Magnesium's Impact on Epigenetic Expression & Health Far Greater Than Previously Imagined
By Sayer Ji •
December 19, 2012
Nutrition research writer Sayer Ji is founder and chair of GreenMedInfo.com – a consumer advocacy site offering 'the world’s largest natural medicine database,’ with a searchable index linking to more than 19,800 biomedical study abstracts. This article, first published May 23, 2012, is reproduced with kind permission from Sayer Ji. ©2012 GreenMedInfo.com all rights reserved.
Magnesium's Importance Far Greater Than Previously Imagined
Calcium deficiency is a common nutritional concern, but how many folks consider the vital importance of magnesium in human health and disease?
New research published in the journal BMC Bioinformatics indicates that magnesium's role in human health and disease is far more significant and complicated than previously imagined.
While it is well known that all living things require magnesium, andthat it is found in over 300 enzymes in the human body, including those enzymes utilizing or synthesizing ATP (the molecular unit of currency for energy transfer), the new study, titled "3,751 Magnesium Binding Sites Have Been Detected on Human Proteins," indicates that a deficiency of magnesium may profoundly affect a far wider range of biological structures than previously understood.(1)
The proteome, or entire set of proteins expressed by the human genome, contains well over 100,000 distinct protein structures, despite the fact that there are believed to be only 20,300 protein-coding genes in the human genome.
The discovery of the "magnesome," as its being called, adds additional complexity to the picture, indicating that the presence or absence of adequate levels of this basic mineral may epigenetically alter the expression and behavior of the proteins in our body, thereby altering the course of both health and disease.
Indeed, modern medicine and nutrition fixates primarily on calcium deficiency (due, in part, to the World Health Organization's highly unscientific definition of osteoporosis), even in the face of accumulating peer-reviewed research indicating that excess calcium consumption can greatly increase cardiac morbidity and mortality.
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. [The free GreenMedInfo membership option allows access to all abstracts in the searchable database.]
For the sake of brevity, we will address seven key therapeutic applications for magnesium as follows:
Not only is magnesium deficiency common in those diagnosed with fibromyalgia,(2,3) 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.(4)
A number of studies now exist showing that magnesium supplementation reduce atrial fibrillation, either by itself, or in combination with conventional drug agents.(5)
Diabetes, Type 2 (‘Adult Onset’)
Magnesium deficiency is common in type 2 diabetics, at an incidence of 13.5% to 47.7% according to a 2007 study.(6) Research has also shown that type 2 diabetics with peripheral neuropathy and coronary artery disease have lower intracellular magnesium levels.(7)
Oral magnesium supplementation has been shown to reduce plasma fasting glucose and raising HDL cholesterol in patients with type 2 diabetes.(8) It has also been shown to improve insulin sensitivity and metabolic control in type 2 diabetic subjects.(9)
Magnesium deficiency has been observed in women affected by premenstrual syndrome.(10) It is no surprise therefore that it has been found to alleviate premenstrual symptoms of fluid retention,(11) 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.(12)
When combined with B6, magnesium supplementation has been found to improve anxiety-related premenstrual symptoms.(13)
Cardiovascular Disease and Mortality
Low serum magnesium concentrations predict cardiovascular and all-cause mortality.(14) There are a wide range of ways that magnesium may confer its protective effects.
• It may act like a calcium channel blocker [relaxing blood vessels and increasing blood & oxygen supply to the heart],(15)
• It is hypotensive [blood pressure lowering],(16)
• It is antispasmodic (which may protect against coronary artery spasm),(17)
• And anti-thrombotic [interferes with blood clot formation].(18)
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. [The process of breaking down amino acids, glucose, and fatty acids to generate energy.]
Blood magnesium levels have been found to be significantly lower in those who suffer from migraine attacks.(19,20)
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."(21)
The 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,(22) and when combined with L-carnitine, is effective at reducing migraine frequency in adults, as well.(23)
While natural aging is a healthy process, accelerated aging has been noted to be a feature of magnesium deficiency,(24) especially 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.(25)
Magnesium supplementation has been shown to reverse age-related neuroendocrine and sleep EEG changes in humans.(26)
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 [telomeres] after they are divided in mitosis.(27)
Best Sources of Magnesium in The Diet
The best source of magnesium is from food, and one way to identify magnesium-containing foods are those which are green, i.e. chlorophyll rich. Chlorophyll, which enable plants to capture solar energy and convert it into metabolic energy, has a magnesium atom at its center. Without magnesium, in fact, plants could not utilize the sun's light energy.
Magnesium, however, in its elemental form is colorless, and many foods that are not green contain it as well. The point is that when found complexed with food cofactors, it is absorbed and utilized more efficiently than in its elemental form, say, extracted from limestone in the form of magnesium oxide.
The following foods contain exceptionally high amounts of magnesium. The portions described are 100 grams, or a little over three ounces.
Rice bran, crude (781 mg)
Seaweed, agar, dried (770 mg)
Chives, freeze-dried (640 mg)
Spice, coriander leaf, dried (694 mg)
Seeds, pumpkin, dried (535 mg)
Cocoa, dry powder, unsweetened (499 mg)
Spices, basil, dried (422 mg)
Seeds, flaxseed (392 mg)
Spices, cumin seed (366 mg)
Nuts, brazil nuts, dried (376 mg)
Parsley, freeze-dried (372 mg)
Seeds, sesame meal (346 mg)
Nut, almond butter (303 mg)
Nuts, cashew nuts, roasted (273 mg)
Soy flour, defatted (290 mg)
Whey, sweet, dried (176 mg)
Bananas, dehydrated (108 mg)
Millet, puffed (106 mg)
Shallots, freeze-dried (104 mg)
Leeks, freeze-dried (156 mg)
Fish, salmon, raw (95 mg)
Onions, dehydrated flakes (92 mg)
Kale, scotch, raw (88 mg)
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.
For those looking to maximize absorption and bioavailability magnesium glycinate is ideal, as glycine is the smallest amino acid commonly found chelated to magnesium, and therefore highly absorbable.
1. 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
2. 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
3. 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
4. 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
5. GreenMedInfo.com, Atrial Fibrillation and Magnesium (5 studies)
6. 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
7. 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
8. 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
9. 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
10. 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
11. 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
12. 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
13. 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
14. 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
15. 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
16. GreenMedInfo.com, Magnesium's Hypotensive Properties.
17. GreenMedInfo.com, Magnesium's Antispasmodic Properties .
18. 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
19. 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
20. 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
21. 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
22. 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
23. 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
24. 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
25. GreenMedInfo.com, What We Learned From The Accelerated Aging of Astronauts
26. 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
27. William J Rowe. Correcting magnesium deficiencies may prolong life. Clin Interv Aging. 2012 ;7:51-4. Epub 2012 Feb 16. PMID: 22379366
* Disclaimer: This information (©2012 GreenMedInfo.com. All Rights Reserved) has not been reviewed by the FDA. It is general information, based on the research of Sayer Ji unless otherwise noted; and does not necessarily reflect the views of GreenMedInfo or its staff, or that of ProHealth, Inc. It is not intended as medical advice, or for prevention, diagnosis or treatment for any condition, illness or disease; and is not meant to replace a one-on-one relationship with a qualified healthcare professional. It is always very important that you make no change in your healthcare plan or health support regimen without researching and discussing it in collaboration with your professional healthcare team.
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