Vitamin Expert

Magnesium Facts

Magnesium (Mg) is the fourth most abundant body mineral. Balance is tightly regulated keeping plasma Mg2+ levels within a typically normal range of 0.7-0.85 mmol/l. Total body content in an average adult is 25 grams with approximately 60% present bone which serves as a reservoir (1).  A further 20% is localised to muscle and the remaining 20% is present in soft tissue and liver (2). In the kidney, approximately 2.5 g of Mg is filtered daily, but, approximately 95%of this load is reabsorbed. (3) Hypomagnesaemia is defined as a serum concentration of less than 0.70 mmol/l and chronic depletion generally becomes clinically evident at serum concentrations of <0.40 mmol/l. (4)

Magnesium is needed for more than 300 biochemical reactions. It is important in the maintenance of normal nerve and muscle function, strong bones, a steady heart rhythm, and a healthy immune system and a deficiency results in numerous medical conditions. (7,8)

About 60% of US adults do not consume the estimated average requirement, yet despite this, widespread pathological conditions attributed to deficiency are not reported. (10) The main reason may be that serum levels are the most commonly used tool to assess mineral status. A study of geriatric outpatients, found that whilst serum Mg levels were within the normal range in all patients, the intra-erythrocyte measurements were low in 57%. (11)  Another study, measuring total serum levels as subjects aged, showed no apparent change, but when the intracellular free Mg concentration was measured, there was clearly a progressive decrease. (12)

US studies also show that between 8% and 30% of hospitalized patients have hypomagnesemia and evidence suggests that the ‘‘American-type diet’’ is low in magnesium. The authors observe that an ‘‘Oriental diet,’’ consisting of more fruits and vegetables, is linked to higher magnesium levels and may attribute to lower levels of coronary heart disease (CHD) amongst oriental populations (13-15).

Three types of diuretics are known to cause hypomagnesaemia-osmotic diuretics, loop diuretics and thiazide-type diuretics. (89)

In many patients serum Mg2+ concentrations during EGFR-targeting treatment are decreased. (90). In trials, 54% of treated patients developed hypomagnesaemia and in 6% of patients hypomagnesaemia was severe. (91, 92). The incidence of Mg2+ deficiency during treatment with cisplatin is around 30% and is amplified with increased dosage or prolonged duration of treatment (93).

Several studies have described proton pump inhibitor-induced hypomagnesaemia in patients treated for more than one year. (94-98) Patients recover relatively quickly upon discontinuation but relapse within days when medication is restarted. Patients suffering from hypomagnesaemia due to PPIs can be treated with supplements or switched to a histamine H2 receptor antagonist.

As many as 25% of aminoglycoside-antibiotic treated patients will develop hypomagnesaemia. (99)  The effect seems to be related to cumulative doses received by the patient during treatment. Onset of hypomagnesaemia can take up to two weeks and can persist after cessation of treatment for several months (100)

Calcineurin inhibitors commonly lead to hypomagnesaemia due to renal Mg2+ wasting, hypercalciuria and hypokalaemia (101).

Sources of magnesium

Leafy vegetables, unrefined grains and nuts generally have higher magnesium contents than meats and dairy products. Tap water varies greatly depending on the mineral content of the supply.  Approximately 300 mg of Mg is ingested on a daily basis, of which 25–75% is absorbed, depending on the bioavailability of the form consumed and needs of the body. (5,6)

Magnesium in health and disease

Asthma

Of nine published studies, seven are randomized controlled trials investigating an intervention of magnesium supplements. (16-24). Four relate to children and five evaluate the benefits in adults. Seven articles reported a statistically significant correlation between high magnesium intake and a decrease in severity of asthma symptoms. (16-19, 22-24)  Of the studies that found positive correlations, five randomized controlled trials used an intervention dose of 340-400 mg/day for adults and 200-300 mg/day for children to produce one or more  significant outcome measures.

Intravenous (IV) magnesium to treat acute asthma attacks in adults is effective in improving peak expiratory flow rate and FEV1. Administration in addition to bronchodilators is safe and beneficial for people with severe asthma attacks or for those in whom bronchodilators do not work (25).  Another study supported the use of nebulised magnesium sulphate in addition to a b2-agonist in the treatment of an acute asthma exacerbation and reported a decrease in hospital admissions. (26)

Migraine

Multiple studies have found IV magnesium successful in the treatment of migraines. It is most effective in participants with acute migraines who are known to be deficient in magnesium. (27-32) Seven studies show a significant correlation between oral magnesium supplementation and a decrease in the frequency or severity of migraines. (33-39) Five were randomized control trials that used a dose ranging between 360-600 mg/day for adults, and 9 mg/kg/day for children.  Duration was either 12 or 16 weeks and each study measured migraine headache frequency and severity as primary outcomes.

A recent paper suggests migraine sufferers may develop deficiency due to genetic inability to absorb magnesium, inherited renal magnesium wasting, excretion of excessive amounts due to stress, and low nutritional intake. It proposes when trials have produced mixed results, it is most likely due to both magnesium deficient and non-deficient patients being assessed. Considering deficiency may be present in 50% of migraine patients, and routine blood tests are not indicative of status, it recommends empiric treatment with at least oral magnesium is warranted in all sufferers. (40) The recommended dose for the prophylaxis of migraine headaches is 600 mg a day of a chelated magnesium preparation. (41)

Coronary Heart Disease

A magnesium rich diet results in fewer complications such as ischemic heart disease, arrhythmias, angina, lower mortality and fewer sudden deaths. (42) Elsewhere, CHD risks have been shown to be inversely correlated to dietary magnesium supplementation.(43-45).  A review of six studies examining the relationship between magnesium and CHD or CHD risk reported supplementation, resulted in better small artery elasticity, favourable effects on exercise tolerance and a reduced risk of CHD (46). Magnesium could also be important in the pathogenesis of sudden death. (47)

Dietary magnesium assessments in 58,615 healthy Japanese found intake was inversely associated with mortality from haemorrhagic stroke in men and with mortality from total and ischemic strokes, coronary heart disease, heart failure and total cardiovascular disease in women.(48)

Compared to controls, patients with heart failure (HF) demonstrated higher baseline C-reactive protein (CRP) levels, independent of co-existing conditions, and lower serum Mg values. Following Mg administration CRP decreased significantly and targeting the inflammatory cascade this way might prove a useful tool for improving the prognosis in HF. (49)

Hypertension

A review of 44 studies examined the use of oral magnesium supplementation for the treatment of hypertension (50). In studies of patients taking antihypertensive medications, the dose range necessary to produce a decrease in blood pressure (BP) was 240-480/day. In studies of patients not receiving antihypertensive medications, seven of the ten found a significant decrease in blood pressure in subjects supplemented with ≥480 mg of magnesium per day. In the studies of participants who were either normotensive or pre-hypertensive, results showed no changes in blood pressure after daily doses of between 97-600 mg. Consumption of 500-1000 mg of magnesium may lower BP as much as 2.7-5.6 mm Hg systolic and 1.7-3.4 mm Hg diastolic (51). Combining magnesium with taurine has additive antihypertensive effects and lowers intracellular sodium and calcium.

Pre-eclampsia

Today, magnesium sulphate is the drug of choice in patients with severe pre-eclampsia and eclampsia. (52)  In one large study, patients who received magnesium sulphate supplementation had a 58% lower risk of eclampsia than those receiving placebo and had lower mortality rates with no substantive harmful effects on either the mother or baby at the time of delivery, no difference in the risk of death or disability for children at 18 months post-delivery, nor for the women at two years after treatment. (53-55)

Diabetes Mellitus

Magnesium plays an important role in glucose metabolism and could influence the release and activity of insulin. (56) In insulin-sensitive tissues, insulin stimulates magnesium uptake. (57)  A study of obese non-diabetic children noted that the dietary magnesium intake was significantly lower in obese children and inversely associated with fasting insulin levels, concluding that the association between insulin resistance and magnesium deficiency was present in childhood, and that increasing magnesium levels could be important in the prevention of type 2 diabetes in children who are obese. (58)  Low magnesium status is also often found in people with the metabolic syndrome and type 2 diabetes, which are associated with higher plasma CRP concentrations. Because a low magnesium status apparently occurs more often in obese than non-obese individuals, one of the stressors causing the activation of inflammatory pathways may be magnesium deficiency.

A review of seven studies found intake was inversely associated with the incidence of type 2 diabetes suggesting that increasing the amount of magnesium in consumed could reduce the risk of developing type 2 diabetes.(59) A further report suggests magnesium supplementation improved insulin sensitivity and could be helpful with cardiovascular risk reduction in patients with mild uncomplicated hypertension. (60)

Diabetic patients, who received 300 mg/day magnesium for more than five years were followed to determine whether long-term supplementation influenced the natural evolution of polyneuropathy. Long-term supplementation was able to normalise magnesium levels and positively influence polyneuropathy.(61)

Depression and Stress 

60% of cases of clinical depression are considered to be treatment-resistant depression (TRD) and brain magnesium has been found low in TRD using phosphorous nuclear magnetic resonance spectroscopy, an accurate means for measuring magnesium. (62) Oral administration of magnesium to animals led to effects  comparable to those of strong anti-depressant drugs (63). Taurine and glycine are also found to be low in TRD and are each important in regulating magnesium homeostasis. (64)

A 1921 study first showed success in TRD cases, but a 2008 randomized clinical trial showed magnesium as effective as the tricyclic anti-depressant imipramine in treating depression in diabetics, without any of the side effects of imipramine (65,66).  Intravenous and oral magnesium in specific protocols have been reported to rapidly terminate TRD safely and without side effects (67). Benefits of IV magnesium treatment of TRD have been found to be extremely rapid and unequivocally strong and are suggested for treatment initiation. (68)

Depression-inducing severe loss of IQ, memory and attention in children due to loss of neuronal Mg has been reported in conditions of exceptional stress. Stress worsened mental health by Mg depletion, but was minimized with magnesium supplementation. (69) Memory loss, IQ loss and attention deficits associated with onset of severe depression appeared completely reversible upon magnesium treatment in a case report (70). In familial depression with low IQ, poor memory and concentration, vitamin B6, magnesium, zinc and manganese deficiencies were common in diets of families of depressives (71). Test anxiety in students resulted in increased losses of magnesium in the urine. (72)

Fibromyalgia (FMS)

Magnesium deficits have been shown to be a causal mechanism in the development of FMS in part because of the role of magnesium in the production of ATP (77). One paper suggests that low magnesium levels are common among FMS patients and supplementation may benefit this subgroup.(78)

In a double-blinded cross-over trial, subjects received either a fixed dose of malic acid and magnesium or  placebo. (79) No treatment effects were observed as measured by tender point index, dolorimetery reading of the tender point average, or pain. In contrast, positive results were obtained on all three of these outcome variables in a subsequent six-month open-label, un-blinded trial. A further open-label randomized, placebo-controlled cross-over trial administered a higher dose of magnesium and malate over eight weeks.(80) Significant differences in tender point index scores in the intervention group were observed, and significant worsening when subjects were crossed-over to placebo.

There are clear indications that IV magnesium has a positive effect on FMS after five and ten weeks of treatment. There are indications that a large subgroup benefits from this treatment. (81)

Chronic Fatigue Syndrome (CFS)

Two systematic reviews of CAM treatments for CFS conclude most supplements failed to show beneficial effects for CFS, with the exception of NADH and magnesium. (82,83) The key trial compared a magnesium supplement with placebo and found beneficial effects on patients’ symptom profiles. (84).

References

  1. Malarky LM et al. Saunders nursing guide to laboratory and diagnostic tests. St Louis, MO: Elsevier Saunders 2005.
  2. Kelepourieis, E and Agus. S Hypomagnesemia:Renal magnesium handling. Seminars in nephrology 1998, 18, 58-73
  3. Quamme, G.A recent developments in the intestine or magnesium absorption. Clin Lab Med 2008, 13, 209-223
  4. Maier JA. Low magnesium and atherosclerosis; an evidence-based link. Mol  Aspects Med. 2003, 24,137-146
  5. National Institute of health office and dietary supplements. Dietary supplements fact sheet magnesium. http://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/.
  6. Institute of medicine. Food and nutrition board. Dietary reference intakes; calcium, phosphorus, magnesium, vitamin D and fluoride. Washington DC; National academies press 1999.
  7. Topf, JM. et al. Hypomagnesaemia and hypermagnesiumia. Rev Endocr. Metab. Disord. 2003, 4, 195-206
  8. Huang Cl. et al. Mechanism of hypokalaemia in magnesium deficiency. J.Am Soc Nephrol. 2007, 18, 2649-2652
  9. Arnaud MJ. Update on the assessment of magnesium status. Br J Nut. 2008, 99 (suppl 3) S24-36
  10. Ford ES et al. Dietary magnesium intake in a national sample of US adults. J Nutr. 2003, 133, 2879-2882
  11. Zekeriya U et al. Intra-erythrocyte magnesium levels and their clinical implication in geriatric patients. J Nutr Health Aging. 2010, 14, 810-814
  12. Barbagallo M et al. Magnesium homoeostasis and ageing. Magnes Res. 2009, 22, 235-246
  13. Maier JAM et al. Low magnesium promotes endothelial cell dysfunction; implications for atherosclerosis, inflammation and thrombosis. Biochimica et Biophysica Acta 2004, 1689, 6-12
  14. Shechter M. Does magnesium have a role in the treatment of patients with coronary artery disease. Am J Cardiovascular Drugs 2003, 3,231-239
  15. Touyz RM. Magnesium in clinical medicine. Frontiers in Bioscience 2004, 9, 1278-1293
  16. Bede O et al. Effective magnesium supplementation on the glutathione redox in atopic asthmatic children. Inflamm Res 2008, 57, 279-286
  17. Gontijo-Amaral C et al. Oral magnesium supplementation in asthmatic children; a double-blind, randomised, placebo-controlled trial. Eur J Clin Nurt 2007, 61, 54-60
  18. Bede O et al. Urinary magnesium excretion in asthmatic children receiving magnesium supplementation; randomised, placebo-controlled, double-blind study. Magnes Res. 2003, 16, 262-270
  19. Britton J et al. Dietary magnesium, lung function, wheezing, and airway hyperactivity in a random adult. Lancet 1994, 344, 357-362
  20. Fogarty A et al. Oral magnesium and vitamin C supplements in asthma; a parallel group randomised, placebo-controlled trial. Clin Exp Allergy 2003, 33, 1355-1359
  21. Fogarty et al. Corticosteroid sparing effects of vitamins C and magnesium in asthma; a randomised trial. Respir Med 2006, 100, 174-179
  22. Hijazi N et al. Diet and childhood asthma in a society in transition; a study in urban and rule Saudi Arabia. Thorax 2000, 55, 775-779
  23. Hill J et al. Investigation of the effect of short-term change in dietary magnesium intake in asthma. Eur Respir J, 1997, 10, 2225-9
  24. Kazaks AG et al. Effective oral magnesium supplementation on measures of airway resistance and subjective assessment of asthma control and quality-of-life in men and women with mild-to-moderate asthma; a randomised placebo-controlled trial. J Asthma 2010, 47, 83-92
  25. Cheuk D et al. A meta-analysis of intravenous magnesium sulphate for treating acute asthma. Arch Dis Child. 2005, 90, 74-77
  26. Blitz M. Inhaled magnesium sulphate in the treatment of acute asthma. Cochrane Database Syst Rev 2005, 4, CD003898
  27. Cady RK et al. The effect of magnesium on the responsiveness of migraineurs to a 5-HT1 agonist. Neurology 1998, 208, 198-200
  28. Mauskop A et al. Intravenous magnesium sulphate relieves migraine attacks in patients with low serum ionised magnesium levels; a pilot study. Clin Sci 1995, 89, 633-6
  29. Bigal et al. Intravenous magnesium sulphate in the acute treatment of migraine without aura and migraine with aura. A randomised, double-blind, placebo-controlled study. Cephalgia 2002, 22, 345-353
  30. Demirkaya et al. Efficacy of intravenous magnesium sulphate in the treatment of acute migraine headaches. Headache 2001,41,171-177
  31. Mauskop A et al. Intravenous magnesium sulphate rapidly alleviates headaches of various types. Headache 1996, 36, 154-160.
  32. Cete Y et al. A randomised prospective placebo-controlled study of intravenous magnesium sulphate versus metoclopramide in the management of acute migraine attacks in the emergency department. Cephalgia 2005, 25, 199-204
  33. Castelli S et al. Magnesium in the prophylaxis of primary headache and other periodic disorders in children. Pediatr Med Chir. 1993, 15, 481-8
  34. Grazzi L et al. Magnesium as a treatment for paediatric tension type headache; a clinical replication series. Neurol Sci 2005, 25, 338-341
  35. Grazzi L et al. Magnesium is a preventative treatment for paediatric episodic tension type headache; results of a one-year follow-up. Neurol Sci 2007, 28, 148-150
  36. Wang F et al. Oral magnesium oxide prophylaxis of frequent migrainous headache in children. A randomised, double-blind, placebo-controlled trial. Headache 2003, 43, 601-610
  37. Facchinetti F et al. Magnesium prophylaxis of menstrual migraine; effect on intracellular magnesium. Headache 1991, 31, 298-301
  38. Koseoglu E et al. The effects of magnesium prophylaxis in migraine without aura. Magnes Res 2008, 21, 101-108
  39. Peikert A et al. Prophylaxis of migraine with or magnesium; results from a prospective, multicentre, placebo-controlled double-blind, randomised study.  Cephalgia 1996, 16, 257-263
  40. Mauskop A, Varughese J. Why all migraine patients should be treated with magnesium. J Neural Transm 2012, 119, 575-579
  41. Mauskop A, Altura BM, magnesium for migraine irrational for use and therapeutic potential CNS Drugs 1998, 185-190
  42. Singh RB. Effect of dietary magnesium supplementation in the prevention of coronary heart disease and sudden cardiac death. Magnes Trcace Elem 1990, 9, 143-151
  43. Abbott RD et al. Dietary magnesium intake and the future risk of coronary artery disease. Am J Cardiol 2003,92, 665-669
  44. Fuentes JC et al. Acute and chronic oral magnesium supplementation; effects on endothelial function, exercise capacity and quality-of-life in patients with symptomatic heart failure. Congest Heart Fail 2006, 12, 9-13
  45. Kelvay LM et al. Low dietary magnesium increases supra-ventricular ectopy Am J Clin Nutr 2002, 75, 550-554
  46. Mathers TW et al. Oral magnesium supplementation in adults with coronary heart disease or coronary heart disease risk. J Am Acad Nurse Pract 2009, 21, 651-657
  47. Baroldi G. E. Acute coronary occlusion as a cause of myocardial infarction and sudden coronary heart death. Am J Cardiol 1965, 16, 859-880
  48. Zhang W et al. Their associations of dietary magnesium intake with mortality from comedy vascular disease; The JACC study. Atherosclerosis 2012, 221, 587-595
  49. Almoznino-Sarafian D et al. Magnesium and C reactive protein in heart failure; and anti-inflammatory effect of magnesium administration. Eur J Nutr 2007, 46, 230-237
  50. Rosanoff A. Magnesium supplements may enhance the effects of antihypertensive medications in stage one hypertensive subjects. Magnes Res 2010;23;27-40
  51. Houston M. The role of magnesium in hypertension and cardiovascular disease. J Clin Hypertension 2011, 13, 843-847
  52. Green MF magnesium sulphate for pre-eclampsia. N Eng J Med 2003, 348, 275-276
  53. McCoy S et al. Pharmacotherapeutic options for the treatment of pre-eclampsia J Obstet Gynaecol Neonatal Nurs 2009, 66, 337-344
  54. Magpie trial follow-up study collaborative group. The magpie trial; a randomised trial comparing magnesium sulphate with placebo for pre-eclampsia. Outcome for women at two years BOJG 2007, 114, 300-309
  55. Magpie trial follow-up study collaborative group. The magpie trial; a randomised trial comparing magnesium sulphate with placebo for pre-eclampsia. Outcome for children at 18 months. BOJG 2007, 114, 289-299
  56. Martini L et al. Role of vitamins and minerals in the prevention and management of type II diabetes mellitus. Nutr Rev 2010, 68, 341-354
  57. Takaya et al. Intracellular magnesium and insulin resistance. Megnes Res 2004, 17, 126-136
  58. Huerta MG et al. Magnesium deficiency is associated with insulin resistance in obese children. Diabetes Care 2005, 28, 1175-1181
  59. Larsson SC, Wolk A. Magnesium intake and risk of type II diabetes; a meta-analysis. J Intern Med 2007, 262, 208-214
  60. Hadjistavri LS et al. Beneficial effects of oral magnesium supplementation on insulin  sensitivity and serum lipid level profile. Med Sci Monit 2010, 16, P113-8
  61. De Leeuw I et al . Long-term magnesium supplementation influences favourably. The natural evolution of neuropathy in magnesium depleted type I diabetic patients. Mag Res 2004, 17, 109-114
  62. Feduka A et al. What happens to patients with treatment resistant depression? Systematic review of medium to long-term outcome studies. J Affect Disord 2009, 116, 4-11
  63. Poleszak E et al. Antidepressant and anxiolytic-like activity of magnesium in mice Pharmacol Biochem Behav 2004, 78, 7-12
  64. Coppen A. The Biochemistry of affective disorders. Br J Psychiatry 1967, 113, 1237-64
  65. Weston PG. Magnesium is a sedative. Am J Psychiatry 1921-22, 1, 637-8
  66. Barragan-Rodriguez L et al. Efficacy and safety of oral magnesium supplementation in the treatment of depression in the elderly with type II diabetes; a randomised equivalent trial. Magnes Res 2008, 21, 218-23
  67. Enya M et al depressive state and paraesthesia dramatically improved by intravenous magnesium sulphate in Gitelman’s syndrome. InternMed 2004; 43; 218-23
  68. Eby GA et al. Magnesium for treatment resistant depression; a review and hypothesis. Med Hypothese 2010, 74, 649-60
  69. Papadopol V et al. Magnesium and some psychological features into groups of pupils. Magnes Res 2001, 14, 27-32
  70. Eby GA et al rapid recovery from major depression using magnesium treatment. Med Hypotheses 2006, 67, 362-70
  71. Reading CM. family tree connection; how your past can shape your future health. A lesson in Orthomolecular medicine J Orthomol Med 1988, 3, 123-34
  72. Grases G et al . Anxiety and stress amongst science students. Study of calcium and magnesium alterations. Mag Res 2006, 19, 102-6
  73. Windebank AJ et al . Chemotherapy induced neuropathy. J Peripher Nerv Sys 2008, 13, 27-46
  74. Grothy A et al. Intravenous calcium and magnesium for oxaliplatin-induced sensory neurotoxicity in adjuvant colon cancer. J Clin Oncol 2011, 29, 421-7
  75. Gamelin L et al. Prevention ofoxaliplatin-related neurotoxicity by calcium and magnesium infusions. Clin Cancer Res 2004, 10, 4055-61
  76. Park H et al. A pilot phase 2 trial of magnesium supplements to reduce menopausal hot flushes in West cancer patients. Support Cancer Care 2011, 19, 859-63
  77. Bazzichi L et al. ATP, calcium and magnesium levels in platelets of patients with primary fibromyalgia. Clin Biochem 2008, 41, 1084-1090
  78. Ramalanjaona G. Magnesium in the treatment of fibromyalgia. Alt Med Alert, 2002, 5, 29-32
  79. Russell IJ et al treatment of fibromyalgia syndrome with super Malic a randomised double-blind placebo-controlled crossover pilot study. J Rheumatol 1995, 22, 953-8
  80. Abraham GE et al. Management of fibromyalgia; a rationale for the use of magnesium and malic acid J Nut Med 1992, 3, 49-59
  81. Baars E et al. The effect of Hepar magnesium D10 on fibromyalgia syndrome-a pilot study. Eur J Integr Med 2010
  82. Alraek T et al. Complementary and alternative medicine for patients with chronic fatigue syndrome; a systematic review. Comp Alt Med 2011, 11, 87-98
  83. Chambers C et al. Interventions the treatment, management and rehabilitation of patients with chronic fatigue syndrome/myalgic encephalomyelitis; an updated systematic review. J Royal Soc Med 2006, 99, 506-520
  84. Cox Im et al. Read blood cell magnesium and chronic fatigue syndrome. Lancet 199, 337, 757-60
  85. Rapkin A. A review of treatment of premenstrual syndrome and premenstrual dysphoria Disorder. Psychoneuroendocrinology 2003, 28, 39-53
  86. Cinar V et al. Effector magnesium supplementation on testosterone levels of athletes and sedentary subjects at rest and after exhaustion. Biol Trace Elem. 2011, 140, 18-23
  87. Ma E et al high dietary intake of magnesium may decrease risk of colorectal cancer in Japanese men J Nutrition 2010, 140, 779-785 .
  88. Siregar MFG et al. Magnesium serum levels of feature of premenstrual syndrome measured by premenstrual symptoms scale. BJOG 2012, P2.05
  89. Lamersis A et al. Drug induced alterations in magnesium homoeostasis. Clin Sci 2012, 123, 1-14
  90. Tejpar S et al. Magnesium wasting associated with epidermal growth factor receptor targeting antibodies in colorectal cancer-a prospective study, Lancet Oncol 2007, 8, 387-394
  91. Cao Y et al. Meta-analysis of incidents and risk of Hypo magnesium with cetuximab for advanced cancer. Chemotherapy 2010, 56, 459-465
  92. Fakih M et al. Cetuximab induced Hypo magnesium in patients with colorectal cancer. Clin Colorectal Cancer. 2006, 6, 152-6
  93. Lajer H, Daugaard G. Cisplatin in Hypomagnesemia. Mancer  Treatment Rev 1999, 25, 47-58
  94. Epstein M et al. Proton pump inhibitors and hypomagnesmic hypoparathyroidism. N Eng J Med  2006, 355, 1834-6
  95. Cundy T et al, Hypomagnesaemia in long-term users of proton pump inhibitors Clin Endocrin 2008, 69, 338-341
  96. Regolisti G et al. Severe Hypomagnesaemia  during long-term treatment with proton pump inhibitor. Am J Kidney Dis 2010, 56, 168-74
  97. Kuipers MT et al. Hypomagnesaemia due to use of proton pump inhibitors-a review Neth J Med 2009, 67, 169-72
  98. Insoga K. The effect of proton pump inhibiting drugs on mineral absorption. Am J Gastroenterol. 2009, 104, S2-4
  99. Shah GM et al. Renal magnesium wasting associated with therapeutic agents. Miner Electrolyte Metab. 1991, 17, 58-64
  100. Wilkinson R et al. Hypomagnesaemic tetany associated with prolonged treatment with aminoglycosides. Br Med J 1986, 292, 818-819
  101. Kim HC et al. Primary immunosuppression with tacrolimus in kidney transplantation; three-year follow-up in a single centre. Transplant Proc 2004, 36, 2082-3