source locator: Publisher PDF p. 4, Table 1 continuation, MDS rows; Table 2, Model 3 categorical MDS rows and footnote b.
### KF5: The component analysis reported an association for proton pump inhibitor use in Model 3: OR 2.24, 95% CI 1.78–2.80, P<0.0001.
Context: Diuretic use, heavy drinking and the renal-function categories had confidence intervals crossing 1 in the same model. These component estimates do not establish medication-induced depression, magnesium mediation, or benefit from stopping a prescribed medication.
| Evidence | Value |
| --- | --- |
| PPI-use OR | 2.24 |
| 95% CI | 1.78–2.80 |
| P | <0.0001 |
| analysis | Survey-weighted component associations, Model 3 |
Source locator: Publisher PDF p. 5, Table 3, Model 3 component rows and footnote a; p. 4, Results 3.2.
### KF6: The restricted cubic spline analysis reported P=0.084 for nonlinearity.
Context: The test did not detect nonlinearity at the paper's 0.05 significance level; this is not proof that the relationship is linear. Figure 2's wording about a beneficial threshold is not adopted as a clinical claim, and no numerical threshold is extracted from the curve.
| Evidence | Value |
| --- | --- |
| nonlinearity P | 0.084 |
| test | Restricted cubic spline; likelihood-ratio assessment |
| reference shown in figure | MDS 0 |
Source locator: Publisher PDF p. 3, Methods 2.5; p. 4, Results 3.2; p. 5, Fig. 2 and its caption.
### KF7: All reported subgroup interaction P values in Table 4 exceeded 0.05.
Context: Failure to detect interaction does not show that every subgroup estimate is statistically significant, identical or clinically useful. Several subgroup confidence intervals cross 1, and some are wide; these stratified analyses are not independent external validation.
| Evidence | Value |
| --- | --- |
| age interaction P | 0.140 |
| sex interaction P | 0.180 |
| race/ethnicity interaction P | 0.134 |
| reported interaction tests | All P>0.05 |
Source locator: Publisher PDF p. 3, Methods 2.5; p. 4, Results 3.3; p. 6, Table 4, interaction column and footnote a.
## Study Design & Analytical Framework
### Study profile
- Study Design: Secondary pooled cross-sectional analysis of NHANES 2005–2018
- Evidence Type: Survey-weighted human prevalence-odds association
- Unique total: 18,247
- Population: Adults aged 20–60 years after exclusions for missing PHQ-9, MDS and specified covariates and for pregnancy
- Primary Endpoint: PHQ-9 score at least 10 at the survey assessment
- Secondary Endpoint: The same PHQ-9 outcome in score-category, component, spline and subgroup analyses; no separate prospective endpoint
- External validation: No
- Data modalities: PHQ-9 symptom questionnaire, medication-use and alcohol variables, estimated glomerular filtration rate, demographic and health covariates, two 24-hour dietary recalls
### Cohort hierarchy
| Cohort | Role | n | Relationship |
| --- | --- | ---: | --- |
| Pooled NHANES 2005–2018 analytic sample | Single cross-sectional analytic sample; 1,753 participants met PHQ-9 at least 10 and 16,494 did not | 18247 | Independent cohort |
## What This Study Adds
- Quantifies the association of an operational magnesium depletion score with concurrent PHQ-9 classification in a pooled NHANES adult sample.
- Separates the per-point association from score-category and component estimates, with their uncertainty.
- Provides spline and subgroup analyses while retaining the limits of non-significant nonlinearity and interaction tests.
## Evidence Scope
### Supports
- Reported survey-weighted MDS–PHQ-9 prevalence-odds associations in the included adults aged 20–60 years.
- Definition of the proxy score, questionnaire outcome, analytic denominator and covariate-adjustment set in the main article.
- Descriptive assessment of score categories, components, spline nonlinearity and subgroup interactions within the same survey sample.
### Does Not Establish
- That magnesium depletion causes depression, or that lowering MDS or magnesium supplementation prevents or treats depression.
- A validated clinical diagnosis, depression screening rule, individual prognosis or treatment threshold derived from MDS.
- Direct measurement of serum or whole-body magnesium, or proof that magnesium mediates the observed medication associations.
- Proof of linearity from P=0.084, identical effects across subgroups, or statistical significance in every subgroup.
- Numerical results from Supplementary Tables 1–2, which were referenced by the paper but not obtained for this audit.
### Limitations
- The cross-sectional design cannot establish temporal direction; reverse causation and residual confounding remain possible (Discussion, p. 5).
- MDS combines medication use, kidney function and drinking behavior; it is not a biochemical magnesium measurement, and serum-magnesium comparison was unavailable (Methods 2.3; Discussion, p. 5).
- PHQ-9 at least 10 is the study's questionnaire-based outcome, not an independently adjudicated clinical diagnosis (Methods 2.2).
- Participants with specified missing data were excluded. The main text reports use of recommended NHANES weights but does not identify the exact weight variable, pooled-weight construction or a missing-data imputation procedure; no participant-level reanalysis is claimed (Fig. 1; Methods 2.1 and 2.5).
- High MDS values were uncommon: scores 3, 4 and 5 contained 325, 41 and 2 participants and were pooled. High-score and subgroup estimates are correspondingly imprecise (Methods 2.3; Tables 2 and 4).
- Supplementary Tables 1–2 were not available for this audit. Dietary-threshold specifications and alternative-category sensitivity estimates from those files are not presented as verified results.
- Figure 2's caption uses beneficial-threshold language, but the design and results do not establish a beneficial or clinical intervention threshold. The nonlinearity P value does not prove linearity.
- Generalization beyond the included US adult survey population requires independent evidence.
## When This Study Is Useful to Cite
### CU1: How is magnesium depletion score associated with depressive symptoms in NHANES adults?
Cite the pooled 18,247-person cross-sectional sample, PHQ-9 at least 10 outcome, and survey-weighted Model 3 OR 1.15 per MDS point (95% CI 1.04–1.26). State that the exposure is a proxy and the estimate concerns prevalent questionnaire-defined symptoms.
Evidence: [KF1](#kf1), [KF2](#kf2), [KF3](#kf3)
### CU2: What did category and component analyses add?
MDS 2 and at least 3 had reported adjusted ORs of 1.41 and 1.58 versus 0; score 1 had an interval crossing 1. PPI use was associated with the same outcome, without establishing medication harm or magnesium mediation. Preserve the 368-person highest-category denominator.
Evidence: [KF4](#kf4), [KF5](#kf5)
### CU3: What can the spline and subgroup tests establish?
The reported nonlinearity P=0.084 and interaction P values above 0.05 are non-rejection results. They do not prove a linear relationship, equivalent subgroup effects, a beneficial threshold or significant results in all strata.
Evidence: [KF6](#kf6), [KF7](#kf7)
## What This Study Should Not Be Cited to Claim
- That magnesium depletion causes depression, or that lowering MDS or magnesium supplementation prevents or treats depression.
- A validated clinical diagnosis, depression screening rule, individual prognosis or treatment threshold derived from MDS.
- Direct measurement of serum or whole-body magnesium, or proof that magnesium mediates the observed medication associations.
- Proof of linearity from P=0.084, identical effects across subgroups, or statistical significance in every subgroup.
- Numerical results from Supplementary Tables 1–2, which were referenced by the paper but not obtained for this audit.
## Evidence Matrix
### Analytic population and PHQ-9 definition
- Context: These are unweighted participant counts after the stated exclusions. PHQ-9 reflects self-reported symptoms in the preceding two weeks; the threshold classification is not an independently confirmed clinical diagnosis or incident depression outcome.
- Finding: The pooled NHANES 2005–2018 cross-sectional analysis included 18,247 adults aged 20–60 years; 1,753 met the study's PHQ-9 threshold of at least 10.
- Evidence Level: Survey-weighted cross-sectional human association; published main-article evidence
- Scope: These are unweighted participant counts after the stated exclusions. PHQ-9 reflects self-reported symptoms in the preceding two weeks; the threshold classification is not an independently confirmed clinical diagnosis or incident depression outcome.
- Source Locator: Publisher PDF p. 2, Methods 2.1–2.2 and Fig. 1; pp. 3–4, Table 1.
- Evidence refs: [KF1](#kf1)
### Operational MDS construct
- Context: The score is an operational proxy assembled from medication, renal-function and alcohol variables. This study did not measure or validate whole-body magnesium deficiency against serum magnesium. A higher score must not be described as a directly measured magnesium concentration.
- Finding: MDS was a 0–5 score assembled from diuretic use, proton pump inhibitor use, reduced estimated glomerular filtration rate and heavy drinking.
- Evidence Level: Survey-weighted cross-sectional human association; published main-article evidence
- Scope: The score is an operational proxy assembled from medication, renal-function and alcohol variables. This study did not measure or validate whole-body magnesium deficiency against serum magnesium. A higher score must not be described as a directly measured magnesium concentration.
- Source Locator: Publisher PDF p. 2, Methods 2.3; p. 5, Discussion limitations.
- Evidence refs: [KF2](#kf2)
### Adjusted continuous-score association
- Context: Model 3 adjusted for age, sex, race/ethnicity, education, marital status, BMI, smoking, diabetes and dietary energy, calcium and magnesium intake. This adjusted prevalence-odds association is neither a prospective risk estimate nor an effect of changing magnesium status.
- Finding: In survey-weighted Model 3, each one-point higher MDS was associated with higher odds of PHQ-9-defined depression: OR 1.15, 95% CI 1.04–1.26, P=0.0100.
- Evidence Level: Survey-weighted cross-sectional human association; published main-article evidence
- Scope: Model 3 adjusted for age, sex, race/ethnicity, education, marital status, BMI, smoking, diabetes and dietary energy, calcium and magnesium intake. This adjusted prevalence-odds association is neither a prospective risk estimate nor an effect of changing magnesium status.
- Source Locator: Publisher PDF p. 3, Methods 2.5; p. 4, Results 3.2 and Table 2, continuous MDS row and footnote a.
- Evidence refs: [KF3](#kf3)
### Score-category associations
- Context: MDS 1 did not show a statistically significant association. The highest category contained only 368 participants, including 71 with PHQ-9 at least 10; sparse high scores limit precision and do not define a clinical screening or treatment threshold.
- Finding: Relative to MDS 0, Model 3 ORs were 1.03 (95% CI 0.87–1.21) for MDS 1, 1.41 (1.12–1.78) for MDS 2, and 1.58 (1.06–2.35) for MDS at least 3.
- Evidence Level: Survey-weighted cross-sectional human association; published main-article evidence
- Scope: MDS 1 did not show a statistically significant association. The highest category contained only 368 participants, including 71 with PHQ-9 at least 10; sparse high scores limit precision and do not define a clinical screening or treatment threshold.
- Source Locator: Publisher PDF p. 4, Table 1 continuation, MDS rows; Table 2, Model 3 categorical MDS rows and footnote b.
- Evidence refs: [KF4](#kf4)
### PPI component association
- Context: Diuretic use, heavy drinking and the renal-function categories had confidence intervals crossing 1 in the same model. These component estimates do not establish medication-induced depression, magnesium mediation, or benefit from stopping a prescribed medication.
- Finding: The component analysis reported an association for proton pump inhibitor use in Model 3: OR 2.24, 95% CI 1.78–2.80, P<0.0001.
- Evidence Level: Survey-weighted cross-sectional human association; published main-article evidence
- Scope: Diuretic use, heavy drinking and the renal-function categories had confidence intervals crossing 1 in the same model. These component estimates do not establish medication-induced depression, magnesium mediation, or benefit from stopping a prescribed medication.
- Source Locator: Publisher PDF p. 5, Table 3, Model 3 component rows and footnote a; p. 4, Results 3.2.
- Evidence refs: [KF5](#kf5)
### Spline interpretation
- Context: The test did not detect nonlinearity at the paper's 0.05 significance level; this is not proof that the relationship is linear. Figure 2's wording about a beneficial threshold is not adopted as a clinical claim, and no numerical threshold is extracted from the curve.
- Finding: The restricted cubic spline analysis reported P=0.084 for nonlinearity.
- Evidence Level: Survey-weighted cross-sectional human association; published main-article evidence
- Scope: The test did not detect nonlinearity at the paper's 0.05 significance level; this is not proof that the relationship is linear. Figure 2's wording about a beneficial threshold is not adopted as a clinical claim, and no numerical threshold is extracted from the curve.
- Source Locator: Publisher PDF p. 3, Methods 2.5; p. 4, Results 3.2; p. 5, Fig. 2 and its caption.
- Evidence refs: [KF6](#kf6)
### Subgroup interpretation
- Context: Failure to detect interaction does not show that every subgroup estimate is statistically significant, identical or clinically useful. Several subgroup confidence intervals cross 1, and some are wide; these stratified analyses are not independent external validation.
- Finding: All reported subgroup interaction P values in Table 4 exceeded 0.05.
- Evidence Level: Survey-weighted cross-sectional human association; published main-article evidence
- Scope: Failure to detect interaction does not show that every subgroup estimate is statistically significant, identical or clinically useful. Several subgroup confidence intervals cross 1, and some are wide; these stratified analyses are not independent external validation.
- Source Locator: Publisher PDF p. 3, Methods 2.5; p. 4, Results 3.3; p. 6, Table 4, interaction column and footnote a.
- Evidence refs: [KF7](#kf7)
## Q&A
### What population and outcome were actually analyzed?
The analytic sample comprised 18,247 NHANES 2005–2018 adults aged 20–60 years; 1,753 had PHQ-9 scores of at least 10. These are unweighted counts. The endpoint was a questionnaire threshold for recent symptoms, not an independently adjudicated diagnosis or new-onset depression.
Evidence: KF1
### Was magnesium measured directly?
No direct serum-magnesium comparison was available in this study. MDS combined diuretic use, proton pump inhibitor use, renal-function categories and heavy drinking into a 0–5 proxy score; the reported association does not validate the score against a biochemical deficiency measure.
Evidence: KF2
### What was the fully adjusted per-point association?
Survey-weighted Model 3 reported OR 1.15 per MDS point, with 95% CI 1.04–1.26 and P=0.0100. Adjustment included demographics, BMI, smoking, diabetes and dietary energy, calcium and magnesium. This is a concurrent prevalence-odds association, not prospective risk or a causal effect.
Evidence: KF3
### Did all MDS categories show the same evidence?
No. Compared with MDS 0, Model 3 estimates were 1.03 (0.87–1.21), 1.41 (1.12–1.78) and 1.58 (1.06–2.35) for scores 1, 2 and at least 3. The score-1 interval crosses 1; the highest category included only 368 participants. These categories do not establish a clinical action threshold.
Evidence: KF4
### Does the PPI component result show that treatment causes depression?
No. The PPI-use estimate was OR 2.24 (95% CI 1.78–2.80) in Model 3, but medication indications, residual confounding and the cross-sectional design prevent a medication-causation or magnesium-mediation conclusion. It is not evidence to stop a prescribed PPI.
Evidence: KF5
### Does P=0.084 establish a linear dose response or a beneficial threshold?
No. The spline test did not detect nonlinearity at the paper's 0.05 level. That is not proof of linearity, and the caption's beneficial-threshold wording does not establish a diagnostic or treatment cutoff.
Evidence: KF6
### Were the associations significant and identical in every subgroup?
No. All reported interaction P values exceeded 0.05, but several stratum-specific confidence intervals crossed 1 and some were wide. A non-significant interaction does not demonstrate equivalence or significance in each subgroup.
Evidence: KF7
### Can these results justify magnesium supplementation for depression?
No. This was an observational cross-sectional score analysis without a supplementation intervention or prospective depression endpoint. It supports an association requiring further research, not prevention or treatment efficacy.
Evidence: KF1, KF2, KF3
## Concepts & Entities
### Population
NHANES 2005–2018, adults aged 20–60 years
### Exposure
magnesium depletion score, proton pump inhibitor use, renal function, heavy drinking
### Outcome
PHQ-9, depressive symptoms, cross-sectional prevalence
### Methods
survey-weighted logistic regression, restricted cubic splines, interaction analysis
## Related Research
- [Association between sleep duration, sleep trouble and all-cause mortality in individuals with hyperuricemia in the United States](https://drgezhang.com/papers/doi-10-3389-fpubh-2025-1521372.html) — Another NHANES observational analysis, examining sleep and mortality in hyperuricemia. Its exposure, population and longitudinal endpoint differ; shared survey infrastructure does not make it replication of the MDS–PHQ-9 result. (DOI: 10.3389/fpubh.2025.1521372)
## Publication & Provenance
- DOI: https://doi.org/10.1016/j.jtemb.2024.127543
- Publication Url: https://doi.org/10.1016/j.jtemb.2024.127543
- Publisher: https://www.sciencedirect.com/science/article/pii/S0946672X24001639
- PubMed: https://pubmed.ncbi.nlm.nih.gov/39406123/
- Data Url: https://www.cdc.gov/nchs/nhanes/index.htm
- Source Version: Seven-page publisher-formatted published article, Journal of Trace Elements in Medicine and Biology 86 (2024), article 127543; online 9 October 2024. Title, 13-author order, DOI and publication identity match the DOI deposit, PubMed and existing site record.
- Review Basis: Full main PDF read and Tables 1–4 plus Figures 1–2 visually checked on 27 October 2026. Main-article denominators, definitions and Model 3 estimates were checked across text and tables. No participant-level reanalysis was performed.
- Fulltext Access: The author supplied access through the normal ResearchGate author-account full-text download. The copyrighted source PDF is retained in the private audit directory and is not redistributed by this website.
- Source Sha256: 7f62346a80463eea31c7f5a70af9529ef8f0f8a80446da00812f58093d5c5be8
- Supplementary Scope: Supplementary Tables 1–2 are referenced in the main article but were not obtained in this audit. Their detailed dietary thresholds and alternative-category estimates are excluded; the displayed findings are supported by the audited main article.
- Reporting Caveats: Figure 2 caption terminology and overbroad interpretations of nonlinearity or subgroup consistency are not adopted. Crossref's retrieved record contained no correction relation; absence of a relation is not proof that no later notice exists.
## Evidence-page notice
Author-controlled evidence synthesis of the published main article, separate from its abstract. Supplementary-table claims and clinical interpretations not supported by the audited evidence are excluded.
## Links
- DOI: https://doi.org/10.1016/j.jtemb.2024.127543
- HTML page: https://drgezhang.com/papers/doi-10-1016-j-jtemb-2024-127543.html
- Google Scholar query: https://scholar.google.com/scholar?q=%22Associations%20between%20magnesium%20depletion%20score%20and%20depression%20among%20individuals%20aged%2020%20to%2060%20years%22
- ORCID: https://orcid.org/0000-0002-3116-3246