Magnesium Wasting Disease

Dr.  Herbert C. Mansmann Jr. was a magnesium researcher who found an answer to his diabetic neuropathy treating it with approximately 20 grams of magnesium a day. One of the reasons he needed such high doses was that he had extensive magnesium wasting disease. He has passed on but has left us with a legacy of extensive magnesium research. He tells us:

Many people already know that when you take diuretics (Water Pills) you need to take a potassium supplement since potassium is lost through the urine. This is also true for Mg. There are certain medications and lifestyle behaviors that can cause excessive Mg loss in the urine. If you are on any of these medications or display any of the lifestyle behaviors you will need to take a Mg supplement to accommodate the loss and prevent hypomagnesemia. There are also specific diseases that can cause Mg loss in the urine and are listed below.

Drugs

Aminoglycoside Antibiotics

amikacin sulfate (Amikin)

gentamicin sulfate (Cidomicin, Garamycin, Gentamicin sulfate, ADD-Vantage, Jenamicin)

neomycin sulfate (Mycifradin, Neo-fradin, Neosulf, Neo-Tabs)

streptomycin sulfate

tobramycin sulfate (Nebcin)

Cisplantin (Platamine, Platinol, Platinol AQ)

Pentamidine isethionate (NebuPent, Pentacarinat, Pentam 300, Pneumopent)

Foscarnet sodium (Foscavir)

Diuretics

Furosemide (Lasix, Apo-Furosemide, Myrosemide, NovoSemide, Urex, Urex-M, Uritol)

Butmetanide (Bumex, Burinex)

Chlorthalidone (Apo-Chlorthalidone, Hygroton, Novo-Thalidone, Thalitone, Uridon)

ethacrynate sodium (Sodium Edecrin)

hydrochlorothiazide (Apo-Hydro, Aquazide-H, Dichlotride, Diuchlor H, Esidrix, Ezide, Hydro-D, Dydro-Diuril, Mictrin, Codema, Novo-Hydrazide, Oretic, Urozide)

indapamide (Lozide, Lozol, Natrilix)

metolazone (Diulo, Mykrox, Zaroxolyn)

torsemide (Demadex)

urea carbamide (Ureaphil)

acetazolamide (Diamox, Acetazolam, Dazamide, AK-Zol)

mannitol (Osmitrol)

Macrolide Anti-Infectives

azithromycin (Zithromax)

clarithromycin (Biaxin)

dirithromycin (Dynabac)

erythromycin (E-Mycin, Erybid, EES, Erythrocin)

tacrolimus (Prograf)

Cyclosporine (Neoral, Sandimmun, Sandimmune)

Potassium phosphate

Calcium Supplements

Vitamin D Supplements

Other Causes

Diabetic Ketoacidosis

Hyperaldosteronism

Hyperglycemia

Refeeding after starvation

Alcohol (Acute ingestion and/or due to transitory hypoparathyroidism

Hyperparathyroidism

Glomerulonephritis

Pyelonephritis

Renal Tubular Acidosis

Bartters syndrome

Gitelmans syndrome

Cirrhosis

Pancreatitis

Burn Patients

Patients receiving sodium rich IV fluids

Thyrotoxicosis

Citrate preservative in blood products

Congenital Magnesium Losing Nephropathy

Urea Osmotic Diuresis

Healthy kidneys are able to limit urinary excretion of magnesium to compensate for low dietary intake. However, excessive loss of magnesium in urine can be a side effect of some medications and can also occur in cases of poorly-controlled diabetes and alcohol abuse

The kidneys play a major role in magnesium homeostasis and in the maintenance of plasma magnesium concentration. Approximately 80% of plasma magnesium is ultrafiltrable. Under normal circumstances, approximately 95% of filtered magnesium is reabsorbed by various parts of the nephron. The plasma magnesium concentration is kept within narrow limits. Extracellular magnesium is in equilibrium with that in the bone, kidneys, intestine, and other soft tissues.

Elimination of magnesium is predominantly renal; the threshold for urinary excretion nears the reference range of serum concentration. Thus, when serum levels are greater than 2.5 mEq/L, magnesium excretion dramatically increases. Conversely, the kidney retains a strong capacity to reabsorb magnesium, and the main site for reabsorption is the thick ascending loop of Henle.

Chronic metabolic acidosis results in renal magnesium wasting, whereas chronic metabolic alkalosis is known to exert the reverse effects. Chronic metabolic acidosis decreases renal TRPM6 expression in DCT, increased magnesium excretion, and decreased serum magnesium concentration, whereas chronic metabolic alkalosis results in the exact opposite effects.

In contrast to other ions, magnesium is treated differently in 2 major respects: (1) no hormonal modulation of urinary magnesium excretion occurs and (2) bone, the principal reservoir of magnesium, does not readily exchange with circulating magnesium in the extracellular fluid space. This inability to mobilize magnesium stores means that in states of negative magnesium balance, initial losses come from the extracellular space; equilibrium with bone stores does not begin for several weeks.

Because urine can be seen as a purified derivative of the blood made by the kidneys it is something we need to pay attention to in medicine for it tells us quite a bit of what is going on in the body. The kidneys are constantly dumping an incredible array of critically important nutrients, enzymes, hormones, natural antibodies and immune defense agents. With constant urination comes a problem few clinicians look on, the problem of nutrient loss through the kidneys.

In 1975, one of the founders of Miles Laboratories, Dr. A.H. Free, published his book Urinalysis in Clinical Laboratory Practice, in which he remarked that not only is urine a sterile body compound but that "it is now recognized that urine contains thousands of compounds, and as new, more sensitive analytical tools evolve, it is quite certain that new constituents of urine will be recognized."

Among the urine constituents mentioned by Dr. Free’s:

Alanine, total ….. 38 mg/day

Arginine, total ….. 32 mg/day

Ascorbic acid ….. 30 mg/day

Allantoin ….. 12 mg/day

Amino acids, total ….. 2.1 g/day

Bicarbonate ….. 140 mg/day

Biotin ….. 35 mg/day

Calcium ….. 23 mg/day

Creatinine ….. 1.4 mg/day

Cystine ….. 120 mg/day

Dopamine ….. 0.40 mg/day

Epinephrine ….. 0.01 mg/day

Folic acid ….. 4 mg/day

Glucose ….. 100 mg/day

Glutamic acid ….. 308 mg/day

Glycine ….. 455 mg/day

Inositol ….. 14 mg/day

Iodine ….. 0.25 mg/day

Iron ….. 0.5 mg/day

Lysine, total ….. 56 mg/day

Magnesium ….. 100 mg/day

Manganese ….. 0.5 mg/day

Methionine, total ….. 10 mg/day

Nitrogen, total ….. 15 g/day

Ornithine ….. 10 mg/day

Pantothenic acid ….. 3 mg/day

Phenylalanine ….. 21 mg/day

Phosphorus, organic ….. 9 mg/day

Potassium ….. 2.5 mg/day

Proteins, total ….. 5 mg/day

Riboflavin ….. 0.9 mg/day

Tryptophan, total ….. 28 mg/day

Tyrosine, total ….. 50 mg/day

Urea ….. 24.5 mg/day

Vitamin B6 ….. 100 mg/day

Vitamin B12 ….. 0.03 mg/day

Zinc ….. 1.4 mg/day

It’s difficult for most people to understand why our bodies excrete elements that are so obviously valuable to human health and well-being. As blood moves through the circulatory system, it flows through the kidneys at a rate of about 1200 ml of blood per minute. Inside the kidneys, the blood is continuously filtered through a huge system of minute tubules called nephron which sift out excess water, vitamins, minerals, enzymes, salts, and hundreds of other elements including vital antibodies, urea and uric acid.

Magnesium is well excreted by the kidneys and so long as the kidneys are functioning well, then magnesium does not accumulate in the blood.

Dr. Sarah Myhill

The kidneys excrete a portion of urine as a way of removing certain key elements in your blood that are simply not needed at a specific point in time. For instance, you’ve just been out jogging. You come home and have one or two big glasses of water to drink. Now at this point you’ve probably taken in more water than your body actually needs. But not to worry — your kidneys will balance the amount of water delivered into your bloodstream by your copious water drinking and through the urine will excrete whatever amount of water from the blood that isn’t needed at the time.

Even water, which is a life-sustaining element the body cannot do without is excreted by the body. There are times when there’s too much water in our systems and we need to dump some. It’s a physiological fact that in order for us to function normally, the amounts or concentrations of every element in our blood must be carefully and strictly controlled and this is done by the kidneys. Too much water in the blood is fatal. Too much salt in the blood is deadly. As wonderful a nutrient as vitamin C is, too high a concentration of it or any nutrient could kill you. This is why the kidneys excrete valuable elements from the body — too much of any good thing isn’t good for your health.

Our kidneys aren’t doing damage to our bodies by getting rid of particular excess nutrients; they’re just simply excreting the precise amount not presently needed by our bodies at a given time. That’s what happens when everything is going normally. What happens to such a delicate mechanism as the kidney’s filtering system when the kidneys themselves move in the direction of pathology? One great problem is magnesium wasting disease.  This is when the kidneys dump something that is not being replaced. Primary renal disorders cause hypomagnesemia by decreased tubular reabsorption of magnesium by the damaged kidneys. This condition occurs in the diuretic phase of acute tubular necrosis, postobstructive diuresis, and renal tubular acidosis.

Bartter’s Syndrome is a kidney problem whereby electrolytes, including magnesium, are lost in the urine. Effectively these patients have a magnesium wasting disorder and clinically this is what I see in many patients with chronic fatigue syndrome. It seems that however much magnesium they take they cannot correct their red cell magnesium levels unless they have regular injections or nebulizer and sometimes even this does not work.

Fluoride (in vitamins or water) interferes with magnesium metabolism in the body according to Dr. John R. Marier, of the Division of  Biological Sciences at the Canadian National Research Council, Ottawa, in a paper published in The Proceedings of the Finnish Dental Society, vol. 76, 1980, pages 82-102.  This is significant because fluoride toxicity is increased when magnesium levels are low.  Magnesium deficiency is widespread in the U.S., especially among children and teenagers, reaching the 99th percentile among young women.

The total body magnesium level of an average adult is 25 g or 1000 mmol. Approximately 60% is present in bone, 20% in muscle, and 20% in soft tissue and the liver. Approximately 99% of the total body magnesium is intracellular, with only 1% in the extracellular space; 80% of plasma magnesium is ionized or complexed to filterable ions (eg, oxalate, phosphate, citrate) and is available for glomerular filtration, while 20% is protein-bound. Normal plasma magnesium concentration is 1.7-2.1 mg/dL (0.7-0.9 mmol or 1.4-1.7 mEq/L).

Expansion of the extracellular fluid volume increases

the excretion of calcium, sodium, and magnesium.

Fatal hypermagnesemia has resulted from the administration of enemas containing magnesium to patients with renal failure. Hypermagnesemia is rarely observed in individuals with a glomerular filtration rate (GFR) that is within reference range. In patients with acute renal failure and hypermagnesemia, levels usually remain less than 4 mEq/L.