Skip to main content
Download PDF
Download ePub

The effect of magnesium supplementation on serum concentration of lipid profile: an updated systematic review and dose-response meta-analysis on randomized controlled trials

Nutrition Journal volume 24, Article number: 24 (2025) Cite this article

Abstract

Background

Some evidence suggests magnesium might reduce serum levels of lipid profile. Due to the significance of this matter on hand, we centralized our aim to conduct a systematic review and meta-analysis to interrogate the effect of magnesium supplementation on serum levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) in the general population aged ≥ 18 years.

Methods

In line with conducting this study first, relevant articles were found through searching databases, including five databases: Cochrane Library, ClinicalTrials.gov, ISI Web of Science, Scopus, and PubMed until January 2024. Following fulfilling the first aim, their mean differences and standard deviations were calculated to conduct the meta-analysis. Ultimately, an assessment of the statistical heterogeneity of intervention effects was performed using I-squared statistics and Cochran’s Q test.

Results

Regarding serum levels of TC, TG, LDL-C, and HDL-C, twenty-one, twenty-three, twenty, and twenty-five studies were included in the meta-analysis. The pooled estimates showed no significant differences in serum levels of TC, TG, and LDL-C between the magnesium group and comparison group (weighted mean difference (WMD) = 0.34 mg/dl, 95% confidence interval (CI): -1.75 to 2.43, P = 0.749, I2 = 99.1%; WMD=-2.06 mg/dl, 95% CI: -6.35 to 2.23, P = 0.346, I2 = 99.1; WMD = 1.71 mg/dl, 95% CI: -0.81 to 4.24, P = 0.183, I2 = 99.4, respectively). However, magnesium significantly increased HDL-C (WMD = 1.21 mg/dl, 95% CI: 0.58 to 1.85, P < 0.001, I2 = 99.5).

Conclusion

In conclusion, our study showed that magnesium significantly increased HDL-C levels. However, due to high heterogeneity, we must note that more research is needed to make robust recommendations regarding magnesium supplementation in clinical practice.

Registry number

This study was registered in PROSPERO under the protocol number CRD42024505142.

Peer Review reports

Introduction

Worldwide, cardiovascular diseases (CVDs) are a primary cause of morbidity and mortality [1]. The major risk factors for CVDs include smoking, diabetes, hypertension, and dyslipidemia [2, 3]. Dyslipidemia involves an abnormality in lipid balance [4]. Therefore, controlling dyslipidemia could reduce the risk of CVD development. A study examining the US population found that a 10% increase in the rate of hyperlipidemia treatment would prevent 8000 deaths per year [5].

Expanding the domain of affecting factors, researchers delineated that low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C), have a significant effect on CVD progression [6, 7]. HDL-C may have a protective function, whereas the other components of the lipid profile may have adverse effects on CVD [8]. The term “lipid profile” refers to lipids, including LDL-C, HDL-C, TG, and TC.

Looking at the deeper layers, scientists recommend that some nutrients might modulate lipid profile [9,10,11,12]. Magnesium is considered one of the important intracellular cations that participates in numerous enzymatic processes as a vital catalyst [13] and is found in leafy green vegetables, whole grains, nuts, and legumes [14, 15]. Some evidence suggests that a higher dietary intake of magnesium may enact beneficial effects and roles on a range of metabolic conditions namely hypertension [16], insulin resistance [17], dyslipidemia [18], metabolic syndrome [19], CVDs [20], and type 2 diabetes mellitus [21]. Observational studies have also highlighted an inverse association between dietary magnesium intake and key biomarkers for these conditions such as TG [22, 23], low HDL-C [22, 23], fasting insulin [24], as well as markers of endothelial dysfunction and inflammation [25].

Within lipid metabolism, magnesium enacts a fundamental role by enhancing the activity of certain enzymes such as lecithin-cholesterol acyltransferase, lipoprotein lipase, and desaturase [26], reducing the activity of β-hydroxy β-methylglutaryl-CoA (HMG-CoA) reductase, and insulin signaling [27]. Putting all this evidence together, the effect of these enzymes on lipid metabolism has remained unclear.

Supporting this issue on hand through the lenses of clinical research, some randomized controlled trials (RCTs) have assessed the effect of magnesium supplementation on serum levels of lipid profile, though their results are contradictory. Some RCTs showed that magnesium supplementation could improve lipid profile [28,29,30,31,32,33,34], while others did not [35,36,37,38,39]. Finding more robust evidence, one systematic review and meta-analysis in 2017 revealed no significant effect of magnesium supplementation on lipid profile [40], whereas another systematic review and meta-analysis in 2020 showed that magnesium significantly led to diminishing serum levels of LDL-C among diabetic patients [41]. However, the effect of magnesium supplementation on the general population aged ≥ 18 years after the publication of new RCTs remained unclear.

Nonetheless, the results of these new RCTs might not be sufficient for concluding about the efficacy of magnesium supplementation in this context. By employing meta-analysis techniques, the sample size increases, the likelihood of random results reduces, and the significance of statistical findings improves. Therefore, we conducted a systematic review and meta-analysis on RCTs results to assess the impact of oral magnesium supplementation on lipid profile among the overall population.

Methods

The present systematic review and meta-analysis followed the guidelines outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and was registered in PROSPERO under the protocol number CRD42024505142.

This systematic search was conducted using various databases, including the Cochrane Library, ClinicalTrials.gov, ISI Web of Science, Scopus, and PubMed until January 2024. Medical subjects heading (MeSH) and non-MeSH terms related to Magnesium, LDL-C, HDL-C, TG, TC, and clinical trials were used to search. Designing systematic search was performed by utilizing asterisks, quotation marks, parentheses, and Boolean operators (AND and OR) to maximize search outcomes. The search strategies for these databases are presented in supplementary Table 1. In line with collecting data, several steps have been taken. At first, the relevant and found articles were exported, and following that their titles and abstracts were separately reviewed by two individuals (MH and AGh) using the EndNote X21 reference manager. Completing the existing stages, efforts were made to find any missed articles by checking the references of relevant and reviewed articles. If there were any uncertainties, clarification was sought by emailing the corresponding authors.

Study eligibility criteria

In this study, PICOS (Patient/Population, Intervention, Comparison, Outcome, Study types) framework was employed as the inclusion criteria. We included RCTs involving magnesium supplements with a comparison arm, employing either a cross-over or parallel design. The study participants were adults aged 18 or above and we considered studies that reported changes in LDL-C, HDL-C, TG, and TC, along with their corresponding standard deviations (SDs), or that provided data allowing for the calculation of these values.

Two independent reviewers (MH and AGh) carried out all aspects of the systematic review, including screening studies, selecting them, assessing methodological quality, assessing based on inclusion and exclusion criteria, and extracting data. Any disagreements were resolved through group discussions until a consensus was reached. The exclusion criteria were established as follows: (1) RCTs where participants consumed other nutrients besides magnesium; (2) RCTs lacking placebo or comparison groups; (3) RCTs lacking data on serum levels of lipid profile before or after intervention in both study groups or any information for calculation; (4) RCTs using figures to show the results instead of clearly reporting the mean and SD of serum levels of lipid profile; (5) RCTs without magnesium dosage; (6) RCTs involving pregnant women; (7) RCTs using intravenous form of magnesium; (8) Non-English trials.

Data extraction

Information was extracted using a data collection form, with two independent investigators extracting the following details: first author’s name, publication year, study title, trial design, geographical region, intervention duration, participants’ age, sex, health status, body mass index (BMI), study sample size, magnesium dose, changes in the mean of lipid profile, and their corresponding SDs. For RCTs with more than one intervention or comparison group, each was considered as a separate study in the systematic review and meta-analysis. Any ambiguous data were addressed by reaching out to the corresponding author for clarification. Discrepancies were resolved through group discussions to reach a consensus during this stage.

Quality assessment

A modified version of the Cochrane risk-of-bias (Rob2) tool and the respective Excel application were used to assess the quality of each RCT [42]. Evaluation of RCTs was performed on the basis of several factors, including the randomization process, bias arising from period and carryover effect (just for cross-over trials), deviations from intended interventions, missing outcome data, measurement of outcome, and selection of reported results. According to the criteria of this tool, RCTs were categorized as having a low risk of bias (good quality), some concerns regarding bias (fair quality), or a high risk of bias (weak quality) [42]. Two reviewers (MH and AGh) independently assessed each RCT, and any disagreements were resolved through discussion and consensus with a third person (MS).

Data synthesis and statistical analysis

By determining the mean differences (MDs) and their SDs for lipid profile, the meta-analysis has been carried out. If these values were not provided, we calculated them using the information in the articles. According to the Cochrane Handbook, we calculated the effect size by taking the changes in the mean of lipid profile from baseline and their SD for both the intervention and the comparison groups [43]. Additionally, when the median or range of lipid profile was provided instead of the mean, we calculated the mean using the Hozo method [44]. If the standard errors (SEs) were reported, we derived the SDs by multiplying the SEs in the square root of the sample size [44]. If there was significant heterogeneity, a summary of the overall effects and heterogeneity using the DerSimonian and Laird random effects model was presented [45]. We assessed the statistical heterogeneity of intervention effects using the I-squared statistic and Cochran’s Q test. We considered significant heterogeneity to be a p-value of ≤ 0.10 by Cochran’s Q test or a value of ≥ 50% in the I-squared statistic [46].

Besides considering the level of significance in heterogeneity, identification of its causes was of great importance and thus, it was carried out by conducting subgroup analyses based on factors such as magnesium dose, trial design, geographical region, intervention duration, baseline lipid profile, participants’ health status, age, sex, BMI, study sample size, RCTs’ quality, and publication year. We assessed publication bias using Begg’s rank correlation test, Egger’s weighted regression test, and visual examination of Begg’s funnel plot [47, 48]. All effect sizes were accompanied by 95% confidence intervals (CIs) and STATA version 14 (Stata Corp, College Station, TX) was utilized for all analyses.

Results

Our systematic search yielded 2889 articles. After removing duplicates, 1789 articles were screened based on their titles and abstracts. Upon review, 1729 articles were excluded for various reasons, such as being cross-sectional studies, study protocols, congress abstracts, lack of lipid profile measurement, non-human studies, and review articles. Subsequently, the full texts of 60 articles were assessed according to our inclusion and exclusion criteria leading to the exclusion of 33 articles for various reasons, including taking magnesium from a diet with a high amount of magnesium instead of a supplement (n = 1), not being randomized (n = 1), taking magnesium besides other nutrients (n = 17), not having comparison group (n = 5), not reporting baseline data (n = 1), not reporting data after intervention (n = 1), not reporting the elemental magnesium-dose (n = 4), conducting the study on pregnant women (n = 2), taking magnesium in intravenous form (n = 1). Finally, twenty-seven articles met our criteria and were included in the systematic review and meta-analysis [28,29,30,31,32,33,34,35,36,37,38,39, 49,50,51,52,53,54,55,56,57,58,59,60,61,62,63] (Fig. 1). However, regarding TG, two studies were excluded from the meta-analysis due to having a large effect size (outliers) compared to the other trials [57, 58].

Fig. 1
figure 1

Flowchart of study selection process

Full size image

Study characteristic

Based on our systematic review results, the effect of magnesium supplementation on serum levels of LDL-C, HDL-C, TG, and TC was assessed in twenty [29, 30, 32,33,34,35,36,37,38,39, 49, 52,53,54,55,56, 59,60,61,62], twenty-five [29, 30, 32,33,34,35,36,37,38,39, 49,50,51,52,53,54,55,56,57,58,59,60,61,62,63], twenty-five [28,29,30,31,32,33,34,35,36,37,38,39, 50,51,52,53,54,55,56,57,58,59,60,61,62], and twenty-one studies [28,29,30, 32,33,34,35,36,37,38,39, 52,53,54,55,56, 59,60,61,62,63], respectively. The dose of magnesium ranged from 20 mg/day to 548 mg/day in the form of magnesium citrate [28, 31], magnesium chloride [29, 50, 51, 57, 58], magnesium oxide [30, 34, 37, 38, 55, 56, 62], magnesium pidolate [32], magnesium bicarbonate [33], magnesium sulfate [39, 49, 61], magnesium hydroxyl [35], magnesium aspartate [53, 63], magnesium lactate [54], while four studies did not report the formulation of magnesium [36, 52, 59, 60]. The intervention duration ranged from 4 weeks to 24 weeks.

The design of three studies was cross-over [31, 32, 54], while twenty-four studies [28,29,30, 33,34,35,36,37,38,39, 49,50,51,52,53, 55,56,57,58,59,60,61,62,63] had a parallel design. Regarding health status, three studies were on subjects with metabolic syndrome [28, 52, 58], nine studies on subjects with diabetes [29, 37, 50, 54,55,56, 59, 61, 62], three studies on obese/overweight participants [31, 39, 53], three studies on prediabetes [38, 51, 60] and healthy subjects [32, 33, 35], two studies on women with polycystic ovary syndrome [30, 34], one study on subjects with moderate coronary artery disease [49], one study on nonalcoholic fatty liver disease [36], one study on metabolically obese normal-weight individuals [57], and one study on mild to moderate hypertension [63].

In one study by Albaker, W. I et al. [29] the effect of magnesium was assessed at different doses, including 20 mg/day and 50 mg/day for twelve weeks; therefore, this study was considered as two studies in the systematic review and meta-analysis. Farshidi, H et al. [49] assessed the effect of magnesium in 12 weeks and 24 weeks; therefore, we considered this study as two separate studies, and two effect sizes were calculated. Furthermore, in two other studies, the effect of magnesium was assessed at two time points; thus, those studies were reviewed as four separate studies in both the systematic review and meta-analysis, and four effect sizes were calculated [35, 39]. Consequently, twenty studies with twenty-four effect sizes assessed the effect of magnesium on LDL-C levels, twenty-five studies with twenty-nine effect sizes assessed the effect of magnesium on HDL-C levels, twenty-five studies with twenty-six effect sizes assessed the effect of magnesium on TG levels, and twenty-one studies with twenty-four effect sizes assessed the effect of magnesium on TC levels. We presented the details of the study characteristics in Table 1.

Table 1 Randomized controlled trial studies included in the systematic review and meta-analysis abbreviations: LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; TG: triglyceride; TC: total cholesterol
Full size table

Quality assessment

Figure 2 shows the results of the quality assessment for each article and the percentage of articles based on quality assessment results in each item. As can be seen, out of twenty-seven studies, ten studies had a high risk of bias [29, 32, 34,35,36, 49, 51, 52, 55, 63] due to deviations from intended interventions [52], missing outcome data [29, 34, 49, 51, 52, 55], and measurement of the outcome [32, 35, 36, 52, 55, 63]. More details are presented in Fig. 2.

Fig. 2
figure 2

Quality assessment

Full size image

Meta-analysis results

Twenty-one studies with twenty-four datasets were included in the meta-analysis of the effect of magnesium on the serum level of TC (Fig. 3A). The high heterogeneity was observed between studies (Cochrane’s Q test, P < 0.001, I2 = 99.1%). As depicted in Fig. 3A, differences in serum levels of TC between the magnesium group and the comparison group (weighted mean difference (WMD) = 0.34 mg/dl, 95% CI: -1.75 to 2.43, P = 0.749) were non-significant. Subgroup analyses also revealed a non-significant change in serum levels of TC following magnesium supplementation in most subgroups with more than two trials (Table 2). The between-group heterogeneity was significant in most subgroups with more than two trials (Table 2).

Fig. 3
figure 3

Forest plot of the effect of magnesium supplementation on serum concentrations of lipid profile. A: TC; B: TG; C: LDL-C; D: HDL-C

Full size image
Table 2 Results of subgroup analyses for studies evaluating the effect of magnesium on serum TC
Full size table

Figure 3B depicts the result of the meta-analysis regarding the effect of magnesium on the serum levels of TG. Twenty-three studies with twenty-six datasets were included in the meta-analysis. Since there was significant heterogeneity (Cochrane’s Q test, P < 0.001, I2 = 99.1%) between studies, the random-effect model was used and its results indicated no significant effect of magnesium on serum levels of TG (WMD=-2.06 mg/dl, 95% CI: -6.35 to 2.23, P = 0.346). The non-significant effect of magnesium supplementation on TG levels did not change in all subgroup analyses (Table 3).

Table 3 Results of subgroup analyses for studies evaluating the effect of magnesium on serum TG
Full size table

The meta-analysis of the results of twenty studies with twenty-four datasets that evaluated the effect of magnesium on serum levels of LDL-C is shown in Fig. 3C. The result of random-effect model showed non-significant differences in serum levels of LDL-C between the magnesium group and the comparison group, with high heterogeneity (WMD = 1.71 mg/dl, 95% CI: -0.81 to 4.24, P = 0.183, Cochrane Q test, P˂0.001, I2 = 99.4%).

The non-significant effect of magnesium on serum levels of LDL-C was shown in most subgroup analyses. More details regarding subgroup analysis results are presented in Table 4.

Table 4 Results of subgroup analyses for studies evaluating the effect of magnesium on serum LDL-C
Full size table

The meta-analysis of the effect of magnesium on serum levels of HDL-C is shown in Fig. 3D. As can be seen in the figure, twenty-five studies with twenty-nine datasets compared the changes in serum levels of HDL-C between the magnesium group and the comparison group. There was high heterogeneity (Cochrane’s Q test, P < 0.001, I2 = 99.5%) between studies, and the random-effect model found a significant increasing effect of magnesium on serum levels of HDL-C (WMD = 1.21 mg/dl, 95% CI: 0.58 to 1.85, P < 0.001).

According to the results of subgroup analysis magnesium supplementation significantly increased serum levels of HDL-C in studies among American (WMD = 3.90 mg/dl, 95% CI: 1.83 to 5.97, P < 0.001) not the Asian (WMD = 0.49 mg/dl, 95% CI: -0.37 to 1.35, P = 0.267) and European participants (WMD = 0.75 mg/dl, 95% CI: -0.77 to 2.27, P = 0.335) and participants with at risk/disease health status (WMD = 1.32 mg/dl, 95% CI: 0.52 to 2.12, P = 0.001) not healthy (WMD = 0.34 mg/dl, 95% CI: -2.08 to 2.75, P = 0.785), and both sex (WMD = 1.65 mg/dl, 95% CI: 0.86 to 2.44, P < 0.001) not female (WMD=-0.08 mg/dl, 95% CI: -0.25 to 0.09, P = 0.376), and studies with magnesium dose ≥ 300 mg/day (WMD = 2.02 mg/dl, 95% CI: 1.23 to 2.81, P < 0.001) not ˂300 mg/day (WMD=-0.22 mg/dl, 95% CI: -1.39 to 0.95, P = 0.716), intervention duration ≥ 84 days (WMD = 1.49 mg/dl, 95% CI: 0.79 to 2.19, P = 0.966) not ˂84 days (WMD = 0.44 mg/dl, 95% CI: -1.70 to 1.77, P < 0.001), baseline HDL-C < 43 mg/dl (WMD = 1.76 mg/dl, 95% CI: 0.78 to 2.73, P < 0.001) not ≥ 43 mg/dl (WMD = 0.74 mg/dl, 95% CI: -0.35 to 1.84, P = 0.184), sample size ≥ 64 persons (WMD = 1.54 mg/dl, 95% CI: 0.74 to 2.35, P < 0.001) not ˂64 persons (WMD = 0.70 mg/dl, 95% CI: -0.42 to 1.82, P = 0.222), and publication date < 2016 (WMD = 1.4 mg/dl, 95% CI: 0.95 to 1.85, P < 0.001) not ≥ 2016 (WMD = 0.76 mg/dl, 95% CI: -0.15 to 1.67, P = 0.104) (Table 5). The heterogeneity was significant in most subgroups with a number of trials more than 2 (Table 5).

Table 5 Results of subgroup analyses for studies evaluating the effect of magnesium on serum HDL-C
Full size table

Meta-regression analysis, publication bias, and sensitivity analysis

Despite the relatively nonsymmetrical visual inspection of the funnel plots for TC, TG, LDL-C, and HDL-C, the results of the Egger and Begg tests revealed no evidence of publication bias (Egger test P = 0.627 and Begg test P = 0.102 for TC; Egger test P = 0.551 and Begg test P = 0.366 for TG; Egger test P = 0.562 and Begg test P = 0.321 for LDL-C; Egger test P = 0.150 and Begg test P = 0.822 for HDL-C) (Fig. 4A, B, C and D). The results of the dose-response meta-regression analysis revealed a non-significant linear association between magnesium supplementation dose and the studied effect size for TC (P = 0.629, Fig. 5A), TG (P = 0.862, Fig. 5B), LDL-C (P = 0.501, Fig. 5C), and HDL-C (P = 0.512, Fig. 5D). According to the result of sensitivity analysis, excluding no trial caused significant changes in the overall effect size of magnesium on TC, TG, LDL-C, and HDL-C (Fig. 6A, B and C, and 6D).

Fig. 4
figure 4

Funnel plots for the studies of the effects of magnesium supplementation on serum concentrations of lipid profile. A: TC; B: TG; C: LDL-C; D: HDL-C

Full size image
Fig. 5
figure 5

Meta-regression plot of the effect of magnesium supplementation dose on serum concentrations of lipid profile. A: TC; B: TG; C: LDL-C; D: HDL-C

Full size image
Fig. 6
figure 6

Sensitivity analysis plots for the studies of the effects of magnesium supplementation on serum concentrations of lipid profile. A: TC; B: TG; C: LDL-C; D: HDL-C

Full size image

Discussion

The present study has been the first systematic review and meta-analysis after the year 2017 which assessed the effects of magnesium supplementation on serum levels of lipid profile in the general population without considering health status. The current meta-analysis combined data from 24, 29, 26, and 24 datasets from twenty, twenty-five, twenty-three, and twenty-one studies to assess the impact of magnesium on serum levels of LDL-C, HDL-C, TG, and TC, respectively. Our results revealed magnesium supplementation cannot significantly change the serum levels of LDL-C, TG, and TC; however, the serum level of HDL-C increased significantly.

The systematic review and meta-analysis in 2017 [40] revealed no significant effect of magnesium supplementation on serum levels of lipid profile. The effect of newly published studies that were not included in that study might cause the discrepancy between our meta-analysis results and those of the earlier study. Another systematic review and meta-analysis investigating the impact of magnesium on lipid profile among diabetic patients indicated that taking magnesium supplements significantly reduced serum levels of LDL-C did not have any effect on serum levels of TG, TC, and HDL-C [41]. The discrepancy in findings might be attributed to different study populations. It should be pinpointed that they limited their study to diabetic patients, while our study has centralized its focus on the general population. Furthermore, in the previous meta-analysis, the inclusion of studies lacking a proper comparison group [64] and those not reporting the exact dosage of elemental magnesium [65,66,67] might also have contributed to the differing results.

Extending and making a bridge between our results and the previous studies, findings from animal studies offer potential mechanisms responsible for the negative effect of magnesium deficiency on lipid profile. In this regard, a decrease in the removal of TG from the bloodstream and the lowered activity of lipoprotein lipase seem to be the primary factors contributing to high levels of lipid profile in magnesium deficiency [68, 69]. Additionally, a significant reduction in the activity of lecithin-cholesterol acyltransferase (LCAT) and decreased insulin sensitivity due to magnesium deficiency are also involved in the onset of dyslipidemia [70].

Magnesium increases the activity of LCAT, which raises HDL-C level [71, 72]; moreover, the activation of desaturase enzymes is increased by magnesium as well [72]. Desaturase catalyzes the first step in the conversion of omega-3 linoleic acid into eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which increases HDL-C [73, 74]. Interestingly, this study provides new evidence to support the hypothesis that magnesium supplementation can protect against CVDs, though the enhancement of HDL-C might be clinically non-significant.

Our results revealed that there was significant heterogeneity among studies, which did not reduce in most subgroups. The reasons for the heterogeneity might be attributed to various formulations/salts of magnesium (magnesium citrate, magnesium chloride, magnesium oxide, magnesium pidolate, magnesium bicarbonate, magnesium sulfate, magnesium hydroxyl, magnesium aspartate, and magnesium lactate) that were used, which could be responsible for the heterogeneity. The formulation of magnesium might affect its bioavailability [75]; therefore, the impact of the administered magnesium salt on bioavailability cannot be ignored and might be a source of heterogeneity that cannot be dismissed with certainty in this study. The penultimate source for heterogeneity might be the wide range of magnesium supplement doses. Since different health statuses might have different effects on lipid profile, the wide range of health statuses among the studied participants might be another source of heterogeneity. Aggregating all these justifications together, our results should be interpreted with caution.

Our results revealed that magnesium supplements cannot reduce serum levels of TC, TG, and LDL-C compared to the control group. One reason for the ineffectiveness of magnesium on these variables might be the homeostasis of magnesium, which is strictly controlled by renal function [76]. In the presence of normal levels of magnesium, the consumption of magnesium supplements leads to increased urinary excretion of magnesium. Hence, the beneficial effect of magnesium supplements may be diminished in normomagnesemic subjects. It is worth mentioning that in our study, in most included studies the participants had normal levels of magnesium. Furthermore, the effects of magnesium might be changed in subjects with impaired renal function. Since, in the present meta-analysis, three studies were conducted on hemodialysis patients [37, 59, 62], impaired renal function might be an important cause of the non-significant effect of magnesium.

Another reason might be the effect of different formulations/salts on magnesium bioavailability [75]. Some evidence suggests that serum levels of magnesium increase during supplementation [77]; therefore, the beneficial effects might be found over a longer period of intervention. Our results confirm this hypothesis. We found in studies with an intervention duration of ≥ 84 days, HDL-C increased significantly, but this effect did not show in studies with an intervention duration of ˂84 days. Our subgroup analysis also revealed magnesium supplements are more effective in the American population compared to the Asian population. In the American population, serum levels of HDL-C significantly increased following the magnesium intake, though this effect has not been found in the Asian population. Dietary magnesium intake, efficiency of absorption in subjects, dietary components, lifestyle factors, genetic background, and medications might be responsible for this difference in results. Our results also revealed that studies with a magnesium dose of ≥ 300 mg/day significantly increased serum levels of HDL-C, but we did not observe this result in studies with a magnesium dose of ˂300 mg/day. This finding might be due to the use of organic magnesium supplementation in some studies with a dose of ≥ 300 mg/day. The organic form of magnesium supplements might be more available than the inorganic form [75]. We also found that unhealthy participants and those with serum levels of HDL-C ˂43 mg/dl derived more benefits from magnesium supplementations, which might be due to lower levels of serum magnesium in this population.

Our study had some limitations that should be kept in mind while interpreting our results. Firstly, renal function can be an important confounder in assessing the magnesium supplementation effect; however, the biomarkers of renal function in most included RCTs in this meta-analysis are missing. Secondly, although most enrolled studies focused on patients, no information was included about their medicine in the articles. Thirdly, different formulations/salts of magnesium were used in trials, but we could not determine the effect of every formulation/salt on magnesium effect due to the low number of clinical trials for each formulation or the lack of reporting on magnesium formulation/salt in several trails [36, 52, 59, 60]. Fourthly, serum levels of magnesium were not reported before and after intervention in most trials; therefore, we did not have any information regarding magnesium hemostasis. Fifthly, although magnesium supplements are more effective in subjects with hypomagnesemia [78], the majority of articles focused on subjects with normal magnesium levels or did not include any information regarding magnesium levels. Sixthly, most trials were conducted in Asia and America and only a few articles were from Europe and Australia; therefore, we could not assess the effect of geographical region on magnesium effect. Seventhly, there were not enough separate studies on males and females; therefore, the effect of sex on magnesium effect remained unclear. Eighthly, the heterogeneity between studies was statistically significant and was not eliminated by statistical methods; therefore, our findings should be interpreted with caution.

Under the shade of these limitations, this systematic review and meta-analysis enjoys.

some strengths. At the first glance, this study is at the top of the hierarchy of clinical evidence. It is noticeable to highlight that as no time limitation was imposed on our systematic search, we tried to find the source of heterogeneity through conducting subgroup analyses. In addition, following PRISMA guidelines, we attempted to perform and report the results and minimized potential bias in the systematic review process through a comprehensive search strategy as well. Finally, we excluded RCTs that assessed the effect of magnesium on lipid profile besides other interventions; consequently, the confounding effect of those interventions was removed.

Conclusion

In conclusion, the findings of the present study supported that magnesium supplementation significantly increased serum levels of HDL-C, but no effects were observed on LDL-C, TG, and TC. However, the results of our subgroup analyses revealed that participants with a BMI˂29.5 might benefit more from magnesium supplementation regarding TC reduction to a higher extent. Our results also indicated higher doses of magnesium (≥ 300 mg/day) and longer intervention durations (≥ 84 days) are critical for increasing HDL-C. Furthermore, magnesium is more effective in participants with disease, health risk factors, and lower HDL-C levels. Considering the high degree of heterogeneity and elucidating the role of nationality, magnesium levels, sex, and food habits on the effect of magnesium supplements, more RCTs are required to confirm these results.

Data availability

The data presented in this study are available on request from the corresponding author.

Abbreviations

BMI:

Body mass index

CI:

Confidence interval

CVD:

Cardiovascular disease

DHA:

Docosahexaenoic acid

EPA:

Eicosapentaenoic acid

HDL-C:

High-density lipoprotein cholesterol

HMG-CoA:

β-hydroxy β-methylglutaryl-CoA

LDL-C:

Low-density lipoprotein cholesterol

MeSH:

Medical subjects heading

MD:

Mean differences

RCTs:

Randomized controlled trials

SD:

Standard deviations

SE:

Standard errors

TC:

Total cholesterol

TG:

Triglyceride

WMD:

Weighted mean difference

References

  1. Institute of Medicine Committee on Preventing the Global Epidemic of Cardiovascular Disease. Meeting the Challenges in Developing C. The National Academies Collection: Reports funded by National Institutes of Health. In: Fuster V, Kelly BB, editors. Promoting Cardiovascular Health in the Developing World: A Critical Challenge to Achieve Global Health. Washington (DC): National Academies Press (US) Copyright © 2010, National Academy of Sciences.; 2010.

  2. Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011;473(7347):317–25.

    Article  CAS  PubMed  Google Scholar 

  3. Teo KK, Rafiq T. Cardiovascular Risk factors and Prevention: a perspective from developing countries. Can J Cardiol. 2021;37(5):733–43.

    Article  PubMed  Google Scholar 

  4. Jain KS, Kathiravan MK, Somani RS, Shishoo CJ. The biology and chemistry of hyperlipidemia. Bioorg Med Chem. 2007;15(14):4674–99.

    Article  CAS  PubMed  Google Scholar 

  5. Pletcher MJ, Lazar L, Bibbins-Domingo K, Moran A, Rodondi N, Coxson P, Lightwood J, Williams L, Goldman L. Comparing impact and cost-effectiveness of primary prevention strategies for lipid-lowering. Ann Intern Med. 2009;150(4):243–54.

    Article  PubMed  Google Scholar 

  6. Alloubani A, Nimer R, Samara R. Relationship between Hyperlipidemia, Cardiovascular Disease and Stroke: a systematic review. Curr Cardiol Rev. 2021;17(6):e051121189015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ueki Y, Itagaki T, Kuwahara K. Lipid-lowering therapy and coronary plaque regression. J Atheroscler Thromb. 2024;31(11):1479–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr., Watson K, Wilson PW. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice guidelines. J Am Coll Cardiol. 2014;63(25 Pt B):2889 – 934.

  9. Khajeh M, Hassanizadeh S, Pourteymour Fard Tabrizi F, Hassanizadeh R, Vajdi M, Askari G. Effect of zinc supplementation on lipid Profile and Body Composition in patients with type 2 diabetes Mellitus: a GRADE-Assessed systematic review and dose-response Meta-analysis. Biol Trace Elem Res. 2024.

  10. Radkhah N, Zarezadeh M, Jamilian P, Ostadrahimi A. The effect of vitamin D supplementation on lipid profiles: an Umbrella review of Meta-analyses. Adv Nutr. 2023;14(6):1479–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Haghighatdoost F, Hariri M. Does alpha-lipoic acid affect lipid profile? A meta-analysis and systematic review on randomized controlled trials. Eur J Pharmacol. 2019;847:1–10.

    Article  CAS  PubMed  Google Scholar 

  12. Askari G, Hajishafiee M, Ghiasvand R, Hariri M, Darvishi L, Ghassemi S, Iraj B, Hovsepian V. Quercetin and vitamin C supplementation: effects on lipid profile and muscle damage in male athletes. Int J Prev Med. 2013;4(Suppl 1):S58–62.

    PubMed  PubMed Central  Google Scholar 

  13. 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).

  14. Razzaque MS, Magnesium. Are We Consuming Enough? Nutrients. 2018;10(12).

  15. Institute of Medicine Standing Committee on the Scientific Evaluation of Dietary Reference I. The National Academies Collection: Reports funded by National Institutes of Health. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington (DC): National Academies Press (US) Copyright © 1997, National Academy of Sciences.; 1997.

  16. Asbaghi O, Hosseini R, Boozari B, Ghaedi E, Kashkooli S, Moradi S. 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):413–24.

    Article  PubMed  Google Scholar 

  17. Veronese N, Dominguez LJ, Pizzol D, Demurtas J, Smith L, Barbagallo M. Oral magnesium supplementation for treating glucose metabolism parameters in people with or at risk of diabetes: a systematic review and Meta-analysis of double-blind randomized controlled trials. Nutrients. 2021;13(11).

  18. Liu Y, Li S. Association between serum magnesium levels and risk of Dyslipidemia: a cross-sectional study from the China Health and Nutrition Survey. Biol Trace Elem Res. 2023.

  19. Sarrafzadegan N, Khosravi-Boroujeni H, Lotfizadeh M, Pourmogaddas A, Salehi-Abargouei A. Magnesium status and the metabolic syndrome: a systematic review and meta-analysis. Nutrition. 2016;32(4):409–17.

    Article  CAS  PubMed  Google Scholar 

  20. Rosique-Esteban N, Guasch-Ferré M, Hernández-Alonso P, Salas-Salvadó J. Dietary Magnesium and Cardiovascular Disease: a review with emphasis in Epidemiological studies. Nutrients. 2018;10(2).

  21. Wu J, Xun P, Tang Q, Cai W, He K. Circulating magnesium levels and incidence of coronary heart diseases, hypertension, and type 2 diabetes mellitus: a meta-analysis of prospective cohort studies. Nutr J. 2017;16(1):60.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Song Y, Ridker PM, Manson JE, Cook NR, Buring JE, Liu S. Magnesium intake, C-reactive protein, and the prevalence of metabolic syndrome in middle-aged and older U.S. women. Diabetes Care. 2005;28(6):1438–44.

    Article  CAS  PubMed  Google Scholar 

  23. Găman MA, Dobrică EC, Cozma MA, Antonie NI, Stănescu AMA, Găman AM, Diaconu CC. Crosstalk of Magnesium and serum lipids in Dyslipidemia and Associated disorders: a systematic review. Nutrients. 2021;13(5).

  24. Shahmoradi S, Chiti H, Tavakolizadeh M, Hatami R, Motamed N, Ghaemi M. The Effect of Magnesium supplementation on insulin resistance and metabolic profiles in women with polycystic ovary syndrome: a Randomized Clinical Trial. Biol Trace Elem Res. 2024;202(3):941–6.

    Article  CAS  PubMed  Google Scholar 

  25. Kostov K, Halacheva L. Role of Magnesium Deficiency in promoting atherosclerosis, endothelial dysfunction, and arterial stiffening as risk factors for hypertension. Int J Mol Sci. 2018;19(6).

  26. Inoue I. [Lipid metabolism and magnesium]. Clin Calcium. 2005;15(11):65–76.

    PubMed  Google Scholar 

  27. Pelczyńska M, Moszak M, Bogdański P. The role of Magnesium in the Pathogenesis of Metabolic disorders. Nutrients. 2022;14(9).

  28. Afitska K, Clavel J, Kisters K, Vormann J, Werner T. Magnesium citrate supplementation decreased blood pressure and HbA1c in normomagnesemic subjects with metabolic syndrome: a 12-week, placebo-controlled, double-blinded pilot trial. Magnes Res. 2021;34(3):130–9.

    CAS  PubMed  Google Scholar 

  29. Albaker WI, Al-Hariri MT, Al Elq AH, Alomair NA, Alamoudi AS, Voutchkov N, Ihm S, Namazi MA, Alsayyah AA, AlRubaish FA, Alohli FT, Zainuddin FA, Alobaidi AA, Almuzain FA, Elamin MO, Alamoudi NB, Alamer MA, Alghamdi AA, AlRubaish NA. Beneficial effects of adding magnesium to desalinated drinking water on metabolic and insulin resistance parameters among patients with type 2 diabetes mellitus: a randomized controlled clinical trial. NPJ Clean Water. 2022;5(1):63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Alizadeh M, Karandish M, Asghari Jafarabadi M, Heidari L, Nikbakht R, Babaahmadi Rezaei H, Mousavi R. Metabolic and hormonal effects of melatonin and/or magnesium supplementation in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Nutr Metab (Lond). 2021;18(1):57.

    Article  CAS  PubMed  Google Scholar 

  31. Chacko SA, Sul J, Song Y, Li X, LeBlanc J, You Y, Butch A, Liu S. Magnesium supplementation, metabolic and inflammatory markers, and global genomic and proteomic profiling: a randomized, double-blind, controlled, crossover trial in overweight individuals. Am J Clin Nutr. 2011;93(2):463–73.

    Article  CAS  PubMed  Google Scholar 

  32. Cosaro E, Bonafini S, Montagnana M, Danese E, Trettene MS, Minuz P, Delva P, Fava C. Effects of magnesium supplements on blood pressure, endothelial function and metabolic parameters in healthy young men with a family history of metabolic syndrome. Nutr Metab Cardiovasc Dis. 2014;24(11):1213–20.

    Article  CAS  PubMed  Google Scholar 

  33. Day RO, Liauw W, Tozer LM, McElduff P, Beckett RJ, Williams KM. A double-blind, placebo-controlled study of the short term effects of a spring water supplemented with magnesium bicarbonate on acid/base balance, bone metabolism and cardiovascular risk factors in postmenopausal women. BMC Res Notes. 2010;3:180.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Farsinejad-Marj M, Azadbakht L, Mardanian F, Saneei P, Esmaillzadeh A. Clinical and metabolic responses to Magnesium supplementation in women with polycystic ovary syndrome. Biol Trace Elem Res. 2020;196(2):349–58.

    Article  CAS  PubMed  Google Scholar 

  35. Itoh K, Kawasaka T, Nakamura M. The effects of high oral magnesium supplementation on blood pressure, serum lipids and related variables in apparently healthy Japanese subjects. Br J Nutr. 1997;78(5):737–50.

    Article  CAS  PubMed  Google Scholar 

  36. Karandish M, Tamimi M, Shayesteh AA, Haghighizadeh MH, Jalali MT. The effect of magnesium supplementation and weight loss on liver enzymes in patients with nonalcoholic fatty liver disease. J Res Med Sci. 2013;18(7):573–9.

    PubMed  PubMed Central  Google Scholar 

  37. Mortazavi M, Moeinzadeh F, Saadatnia M, Shahidi S, McGee JC, Minagar A. Effect of magnesium supplementation on carotid intima-media thickness and flow-mediated dilatation among hemodialysis patients: a double-blind, randomized, placebo-controlled trial. Eur Neurol. 2013;69(5):309–16.

    Article  CAS  PubMed  Google Scholar 

  38. Shahmoradi S, Chiti H, Tavakolizadeh M, Hatami R, Motamed N, Ghaemi M. The Effect of Magnesium supplementation on insulin resistance and metabolic profiles in women with polycystic ovary syndrome: a Randomized Clinical Trial. Biol Trace Elem Res. 2023.

  39. Solati M, Kazemi L, Shahabi Majd N, Keshavarz M, Pouladian N, Soltani N. Oral herbal supplement containing magnesium sulfate improve metabolic control and insulin resistance in non-diabetic overweight patients: a randomized double blind clinical trial. Med J Islam Repub Iran. 2019;33:2.

    PubMed  PubMed Central  Google Scholar 

  40. Simental-Mendía LE, Simental-Mendía M, Sahebkar A, Rodríguez-Morán M, Guerrero-Romero F. Effect of magnesium supplementation on lipid profile: a systematic review and meta-analysis of randomized controlled trials. Eur J Clin Pharmacol. 2017;73(5):525–36.

    Article  PubMed  Google Scholar 

  41. Asbaghi O, Moradi S, Nezamoleslami S, Moosavian SP, Hojjati Kermani MA, Lazaridi AV, Miraghajani M. The effects of Magnesium supplementation on lipid Profile among type 2 diabetes patients: a systematic review and Meta-analysis of Randomized controlled trials. Biol Trace Elem Res. 2021;199(3):861–73.

    Article  CAS  PubMed  Google Scholar 

  42. Higgins JP, Savović J, Page MJ, Elbers RG, Sterne J. Assessing risk of bias in a randomized trial. Cochrane Handb Syst Reviews Interventions. 2019;6:205–28.

    Article  Google Scholar 

  43. Higgins JP, Thomas J. Cochrane handbook for systematic reviews of interventions. wiley blackwell; 2020.

  44. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005;5(1):13.

    Article  PubMed  PubMed Central  Google Scholar 

  45. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88.

    Article  CAS  PubMed  Google Scholar 

  46. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539–58.

    Article  PubMed  Google Scholar 

  47. Begg CB, Berlin JA. Publication bias and dissemination of clinical research. J Natl Cancer Inst. 1989;81(2):107–15.

    Article  CAS  PubMed  Google Scholar 

  48. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Farshidi H, Sobhani AR, Eslami M, Azarkish F, Eftekhar E, Keshavarz M, Soltani N. Magnesium Sulfate Administration in Moderate Coronary Artery Disease patients improves atherosclerotic risk factors: a double-blind clinical trial study. J Cardiovasc Pharmacol. 2020;76(3):321–8.

    Article  CAS  PubMed  Google Scholar 

  50. 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 Hum Hypertens. 2009;23(4):245–51.

    Article  CAS  PubMed  Google Scholar 

  51. Guerrero-Romero F, Simental-Mendía LE, Hernández-Ronquillo G, Rodriguez-Morán M. Oral magnesium supplementation improves glycaemic status in subjects with prediabetes and hypomagnesaemia: a double-blind placebo-controlled randomized trial. Diabetes Metab. 2015;41(3):202–7.

    Article  CAS  PubMed  Google Scholar 

  52. Lima de Souza ESML, Cruz T, Rodrigues LE, Ladeia AM, Bomfim O, Olivieri L, Melo J, Correia R, Porto M, Cedro A. Magnesium replacement does not improve insulin resistance in patients with metabolic syndrome: a 12-week randomized double-blind study. J Clin Med Res. 2014;6(6):456–62.

    Google Scholar 

  53. Mooren FC, Krüger K, Völker K, Golf SW, Wadepuhl M, Kraus A. Oral magnesium supplementation reduces insulin resistance in non-diabetic subjects - a double-blind, placebo-controlled, randomized trial. Diabetes Obes Metab. 2011;13(3):281–4.

    Article  CAS  PubMed  Google Scholar 

  54. Navarrete-Cortes A, Ble-Castillo JL, Guerrero-Romero F, Cordova-Uscanga R, Juárez-Rojop IE, Aguilar-Mariscal H, Tovilla-Zarate CA, Lopez-Guevara Mdel R. No effect of magnesium supplementation on metabolic control and insulin sensitivity in type 2 diabetic patients with normomagnesemia. Magnes Res. 2014;27(2):48–56.

    Article  PubMed  Google Scholar 

  55. Rashvand S, Mobasseri M, Tarighat-Esfanjani A. Effects of Choline and Magnesium Concurrent supplementation on coagulation and lipid Profile in patients with type 2 diabetes Mellitus: a pilot clinical trial. Biol Trace Elem Res. 2020;194(2):328–35.

    Article  CAS  PubMed  Google Scholar 

  56. Razzaghi R, Pidar F, Momen-Heravi M, Bahmani F, Akbari H, Asemi Z. Magnesium supplementation and the effects on Wound Healing and Metabolic Status in patients with Diabetic Foot Ulcer: a Randomized, Double-Blind, placebo-controlled trial. Biol Trace Elem Res. 2018;181(2):207–15.

    Article  CAS  PubMed  Google Scholar 

  57. Rodríguez-Moran M, Guerrero-Romero F. Oral magnesium supplementation improves the metabolic profile of metabolically obese, normal-weight individuals: a randomized double-blind placebo-controlled trial. Arch Med Res. 2014;45(5):388–93.

    Article  PubMed  Google Scholar 

  58. Rodríguez-Morán M, Simental-Mendía LE, Gamboa-Gómez CI, Guerrero-Romero F. Oral magnesium supplementation and metabolic syndrome: a Randomized double-blind placebo-controlled clinical trial. Adv Chronic Kidney Dis. 2018;25(3):261–6.

    Article  PubMed  Google Scholar 

  59. Sadeghian M, Azadbakht L, Khalili N, Mortazavi M, Esmaillzadeh A. Oral magnesium supplementation improved lipid Profile but increased insulin resistance in patients with Diabetic Nephropathy: a double-blind Randomized Controlled Clinical Trial. Biol Trace Elem Res. 2020;193(1):23–35.

    Article  CAS  PubMed  Google Scholar 

  60. Salehidoost R, Boroujeni GT, Feizi A, Aminorroaya A, Amini M. Effect of oral magnesium supplement on cardiometabolic markers in people with prediabetes: a double blind randomized controlled clinical trial. Sci Rep. 2022;12(1).

  61. Solati M, Ouspid E, Hosseini S, Soltani N, Keshavarz M, Dehghani M. Oral magnesium supplementation in type II diabetic patients. Med J Islam Repub Iran. 2014;28:67.

    PubMed  PubMed Central  Google Scholar 

  62. Talari HR, Zakizade M, Soleimani A, Bahmani F, Ghaderi A, Mirhosseini N, Eslahi M, Babadi M, Mansournia MA, Asemi Z. Effects of magnesium supplementation on carotid intima-media thickness and metabolic profiles in diabetic haemodialysis patients: a randomised, double-blind, placebo-controlled trial. Br J Nutr. 2019;121(7):809–17.

    Article  CAS  PubMed  Google Scholar 

  63. Witteman JC, Grobbee DE, Derkx FH, Bouillon R, de Bruijn AM, Hofman A. Reduction of blood pressure with oral magnesium supplementation in women with mild to moderate hypertension. Am J Clin Nutr. 1994;60(1):129–35.

    Article  CAS  PubMed  Google Scholar 

  64. Barragán-Rodríguez L, Rodríguez-Morán M, Guerrero-Romero F. Efficacy and safety of oral magnesium supplementation in the treatment of depression in the elderly with type 2 diabetes: a randomized, equivalent trial. Magnes Res. 2008;21(4):218–23.

    PubMed  Google Scholar 

  65. Corica F, Allegra A, Di Benedetto A, Giacobbe MS, Romano G, Cucinotta D, Buemi M, Ceruso D. Effects of oral magnesium supplementation on plasma lipid concentrations in patients with non-insulin-dependent diabetes mellitus. Magnes Res. 1994;7(1):43–7.

    CAS  PubMed  Google Scholar 

  66. de Valk HW, Verkaaik R, van Rijn HJ, Geerdink RA, Struyvenberg A. Oral magnesium supplementation in insulin-requiring type 2 diabetic patients. Diabet Med. 1998;15(6):503–7.

    Article  PubMed  Google Scholar 

  67. Eibl NL, Kopp HP, Nowak HR, Schnack CJ, Hopmeier PG, Schernthaner G. Hypomagnesemia in type II diabetes: effect of a 3-month replacement therapy. Diabetes Care. 1995;18(2):188–92.

    Article  CAS  PubMed  Google Scholar 

  68. Bo S, Pisu E. Role of dietary magnesium in cardiovascular disease prevention, insulin sensitivity and diabetes. Curr Opin Lipidol. 2008;19(1):50–6.

    Article  CAS  PubMed  Google Scholar 

  69. Dos Santos LR, Melo SRS, Severo JS, Morais JBS, da Silva LD, de Paiva Sousa M, de Sousa TGV, Henriques GS. Do Nascimento Marreiro D. Cardiovascular diseases in obesity: what is the role of Magnesium? Biol Trace Elem Res. 2021;199(11):4020–7.

    Article  CAS  PubMed  Google Scholar 

  70. Sales CH, Santos AR, Cintra DE, Colli C. Magnesium-deficient high-fat diet: effects on adiposity, lipid profile and insulin sensitivity in growing rats. Clin Nutr. 2014;33(5):879–88.

    Article  CAS  PubMed  Google Scholar 

  71. Rosanoff A, Seelig MS. Comparison of mechanism and functional effects of magnesium and statin pharmaceuticals. J Am Coll Nutr. 2004;23(5):s501–5.

    Article  Google Scholar 

  72. Nartea R, Mitoiu BI, Ghiorghiu I. The link between Magnesium supplements and statin medication in dyslipidemic patients. Curr Issues Mol Biol. 2023;45(4):3146–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Zhang JY, Kothapalli KS, Brenna JT. Desaturase and elongase-limiting endogenous long-chain polyunsaturated fatty acid biosynthesis. Curr Opin Clin Nutr Metab Care. 2016;19(2):103–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Czumaj A, Śledziński T. Biological role of unsaturated fatty acid desaturases in Health and Disease. Nutrients. 2020;12(2).

  75. Coudray C, Rambeau M, Feillet-Coudray C, Gueux E, Tressol JC, Mazur A, Rayssiguier Y. Study of magnesium bioavailability from ten organic and inorganic mg salts in Mg-depleted rats using a stable isotope approach. Magnes Res. 2005;18(4):215–23.

    CAS  PubMed  Google Scholar 

  76. Romani AM. Magnesium in health and disease. Met Ions Life Sci. 2013;13:49–79.

    PubMed  Google Scholar 

  77. Marques B, Klein M, da Cunha MR, de Souza Mattos S, de Paula Nogueira L, de Paula T, Corrêa FM, Oigman W, Neves MF. Effects of oral magnesium supplementation on vascular function: a systematic review and Meta-analysis of Randomized controlled trials. High Blood Press Cardiovasc Prev. 2020;27(1):19–28.

    Article  CAS  PubMed  Google Scholar 

  78. Al Alawi AM, Majoni SW, Falhammar H. Magnesium and Human Health: perspectives and research directions. Int J Endocrinol. 2018;2018:9041694.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to extend deep gratitude to Mrs. Taheri Shargh for assisting in searching databases and getting the full text of some articles.

Funding

The research leading to these results has received funding from Neyshabur University of Medical Sciences (Grant Code: 140201391; Ethical Code: IR.NUMS.REC.1403.005).

Author information

Authors and Affiliations

  1. Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran

    Mitra Hariri & Ali Gholami

  2. Healthy Ageing Research Centre, Neyshabur University of Medical Sciences, Neyshabur, Iran

    Mitra Hariri

  3. Gastrointestinal and Liver Disease Research Center (GILDRC), Firoozgar Hospital, University of Medical Sciences, Tehran, Iran

    Masoudreza Sohrabi

  4. Department of Epidemiology and Biostatistics, School of Public Health, Neyshabur University of Medical Sciences, Neyshabur, Iran

    Ali Gholami

Authors
  1. Mitra Hariri
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Masoudreza Sohrabi
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Ali Gholami
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

The design of search strategy was done by AGh. Searching data bases was done by MH and AGh, they also choose relevant RCTs based on inclusion and exclusion criteria. Reading articles full text, and data extraction was done by all authors. AGh performed statistical analysis. The manuscript was written by All authors. All discrepancies in every stage were solved through group discussions.

Corresponding author

Correspondence to Ali Gholami.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Supplementary Material 2

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hariri, M., Sohrabi, M. & Gholami, A. The effect of magnesium supplementation on serum concentration of lipid profile: an updated systematic review and dose-response meta-analysis on randomized controlled trials. Nutr J 24, 24 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12937-025-01085-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12937-025-01085-w

Keywords

Nutrition Journal

ISSN: 1475-2891

Contact us