Magnesium Abstracts 6


The relationship between dietary magnesium intake, stroke and its major risk factors, blood pressure and cholesterol, in the EPIC-Norfolk cohort.
            (Bain et al., 2015) Download
BACKGROUND:  Dietary magnesium could modify the major stroke risk factors, high blood pressure (BP) and cholesterol, but has been understudied in both sexes in a single population. This study aimed to investigate if dietary magnesium intake was associated with BP, total cholesterol (TC) and incident stroke risk in an adult population. METHODS:  We conducted cross-sectional analyses in a case-cohort study of 4443, men and women aged 40-75, representative of 25,639 participants years of the EPIC (European Prospective Investigation into Cancer)-Norfolk cohort. The cohort included 928 stroke cases (42,556.5 person years). Dietary data from 7 day food diaries were analysed using multivariate regression to assess associations between quintiles or data-derived categories of dietary magnesium intake and BP, TC and stroke risk, adjusted for relevant confounders. RESULTS:  We observed differences of -7 mmHg systolic BP (P trend ≤ 0.01) and -3.8 mmHg diastolic BP (P trend=0.01) between extreme intakes of magnesium in men, a significant inverse association with TC was observed (P trend=0.02 men and 0.04 women). Compared to the bottom 10%, the top 30% of magnesium intake was associated with a 41% relative reduction in stroke risk (HR 0.59; 95% CI 0.38-0.93) in men. CONCLUSIONS:  Lower dietary magnesium intake was associated with higher BP and stroke risk, which may have implications for primary prevention.

Urinary magnesium excretion in asthmatic children receiving magnesium supplementation: a randomized, placebo-controlled, double-blind study.
            (Bede et al., 2003) Download
The aims of this study were to establish whether a magnesium (Mg) deficit indicated by a decreased urinary excretion exists and to determine whether 12-week oral Mg supplementation affects the Mg status and bronchodilator use in children with stable bronchial asthma. The effects of long-lasting Mg supplementation were investigated in 89 children 4 to 16 years of age with mild or moderate persistent bronchial asthma in a randomized, double-blind, placebo-controlled, prospective study. Each subject received one capsule of Mg citrate per day (= 7 years: 200 mg, > 7 years: 290 mg) or one capsule of placebo containing 260 mg glucose during 12 weeks. Evaluation was performed at 4-week intervals. Venous blood serum total and free Mg and urine Mg levels were determined at the beginning and end of the 12-week period. Parents recorded the number of bronchodilator doses twice daily. A urinary Mg loss (6.81 +/- 3.9 versus 2.79 +/- 1.39 mmol/day, p = 0.01) was observed in the placebo-treated persistent moderate asthmatics. Bronchodilator use was significantly higher after 8 and 12 weeks in the placebo-treated than in the Mg-treated patients with moderate asthma (31.1 +/- 1.8 versus 29.5 +/- 1.2 puffs per patient/4 weeks, p < 0.05, and 31.0 +/- 2.3 versus 29.3 +/- 0.9 puffs per patient/4 weeks, p < 0.05, respectively). Long-lasting Mg supplementation is clearly of benefit in mildly to moderately asthmatic children and is recommended as a concomitant drug in stable asthma.

Declining fruit and vegetable nutrient composition: What is the evidence?
            (Davis, 2009) Download
Three kinds of evidence point toward declines of some nutrients in fruits and vegetables available in the United States and the United Kingdom: 1) early studies of fertilization found inverse relationships between crop yield and mineral concentrations—the widely cited ‘‘dilution effect’’; 2) three recent studies of historical food composition data found apparent median declines of 5% to 40% or more in some minerals in groups of vegetables and perhaps fruits; one study also evaluated vitamins and protein with similar results; and 3) recent side-by-side plantings of low- and high-yield cultivars of broccoli and grains found consistently negative correlations between yield and concentrations of minerals and protein, a newly recognized genetic dilution effect. Studies of historical food composition data are inherently limited, but the other methods can focus on single crops of any kind, can include any nutrient of interest, and can be carefully controlled. They can also test proposed methods to minimize or overcome the diluting effects of yield whether by environmental means or by plant breeding.

Circulating and dietary magnesium and risk of cardiovascular disease: a systematic review and meta-analysis of prospective studies.
            (Del Gobbo et al., 2013) Download
BACKGROUND:  Clinical hypomagnesemia and experimental restriction of dietary magnesium increase cardiac arrhythmias. However, whether or not circulating or dietary magnesium at usual concentrations or intakes influences the risk of cardiovascular disease (CVD), including fatal ischemic heart disease (IHD), is unclear. OBJECTIVE:  We performed a systematic review and meta-analysis to investigate prospective associations of circulating and dietary magnesium with incidence of CVD, IHD, and fatal IHD. DESIGN:  Multiple literature databases were systematically searched without language restriction through May 2012. Inclusion decisions and data extraction were performed in duplicate. Linear dose-response associations were assessed by using random-effects meta-regression. Potential nonlinear associations were evaluated by using restricted cubic splines. RESULTS:  Of 2303 articles, 16 studies met the eligibility criteria; these studies comprised 313,041 individuals and 11,995 CVD, 7534 IHD, and 2686 fatal IHD events. Circulating magnesium (per 0.2 mmol/L increment) was associated with a 30% lower risk of CVD (RR: 0.70; 95% CI: 0.56, 0.88 per 0.2 mmol/L) and trends toward lower risks of IHD (RR: 0.83; 95% CI: 0.75, 1.05) and fatal IHD (RR: 0.61; 95% CI: 0.37, 1.00). Dietary magnesium (per 200-mg/d increment) was not significantly associated with CVD (RR: 0.89; 95% CI: 0.75, 1.05) but was associated with a 22% lower risk of IHD (RR: 0.78; 95% CI: 0.67, 0.92). The association of dietary magnesium with fatal IHD was nonlinear (P < 0.001), with an inverse association observed up to a threshold of ∼250 mg/d (RR: 0.73; 95% CI: 0.62, 0.86), compared with lower intakes. CONCLUSION:  Circulating and dietary magnesium are inversely associated with CVD risk, which supports the need for clinical trials to evaluate the potential role of magnesium in the prevention of CVD and IHD.

Oral magnesium supplementation in asthmatic children: a double-blind randomized placebo-controlled trial.
            (Gontijo-Amaral et al., 2007) Download
OBJECTIVE:  To investigate the long-term effect of oral magnesium supplementation on clinical symptoms, bronchial reactivity, lung function and allergen-induced skin responses in children and adolescents with moderate persistent asthma. DESIGN:  A double-blind randomized parallel placebo-controlled study. SETTING AND SUBJECTS:  The patients were recruited from the Pediatric Outpatient Clinic, Division of Pulmonology, Allergy and Immunology, and followed at the Center for Investigation in Pediatrics at State University of Campinas Hospital, Brazil. Thirty-seven out of 72 patients met the study criteria. There were no dropouts. INTERVENTION:  The 37 patients (aged 7-19 years, 19 males) were randomized in two groups: magnesium (n=18, 300 mg/day) and placebo (n=19), during 2 months. Both patient groups received inhaled fluticasone (250 microg twice a day) and salbutamol as needed. The primary outcome was bronchial reactivity evaluated with methacholine challenge test (PC20). RESULTS:  After a follow-up of 2 months, the methacholine PC20 for testing bronchial reactivity has augmented significantly in the magnesium group only. The skin responses to recognized antigens have also decreased in patients treated with magnesium. The forced vital capacity (FVC), the forced expiratory volume at first second (FEV1), the forced expiratory flow at 25-75 and the FEV1/FVC ratio were similar in both groups. The magnesium group presented fewer asthma exacerbations and used less salbutamol compared to the placebo group. CONCLUSIONS:  Oral magnesium supplementation helped to reduce bronchial reactivity to methacholine, to diminish their allergen-induced skin responses and to provide better symptom control in pediatric patients with moderate persistent asthma treated with inhaled fluticasone.

Hypomagnesemia in patients with eating disorders
            (Hall et al., 1988) Download
175 patients admitted to the Eating Disorder Unit of Florida were evaluated. 100 eating-disorder patients with normal magnesium were used as controls. The study demonstrated an incidence of hypomagnesia of 25% (42 of 175). Eight symptoms statistically defined the hypomagnesia group: muscular weakness, cramping of the extremities, restlessness, parasthesias, cardiac arrythmias, hypertension and diminished recent memory.

Hypomagnesemia in eating disorder patients: clinical signs and symptoms
            (Hall et al., 1989) Download
Serum magnesium assays coupled with 24 hour urinary excretion patterns and magnesium loading tests establish the diagnosis.

Magnesium intake and incidence of metabolic syndrome among young adults.
            (He et al., 2006) Download
BACKGROUND:  Studies suggest that magnesium intake may be inversely related to risk of hypertension and type 2 diabetes mellitus and that higher intake of magnesium may decrease blood triglycerides and increase high-density lipoprotein (HDL) cholesterol levels. However, the longitudinal association of magnesium intake and incidence of metabolic syndrome has not been investigated. METHODS AND RESULTS:  We prospectively examined the relations between magnesium intake and incident metabolic syndrome and its components among 4637 Americans, aged 18 to 30 years, who were free from metabolic syndrome and diabetes at baseline. Metabolic syndrome was diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III definition. Diet was assessed by an interviewer-administered quantitative food frequency questionnaire, and magnesium intake was derived from the nutrient database developed by the Minnesota Nutrition Coordinating Center. During the 15 years of follow-up, 608 incident cases of the metabolic syndrome were identified. Magnesium intake was inversely associated with incidence of metabolic syndrome after adjustment for major lifestyle and dietary variables and baseline status of each component of the metabolic syndrome. Compared with those in the lowest quartile of magnesium intake, multivariable-adjusted hazard ratio of metabolic syndrome for participants in the highest quartile was 0.69 (95% confidence interval [CI], 0.52 to 0.91; P for trend <0.01). The inverse associations were not materially modified by gender and race. Magnesium intake was also inversely related to individual component of the metabolic syndrome and fasting insulin levels. CONCLUSIONS:  Our findings suggest that young adults with higher magnesium intake have lower risk of development of metabolic syndrome.


The effect of magnesium supplementation on blood pressure: a meta-analysis of randomized clinical trials.
            (Jee et al., 2002) Download
BACKGROUND:  An increased intake of magnesium might lower blood pressure (BP), yet evidence from clinical trials is inconsistent, perhaps as a result of small sample size or heterogeneity in study design. METHODS:  We performed a meta-analysis of randomized trials that tested the effects of magnesium supplementation on BP. Twenty trials meeting the inclusion criteria were identified. Random effects models and meta-regression methods were used to pool study results and to determine the dose-response relationship of magnesium to BP. RESULTS:  The 20 studies included 14 of hypertensive and 6 of normotensive persons totaling 1220 participants. The doses of magnesium ranged from 10 to 40 mmol/day (median, 15.4 mmol/day). Magnesium supplementation resulted in only a small overall reduction in BP. The pooled net estimates of BP change (95% confidence interval [CI]) were -0.6 (-2.2 to 1.0) mm Hg for systolic BP and -0.8 (-1.9 to 0.4) mm Hg for diastolic BP. However, there was an apparent dose-dependent effect of magnesium, with reductions of 4.3 mm Hg systolic BP (95% CI 6.3 to 2.2; P < .001) and of 2.3 mm Hg diastolic BP (95% CI 4.9 to 0.0; P = .09) for each 10 mmol/day increase in magnesium dose. CONCLUSIONS:  Our meta-analysis detected dose-dependent BP reductions from magnesium supplementation. However, adequately powered trials with sufficiently high doses of magnesium supplements need to be performed to confirm this relationship.

Metal ions: supporting actors in the playbook of small ribozymes.
            (Johnson-Buck et al., 2011) Download
Since the 1980s, several small RNA motifs capable of chemical catalysis have been discovered. These small ribozymes, composed of between approximately 40 and 200 nucleotides, have been found to play vital roles in the replication of subviral and viral pathogens, as well as in gene regulation in prokaryotes, and have recently been discovered in noncoding eukaryotic RNAs. All of the known natural small ribozymes - the hairpin, hammerhead, hepatitis delta virus, Varkud satellite, and glmS ribozymes--catalyze the same self-cleavage reaction as RNase A, resulting in two products, one bearing a 2'-3' cyclic phosphate and the other a 5'-hydroxyl group. Although originally thought to be obligate metalloenzymes like the group I and II self-splicing introns, the small ribozymes are now known to support catalysis in a wide variety of cations that appear to be only indirectly involved in catalysis. Nevertheless, under physiologic conditions, metal ions are essential for the proper folding and function of the small ribozymes, the most effective of these being magnesium. Metal ions contribute to catalysis in the small ribozymes primarily by stabilizing the catalytically active conformation, but in some cases also by activating RNA functional groups for catalysis, directly participating in catalytic acid-base chemistry, and perhaps by neutralizing the developing negative charge of the transition state. Although interactions between the small ribozymes and cations are relatively nonspecific, ribozyme activity is quite sensitive to the types and concentrations of metal ions present in solution, suggesting a close evolutionary relationship between cellular metal ion homeostasis and cation requirements of catalytic RNAs, and perhaps RNA in general.

Serum Magnesium and the Risk of Death From Coronary Heart Disease and Sudden Cardiac Death.
            (Kieboom et al., 2016) Download
BACKGROUND:  Low serum magnesium has been implicated in cardiovascular mortality, but results are conflicting and the pathway is unclear. We studied the association of serum magnesium with coronary heart disease (CHD) mortality and sudden cardiac death (SCD) within the prospective population-based Rotterdam Study, with adjudicated end points and long-term follow-up. METHODS AND RESULTS:  Nine-thousand eight-hundred and twenty participants (mean age 65.1 years, 56.8% female) were included with a median follow-up of 8.7 years. We used multivariable Cox proportional hazard models and found that a 0.1 mmol/L increase in serum magnesium level was associated with a lower risk for CHD mortality (hazard ratio: 0.82, 95% CI 0.70-0.96). Furthermore, we divided serum magnesium in quartiles, with the second and third quartile combined as reference group (0.81-0.88 mmol/L). Low serum magnesium (≤0.80 mmol/L) was associated with an increased risk of CHD mortality (N=431, hazard ratio: 1.36, 95% CI 1.09-1.69) and SCD (N=217, hazard ratio: 1.54, 95% CI 1.12-2.11). Low serum magnesium was associated with accelerated subclinical atherosclerosis (expressed as increased carotid intima-media thickness: +0.013 mm, 95% CI 0.005-0.020) and increased QT-interval, mainly through an effect on heart rate (RR-interval: -7.1 ms, 95% CI -13.5 to -0.8). Additional adjustments for carotid intima-media thickness and heart rate did not change the associations with CHD mortality and SCD. CONCLUSIONS:  Low serum magnesium is associated with an increased risk of CHD mortality and SCD. Although low magnesium was associated with both carotid intima-media thickness and heart rate, this did not explain the relationship between serum magnesium and CHD mortality or SCD. Future studies should focus on why magnesium associates with CHD mortality and SCD and whether intervention reduces these risks.

Dietary magnesium and C-reactive protein levels.
            (King et al., 2005) Download
OBJECTIVE:  Current dietary guidelines recommend adequate intake of magnesium (310-420 mg daily) in order to maintain health and lower the risk of cardiovascular disease. Recent evidence from animal and clinical studies suggests that magnesium may be associated with inflammatory processes. The objective of this study was to determine whether dietary magnesium consumption is associated with C-reactive protein (CRP), a marker of inflammation, in a nationally representative sample. METHODS:  Analysis of adult (> or =17 years) participants in a cross-sectional nationally representative survey (National Health and Nutrition Examination Survey 1999-2000 [NHANES]) who were not taking magnesium or magnesium-containing supplements. The primary outcome measure was high sensitivity CRP (elevated > or =3.0 mg/L). RESULTS:  Among US adults, 68% consumed less than the recommended daily allowance (RDA) of magnesium, and 19% consumed less than 50% of the RDA. After controlling for demographic and cardiovascular risk factors, adults who consumed <RDA of magnesium were 1.48-1.75 times more likely to have elevated CRP than adults who consumed > or =RDA (Odds Ratio [OR] for intake <50% RDA = 1.75, 95% Confidence Interval [CI] 1.08-2.87). Adults who were over age 40 with a BMI >25 and who consumed <50% RDA for magnesium were 2.24 times more likely to have elevated CRP (95% CI 1.13-4.46) than adults > or =RDA. CONCLUSIONS:  Most Americans consume magnesium at levels below the RDA. Individuals with intakes below the RDA are more likely to have elevated CRP, which may contribute to cardiovascular disease risk.

Dietary magnesium intake and risk of cancer: a meta-analysis of epidemiologic studies.
            (Ko et al., 2014) Download
The aim of this study was to investigate the association between dietary magnesium and the risk of overall cancer using a meta-analysis. We searched PubMed, SCOPUS, and the Cochrane Review through November 2012. All the articles searched were independently reviewed by 3 authors based on predetermined selection criterion. A total of 13 epidemiologic studies, 6 case-control studies, and 7 prospective cohort studies involving 1,236,004 participants were included in the final analysis. When all studies were pooled, the relative risk (RR) of overall cancer for the highest level of dietary magnesium intake was 0.801 [95% confidence interval (CI): 0.664-0.966) compared with the lowest level of dietary magnesium intake. In subgroup meta-analyses by study design, there was a significant inverse association between dietary magnesium and the risk of cancer in case-control studies (RR = 0.663, 95% CI: 0.475-0.925), whereas there was no significant association in prospective cohort studies (RR = 0.888, 95% CI: 0.745-1.060). Furthermore, there was a significant preventive effect of dietary magnesium for colorectal cancer (RR = 0.775, 95% CI: 0.655-0.919), but not for other cancer. Our meta-analysis showed that higher dietary magnesium intake seems to have a protective effect for cancer, especially colorectal cancer and in females.


Correcting magnesium deficiencies may prolong life.
            (Rowe, 2012) Download
The International Space Station provides an extraordinary facility to study the accelerated aging process in microgravity, which could be triggered by significant reductions in magnesium (Mg) ion levels with, in turn, elevations of catecholamines and vicious cycles between the two. With space flight there are significant reductions of serum Mg (P < 0.0001) that have been shown in large studies of astronauts and cosmonauts. The loss of the functional capacity of the cardiovascular system with space flight is over ten times faster than the course of aging on Earth. Mg is an antioxidant and calcium blocker and in space there is oxidative stress, insulin resistance, and inflammatory conditions with evidence in experimental animals of significant endothelial injuries and damage to mitochondria. The aging process is associated with progressive shortening of telomeres, repetitive DNA sequences, and proteins that cap and protect the ends of chromosomes. Telomerase can elongate pre-existing telomeres to maintain length and chromosome stability. Low telomerase triggers increased catecholamines while the sensitivity of telomere synthesis to Mg ions is primarily seen for the longer elongation products. Mg stabilizes DNA and promotes DNA replication and transcription, whereas low Mg might accelerate cellular senescence by reducing DNA stability, protein synthesis, and function of mitochondria. Telomerase, in binding to short DNAs, is Mg dependent. On Earth, in humans, a year might be required to detect changes in telomeres, but in space there is a predictably much shorter duration required for detection, which is therefore more reasonable in time and cost. Before and after a space mission, telomere lengths and telomerase enzyme activity can be determined and compared with age-matched control rats on Earth. The effect of Mg supplementation, both on maintaining telomere length and extending the life span, can be evaluated. Similar studies in astronauts would be fruitful.

Dietary magnesium intake and risk of cardiovascular disease among women.
            (Song et al., 2005) Download
This study assessed the hypothesis that greater magnesium intake is associated with reduced risk for cardiovascular disease (CVD), including myocardial infarction (MI) and stroke, in a large prospective cohort of women. In 1993, a semi-quantitative food frequency questionnaire was used to assess magnesium intake in 39,876 female health professionals aged 39 to 89 years who had no history of CVD or cancer. During a median of 10 years of follow-up, 1,037 incident cases of CVD were identified, including 280 nonfatal MIs and 368 strokes. After adjustment for age and randomized treatment status, magnesium intake was not significantly associated with risk for incident CVD. Comparing the highest quintile of magnesium intake (median 433 mg/day) with the lowest quintile (median 255 mg/day), the relative risks were 0.87 (95% confidence interval [CI] 0.72 to 1.05, p for trend = 0.24) for total CVD, 0.88 (95% CI 0.70 to 1.12, p for trend = 0.34) for coronary heart disease (CHD), 1.03 (95% CI 0.72 to 1.49, p for trend = 0.96) for nonfatal MI, 1.11 (95% CI 0.61 to 2.00, p for trend = 0.95) for CVD death, and 0.87 (95% CI 0.64 to 1.18, p for trend = 0.55) for total stroke. Additional adjustment for other CVD risk factors did not materially change the observed null associations. In conclusion, the results do not support the hypothesis that magnesium intake reduces the development of CHD, although a modest inverse association with stroke cannot be ruled out.

Magnesium intake and colorectal tumor risk: a case-control study and meta-analysis.
            (Wark et al., 2012) Download
BACKGROUND:  Dietary magnesium might be related to colorectal tumor risk through the pivotal roles of magnesium in cellular metabolism, insulin resistance, and systemic inflammation. OBJECTIVE:  We evaluated the hypothesis of whether higher dietary magnesium intake is associated with reduced colorectal tumor risk. DESIGN:  A case-control study on colorectal adenomas (768 cases; 709 polyp-free control subjects) and a meta-analysis of colorectal adenomas (3 case-control studies) and carcinomas (6 prospective cohort studies) were conducted. Dietary magnesium was estimated from food-frequency questionnaires in the case-control study and most studies in the meta-analyses. Data analysis comprised multiple logistic regression analysis (case-control study) and fixed- and random-effects meta-analyses. RESULTS:  The case-control study showed a nonsignificant inverse association between dietary magnesium intake and risk of colorectal adenomas (OR for every 100-mg/d increase: 0.81; 95% CI: 0.62, 1.06). However, inverse associations were observed only in subjects with BMI (in kg/m²) ≥25, in subjects aged ≥55 y, and for advanced adenomas. Associations did not vary by the calcium-to-magnesium intake ratio. In the meta-analysis, every 100-mg/d increase in magnesium intake was associated with 13% lower risk of colorectal adenomas (OR: 0.87; 95% CI: 0.75, 1.00) and 12% lower risk of colorectal cancer (RR: 0.88; 95% CI: 0.81, 0.97). CONCLUSIONS:  Our findings support the hypothesis that higher intakes of dietary magnesium are associated with lower risk of colorectal tumors. The consumption of magnesium-rich foods may be a new avenue to explore further in the search for cancer-prevention strategies.


The dose-dependent reduction in blood pressure through administration of magnesium. A double blind placebo controlled cross-over study.
            (Widman et al., 1993) Download
Seventeen patients with a diastolic blood pressure over 90 mm Hg were recruited from a running health screening program to participate in a double blind cross-over study of magnesium supplementation (15 mmol Mg2+/day (Emgesan, Kabi Pharmacia) for 3 weeks, followed by 30 mmol Mg2+/day for another 3 weeks, finishing with 40 mmol Mg2+/day for a final 3 weeks). A significant decrease in the mean systolic blood pressure was recorded from 154.0 +/- 10.7 mm Hg to 146.1 +/- 16.9 mm Hg (P = .031) while the mean diastolic blood pressure decreased from 100.2 +/- 4.2 mm Hg to 92.0 +/- 6.6 mm Hg (P = .0001).



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Song, S, et al. (2015), ‘Long-Term Diabetes Mellitus Is Associated with an Increased Risk of Pancreatic Cancer: A Meta-Analysis.’, PLoS One, 10 (7), e0134321. PubMed: 26222906
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