Lab Diagnosis of Magnesium Deficiency

by Herbert C. Mansmann, Jr. M.D.

The definition of magnesium deficiency (MgD) is “a reduction in the total body Mg content” (Welt 1965) (Elin 1988). This includes any test for Mg content that is decrease below the lowest normal reference level in any of the laboratory methods of measuring Mg regardless of the body sample studied. For years the medical profession has recognized that serum magnesium (sMg) less than 1.7mg/dL (1.32mEq/L or 0.7mmol/L) was diagnostic of MgD, a serious medical problem.

The current data shows that the sMg level only reflexes the tip of the iceberg of clinical MgD, and the loss of intracellular Mg content is equally important. The serum contains only 0.3% of the body’s total magnesium. More than half of the total content is in bones and nearly half is intracellular. The bone Mg is in equilibrium with sMg, whereas red blood cell Mg (rbcMg) reflects sMg concentration while each red blood cell is maturing before entering the circulation. The kidney controls the sMg by reabsorption up to a serum TM level for Mg, which is 3mg/dL (Elin 1988) (Ryzen 1985).

The situation is somewhat confusing because laboratories and medical writers use three different unit methods to record the values of Mg in tests. The following tables are an effort to let the reader compare reference values and different units of reporting laboratory tests.

Units Conversions and Equivalents

Atomic number: 24.3

For magnesium: 1mmol/L = 2mEq/L = 24.3mg/L (2.43mg/dL).

Conversion equation: mmol/L x 2.433 = mg of Mg/dL

REFERENCE VALUES FOR LABORATORY TESTS FOR MAGNESIUM

COMPARISON OF THREE DIFFERENT REPORTING VALUE METHODS

mmol/L

mEq/L

mg/dL

Total

sMg

0.7-1.1

1.3-2.1

1.7-2.5

NA1

rbc Mg

2.4-2.57

3.37-5.77

4.04-6.9

NA

24hr uMg

3.o-4.37

6.0-8.5

 

120-150mg

1. NA=Non-applicable

(Elin 1988)

 

Cation (+)et anion (-)

Example

Equivalence

monovalent

Na+, K+, HCO3-, Cl-

1 mmol = 1 mEq

bivalent

Ca2+, Mg2+, SO42-, HPO42-

1 mmol = 2 mEq

trivalent

C6H5O73-, PO43-

1 mmol = 3 mEq

Magnesium Deficiency Tests

The diagnosis of MgD is established whenever the sMg is below the normal range, the red blood cell Mg (rbcMg) is below the normal range (an indication of chronic intracellular deficiency), or if a decreased 24hr urinary Mg content (uMg), below 100 mg/day, is present and the kidneys are trying to conserve Mg in the presence of MgD. Equally important is when the uMg content is above 150 mg/day, called uMg wasting.. If any of these tests are positive, that test makes the diagnosis of MgD alone. If more than one of these is positive the Stage of MgD changes, which demonstrates the severity of MgD and is illustrated below.

LOW DOSE MAGNESIUM LOAD TEST AND THE 24hr URINE MAGNESIUM CONTENT

The “Gold Standard” for MgD is the Mg load test (MgLT), which is abnormal in each of the above-confirmed MgD tests. Therefore there is no absolute need for a MgLT. However if we had the choice of only one test we would do the MgLT, if we could do a second test we would add the rbcMg test. Our second choice for a single test is the RBCMg test-see comments below. The MgLT requires a pre-test 24hr uMg content, followed by a second 24hr uMg, after initiating the IV MgSO4 infusion – one gains a lot of information from this combined test. It should be noted that Elin, former Director of the Clinical Laboratories at the National Institute of Health has said, see reference listed at the end, in an excellent monograph on Magnesium in Health and Disease that the upper limit of normal for a 24hr uMg content is 150 mg of Mg. Another important book is Tietz’s Clinical Guide to Laboratory Tests, 3rd ED., which says the upper limit is 120 mg. Then with the loading test on the next day a retention of over 25% of a four-hour low Mg dose MgLT, an infusion of 0.2 mEq Mg/kg lean body weight given in 5% Dextrose in water, (NOTE do not use any saline solution) over 4 hour, (Ryzen 1985) is diagnostic of Mg depletion. A 50% retention reflect a more sever Stage of MgD. This latter effect must take several months of chronic uMg loss, since the bones contain 50% of the total body Mg.

Two other tests have been proposed because of the need for two 24-hr urine collections to do the most accurate test as stated above. The First Proposal (Tang, NL Clinical Biochemistry 2000;33:675-678) suggested doing a random spot-sample of urine would be an excellent way to diagnosis urinary Mg deficiency. Their paper used the urine Mg/creatinine ratio, but it only measures insufficient Mg intake. The 24-hr test corrects the errors that occur due to the uMg content variations of the excretion over the 24 hours, known as circadian rhythm effect of the kidneys. They concluded that this is only useful as a screening test for dietary Mg induced MgD, and it does not accurately measure uMg wasting. Moreover we already know that in the USA dietary induced MgD is very common. The Second Proposal (Rob PM et el. J Intern Med 1999;246:273-378) is a one hour infusion of the same amount of el. Mg as the Ryzen paper, above, over a 4 hour infusion, although a they used a different salt. To me this is a fatally flawed paper, since as Ryzen points out that her 4 hours infusion which enables the dose to be better retained in the body tissues, rather than being rapidly excreted by the kidneys that is known to occur in a one hour infusion. They gave their Mg load with normal saline, a salt solution, which is known to increase uMg excretion. Moreover they did not do the first day excretion analysis, thus they had no baseline uMg content on their subjects, to compare with the Mg load day.

INDICATIONS FOR THE USE OF THE MAGNESIUM LOAD TEST

  1. All research or case reports on magnesium (Mg) patients that will or might be published. The data is necessary so we can learn more.
  2. On all patients with normal levels of serum Mg (sMg), red blood cell Mg (RBCMg), 24hr urinary Mg (uMg), but with one or more risk factors and/or symptoms of Mg deficiency (MgD) requiring daily Mg supplementation (MgS). Many, likely 30%, will have normomagnesemia MgD, (NMgD), requiring oral Mg.
  3. On patients with decreased sMg, and normal RBCMg and/or 24hr uMg. The RBCMg has about a 30% false negative rate for NMgD, but if the level is decreased the diagnosis is intracellular MgD, which is a NMgD. A 24hr uMg is of little value unless it is increased, indicating uMg wasting, or decreased, indicating depleted Mg storage sites, usually bone.
  4. Patients or their physician who need to be convinced that it is in their best interest to take daily MgS, when there is never obvious symptoms nor objective signs of MgD from their chronic disease, such as hypertension or a silent cardiac arrhythmia.
  5. Patients that have recurrent symptoms, such as premenstrual syndrome and migraine, where there are symptom-free periods, normal sMg and rbcMg, that then are triggered by uncontrollable or intermittent events, where MgS would serve as a preventive.

SUGGESTED PROTOCOL FOR USE OF MAGNESIUM TOLERANCE TEST1

  1. Collect baseline 24-h urine for magnesium/creatinine ratio.
  2. Infuse 0.2 mEq (2.4 mg) elemental magnesium per kilogram of lean body weight in 50 ml of 5% dextrose over 4h.
  3. Collect urine (starting with infusion) for magnesium and creatinine for 24 h.
  4. Percentage magnesium retained is calculated by the formula below.
  5. Criteria for Mg deficiency >50% retention at 24 h = definite deficiency >25% retention at 24 h = probable deficiency.
  6. A fasting 2-h spot or shorter timed-urine may be used.

THE SERUM MAGNESIUM

The sMg test is of little value unless there is a value lower than 1.7 mg/dl, a rare event in MgD, like the tip of an iceberg. This is then called hypomagnesemia, and emergency treatment is often indicated. Some patients with migraine have acute fall in their sMg levels and can often correlated this fall in sMg with their aura of an attack. This test is of no value when trying to follow oral Mg treatment, since levels in the normal range do not change, because the kidney will not let the sMg go above the individual patient’s set normal TM value for Mg. One’s highest level, somewhere between 1.7 and 2.5 mg/dl, should be that patient’s guide and usually remains constant through out life, in spite of a high oral intake of MgS. Thus one cannot expect it to even go as high or higher than 2.5 mg/dl, which is someone else’s preset normal level (this occurs in one out of a thousand). This is very specific, much like a person’s DNA, but it can go higher if there is kidney disease present preventing Mg excretion.

THE RED BLOOD CELL MAGNESIUM

This test should be the clinical practice “Gold Standard” for the diagnosis of Normomagnesemia MgD. This is because it truly measures latent and intracellular MgD, those patients below the tip of the iceberg of MgD. All clinical lavatories can get it done. It should be noted that over time, during Mg supplement treatment, the rbcMg slowly returns to normal in about 4 months. This is the only test that can be used to monitor, thereby indicating to the physician that the patient is getting their maximum dose to maintain positive Mg balance (PMgB) (more being absorbed, than coming out in the urine). Once the diagnosis is made it is important to identify the cause or causes (usually the case), this is especially true in regard to uMg wasting. There are many causes of uMg wasting; some of these drugs can be changed to a non-wasting medication. If this is impossible, the oral intake of Mg will need to be increased in order to reduce MgD symptoms and to maintain PMgB. (Elin 1988) (Millard 1995)

The staging of MAgNESIUM DEFICIENCY

It had been proposed that the multiple variables in assessing negative Mg balance (NMgB) could be separated into Stages varying from the beginning, called Type I, Stage 1 Latent MgD to Type II, Stage 8 death due to MgD, demonstrating a progressive advance in severity as illustrated by the currently available Mg laboratory tests. Absent from this table is ionized Mg (IMg), which is likely to add to the validity of this method of looking at MgD. This will make the following of a patient from Type II – Stage 5, during MgS treatment, to Type I – Stage 1 more accurate. There is a need now apparent; to include a Stage 4 under the Type 1 called Chronic Intracellular MgD in this previously published table. This stage is likely to have a decreased IMg (Mansmann-1993), as will Stages 6 and 7. The experiments are underway which will be able to generate additional information on Ionized Magnesium (iMg) and its relationship to staging of MgD, which will enhance the present classification.

Classification of Magnesium Deficiency-2001

Type

Stage

Diagnosis

sMg

RBCMg

uMg

MgLT1

IMg2

 

 

 

 

 

 

 

 

I INTRACELLULAR MgD – Normomagnesemia

 

 

1

Latent MgD

N3

N

N

>25%R

UK3

 

2

Occult MgD

N

N

N

>50%R

UK

 

3

Subclinical MgD

N

D

I/D

>50%R

UK

 

4

Chronic MgD

N

D

I/D

>50%R

UK

 

II EXTRACELLULAR MgD – Hypomagnesemia

 

 

5

Acute MgD

D

N

N

N/R

UK

 

6

Advanced MgD

D

D

D

>50%R

UK

 

7

Extreme MgD

D

D

D

>50%R

UK

 

8

Death due to MgD

D

N/D

I/D

N/R

UK

<!–[if !supportLists]–>1) <!–[endif]–>Mg load test: >25%R = retention is probable MgD, >50%R – retention is definite MgD.

<!–[if !supportLists]–>2) <!–[endif]–>Ionized Magnesium results presently indeterminate.

<!–[if !supportLists]–>3) <!–[endif]–>N = Normal, D = Decrease, I = Increased, R = Retented, UK = Unknown.


 

References

1. Elin,RJ. Magnesium Metabolism in health and disease. DM, XXXIV, No.4, April 1988

2. Mansmann Jr., HC. Consider magnesium homeostasis. II. Staging of magnesium deficiencies. Ped Asthma Allergy Immunol, 1993;7:211-215.

3. Mansmann Jr., HC. Consider Magnesium Homeostasis. III. Cytochrome P-450 Enzymes and Drug Toxicity. Ped Asthma Allergy Immunol, 1994;8:7-28.

4. Millart H, Durlach V, Durlach J. Red blood cell magnesium concentrations: analytical problems and significance. Magnesium Research. 1995;8(1):65-76.

5. Ryzen E, Elbaum N, Singer FR, Rude RK. Parenteral magnesium tolerance testing in the evaluation of magnesium deficiency. Magnesium. 1985;4:137-147.

6. Sauberlich, HE. Laboratory tests for the assessment of nutritional status. 2nd ED, CRC Press, Boca Raton, 1999.

7. Tietz, NW. Clinical guide to laboratory tests. 3rd ED, WB Saunders Co. Philadelphia, 1995.

8. Welt LG, Gitelman H. Disorders of magnesium metabolism. DM, 1965;11:1-32.

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