Magnesium Abstracts 1 - Deficiency

© 2012

Magnesium and aging

            (Barbagallo and Dominguez 2010) Download

Over the past decades, the clinical relevance and biological significance of magnesium (Mg) have been documented. Deficiency in Mg, aside from having a negative impact on the energy production pathway required by mitochondria to generate ATP, also reduces the threshold antioxidant capacity of the aging organism and its resistance to free-radical damage. Mg also acts as an antioxidant against free radical damage of the mitochondria. Chronic inflammation and oxidative stress have both been identified as pathogenic factors in aging and in several age-related diseases. Chronic Mg deficiency results in excessive production of oxygen-derived free radicals and low grade inflammation. Aging is very often associated with Mg inadequacy and with increased incidence of many chronic diseases, with muscle loss and sarcopenia, altered immune responses, and vascular and metabolic conditions, such as atherosclerosis, diabetes and the cardiometabolic syndrome. The most common cause of Mg deficit in the elderly population is dietary Mg deficiency, although secondary Mg deficit in aging may also results from many different mechanisms. The aim of the present manuscript is to discuss the mechanisms and consequences of the modifications of Mg metabolism with age, the difficulties in the measurement of Mg status, and to review the current evidences suggesting that age-related chronic Mg deficits may be proposed as one of the physiopathological links that may help to explain the interactions between inflammation, oxidative stress with the aging process and many age-related diseases.


Blood magnesium, and the interaction with calcium, on the risk of high-grade prostate cancer

            (Dai, Motley et al. 2011) Download

BACKGROUND: Ionized calcium (Ca) and magnesium (Mg) compete as essential messengers to regulate cell proliferation and inflammation. We hypothesized that inadequate Mg levels, perhaps relative to Ca levels (e.g. a high Ca/Mg ratio) are associated with greater prostate cancer risk. STUDY DESIGN: In this biomarker sub-study of the Nashville Men's Health Study (NMHS), we included 494 NMHS participants, consisting of 98 high-grade (Gleason>/=7) and 100 low-grade cancer cases, 133 prostate intraepithelial neoplasia (PIN) cases, and 163 controls without cancer or PIN at biopsy. Linear and logistic regression were used to determine associations between blood Ca, Mg, and the Ca/Mg ratio across controls and case groups while adjusting for potential confounding factors. RESULTS: Serum Mg levels were significantly lower, while the Ca/Mg ratio was significantly higher, among high-grade cases vs. controls (p = 0.04, p = 0.01, respectively). Elevated Mg was significantly associated with a lower risk of high-grade prostate cancer (OR = 0.26 (0.09, 0.85)). An elevated Ca/Mg ratio was also associated with an increased risk of high-grade prostate cancer (OR = 2.81 (1.24, 6.36) adjusted for serum Ca and Mg). In contrast, blood Ca levels were not significantly associated with prostate cancer or PIN.Mg, Ca, or Ca/Mg levels were not associated with low-grade cancer, PIN, PSA levels, prostate volume, or BPH treatment. CONCLUSION: Low blood Mg levels and a high Ca/Mg ratio were significantly associated with high-grade prostate cancer. These findings suggest Mg affects prostate cancer risk perhaps through interacting with Ca.

Re-evaluation of the concept of chronic, latent, magnesium deficiency

            (Elin 2011) Download

Hypomagnesaemia due to use of proton pump inhibitors--a review

            (Kuipers, Thang et al. 2009) Download

Magnesium homeostasis is essential for many intracellular processes and depends on the balance of intestinal absorption and renal excretion. Hypomagnesaemia may arise from various disorders. We review the literature on hypomagnesaemia due to the use of proton pump inhibitors, as illustrated by a case of a 76-year-old woman with muscle cramps and lethargy caused by hypomagnesaemia and hypocalcaemia with a low parathyroid hormone level while using esomeprazole, a proton pump inhibitor (PPI). After oral magnesium repletion both abnormalities resolved. Fractional magnesium excretion was low, excluding excessive renal loss. A causal relation with PPI use was supported by the recurrence of hypomagnesaemia after rechallenge. In the past decade our understanding of transcellular magnesium transport was enhanced by the discovery of several gene mutations i.e. transient receptor potential melastin (TR PM) 6 and 7. In this light we discuss the possible aetiology of proton pump inhibitor related hypomagnesaemia.

Skeletal and hormonal effects of magnesium deficiency

         (Rude, Singer et al. 2009) Download

Magnesium (Mg) is the second most abundant intracellular cation where it plays an important role in enzyme function and trans-membrane ion transport. Mg deficiency has been associated with a number of clinical disorders including osteoporosis. Osteoporosis is common problem accounting for 2 million fractures per year in the United States at a cost of over $17 billion dollars. The average dietary Mg intake in women is 68% of the RDA, indicating that a large proportion of our population has substantial dietary Mg deficits. The objective of this paper is to review the evidence for Mg deficiency-induced osteoporosis and potential reasons why this occurs, including a cumulative review of work in our laboratories and well as a review of other published studies linking Mg deficiency to osteoporosis. Epidemiological studies have linked dietary Mg deficiency to osteoporosis. As diets deficient in Mg are also deficient in other nutrients that may affect bone, studies have been carried out with select dietary Mg depletion in animal models. Severe Mg deficiency in the rat (Mg at <0.0002% of total diet; normal = 0.05%) causes impaired bone growth, osteopenia and skeletal fragility. This degree of Mg deficiency probably does not commonly exist in the human population. We have therefore induced dietary Mg deprivation in the rat at 10%, 25% and 50% of recommended nutrient requirement. We observed bone loss, decrease in osteoblasts, and an increase in osteoclasts by histomorphometry. Such reduced Mg intake levels are present in our population. We also investigated potential mechanisms for bone loss in Mg deficiency. Studies in humans and and our rat model demonstrated low serum parathyroid hormone (PTH) and 1,25(OH)(2)-vitamin D levels, which may contribute to reduced bone formation. It is known that cytokines can increase osteoclastic bone resorption. Mg deficiency in the rat and/or mouse results in increased skeletal substance P, which in turn stimulates production of cytokines. With the use of immunohistocytochemistry, we found that Mg deficiency resulted in an increase in substance P, TNFalpha and IL1beta. Additional studies assessing the relative presence of receptor activator of nuclear factor kB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG), found a decrease in OPG and an increase in RANKL favoring an increase in bone resorption. These data support the notion at dietary Mg intake at levels not uncommon in humans may perturb bone and mineral metabolism and be a risk factor for osteoporosis.


Magnesium deficiency: a cause of heterogeneous disease in humans

            (Rude 1998) Download

Magnesium deficiency induces anxiety and HPA axis dysregulation: modulation by therapeutic drug treatment

            (Sartori, Whittle et al. 2012) Download

Preclinical and some clinical studies suggest a relationship between perturbation in magnesium (Mg(2+)) homeostasis and pathological anxiety, although the underlying mechanisms remain largely unknown. Since there is evidence that Mg(2+) modulates the hypothalamic-pituitary adrenal (HPA) axis, we tested whether enhanced anxiety-like behaviour can be reliably elicited by dietary Mg(2+) deficiency and whether Mg(2+) deficiency is associated with altered HPA axis function. Compared with controls, Mg(2+) deficient mice did indeed display enhanced anxiety-related behaviour in a battery of established anxiety tests. The enhanced anxiety-related behaviour of Mg(2+) deficient mice was sensitive to chronic desipramine treatment in the hyponeophagia test and to acute diazepam treatment in the open arm exposure test. Mg(2+) deficiency caused an increase in the transcription of the corticotropin releasing hormone in the paraventricular hypothalamic nucleus (PVN), and elevated ACTH plasma levels, pointing to an enhanced set-point of the HPA axis. Chronic treatment with desipramine reversed the identified abnormalities of the stress axis. Functional mapping of neuronal activity using c-Fos revealed hyper-excitability in the PVN of anxious Mg(2+) deficient mice and its normalisation through diazepam treatment. Overall, the present findings demonstrate the robustness and validity of the Mg(2+) deficiency model as a mouse model of enhanced anxiety, showing sensitivity to treatment with anxiolytics and antidepressants. It is further suggested that dysregulations in the HPA axis may contribute to the hyper-emotionality in response to dietary induced hypomagnesaemia. This article is part of a Special Issue entitled 'Anxiety and Depression'.

Magnesium metabolism and its disorders

            (Swaminathan 2003) Download

Magnesium is the fourth most abundant cation in the body and plays an important physiological role in many of its functions. Magnesium balance is maintained by renal regulation of magnesium reabsorption. The exact mechanism of the renal regulation is not fully understood. Magnesium deficiency is a common problem in hospital patients, with a prevalence of about 10%. There are no readily available and easy methods to assess magnesium status. Serum magnesium and the magnesium tolerance test are the most widely used. Measurement of ionised magnesium may become more widely available with the availability of ion selective electrodes. Magnesium deficiency and hypomagnesaemia can result from a variety of causes including gastrointestinal and renal losses. Magnesium deficiency can cause a wide variety of features including hypocalcaemia, hypokalaemia and cardiac and neurological manifestations. Chronic low magnesium state has been associated with a number of chronic diseases including diabetes, hypertension, coronary heart disease, and osteoporosis. The use of magnesium as a therapeutic agent in asthma, myocardial infarction, and pre-eclampsia is also discussed. Hypermagnesaemia is less frequent than hypomagnesaemia and results from failure of excretion or increased intake. Hypermagnesaemia can lead to hypotension and other cardiovascular effects as well as neuromuscular manifestations. Causes and management of hypermagnesaemia are discussed.

Magnesium: nutrition and metabolism

            (Vormann 2003) Download

Magnesium is an essential mineral that is needed for a broad variety of physiological functions. The usual daily magnesium uptake with a western diet is sufficient to avoid deficiency but seems not to be high enough to establish high normal serum magnesium concentrations that are protective against various diseases. Changes in magnesium homeostasis mainly concern the extracellular space, as the intracellular magnesium concentration is well regulated and conserved. The extracellular magnesium concentration is primarily regulated by the kidney, the mechanisms of this regulation have been elucidated recently. Due to the growing knowledge about the regulation of extra- and intracellular magnesium concentrations and the effects of changed extracellular magnesium levels the use of magnesium in therapy gains more widespread attention.

Magnesium

            (Wester 1987) Download


References

Barbagallo, M. and L. J. Dominguez (2010). "Magnesium and aging." Curr Pharm Des 16(7): 832-9.

Dai, Q., S. S. Motley, et al. (2011). "Blood magnesium, and the interaction with calcium, on the risk of high-grade prostate cancer." PLoS One 6(4): e18237.

Elin, R. J. (2011). "Re-evaluation of the concept of chronic, latent, magnesium deficiency." Magnes Res 24(4): 225-7.

Kuipers, M. T., H. D. Thang, et al. (2009). "Hypomagnesaemia due to use of proton pump inhibitors--a review." Neth J Med 67(5): 169-72.

Rude, R. K. (1998). "Magnesium deficiency: a cause of heterogeneous disease in humans." J Bone Miner Res 13(4): 749-58.

Rude, R. K., F. R. Singer, et al. (2009). "Skeletal and hormonal effects of magnesium deficiency." J Am Coll Nutr 28(2): 131-41.

Sartori, S. B., N. Whittle, et al. (2012). "Magnesium deficiency induces anxiety and HPA axis dysregulation: modulation by therapeutic drug treatment." Neuropharmacology 62(1): 304-12.

Swaminathan, R. (2003). "Magnesium metabolism and its disorders." Clin Biochem Rev 24(2): 47-66.

Vormann, J. (2003). "Magnesium: nutrition and metabolism." Mol Aspects Med 24(1-3): 27-37.

Wester, P. O. (1987). "Magnesium." Am J Clin Nutr 45(5 Suppl): 1305-12.