The multifaceted and widespread pathology of magnesium deficiency

doi:10.1054/mehy.2000.1133

Medical Hypotheses

Volume 56, Issue 2, February 2001, Pages 163-170

https://doi.org/10.1054/mehy.2000.1133 Get rights and content

Abstract

Even though Mg is by far the least abundant serum electrolyte, it is extremely important for the metabolism of Ca, K, P, Zn, Cu, Fe, Na, Pb, Cd, HCl, acetylcholine, and nitric oxide (NO), for many enzymes, for the intracellular homeostasis and for activation of thiamine and therefore, for a very wide gamut of crucial body functions. Unfortunately, Mg absorption and elimination depend on a very large number of variables, at least one of which often goes awry, leading to a Mg deficiency that can present with many signs and symptoms. Mg absorption requires plenty of Mg in the diet, Se, parathyroid hormone (PTH) and vitamins B6 and D. Furthermore, it is hindered by excess fat. On the other hand, Mg levels are decreased by excess ethanol, salt, phosphoric acid (sodas) and coffee intake, by profuse sweating, by intense, prolonged stress, by excessive menstruation and vaginal flux, by diuretics and other drugs and by certain parasites (pinworms). The very small probability that all the variables affecting Mg levels will behave favorably, results in a high probability of a gradually intensifying Mg deficiency. It is highly regrettable that the deficiency of such an inexpensive, low-toxicity nutrient result in diseases that cause incalculable suffering and expense throughout the world. The range of pathologies associated with Mg deficiency is staggering: hypertension (cardiovascular disease, kidney and liver damage, etc.), peroxynitrite damage (migraine, multiple sclerosis, glaucoma, Alzheimers disease, etc.), recurrent bacterial infection due to low levels of nitric oxide in the cavities (sinuses, vagina, middle ear, lungs, throat, etc.), fungal infections due to a depressed immune system, thiamine deactivation (low gastric acid, behavioral disorders, etc.), premenstrual syndrome, Ca deficiency (osteoporosis, hypertension, mood swings, etc.), tooth cavities, hearing loss, diabetes type II, cramps, muscle weakness, impotence (lack of NO), aggression (lack of NO), fibromas, K deficiency (arrhythmia, hypertension, some forms of cancer), Fe accumulation, etc. Finally, because there are so many variables involved in the Mg metabolism, evaluating the effect of Mg in many diseases has frustrated many researchers who have simply tried supplementation with Mg, without undertaking the task of ensuring its absorption and preventing excessive elimination, rendering the study of Mg deficiency much more difficult than for most other nutrients.

References (18)

I.S. Koltas et al.
Serum copper, zinc and magnesium in children with enterobiosis
J Trace Elem Med Biol
(1997)
F. Liao et al.
Is low magnesium concentration a risk factor for coronary heart disease? The atherosclerosis risk in communities (ARIC) study
Am Heart J
(1998)
N. Simon
Infantile autism and Wernicke’s encephalopathy
Med Hypotheses
(1990)
L. Mortensen et al.
Effect of vitamin D treatment in hypoparathyroid patients: a study on calcium, phosphate and Mg homeostasis
Eur J Endocrinol
(1997)
A. Toromanoff et al.
Parathyroid hormone increases bone formation and improves mineral balance in vitamin D-deficient female rats
Endocrinology
(1997)
S.A. Price et al.
Pathophysiology.
(1997)
S.A. Price et al.
Pathophysiology. 5^thedition
(1997)
N. Chareonpong Kawamoto et al.
Selenium deficiency as a cause of overload of Fe and unbalanced distribution of other mineral
Biosci Biotechnol Biochem
(1995)

There are more references available in the full text version of this article.

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Mg is the fourth most abundant mineral in the body and is essential for DNA and RNA synthesis, reproduction, protein synthesis, and active transport of Ca and potassium across cell membranes [55]. Mg deficiency is more prevalent in industrialized countries, in association with diet habits that reduce its intake amount and absorption [2,33,56]. Low levels of Mg in the body have been associated with several conditions such as impaired insulin resistance, cardiovascular disease, osteoporosis, type 2 diabetes mellitus and other chronic diseases [55].
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Even though magnesium is by far the least abundant serum electrolyte, it is extremely important for the metabolism of Ca, K, P, Zn, Cu, Fe, Na, Pb, Cd, HCL, acetylcholine, and nitric oxide. It is therefore important for a wide gamut of crucial body functions as is thiamin (Johnson, 2001). Perhaps the commonest method of depicting thiamin deficiency is by an analysis of its concentration in the blood.
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The aim of the present study was to assess whether dietary magnesium deficiency can alter distribution of macroelements and trace elements in different organs and tissues. Experiments were carried out on 12 adult female Wistar rats, which were fed either a diet with low Mg content (≤20 mg kg⁻¹ of diet) (LMgD) or a diet with daily recommended Mg content (≈500 mg kg⁻¹) as control group (CG) for 70 days. On the 70th day of the experiment heart, aorta, femoral skeletal muscle, forebrain, cerebellum, pituitary gland, thyroid gland, ovaries, uterus, liver, kidneys, and spleen were taken for analysis of mineral content. Concentrations of Fe and Ca were measured by inductively coupled plasma-atomic emission spectrometry, and levels of Na, K, Mg, Co, Cu, Zn, Ni, Se, I were determined by inductively coupled plasma mass spectrometry. On the 70th day, LMgD led to significant reduction of Mg level in red blood cells, plasma, aorta, uterus and thyroid gland compared to CG as well as resulted in significant decrease of Mg/Ca ratio in kidneys, spleen and ovaries. Contrary to this, an increase of Mg/Ca ratio was found in cerebellum of LMgD group. Significant decrease of K concentration was shown in aorta of LMgD animals compared to CG whereas myocardial K concentration was increased in LMgD group. Na level was two-fold higher in skeletal muscles of rats that received LMgD in comparison to CG (p = 0.006). Increased concentrations of Fe in ovaries and uterus were found in LMgD. Mg restriction did not affect Zn concentration in any of tasted tissues. Se level was higher in spleen and lower in uterus of LMgD animals compared to CG. MgD was accompanied by increased level of Co in skeletal muscles and decreased its level in kidneys and uterus. LMgD feeding was associated with decreased concentrations of Ni in heart, thyroid gland, spleen, uterus and Co in heart, aorta, liver, kidneys, spleen and ovaries. The changes of Mg, K, Co content were accompanied by dramatic (10-fold) decrease of I concentration in aorta of LMgD animals. LMgD causes decrease of I content in ovaries and increase of I level in uterus vs CG. Thus, distribution of macroelements (Ca, Na, K) was weakly affected by Mg restriction that led to the most evident alterations of Co and Ni tissue levels. Moreover, mineral balance of uterus seems to be the most susceptible to low Mg intake. Hypomagnesaemia resulted in significant changes of 5 studied trace elements (Fe, Se, Cu, Ni and Co).

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Regular ArticleThe multifaceted and widespread pathology of magnesium deficiency

Abstract

J Trace Elem Med Biol

Am Heart J

Med Hypotheses

Effect of vitamin D treatment in hypoparathyroid patients: a study on calcium, phosphate and Mg homeostasis

Eur J Endocrinol

Parathyroid hormone increases bone formation and improves mineral balance in vitamin D-deficient female rats

Endocrinology

Pathophysiology.

Pathophysiology. 5thedition

Selenium deficiency as a cause of overload of Fe and unbalanced distribution of other mineral

Biosci Biotechnol Biochem

Regular Article
The multifaceted and widespread pathology of magnesium deficiency

Pathophysiology. 5^thedition