Hypomagnesia, Causes, Symptoms, Treatment

Hypomagnesia
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Hypomagnesia/Magnesium deficiency (not to be confused with hypomagnesemia) refers to inadequate intake of dietary magnesium or impaired absorption of magnesium, which can result in numerous symptoms and diseases. It is generally corrected by an increase of magnesium in diet, oral supplements, and in severe cases, intravenous supplementation.

‘Normal’ Serum Magnesium Levels

0.75–0.95 mmol/L

  • A serum magnesium <0.82 mmol/L (2.0 mg/dL) with a 24-hour urinary magnesium excretion of 40–80 mg/day is highly suggestive of magnesium deficiency.
  • One group of experts has recommended magnesium supplementation in subjects experiencing symptoms that reflect magnesium deficiency if the serum level is below 0.9 mmol/L, with levels less than 0.8 mmol/L necessitating magnesium.
  • Serum magnesium levels above 0.95 mmol/L may indicate hypermagnesaemia.

Magnesium requirements based on older balance studies

Age Requirement
Infants 150–200 mg/day
Children 200–250 mg/day
Adults 250–300 mg/day
Lactating women 400 mg/day

Causes of Magnesium Deficiency

Magnesium: Deficiency signs and symptoms [].

  • General  – Anxiety, lethargy, weakness, agitation, depression, dysmenorrhea, hyperactivity, headache, irritability, dysacusis, low stress tolerance, loss of appetite, nausea, sleep disorders, impaired athletic performance.
  • Musculature – Muscle spasm, cramps in the soles of the feet, leg cramps, facial muscles, masticatory muscles, and calves, carpopedal spasm, back aches, neck pain, urinary spasms, magnesium deficiency tetany.
  • Nerves/CN – Nervousness, increased sensitivity of NMDA receptors to excitatory neurotransmitters, migraine, depression, nystagmus, paraesthesia, poor memory, seizures, tremor, vertigo.
  • Gastrointestinal tract – Constipation.
  • Cardiovascular syste – Risk of arrhythmias, supraventricular or ventricular arrhythmias, hypertension, coronary spasm, decreased myocardial pump function, digitalis sensitivity, Torsade de pointes, death from heart disease.
  • Electrolytes – Hypokalaemia, hypocalcaemia, retention of sodium.
  • Metabolism – Dyslipoproteinemia (increased blood triglycerides and cholesterol), decreased glucose tolerance, insulin resistance, increased risk of metabolic syndrome, disturbances of bone and vitamin D metabolism, resistance to PTH, low circulating levels of PTH, resistance to vitamin D, low circulating levels of 25(OH)D, recurrence of calcium oxalate calculi.
  • Miscellaneous – Asthma, chronic fatigue syndrome, osteoporosis, hypertension, altered glucose homeostasis.
  • Pregnancy -m Pregnancy complications (e.g., miscarriage, premature labor, eclampsia).

  • Acetaminophen toxicity.
  • Alcoholism.
  • Aluminium (environmental and dietary).
  • Aldosteronism.
  • Alcohol.
  • Ageing  (hypochlorhydria, ie, decreased acid in the stomach).
  • Antacid (including ranitidine and famotidine).
  • Bariatric surgery (small intestinal bypass surgery).
  • Calcium supplements (or a high calcium to magnesium diet).
  • Caffeine.
  • Cancer.
  • Coeliac disease.
  • Colon removal
  • Chronic stress
  • Cisplatin
  • Crohn’s disease.
  • Ciclosporin.
  • Type 1 and type 2 diabetes (uncontrolled glucose levels).
  • Diarrhoea.
  • Diet high in fat or sugar.
  • Digoxin
  • Diuretics non-potassium-sparing diuretics (thiazide and loop diuretics).
  • Excessive ingestion of poorly absorbable magnesium (such as magnesium oxide), leading to diarrhoea and magnesium loss.
  • Emotional and/or psychological stress (overactivation of the sympathetic nervous system).
  • Enzymatic dysfunction (impaired magnesium distribution).
  • Oestrogen therapy (shifts magnesium to soft and hard tissues lowering serum levels).
  • Excessive or prolonged lactation
  • Excessive menstruation.
  • Fasting (or low magnesium intake).
  • Foscarnet
  • Gentamicin and tobramycin.
  • Hyperparathyroidism and hypoparathyroidism.
  • Hyperthyroidism.
  • Kidney diseases (glomerulonephritis, pyelonephritis, hydronephrosis, nephrosclerosis and renal tubular acidosis).
  • Heart failure.
  • Haemodialysis.
  • High phosphorus in the diet (soda, inorganic phosphates contained in many inactive ingredients in processed foods).
  • Hyperinsulinaemia (and insulin therapy).
  • Insulin resistance (intracellular magnesium depletion).
  • Laxatives.
  • Low salt intake.
  • Low selenium intake.
  • Gastrointestinal disorders—malabsorption syndromes (coeliac disease, non-tropical sprue, bowel resection, Crohn’s disease, ulcerative colitis, steatorrhoea), prolonged diarrhoea or vomiting.
  • Liver disease (acute or chronic liver disease, including cirrhosis).
  • Metabolic acidosis (latent or clinical).
  • Pancreatitis(acute and chronic).
  • Parathyroidectomy.
  • Pentamidine.
  • Peritoneal dialysis.
  • Porphyria with inappropriate secretion of antidiuretic hormone.
  • Pregnancy.
  • Proton pump inhibitors.
  • Strenuous exercise.
  • Tacrolimus.
  • Vitamin B6 (pyridoxine) deficiency.
  • Vitamin D excess or deficienc (chronic kidney disease and liver disease can prevent the activation of vitamin D).

Potential clinical signs of magnesium deficiency

Less severe signs

  • Aggression.
  • Anxiety.
  • Ataxia.
  • Chvostek sign (twitching of the facial muscles in response to tapping over the area of the facial nerve).
  • Confusion.
  • Cramps (spontaneous carpopedal spasm or painful cramps of the muscles in your hands and feet).
  • Disorientation.
  • Fasciculations (‘a brief, spontaneous contraction affecting a small number of muscle fibres, often causing a flicker of movement under the skin. It can be a symptom of disease of the motor neurons)’.
  • Hyper-reflexia.
  • Irritability.
  • Muscular weakness.
  • Neuromuscular irritability.
  • Pain or hyperalgesia (decreases the nociceptive threshold).
  • Photosensitivity.
  • Spasticity.
  • Tetany (involuntary muscle spasms).
  • Tinnitus (ringing in the ears).
  • Tremors.
  • Trousseau sign.
  • Vertigo.
  • Vitamin D resistance.

Severe signs

  • Arrhythmias (caused by over-excitation of the heart due to enhanced depolarisation susceptibility, especially torsades de pointes or ventricular tachycardia with a prolonged QT interval).
  • Calcifications (soft tissue).
  • Cataracts.
  • Convulsions.
  • Coronary artery disease.
  • Depressed immune response.
  • Depression.
  • Hearing loss.
  • Heart failure.
  • Hypertension.
  • Migraines/headaches.
  • Mitral valve prolapse.
  • Osteoporosis.
  • Parathyroid hormone resistance and impaired parathyroid hormone release/function.
  • Psychotic behavior.
  • Seizures (overexcitation of the nervous system (nerve cells), which are more likely to fire due to a reduced electric potential difference between the outer and inner surfaces of the membrane).
  • Sudden cardiac death.
  • Tachycardia.

Lab and ECG signs of magnesium deficiency

  • Hypomagnesaemia.
  • Hypocalcemia.
  • Hypokalaemia.
  • Prolonged QTc.
  • ST segment depression (in animals).

Measurements to diagnose magnesium deficiency (best to worst)

Reliable methods

  • Retention of magnesium load (intravenous or oral) after its administration is likely the best indicator of magnesium deficiency. However, the retention test assumes normal kidney function for intravenous magnesium loads and normal gastrointestinal and renal function for oral load tests and is cumbersome and invasive.
  • Mononuclear cell magnesium and muscle magnesium content (muscle biopsy).

Less reliable methods

  • Hair magnesium content (one study concluded: ‘magnesium hair concentration may be an easier, cheaper and less invasive indicator of body magnesium depletion’).
  • Bone magnesium (magnesium depletion in the coccyx may indicate magnesium deficiency).
  • The ratio of ionized magnesium to total magnesium (serum or plasma).
  • Ionized magnesium levels (serum or erythrocytes, ionized magnesium is the physiologically active magnesium not bound to proteins). However, this biomarker is controversial and not always available in clinical labs and hard to measure reliably.
  • Lymphocyte magnesium.
  • Urinary or fecal magnesium excretion (low or high levels may indicate deficiency).
  • Urinary fractional magnesium excretion >4% (some authors have suggested >2% in those with normal kidney function).
  • Total erythrocyte magnesium levels (magnesium deficiency has been suggested when erythrocyte magnesium levels are <1.65 mmol/L).
  • Total serum magnesium levels.
  • It is important to note that choosing only one of the aforementioned methods of measuring magnesium deficiency is not appropriate for diagnosing magnesium deficiency. In general, either symptom of magnesium deficiency must accompany the more reliable methods to diagnose magnesium deficiency (eg, intravenous/oral magnesium load, mononuclear cell or muscle), or two or more of the reliable measurements (eg, intravenous/oral magnesium load, mononuclear cell or muscle) should be used in supporting a diagnosis of magnesium deficiency.

Causes of hypermagnesaemia

  • Oversupplementation (mainly from magnesium-containing antacids).
  • Kidney damage.
  • Inflammation and cellular injury (significant increases in total and ionized magnesium in animals during endotoxin challenge).

Magnesium Deficiency & it Basic Role in Human Body

It is an antidote to stress, the most powerful relaxation mineral available, and it can help improve your sleep.

I find it very funny that more doctors aren’t clued in to the benefits of magnesium, because we use it all the time in conventional medicine. But we never stop to think about why or how important it is to our general health or why it helps our bodies function better.

I remember using magnesium when I worked in the emergency room. It was a critical “medication” on the crash cart. If someone was dying of a life-threatening arrhythmia (or irregular heart beat), we used intravenous magnesium. If someone was constipated or needed to prepare for colonoscopy, we gave them milk of magnesia or a green bottle of liquid magnesium citrate, which emptied their bowels.

Magnesium Deficiency
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If pregnant women came in with pre-term labor, or high blood pressure of pregnancy (pre-eclampsia) or seizures, we gave them continuous high doses of intravenous magnesium.

But you don’t have to be in the hospital to benefit from getting more magnesium. You can start taking regular magnesium supplementation today and see results.

The Relaxation Mineral 

Think of magnesium as the relaxation mineral. Anything that is tight, irritable, crampy, and stiff — whether it is a body part or an even a mood — is a sign of magnesium deficiency.

This critical mineral is actually responsible for over 300 enzyme reactions and is found in all of your tissues — but mainly in your bones, muscles, and brain. You must have it for your cells to make energy, for many different chemical pumps to work, to stabilize membranes, and to help muscles relax.

When was the last time you had a good dose of seaweed, nuts, greens, and beans? If you are like most Americans, your nut consumption mostly comes from peanut butter.

That is why the list of conditions that are found related to magnesium deficiency is so long. In fact, there are over 3,500 medical references on magnesium deficiency!

Even so, this mineral is mostly ignored because it is not a drug, even though it is MORE powerful than drugs in many cases. That’s why we use it in the hospital for life-threatening and emergency situations like seizures and heart failure.

Magnesium Deficiency Symptoms/Hypomagnesia

Magnesium deficiency has even has been linked to inflammation in the body and higher CRP levels.

  • In our society, magnesium deficiency is a huge problem. By conservative standards of measurement (blood, or serum, magnesium levels), 65 percent of people admitted to the intensive care unit — and about 15 percent of the general population — have a magnesium deficiency.
  • But this seriously underestimates the problem, because a serum magnesium level is the LEAST sensitive way to detect a drop in your total body magnesium level. So rates of magnesium deficiency could be even higher!
  • The reason we are so deficient is simple: Many of us eat a diet that contains practically no magnesium — a highly-processed, refined diet that is based mostly on white flour, meat, and dairy (all of which have no magnesium).
  • When was the last time you had a good dose of sea vegetables (seaweed), nuts, greens, and beans? If you are like most Americans, your nut consumption mostly comes from peanut butter, and mostly in chocolate peanut butter cups.
  • Much of modern life conspires to help us lose what little magnesium we do get in our diet. Magnesium levels are decreased by excess alcohol, salt, coffee, phosphoric acid in colas, profuse sweating, prolonged or intense stress, chronic diarrhea, excessive menstruation, diuretics (water pills), antibiotics and other drugs, and some intestinal parasites. In fact, in one study in Kosovo, people under chronic war stress lost large amounts of magnesium in their urine.
  • This is all further complicated by the fact that magnesium is often poorly absorbed and easily lost from our bodies. To properly absorb magnesium we need a lot of it in our diet, plus enough vitamin B6, vitamin D, and selenium to get the job done.
  • A recent scientific review of magnesium concluded, “It is highly regrettable that the deficiency of such inexpensive, low-toxicity nutrient results in diseases that cause incalculable suffering and expense throughout the world.” (ii) I couldn’t’ have said it better myself.
  • It is difficult to measure and hard to study, but magnesium deficiency accounts for untold suffering — and is simple to correct. So if you suffer from any of the symptoms I mentioned or have any of the diseases I noted, don’t worry — it is an easy fix!! Here’s how.
  • Magnesium deficiency can be harmful! Low magnesium levels can cause fatigue, seizures, high blood pressure, blood clots, muscle cramps and so on.
  • It’s estimated that 80 percent of Americans have a magnesium deficiency. And this is not a good thing since this mineral affects every organ in the body.
  • According to the Institute of medicine, adult men should consume 400 –
  • 420 mg of magnesium while women should aim for 310 – 360 mg per day. Now, the foods below can help get the recommended amount of magnesium without supplementation.

Magnesium Rich Food to Improve Your Overall Health

Functions of magnesium (selection) [,,,,].

  • Magnesium is involved in more than 300 essential metabolic reactions (e.g., all Adenosine Triphosphate (ATP)-dependent reactions).
Energy production (→ ATP production)
  • Breakdown and energetic utilization of carbohydrates, proteins and fats in intermediate metabolism (e.g., glycolysis, respiratory chain phosphorylation). ATP exists primarily as a complex with magnesium (MgATP).
Enzyme activation (examples)
  • Mitochondrial ATP synthase, Na+/K+-ATPase, Hexokinase, Creatine kinase, Adenylate cyclase, Phosphofructokinase, tyrosine kinase activity of the insulin receptor.
Calcium antagonist/NMDA-receptor antagonist
  • Control of calcium influx at the cell membrane (course of contractions, regulation of vascular muscle tone): muscle contraction/relaxation, neurotransmitter release, action potential conduction in nodal tissue, neuromuscular impulse conduction (inhibition of calcium-dependent acetylcholine release at the motor end plate), maintenance and stabilization of membrane physiology, muscle contraction.
Cardiovascular system
  • Economization of cardiac pump function, regulation of potassium movement in myocardial cells, protection against stress, vasodilation of the coronary and peripheral arteries, reduction of platelet aggregation.
Membrane function
  • Transmembrane electrolyte flux, active transport of potassium and calcium across cell membranes, regulation of cell adhesion and cell migration.
Structural roles
  • Component of mineralized bone (structure, microarchitecture), multiple enzyme complexes, mitochondria, proteins, polyribosomes, and nucleic acids.
Nutrient metabolism
  • Metabolic activation and the utilisation of vitamin D, B-vitamins (e.g., thiamine) and glutathione.

Magnesium Deficiency

  • Okra –  One cup of okra has 70 mg of magnesium – approx. 15 percent of the recommended daily intake. Avoid fried okra, boil or roast it.
  • Dark chocolate – A bar of chocolate has more than half of the daily recommended magnesium.
  • Pumpkin – A cup of chopped pumpkin has 60 mg of magnesium. This food also other numerous benefits so eat it as often as possible.
  • Brown rice – A cup of brown rice supplies about 20 percent of recommended magnesium.
  • Avocado – This alkaline food is a great magnesium source. One medium-size avocado has about 15 percent of the magnesium you need in a day.
  • Almonds – One ounce of this healthy nut has approx. 20 percent of magnesium you need.
  • Beet greens – Beet greens may not be popular, but they have lots of magnesium. One cup has 100 mg of magnesium.
  • Spinach – A cup of spinach has 150 mg of magnesium. This is definitely one of the best sources of this mineral.
  • Squash – This pumpkin-like will give lots of magnesium. One cup has about 40 mg.
  • Broccoli – If you’ve never liked broccoli, its magnesium content might change your mind. A cup has 33 mg.
  • Figs – 4 cups of dried figs can give you all the magnesium you need in a day.
  • Cashew nuts – An ounce of cashew nuts has about 20 percent of the magnesium you need.
  • Bananas – Bananas may be known for being potassium-rich, but they also contain some magnesium.
  • Pumpkin seeds – Pumpkin and squash seeds contain about 19 percent of recommended magnesium per ounce.
  • Lentils – A cup of lentils will give you 18 percent of recommended magnesium.
  • Cucumbers – A cup of cucumbers has about 40 mg of magnesium.
  • Peas – You can get 70 mg of magnesium from a cup of peas.

Magnesium and drug interactions. 

Medications that reduce magnesium levels:
(i) H2 blockers: for example, cimetidine and nizatidine
(ii) Proton pump inhibitors: for example, esomeprazole, omeprazole, and pantoprazole (FDA WARNING: supplementing magnesium will not correct deficiency; you must stop the drug)
(iii) Antacids: aluminum and magnesium hydroxide and sodium bicarbonate
(iv) Antibiotics: for example, amoxicillin, azithromycin, doxycycline, minocycline, levofloxacin, ciprofloxacin, cephalexin,
sulfamethoxazole and trimethoprim, and tetracycline
(v) Antihistamines: for example, astemizole and terfenadine
(vi) Antivirals: for example, delavirdine, lamivudine, and zidovudine
(vii) Antiepileptic medications: phenytoin and phenobarbital
(viii) Blood pressure drugs: hydralazine and combination of ACE inhibitors with HCTZ (enalapril and HCTZ)
(ix) Diuretics: for example, furosemide, ethacrynic acid, chlorothiazide, chlorthalidone, metolazone, and indapamide
(x) Cardiac glycoside: digoxin
(xi) Cardiac drugs: sotalol, amiodarone, bretylium, and quinidine
(xii) CNS stimulants: methylphenidate
(xiii) Cholesterol agents: cholestyramine and colestipol
(xiv) Corticosteroids: betamethasone, dexamethasone, hydrocortisone, prednisone, and triamcinolone
(xv) Inhaled corticosteroids: fluticasone, flunisolide, and triamcinolone
(xvi) Estrogens: DES, estradiol, estring, and estrogen-containing drugs: HRT and BCP
(xvii) Immunosuppressants: cyclosporine and tacrolimus
(xviii) Nonsteroidal aromatase inhibitors for breast cancer: anastrozole
(xix) Osteoporosis: raloxifene
(a) On the other hand, magnesium decreases bisphosphonate absorption
(xx) SERMs (selective estrogen receptor modulators): raloxifene, tamoxifen, and toremifene
(xxi) Sulfonamides: antibiotics and some diabetic medications
(xxii) Nutraceuticals: for example, high-dose calcium, high-dose vitamin D, and caffeine
Medications that may increase serum magnesium:
(i) Lithium carbonate
(ii) Antidepressants: for example, sertraline and amitriptyline
(iii) Potassium sparing diuretics: amiloride and spironolactone reduce magnesium excretion

References

Hypomagnesia

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