Table 3.
Clinical studies that have evaluated the effects of oral magnesium supplementation on muscle-related outcomes.
| Author/Year | Study Design | Subjects (Age) | Intervention Dose and Duration | Source | Main Findings |
|---|---|---|---|---|---|
| (i) Magnesium supplementation in exercise performance | |||||
| Brilla et al., 2003 [86] | Randomized, double-blind, placebo-controlled trial | 35 recreationally active healthy subjects (19–24 y) | Placebo or 800 mg of Mg and 5 g of creatine per day for 2 weeks | MgO + creatine (MgOC) or Mg creatine chelate (MgCC) | MgOC and MgCC showed increases in bw and power. Only MgCC decreased ECW and increased ICW and peak T, suggesting that MgCC affects cellular fluid compartments and may enhance muscle creatine uptake, cellular hydration, and potentially protein synthesis. |
| Brilla and Haley, 1992 [83] | Randomized, double-blind, placebo-controlled trial | 26 untrained subjects (18–30 y) | Mg supplement to achieve an intake of 8 mg/kg bw for 7 weeks | MgO | Significant increase in strength for the Mg group vs. control group, with improvements in absolute quadriceps T, relative T adjusted for bw, and relative T adjusted for LBM. |
| Finstad et al., 2001 [191] | Randomized, double-blind, placebo-controlled, crossover trial | 121 physically active women (21 ± 3 y) | Placebo or 212 mg of Mg for 4 weeks, followed by a 6-week washout period and treatment crossover | MgO | Mg increased resting ionic Mg levels but did not significantly affect performance or recovery indices. |
| Golf et al., 1998 [192] | Randomized, double-blind, placebo-controlled trial | 23 competitive triathletes (29.4 ± 3.3 y) | Placebo or 17 mmol/d of Mg for 4 weeks | Mg orotate | Mg improved performance times in triathlon events, increased serum glucose and higher oxygen uptake, reduced stress responses (lower cortisol levels and leukocyte count), and showed a milder increase in CK post-test, indicating enhanced metabolic efficiency and reduced physiological stress during competition. |
| Kass and Poeira, 2015 [194] | Randomized, double-blind, placebo-controlled, crossover trial | 13 normotensive male and female subjects (38.5 ± 5.3 y) | 300 mg of Mg for 1 week (acute) or 4 weeks (chronic) | Mg citrate | Acute Mg increased bench press performance by 17.7% on day 1, with sustained performance on day 2. Chronic Mg resulted in a 32.1% performance decline on day 2. Both acute and chronic Mg reduced post-exercise SBP on day 2, while only acute Mg reduced DBP. TPR decreased with acute Mg but not with chronic Mg. |
| Kass et al., 2013 [207] | Randomized, controlled, pilot trial | 16 healthy and physically active male subjects (19–24 y) | No treatment or 300 mg of Mg * for 14 days | MgO | Mg reduced resting and post-exercise BP, with a greater effect on resting BP in low-dietary Mg intake individuals and a more pronounced reduction in post-exercise BP in high-dietary Mg intake individuals. No change in performance indicators. |
| Martinez et al., 2017 [211] | Nonrandomized controlled trial | 12 elite (25.3 ± 4.4 y) and 12 recreational (22 ± 3.8 y) male basketball players | No treatment or 400 mg/day of Mg for 32 weeks (measurements in 4 time points, each 8 weeks apart: T1, T2, T3, and T4) | Mg lactate | Serum Mg significantly decreased in T3 but increased after supplementation with T4. Muscle damage markers remained stable, except for creatinine, which decreased post-T2 and then increased in T3 and T4 compared to T2. Mg may prevent tissue damage associated with intense physical activity. |
| Zajac et al., 2020 [199] | Randomized, placebo-controlled trial | 16 elite soccer players (25.6 ± 3.7) | Placebo or 500 mg of Mg (0.07 g/kg bw) for 16 weeks | Mg creatine chelate | Mg improved total time and power in the RAST, enhancing the first and sixth 35 m sprints, with no significant changes in placebo. Mg increased creatinine, lactate, and bicarbonate levels while lowering pH values post-RAST, indicating improved sprint performance and metabolic response. |
| Moslehi et al., 2013 [195] | Randomized, double-blind, placebo-controlled trial | 74 healthy overweight women with BMI 25–30 kg/m² (40–55 y) | Placebo or 250 mg of Mg for 8 weeks | MgO | Mg increased LBM, decreased fat mass, and improved handgrip strength and TGUG vs. baseline. No significant enhancement in knee extension strength. |
| Setaro et al., 2014 [197] | Randomized, double-blind, placebo-controlled trial | 25 professional male volleyball players (Mg: 17.42 ± 1.56 y; C: 17.85 ± 0.99 y) | Placebo or 350 mg of Mg for 4 weeks | MgO | Mg led to decreased lactate production and enhanced plyometric performance, indicating improved alactic anaerobic metabolism. Mg erythrocyte levels, [Mg]U, CK activity, and VO2 max remained within normal ranges. |
| Steward et al., 2019 [197] | Counterbalanced, double-blind, placebo-controlled, crossover study | 9 male recreational runners (27 ± 4 y) | Placebo or 500 mg/day of Mg for 7 days before a 10 km downhill running time trial | MgO + Mg stearate | Mg lowered IL-6 levels, reduced muscle soreness, and improved the recovery of blood glucose post-exercise. No differences in glucose and lactate during the trial or in post-measures of creatine kinase or maximal muscle force. |
| Terblanche et al., 1992 [212] | Double-blind, placebo-controlled trial | 20 marathon runners (25–49 y) | Placebo or 365 mg of Mg for 4 weeks before and 6 weeks after a marathon | Mg-L-aspartate-HCl | In Mg-replete subjects, Mg did not increase muscle or serum Mg concentrations and had no effect on marathon running performance. It also did not influence the extent of muscle damage or the rate of recovery of muscle function post-marathon. |
| Veronese et al., 2014 [208] | Randomized, controlled trial | 139 healthy elderly women (71.5 ± 5.2 y) | No treatment or 300 mg of Mg per day for 12 weeks | MgO | Mg group showed significant improvement in total SPPB score, chair stand times, and 4-m walking speeds vs. control group. No significant differences in secondary outcomes and no serious adverse effects reported. |
| Selsby et al., 2004 [196] | Randomized, double-blind, placebo-controlled trial | 31 weight-trained male subjects (18–24 y) | placebo or 2.5 g of Cr or Mg-creatine chelate (providing 2.5 g of Cr) for 10 days | Mg creatine chelate (MgCC) | Cr and MgCC showed increases in work performed at 70% of 1RM for the bench press vs. placebo. No significant differences between the Cr and MgCC groups in performance tests, suggesting that a low dose of Cr, with or without Mg chelation, can enhance performance. |
| Zorbas et al., 2010 [209] | Randomized, controlled trial | 40 physically healthy male subjects (21.5 ± 3.0 y) | Control subjects (UCS); hypokinetic subjects (UES); control subject + 3.0 mmol of Mg/kg (SCS); hypokinetic subjects + 3.0 mmol of Mg/kg (SES) | MgCl2 | Decreased muscle Mg and increased plasma Mg and urinary/fecal Mg loss in SES and UES groups vs. controls; more pronounced effects in SES. No changes in control groups. |
| (ii) Magnesium supplementation in clinical conditions | |||||
| Aagaard et al., 2005 [190] | Ranadomized, placebo-controlled trial | 59 patients with alcoholic liver disease (34–61 y) | 2 days of infused Mg (30 mmol in 1 L of glucose solution 55 g/L) + 6–7 weeks 12.5 mmol of Mg orally or placebo | MgSO4 (iv) and MgO (oral) | Muscle Mg concentration was 7% higher in the Mg-treated vs. placebo group. Mg had no effect on muscle strength or mass. |
| Gullestad et al., 1992 [193] | Randomized, double-blinded, placebo-controlled trial | 49 chronic alcoholics (28–84 y) | Placebo or 15 mmol Mg for 6 weeks | Mg citrate lactate | Mg significantly reduced liver enzymes (ASAT, ALAT, GOT), slightly increased serum K and Mg, and significantly improved muscle strength. Alcohol consumption remained constant, indicating that the effects were due to Mg supplementation. |
| Bayram et al., 2021 [210] | Prospective, randomized, open-label trial | 209 subjects with acute musculoskeletal low back pain (18–65 y) | NSAID + 365 mg of Mg, NSAID + paracetamol, NSAID | NK | Improvements in functional outcome and musculoskeletal pain intensity from the initial visit to the 4th day with Mg showed greater enhancement than with NSAID alone and NSAID + paracetamol. No significant difference in these improvements or lumbar mobility between groups by the 10th day. |
| Yousef and Al-deeb, 2013 [205] | Randomized, double-blinded, placebo-controlled trial | 80 patients with chronic low back pain (56.4 ± 13.6 y) | Placebo for 6 weeks or iv Mg for 2 weeks followed by oral Mg for 4 weeks. | MgSO4 (iv) and MgO + Mg gluconate (oral) | Significant reduction in pain intensity (7.5 to 4.7) and improvement in lumbar spine flexion, extension, and lateral flexion movements over 6 months in the Mg group. |
| (iii) Magnesium supplementation in nocturnal leg cramps | |||||
| Maor et al., 2017 [206] | Randomized, double-blind, placebo-controlled trial | 88 male and female subjects with NLC (64.9 ± 11.1 y) | Placebo or 520 mg of Mg for 4 weeks | MgO | There was a mean change in weekly NLC of −3.41 in Mg group and −3.03 in placebo group, with no significant difference between groups. No differences were observed in severity and duration of NLC, QoL, or QoS. |
| Dahle et al., 1995 [200] | Randomized, double-blind, placebo-controlled trial | 73 pregnant women with NLC (NK age) | Placebo or 360 mg of Mg for 3 weeks | Mg citrate lactate | Mg decreased NLC vs. baseline and placebo, but did not significantly increase serum Mg levels, excess magnesium being excreted as measured by an increase [Mg]U. |
| Frusso et al., 1999 [201] | Randomized, double-blind, placebo-controlled, crossover trial | 45 male and female subjects with NLC (28–87 y) | Placebo or 1800 mg of Mg for 30 days, followed by a 30-day washout period | Mg citrate | No significant differences between Mg and placebo in any of the evaluated outcomes, including mean number of cramps. |
| Roffe et al., 2002 [202] | Randomized, double-blind, placebo-controlled, crossover trial | 73 male and female subjects with NLC (Mg: 61 ± 11 y, C: 64 ± 10 y) | Placebo or 300 mg of Mg for 6 weeks | Mg citrate | There was a trend towards less NLC on Mg (p = 0.07). No difference in cramp severity and duration between groups. Significantly more subjects thought that the treatment had helped after Mg than after placebo, suggesting that Mg may be effective in NLC. |
| Nygaard et al., 2008 [203] | Randomized, double-blind, placebo-controlled trial | 45 pregnant women with NLC (Mg: 32 ± 4 y, C: 30 ± 3 y) | Placebo or 360 mg of Mg for 2 weeks | Mg citrate lactate | Mg had no significant effect on frequency or intensity of NLC. |
| Supakatisant and Phupong, 2012 [204] | Randomized, double-blind, placebo-controlled trial | 86 pregnant women with NLC (Mg: 29 ± 6 y, C: 29 ± 5 y) | Placebo or 300 mg of Mg for 4 weeks | Mg bisglycinate chelate | Mg resulted in significant lower cramp frequency and intensity vs. placebo. No significant differences in terms of side effects. |
| (iv) Magnesium supplementation and its distribution | |||||
| Wary et al., 1999 [198] | Randomized, double-blind, placebo-controlled trial | 30 young healthy male volunteers (23.7 ± 4.5 y) | Placebo or 12 mmol Mg for 1 month | Mg lactate | Significant change in 24-h [Mg]U after Mg treatment. No differences in other clinical, biological, or Mg status parameters between groups, including intracellular free Mg concentrations of skeletal muscle. |
1RM, 1 repetition maximum; ALAT, alanine aminotransferase; ASAT, aspartate aminotransferase; BMI, body mass index; bw, body weight; C, control; CK, creatine kinase; Cr, creatine; DBP, diastolic blood pressure; ECW, extracellular water; GOT, glutamic oxaloacetic transaminase; ICW, intracellular water; iv, intravenously; LBM, lean body mass; NK, not known; NLC, nocturnal leg cramp; NSAID, nonsteroidal anti-Inflammatory drug; QoL, quality of Life; QoS, quality of sleep; RAST, repeated sprint ability test; SBP, systolic blood pressure; SCS, supplemented control subject; SES, supplemented experimental subject; UCS, unsupplemented control subject; UES, unsupplemented experimental subject; SPPB, short physical performance battery; T, torque; TGUG, time get up and go test; TPR, total peripheral resistance; VO2max, maximum oxygen volume; y, years; [Mg]U, urinary magnesium concentration. * 300 mg refers to the weight of magnesium oxide (dosage of elemental magnesium not provided).