Magnesium's Pain-Relieving and Anti-Inflammatory Effects

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Did you know that magnesium has the power to both relieve your pain and help you reduce inflammation throughout your body?

Magnesium (Mg) is a natural mineral that may provide profound pain relief for severe pain such as in renal colic, neuropathic pain and migraines. Mg also fights inflammation, which can lead to multiple diseases from arthritis, asthma, cardiovascular diseases, diabetes, metabolic disorders and spinal nerve injuries to gallbladder infections and brain disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD).

In addition, magnesium sulfate (MgSO) is neuroprotective, decreases inflammation in your brain and can help prevent cerebral palsy in preterm infants and reduce depression and memory loss.

Pain Relief

Renal Colic

One of the most severe pains experienced by patients is renal colic from passing kidney stones. The usual treatment is intravenous (IV) infusion with morphine sulfate. Risks of addiction, abuse and misuse can result from morphine, which may lead to overdose and death.[i]

In a randomized clinical trial of 80 renal colic patients with pain from passing kidney stones, half received 50 milligrams (mg) per kilogram (kg) of MgSO IV and half (the control group) was given a 0.1 mg per kg morphine IV. The pain mean scores between the two groups were statistically the same, meaning magnesium sulfate could be as effective as morphine in reducing pain from kidney stones without the side effects or complications of morphine.[ii]

Neuropathic Pain

Spinal cord injury has many severe and disabling consequences including chronic pain called neuropathic pain. Thirty-two adult male rats weighing from 300 to 350 grams were induced with a spinal cord injury and treated with a single dose of 300 or 600 mg per kg of MgSO4, which significantly decreased their neuropathic pain in a dose dependent manner.[iii] In addition to decreasing chronic pain, MgSO also helped lessen memory deficits associated with neuropathic pain.[iv]


Migraines are a very disabling disorder that affect the quality of life of patients primarily due to pain, and the frequency and duration of migraine attacks. In a crossover trial of 63 patients experiencing migraines, 31 were in the magnesium oxide-valproate group and 32 patients were in the valproate followed by magnesium oxide group in two sequences over two periods of eight weeks each.

After the two sequences, the intervention group received magnesium oxide of 500 mg and the control group received two tablets of 400 mg of valproate sodium per day for eight weeks.

The treatment group with magnesium oxide had similar effectiveness in migraine management -- mean number of migraine attacks, days per month of mild or severe migraine headaches, and mean duration of attacks -- compared to the control group using valproate sodium for the final eight weeks without significant adverse effects like pancreatitis, nausea, depression and hepatotoxicity.[v],[vi]


Gallstones and Gallbladder Disease

Gallstones are crystals that form in the gallbladder, which sometimes block the flow of bile out of the gallbladder into the digestive system. This roadblock leads to cholecystitis -- inflammation of the gallbladder. When gallstones become painful and/or dangerous, doctors perform a laparoscopic cholecystectomy to treat gallbladder disease.[vii]

In a study of 114 patients scheduled for laparoscopic cholecystectomy, people were randomized into three treatment groups -- lidocaine, magnesium sulphate or 0.9% saline administered through an IV, 10 minutes before the procedure. Only the MgSO group had an eight-point improvement in quality of recovery over the placebo group by increasing physical comfort and physical independence in cholecystectomy patients, due to MgSO's powerful stress-reducing and anti-inflammatory effects.[viii]

Neural Inflammation

MgSO -- also known as Epsom salt -- exposure before preterm birth is neuroprotective, reducing the risk of cerebral palsy and major motor dysfunction. Neonatal inflammatory cytokine levels correlate with neurologic outcomes and researchers found reduced maternal inflammatory markers of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) production after in vivo MgSO treatment.[ix]

Ten studies involving 18,655 preterm infants were analyzed with MgSO4 as a treatment for brain inflammation and results showed reduced risk of moderate to severe cerebral palsy (CP) without obvious adverse side effects on preterm babies. MgSO4 is both beneficial and safe to use when mothers are at risk of having a premature infant and the risk of CP is moderate to severe.[x]

Based upon their review of animal and human research studies, scientists confirm that a magnesium deficiency (MgD) has significant effects on neurological disorders, such as cerebral vasospasm, AD, PD, stroke, anxiety and migraines. Mg is neuroprotective, impacts cell signaling molecules and plays important roles in the nervous, muscle and immune systems.[xi],[xii]

In a longitudinal study of 249 patients with diagnosed PD and 368 control patients without a neurodegenerative disease, all took a diet history questionnaire and higher intake of magnesium was independently associated with a reduced risk of PD.[xiii]

In a meta-analysis of 21 studies including 1,112 AD patients and 1,001 healthy controls, serum and plasma Mg levels and circulating Mg levels were significantly reduced in AD patients compared with healthy controls. MgD is seen as a risk factor for AD and Mg supplementation is recommended as an adjuvant AD treatment.[xiv]

Low-Grade Chronic Inflammation

A review of animal and in vitro studies provides convincing evidence that MgD contributes significantly to chronic low-grade inflammation -- a risk factor for a variety of pathological conditions such as cardiovascular disease,[xv] high blood pressure[xvi],[xvii] and diabetes.[xviii] Magnesium should be considered an element of significant nutritional concern for health and well-being in those with a MgD or low magnesium level.[xix]

The ideal way to address MgD is by eating magnesium-rich foods such as green leafy vegetables, figs, avocados, bananas, raspberries, nuts and seeds, legumes, broccoli, cabbage, asparagus, green beans, salmon, tuna, oats and artichokes, since you can eat as much as you like and the magnesium is natural.

If you need a magnesium supplement, discuss the best dosage with your health care provider and limit your consumption of alcohol -- a Mg diuretic -- to optimize this essential mineral.[xx]

Results of a meta-analysis of 11 studies indicated that Mg supplementation reduced serum C reactive protein (CRP) levels among individuals with inflammation and recommended Mg supplementation to manage low-grade chronic inflammation.[xxi]

Inflammatory Diseases

With MgD being linked to inflammation in the body, it is not surprising that researchers have found magnesium plays an important role in the development of inflammatory diseases including diabetes,[xxii] asthma,[xxiii] preeclampsia,[xxiv] atherosclerosis,[xxv] heart disease/damage[xxvi],[xxvii] and rheumatoid arthritis.[xxviii]

Depression -- another inflammatory disease -- is also associated with chronic low-grade inflammation, activation of cell-mediated immunity and compensatory anti-inflammatory reflex system.[xxix] In a meta-analysis, a review of 11 studies showed dietary Mg intake was significantly associated with a reduced risk of depression and the most effective dosage was 320 mg per day.[xxx]

In a study of 60 depressed patients suffering from MgD, 500 mg magnesium oxide tablets daily for eight weeks or more led to significant improvements in depression status and magnesium levels.[xxxi]

In a review of 14 studies studying a total of 2,313 people with acute asthma attacks that led them to the emergency room, a single infusion of 1.2 grams or 2 grams of MgSO4 through an IV for 15 to 30 minutes reduced hospital admissions and improved lung function in adults with acute asthma who did not respond sufficiently to oxygen, nebulized short-acting beta2-agonists and corticosteroids.[xxxii]

Adding MgSO to standard therapy in patients with moderate to severe asthma attacks in a study of 50 emergency room patients contributed to greater and faster improvement in their peak expiratory flow rate, respiratory rate, oxygen saturation and shortness of breath severity. MgSO also reduced hospitalization rates in this patient population.[xxxiii]

In a systematic review of Mg supplementation and inflammation in 17 trials with 889 participants, Mg significantly improved two inflammatory biomarkers -- decreased CRP and increased nitric oxide levels.[xxxiv]

Also, Mg suppressed the development of atherosclerotic lesions in the aorta of cholesterol-fed rabbits without affecting plasma total cholesterol and high-density lipoprotein cholesterol concentrations. Mg works as a mediator for atherosclerosis because of its calcium entry blocking action.[xxxv]

Alcohol-Mediated Diseases

Alcohol-mediated diseases such as alcoholic liver disease, alcoholic cardiomyopathy heart disease, alcoholic gastritis and alcoholism are also accompanied by inflammation and memory impairment. In a chronic-plus-binge alcohol feeding mice model, magnesium-l-threonate (MgT) treatment relieved inflammation in the gut-brain axis of mice, reshaped gut microbiota and enhanced the amino acids and glutamate metabolism, which helps to prevent inflammation and memory impairment induced by alcohol abuse.[xxxvi]

In a review of 13,504 participants who completed a liver ultrasound examination for hepatic steatosis, every 100 mg increase of magnesium intake was associated with a 49% reduction in the risk for mortality due to liver diseases and this effect was the strongest among alcohol drinkers and those with liver steatosis.[xxxvii]

Peripheral Nerve Disorders

Magnesium also helps in the treatment of peripheral nerve disorders. In a sciatic nerve crush injury mouse model, animals were given either 10, 100 or 200% Mg of the base diet. Improved neurological function recovery and enhanced nerve regeneration were found in mice with a sciatic nerve injury that were fed a high-Mg diet. By increasing Schwann cells -- known to help repair peripheral nerves and injuries to human spinal cords[xxxviii] -- Mg is believed to stop critical cell death by the suppression of inflammatory responses.[xxxix]


[i], Morphine Side Effects: Common, Severe, Long Term.

[ii] Zolfaghari Sadrabad A, Azimi Abarghouei S, Farahmand Rad R, Salimi Y. Intravenous magnesium sulfate vs. morphine sulfate in relieving renal colic: A randomized clinical trial. Am J Emerg Med. 2021 Aug;46:188-192. doi: 10.1016/j.ajem.2020.07.035. Epub 2020 Jul 21. PMID: 33071088.

[iii] Leila Farsi, Khashayar Afshari, Mansoor Keshavarz, Maryam NaghibZadeh, Fereidoon Memari, Abbas Norouzi-Javidan. Postinjury treatment with magnesium sulfate attenuates neuropathic pains following spinal cord injury in male rats. Behav Pharmacol. 2015 Apr ;26(3):315-20. PMID: 25369748

[iv] Jun Wang, Yong Liu, Li-Jun Zhou, Ying Wu, Fei Li, Ka-Feng Shen, Rui-Ping Pang, Xu-Hong Wei, Yong-Yong Li, Xian-Guo Liu. Magnesium L-threonate prevents and restores memory deficits associated with neuropathic pain by inhibition of TNF-α. Pain Physician. 2013 Sep-Oct;16(5):E563-75. PMID: 24077207

[v] Karimi N, Razian A, Heidari M. The efficacy of magnesium oxide and sodium valproate in prevention of migraine headache: a randomized, controlled, double-blind, crossover study. Acta Neurol Belg. 2021 Feb;121(1):167-173. doi: 10.1007/s13760-019-01101-x. Epub 2019 Feb 23. PMID: 30798472.

[vi] Valproate Sodium Side Effects: Common, Severe, Long Term.

[vii] Cleveland Clinic. Health. Treatments. Laparoscopic Cholecystecormy: Gallbladder Removal.

[viii] Lu J, Wang JF, Guo CL, Yin Q, Cheng W, Qian B. Intravenously injected lidocaine or magnesium improves the quality of early recovery after laparoscopic cholecystectomy: A randomised controlled trial. Eur J Anaesthesiol. 2021 Mar 1;38(Suppl 1):S1-S8. doi: 10.1097/EJA.0000000000001348. PMID: 33074940.

[ix] Jun Sugimoto, Andrea M Romani, Alice M Valentin-Torres, Angel A Luciano, Christina M Ramirez Kitchen, Nicholas Funderburg, Sam Mesiano, Helene B Bernstein. Magnesium decreases inflammatory cytokine production: a novel innate immunomodulatory mechanism. J Immunol. 2012 Jun 15 ;188(12):6338-46. Epub 2012 May 18. PMID: 22611240

[x] Xianling Zeng, Yan Xue, Quan Tian, Rong Sun, Ruifang An. Effects and Safety of Magnesium Sulfate on Neuroprotection: A Meta-analysis Based on PRISMA Guidelines. Medicine (Baltimore). 2016 Jan ;95(1):e2451. PMID: 26735551

[xi] Wenwen Xue, Jing You, Yingchao Su, Qinglu Wang. The Effect of Magnesium Deficiency on Neurological Disorders: A Narrative Review Article. Iran J Public Health. 2019 Mar ;48(3):379-387. PMID: 31223564

[xii] Anna E Kirkland, Gabrielle L Sarlo, Kathleen F Holton. The Role of Magnesium in Neurological Disorders. Nutrients. 2018 Jun 6 ;10(6). Epub 2018 Jun 6. PMID: 29882776

[xiii] Miyake Y, Tanaka K, Fukushima W, Sasaki S, Kiyohara C, Tsuboi Y, Yamada T, Oeda T, Miki T, Kawamura N, Sakae N, Fukuyama H, Hirota Y, Nagai M; Fukuoka Kinki Parkinson's Disease Study Group. Dietary intake of metals and risk of Parkinson's disease: a case-control study in Japan. J Neurol Sci. 2011 Jul 15;306(1-2):98-102. doi: 10.1016/j.jns.2011.03.035. Epub 2011 Apr 16. PMID: 21497832.

[xiv] Du K, Zheng X, Ma ZT, Lv JY, Jiang WJ, Liu MY. Association of Circulating Magnesium Levels in Patients With Alzheimer's Disease From 1991 to 2021: A Systematic Review and Meta-Analysis. Front Aging Neurosci. 2022 Jan 10;13:799824. doi: 10.3389/fnagi.2021.799824. PMID: 35082658; PMCID: PMC8784804.

[xv] James J DiNicolantonio, James H O'Keefe, William Wilson. Subclinical magnesium deficiency: a principal driver of cardiovascular disease and a public health crisis. Open Heart. 2018 ;5(1):e000668. Epub 2018 Jan 13. PMID: 29387426

[xvi] Thorsten Reffelmann, Till Ittermann, Marcus Dörr, Henry Völzke, Markus Reinthaler, Astrid Petersmann, Stephan B Felix. Low serum magnesium concentrations predict cardiovascular and all-cause mortality. Atherosclerosis. 2011 Jun 12. Epub 2011 Jun 12. PMID: 21703623

[xvii] Samad Ghaffari, Neda Roshanravan. The role of nutraceuticals in prevention and treatment of hypertension: An updated review of the literature. Food Res Int. 2020 Feb ;128:108749. Epub 2019 Nov 7. PMID: 31955788

[xviii] J Ma, A R Folsom, S L Melnick, J H Eckfeldt, A R Sharrett, A Nabulsi, R G Hutchinson, P A Metcalf. Associations of serum and dietary magnesium with cardiovascular disease, hypertension, diabetes, insulin, and carotid arterial wall thickness: the ARIC study. Atherosclerosis Risk in Communities Study. J Clin Epidemiol. 1995 Jul;48(7):927-40. PMID: 7782801

[xix] Forrest H Nielsen. Magnesium deficiency and increased inflammation: current perspectives. J Inflamm Res. 2018 ;11:25-34. Epub 2018 Jan 18. PMID: 29403302

[xx] 1MD. 10 Signs and Symptoms of a Magnesium Deficiency.

[xxi] Luis E Simental-Mendia, Amirhossein Sahebkar, Martha Rodriguez-Moran, Graciela Zambrano-Galvan, Fernando Guerrero-Romero. Effect of Magnesium Supplementation on Plasma C-reactive Protein Concentrations: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Curr Pharm Des. 2017 ;23(31):4678-4686. PMID: 28545353

[xxii] N Veronese, S F Watutantrige, C Luchini, M Solmi, G Sartore, G Sergi, E Manzato, M Barbagallo, S Maggi, B Stubbs. Effect of magnesium supplementation on glucose metabolism in people with or at risk of diabetes: a systematic review and meta-analysis of double-blind randomized controlled trials. Eur J Clin Nutr. 2016 Aug 17. Epub 2016 Aug 17. PMID: 27530471

[xxiii] Aggarwal P, Sharad S, Handa R, Dwiwedi SN, Irshad M. Comparison of nebulised magnesium sulphate and salbutamol combined with salbutamol alone in the treatment of acute bronchial asthma: a randomised study. Emerg Med J. 2006 May;23(5):358-62. doi: 10.1136/emj.2005.026203. PMID: 16627836; PMCID: PMC2564084.

[xxiv] Amash A, Holcberg G, Sheiner E, Huleihel M. Magnesium sulfate normalizes placental interleukin-6 secretion in preeclampsia. J Interferon Cytokine Res. 2010 Sep;30(9):683-90. doi: 10.1089/jir.2010.0011. PMID: 20715974.

[xxv] J Ma, A R Folsom, S L Melnick, J H Eckfeldt, A R Sharrett, A Nabulsi, R G Hutchinson, P A Metcalf. Associations of serum and dietary magnesium with cardiovascular disease, hypertension, diabetes, insulin, and carotid arterial wall thickness: the ARIC study. Atherosclerosis Risk in Communities Study. J Clin Epidemiol. 1995 Jul;48(7):927-40. PMID: 7782801

[xxvi] Abbott RD, Ando F, Masaki KH, Tung KH, Rodriguez BL, Petrovitch H, Yano K, Curb JD. Dietary magnesium intake and the future risk of coronary heart disease (the Honolulu Heart Program). Am J Cardiol. 2003 Sep 15;92(6):665-9. doi: 10.1016/s0002-9149(03)00819-1. PMID: 12972103.

[xxvii] Almoznino-Sarafian D, Berman S, Mor A, Shteinshnaider M, Gorelik O, Tzur I, Alon I, Modai D, Cohen N. Magnesium and C-reactive protein in heart failure: an anti-inflammatory effect of magnesium administration? Eur J Nutr. 2007 Jun;46(4):230-7. doi: 10.1007/s00394-007-0655-x. Epub 2007 May 3. PMID: 17479208.

[xxviii] Abbas Shahi, Saeed Aslani, MohammadReza Ataollahi, Mahdi Mahmoudi. The role of magnesium in different inflammatory diseases. Inflammopharmacology. 2019 Aug ;27(4):649-661. Epub 2019 Jun 6. PMID: 31172335

[xxix] Rogue Health and Fitness. Depression Is An Inflammatory Disease.

[xxx] Bingrong Li, Jing Lv, Weijing Wang, Dongfeng Zhang. Dietary magnesium and calcium intake and risk of depression in the general population: A meta-analysis. Aust N Z J Psychiatry. 2017 Mar ;51(3):219-229. Epub 2016 Nov 2. PMID: 27807012

[xxxi] Afsaneh Rajizadeh, Hassan Mozaffari-Khosravi, Mojtaba Yassini-Ardakani, Ali Dehghani. Effect of magnesium supplementation on depression status in depressed patients with magnesium deficiency: A randomized, double-blind, placebo-controlled trial. Nutrition. 2017 Mar ;35:56-60. Epub 2016 Nov 9. PMID: 28241991

[xxxii] Kayleigh M Kew, Liza Kirtchuk, Clare I Michell. Intravenous magnesium sulfate for treating adults with acute asthma in the emergency department. Cochrane Database Syst Rev. 2014 ;5:CD010909. Epub 2014 May 28. PMID: 24865567

[xxxiii] Shaker Hossein, Akhavan Pegah, Farsi Davood, Abbasi Said, Mahshidfar Babak, Mofidi Mani, Rezai Mahdi, Hafezimoghadam Peyman. The effect of nebulized magnesium sulfate in the treatment of moderate to severe asthma attacks: a randomized clinical trial. Am J Emerg Med. 2016 May ;34(5):883-6. Epub 2016 Jan 21. PMID: 26964827

[xxxiv] Nicola Veronese, Damiano Pizzol, Lee Smith, Ligia J Dominguez, Mario Barbagallo. Effect of Magnesium Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled Trials. Nutrients. 2022 Feb 5 ;14(3). Epub 2022 Feb 5. PMID: 35277037

[xxxv] H Orimo, Y Ouchi. The role of calcium and magnesium in the development of atherosclerosis. Experimental and clinical evidence. Ann N Y Acad Sci. 1990;598:444-57. PMID: 2248457

[xxxvi] Chang Liu, Yuliang Cheng, Yahui Guo, He Qian. Magnesium-L-threonate alleviate colonic inflammation and memory impairment in chronic-plus-binge alcohol feeding mice. Brain Res Bull. 2021 Jun 16 ;174:184-193. Epub 2021 Jun 16. PMID: 34144203

[xxxvii] Lijun Wu, Xiangzhu Zhu, Lei Fan, Edmond K Kabagambe, Yiqing Song, Menghua Tao, Xiaosong Zhong, Lifang Hou, Martha J Shrubsole, Jie Liu, Qi Dai. Magnesium intake and mortality due to liver diseases: Results from the Third National Health and Nutrition Examination Survey Cohort. Sci Rep. 2017 Dec 20 ;7(1):17913. Epub 2017 Dec 20. PMID: 29263344

[xxxviii] Oudega M, Xu XM. Schwann cell transplantation for repair of the adult spinal cord. J Neurotrauma. 2006 Mar-Apr;23(3-4):453-67. doi: 10.1089/neu.2006.23.453. PMID: 16629629.

[xxxix] Hung-Chuan Pan, Meei-Ling Sheu, Hong-Lin Su, Ying-Ju Chen, Chun-Jung Chen, Dar-Yu Yang, Wen-Ta Chiu, Fu-Chou Cheng. Magnesium supplement promotes sciatic nerve regeneration and down-regulates inflammatory response. Magnes Res. 2011 Jun ;24(2):54-70. PMID: 21609904

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