Part 1: Why A Serum Magnesium Test Doesn’t Detect Whole-Body Magnesium Deficiency

Although magnesium is crucial for overall health, 48% of Americans do not get enough of it. Most people don’t even know they’re deficient because hospitals and clinics don’t routinely screen for magnesium deficiencies. The most common serum magnesium tests don’t work that well, especially when trying to test for your whole-body magnesium status.

The problem is that magnesium is a key electrolyte in your serum, the liquid portion of your blood. To keep you alive, your body keeps serum magnesium within a very narrow normal range so the vital organs can function, even when the rest of your body lacks magnesium. 

The medical definition of hypomagnesemia (low magnesium) and hypermagnesemia (excess magnesium) means your serum magnesium is so low or so high that it could be life-threatening.

Here, we’re asking a completely different question: “Do you have enough magnesium for your whole body to work its best?” Typically, serum magnesium doesn’t reflect magnesium in your entire body and thus doesn’t answer this question. Continue reading this article to learn why. 

On average, the adult body contains 25 g of magnesium – over half is in the bones and most of the rest is within soft tissues like muscle. Less than 0.8 – 1% of your body’s total magnesium is in your blood. Despite this, serum magnesium tests remain the most used when evaluating magnesium deficiency.

Challenges With Testing Whole-Body Magnesium Status

Unlike assessing other nutrient levels, testing for whole-body magnesium status is not as clear-cut. There is no universally accepted gold standard test for evaluating whole-body magnesium status, and each test that exists has limitations.

Some of the important challenges with testing magnesium levels include:

• Magnesium distribution in the body: Magnesium is primarily inside cells (intracellular), and 0.8 – 1% circulates within the blood. This makes blood tests, especially serum tests, less reflective of whole-body magnesium and even magnesium inside your cells. 

• Interfering health factors : Certain medications and medical conditions can impact magnesium levels or interfere with testing. The most common medications that can interfere with magnesium test results include diuretics, proton pump inhibitors, and some antibiotics. 

Conditions that can affect magnesium status include kidney disease, digestive disorders, and some hormonal imbalances. It is important to be aware of these factors when interpreting results.

• Day/night variation: Your body is always taking, using, and eliminating magnesium. So, serum magnesium levels are not static and can vary throughout the day. Typically, you have higher levels in the morning, and lower levels in the evening. This is important to keep in mind when undergoing magnesium testing, as the time it is done can impact your results.

• Reference range inconsistencies: Reference ranges, or what will be flagged as normal or abnormal, can differ between laboratories. Therefore, the interpretation of test results should always refer to the ranges from the testing lab.

• Symptoms versus laboratory results : An excess or deficiency of magnesium does not always correlate with clinical symptoms. For some, symptoms may be present despite normal lab values. For others, no symptoms may exist despite levels falling below the reference range.  

• Interfering technical factors and methodological limitations: As you will learn below, magnesium testing is complex, and not a perfect science. Test results can be incorrect due to substances present in the blood sample, or contamination during processing. 

It is important to keep these factors in mind when assessing magnesium status. A proper evaluation should be comprehensive and take into account lab results, but also symptoms, history, health status, and lifestyle factors in order to get a comprehensive understanding of magnesium status.

Why Serum Magnesium Does Not Reflect Whole-Body Or Intracellular Magnesium Status

Your whole blood has a liquid and a solid portion. The liquid portion is the serum or plasma that has dissolved, proteins, and hormones. Whereas the solid portion contains cells like red and white blood cells. 

Serum magnesium levels measure the concentration of magnesium dissolved in the liquid portion. As described above, 0.8 – 1% of magnesium is in the blood. Among this, about 0.3% is in your serum and 0.5% is in your red blood cells.

To stay alive, your body will try its best to keep serum magnesium normal, even at the expense of magnesium inside your cells and bones. Therefore the serum test is unlikely to reflect whole-body magnesium.

The major reasons for this include:

• Cellular Distribution: As you learned above, only 0.8 – 1% of the body’s total magnesium is found in the bloodstream. ~99% of whole body magnesium is inside the cells. 

So many factors are involved in moving magnesium in and outside of your cells that serum magnesium can hardly be reflective of magnesium inside your cells.

• Homeostasis and regulation: The body tightly regulates magnesium levels to maintain homeostasis. Homeostasis is a word used to describe a stable equilibrium or balance. 

For example, when serum magnesium levels decrease, the body compensates by eliminating less magnesium through the urine. This regulatory mechanism allows magnesium levels to remain stable in the serum, even if magnesium inside your cells and whole body are depleted.

• Buffering: serum magnesium levels are buffered by proteins in the body, such as albumin. These proteins bind and help maintain stable serum levels, even if there are changes in cellular magnesium levels. This effect is the main reason why there are poor correlations between serum and intracellular magnesium levels.

• Magnesium transport: Many factors control magnesium movement, including hormones, cellular demand, and existing intracellular levels. The transports and channels described above can differ between different cell types and tissues, and therefore change the rate that magnesium enters or exits cells. This can make it challenging to infer intracellular magnesium levels from serum measurements.

Serum magnesium measurements provide only limited insight into the body’s magnesium within cells. To directly assess magnesium inside cells beyond the blood, you’d typically need to cut out a tissue (biopsy), so this is rarely done except in research contexts. Thankfully, serum magnesium and tissue biopsy are not the only option. In the next article, part 2, we’ll cover:

• All currently available magnesium tests 
• How accurately each of these tests reflect whole-body magnesium levels
• Their pros and cons
• References and normal ranges

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