Friday, October 1, 2010

Diabetes and Magnesium


Magnesium is necessary for both the action
of insulin and the manufacture of insulin.

Magnesium is a basic building block to life and is present in ionic form throughout the full landscape of human physiology. Without insulin though, magnesium doesn’t get transported from our blood into our cells where it is most needed.

When Dr. Jerry Nadler of the Gonda Diabetes Center at the City of Hope Medical Center in Duarte, California, and his colleagues placed 16 healthy people on magnesium-deficient diets, their insulin became less effective at getting sugar from their blood into their cells, where it’s burned or stored as fuel. In other words, they became less insulin sensitive or what is called insulin resistant. And that’s the first step on the road to both diabetes and heart disease.

Insulin is a common denominator, a central figure in life as is magnesium. The task of insulin is to store excess nutritional resources. This system is an evolutionary development used to save energy and other nutritional necessities in times (or hours) of abundance in order to survive in times of hunger.

Little do we appreciate that insulin is not just responsible for regulating sugar entry into the cells but also magnesium, one of the most important substances for life. It is interesting to note here that the kidneys are working at the opposite end physiologically dumping from the blood excess nutrients that the body does not need or cannot process in the moment.

Controlling the level of blood sugars is only one of the many functions of insulin.

Insulin plays a central role in storing magnesium but if our cells become resistant to insulin, or if we do not produce enough insulin, then we have a difficult time storing magnesium in the cells where it belongs.

When insulin processing becomes problematic magnesium gets excreted through our urine instead and this is the basis of what is called magnesium wasting disease.

There is a strong relationship between magnesium and insulin action.
Magnesium is important for the effectiveness of insulin. A reduction
of magnesium in the cells strengthens insulin resistance.
[1] Paolisso G, Scheen A, D’Onofrio F, Lefebvre P: Magnesium and glucose homeostasis. Diabetologia 33:511–514, 1990[Medline]
[2] Nadler JL, Buchanan T, Natarajan R, Antonipillai I, Bergman R, Rude R: Magnesium deficiency produces insulin resistance and increased thromboxane synthesis. Hypertension 21:1024–1029, 1993

Low serum and intracellular magnesium concentrations are associated with insulin resistance, impaired glucose tolerance, and decreased insulin secretion. [3],[4],[5]
[3]Ma J, Folsom AR, Melnick SL, Eckfeldt JH, Sharrett AR, Nabulsi AA, Hutchinson RG, Metcalf PA: Associations of serum and dietary magnesium with cardiovascular disease, hypertension, diabetes, insulin, and carotid wall thickness: the ARIC study. J Clin Epidemiol 48:927–940, 1985
[4] Rosolova H, Mayer O Jr, Reaven GM: Insulin-mediated glucose disposal is decreased in normal subjects with relatively low plasma magnesium concentrations. Metabolism 49:418–420, 2000[Medline]
[5] Resnick LM, Gupta RK, Gruenspan H, Alderman MH, Laragh JH: Hypertension and peripheral insulin resistance: possible mediating role of intracellular free magnesium. Am J Hypertens 3:373–379, 1990[Medline]

Magnesium improves insulin sensitivity thus lowering insulin resistance. Magnesium and insulin need each other. Without magnesium, our pancreas won’t secrete enough insulin–or the insulin it secretes won’t be efficient enough–to control our blood sugar.

Magnesium in our cells helps the muscles to relax but if we can’t store magnesium because the cells are resistant then we lose magnesium which makes the blood vessels constrict, affects our energy levels, and causes an increase in blood pressure. We begin to understand the intimate connection between diabetes and heart disease when we look at the closed loop between declining magnesium levels and declining insulin efficiency.

In a study from Taiwan, the risk of dying
from diabetes was inversely proportional to
the level of magnesium in the drinking water.
Dr. Jerry L. Nadler

Diabetes mellitus is associated with magnesium depletion, which in turn contributes to metabolic complications of diabetes including vascular disease and osteoporosis. Intracellular depletion is directly connected to the impaired ability of insulin to increase intracellular magnesium during insulin deficiency or insulin resistance. Magnesium deficiency per se has been reported to result in insulin resistance.

Insulin resistance and magnesium depletion result in a vicious cycle of worsening insulin resistance and decrease in intracellular Mg(2+) which limits the role of magnesium in vital cellular processes.[7]
[7] Magnesium transport induced ex vivo by a pharmacological dose of insulin is impaired in non-insulin-dependent diabetes mellitus. Hua, H : Gonzales, J : Rude, R K Magnes-Res. 1995 Dec; 8(4): 359-66

Magnesium is an important cofactor for enzymes involved in carbohydrate metabolism so anything threatening magnesium levels threatens overall metabolism. Large epidemiologic studies in adults indicate that lower dietary magnesium and lower serum magnesium are associated with increased risk for type 2 diabetes.[8],[9]
[8] Lopez-Ridaura R, Willett WC, Rimm EB, Liu S, Stampfer MJ, Manson JE, Hu FB: Magnesium intake and risk of type 2 diabetes in men and women. Diabetes Care 27:134–140, 2004
[9] Kao WH, Folsom AR, Nieto FJ, Mo JP, Watson RL, Brancati FL: Serum and dietary magnesium and the risk for type 2 diabetes mellitus: the Atherosclerosis Risk in Communities Study. Arch Intern Med 159:2151, 1999

Researchers at the Institute of Internal Medicine, University of Palermo wrote, “Intracellular magnesium concentration has also been shown to be effective in modulating insulin action (mainly oxidative glucose metabolism), offset calcium-related excitation-contraction coupling, and decrease smooth cell responsiveness to depolarizing stimuli. A poor intracellular Mg concentration, as found in noninsulin-dependent diabetes mellitus (NIDDM) and in hypertensive patients, may result in a defective tyrosine-kinase activity at the insulin receptor level and exaggerated intracellular calcium concentration.” [10]
[10] Mol Aspects Med. 2003 Feb-Jun;24(1-3):39-52. Role of magnesium in insulin action, diabetes and cardio-metabolic syndrome X.Barbagallo M, Dominguez LJ, Galioto A, Ferlisi A, Cani C, Malfa L, Pineo A, Busardo’ A, Paolisso G. Institute of Internal Medicine and Geriatrics, University of Palermo, Via F Scaduto 6/C, Palermo, Italy.

The link between diabetes mellitus and magnesium deficiency
is well known. A growing body of evidence suggests that
magnesium plays a pivotal role in reducing cardiovascular
risks and may be involved in the pathogenesis of diabetes itself.

Dr. Jerry L. Nadler

Magnesium improves and helps correct insulin sensitivity, which is the fundamental defect that characterizes pre-diabetes, metabolic syndrome and even full blown diabetes and heart disease.

An intracellular enzyme called tyrosine kinase requires magnesium to allow insulin to exert its blood-sugar-lowering effects. In several studies, daily oral magnesium supplementation substantially improved insulin sensitivity by 10% and reduced blood sugar by 37%.[11],[12]
[11] Guerrero-Romero F, Tamez-Perez HE, Gonzalez-Gonzalez G et al. Oral magnesium supplementation improves insulin sensitivity in non-diabetic subjects with insulin resistance. A double-blind placebo-controlled randomized trial. Diabetes Metab. 2004 Jun;30(3):253-8.
[12] Rodriguez-Moran M and Guerrero-Romero F. 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.

Magnesium also helps correct abnormal lipoprotein patterns. We would expect to find larger improvements in this increased insulin sensitivity if magnesium is supplemented in a correct way meaning through transdermal and oral methods combined using liquid magnesium chloride (magnesium oil) as compared to the very inefficient oral solid forms commonly used.

Improved insulin sensitivity from magnesium replacement can markedly reduce triglyceride levels.[13]
[13] Yokota K, Kato M, Lister F, et al. Clinical efficacy of magnesium supplementation in patients with type 2 diabetes. J Am Coll Nutr. 2004 Oct;23(5):506S-9S.

Reduced triglyceride availability, in turn, reduces triglyceride-rich particles, such as very low-density lipoprotein (VLDL) and small low-density lipoprotein (small LDL), both of which are powerful contributors to heart disease. Magnesium supplementation can also raise levels of beneficial high-density lipoprotein (HDL).[14]
[14] Rasmussen HS, Aurup P, Goldstein K, et al. Influence of magnesium substitution therapy on blood lipid composition in patients with ischemic heart disease. A double-blind, placebo controlled study. Arch Intern Med. 1989 May;149(5):1050-3.

Insulin regulates intracellular magnesium levels via
activation of Na+/Mg2+ exchange. Insulin’s effect on Na/Mg
exchange may explain the low cellular magnesium levels
observed in vivo under hyperinsulinemic conditions.
[15] Am J Hypertens (2002) 15, 104A–104A; doi:S0895-7061(02)02558-X
P-207: Insulin regulates human erythrocyte Na+/Mg2+ exchange. Ana Ferreira1, Jose R. Romero1 and Alicia Rivera. Pathology, Harvard Medical School; Medicine, Harvard Medical School, Boston, MA, United States

Insulin is a hormone. And like many hormones, insulin is a protein.  Insulin is secreted by groups of cells within the pancreas called islet cells. Insulin is much more important and has many more functions then we realize. It regulates:
lifespan -  Lower insulin levels equate to a longer life.
blood sugar
blood lipids
excess nutrients (from glucose, carbs and calories) and converts them to fat
builds muscle
stores protein
magnesium levels in our body
calcium levels in the body
retains sodium levels
cell division
growth hormone
liver functions
sex hormones, estrogen, progesterone, testosterone
cholesterol in the body
fat in our body

Magnesium is a cofactor for multiple enzymes involved in carbohydrate metabolism.[16]
[16] Paolisso G, Scheen A, D’Onofrio F, Lefebvre P: Magnesium and glucose homeostasis. Diabetologia 33:511–514, 1990[Medline]

Adipocyte cells placed in low-magnesium media show reduction in insulin-stimulated glucose uptake.[17]
[17] Kandeel FR, Balon E, Scott S, Nadler JL: Magnesium deficiency and glucose metabolism in rat adipocytes. Metabolism 45:838–843, 1996[Medline]

Magnesium deficiency is associated with increased intracellular calcium levels, which may lead to insulin resistance. Low erythrocyte magnesium content increases membrane microviscosity, which may impair insulin interaction with its receptor.[18]
[18] Tongyai S, Rayssiguier Y, Motta C, Gueux E, Maurois P, Heaton FW: Mechanism of increased erythrocyte membrane fluidity during magnesium deficiency in weanling rats. Am J Physiol 257:C270–C276, 1989

Tyrosine kinase activity is decreased in muscle insulin receptors of rats fed a low-magnesium diet.[19]
[19] Suarez A, Pulido N, Casla A, Casanova B, Arrieta FJ, Rovira A: Impaired tyrosine-kinase activity of C

These findings indicate that magnesium deficiency directly affects insulin signaling.

When magnesium levels fall hypersecretion of adrenalin and insulin compensate. Their increased secretion help maintain the constancy of the levels in intracellular magnesium in the soft tissues. Plasma and intracellular magnesium concentrations are tightly regulated by insulin. In vitro and in vivo studies have demonstrated that insulin modulates the shift of magnesium from extracellular to intracellular space.

Dr. Ron Rosedale says that, “Insulin floating around in the blood causes plaque build-up. They didn’t know why, but we know that insulin causes endothelial proliferation. Every step of the way, insulin is causing cardiovascular disease. It fills the body with plaque, it constricts the arteries, it stimulates the sympathetic nervous system, it increases platelet adhesiveness and coaguability of the blood.”

Diabetic Neuropathy and transdermal magnesium
Magnesium and Diabetic Neuropathy
By Mark Sircus Ac., OMD

When we confront the fact that every 30 seconds a leg is lost because of diabetes somewhere in the world, there is much to get excited about in our safe and natural treatment for Diabetic Neuropathy.

Something is wrong with the way allopathic medicine is dealing with diabetes and that starts with its refusal to look honestly at what is causing the disease.

Magnesium is known to be necessary for nerve conduction; deficiency is known to cause peripheral neuropathy symptoms and studies suggest that a deficiency in magnesium may worsen blood glucose control in type 2 diabetes. Scientists believe that a deficiency of magnesium interrupts insulin secretion in the pancreas and increases insulin resistance in the body's tissues.

Magnesium deficiency played a role in the constriction of arteries and enhanced injury to the cellular tissues lining the blood vessels. Peripheral artery disease, or peripheral vascular disease, refers to diseases of the arteries and veins of the extremities, especially atherosclerosis with narrowing of the arteries. This opens the door to the development and progression of atherosclerosis and sets the stage for the development of neurological events such as strokes. These same conditions set the stage for the development of peripheral diabetic neuropathy.[i]

[i]Amighi J, Sabeti S, Schlager O, Mlekusch W, Exner M, Lalouschek W, Ahmadi R, Minar E, Schillinger M. Low serum magnesium predicts neurological events in patients with advanced atherosclerosis. Stroke. 2004 Jan; 35(1): 22-7. Epub 2003 Dec 04. Researchers conducted the study to see if magnesium levels were associated with stroke risk in patients with peripheral artery disease. The study authors followed 323 patients with symptomatic peripheral artery disease and intermittent claudication (www. age was 68 years) for 12 to 25 months. Thirty-five of the subjects (11%) developed neurologic events such as strokes. Subjects who had the lowest magnesium serum levels had triple the risk for stroke and other harmful neurologic events compared to the patients with the highest serum magnesium levels.

This entire scenario described here also sets the stage for the development of peripheral neuropathy even when diabetes is not present.

A recent analysis showed that people with higher dietary intakes of magnesium (through consumption of whole grains, nuts, and green leafy vegetables) had a decreased risk of type 2 diabetes.[ii]

Magnesium has potentially beneficial effects at several key steps of glucose and insulin metabolism. In animal studies, dietary magnesium supplementation can prevent fructose-induced insulin resistance and elevations of blood pressure in rats.

[iii] Total serum magnesium was reduced in the high-fructose group compared with control or high-fructose plus magnesium-supplemented groups. Blood pressure and fasting insulin levels were also lower in the magnesium-supplemented group. These results suggest that magnesium deficiency and not fructose ingestion per se leads to insulin insensitivity in skeletal muscle and changes in blood pressure. Dietary magnesium prevents fructose-induced insulin insensitivity in rats.Batan; Hypertension. 1994 Jun;23(6 Pt 2):1036-9.

The convergence of large drops in cellular magnesium, which offers protective coverage against chemical toxicity, with increasing poisoning of people’s blood streams with heavy metals like arsenic, mercury, and lead, as well as a literal host of other chemical toxins in the environment, are teaming up to disrupt normal cell physiological.

Eating junk food fits into an alarming picture for modern diets of highly processed foods translates into magnesium deficiencies, and processed food are also high in chemical preservatives, pesticides, and food additives that are harmful to health and put further strains on magnesium reserves in the body.

Magnesium deficiency is associated with insulin
resistance and increased platelet reactivity.

An abstract from Disorders of Magnesium Metabolism[iv] concludes, “Magnesium depletion is more common than previously thought. It seems to be especially prevalent in patients with diabetes mellitus. It is usually caused by losses from the kidney or gastrointestinal tract. A patient with magnesium depletion may present with neuromuscular symptoms, hypokalemia, hypocalcemia, or cardiovascular complication. Physicians should maintain a high index of suspicion for magnesium depletion in patients at high risk and should implement therapy early.”
[iv] Endocrinology & Metabolism Clinics of North America. 24(3):623-41, 1995 Sep.

A separate Gallup survey (in 1995) of 500 adults with diabetes
reported that 83 percent of those with diabetes are consuming
insufficient magnesium from food, with many by significant margins.[v]
[v] v57, Better Nutrition for Today's Living, March '95, p34.

Diabetic neuropathy and other complications of diabetes are made worse as a result of concurrent magnesium deficiency. Up to 80% of type 2 diabetics have a magnesium deficiency.[vi]
[vi] Carper, J. Mighty Magnesium. USA Weekend. 2002 Aug 30-Sept 1.

Children labeled "pre diabetic" (now 41 million) are in great need of magnesium, which has been linked to preventing the development of type 2 diabetes.[vii]
[vii]Magnesium Deficiency Linked to Type 2 Diabetes

Studies conducted at Harvard University indicate that people who have high levels of magnesium in their blood are less likely to develop type 2 diabetes or insulin resistance than those with lower levels. Studies in Mexico have also found an alleviation of diabetes symptoms in patients who took dietary supplements containing magnesium.
Original Source:,31268.asp 

In a series of papers, Dr. L. M. Resnick has shown in the test tube that an increase in glucose in the fluid leads to the release and/or displacement of magnesium from the red blood cells, thus in the body hyperglycemia, high blood sugar, will cause a total body magnesium deficiency.[viii]
[viii] Diabetologia 36(8):767-70, 1993

A more recent study shows us that “Serum magnesium depletion is present and shows a strong relationship with foot ulcers in subjects with type 2 diabetes and foot ulcers, a relationship not previously reported.”

Hypomagnesemia is associated with the development of neuropathy and abnormal platelet activity, both of which are risk factors for the progression of ulcers of the feet.[ix]

[ix] Low serum magnesium levels and foot ulcers in subjects with type 2 diabetes. Rodriguez-Moran M, Guerrero-Romero F. Arch Med Res. 2001 Jul-Aug;32(4):300-3.

Lower serum magnesium levels are associated
with more rapid decline of renal function.

Thus we can expect to find that magnesium can be used to prevent and treat both diabetes and the complications that come from it including severe peripheral neuropathy.

Dr. S. E. Browne makes a strong case for intravenous magnesium treatment of arterial disease and has used magnesium sulphate in his general practice for over three decades. “Magnesium sulphate (MgSO4) in a 50% solution was injected initially intramuscularly and later intravenously into patients with peripheral vascular disease (including gangrene, claudication, leg ulcers, and thrombophlebitis), angina, acute myocardial infarction (AMI), non-haemorrhagic cerebral vascular disease and congestive cardiac failure. A powerful vasodilator effect with marked flushing was noted after intravenous (IV) injection of 4-12 mmol of magnesium (Mg) and excellent therapeutic results were noted in all forms of arterial disease.”[x]
[x] S. E. BROWNE. The Case for Intravenous Magnesium Treatment of Arterial Disease in General Practice. Journal of Nutritional Medicine (1994) 4, 169-177

Dr. Herbert Mansmann Jr., Director of the Magnesium Research Lab,[xi] who is a diabetic with congenital magnesium deficiency and severe peripheral neuropathy, shares that he was able to reverse the neuropathy and nerve degeneration with a year of using oral magnesium preparations at very high doses
[xi] Herbert C. Mansmann Jr. MD. Honorary Professor of Pediatrics. P.O. Box 791, Rangeley, ME 04970 Associate Professor of Medicine (1968-03) Director of the Magnesium Research. Laboratory (1989-03) Thomas Jefferson University 

Dr. Mansmann concludes, “I have had diabetic neuropathy for over 10 years. The most significant symptom is my neuropathic pain of burning feet, called erythromelalgia. It is my belief that every one with diabetes should be taking Mg supplementation to the point of one’s Maximum Tolerated Dose, which is until one has soft-semi, formed stools. In addition, anyone with neuropathy, without a known cause, must be adequately evaluated for diabetes and especially those with poorly, slowly, healing foot sores of any kind. Since the use of Mg is safe I see no reason that this should not be “the standard of care”.[xiii]

Prolonged use of Magnesium will prevent
chronic complications from diabetes.[xiv]

[xiv] The effect of magnesium supplementation in increasing doses on the control of type 2 diabetes. Diabetes Care. 1998 May;21(5):682-6.

Poorly controlled diabetes increases loss of magnesium in urine.

It would be prudent for physicians who treat diabetic patients to consider magnesium deficiency as a contributing factor in many diabetic complications and as a main factor in exacerbation of the disease itself.

Recent research from many sources suggests that magnesium for the treatment of diabetes should be paramount in physicians’ minds. The most recent example, after only 8 weeks of oral magnesium, thermal hyperalgesia was normalized and plasma magnesium and glucose levels were restored towards normal in rats.[xvi]
[xvi] Hasanein P. et al. Oral magnesium administration prevents thermal hyperalgesia induced by diabetes in rats. Department of Biology, Bu-Ali Sina University, Hamadan, Iran. Diabetes Res Clin Pract. 2006 Jan 14

Repletion of the deficiency with transdermal magnesium chloride mineral therapy is the ideal way of administering magnesium in medically therapeutic doses.

 Such treatments will, in all likelihood, help avoid or ameliorate such complications as diabetic peripheral neuropathy, arrhythmias, hypertension, and sudden cardiac death and will even improve the course of the diabetic condition in general.[xviii]
[xviii] Long term magnesium supplementation influences favourably the natural evolution of neuropathy in Mg-depleted type 1 diabetic patients (T1dm); De Leeuw et al; Magnes Res. 2004 Jun; 17(2):109-14 

Statins are also known to cause peripheral neuropathy with long term use.

[xxi] Statins and peripheral neuropathy; U. Jeppesen , D. Gaist , T. Smith S. H. Sindrup European Journal of Clinical Pharmacology Volume 54, Number 11;835 - 838 January 1999
[xxii] The Peripheral Neuropathy Caused by Statins Petition to Pharmaceutical Researchers and Manufacturers of America and companies listed was created by DrugIntel Statin Users with Neuropathy and written by John Lehmann. The petition will be presented to the Pharmaceutical Researchers and Manufactuers Association and to the Medical Affairs Departments of the companies listed, as well as any additional companies that may be identified as relevant over time. 
[xxiii] Statins and risk of polyneuropathy
D Gaist, MD PhD, U Jeppesen, M Andersen, LAG Neurology 2002;58:1333-1337 © 2002 American Academy of Neurology
Statins and risk of polyneuropathy

During a stroke or heart attack it would be cruel, medically incompetent and life threatening to not use magnesium chloride or magnesium sulfate immediately. The same kind of treatment that saves lives in dramatic life threatening situations is urgently needed in the treatment of diabetes and diabetic neuropathy.
Rapid increase of magnesium stores are necessary
in some cases and may be lifesaving for diabetics
as they are for other patients in emergency rooms.

The safety profile of magnesium chloride is extraordinary compared to today’s pharmaceutical drugs. It is only with severe renal insufficiency that problems have been observed with magnesium treatments. The elderly are at risk of magnesium toxicity only because of possible decreased renal function so caution is necessary.

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