Nutritional Deficiencies - Health Concerns

Magnesium - updated: 01 December 2008

Magnesium in clinical medicine

Front Biosci. 2004 May 1;9:1278-93

Touyz RM.

Until recently the physiological role of magnesium was essentially ignored. However, with the development of new technologies to measure the intracellular free concentration of magnesium ([Mg2+]i), the biologically important fraction, there has been an explosion of interest in the molecular, biochemical, physiological and pharmacological functions of magnesium. In addition improved methods for assessing magnesium status in the clinic have contributed to the further understanding of magnesium regulation in health and disease. Magnesium deficiency is now considered to contribute to many diseases and the role for magnesium as a therapeutic agent is being tested in numerous large clinical trials. This review focuses on clinical manifestations associated with magnesium deficiency and highlights the clinical significance of hypermagnesemia. Specific clinical conditions in which magnesium deficiency has been implicated to play a pathophysiological role, namely hypertension, ischemic heart disease, arrhythmias, prec-eclampsia, asthma and critical illness will be discussed and the possible therapeutic role of magnesium will be considered. Although there is still much to be learnt regarding the exact role of magnesium in clinical medicine, there are two conditions where magnesium is now considered the therapeutic agent of choice, pre-eclampsia and torsades de pointes. Future research, both at the fundamental and clinical levels, will certainly facilitate our understanding of how magnesium contributes to pathological processes and under what circumstances it should be used therapeutically.

Publication Types:

• Review

Magnesium intake and reduced risk of colon cancer in a prospective study of women

Am J Epidemiol. 2006 Feb 1;163(3):232-5

Folsom AR, Hong CP.

A recent prospective study among Swedish women suggested an inverse association of dietary magnesium intake with incidence of colorectal cancer. The authors assessed this association in a cohort of 35,196 Iowa women initially free of cancer and aged 55-69 years in 1986. Intakes of magnesium and other nutrients were assessed by food frequency questionnaire at baseline. Over 17 years of follow-up through 2002, 1,112 women developed colorectal cancer. After adjustment for age, energy, other nutrients, and risk factors for colorectal cancer, the hazard ratios of colorectal cancer across quintiles of magnesium intake were 1.00, 0.96, 0.83, 0.87, and 0.80 (95% confidence interval: 0.62, 1.03; p(trend) = 0.06). The association was largely absent for rectal cancer but, for colon cancer, the hazard ratios were 1.00, 1.00, 0.88, 0.85, and 0.77 (95% confidence interval: 0.58, 1.03; p(trend) = 0.04). These findings offer further evidence that a diet high in magnesium may reduce the occurrence of colon cancer among women. If replicated by other observational studies, a clinical trial would be needed to determine whether it is magnesium, specifically, and not other aspects of the contributing foods, that may offer benefit.

Publication Types:

• cohort of 35,196 Iowa women

Nutrition and cardiovascular disease

Eur J Med Res. 1997 Jun 16;2(6):243-57

Klör HU, Hauenschild A, Holbach I, Schnell-Kretschmer H, Stroh S.

The association between nutrition and coronary heart disease is mainly due to the effect of nutrients on serum lipids and lipoproteins. Cholesterol intake does not play a very important role for plasma cholesterol although there is a strong interindividual difference in response. The intake of saturated fatty acids strongly negatively affects plasma low-density lipoprotein cholesterol concentration while mono- and polyunsaturated fatty acids are generally regarded as beneficial. Omega-3 fatty acids mainly decrease triglyceride concentration while omega-6 polyunsaturated fatty acids mainly affect low-density lipoprotein cholesterol. Other nutrients which affect risk for coronary heart disease are dietary fiber, calcium, magnesium, iron, antioxidants as well as vitamins. Dietary fiber decrease intake of calories and fat, while iron and antioxidants play a role in oxidative modification of low-density lipoproteins. A low intake would lead to an accelerated uptake of low-density lipoprotein into the macrophage. Yet, intervention studies have not shown conclusively the benefit of a high-dose supplementation of the antioxidants vitamin E or beta-carotene on coronary heart disease. Homocysteine plasma concentration is influenced by folate as well as vitamin B6 and B12. Whether a high-dose supplementation with these substances does not only decrease plasma concentrations of homocysteine but also positively influence the course of coronary heart disease remains to be established.

Publication Types:

• Review

Environmental magnesium deficiency as a cardiovascular risk factor

J Cardiovasc Risk. 1996 Feb;3(1):4-10

Rylander R.

Magnesium is abundant in nature and the major routes of intake are through food and water. Through changes in the treatment of foodstuffs and altered diets, as well as increased use of surface water with low magnesium content, magnesium deficiency is present in modern society. Magnesium deficiency causes cardiac arrhythmia and several studies suggest that a low level of magnesium in drinking water is a risk factor for myocardial infarction, particularly among men. Before general prevention programmes can be recommended, risk groups must be defined and experimental intervention programmes performed.

Publication Types:

• Review

Review of epidemiological studies on drinking water hardness and cardiovascular diseases

Eur J Cardiovasc Prev Rehabil. 2006 Aug;13(4):495-506

Monarca S, Donato F, Zerbini I, Calderon RL, Craun GF.

BACKGROUND: Major risk factors do not entirely explain the worldwide variability of morbidity and mortality due to cardiovascular disease. Environmental exposures, including drinking water minerals may affect cardiovascular disease risks. METHOD: We conducted a qualitative review of the epidemiological studies of cardiovascular disease and drinking water hardness and calcium and magnesium levels. RESULTS: Many but not all ecological studies found an inverse (i.e., protective) association between cardiovascular disease mortality and water hardness, calcium, or magnesium levels; but results are not consistent. Some case-control studies and one cohort study found either a reduced cardiovascular disease mortality risk with increased drinking water magnesium levels or an increased risk with low magnesium levels. However, the analytical studies provide little evidence that cardiovascular risks are associated with drinking water hardness or calcium levels. CONCLUSION: Information from epidemiological and other studies supports the hypothesis that a low intake of magnesium may increase the risk of dying from, and possibly developing, cardiovascular disease or stroke. Thus, not removing magnesium from drinking water, or in certain situations increasing the magnesium intake from water, may be beneficial, especially for populations with an insufficient dietary intake of the mineral.

Publication Types:

• Review

Magnesium in cardiovascular and other disorders

Am J Health Syst Pharm. 2004 Aug 1;61(15):1569-76

Gums JG.

PURPOSE: The physiological role and metabolism of magnesium, the causes of magnesium deficiency, clinical data on the benefits of magnesium supplementation, and the management of magnesium deficiency are discussed. SUMMARY: Magnesium is an often overlooked electrolyte that is essential to life. Magnesium plays a role in more than 300 enzymatic reactions and is critically involved in energy metabolism, glucose utilization, protein synthesis, fatty acid synthesis and breakdown, ATPase functions, and virtually all hormonal reactions. Magnesium is closely involved in maintaining cellular ionic balance through its association with sodium, potassium, and calcium. Deficiency of magnesium is becoming more common in the U.S. population and may be attributed to decreased dietary consumption and the use of diuretics; in the elderly, magnesium deficiency may be a consequence of reduced appetite, decreased mitochondrial respiratory activity, and increased myocardial collagen. Conditions that may be associated with magnesium deficiency include hypertension, congestive heart failure, arrhythmia, myocardial infarction, diabetes mellitus, and preeclampsia; in many of these, magnesium supplementation has been found beneficial in clinical studies. Supplementation should be considered for patients with risk factors for deficiency and should be instituted for patients showing symptoms of deficiency. In addition to instituting supplementation when appropriate, the clinician should identify and correct the underlying cause of the deficiency. CONCLUSION: Magnesium deficiency may contribute to pathological processes. Clinicians should consider using magnesium supplementation to prevent deficiency in patients at risk and to treat deficiency when it occurs.

Publication Types:

• Review

Magnesium intake and the metabolic syndrome: epidemiologic evidence to date

J Cardiometab Syndr. 2006 Fall;1(5):351-5

He K, Song Y, Belin RJ, Chen Y.

The importance of magnesium intake in relation to the metabolic syndrome has been increasingly recognized. Magnesium is an essential mineral, critical for a number of metabolic functions in the human body. The major dietary sources of magnesium intake include whole grains, legumes, nuts, and green leafy vegetables. Animal studies indicate a pivotal role of magnesium in glucose homeostasis and insulin secretion and action. Experimental and clinical studies suggest that magnesium intake may be inversely related to the risk of hypertension and type 2 diabetes mellitus, and may decrease blood triglyceride and increase high-density lipoprotein cholesterol levels. The purpose of this brief review is to summarize the epidemiologic data relating magnesium to the metabolic syndrome and to discuss the potential mechanisms.

Publication Types:

• Review

High fructose consumption combined with low dietary magnesium intake may increase the incidence of the metabolic syndrome by inducing inflammation

Magnes Res. 2006 Dec;19(4):237-43

Rayssiguier Y, Gueux E, Nowacki W, Rock E, Mazur A.

The metabolic syndrome is a cluster of common pathologies: abdominal obesity linked to an excess of visceral fat, insulin resistance, dyslipidemia and hypertension. This syndrome is occurring at epidemic rates, with dramatic consequences for human health worldwide, and appears to have emerged largely from changes in our diet and reduced physical activity. An important but not well-appreciated dietary change has been the substantial increase in fructose intake, which appears to be an important causative factor in the metabolic syndrome. There is also experimental and clinical evidence that the amount of magnesium in the western diet is insufficient to meet individual needs and that magnesium deficiency may contribute to insulin resistance. In recent years, several studies have been published that implicate subclinical chronic inflammation as an important pathogenic factor in the development of metabolic syndrome. Pro-inflammatory molecules produced by adipose tissue have been implicated in the development of insulin resistance. The present review will discuss experimental evidence showing that the metabolic syndrome, high fructose intake and low magnesium diet may all be linked to the inflammatory response. In many ways, fructose-fed rats display the changes observed in the metabolic syndrome and recent studies indicate that high-fructose feeding is associated with NADPH oxidase and renin-angiotensin activation. The production of reactive oxygen species results in the initiation and development of insulin resistance, hyperlipemia and high blood pressure in this model. In this rat model, a few days of experimental magnesium deficiency produces a clinical inflammatory syndrome characterized by leukocyte and macrophage activation, release of inflammatory cytokines, appearance of the acute phase proteins and excessive production of free radicals. Because magnesium acts as a natural calcium antagonist, the molecular basis for the inflammatory response is probably the result of a modulation of the intracellular calcium concentration. Potential mechanisms include the priming of phagocytic cells, the opening of calcium channels, activation of N-methyl-D-aspartate (NMDA) receptors, the activation of nuclear factor-kappaB (NFkB) and activation of the renin-angiotensin system. Since magnesium deficiency has a pro-inflammatory effect, the expected consequence would be an increased risk of developing insulin resistance when magnesium deficiency is combined with a high-fructose diet. Accordingly, magnesium deficiency combined with a high-fructose diet induces insulin resistance, hypertension, dyslipidemia, endothelial activation and prothrombic changes in combination with the upregulation of markers of inflammation and oxidative stress.

Publication Types:

• Review

Low serum magnesium levels and metabolic syndrome

Acta Diabetol. 2002 Dec;39(4):209-13

Guerrero-Romero F, Rodríguez-Morán M.

Low serum magnesium levels are related to diabetes mellitus (DM) and high blood pressure (HBP), but as far as we know, there are no previous reports that analyzed the serum magnesium concentration in individuals with metabolic syndrome (MS). We performed a cross-sectional population-based study to compare 192 individuals with MS and 384 disorder-free control subjects, matched by age and gender. Magnesium supplementation treatment and conditions likely to provoke hypomagnesemia, including previous diagnosis of diabetes mellitus (DM) and/or high blood pressure (HBP), were exclusion criteria. In this regard, only incident cases of DM and HBP were included. MS was defined by the presence at least of two of the following features: hyperglycemia (> or =7.0 mmol/l); HBP (> or =160/90 mmHg); dyslipidemia (fasting triglycerides > or =1.7 mmol/l and/or HDL-cholesterol <1.0 mmol/l); and obesity (body mass index > or =30 kg/m(2) and/or waist-to-hip ratio > or =0.85 in women or > or =0.9 in men). Low serum magnesium levels were identified in 126 (65.6%) and 19 (4.9%) individuals with and without MS, p<0.00001. The mean serum magnesium level among subjects with MS was 1.8+/-0.3 mg/dl, and among control subjects 2.2+/-0.2 mg/dl, p<0.00001. There was a strong independent relationship between low serum magnesium levels and MS (odds ratio (OR)=6.8, CI(95%) 4.2-10.9). Among the components of MS, dyslipidemia (OR 2.8, CI(95%) 1.3-2.9) and HBP (OR 1.9, CI(95%) 1.4-2.8) were strongly related to low serum magnesium levels. This study reveals a strong relationship between decreased serum magnesium and MS.

Publication Types:

• cross-sectional population-based study

Publication Types:

• Review