Magnesium (L-Threonate)

PURPOSE: To investigate the effects of oral administration of magnesium-L-threonate, a novel magnesium compound, on the analgesic effect of opioids in patients with advanced cancer. METHODS: We performed a prospective, randomized, double-blind trial at a tertiary hospital in Shanghai, China. Eligible cancer patients who took opioids orally were assigned randomly to receive L-TAMS capsules (1.5 g or 2.0 g according to weight) or a placebo (starch capsules). The primary outcome was the increase in the daily oral dose of morphine in each of the two groups, measured at 7, 14, 21, 30, 60, and 90 days during this trial. RESULTS: A total of 116 patients from the oncology and pain departments, including inpatients and outpatients, were screened; 83 were enrolled. The increases in daily morphine doses began to differ from day 30 (L-TAMS group 9.85 mg/d vs. Placebo group 20.49 mg/d, p < 0.05); the differences persisted on day 60 (L-TAMS group 15.96 mg/d vs. Placebo group 29.06 mg/d, p < 0.05) and on day 90 (L-TAMS group 21.20 mg/d vs. Placebo group 40.44 mg/d, p < 0.01). CONCLUSIONS: L-TAMS outperforms a placebo in enhancing the analgesic effect of opioids and reducing the necessary opioid dosage. Moreover, L-TAMS can significantly relieve opioid-induced constipation. These advantages may be beneficial to patients with advanced cancer. © 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Magnesium is one of the most abundant essential minerals in the body. Magnesium supplements mostly have low bioavailability, except magnesium L-threonate. In 2010, a novel magnesium compound, magnesium L-threonate (Magtein®) was identified and was shown to raise the magnesium levels in the brain and neurons effectively. In this double-blind, placebo-controlled study, Magtein®PS, a magnesium L-threonate (Magtein®)- and phosphatidylserine-based formulation additionally containing vitamins C and D, was tested for its cognitive benefits in 109 healthy Chinese adults aged 18-65 years. Subjects were randomly assigned to receive either Magtein®PS or placebo (starch) capsules, at a dose of 2 g/day. "The Clinical Memory Test", the standard test commonly used in Chinese hospitals and academic institutes for cognitive evaluation, was administered before and 30 days after subjects received the supplement. Subjects receiving Magtein®PS showed significant improvements over the control group in all five subcategories of "The Clinical Memory Test" as well as the overall memory quotient scores. The older participants showed more improvement than younger participants. Results indicated significant benefits of Magtein®PS in improving memory and cognition in healthy Chinese adults.

X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus (EBV) infection and N-linked glycosylation defect (XMEN) disease is an inborn error of immunity caused by loss-of-function mutations in the magnesium transporter 1 (MAGT1) gene. The original studies of XMEN patients focused on impaired magnesium regulation, leading to decreased EBV-cytotoxicity and the loss of surface expression of the activating receptor "natural killer group 2D" (NKG2D) on CD8+ T cells and NK cells. In vitro studies showed that supraphysiological supplementation of magnesium rescued these defects. Observational studies in 2 patients suggested oral magnesium supplementation could decrease EBV viremia. Hence, we performed a randomized, double-blind, placebo-controlled, crossover study in 2 parts. In part 1, patients received either oral magnesium L-threonate (MLT) or placebo for 12 weeks followed by 12 weeks of the other treatment. Part 2 began with 3 days of high-dose intravenous (IV) magnesium sulfate (MgSO4) followed by open-label MLT for 24 weeks. One EBV-infected and 3 EBV-naïve patients completed part 1. One EBV-naïve patient was removed from part 2 of the study due to asymptomatic elevation of liver enzymes during IV MgSO4. No change in EBV or NKG2D status was observed. In vitro magnesium supplementation experiments in cells from 14 XMEN patients failed to significantly rescue NKG2D expression and the clinical trial was stopped. Although small, this study indicates magnesium supplementation is unlikely to be an effective therapeutic option in XMEN disease. © 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Background: There is a growing number of studies suggesting the effectiveness of dietary supplements in preventing and treating endometriosis. It has been suggested that deficiencies in vitamins D and E as well as zinc are associated with the increased risk of endometriosis development. Beneficial effects of magnesium, curcumin, resveratrol and epigallocatechin-3-gallate were found in experimental animal studies. A reduction in pain related to endometriosis was shown in women using omega-3 and alpha-lipoic acid. Meanwhile, decreasing endometriotic lesion size after the supplementation of omega-3, N-acetylcysteine, vitamin C and epigallocatechin-3-gallate was observed in animal and human studies. Thus, the aim of this critical review was to summarize the available data describing the effects of dietary supplements used in the treatment of endometriosis. Material and Methods: The PubMed, Embase, Cochrane, and Web of Science databases were searched for related studies until 15 December 2025. Finally, 34 studies were included in the synthesis. Results: Of these 34 studies, only 23 were randomized, placebo-controlled trials. There have been no RCTs evaluating the effectiveness of vitamin E, zinc, alpha-LA, EGCG and DIM in the treatment of endometriosis. Single studies evaluating the effectiveness of vitamin C, magnesium, resveratrol, NAC and PEA with PLD have not confirmed it. Meanwhile single studies evaluating the effectiveness of selenium, propolis and quercetin have confirmed it. Of the four studies assessing the effectiveness of vitamin D, two confirmed it and two did not; of the two studies assessing probiotics, one confirmed its effectiveness and one did not; of the two studies assessing curcumin, one confirmed its effectiveness and one did not; and of the three studies assessing omega-3, two confirmed its effectiveness and one did not. All four RCTs assessing the combination of vitamins C and E confirmed their effectiveness. Conclusions: Despite encouraging observations from experimental studies, the results of RCTs are less encouraging and do not allow for the formulation of recommendations concerning the use of supplements in the treatment of endometriosis

OBJECTIVES: To evaluate the effectiveness of magnesium supplementation as an adjunct to fluoxetine therapy for improving depressive symptoms and serum serotonin levels in patients with depression. METHODS: Consecutive patients aged 18 to 45 years who had been prescribed fluoxetine therapy for new-onset or chronic depression were recruited between November 2024 and February 2025 at the outpatient psychiatry clinic of Wahidin Sudirohusodo General Hospital and three affiliated hospitals in Makassar, Indonesia. Participants were randomised in an alternating sequence to receive either fluoxetine 20 mg/day alone or in combination with oral magnesium supplementation 250 mg/day. Outcomes were assessed at baseline and week 6. The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). Blood samples were collected to measure serum serotonin levels. RESULTS: In total, 32 women and 8 men who received either fluoxetine alone (n = 20) or in combination with magnesium (n = 20) were included in the analysis. Both groups showed significant reductions in HDRS total score from baseline to week 6 (p < 0.001), but changes in serum serotonin level were not significant in either group. The reduction in HDRS total score was greater in the intervention group than in the control group (-6.35 vs -2.80, p < 0.001), particularly in the domains of mood and insomnia. The median reduction in HDRS total score was greater in the intervention group than in the control group (-6 vs -2, p < 0.001). The group effect remained significant (F(1,30) = 33.51, partial η2 = 0.528, p < 0.001) after adjustment for baseline HDRS score and demographic covariates, indicating a large effect size. CONCLUSION: Magnesium supplementation as an adjunct to fluoxetine therapy improves HDRS total score in patients with depression.

BACKGROUND: Medial arterial calcification (MAC) and increased arterial stiffness contribute to cardiovascular disease risk in type 2 diabetes mellitus (T2DM). Experimental studies suggest that magnesium supplementation may halt arterial calcification and improve arterial stiffness. OBJECTIVES: This study aimed to evaluate the effect of 6-mo oral magnesium citrate supplementation on calciprotein crystallization (T50) and carotid-femoral pulse wave velocity (cfPWV) in individuals with T2DM and peripheral MAC. METHODS: This double-blind, placebo-controlled trial randomly assigned 74 participants with T2DM [78% males, 72 (68-76) y] with peripheral MAC and cfPWV≥12.0 m/s to magnesium citrate (350 mg/d; n = 37) or placebo (n = 37). Nephelometry-based T50 measurements, cfPWV measurements, and 24-h urine collections were obtained at baseline, 3 and 6 mo. Longitudinal analysis of covariance adjusted for baseline T50 and cfPWV was used to study the treatment effects on T50 and cfPWV. RESULTS: Baseline mean T50 and cfPWV were similar between the magnesium group (T50 348 ± 54 min; cfPWV 15.9 ± 2.2 m/s) and the placebo group (362 ± 54 min; 15.6 ± 2.0 m/s). Magnesium in serum and in 24-h urine were lower in the magnesium group [0.74 (0.71-0.77) mmol/L and 3.30 (2.06-4.71) mmol/24 h] compared with the placebo group [0.81 (0.74-0.86) mmol/L and 4.31 (3.09-5.54) mmol/24 h]. Supplementation increased 24-h urine magnesium excretion (P < 0.001), but not serum magnesium concentration (P = 0.073) over time in the magnesium group relative to the placebo group. Magnesium supplementation did not increase T50 [ẞ = 6 min (-11, 22), P = 0.491] but did increase cfPWV [ẞ = 0.8 m/s (0.1, 1.5), P = 0.021] over 6 mo in the magnesium group relatively to the placebo group, but the statistical significance was lost after adjusting for clinically relevant baseline differences [T50: ẞ = 7 min (-12, 25), P = 0.482; cfPWV: ẞ = 0.5 m/s (-0.2, 1.3), P = 0.180]. CONCLUSIONS: Six-month magnesium citrate supplementation did not reduce calciprotein crystallization and arterial stiffness in older individuals with T2DM with peripheral MAC. Daily supplementation of 350 mg appears to be ineffective in this popu

As the global population ages, frailty and sarcopenia have emerged as pressing public health challenges due to their impact on functional decline and increased health care burden. This study assessed the efficacy of lactic acid bacteria-fermented whey protein (LAB-FWP) supplementation for improving physical function and nutritional markers in community-dwelling older Korean adults. A total of 45 individuals aged 65 years and older (body mass index 18.5-30) who had not used protein supplements in the prior 6 months were enrolled in a 10-week, randomized, blinded trial. Participants were assigned to either the intervention group (n = 22), which received 38 g/day of LAB-FWP, or the control group (n = 23), which received a taste- and texture-matched dextrin placebo. The intervention group demonstrated significant improvements in physical performance, including an increase in electronic Short Physical Performance Battery (eSPPB) scores (P = .034) and hand grip strength (P = .043). Nutritional biomarkers also improved markedly: dietary vitamin D intake increased from 2.2 to 11.6 µg, calcium intake from 280.9 to 566.7 mg, and magnesium intake from 135.5 to 316.3 mg (all P < .001). Compared with controls, the intervention group showed greater gains in skeletal muscle mass index (Δ = 1.5, P = .004) and eSPPB scores (Δ = 1.4, P = .017). Regression analysis revealed that physical function was positively associated with improvements in nutrition. Daily supplementation with LAB-FWP led to clinically meaningful enhancements in both functional capacity and nutritional status, suggesting its potential as a practical strategy to mitigate age-related frailty and sarcopenia.

PURPOSE: Pre-diabetes significantly increases the risk of type 2 diabetes and cardiovascular disease. Magnesium deficiency is common and may contribute to dysglycemia. However, evidence for the efficacy of magnesium supplementation in pre-diabetes, especially in older adults with hypomagnesemia, remains limited and inconclusive. This exploratory trial aimed to evaluate the effects of oral magnesium supplementation on glycemic parameters and conducted exploratory metabolomic profiling in this population. METHODS: In this 4-month, randomized, double-blind, placebo-controlled trial, 71 community-dwelling older adults (mean age 68.7 ± 6.0 years) with pre-diabetes (fasting plasma glucose ≥5.6 mmol/L and/or HbA1c 5.7%-6.5%) and hypomagnesemia (plasma magnesium ≤ 0.80 mmol/L) were enrolled. Participants were randomly assigned to receive either magnesium oxide (360 mg elemental Mg/day) or an identical placebo once daily. The primary outcome was the change in fasting plasma glucose (FPG). Secondary outcomes included changes in insulin, HOMA-IR, HbA1c, glycated albumin, and inflammatory markers (hs-CRP, IL-6). Exploratory non-targeted metabolomic profiling was performed. Data were analyzed using ANCOVA adjusted for baseline values, following the intention-to-treat principle. RESULTS: Sixty-five participants completed the trial. At baseline, the magnesium group had significantly higher insulin and HOMA-IR levels (both p < 0.05); analyses were adjusted accordingly. Compared to placebo, magnesium supplementation significantly increased plasma magnesium (adjusted mean difference: 0.056 mmol/L, 95% CI: 0.028 to 0.085; p < 0.001) and reduced FPG (adjusted mean difference: -0.497 mmol/L, 95% CI: -0.818 to -0.176; p = 0.003). The reduction in HOMA-IR favored the magnesium group but was not statistically significant after adjustment (p = 0.296). No significant between-group differences were observed for HbA1c, insulin, C-peptide, glycated albumin, or inflammatory markers. Exploratory metabolomics revealed alterations in putatively identified metabolites, with pathway analysis suggesting involvement of lipid and insulin resistance-related pathways; these findings are considered hyp

AIM: This study aimed to examine the trends and determinants of dietary supplement use and to assess the prevalence and predictors of potential drug-supplement interactions among older adults over a 16-year follow-up. METHODS: This repeated cross-sectional study included adults aged ≥ 50 years who participated in the third (2006–2008; n = 3,484), fourth (2009–2011; n = 4,020), fifth (2012–2014; n = 4,342), sixth (2015–2017; n = 4,598), and seventh (2018–2022; n = 4,750) examinations of the Tehran Lipid and Glucose Study (TLGS). Information on dietary supplement use, including individual vitamin supplements and prescription medication use was collected using standardized questionnaires. Trends in supplement use and participant characteristics were evaluated across study phases. Clinically relevant mild-to-moderate potential drug-supplement interactions were defined as the concurrent use of specific dietary supplements and commonly prescribed medications and were classified according to Stockley’s framework. Multivariable logistic regression models were used to identify factors associated with dietary supplement use and potential drug-supplement interactions in the 2018–2022 examination. RESULTS: Over 16 years, dietary supplement use increased more than 2-fold from 10.4% to 21.1%, mainly from increases in thiamin (2.2% to 13.4%), cobalamin (1.8% to 9.8%), vitamin C (1.3% to 7.9%), vitamin E (1.8% to 8.7%), and zinc (0.2% to 3.3%). Female sex, higher education, and diabetes were associated with higher likelihood of supplement use. In 2018–2022, 4.8% of participants had potential drug-supplement interactions, most commonly vitamin E with aspirin (2.3%) and magnesium or potassium with antihypertensive medications. The likelihood of potential drug-supplement interactions was higher in women (OR = 2.03, 95%CI = 1.61–2.56), participants with primary education (OR = 1.45, 95% CI = 1.09–1.96), smokers (OR = 1.50, 95%CI = 1.07–2.12), and individuals with diabetes (OR = 2.80, 95%CI = 2.13–3.68), hypertension (OR = 2.20, 95%CI = 1.78–2.73), chronic kidney disease (OR = 2.35, 95%CI = 1.88–2.94), or multimorbidity (OR = 2.46, 95%CI = 1.85–3.26). CONCLUSION: Over 16 years, supp

BACKGROUND: Leg cramps are common among older adults and often lead to sleep disturbances and reduced quality of life. However, there is no consensus on how to treat this condition. This study aimed to evaluate the effectiveness of compression stockings in preventing leg cramps in individuals aged 50 to 85. METHODS: This study was a three-arm, parallel-group, partially blinded, randomized placebo-controlled trial conducted in Finland. Participants were recruited nationwide through online advertisements and primary care centers. Eligible individuals had experienced at least two leg cramps per week during the previous 4 weeks. Participants were randomized to receive either knee-high medical compression stockings, magnesium hydrochloride, or placebo pills, to be used daily for 4 weeks. The primary outcome was the change in leg cramp frequency at week 8. Secondary outcomes included the number of leg cramp-related nocturnal awakenings and the perceived pain intensity on an ordinal scale. RESULTS: A total of 121 participants were randomized, and 109 (90.1%) completed the trial. The primary outcome analysis included 114 participants. The mean age was 65.8 years (SD 7.8), and 87 (71.9%) were women. At baseline, the median number of weekly leg cramps was 4 (IQR 3-7). At week 8, the median weekly leg cramp frequency was 2 (IQR 1-2.5) in the compression stockings group, 3 (IQR 2-6) in the magnesium group, and 3 (IQR 2-5) in the placebo group. The baseline-adjusted mean difference in leg cramp frequency between the compression stockings and placebo group was -1.43 (95% CI -2.36 to -0.50; P = .001). No significant difference was observed between the magnesium and placebo groups, with an adjusted mean difference of -0.20 (95% CI -1.49 to 1.09; P = 0.929). Four participants discontinued compression stockings due to adverse reactions. No serious adverse events were reported. CONCLUSIONS: Among older adults, daily use of compression stockings was effective in reducing the frequency and pain intensity of leg cramps, as well as the number of nocturnal awakenings caused by them. TRIAL REGISTRATION: ClinicalTrials.gov NCT04694417. Registered on 4 January 2021. © 2026. The Author(s)

Erratum in Front Nutr. 2026 Oct 15;13:2010644. doi: 10.3389/fnut.2026.2010644. BACKGROUND/OBJECTIVES: Magnesium may help support cognition and sleep. The purpose of this two-arm, 6-week, parallel-group, randomised, double-blind, placebo-controlled trial was to examine the effects of magnesium L-threonate (Magtein®) supplementation on cognitive performance, cognitive age, sleep quality, and selected physiological indicators in adults. METHODS: One hundred adults aged 18 to 45 with self-reported dissatisfied sleep were supplemented with 2 g daily of Magtein® or a placebo. Outcome measures comprised the computer-based National Institute for Health (NIH) Cognitive Toolbox and Raven's Progressive Matrices Version 2 for the assessment of cognitive function, self-report evaluations of sleep quality and emotional wellbeing, a reaction time test, and physiological data obtained from a sleep-tracking wearable device (Oura Ring), including resting heart rate (HR) and heart rate variability (HRV) during sleep. RESULTS: Compared to the placebo, Magtein® was associated with greater improvements in overall cognitive performance as measured by the NIH Total Cognition Composite (p = 0.043), with larger treatment effects on working and episodic memory. There was also a 7.5-year reduction in estimated brain cognitive age and a greater improvement in reaction time (p = 0.031). However, there were no group differences in changes in the Raven's test (p = 0.953). Based on self-report measures, there was a greater improvement in sleep-related impairment (p = 0.043), but no group differences in changes in sleep disturbances (p = 0.316), restorative sleep (p = 0.439), or general wellbeing (p = 0.436); although in a subset of participants with more severe sleep-related problems, group differences in sleep-disturbances were identified (p = 0.031). Based on data from the sleep tracking ring, there were no group differences in sleep outcomes, although there was a greater reduction in HR (p = 0.030) and an increase in HRV (p = 0.036), a physiological marker of stress reduction and improved autonomic balance. Magtein® was well-tolerated, and there were no reports of significant adverse reacti

BACKGROUND: Polycystic ovary syndrome (PCOS) often leads to insulin resistance, affecting glucose and fat metabolism. This study aimed to explore the impact of mineral supplements on insulin resistance, blood sugar, and lipid profiles in women with PCOS. METHODS: A systematic review of randomized controlled trials (RCTs) was conducted across four databases. The risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Mineral supplements were compared with a placebo in all studies, and data were analyzed using fixed-effect and random-effects models to assess the impact on metabolic parameters. RESULTS: This meta-analysis included 11 RCTs involving 618 women with PCOS. Mineral supplementation was associated with significant reductions in fasting blood glucose (SMD = − 0.34, p < 0.001), fasting insulin (SMD = − 0.72, p < 0.001), and HOMA-IR (SMD = − 0.75, p < 0.001). In addition, total cholesterol (SMD = − 0.35, p < 0.001) and triglyceride levels (SMD = − 0.58, p < 0.001) were significantly reduced. A small but statistically significant reduction in HDL levels was also observed (SMD = − 0.19, p = 0.04). No significant effect was found on LDL-C (SMD = − 0.11, p = 0.55). CONCLUSION: Mineral supplementation may improve insulin resistance and selected metabolic parameters in PCOS, with the most consistent effects observed for glycemic indices. Effects on lipid parameters were mixed. Further large-scale, well-designed trials are needed to clarify long-term benefits and optimal supplementation strategies. CLINICAL TRIAL NUMBER: Not applicable.

BACKGROUND: Bisphosphonates (BP) are a recommended treatment for osteoporosis and an analgesic effect has been suggested. Magnesium is involved in pain mechanisms, mood disorders and also in bone homeostasis. Association of BPs and magnesium has however not been studied to explore pain processes in post-menopausal osteoporosis. METHODS: In this pilot ancillary study of a randomized clinical trial in post-menopausal osteoporosis, women were randomized to standard care with intravenous Zoledronate (BP group, n = 22) or BP with oral magnesium (BPMg group, n = 22), 200 mg/day for 3 months. Endpoints were quantified before and 1 year after treatment as spontaneous pain, anxiety, depression and sleep quality, as well as quantitative sensory testing of pain sensitivity by thermal thresholds and conditioned pain modulation (CPM), a psychophysical marker of the functionality of pain modulation at spinal level. RESULTS: Thirty-five women (68.2 ± 7.3 years old) with post-menopausal osteoporosis completed the analysis. Compared with baseline, magnesium supplementation did not change significantly any of the endpoints. CPM at baseline was low (-0.92 ± 1.14) and not reversed by treatment. CONCLUSIONS: This study in post-menopausal osteoporosis underlines for the first time that zoledronate or zoledronate with magnesium have no effect on pain characteristics and thresholds. It shows a dysfunction of pain inhibitory pain pathways and its non-reversibility with treatments. It points towards the lack of any analgesic effect of zoledronate, and above all to a latent vulnerability of osteoporotic women who are at a potential risk of fracture with a poor pain modulation that needs to be researched further to limit future chronification. TRIAL REGISTRATION NUMBER: (NCT05328154), 15/03/2022. TRIAL: Protocol, statistical analysis plan, participant data and other materials (including data dictionary) can be accessed on request to the corresponding author. © 2026. The Author(s).

OBJECTIVE: To explore the effects of multivitamin combined with magnesium sulfate on placental hemodynamics, coagulation function, and maternal and infant outcomes in preeclampsia patients. METHODS: A randomized controlled study was conducted among 194 pregnant women diagnosed with preeclampsia between April 2022 and April 2023. Participants were randomly assigned to either the control group (n = 97), receiving intravenous magnesium sulfate alone, or the observation group (n = 97), receiving magnesium sulfate combined with multivitamin supplementation. Magnesium sulfate was administered with a loading dose of 2.5-5 g via rapid IV infusion and a maintenance dose of 5-20 g by continuous drip. The observation group additionally received one oral multivitamin tablet (Bayer S.A., 30 tablets/box) once daily in the morning. The treatment duration for both groups was two weeks. Blood pressure, 24-hour urinary protein, placental Doppler indices (RI, PI, S/D), coagulation markers (PT, APTT, FIB, TT), and maternal-infant outcomes were measured and compared. RESULTS: After treatment, both groups showed significant reductions in systolic and diastolic blood pressure, but there was no significant difference between them. However, the observation group had significantly lower 24-hour urinary protein levels (0.71 ± 0.31 g vs. 0.92 ± 0.28 g, P < 0.001). Coagulation function improved in both groups, with the observation group showing greater improvements: longer PT, APTT, and TT times, and lower FIB levels (P < 0.01). Placental hemodynamics also improved more in the observation group, with lower resistance indices and S/D ratios in both the umbilical and spiral arteries (P < 0.001). The observation group had better maternal and neonatal outcomes, including fewer cases of postpartum hemorrhage (10 vs. 22, P = 0.020), low birth weight (10 vs. 23, P = 0.013), and NICU admissions (9 vs. 21, P = 0.018). Eclampsia occurred only in the control group (3 cases), though this was not statistically significant (P = 0.081). Other outcomes, such as uterine inertia and neonatal asphyxia, were similar between groups. Subgroup analysis showed that patients with severe preeclampsia in the observat

Comment in JAMA Intern Med. 2026 Feb 1;186(2):190-191. doi: 10.1001/jamainternmed.2025.6579. IMPORTANCE: Magnesium supplementation is regularly given to acutely ill patients with serum levels below the standard reference range, primarily for the prevention of tachyarrhythmias, such as atrial fibrillation. The evidence for this practice and the specific treatment thresholds used is limited. Conventional observational studies of this question are at risk of confounding by indication and other biases. OBJECTIVE: To determine whether giving magnesium supplementation to patients with hypomagnesemia, as defined by a given institution's usual treatment cutoff, reduces adverse clinical outcome using a quasi-experimental study design that plausibly allows for causal inference. DESIGN, SETTING, AND PARTICIPANTS: This nonrandomized clinical trial of intensive care unit (ICU) patients undergoing serum magnesium testing was conducted in 93 ICUs across the US and Europe between 2003 and 2022. A fuzzy regression discontinuity design was used, in which individuals just either side of the eligibility cutoff for magnesium supplementation were compared with regard to the study outcomes. This comparison was performed across a range of treatment cutoffs in current use, ranging from 1.6 mg/dL to 2.0 mg/dL. Data were analyzed from August to October 2025. EXPOSURES: Magnesium supplementation. MAIN OUTCOMES AND MEASURES: The primary outcome was ventricular or supraventricular tachyarrhythmia in the 24 hours after magnesium testing. Secondary outcomes were the occurrence of hypotension or death. RESULTS: A total of 478 901 twenty-four-hour treatment windows from 171 727 ICU admissions were included in the study. A total of 72 767 admitted patients (42.4%) were female, 98 960 (57.6%) were male, and the mean (SD) age of the cohort was 63 (16) years. There was no evidence of an effect of magnesium supplementation on the occurrence of tachyarrhythmia, with a risk difference of 0.1% (95% CI, -4.2 to 6.9). This was true across all the cutoff levels evaluated. There was similarly no association with the occurrence of hypotension (risk difference, 1.2%; 95% CI, -0.9 to 17.7) or death (risk diff

OBJECTIVE: Postoperative hypocalcemia and hypoparathyroidism are common complications after thyroidectomy, often impairing quality of life (QoL). This study investigates the impact of preoperative calcium and magnesium supplementation on postoperative QoL and hypocalcemia in patients undergoing total thyroidectomy for symptomatic nodular goitre or Graves' disease. METHODS: A total of 62 patients undergoing thyroidectomy for benign thyroid diseases were randomised into two groups. The intervention group (IG, n = 31) received 500 mg calcium carbonate thrice daily and 300 mg magnesium carbonate once daily for 2 weeks preoperatively, while the control group (CG, n = 31) received no supplementation. Laboratory parameters (Ca, Mg, PTH, 25-OH-Vitamin D) were measured at study enrolment (T1), preoperatively (T2), immediately postoperatively (T3) and 6 weeks post-discharge (T4). QoL was assessed using EQ-5D and ThyPro39de questionnaires. RESULTS: QoL significantly improved postoperatively in both groups. Patients with Graves' disease in the IG reported earlier QoL improvements immediately post-surgery (T3). Postoperative hypocalcemia occurred in 19.4% of IG patients and 25% of CG patients, with hypoparathyroidism in 16% and 23%, respectively. The IG demonstrated higher postoperative calcium levels and fewer hypocalcemia symptoms, especially in Graves' disease patients (not significant). Vitamin D deficiency was prevalent (66.7%) but showed no correlation with hypocalcemia. DISCUSSION: Preoperative calcium and magnesium supplementation might have positive effects on postoperative QoL, especially in Graves' disease patients, and may reduce hypocalcemia symptoms. This simple, inexpensive and low-risk intervention may be beneficial in the preoperative setting prior to thyroidectomy. Although the observed effect did not reach statistical significance, it could still be of clinical relevance. The additional benefit of preoperative magnesium supplementation seems to be of minor significance, while the effect of pre-existing vitamin D deficiency remains uncertain. © 2025 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.

The mechanism of action of integrase strand transfer inhibitors involves binding to magnesium ions in the active site of the HIV integrase enzyme, making them susceptible to chelation-type drug-drug interactions with metal cation-containing medications. This study evaluated the potential of metal cation-containing antacids and mineral supplements to impact bictegravir (BIC) exposure and assessed alternative approaches for combined use. This was an open-label, single-dose, Phase 1 study in adult participants without HIV. The pharmacokinetics and safety of BIC (administered as part of a single-tablet combination with emtricitabine [F] and tenofovir alafenamide [TAF; B/F/TAF]) were assessed when co-administered with maximum-strength aluminum/magnesium-containing antacid (referred to as "aluminum/magnesium-containing antacid"), calcium carbonate, or ferrous fumarate under fasted and fed conditions, and administered 2 hours before or after the antacid. Pharmacokinetic parameters were compared using analysis of variance to calculate geometric least-squares mean ratios and 90% confidence intervals. Forty-two participants were enrolled. BIC exposure (area under the plasma concentration-time curve extrapolated to infinity) was reduced by 79%, 33%, and 63%, respectively, when co-administered with aluminum/magnesium-containing antacid, calcium carbonate, and ferrous fumarate under fasted conditions. Co-administration of B/F/TAF with calcium carbonate or ferrous fumarate with a meal and administration of B/F/TAF 2 hours before the antacid reduced the impact of the interactions. B/F/TAF was well tolerated alone or in combination with metal cation-containing medications. Co-administration of BIC and calcium/iron-containing supplements with a meal and administration of BIC 2 hours or more before aluminum/magnesium-containing antacids are some of the effective strategies to mitigate chelation effects on BIC exposure.This study was registered at NCT05502341/NCT06333808.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the benefits and harms of magnesium supplementation for preventing episodic or chronic migraine in children and adults compared to usual pharmacological treatment or placebo. Secondary objective To evaluate the benefits and harms of magnesium supplementation in different groups, specifically in terms of equity-related characteristics such as economic status, age, or sex.