Posted on: Monday, March 25th 2019 at 7:45 am Written By: Sayer Ji, Founder
Monday, March 25th 2019 at 7:45 am
Sayer Ji, Founder
This article is copyrighted by GreenMedInfo LLC, 2019
A powerful clinical study shows that pennies worth of magnesium a day provides an effective, safe, affordable alternative to dangerous and relatively ineffective pharmaceutical antidepressants.
Depression is one of the most widely diagnosed conditions of our time, with over 3 million cases in the U.S. every year, and 350 million believed affected worldwide.1 Conventional medicine considers antidepressant drugs first-line treatments, including the newly approved injected postpartum drug costing $34,000 a treatment, to the tune of a 16 billion dollars in global sales by 2023. Despite their widespread use, these drugs are fraught with a battery of serious side effects, including suicidal ideation and completion -- the last two things you would hope to see in a condition that already has suicidality as a co-morbidity. For this reason alone, natural, safe, and effective alternatives are needed more than ever before.
While research into natural alternatives for depression is growing daily -- GreenMedInfo.com’s Depression database contains 647 studies on over 100 natural substances that have been studied to prevent or treat depression -- it is rare to find quality human clinical research on the topic published in well-respected journals. That’s why a powerful study published in PLOS One titled, “Role of magnesium supplementation in the treatment of depression: A randomized clinical trial,” is so promising. Not only is magnesium safe, affordable, and easily accessible, but according to this recent study, effective in treating mild-to moderate symptoms of depression.
While previous studies have looked at the association between magnesium and depression,2-7 this is the first placebo-controlled clinical study to evaluate whether the use of over-the-counter magnesium chloride (248 mg elemental magnesium a day for 6 weeks) improves symptoms of depression.
The study design was a follows:
“ An open-label, blocked, randomized, cross-over trial was carried out in outpatient primary care clinics on 126 adults (mean age 52; 38% male) diagnosed with and currently experiencing mild-to-moderate symptoms with Patient Health Questionnaire-9 (PHQ-9) scores of 5–19. The intervention was 6 weeks of active treatment (248 mg of elemental magnesium per day) compared to 6 weeks of control (no treatment). Assessments of depression symptoms were completed at bi-weekly phone calls. The primary outcome was the net difference in the change in depression symptoms from baseline to the end of each treatment period. Secondary outcomes included changes in anxiety symptoms as well as adherence to the supplement regimen, appearance of adverse effects, and intention to use magnesium supplements in the future. Between June 2015 and May 2016, 112 participants provided analyzable data.”
The study results were as follows:
“Consumption of magnesium chloride for 6 weeks resulted in a clinically significant net improvement in PHQ-9 scores of -6.0 points (CI -7.9, -4.2; P<0.001) and net improvement in Generalized Anxiety Disorders-7 scores of -4.5 points (CI -6.6, -2.4; P<0.001). Average adherence was 83% by pill count. The supplements were well tolerated and 61% of participants reported they would use magnesium in the future. Similar effects were observed regardless of age, gender, baseline severity of depression, baseline magnesium level, or use of antidepressant treatments. Effects were observed within two weeks. Magnesium is effective for mild-to-moderate depression in adults. It works quickly and is well tolerated without the need for close monitoring for toxicity.”
For perspective, conventional antidepressant drugs are considering to generate an “adequate or complete treatment response” with a PHQ-9 score “decrease of 5 points or more from baseline.” At this level of efficacy, their recommended action is: “Do not change treatment; conduct periodic follow-up.” The magnesium’s score of -6.0 therefore represents the height of success within conventional expectations for a complete response, which is sometimes termed “remission.” In contradistinction, conventional antidepressant drugs result in nearly half of patients discontinuing treatment during the first month, usually due to their powerful and sometimes debilitating side effects.8
To summarize the main study outcomes:
There was a clinically significant improvement in both Depression and Anxiety scores.
61% of patients reported they would use magnesium in the future.
Similar effects occurred across age, gender, severity of depression, baseline magnesium levels, or use of antidepressant treatments.
Effects were observed within two weeks.
The study authors concluded:
“Magnesium is effective for mild-to-moderate depression in adults. It works quickly and is well tolerated without the need for close monitoring for toxicity.”
Beyond Depression: Magnesium’s Many Health Benefits
Magnesium is a central player in your body’s energy production, as its found within 300 enzymes in the human body, including within the biologically active form of ATP known as MG-ATP. In fact, there have been over 3,751 magnesium binding sites identified within human proteins, indicating that it’s central nutritional importance has been greatly underappreciated.
Research relevant to magnesium has been accumulating for the past 40 years at a steady rate of approximately 2,000 new studies a year. Our database project has indexed well over 100 health benefits of magnesium thus far. For the sake of brevity, we will address seven key therapeutic applications for magnesium as follows:
Fibromyalgia: Not only is magnesium deficiency common in those diagnosed with fibromyalgia, 9,10 but relatively low doses of magnesium (50 mg), combined with malic acid in the form of magnesium malate, has been clinically demonstrated to improve pain and tenderness in those to which it was administered.11
Atrial Fibrillation: A number of studies now exist showing that magnesium supplementation reduce atrial fibrillation, either by itself, or in combination with conventional drug agents.12
Diabetes, Type 2: Magnesium deficiency is common in type 2 diabetics, at an incidence of 13.5 to 47.7% according to a 2007 study. 13 Research has also shown that type 2 diabetics with peripheral neuropathy and coronary artery disease have lower intracellular magnesium levels. 14 Oral magnesium supplementation has been shown to reduce plasma fasting glucose and raising HDL cholesterol in patients with type 2 diabetes.15 It has also been shown to improve insulin sensitivity and metabolic control in type 2 diabetic subjects.16
Premenstrual Syndrome: Magnesium deficiency has been observed in women affected by premenstrual syndrome.17 It is no surprise therefore that it has been found to alleviate premenstrual symptoms of fluid retention, 18 as well as broadly reducing associated symptoms by approximately 34% in women, aged 18-45, given 250 mg tablets for a 3-month observational period.20 When combined with B6, magnesium supplementation has been found to improve anxiety-related premenstrual symptoms.19
Cardiovascular Disease and Mortality: Low serum magnesium concentrations predict cardiovascular and all-cause mortality.21 There are a wide range of ways that magnesium may confer its protective effects. It may act like a calcium channel blocker,22it is hypotensive,23 it is antispasmodic (which may protect against coronary artery spasm),24 and anti-thrombotic.25 Also, the heart muscle cells are exceedingly dense in mitochondria (as high as 100 times more per cell than skeletal muscle), the "powerhouses" of the cell," which require adequate magnesium to produce ATP via the citric acid cycle.
Migraine Disorders: Blood magnesium levels have been found to be significantly lower in those who suffer from migraine attacks.26,27 A recent Journal of Neural Transmission article titled, "Why all migraine patients should be treated with magnesium," pointed out that routine blood tests do not accurately convey the true body magnesium stores since less than 2% is in the measurable, extracellular space, "67% is in the bone and 31% is located intracellularly."28The authors argued that since "routine blood tests are not indicative of magnesium status, empiric treatment with at least oral magnesium is warranted in all migraine sufferers." Indeed, oral magnesium supplementation has been found to reduce the number of headache days in children experiencing frequent migranous headaches,29and when combined with l-carnitine, is effective at reducing migraine frequency in adults, as well.30
Aging: While natural aging is a healthy process, accelerated aging has been noted to be a feature of magnesium deficiency,31especially evident in the context of long space-flight missions where low magnesium levels are associated with cardiovascular aging over 10 times faster than occurs on earth.32 Magnesium supplementation has been shown to reverse age-related neuroendocrine and sleep EEG changes in humans.33 One of the possible mechanisms behind magnesium deficiency associated aging is that magnesium is needed to stabilize DNA and promotes DNA replication. It is also involved in healing up of the ends of the chromosomes after they are divided in mitosis.34
It is quite amazing to consider the afformentioned side benefits of magnesium consumption or supplementation within the context of the well-known side effects of pharmaceutical approaches to symptom management of disease. On average, conventional drugs have 75 side effects associated with their use, including lethal ones (albeit sometimes rare). When considering magnesium's many side benefits and extremely low toxicity, clearly this fundamental mineral intervention (and dietary requirement) puts pharmaceutical approaches to depression to shame.
Fortunately, for those who need higher doses, or are not inclined to consume magnesium rich foods, there are supplemental forms commonly available on the market. Keep in mind, for those who wish to take advantage of the side benefit of magnesium therapy, namely, its stool softening and laxative properties, magnesium citrate or oxide will provide this additional feature.
1) World Health Organization. Depression fact sheet no. 369 2012 [cited 2016 December 20]. Available from: http://www.who.int/mediacentre/factsheets/fs369/en/.
2) Jacka FN, Overland S, Stewart R, Tell GS, Bjelland I, Mykletun A. Association between magnesium intake and depression and anxiety in community-dwelling adults: the Hordaland Health Study. Aust N Z J Psychiatry. 2009;43(1):45–52. Pmid:19085527.
3) Huang JH, Lu YF, Cheng FC, Lee JN, Tsai LC. Correlation of magnesium intake with metabolic parameters, depression and physical activity in elderly type 2 diabetes patients: a cross-sectional study. Nutrition J. 2012;11(1):41. pmid:22695027; PubMed Central PMCID: PMC3439347.
4) Tarleton EK, Littenberg B. Magnesium intake and depression in adults. J Am Board Fam Med. 2015;28(2):249–56. Pmid:25748766
5) Yary T, Lehto SM, Tolmunen T, Tuomainen T-P, Kauhanen J, Voutilainen S, et al. Dietary magnesium intake and the incidence of depression: a 20-year follow-up study. J Affect Disord. 2016;193:94–8. Pmid:26771950
6) Eby GA, Eby KL. Rapid recovery from major depression using magnesium treatment. Med Hypotheses. 2006;67(2):362–70. pmid:16542786
7) N Engl J Med. 2000 Dec 28;343(26):1942-50. Managing depression in medical outpatients.
8) Damiano Piovesan, Giuseppe Profiti, Pier Luigi Martelli, Rita Casadio. 3,751 magnesium binding sites have been detected on human proteins. BMC Bioinformatics. 2012 ;13 Suppl 14:S10. Epub 2012 Sep 7. PMID: 23095498
9) G Moorkens, B Manuel y Keenoy, J Vertommen, S Meludu, M Noe, I De Leeuw. Magnesium deficit in a sample of the Belgian population presenting with chronic fatigue. Magnes Res. 1997 Dec;10(4):329-37. PMID: 9513929
10) J Eisinger, A Plantamura, P A Marie, T Ayavou. Selenium and magnesium status in fibromyalgia. Magnes Res. 1994 Dec;7(3-4):285-8. PMID: 7786692
11) I J Russell, J E Michalek, J D Flechas, G E Abraham. Treatment of fibromyalgia syndrome with Super Malic: a randomized, double blind, placebo controlled, crossover pilot study. J Rheumatol. 1995 May;22(5):953-8. PMID: 8587088
12) GreenMedInfo.com, Atrial Fibrillation and Magnesium (5 studies)
13) Phuong-Chi T Pham, Phuong-Mai T Pham, Son V Pham, Jeffrey M Miller, Phuong-Thu T Pham . Hypomagnesemia in patients with type 2 diabetes. Clin J Am Soc Nephrol. 2007 Mar;2(2):366-73. Epub 2007 Jan 3. PMID: 17699436
14) M de Lordes Lima, T Cruz, J C Pousada, L E Rodrigues, K Barbosa, V Canguçu. The effect of magnesium supplementation in increasing doses on the control of type 2 diabetes. Diabetes Care. 1998 May;21(5):682-6. PMID: 9589224
15) Y Song, K He, E B Levitan, J E Manson, S Liu. Effects of oral magnesium supplementation on glycaemic control in Type 2 diabetes: a meta-analysis of randomized double-blind controlled trials. Cardiovasc Toxicol. 2008;8(3):115-25. Epub 2008 Jul 8. PMID: 16978367
16) Martha Rodríguez-Morán, Fernando Guerrero-Romero. Oral magnesium supplementation improves insulin sensitivity and metabolic control in type 2 diabetic subjects: a randomized double-blind controlled trial. Diabetes Care. 2003 Apr;26(4):1147-52. PMID: 12663588
17) F Facchinetti, P Borella, G Sances, L Fioroni, R E Nappi, A R Genazzani. Oral magnesium successfully relieves premenstrual mood changes. Obstet Gynecol. 1991 Aug;78(2):177-81. PMID: 2067759
18) A F Walker, M C De Souza, M F Vickers, S Abeyasekera, M L Collins, L A Trinca. Magnesium supplementation alleviates premenstrual symptoms of fluid retention. J Womens Health. 1998 Nov;7(9):1157-65. PMID: 9861593
19) S Quaranta, M A Buscaglia, M G Meroni, E Colombo, S Cella. Pilot study of the efficacy and safety of a modified-release magnesium 250 mg tablet (Sincromag) for the treatment of premenstrual syndrome. Am J Gastroenterol. 2008 Dec;103(12):2972-6. PMID: 17177579
20) M C De Souza, A F Walker, P A Robinson, K Bolland. A synergistic effect of a daily supplement for 1 month of 200 mg magnesium plus 50 mg vitamin B6 for the relief of anxiety-related premenstrual symptoms: a randomized, double-blind, crossover study. J Womens Health Gend Based Med. 2000 Mar;9(2):131-9. PMID: 10746516
21) 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
22) Andrea Rosanoff, Mildred S Seelig. Comparison of mechanism and functional effects of magnesium and statin pharmaceuticals. J Am Coll Nutr. 2004 Oct;23(5):501S-505S. PMID: 15466951
23) GreenMedInfo.com, Magnesium's Hypotensive Properties.
24) GreenMedInfo.com, Magnesium's Antispasmodic Properties.
25) Joen R Sheu, George Hsiao, Ming Y Shen, Yen M Lee, Mao H Yen . Antithrombotic effects of magnesium sulfate in in vivo experiments. Int J Hematol. 2003 May;77(4):414-9. PMID: 12774935
26) Afshin Samaie, Nabiollah Asghari, Raheb Ghorbani, Jafar Arda. Blood Magnesium levels in migraineurs within and between the headache attacks: a case control study. Pan Afr Med J. 2012 ;11:46. Epub 2012 Mar 15. PMID: 22593782
27) Mahnaz Talebi, Dariush Savadi-Oskouei, Mehdi Farhoudi, Solmaz Mohammadzade, Seyyedjamal Ghaemmaghamihezaveh, Akbar Hasani, Amir Hamdi. Relation between serum magnesium level and migraine attacks. Neurosciences (Riyadh). 2011 Oct ;16(4):320-3. PMID: 21983373
28) Alexander Mauskop, Jasmine Varughese. Why all migraine patients should be treated with magnesium. J Neural Transm. 2012 May ;119(5):575-9. Epub 2012 Mar 18. PMID: 22426836
29) Fong Wang, Stephen K Van Den Eeden, Lynn M Ackerson, Susan E Salk, Robyn H Reince, Ronald J Elin. Oral magnesium oxide prophylaxis of frequent migrainous headache in children: a randomized, double-blind, placebo-controlled trial. Eur J Endocrinol. 2009 Apr;160(4):611-7. Epub 2009 Jan 29. PMID: 12786918
30) Ali Tarighat Esfanjani, Reza Mahdavi, Mehrangiz Ebrahimi Mameghani, Mahnaz Talebi, Zeinab Nikniaz, Abdolrasool Safaiyan. The effects of magnesium, L-carnitine, and concurrent magnesium-L-carnitine supplementation in migraine prophylaxis. Biol Trace Elem Res. 2012 Dec ;150(1-3):42-8. Epub 2012 Aug 17. PMID: 22895810
31) David W Killilea, Jeanette A M Maier. A connection between magnesium deficiency and aging: new insights from cellular studies. Magnes Res. 2008 Jun;21(2):77-82. PMID: 18705534
32) GreenMedInfo.com, What We Learned From The Accelerated Aging of Astronauts
33) Katja Held, I A Antonijevic, H Künzel, M Uhr, T C Wetter, I C Golly, A Steiger, H Murck. Oral Mg(2+) supplementation reverses age-related neuroendocrine and sleep EEG changes in humans. Pharmacopsychiatry. 2002 Jul;35(4):135-43. PMID: 12163983
34) William J Rowe. Correcting magnesium deficiencies may prolong life. Clin Interv Aging. 2012 ;7:51-4. Epub 2012 Feb 16. PMID: 22379366
Sayer Ji is founder of Greenmedinfo.com, a reviewer at the International Journal of Human Nutrition and Functional Medicine, Co-founder and CEO of Systome Biomed, Vice Chairman of the Board of the National Health Federation, Steering Committee Member of the Global Non-GMO Foundation.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of GreenMedInfo or its staff.