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Impact of Magnesium Supplementation on Blood Pressure: An Umbrella Meta-Analysis of Randomized Controlled Trials - PMC

Conflicting results on the effect of magnesium supplementation on blood pressure have been published in previous meta-analyses; hence, we conducted this umbrella meta-analysis of RCTs to provide a more robust conclusion on its effects. Four ...

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Curr Ther Res Clin Exp
. 2024 Jul 31;101:100755. doi:
10.1016/j.curtheres.2024.100755

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Impact of Magnesium Supplementation on Blood Pressure: An Umbrella Meta-Analysis of Randomized Controlled Trials

Abdullah M Alharran

Abdullah M Alharran

1
College of Medicine & Medical Sciences, Arabian Gulf University, Manama, Bahrain

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Abdullah M Alharran

1
,
Mooza M Alzayed

Mooza M Alzayed

1
College of Medicine & Medical Sciences, Arabian Gulf University, Manama, Bahrain

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Mooza M Alzayed

1
,
Parsa Jamilian

Parsa Jamilian

2
School of Medicine, Keele University, Staffordshire, United Kingdom

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Parsa Jamilian

2,
⁎⁎
,
Kousalya Prabahar

Kousalya Prabahar

3
Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia

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Kousalya Prabahar

3
,
Aminah Hassan Kamal

Aminah Hassan Kamal

4
Department of Adult Cardiology, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia

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Aminah Hassan Kamal

4
,
Muteb N Alotaibi

Muteb N Alotaibi

5
College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

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Muteb N Alotaibi

5
,
Omar E Elshaer

Omar E Elshaer

5
College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

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5
,
Mshal Alhatm

Mshal Alhatm

5
College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

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5
,
Mohd Diya Masmoum

Mohd Diya Masmoum

5
College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

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,
Benjamin Hernández-Wolters

Benjamin Hernández-Wolters

6
University Center for Health Science, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico

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Benjamin Hernández-Wolters

6
,
Raghad Sindi

Raghad Sindi

7
Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia

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7
,
Hamed Kord-Varkaneh

Hamed Kord-Varkaneh

8
Department of Nutrition and Food Hygiene, School of Medicine, Nutrition Health Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

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⁎
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Ahmed Abu-Zaid

Ahmed Abu-Zaid

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College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

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Author information

Article notes

Copyright and License information

1
College of Medicine & Medical Sciences, Arabian Gulf University, Manama, Bahrain

2
School of Medicine, Keele University, Staffordshire, United Kingdom

3
Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia

4
Department of Adult Cardiology, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia

5
College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

6
University Center for Health Science, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico

7
Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia

8
Department of Nutrition and Food Hygiene, School of Medicine, Nutrition Health Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

⁎
Address correspondence to: Hamed Kord-Varkaneh, Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
hamedkord39@yahoo.com

⁎⁎
Address correspondence to: Parsa Jamilian, School of Medicine, Keele University, Staffordshire, United Kingdom.
Jamilianparsa@gmail.com

Received 2024 Mar 25; Accepted 2024 Jul 16; Collection date 2024.

© 2024 The Author(s)

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

PMC Copyright notice

PMCID: PMC11401110 PMID:
39280209

Abstract

Background and aim

Conflicting results on the effect of magnesium supplementation on blood pressure have been published in previous meta-analyses; hence, we conducted this umbrella meta-analysis of RCTs to provide a more robust conclusion on its effects.
Methods

Four databases including PubMed, Scopus, EMBASE, and Web of Science were searched to find pertinent papers published on international scientific from inception up to July 15, 2024. We utilized STATA version 17.0 to carry out all statistical analyses (Stata Corporation, College Station, TX, US). The random effects model was used to calculate the overall effect size ES and CI.
Findings

Ten eligible review papers with 8610 participants studied the influence of magnesium on SBP and DBP. The pooling of their effect sizes resulted in a significant reduction of SBP (ES = -1.25 mmHg; 95% CI: -1.98, -0.51,
P
= 0.001) and DBP (ES = -1.40 mmHg; 95% CI: -2.04, -0.75,
P
= 0.000) by magnesium supplementation. In subgroup analysis, a significant reduction in SBP and DBP was observed in magnesium intervention with dosage ≥400 mg/day (ES for SBP = -6.38 mmHg; ES for DBP = -3.71mmHg), as well as in studies with a treatment duration of ≥12 weeks (ES for SBP = -0.42 mmHg; ES for DBP = -0.45 mmHg).
Implications

The findings of the present umbrella meta-analysis showed an overall decrease of SBP and DBP with magnesium supplementation, particularly at doses of ≥400 mg/day for ≥12 weeks.
Key words:
blood pressure, magnesium, systematic review, umbrella of meta-analysis
Introduction

Systemic hypertension, a persistent elevation of the systemic arterial blood pressure (BP), is a highly prevalent condition and a major independent risk factor of mortality and cardiovascular disease.
1
Preventing and treating hypertension has become a significant factor in decreasing the risk and burden of various diseases, thus reducing disease-related mortality.
2
,
3
However, inadequate management of BP still remains one of the greatest individual risk factors of all-cause mortality globally,
4
and each 10 mmHg rise in average systolic blood pressure (SBP) has been previously associated with an increase in cardiovascular disease (CVD) and chronic kidney disease risk by up to 16%.
5
Dietary and lifestyle modifications play major role in managing BP.
6
,
7
For this reason, the pressure-lowering effect of natural supplements has been widely studied, and beneficial effects with minimal adverse effects have been discovered for many substances.
3

Magnesium is the fourth most common cation in the human body,
8
and a deficient intake of magnesium has been associated with various diseases, including asthma, diabetes mellitus, hypertension, stroke, heart disease, hypertension, and even cancer.
9
,
10
Therefore, magnesium has been proposed as a treatment for hypertension.
11
By inducing the formation of nitric oxide and prostacyclin,
12
magnesium helps in modulating vasodilation, decreasing vascular tone and vascular reactivity.
13
Magnesium also possess anti-inflammatory and as antioxidant properties
14
and interacts with calcium,
12
decreasing peripheral vascular resistance
15
and decreasing blood pressure.
16

Observational epidemiological studies have reported a negative association between dietary magnesium supplementation and BP,
17
and various clinical trials have been conducted in the past years to study the effects of magnesium on BP, with inconsistent results published.
16
Even systematic reviews conducted on RCTs provided inconclusive results on the effects of magnesium on SBP and DBP. For instance, one meta-analysis reported a significant reduction in DBP and a nonsignificant reduction in SBP,
18
while another meta-analysis reported that magnesium supplementation resulted in significant reduction of SBP and DBP,
19
and a third meta-analysis reported only a slight decrease in BP.
20
In patients with type 2 diabetes mellitus a meta-analysis reported beneficial effect of magnesium on BP,
21
while a second one showed a favorable effect on SBP but not on DBP.
22

Conflicting results were obtained from various studies and hence we conducted this umbrella meta-analysis of RCTs to provide clear evidence and conclusion on the effect of magnesium supplementation on blood pressure.
Methods

This study was implemented based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines.
23

Search strategy and study selection

Four databases including PubMed, Scopus, EMBASE, and Web of Science were searched to find pertinent papers published on international scientific journals from inception up to July 15, 2024. The search strategy was established using the following keywords and MeSH terms: (((((“Magnesium”[Mesh]) OR “Magnesium”[tiab]))) AND (((((((((Blood Pressure [Title/Abstract] OR Systolic Blood Pressure[Title/Abstract]) OR diastolic Blood Pressure[Title/Abstract]) OR “Blood Pressure”[Mesh]) OR SBP[Title/Abstract]) OR DBP[Title/Abstract]))) AND (((“systematic review” [Title/Abstract] OR “meta-analyses” [Title/Abstract] OR “meta-analysis” [Title/Abstract]))) (Supplementary Table 1).
Inclusion and exclusion criteria

We included articles in the present umbrella meta-analysis according to PICO criteria: Population/Patients (P: subjects treated with magnesium); Intervention (I: magnesium); Comparison (C: control or placebo group); and Outcome (O: SBP and DBP). Meta-analysis articles examining the effects of magnesium on blood pressure (SBP and DBP) in humans with reported effect sizes (ESs) and confidence intervals (CI), were included in the current umbrella meta-analysis. Moreover, observational studies, case reports, controlled clinical trials, prospective studies, studies with a “low quality” score, and articles in languages other than English were excluded.
Methodological quality assessment and grading of the evidence

Two independent researchers utilized the A Measurement Tool to Assess Systematic Reviews (AMSTAR)2 questionnaire to evaluate the methodological quality of eligible meta-analyses.
24
This tool contains 16 items that require referees to answer “Yes,” “Partial Yes,” “No,” or “No Meta-analysis.” The AMSTAR2 list was categorized into “high quality,” “moderate quality,” “low quality,” and “critically low quality.” We appraised the general strength and quality of evidence using GRADE based on the Cochrane Handbook of systematic reviews of interventions.
25
Study selection and data extraction

Two independent investigators reviewed the papers to select those fulfilling the eligibility criteria and discrepancy was resolved by the corresponding author. The following items were extracted from the included articles: year of publication, first author's name, study location, sample size, magnesium supplementation dosage, and effect sizes and CIs for SBP and DBP.
Data synthesis and statistical analysis

We utilized STATA version 17.0 to carry out all statistical analyses (Stata Corporation, College Station, TX, US). To calculate the overall ES and Cis, the random-effects model was used. Heterogeneity among studies was assessed using the I
2
statistic and Cochrane's Q-test, with a
P
< 0.1 or I
2
value >50% regarded as significant. Subgroup analyses were conducted to detect potential sources of heterogeneity based on the reported median predetermined variables, namely duration of intervention and magnesium supplementation dosage. We applied sensitivity analyses to survey the influence of any particular effect size removal on the combined results. Formal Egger's tests and funnel plots visual checking were also performed to detect publication bias, with a
P
-value < 0.05 regarded as meaningful.
Results

Study characteristics

Figure 1
shows the flow diagram of the literature search process. 507 papers were recovered in the electronic database searches, out of which 178 were excluded for being duplications. After screening the titles and abstracts of the remaining 329 publications, 315 articles were removed. Ultimately, 10 meta-analyses published between 2002 and 2021 were included in the umbrella meta-analysis, amounting to a total of 8610 participants.
21
,
22
,
26
,
27
,
28
,
29
,
19
,
30
,
31
,
32
Mean magnesium dose varied from 364 to 440 IU/day, and intervention duration ranged between 8.85 and 14.54 weeks. Detailed characteristics of the included meta-analyses are outlined in
Table 1
. Most of the included meta-analyses in this umbrella review were graded as having moderate to high quality; the results of the quality assessment of every article in each of the AMSTAR2 questionnaire items are presented in
Table 2
.

Figure 1.

Open in a new tab

Flow chart of the study selection process for the umbrella meta-analysis.
Table 1.

Study characteristics of included studies.

Citation (First author et al., year)

No. of studies in meta-analysis

Mean BMI

No. of participants in meta-analysis

Study duration (weeks)

Type of population

Mean age

Mean dosage (mg/day)

Outcomes

Asbaghi (2021)
21

7

28.33

357

11.42

Type 2 diabetes patient

59.75

364

SBP, DBP

Zhao (2020)
26

16

29.2

1105

13.25

Different

48.14

383.18

SBP, DBP

Verma (2017)
22

19

28.2

1296

12.63

Different

49.54

412

SBP, DBP

Dibaba (2017)
27

11

nr

543

14.54

Different

54.85

401

SBP, DBP

Zhang (2016)
28

34

nr

1999

12.31

Different

55.84

399

SBP, DBP

Rosanoff (2013)
29

7

nr

135

8.85

Hypertensive subjects

nr

340

SBP, DBP

Kass (2012)
19

23

nr

1173

11.3

Different

50.1

410

SBP, DBP

Song (2006)
30

4

nr

237

12.5

Type 2 diabetes patient

59.41

440

SBP, DBP

Dickinson (2006)
31

12

nr

545

11

Hypertensive subjects

54

413

SBP, DBP

Jee (2002)
32

20

nr

1220

12.95

Different

52.2

443

SBP, DBP

Open in a new tab
Table 2.

Results of the assessment of the methodological quality of meta-analysis.

Study

A priori design

Selection and data extraction

Literature search

Publication type

List of studies

Characteristics of the included studies

Assessed scientific quality

Scientific quality formulating conclusions

Methods used to combine the findings

Assessed publication bias

Conflict of interest stated

Quality score

Asbaghi, O., 2021
21

+

+

+

+

+

+

+

+

+

+

+

11

Zhao, B., 2020
26

+

+

+

+

+

+

+

+

+

+

+

11

Verma, H., 2017
22

+

+

+

+

+

+

+

-

+

+

+

10

Dibaba, D. T., 2017
27

+

+

+

+

+

+

+

+

+

+

+

11

Zhang, X., 2016
28

+

+

+

+

+

+

-

-

+

-

+

8

Rosanoff, A., 2013
29

+

+

+

+

+

+

-

-

+

-

+

8

Kass, L., 2012
19

+

+

+

+

+

+

-

-

+

-

+

8

Song, Y., 2006
30

+

+

+

+

+

+

+

-

+

+

+

10

Dickinson, H. O., 2006
31

+

+

+

+

+

+

+

+

+

+

+

11

Jee, S. H. A., 2002
32

+

+

+

+

+

+

-

-

+

-

+

8

Open in a new tab
The effects of magnesium supplementation on systolic blood pressure

10 eligible review papers with 8610 participants studied the effect of magnesium on SBP. Pooling their effect sizes based on the random effects model, a significant reduction in SBP after magnesium supplementation was discovered (ES = -1.25 mmHg; 95% CI: -1.98, -0.51,
P
= 0.001) (
Figure 2
). However, a significant heterogeneity among studies was detected (I
2
= 92%, p= 0.000). In subgroup analysis, a significant reduction in systolic blood pressure was observed in magnesium intervention with doses ≥400 mg/day (ES = -6.38 mmHg; 95% CI: -11.56, -1.19,
P
= 0.016) and treatment duration ≥12 weeks (ES = -0.42 mmHg; 95% CI: -0.78, -0.06,
P
= 0.020) (Supplementary Figure 1).

Figure 2.

Open in a new tab

Forest plot of the umbrella review on the effects of magnesium intervention on systolic blood pressure.
The effects of magnesium supplementation on diastolic blood pressure

Ten eligible review papers with 8610 participants scrutinized the influence of magnesium on DBP. The effect size pooling according to the random effects model discovered that magnesium supplementation significantly decreased DBP (ES = -1.40 mmHg; 95% CI: -2.04, -0.75,
P
= 0.000) (
Figure 2
), with a significant heterogeneity among studies (I
2
= 93%,
P
= 0.000). In subgroup analysis, a significant reduction in diastolic blood pressure was found in magnesium intervention with doses ≥400 mg/day (ES = -3.71 mmHg; 95% CI: -6.88, -0.53,
P
= 0.022) and treatment duration ≥12 weeks (ES = -0.45 mmHg; 95% CI: -0.76, -0.14,
P
= 0.004) (Supplementary Figure 1).
Meta-regression

Subsequent analysis of the relationship between intervention duration (week) and magnesium supplementation dosage (mg/day) with SBP and DBP alterations revealed a significant correlation (Supplementary Figure 2) (
Figure 3
).

Figure 3.

Open in a new tab

Forest plot of the umbrella review on the effects of magnesium intervention on diastolic blood pressure.
Sensitivity analysis and publication bias

After sensitivity analysis, no special arm was found to affect the combined effect size (Supplementary Figure 3). Egger's tests and visual inspection of the funnel plots showed no sign of publication bias (
Figure 4
).

Figure 4.

Open in a new tab

Funnel plot of the WMD versus the SE of the WMD. WMD, weighted mean difference; CI, confidence interval; SE, Standard error.
Discussion

The present umbrella meta-analysis on the effect of magnesium supplementation on blood pressure summarized the results of 10 meta-analyses. The findings of this assessment support the evidence that magnesium supplementation lowers DBP and SBP in a statistically significant manner, although the effect size is small, hence, suggesting the potential use of magnesium as part of the dietary interventions for the management of hypertension. Although cost-utility analyses are lacking, magnesium supplementation could potentially reduce the economic costs of hypertension treatment. Sufficient evidence demonstrates the link between hypertension and various chronic diseases,
33
but further investigations are warranted to study the effects of magnesium supplementation on other chronic diseases.

Magnesium is one of the most common minerals in the human body, with 99% of it distributed intracellularly.
34
The role of magnesium in reducing hypertension has been attributed to multiple mechanisms of action, including acting as a calcium channel blocker, competing with sodium binding sites on vascular smooth muscle cells, decreasing intracellular sodium and calcium, enhancing prostaglandin E, binding cooperatively with potassium, inducing vasodilation, improving endothelial dysfunction in diabetic and hypertensive patients.
35
Moreover, magnesium induces nitric oxide release from endothelial cells, which acts as vasoactive mediator and produces a synergistic effect with antihypertensive medications.
36
The effect of magnesium on osteopontin has also been proposed to be one of the mechanisms involved in inhibiting vascular calcification and reducing BP.
37

According to our umbrella meta-analysis, magnesium supplementation resulted in a statistically significant decrease in SBP (ES = -1.25 mmHg; 95% CI: -1.98, -0.51,
P
= 0.001) and DBP (ES = -1.40 mmHg; 95% CI: -2.04, -0.75,
P
= 0.000). Similar results have been obtained by several meta-analyses, including a meta-analysis of 11 RCTs conducted by Asbaghi et al. with magnesium doses ranging from 36.49 to 500 mg/day and intervention duration of 4 to 24 weeks, which reported a significant reduction of SBP and DBP,
21
as well as one by Dibaba et al. which reported that administration of 365 to 450 mg/day of elemental magnesium resulted in a reduction of SBP by 4.18 mmHg and DBP by 2.27 mmHg,
27
and other meta-analyses.
38

In contrast with our study results, Verma et al. reported that magnesium supplementation provides a moderate beneficial impact on SBP but not on DBP,
22
which could be because their meta-analysis on hypertension included only four studies, with a high heterogeneity among those studies. Song et al. reported that magnesium supplementation did not provide beneficial effects on SBP and DBP,
30
however, the study population of the meta-analysis included only patients with type 2 diabetes mellitus, which could be the reason for this conflicting result; moreover, the main focus of the study was the effect of magnesium on glycemic control rather than blood pressure.

According to The American Food and Nutrition Board, the recommended dietary magnesium intake for people aged 31–70 years is 420 mg/day for males and 320 mg/day for females.
39
In our subgroup analysis, a significant reduction in SBP and DBP was observed in magnesium supplementation with doses ≥400 mg/day and treatment duration ≥12 weeks. In line with our results, a meta-analysis conducted by Asbaghi et al. reported in their subgroup analysis that magnesium supplementation at a dose of >300 mg/day or with a duration of >12 weeks provided significant beneficial effects on both SBP and DBP.
21
In another meta-analysis, magnesium supplementation of >370 mg/day resulted in SBP reduction by 0.66 mmHg and DBP reduction by 0.57 mmHg.
19

The reduction in BP due to magnesium supplementation could have beneficial effects on cardiovascular outcomes. A clinical trial reported that 0.8 to 2 mmHg reduction of SBP could help in decreasing the risks of coronary artery disease, stroke, and heart failure, with a 2 to 3 mmHg decrease of BP reducing the risk of stroke by up to 6 to 12%.
40
Hence, the reduction of BP by magnesium supplementation, although not enough to recommend magnesium as an antihypertensive monotherapy, could have clinical significance when used as a dietary supplement in addition to other antihypertensive medications in subjects with hypertension.
Clinical Implications

Our umbrella meta-analysis of randomized controlled trials revealed that magnesium supplementation significantly reduced SBP and DBP. Hence, magnesium supplementation can be used in conjunction with antihypertensive medications to cause a significant decrease in blood pressure.
Strengths and Limitations

To the best of our knowledge, this is the first umbrella meta-analysis to find the effect of magnesium supplementation on BP. We performed subgroup analysis based on the dose and duration of magnesium. Since our review included only meta-analyses of RCTs, bias was significantly reduced. In addition, Egger's test and visual inspection of the funnel plot revealed no publication bias.

However, our review is not without limitations. Significant heterogeneity was found among the included meta-analysis, and the dose and duration of magnesium interventions in patients with specific comorbidities were not reported. Thus, we recommend that future studies focus on the effects of magnesium supplementation on blood pressure in patients with comorbidities. Moreover, overlapping is unavoidable in any umbrella review which is another limitation of this review.
Conclusion

The findings of the present umbrella meta-analysis showed a small but statistically significant decrease of SBP and DBP with magnesium supplementation, with significant effects with doses ≥400 mg/day and duration ≥12 weeks. Although the reduction of BP by magnesium supplementation is not enough to recommend its use as monotherapy for hypertension, it could have clinical significance when used as a dietary supplement in addition to other antihypertensive medications in patients with hypertension. Further studies are required to determine the effects of magnesium supplementation on BP in patients with comorbidities.
Declaration of competing interest

No conflict of interest to declare.
Acknowledgments

Funding

None.
Author Contributions

A.M.A., P.J., H.K.-V., and A.A.-Z. carried out the concept, design, and drafting of this study. K.P. and H.K.-V. searched databases and screened articles. M.M.A., A.H.K., M.N.A., O.E.E., M.A., M.D.M., B.H.-W., and R.S. contributed to literature review, data collection, data interpretation, and reviewing of manuscript for editorial and intellectual contents. B.H.-W., H.K.-V., and A.A.-Z. supervised the study and performed statistical analysis. All authors approved the final version of the manuscript.
Footnotes

Supplementary material associated with this article can be found, in the online version, at
doi:10.1016/j.curtheres.2024.100755
.
Contributor Information

Parsa Jamilian, Email: Jamilianparsa@gmail.com.

Hamed Kord-Varkaneh, Email: hamedkord39@yahoo.com.
Appendix. Supplementary materials

mmc1.docx
(18.8KB, docx)

mmc2.docx
(71.2KB, docx)

mmc3.docx
(31KB, docx)

mmc4.docx
(87.2KB, docx)

References

1.
Cooper RS, Amoah AG, Mensah GA. High blood pressure. Ethnic Dis. 2003;13:48–52.
[
PubMed
] [
Google Scholar
]

2.
Oparil S, Weber MA. Hypertension: a companion to Brenner and Rector's the kidney. 2nd ed ed: Elsevier Saunders; 2005.

3.
Brunström M, Carlberg B. Association of blood pressure lowering with mortality and cardiovascular disease across blood pressure levels: a systematic review and meta-analysis. JAMA Internal Med. 2018;178(1):28–36. doi: 10.1001/jamainternmed.2017.6015.
[
DOI
] [
PMC free article
] [
PubMed
] [
Google Scholar
]

4.
Collaborators GRF Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet (London, England) 2016;388(10053):1659. doi: 10.1016/S0140-6736(16)31679-8.
[
DOI
] [
PMC free article
] [
PubMed
] [
Google Scholar
]

5.
Wan EYF, Yu EYT, Chin WY, et al. Association of blood pressure and risk of cardiovascular and chronic kidney disease in Hong Kong hypertensive patients. Hypertension. 2019;74(2):331–340. doi: 10.1161/HYPERTENSIONAHA.119.13123.
[
DOI
] [
PMC free article
] [
PubMed
] [
Google Scholar
]

6.
Lee CJ, Kim JY, Shim E, et al. The effects of diet alone or in combination with exercise in patients with prehypertension and hypertension: a randomized controlled trial. Korean Circulat J. 2018;48(7):637–651. doi: 10.4070/kcj.2017.0349.
[
DOI
] [
PMC free article
] [
PubMed
] [
Google Scholar
]

7.
Dickey RA, Janick JJ. Lifestyle modifications in the prevention and treatment of hypertension. Endocrine Pract. 2001;7(5):392–399. doi: 10.4158/EP.7.5.392.
[
DOI
] [
PubMed
] [
Google Scholar
]

8.
Fiorentini D, Cappadone C, Farruggia G, Prata C. Magnesium: biochemistry, nutrition, detection, and social impact of diseases linked to its deficiency. Nutrients. 2021;13(4):1136. doi: 10.3390/nu13041136.
[
DOI
] [
PMC free article
] [
PubMed
] [
Google Scholar
]

9.
De Baaij JH, Hoenderop JG, Bindels RJ. Magnesium in man: implications for health and disease. Physiolog Rev. 2015;95(1):1–46. doi: 10.1152/physrev.00012.2014.
[
DOI
] [
PubMed
] [
Google Scholar
]

10.
Volpe SL. Magnesium in disease prevention and overall health. Adv Nutr. 2013;4(3):378S–383S. doi: 10.3945/an.112.003483.
[
DOI
] [
PMC free article
] [
PubMed
] [
Google Scholar
]

11.
Houston M. The role of magnesium in hypertension and cardiovascular disease. J Clin Hypertens. 2011;13(11):843–847. doi: 10.1111/j.1751-7176.2011.00538.x.
[
DOI
] [
PMC free article
] [
PubMed
] [
Google Scholar
]

12.
Satake K, Lee JD, Shimizu H, et al. Effects of magnesium on prostacyclin synthesis and intracellular free calcium concentration in vascular cells. Magnesium research. 2004;17(1):20–27.
[
PubMed
] [
Google Scholar
]

13.
Landau R, Scott JA, Smiley RM. Magnesium-induced vasodilation in the dorsal hand vein⋆. BJOG. 2004;111(5):446–451. doi: 10.1111/j.1471-0528.2004.00114.x.
[
DOI
] [
PubMed
] [
Google Scholar
]

14.
Patni N, Fatima M, Lamis A, et al. Magnesium and hypertension: decoding novel anti-hypertensives. Cureus. 2022;14(6) doi: 10.7759/cureus.25839.
[
DOI
] [
PMC free article
] [
PubMed
] [
Google Scholar
]

15.
Feyh A, Bracero L, Lakhani HV, et al. Role of dietary components in modulating hypertension. J Clin Experim Cardiol. 2016;7(4) doi: 10.4172/2155-9880.1000433.
[
DOI
] [
PMC free article
] [
PubMed
] [
Google Scholar
]

16.
Rosanoff A. Magnesium supplements may enhance the effect of antihypertensive medications in stage 1 hypertensive subjects. Magnes Res. 2010;23(1):27–40. doi: 10.1684/mrh.2010.0198.
[
DOI
] [
PubMed
] [
Google Scholar
]

17.
Mizushima S, Cappuccio F, Nichols R, Elliott P. Dietary magnesium intake and blood pressure: a qualitative overview of the observational studies. J Human hypertens. 1998;12(7):447–453. doi: 10.1038/sj.jhh.1000641.
[
DOI
] [
PubMed
] [
Google Scholar
]

18.
Dickinson HO, Nicolson D, Campbell F, et al. Magnesium supplementation for the management of primary hypertension in adults. Cochrane Database Syst Rev. 2006;(3):1465–1858. doi: 10.1002/14651858.CD004641.pub2.
[
DOI
] [
PubMed
] [
Google Scholar
]

19.
Kass L, Weekes J, Carpenter L. Effect of magnesium supplementation on blood pressure: a meta-analysis. Eur J Clin Nutr. 2012;66(4):411–418. doi: 10.1038/ejcn.2012.4.
[
DOI
] [
PubMed
] [
Google Scholar
]

20.
Jee SH, Miller ER, Guallar E, et al. The effect of magnesium supplementation on blood pressure: a meta-analysis of randomized clinical trials. Am J Hypertens. 2002;15(8):691–696. doi: 10.1016/s0895-7061(02)02964-3.
[
DOI
] [
PubMed
] [
Google Scholar
]

21.
Asbaghi O, Hosseini R, Boozari B, et al. The effects of magnesium supplementation on blood pressure and obesity measure among type 2 diabetes patient: a systematic review and meta-analysis of randomized controlled trials. Biol Trace Elem Res. 2021;199(2):413–424. doi: 10.1007/s12011-020-02157-0.
[
DOI
] [
PubMed
] [
Google Scholar
]

22.
Verma H, Garg R. Effect of magnesium supplementation on type 2 diabetes associated cardiovascular risk factors: a systematic review and meta-analysis. J Human Nutr Dietet. 2017;30(5):621–633. doi: 10.1111/jhn.12454.
[
DOI
] [
PubMed
] [
Google Scholar
]

23.
Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4(1):1–9. doi: 10.1186/2046-4053-4-1.
[
DOI
] [
PMC free article
] [
PubMed
] [
Google Scholar
]

24.
Shea BJ, Reeves BC, Wells G, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017:358. doi: 10.1136/bmj.j4008.
[
DOI
] [
PMC free article
] [
PubMed
] [
Google Scholar
]

25.
Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924–926. doi: 10.1136/bmj.39489.470347.AD.
[
DOI
] [
PMC free article
] [
PubMed
] [
Google Scholar
]

26.
Zhao B, Deng H, Li B, et al. Association of magnesium consumption with type 2 diabetes and glucose metabolism: a systematic review and pooled study with trial sequential analysis. Diabetes Metab Res Rev. 2020;36(3):e3243. doi: 10.1002/dmrr.3243.
[
DOI
] [
PubMed
] [
Google Scholar
]

27.
Dibaba DT, Xun P, Song Y, et al. The effect of magnesium supplementation on blood pressure in individuals with insulin resistance, prediabetes, or noncommunicable chronic diseases: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2017;106(3):921–929. doi: 10.3945/ajcn.117.155291.
[
DOI
] [
PMC free article
] [
PubMed
] [
Google Scholar
]

28.
Zhang X, Li Y, Del Gobbo LC, et al. Effects of magnesium supplementation on blood pressure: a meta-analysis of randomized double-blind placebo-controlled trials. Hypertension. 2016;68(2):324–333. doi: 10.1161/HYPERTENSIONAHA.116.07664.
[
DOI
] [
PubMed
] [
Google Scholar
]

29.
Rosanoff A, Plesset MR. Oral magnesium supplements decrease high blood pressure (SBP>155 mmHg) in hypertensive subjects on anti-hypertensive medications: a targeted meta-analysis. Magnes Res. 2013;26(3):93–99. doi: 10.1684/mrh.2013.0343.
[
DOI
] [
PubMed
] [
Google Scholar
]

30.
Song Y, He K, Levitan EB, et al. Effects of oral magnesium supplementation on glycaemic control in Type 2 diabetes: a meta-analysis of randomized double-blind controlled trials. Diabet Med. 2006;23(10):1050–1056. doi: 10.1111/j.1464-5491.2006.01852.x.
[
DOI
] [
PubMed
] [
Google Scholar
]

31.
Dickinson HO, Nicolson DJ, Campbell F, et al. Magnesium supplementation for the management of essential hypertension in adults. Cochrane Database Syst Rev. 2006;(3) doi: 10.1002/14651858.CD004640.pub2.
[
DOI
] [
PMC free article
] [
PubMed
] [
Google Scholar
]

32.
Jee SHA, Miller Iii ER, Guallar E, et al. The effect of magnesium supplementation on blood pressure: a meta-analysis of randomized clinical trials. Am J Hypertens. 2002;15(8):691–696. doi: 10.1016/s0895-7061(02)02964-3.
[
DOI
] [
PubMed
] [
Google Scholar
]

33.
Kokubo Y, Iwashima Y. Higher blood pressure as a risk factor for diseases other than stroke and ischemic heart disease. Hypertension. 2015;66(2):254–259. doi: 10.1161/HYPERTENSIONAHA.115.03480.
[
DOI
] [
PubMed
] [
Google Scholar
]

34.
Jahnen-Dechent W, Ketteler M. Magnesium basics. Clin Kidney J. 2012;5(Suppl_1):i3–i14. doi: 10.1093/ndtplus/sfr163.
[
DOI
] [
PMC free article
] [
PubMed
] [
Google Scholar
]

35.
Guerrero-Romero F, Rodríguez-Morán M. The effect of lowering blood pressure by magnesium supplementation in diabetic hypertensive adults with low serum magnesium levels: a randomized, double-blind, placebo-controlled clinical trial. J Human Hypertens. 2009;23(4):245–251. doi: 10.1038/jhh.2008.129.
[
DOI
] [
PubMed
] [
Google Scholar
]

36.
Sandoo A, Van Zanten JJV, Metsios GS, et al. The endothelium and its role in regulating vascular tone. Open Cardiovasc Med J. 2010;4:302. doi: 10.2174/1874192401004010302.
[
DOI
] [
PMC free article
] [
PubMed
] [
Google Scholar
]

37.
Mehansho H, Majeti S, Tzeghai G. Prevention of vascular calcification by magnesium and selected polyphenols. Adv Prevent Med. 2021;2021:1–5. doi: 10.1155/2021/6686597.
[
DOI
] [
PMC free article
] [
PubMed
] [
Google Scholar
]

38.
Zhao B, Deng H, Li B, et al. Association of magnesium consumption with type 2 diabetes and glucose metabolism: a systematic review and pooled study with trial sequential analysis. Diab metabol Res Rev. 2020;36(3):e3243. doi: 10.1002/dmrr.3243.
[
DOI
] [
PubMed
] [
Google Scholar
]

39.
Intakes IoMSCotSEoDR. Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride. 1997.
[
PubMed
]

40.
Group CftACR.  The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT-LLT) JAMA. 2002;288:2981–2997. doi: 10.1001/jama.288.23.2998.
[
DOI
] [
PubMed
] [
Google Scholar
]

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</reference>

<statements>
1. Magnesium supplementation lowered blood pressure modestly (systolic −1.25 mmHg; diastolic −1.40 mmHg) without supplied cardiovascular outcome data
2. An umbrella meta-analysis of 10 meta-analyses including 8,610 participants found that magnesium supplementation significantly reduced systolic blood pressure by 1.25 mmHg (95% CI −1.98 to −0.51) and diastolic blood pressure by 1.40 mmHg (95% CI −2.04 to −0.75), although heterogeneity was high (I² = 92% for systolic and 93% for diastolic pressure)
3. In subgroup analysis, doses of at least 400 mg/day were associated with larger reductions: systolic pressure by 6.38 mmHg (95% CI −11.56 to −1.19) and diastolic pressure by 3.71 mmHg (95% CI −6.88 to −0.53)
4. Studies lasting at least 12 weeks showed smaller but significant effects: systolic pressure by 0.42 mmHg (95% CI −0.78 to −0.06) and diastolic pressure by 0.45 mmHg (95% CI −0.76 to −0.14)
5. The authors note that the effect is not large enough to recommend magnesium as antihypertensive monotherapy, but it may be clinically meaningful as a dietary supplement alongside other antihypertensive treatments
6. Proposed mechanisms include nitric oxide release, vasodilation, reduced vascular tone, anti-inflammatory and antioxidant effects, and interaction with calcium and potassium pathways
7. Previous meta-analyses have conflicted: one reported benefit on systolic but not diastolic pressure, and another found no beneficial effect on either, underscoring heterogeneity and population dependence
8. Magnesium supplementation is feasible and modestly lowers blood pressure, but the supplied evidence does not establish cardiovascular outcome benefit
</statements>

Begin the assessment now. Output only the JSON list, without any conversational text or explanations.