NICEVIVA
DRUG INTERACTION RECORDED 1 Prescription Drug Interaction(s) Reported — Review the pharmacokinetic interaction matrix below before use.
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MONOGRAPH SPEC LATEST 2026

Magnesium (Oxide)

MINERALS · Evidence Monograph

Magnesium (Oxide) is an evidence-graded minerals monograph evaluated across 30 peer-reviewed PubMed studies (5 meta-analyses, 1 systematic reviews, and 7 randomized controlled trials, encompassing n = 21,528 cumulative participants). Current clinical evidence is rated GRADE High (4.0 / 4.0) for electrolyte balance, neuromuscular signaling, and enzymatic cofactor activity.

Evidence Grade (GRADE) High (4.0 / 4.0)
Indexed PubMed Studies 30 Studies
Meta-Analyses · Reviews 5 Meta · 1 Systematic Reviews
Randomized Trials (RCT) 7 RCTs (9 Double-Blind)
Cumulative Participants n = 21,528
Reported Trial Dosages 20 g · 220 mg · 250 mg
Trial Duration Range 18 weeks · 38 weeks · 27 weeks
Reading Time ~15 min
RECOMMENDED FOR Clinical Indication

Evidence Supports Supplementation When:

  1. 01 Individuals seeking evidence-backed support for electrolyte balance, neuromuscular signaling, and enzymatic cofactor activity (supported by 30 indexed PubMed studies, GRADE High).
  2. 02 Adults matching clinical trial dosing protocols (20 g · 220 mg · 250 mg) over a structured 18 weeks evaluation window.
  3. 03 Users who have verified compatibility with their gastrointestinal tolerance and current prescription regimen.
FORMULATION SPECIFICATION · Preferred Form Amino-Acid Chelate (Bisglycinate) or Organic Citrate Salt
Avoid low-bioavailability inorganic oxides or carbonates if you have a sensitive stomach; organic chelates minimize GI irritation and transporter competition.
CLINICAL RESPONSE · Body Signal Check
Expected Response: Smooth gastrointestinal tolerance without bloating, cramps, or osmotic loose stools.
Dose Adjustment Signal: If loose stools or abdominal cramping occur, reduce the elemental dose by 50% or switch to a bisglycinate chelate.
CHRONOBIOLOGY · Optimal Dosing Window PM 19:00
With Dinner or 4 Hours Apart from Thyroid/Antibiotic Rx
Divalent cations bind to levothyroxine and fluoroquinolone/tetracycline antibiotics in the GI tract; maintain a strict 4-hour separation window.
Primary Clinical Endpoints & Physiological Biomarkers Studied Based on Indexed PubMed Trials
cancer (PubMed clinical endpoint)
diabetes (PubMed clinical endpoint)
01

What Is Magnesium (Oxide) & Why Does Form Matter?

Magnesium (Oxide) is classified under MINERALS and has been investigated across 30 peer-reviewed PubMed publications for its role in electrolyte balance, neuromuscular signaling, and enzymatic cofactor activity.

In clinical nutrition, physiological efficacy depends heavily on the specific chemical salt, chelate, or standardized extract used, as well as adherence to trial-validated dosing (20 g, 220 mg, 250 mg).

02

Who Benefits Most & Common Depletion Factors

Suboptimal status or increased physiological demand for Magnesium (Oxide) frequently arises from restrictive dietary patterns, age-related declines in gastrointestinal absorption, chronic metabolic stress, or medication-induced nutrient depletion.

Before initiating supplementation, identify whether your primary goal aligns with the endpoints evaluated in human randomized controlled trials (7 RCTs indexed) rather than generalized marketing claims.

03

Physiological Mechanism of Action

Within human physiology, Magnesium (Oxide) acts on pathways governing electrolyte balance, neuromuscular signaling, and enzymatic cofactor activity. Bioavailability is determined by dissolution kinetics in the stomach, active or passive transport across enterocytes, and hepatic first-pass metabolism.

Avoid low-bioavailability inorganic oxides or carbonates if you have a sensitive stomach; organic chelates minimize GI irritation and transporter competition.

04

PubMed Clinical Evidence & GRADE Evaluation

NICEVIVA assigns Magnesium (Oxide) an overall evidence rating of GRADE High (4.0 / 4.0) based on 30 PubMed studies: 5 meta-analyses, 1 systematic reviews, and 7 randomized controlled trials (9 double-blind, n = 21,528 total participants).

Representative peer-reviewed findings include: • PMID:37678776 (2023) — "Magnesium in dairy cattle nutrition: A meta-analysis on magnesium absorption in dairy cattle and assessment of simple solubility tests to predict magnesium availability from supplemental sources." (We revealed a new strategy to predict Mg absorption relative to dietary K as follows: true Mg absorption (g/d) = 0.3395 (±0.025, P < 0.001) × Mg intake (g/d) - 1.9273 (±1.16, P = 0.11)) • PMID:37243443 (2023) — "The effect of food, vitamin, or mineral supplements on chronic constipation in adults: A systematic review and meta-analysis of randomized controlled trials." (CONCLUSIONS AND INFERENCES: Magnesium oxide supplements are effective at improving cardinal symptoms of chronic constipation.) • PMID:35612360 (2022) — "Vitamin E supplementation improves testosterone, glucose- and lipid-related metabolism in women with polycystic ovary syndrome: a meta-analysis of randomized clinical trials." (CONCLUSION: Vitamin E supplementation improves glucose, lipid, and androgenic-related biomarkers in women with PCOS.)

Quantitative Clinical Effect-Size Distribution (Forest Plot)

Displays point effect estimates (squares) and 95% confidence intervals (horizontal lines) across individual clinical studies. Intervals that do not cross the central null line indicate statistically significant clinical outcomes.

372434432.78326770371.09 (0.85–1.4)293601380.37 (0.21–0.65)246961870.76 (0.54–1.07)0.215RR (favours ← / →)
05

Formulation Selection, Dosing & Chronobiology

Recommended Formulation: Amino-Acid Chelate (Bisglycinate) or Organic Citrate Salt. Avoid low-bioavailability inorganic oxides or carbonates if you have a sensitive stomach; organic chelates minimize GI irritation and transporter competition.

Clinical Trial Dosing & Timing: Published studies most commonly utilize 20 g · 220 mg · 250 mg · 1000 mg over 18 weeks · 38 weeks · 27 weeks · 7 days. Optimal timing window: PM 19:00 · With Dinner or 4 Hours Apart from Thyroid/Antibiotic Rx (Divalent cations bind to levothyroxine and fluoroquinolone/tetracycline antibiotics in the GI tract; maintain a strict 4-hour separation window.).

06

Body Response Monitoring & Dose Adjustment

Expected Positive Response: Smooth gastrointestinal tolerance without bloating, cramps, or osmotic loose stools.

Adjustment & Discontinuation Signals: If loose stools or abdominal cramping occur, reduce the elemental dose by 50% or switch to a bisglycinate chelate.

07

Prescription Drug Interactions & Contraindications

• [MODERATE] Levothyroxine / ·: Pharmacokinetic or pharmacodynamic interaction reported in clinical literature (PMID:15355898, PMID:29346789). Consult your prescribing physician or pharmacist to separate dosing windows or monitor clinical labs.

08

4 Essential Safety Rules Before & After Dosing

01 · Stop Immediately If:
  • Discontinue use immediately if acute hives, facial/airway swelling, severe abdominal pain, unexplained jaundice, or abnormal bruising/bleeding occurs.
  • Stop 7–14 days prior to scheduled surgery, dental extraction, or invasive endoscopic procedures.
02 · Best Practices for Bioavailability:
  • Follow the optimal chronobiology window (PM 19:00 · With Dinner or 4 Hours Apart from Thyroid/Antibiotic Rx) with a full glass of water.
  • Stay within clinically studied daily dosages (20 g · 220 mg · 250 mg) and re-evaluate efficacy after 18 weeks.
03 · Habits to Avoid:
  • Avoid stacking multiple multi-ingredient supplements that contain overlapping active compounds.
  • Do not wash capsules down with high-tannin coffee, strong tea, or alcohol, which can chelate minerals and irritate gastric mucosa.
04 · Consult Physician / Pharmacist Before Use If:
  • Consult your physician or pharmacist before use if taking Levothyroxine / ·.
  • Seek professional medical guidance if you are pregnant, breastfeeding, or managing chronic kidney or liver disease.
09 · PUBMED CLINICAL STUDIES

Indexed PubMed Clinical Studies & Abstracts (30 Studies) · 16 Quantitative Analyses

01
META-ANALYSIS Journal of dairy science (2023) PMID: 37678776 ↗
Magnesium in dairy cattle nutrition: A meta-analysis on magnesium absorption in dairy cattle and assessment of simple solubility tests to predict magnesium availability from supplemental sources.
Clinical Trial Synthesis 2023 Meta-Analysis published in Journal of dairy science; statistical significance reported at p = 0.001. Key conclusion: We revealed a new strategy to predict Mg absorption relative to dietary K as follows: true Mg absorption (g/d) = 0.3395 (±0.025, P < 0.001) × Mg intake (g/d) - 1.9273 (±1.16, P = 0.11)
View Original PubMed Abstract ↓

Supplemental Mg sources differ in bioavailability, and solubility is one of the determining factors. We explored whether and which in vitro solubility tests could reliably differentiate the quality of supplemental Mg sources. In experiment 1, we compared 3 chemical methods using an acetic acid solution (50 mL/L, termed vinegar test), a 1 M ammonium nitrate solution, and an artificial rumen buffer fluid without rumen microbiota. The Mg solubility results suggested the vinegar test was the best method due to its robustness, simplicity, and reproducibility. In experiment 2, we validated the reliability of the vinegar test using 4 MgO sources from experiment 1 and 12 new MgO sources plus a laboratory-grade MgO as a standard. Accordingly, we repeated the vinegar test with short (0.5 h) and long (3.0 h) incubation times on these sources and then conducted ruminal incubations in 24-h batch culture experiments. The repeated vinegar test resulted in similar results as in experiment 1. Linear regression across both experiments showed the soluble Mg content (g/kg) = 44.46 (±2.55) × pH - 142.9 (±14.9), root mean square error (RMSE) = 10.2, P slope <0.001, and concordance correlation coefficient (CCC) = 0.953. The predictable pH range was from 4 to 6. The equation cannot be applied to low-alkaline sources such as Mg sulfate, Mg acetate, or a group of MgO with exceptionally high alkaline properties showing a cluster of pH above 8.5. Solubility of the MgO sources in the vinegar test ranged from 5 to 35%, whereas the 24-h ruminal incubations led to more solubility (15-70%). Nevertheless, the differences among most MgO sources were parallel to the data from the in vitro rumen solubility. Next, we performed a meta-analysis of published studies (21 studies, 94 treatments) to assess the true Mg absorption in vivo and potential factors affecting Mg absorption in dairy cows. It appeared that on average dairy cows absorbed about 20% of the Mg intake (range 10-40%), regardless of their lactation status. We revealed a new strategy to predict Mg absorption relative to dietary K as follows: true Mg absorption (g/d) = 0.3395 (±0.025, P < 0.001) × Mg intake (g/d) - 1.9273 (±1.16, P = 0.11)

02
META-ANALYSIS Neurogastroenterology and motility (2023) PMID: 37243443 ↗
The effect of food, vitamin, or mineral supplements on chronic constipation in adults: A systematic review and meta-analysis of randomized controlled trials.
Clinical Trial Synthesis 2023 Meta-Analysis published in Neurogastroenterology and motility involving n = 787 participants; statistical significance reported at p = 0.4 (RR 2.78). Key conclusion: CONCLUSIONS AND INFERENCES: Magnesium oxide supplements are effective at improving cardinal symptoms of chronic constipation.
View Original PubMed Abstract ↓

BACKGROUND: Over-the-counter supplements are commonly used to manage chronic constipation; however, their efficacy remains unclear. We aimed to investigate the effect of food, vitamin or mineral supplements on stool output, gut transit time, symptoms, and quality of life in adults with chronic constipation via a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: Studies were identified using electronic databases, backward citation, and hand-searching abstracts. RCTs reporting administration of food supplements (e.g., fruit extract supplements), vitamin or mineral supplements in adults with chronic constipation were included. Studies administering whole foods (e.g., fruits) were excluded. Risk of bias (RoB) was assessed with Cochrane RoB 2.0. Relative risks (RR), mean differences (MD), or standardized mean differences (95% confidence intervals [CI]) were calculated using a random-effects model. KEY RESULTS: Eight RCTs (787 participants) were included, investigating kiwifruit (n = 3 RCTs), senna (n = 2), magnesium oxide (n = 2), Ziziphus jujuba (n = 1), and Malva Sylvestris (n = 1) supplements. Kiwifruit supplements did not impact stool frequency (MD 0.24 bowel movements/week [-0.32, 0.80]; p = 0.40) or consistency (MD -0.11 Bristol points [-0.31, 0.09], p = 0.29). Overall, 61% responded to senna and 28% to control; however, this did not reach statistical significance (RR 2.78, [0.93, 8.27]; p = 0.07). Overall, 68% responded to magnesium oxide and 19% to control (RR 3.32 [1.59, 6.92]; p = 0.001). Magnesium oxide improved stool frequency (MD 3.72 bowel movements/week [1.41, 6.03]; p = 0.002) and consistency (MD 1.14 Bristol points [0.48, 1.79]; p = 0.0007). CONCLUSIONS AND INFERENCES: Magnesium oxide supplements are effective at improving cardinal symptoms of chronic constipation. Senna and kiwifruit supplements did not impact symptoms; however, findings were based on a small number of studies. Further research is required to investigate the effect of food supplements (e.g., kiwifruit supplements), as well as their whole food equivalents (e.g., whole kiwifruits) in chronic constipation. © 2023 The Authors. Neurogastroenterology &

03
META-ANALYSIS Gynecological endocrinology (2022) PMID: 35612360 ↗
Vitamin E supplementation improves testosterone, glucose- and lipid-related metabolism in women with polycystic ovary syndrome: a meta-analysis of randomized clinical trials.
Clinical Trial Synthesis 2022 Meta-Analysis published in Gynecological endocrinology (MD -1.92). Key conclusion: CONCLUSION: Vitamin E supplementation improves glucose, lipid, and androgenic-related biomarkers in women with PCOS.
View Original PubMed Abstract ↓

AIM: This systematic review and meta-analysis assessed the effect of vitamin E supplementation on testosterone, glucose, lipid profile, pregnancy rate, hirsutism, and body mass index (BMI) in women with polycystic ovary syndrome (PCOS). METHODS: A multi-database search was performed from inception to January 2022 for randomized controlled trials (RCTs) reporting the effects of vitamin E supplementation with or without another nutritional supplement on women with PCOS. A random-effects model was used to obtain mean differences (MDs) and its 95% confidence intervals (95%CI). Evidence certainty was assessed with GRADE methodology. RESULTS: We meta-analyzed eight RCTs reporting vitamin E supplementation alone or combined with other individual substances like omega-3, vitamin D3, or magnesium oxide in adult women ≤40 years old with PCOS. Vitamin E supplementation reduced fasting glucose (MD: -1.92 mg/dL, 95%CI: -3.80 to -0.05), fasting insulin (MD: -2.24 µIU/mL, 95%CI: -3.34 to -1.14), HOMA-IR (MD: -0.42, 95%CI: -0.65 to -0.19), total cholesterol (MD: -18.12 mg/dL, 95%CI: -34.37 to -1.86), LDL-cholesterol (MD: -15.92 mg/dL, 95%CI: -29.93 to -1.90), triglycerides (MD: -20.95 mg/dL, 95%CI: -37.31 to -4.58), total testosterone (MD: -0.42 ng/mL, 95%CI: -0.55 to -0.29), and increased sex hormone-binding globulin (MD: 7.44 nmol/L, 95%CI: 2.68 to 12.20). However, it had no impact on female sex hormones, HDL-cholesterol, BMI, and hirsutism. Two RCTs assessed pregnancy and implantation rates with inconsistent results. The certainty of the evidence was very low to moderate. CONCLUSION: Vitamin E supplementation improves glucose, lipid, and androgenic-related biomarkers in women with PCOS.

04
CLINICAL STUDY The Cochrane database of systematic reviews (2020) PMID: 32677037 ↗
Nutritional interventions for treating foot ulcers in people with diabetes.
Clinical Trial Synthesis 2020 Randomized Controlled Trial (RCT) published in The Cochrane database of systematic reviews involving n = 629 participants. Key conclusion: Nutritional interventions may improve wound healing of foot ulcers in people with diabetes.
View Original PubMed Abstract ↓

BACKGROUND: Foot ulcers in people with diabetes are non-healing, or poorly healing, partial, or full-thickness wounds below the ankle. These ulcers are common, expensive to manage and cause significant morbidity and mortality. The presence of a wound has an impact on nutritional status because of the metabolic cost of repairing tissue damage, in addition to the nutrient losses via wound fluid. Nutritional interventions may improve wound healing of foot ulcers in people with diabetes. OBJECTIVES: To evaluate the effects of nutritional interventions on the healing of foot ulcers in people with diabetes. SEARCH METHODS: In March 2020 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated the effect of nutritional interventions on the healing of foot ulcers in people with diabetes. DATA COLLECTION AND ANALYSIS: Two review authors, working independently, assessed included RCTs for their risk of bias and rated the certainty of evidence using GRADE methodology, using pre-determined inclusion and quality criteria. MAIN RESULTS: We identified nine RCTs (629 participants). Studies explored oral nutritional interventions as follows: a protein (20 g protein per 200 mL bottle), 1 kcal/mL ready-to-drink, nutritional supplement with added vitamins, minerals and trace elements; arginine, glutamine and β-hydroxy-β-methylbutyrate supplement; 220 mg zinc sulphate supplements; 250 mg magnesium oxide supplements; 1000 mg/day omega-3 fatty acid from flaxseed oil; 150,000 IU of vitamin D, versus 300,000 IU of vitamin D; 250 mg magnesium oxide plus 400 IU vitamin E and 50,000 IU vitamin D supplements. The comparator in eight studies was placebo, and in one study a different dos

05
CLINICAL STUDY The Cochrane database of systematic reviews (2018) PMID: 29360138 ↗
Interventions to reduce acute and late adverse gastrointestinal effects of pelvic radiotherapy for primary pelvic cancers.
Clinical Trial Synthesis 2018 Randomized Controlled Trial (RCT) published in The Cochrane database of systematic reviews involving n = 10,000 participants. Key conclusion: OBJECTIVES: To determine which prophylactic interventions reduce the incidence, severity or both of adverse gastrointestinal effects among adults receiving radiotherapy to treat primary pelvic cancers.
View Original PubMed Abstract ↓

BACKGROUND: An increasing number of people survive cancer but a significant proportion have gastrointestinal side effects as a result of radiotherapy (RT), which impairs their quality of life (QoL). OBJECTIVES: To determine which prophylactic interventions reduce the incidence, severity or both of adverse gastrointestinal effects among adults receiving radiotherapy to treat primary pelvic cancers. SEARCH METHODS: We conducted searches of CENTRAL, MEDLINE, and Embase in September 2016 and updated them on 2 November 2017. We also searched clinical trial registries. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of interventions to prevent adverse gastrointestinal effects of pelvic radiotherapy among adults receiving radiotherapy to treat primary pelvic cancers, including radiotherapy techniques, other aspects of radiotherapy delivery, pharmacological interventions and non-pharmacological interventions. Studies needed a sample size of 20 or more participants and needed to evaluate gastrointestinal toxicity outcomes. We excluded studies that evaluated dosimetric parameters only. We also excluded trials of interventions to treat acute gastrointestinal symptoms, trials of altered fractionation and dose escalation schedules, and trials of pre- versus postoperative radiotherapy regimens, to restrict the vast scope of the review. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. We used the random-effects statistical model for all meta-analyses, and the GRADE system to rate the certainty of the evidence. MAIN RESULTS: We included 92 RCTs involving more than 10,000 men and women undergoing pelvic radiotherapy. Trials involved 44 different interventions, including radiotherapy techniques (11 trials, 4 interventions/comparisons), other aspects of radiotherapy delivery (14 trials, 10 interventions), pharmacological interventions (38 trials, 16 interventions), and non-pharmacological interventions (29 trials, 13 interventions). Most studies (79/92) had design limitations. Thirteen studies had a low risk of bias, 50 studies had an unclear risk of bias and 29 studies had a high risk of bias. Main findings include the following:Radiotherap

06
CLINICAL STUDY The Cochrane database of systematic reviews (2014) PMID: 24696187 ↗
Magnesium supplementation in pregnancy.
Clinical Trial Synthesis 2014 Randomized Controlled Trial (RCT) published in The Cochrane database of systematic reviews involving n = 9,090 participants. Key conclusion: Magnesium supplementation during pregnancy may be able to reduce fetal growth restriction and pre-eclampsia, and increase birthweight.
View Original PubMed Abstract ↓

BACKGROUND: Magnesium is an essential mineral required for regulation of body temperature, nucleic acid and protein synthesis and in maintaining nerve and muscle cell electrical potentials. Many women, especially those from disadvantaged backgrounds, have low intakes of magnesium. Magnesium supplementation during pregnancy may be able to reduce fetal growth restriction and pre-eclampsia, and increase birthweight. OBJECTIVES: To assess the effects of magnesium supplementation during pregnancy on maternal, neonatal/infant and paediatric outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2013). SELECTION CRITERIA: Randomised and quasi-randomised trials assessing the effects of dietary magnesium supplementation during pregnancy were included. The primary outcomes were perinatal mortality (including stillbirth and neonatal death prior to hospital discharge), small-for-gestational age, maternal mortality and pre-eclampsia. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. MAIN RESULTS: Ten trials involving 9090 women and their babies were included; one trial had a cluster design (with randomisation by study centre). All 10 trials randomly allocated women to either an oral magnesium supplement or a control group; in eight trials a placebo was used, and in two trials no treatment was given to the control group. In the 10 included trials, the compositions of the magnesium supplements, gestational ages at commencement, and doses administered varied, including: magnesium oxide, 1000 mg daily from ≤ four months post-conception (one trial); magnesium citrate, 365 mg daily from ≤ 18 weeks until hospitalisation after 38 weeks (one trial), and 340 mg daily from nine to 27 weeks' gestation (one trial); magnesium gluconate, 2 to 3 g from 28 weeks' gestation until birth (one trial), and 4 g daily from 23 weeks' gestation (one trial); magnesium aspartate, 15 mmol daily (three trials, commencing from either six to 21 weeks' gestation until birth, ≤ 16 weeks' gestation until birth, or < 12 weeks until birth), or 365 mg d

07
CLINICAL STUDY Nutrients (2024) PMID: 39770988 ↗
Comparative Clinical Study on Magnesium Absorption and Side Effects After Oral Intake of Microencapsulated Magnesium (MAGSHAPE(TM) Microcapsules) Versus Other Magnesium Sources.
Clinical Trial Synthesis 2024 Randomized Controlled Trial (RCT) published in Nutrients. Key conclusion: CONCLUSIONS: Altogether, this clinical study introduced MAGSHAPETM microcapsules as a bioavailable and well-tolerated alternative to existing Mg-based ingredients used in food supplements.
View Original PubMed Abstract ↓

BACKGROUND/OBJECTIVES: Magnesium (Mg)-based food supplements contribute to the maintenance of adequate levels of Mg that are essential for overall health and well-being. The aim of this double-blind, randomized, cross-over clinical study was to assess the plasma Mg levels in volunteers following the oral administration of a magnesium-based nutraceutical ingredient, MAGSHAPETM microcapsules (Mg-MS), in comparison to other commonly used magnesium sources, including the following: Mg Oxide (MgO), Mg Citrate (Mg-C), and Mg bisglycinate (Mg-BG). METHODS: A total of 40 healthy women and men were put on a low-Mg diet for 7 days, and after 8 h of fasting, a blood sample was taken from a digital puncture before (0 h) and 1 h, 4 h, and 6 h after the oral intake of each product. RESULTS: Our results showed that the blood plasma levels of Mg increased significantly at all tested time-points after the oral intake of Mg-MS, while the blood plasma levels of Mg increased significantly only after 1 and 4 h of the oral intake of MgO and Mg-C, respectively. However, no significant increase in Mg levels was observed upon the intake of Mg-BG. Interestingly, the Mg-MS microencapsulation technology was observed to enable a sustained increase in plasma Mg levels over the duration of this study, i.e., 1, 4, and 6 h after oral intake. A direct comparison of the increase in plasma Mg levels over the 6 h period revealed that the Mg-MS microencapsulation technology significantly increased Mg bioavailability compared to the non-microencapsulated MgO. Our study also showed that, compared to the other Mg sources tested, the Mg-MS microencapsulation technology reduced adverse side effects commonly associated with Mg supplementation, specifically with regard to increased intestinal motility and sensations of gastric heaviness following oral administration. CONCLUSIONS: Altogether, this clinical study introduced MAGSHAPETM microcapsules as a bioavailable and well-tolerated alternative to existing Mg-based ingredients used in food supplements.

08
RANDOMIZED TRIAL (RCT) Japanese journal of clinical oncology (2025) PMID: 39354673 ↗
Effect of add-on naldemedine treatment in patients with cancer and opioid-induced constipation insufficiently responding to magnesium oxide: a pooled, subgroup analysis of two randomized controlled trials.
Clinical Trial Synthesis 2025 Randomized Controlled Trial (RCT) published in Japanese journal of clinical oncology involving n = 116 participants; statistical significance reported at p = 0.0001. Key conclusion: CONCLUSION: The study suggested the addition of naldemedine as an effective treatment option for opioid-induced constipation in cancer patients insufficiently responding to magnesium oxide treatment.
View Original PubMed Abstract ↓

OBJECTIVE: To evaluate the additive effect of naldemedine tosylate (naldemedine) on opioid-induced constipation in cancer patients insufficiently responding to magnesium oxide treatment. METHODS: We combined two randomized, double-blind, placebo-controlled, phase IIb and III trials of naldemedine and conducted a post hoc subgroup analysis. We evaluated the effect and safety of naldemedine in 116 patients who received naldemedine in addition to magnesium oxide (naldemedine group) and 117 patients who received placebo in addition to magnesium oxide (placebo group). Both groups included patients insufficiently responding to magnesium oxide for opioid-induced constipation. Effect was assessed using spontaneous bowel movement responder rate, complete spontaneous bowel movement responder rate, changes in spontaneous bowel movements and complete spontaneous bowel movements. Safety was also assessed. RESULTS: During the 2-week treatment period, the responder rates for spontaneous bowel movement and complete spontaneous bowel movement were 73.3 and 43.1% in naldemedine group, respectively, which were significantly higher (P < 0.0001) than 41.9 and 14.5% in placebo group, respectively. Median time to first spontaneous bowel movement and first complete spontaneous bowel movement was significantly shorter (P < 0.0001) in the naldemedine group (4.0 and 21.3 h, respectively) than in the placebo group (27.7 and 211.7 h, respectively). The incidence of adverse events and diarrhoea was significantly higher (P < 0.05) in the naldemedine group than in the placebo group, while the incidence of serious adverse events and severe diarrhoea was not significantly different between the naldemedine and placebo groups. CONCLUSION: The study suggested the addition of naldemedine as an effective treatment option for opioid-induced constipation in cancer patients insufficiently responding to magnesium oxide treatment. © The Author(s) 2024. Published by Oxford University Press.

09
RANDOMIZED TRIAL (RCT) Magnesium research (2024) PMID: 39077820 ↗
Effect of magnesium oxide or citrate supplements on metabolic risk factors in kidney stone formers with idiopathic hyperoxaluria: a randomized clinical trial.
Clinical Trial Synthesis 2024 Randomized Controlled Trial (RCT) published in Magnesium research involving n = 76 participants; statistical significance reported at p = 0.011. Key conclusion: Clinically, both MgO and MgCit reduced 24-U oxalate and CaOx SS compared to placebo.
View Original PubMed Abstract ↓

Magnesium is one of the recommended treatments for calcium stone formers (CSFs) with hyperoxaluria. In this study, we compared the effect of magnesium oxide (MgO) or magnesium citrate (MgCit) with placebo on 24-hour urine (24-U) metabolites and the calcium oxalate supersaturation index (CaOx SS). In a randomized, double-blind, placebo-controlled clinical trial, 90 CSFs with idiopathic hyperoxaluria were recruited from a tertiary stone prevention clinic. Patients were randomly assigned into three groups: 120 mg MgO, 120 mg MgCit or placebo (supplements were taken three times per day, with meals). Finally, 76 patients were included in the final analysis. Analyses of 24-U were performed at baseline and after eight weeks. Study outcomes included changes in 24-U oxalate, magnesium, citrate, and CaOx SS. Dietary factors were controlled by 24-hour food recalls. Repeated measure ANOVA was used to compare the results. After the intervention, both MgO and MgCit supplements decreased 24-U oxalate excretion (-8.13±16.45 in the MgO group and -16.99±18.02 in the MgCit group) and CaOx SS compared to the placebo, with the effects of MgCit reaching statistical significance (p=0.011 and p=0.010, respectively). An increasing trend was observed for 24-U magnesium and citrate excretion without significant differences among groups. Interestingly, MgCit exhibited a significantly greater inhibitory effect on 24-U oxalate in patients with normal urine magnesium levels (p=0.021). Clinically, both MgO and MgCit reduced 24-U oxalate and CaOx SS compared to placebo. However, MgCit demonstrated a greater effect, especially in patients with normal urine magnesium levels.

10
RANDOMIZED TRIAL (RCT) International journal of molecular sciences (2023) PMID: 37685975 ↗
A Citrus and Pomegranate Complex Reduces Methylglyoxal in Healthy Elderly Subjects: Secondary Analysis of a Double-Blind Randomized Cross-Over Clinical Trial.
Clinical Trial Synthesis 2023 Randomized Controlled Trial (RCT) published in International journal of molecular sciences; statistical significance reported at p = 0.042. Key conclusion: Our findings suggest that CPC supplementation may represent a promising strategy for mitigating the conditions associated with MGO involvement.
View Original PubMed Abstract ↓

Reactive α-dicarbonyls (α-DCs), such as methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG), are potent precursors in the formation of advanced glycation end products (AGEs). In particular, MGO and MGO-derived AGEs are thought to be involved in the development of vascular complications in diabetes. Experimental studies showed that citrus and pomegranate polyphenols can scavenge α-DCs. Therefore, the aim of this study was to evaluate the effect of a citrus and pomegranate complex (CPC) on the α-DCs plasma levels in a double-blind, placebo-controlled cross-over trial, where thirty-six elderly subjects were enrolled. They received either 500 mg of Citrus sinensis peel extract and 200 mg of Punica granatum concentrate in CPC capsules or placebo capsules for 4 weeks, with a 4-week washout period in between. For the determination of α-DCs concentrations, liquid chromatography tandem mass spectrometry was used. Following four weeks of CPC supplementation, plasma levels of MGO decreased by 9.8% (-18.7 nmol/L; 95% CI: -36.7, -0.7 nmol/L; p = 0.042). Our findings suggest that CPC supplementation may represent a promising strategy for mitigating the conditions associated with MGO involvement. This study was registered on clinicaltrials.gov as NCT03781999.

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