TABLE 3.
Studies that prespecified evaluation of side effects or adverse event outcomes, 1997–2022
| Reference | Population | Study design | Sample size | Mg formulation | Daily dose | Duration | Side effects/AEs | Comments |
|---|---|---|---|---|---|---|---|---|
| Baker et al., 2009 (35) | Men and women with elevated blood pressure and implantable cardioverter defibrillator (mean age, 61–68 y) | Double-blind RCT | 70 | Mg L-lactate | 504 mg (21 mmol) | 12 wk | Overall incidence of AEs and rate of discontinuations due to AEs were similar in both the Mg L-lactate and placebo groups. The most commonly reported AEs included pill burden, diarrhea, fatigue, itching, and infection | 20 patients dropped out by week 12; data analysis was based on 50 patients. 86% of patients enrolled had Mg deficiency. Patients were instructed to take study medication without regard to meals |
| Dickinson et al., 2006 (30) | Adults with essential hypertension (overall mean age, 54 y; range, 20–77 y) | Meta-analysis of 12 RCTs | 545 | MgO (3 studies); Mg pidolate and Mg lactate (3 studies); Mg lactate and citrate; Mg aspartate; Mg aspartate hydrochloride (3 studies); Mg (not specified) | Mean: 413 mg (17 mmol); range, 243–972 mg; range, 10–40 mmol | Median follow-up duration of 11 wk (range, 8–26 wk) | Meta-analyses restricted to GI effects and other AEs showed no difference in risk between Mg (risk difference = 0.00 [95% CI, −0.05 to 0.05], I2 = 0%) and control groups (risk difference = 0.00 [95% CI, 0.07 to 0.06], I2 = 0%) | Withdrawal from treatment for all causes was 7% among participants receiving Mg and 8% among the control group. Patients in 4 studies were taking antihypertensive medication (e.g., calcium antagonists, β-blockers, ACE inhibitors, thiazides, spironolactone, and α-blockers) |
| Garrison et al., 2020 (31) | Individuals with skeletal muscle cramps for multiple conditions (mean age, 61–69 y) | Meta-analysis of 11 trials | 735 | Mg lactate and Mg citrate; tri-Mg dictrate; slow-release Mg lactate; Mg bisglycinate; 8% milk of Mg suspension; MgO and Mg aspartate | 200–520 mg (8.2–21.4 mmol) | 14–56 d | Diarrhea was experienced by 11%–37% of the Mg group and 10%–14% of the control group. Withdrawals due to GI AEs were not significantly different from placebo | 1 study enrolled 29 people with liver cirrhosis, and 1 study used IV Mg sulfate; 3 studies used once-daily dosing |
| Kass et al., 2012 (32) | Hypertensive and normotensive men and women from 12 different countries (mean age, 50–52 y) | Meta-analysis of 22 RCTs | 1173 | 7 different Mg formulations: oxide, aspartate, chloride, lactate, citrate, pidolate, and hydroxide | Mean: 410 mg (16.9 mmol); (range, 120–973 mg; range, 5–40 mmol] | Mean, 11.3 wk (range, 3–24 wk) | 13 studies reported AEs from the Mg and placebo treatments. AEs were largely either diarrhea or nonspecific mild abdominal or bone pain. Only 3 studies reported serious AEs that led to withdrawal (treatment arm not specified in 2 studies) | Some patients were taking antihypertensive medications and diuretics. Greater BP lowering would have been seen at dosages >370 mg/d |
| Liu et al., 2021 (33) | Pregnant women with leg cramps (mean age, 19–45 y) | Meta-analysis of 4 RCTs | 332 | Mg lactate or citrate (2 studies), Mg bisglycinate chelate (1 study), and Mg citrate (1 study) | 300–360 mg (12.3–14.8 mmol) | 2–4 wk | No significant side effects in the treatment group compared with the control group (OR, 1.82 [95% CI, 0.90 to 3.69]; P = 0.094) | Documentation of side effects was part of the inclusion criteria in the meta-analysis. Doses given 2 times/d (2 studies), 3 times/d (1 study), and once daily (1 study) |
| Mah and Pitre, 2021 (34) | Older adults with insomnia, mostly without comorbidities (mean age, 51–80 y) | Meta-analysis of 3 RCTs | 151 | MgO or citrate | 320–729 mg (13.1–30.0 mmol) | 20 d to 8 wk | Participants in 1 study reported soft stools | Doses are given 2 or 3 times/d |
| Makrides et al., 2014 (36) | Morbidity and mortality outcomes for pregnant women and their infants from 7 different countries | 10 RCTs | 9090 | MgO, 1000 mg (41 mmol) (1 trial); Mg citrate, 365 mg (15 mmol) (1 trial), and 340 mg 14 mmol) from 9 to 27 wk gestation (1 trial); Mg gluconate, 108–161 mg (4.4–6.6 mmol) (1 trial) and 215 mg (8.8 mmol) (1 trial); Mg aspartate, 15 mmol (365 mg) (3 trials), Mg aspartate hydrochloride 365 mg (1 trial); and Mg stearate, 128 mg (5.3 mmol) (1 trial) | 4 trials (1388 women) reported on GI symptoms and found no significant difference between the Mg group and control group (RR, 0.88 [95% CI, 0.69 to 1.12]) | Compositions of the Mg supplements, gestational ages at commencement, and doses administered varied | ||
| Park et al., 2014 (37) | Postmenopausal women with a history of hot flashes (84% ≥ 50 y) | Double-blind RCT with 4 study arms (2 Mg and 2 placebo) | 289 | MgO | 800 or 1200 mg (32.9–49.4 mmol) | 8 wk | The incidence of diarrhea with Mg was more prevalent than in the placebo arm; constipation was reported less frequently with Mg. There were no significant toxicity differences between the study arms | Toxicities were included as a secondary study end point and coded using CTCAE version 4. A self-reported validated survey instrument and telephone interviews were used to collect data on the frequency and severity of hot flashes and potential toxicities |
| Schutten et al., 2022 (38) | Adults with overweight or slight obesity (mean age, 63 y) | Double-blind, parallel-group RCT | 164 | Mg citrate, MgO, or Mg sulfate. | All are equivalent to 450 mg | 24 wk | 6 patients discontinued the study due to GI symptoms (2 from Mg citrate, 2 from Mg sulfate, and 2 from placebo). Mild diarrhea was noted for 5 patients taking Mg citrate, 1 taking Mg sulfate, 1 taking MgO, and 2 taking placebo | Mg supplement is taken 3 times/d. Patients completed the PHQ-15 (which includes 3 GI questions) and a 3-d food diary at baseline and study end; 15% were taking antihypertensive medications |
| Supakatisant and Vorapong Phupong, 2015 (39) | Pregnant women 14–34 wk of gestation with leg cramps (mean age, 29 y) | Double-blind RCT | 86 | Mg bisglycinate chelate | 300 mg (12.3 mmol) | 4 wk | No significant differences between groups in terms of side effects such as nausea (P < 0.10) and diarrhea (P < 0.27) | Compliance evaluated from returned tablets showed no differences between groups (P = 0.26) |
Abbreviations: AE, adverse event; CTCAE, Common Terminology Criteria for Adverse Events; GI, gastrointestinal; IV, intravenous; Mg, magnesium; MgO, magnesium oxide; PHQ-15, Patient Health Questionnaire-15; RCT, randomized controlled trial; RR, risk ratio.