Intracellular Calcium and Magnesium Levels – Age-Related Changes and Relationship to Hypertension and Diabetes

Intracellular Calcium and Magnesium Levels – Age-Related Changes and Relationship to Hypertension and Diabetes

By Ward Dean, MD

Magnesium and potassium are the principal intracellular cations (positive ions), while calcium and sodium are the principal extracellular cations. Although magnesium plays a universal role in cellular biochemistry, and is critical to enzyme activation, nerve conduction, ion transport, and hundreds of other functions, little is known about the effect of age on magnesium metabolism.Because only about 1% of magnesium is extracellular, serum magnesium levels do not accurately reflect intracellular magnesium content. Furthermore, only 10-15% of intracellular magnesium is in the free, active form.1

Age-Related Changes in Intracellular Ca/Mg Levels

Recently, a team of researchers performed a study on 103 subjects of various ages, utilizing 31P-nuclear magnetic (NMR) and 19F-NMR techniques to determineintracellular levels of magnesium and calcium, respectively.2 The scientists analyzed the levels of calcium and magnesium, using red blood cells, drawn at 9 AM.Characteristics of the participants in this study were as follows: Seventy-one of the subjects were less than 65-years old, and thirty-two subjects were older than 65. Thirty-seven of the subjects were “healthy normals” (eleven of whom were older than 65, and twenty-six were younger than 65). Thirty-nine were hypertensive (nine were older than 65, and thirty were younger than 65). Twenty-seven had non-insulin dependent diabetes mellitus (NIDDM) (12 were older than 65, and 15 were younger than 65).

Interestingly, the scientists found that there were no differences of serum (i.e., the liquid portion of blood, minus the red and white blood cells) levels of calcium and magnesium in any of the participants—i.e., neither age nor disease (hypertension or diabetes) had any effect on serum concentrations of these minerals.

However, younger normal subjects had higher levels of intracellular magnesium, and lower levels of intracellular calcium (Figs. 1 and 2) than the normal older subjects. Fleckenstein (1983) found similar changes in tissue calcium and magnesium levels in the aortas of humans who died at various ages. Fleckenstein demonstrated the progressive accumulation of calcium in arterial tissue, resulting in a shift of the calcium/magnesium ratio in favor of calcium (Fig. 3).3

Intracellular Mineral Levels and Disease

Significantly, subjects with hypertension or non-insulin dependent diabetes mellitus (NIDDM) had higher levels of intracellular calcium and lower levels of intracellular magnesium—even worse than the levels seen in older normal subjects (Figs. 4 and 5).

Based on these results, the authors formulated an “ionic hypothesis” in which they proposed that an intracellular profile characterized by excess calcium and depleted magnesium resulted in insulin resistance (resulting in obesity and NIDDM), hypertension, and aging.

Measuring Tissue Calcium and Magnesium Levels

The data described in this study appear to indicate that intracellular calcium and magnesium may be a useful biomarker of aging. However, as noted by the authors in this study, intracellular calcium and magnesium levels are not accurately assessed by routine blood (serum) analysis. Furthermore, the techniques utilized by the authors to gather these data are not readily available outside of major research institutes.There are several techniques that are readily available to accomplish this, however. An innovative technique has been developed to non-invasively and fairly inexpensively (about $70) measure levels of intracellular minerals. The test involves scraping cells from the floor of the mouth with a small spatula (ice cream stick), and sending the slide to IntraCellular Diagnostics. (800-874-4804). There, scientists use scanning electron microscopy and X-ray fluorescence to determine levels of calcium andmagnesium, plus sodium, potassium, chlorine and phosphorous. Another technique that measures tissue mineral levels is to use hair analysis (available from VRP). Although blood tests measure levels of various substances over very narrow periods of time, hair mineral levels reveal stable tissue mineral levels based on accumulation over weeks to months. Hair elemental analysis can be a source of important information for healthcare practitioners and their patients. With proper interpretation, hair analysis test results can point to hidden causes of chronic illness,
and help physicians design nutritional interventions.

Optimizing Calcium/Magnesium Balance

The observations in this study—that elevated levels of intracellular calcium, and depressed levels of intracellular magnesium—clearly indicate the contribution of this pattern to many chronic degenerative diseases, including diabetes, hypertension, atherosclerosis, obesity and aging. These findings appear to validate the calcium/magnesium balance in VRP’s multi-nutrient and multi-mineral formulas, which are generally weighted in favor of magnesium-to-calcium. The rationale for these higher magnesium-to-calcium ratios has been previously explained in detail in the Customers’ Corner in the March, 2000 issue of Vitamin Research News. (On the internet go to www.vrp.com, choose “library,” and enter “calcium” in the search engine.)


1. Gupta, R.K., Gupta, P., Yushok, W.D., Rose, Z.B. Measurement of the dissociation constant of magnesium ATP of 31P-NMR and optical absorbance spectroscopy.
Biochem Biophys Res Commun, 1983, 253: 6172-6176.
2. Barbagallo, M., Gupta, R.K., Dominguez, L.J., and Resnick, L.M. Cellular ionic alterations with age: Relation to hypertension and diabetes. J American Geriatrics Society, 2000, 48: 1111-1116.
3. Fleckenstein, A. Calcium Antagonism in Heart and Smooth Muscle, John Wiley & Sons, New York, 1983.

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