
==== Front
Curr Ther Res Clin Exp
Curr Ther Res Clin Exp
Current Therapeutic Research, Clinical and Experimental
0011-393X
1879-0313
Elsevier

S0011-393X(24)00025-0
10.1016/j.curtheres.2024.100755
100755
Review Article
Impact of Magnesium Supplementation on Blood Pressure: An Umbrella Meta-Analysis of Randomized Controlled Trials
Alharran Abdullah M 1
Alzayed Mooza M 1
Jamilian Parsa Jamilianparsa@gmail.com
2⁎⁎
Prabahar Kousalya 3
Kamal Aminah Hassan 4
Alotaibi Muteb N 5
Elshaer Omar E 5
Alhatm Mshal 5
Masmoum Mohd Diya 5
Hernández-Wolters Benjamin 6
Sindi Raghad 7
Kord-Varkaneh Hamed hamedkord39@yahoo.com
8⁎
Abu-Zaid Ahmed 5
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
31 7 2024
2024
31 7 2024
101 10075525 3 2024
16 7 2024
© 2024 The Author(s)
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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
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pmcIntroduction

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 properties14 and interacts with calcium,12 decreasing peripheral vascular resistance15 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 I2 statistic and Cochrane's Q-test, with a P < 0.1 or I2 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 Flow chart of the study selection process for the umbrella meta-analysis.

Figure 1

Table 1 Study characteristics of included studies.

Table 1Citation (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	

Table 2 Results of the assessment of the methodological quality of meta-analysis.

Table 2: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., 202121	+	+	+	+	+	+	+	+	+	+	+	11	
Zhao, B., 202026	+	+	+	+	+	+	+	+	+	+	+	11	
Verma, H., 201722	+	+	+	+	+	+	+	-	+	+	+	10	
Dibaba, D. T., 201727	+	+	+	+	+	+	+	+	+	+	+	11	
Zhang, X., 201628	+	+	+	+	+	+	-	-	+	-	+	8	
Rosanoff, A., 201329	+	+	+	+	+	+	-	-	+	-	+	8	
Kass, L., 201219	+	+	+	+	+	+	-	-	+	-	+	8	
Song, Y., 200630	+	+	+	+	+	+	+	-	+	+	+	10	
Dickinson, H. O., 200631	+	+	+	+	+	+	+	+	+	+	+	11	
Jee, S. H. A., 200232	+	+	+	+	+	+	-	-	+	-	+	8	

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 (I2 = 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 Forest plot of the umbrella review on the effects of magnesium intervention on systolic blood pressure.

Figure 2

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 (I2 = 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 Forest plot of the umbrella review on the effects of magnesium intervention on diastolic blood pressure.

Figure 3

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

Figure 4

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.

Appendix Supplementary materials

Image, application 1

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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.

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

1 Cooper RS Amoah AG Mensah GA High blood pressure Ethnic Dis 13 2003 48 52
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 178 1 2018 28 36 29131895
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) 388 10053 2016 1659 27733284
5 Wan EYF Yu EYT Chin WY Association of blood pressure and risk of cardiovascular and chronic kidney disease in Hong Kong hypertensive patients Hypertension 74 2 2019 331 340 31230539
6 Lee CJ Kim JY Shim E The effects of diet alone or in combination with exercise in patients with prehypertension and hypertension: a randomized controlled trial Korean Circulat J 48 7 2018 637 651
7 Dickey RA Janick JJ Lifestyle modifications in the prevention and treatment of hypertension Endocrine Pract 7 5 2001 392 399
8 Fiorentini D Cappadone C Farruggia G Prata C Magnesium: biochemistry, nutrition, detection, and social impact of diseases linked to its deficiency Nutrients 13 4 2021 1136 33808247
9 De Baaij JH Hoenderop JG Bindels RJ Magnesium in man: implications for health and disease Physiolog Rev 95 1 2015 1 46
10 Volpe SL Magnesium in disease prevention and overall health Adv Nutr 4 3 2013 378S 383S 23674807
11 Houston M The role of magnesium in hypertension and cardiovascular disease J Clin Hypertens 13 11 2011 843 847
12 Satake K Lee JD Shimizu H Effects of magnesium on prostacyclin synthesis and intracellular free calcium concentration in vascular cells Magnesium research. 17 1 2004 20 27 15083565
13 Landau R Scott JA Smiley RM Magnesium-induced vasodilation in the dorsal hand vein⋆ BJOG 111 5 2004 446 451 15104608
14 Patni N Fatima M Lamis A Magnesium and hypertension: decoding novel anti-hypertensives Cureus 14 6 2022 e25839
15 Feyh A Bracero L Lakhani HV Role of dietary components in modulating hypertension J Clin Experim Cardiol 7 4 2016
16 Rosanoff A Magnesium supplements may enhance the effect of antihypertensive medications in stage 1 hypertensive subjects Magnes Res 23 1 2010 27 40 20228010
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 12 7 1998 447 453 9702930
18 Dickinson HO Nicolson D Campbell F Magnesium supplementation for the management of primary hypertension in adults Cochrane Database Syst Rev 3 2006 1465 1858
19 Kass L Weekes J Carpenter L Effect of magnesium supplementation on blood pressure: a meta-analysis Eur J Clin Nutr 66 4 2012 411 418 22318649
20 Jee SH Miller ER Guallar E The effect of magnesium supplementation on blood pressure: a meta-analysis of randomized clinical trials Am J Hypertens 15 8 2002 691 696 12160191
21 Asbaghi O Hosseini R Boozari B 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 199 2 2021 413 424 32385715
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 30 5 2017 621 633
23 Moher D Shamseer L Clarke M Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement Syst Rev 4 1 2015 1 9 25554246
24 Shea BJ Reeves BC Wells G AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both BMJ 2017 358
25 Guyatt GH Oxman AD Vist GE GRADE: an emerging consensus on rating quality of evidence and strength of recommendations BMJ 336 7650 2008 924 926 18436948
26 Zhao B Deng H Li B 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 36 3 2020 e3243 31758631
27 Dibaba DT Xun P Song Y 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 106 3 2017 921 929 28724644
28 Zhang X Li Y Del Gobbo LC Effects of magnesium supplementation on blood pressure: a meta-analysis of randomized double-blind placebo-controlled trials Hypertension 68 2 2016 324 333 27402922
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 26 3 2013 93 99 24134861
30 Song Y He K Levitan EB Effects of oral magnesium supplementation on glycaemic control in Type 2 diabetes: a meta-analysis of randomized double-blind controlled trials Diabet Med 23 10 2006 1050 1056 16978367
31 Dickinson HO Nicolson DJ Campbell F Magnesium supplementation for the management of essential hypertension in adults Cochrane Database Syst Rev 3 2006 Cd004640
32 Jee SHA Miller Iii ER Guallar E The effect of magnesium supplementation on blood pressure: a meta-analysis of randomized clinical trials Am J Hypertens 15 8 2002 691 696 12160191
33 Kokubo Y Iwashima Y Higher blood pressure as a risk factor for diseases other than stroke and ischemic heart disease Hypertension 66 2 2015 254 259 26077565
34 Jahnen-Dechent W Ketteler M Magnesium basics Clin Kidney J 5 Suppl_1 2012 i3 i14 26069819
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 23 4 2009 245 251 19020533
36 Sandoo A Van Zanten JJV Metsios GS The endothelium and its role in regulating vascular tone Open Cardiovasc Med J 4 2010 302 21339899
37 Mehansho H Majeti S Tzeghai G Prevention of vascular calcification by magnesium and selected polyphenols Adv Prevent Med 2021 2021 1 5
38 Zhao B Deng H Li B 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 36 3 2020 e3243
39 Intakes IoMSCotSEoDR. Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride. 1997.
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 288 2002 2981 2997 12479763
