Center for Magnesium Education and Research

Pahoa, HI, United States

Center for Magnesium Education and Research

Pahoa, HI, United States
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Kass L.,University of Hertfordshire | Rosanoff A.,Center for Magnesium Education and Research | Tanner A.,University of Hertfordshire | Sullivan K.,University of Hertfordshire | And 2 more authors.
PLoS ONE | Year: 2017

Background Oral magnesium supplementation is commonly used to support a low magnesium diet. This investigation set out to determine whether magnesium in a cream could be absorbed transdermally in humans to improve magnesium status. Methods and findings In this single blind, parallel designed pilot study, n = 25 participants (aged 34.3+/-14.8y, height 171.5+/-11cm, weight 75.9 +/-14 Kg) were randomly assigned to either a 56mg/day magnesium cream or placebo cream group for two weeks. Magnesium serum and 24hour urinary excretion were measured at baseline and at 14 days intervention. Food diaries were recorded for 8 days during this period. Mg test and placebo groups' serum and urinary Mg did not differ at baseline. After the Mg2+ cream intervention there was a clinically relevant increase in serum magnesium (0.82 to 0.89 mmol/l,p = 0.29) that was not seen in the placebo group (0.77 to 0.79 mmol/L), but was only statistically significant (p = 0.02)) in a subgroup of non-athletes. Magnesium urinary excretion increased from baseline slightly in the Mg2+ group but with no statistical significance (p = 0.48). The Mg2+ group showed an 8.54% increase in serum Mg2+ and a 9.1% increase in urinary Mg2+ while these figures for the placebo group were smaller, i.e. +2.6% for serum Mg2+ and -32% for urinary Mg2+. In the placebo group, both serum and urine concentrations showed no statistically significant change after the application of the placebo cream. Conclusion No previous studies have looked at transdermal absorbency of Mg2+ in human subjects. In this pilot study, transdermal delivery of 56 mg Mg/day (a low dose compared with commercial transdermal Mg2+ products available) showed a larger percentage rise in both serum and urinary markers from pre to post intervention compared with subjects using the placebo cream, but statistical significance was achieved only for serum Mg2+ in a subgroup of nonathletes. Future studies should look at higher dosage of magnesium cream for longer durations. © 2017 Kass et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


PubMed | University of Minnesota, Northwestern University, Indiana University, University of Louisville and 5 more.
Type: Journal Article | Journal: Advances in nutrition (Bethesda, Md.) | Year: 2017

The 2015 Dietary Guidelines Advisory Committee indicated that magnesium was a shortfall nutrient that was underconsumed relative to the Estimated Average Requirement (EAR) for many Americans. Approximately 50% of Americans consume less than the EAR for magnesium, and some age groups consume substantially less. A growing body of literature from animal, epidemiologic, and clinical studies has demonstrated a varied pathologic role for magnesium deficiency that includes electrolyte, neurologic, musculoskeletal, and inflammatory disorders; osteoporosis; hypertension; cardiovascular diseases; metabolic syndrome; and diabetes. Studies have also demonstrated that magnesium deficiency is associated with several chronic diseases and that a reduced risk of these diseases is observed with higher magnesium intake or supplementation. Subclinical magnesium deficiency can exist despite the presentation of a normal status as defined within the current serum magnesium reference interval of 0.75-0.95 mmol/L. This reference interval was derived from data from NHANES I (1974), which was based on the distribution of serum magnesium in a normal population rather than clinical outcomes. What is needed is an evidenced-based serum magnesium reference interval that reflects optimal health and the current food environment and population. We present herein data from an array of scientific studies to support the perspective that subclinical deficiencies in magnesium exist, that they contribute to several chronic diseases, and that adopting a revised serum magnesium reference interval would improve clinical care and public health.


Zhang X.,Indiana University | Del Gobbo L.C.,Stanford University | Hruby A.,Harvard University | Rosanoff A.,Center for Magnesium Education and Research | And 5 more authors.
Journal of Nutrition | Year: 2016

Background: Accurate determination of Mgstatus is important for improving nutritional assessment and clinical risk stratification. Objective: We aimed to quantify the overall responsiveness of Mg biomarkers to oral Mg supplementation among adults without severe diseases and their dose- and time responses using available data from randomized controlled trials (RCTs). Methods: We identified 48 Mg supplementation trials (n = 2131) through searches of MEDLINE and the Cochrane Library up to November 2014. Random-effects meta-analysis was used to estimate weighted mean differences of biomarker concentrations between intervention and placebo groups. Restricted cubic splines were used to determine the dose- and time responses of Mg biomarkers to supplementation. Results: Among the 35 biomarkers assessed, serum, plasma, and urineMg were most commonlymeasured. ElementalMg supplementation doses ranged from 197 to 994 mg/d. Trials ranged from 3 wk to 5 y (median: 12 wk).Mg supplementation significantly elevated circulating Mg by 0.04 mmol/L (95% CI: 0.02, 0.06) and 24-h urine Mg excretion by 1.52 mmol/24 h (95% CI: 1.20, 1.83) as compared to placebo. Circulating Mg concentrations and 24-h urine Mg excretion responded to Mg supplementation in a dose- and time-dependent manner, gradually reaching a steady state at doses of 300 mg/d and 400 mg/d, or after ~20 wk and 40 wk, respectively (all P-nonlinearity ≤ 0.001). The higher the circulating Mg concentration at baseline, the lower the responsiveness of circulating Mg to supplementation, and the higher the urinary excretion (all Plinearity < 0.05). In addition, RBC Mg, fecal Mg, and urine calcium were significantly more elevated byMg supplementation than by placebo (all P-values < 0.05), but there is insufficient evidence to determine their responses to increasingMg doses. Conclusions: This meta-analysis of RCTs demonstrated significant dose- and time responses of circulating Mg concentration and 24-h urine Mg excretion to oral Mg supplementation.


PubMed | Vanderbilt University, Center for Magnesium Education and Research and Rutgers University
Type: Journal Article | Journal: Advances in nutrition (Bethesda, Md.) | Year: 2016

Although much is known about magnesium, its interactions with calcium and vitamin D are less well studied. Magnesium intake is low in populations who consume modern processed-food diets. Low magnesium intake is associated with chronic diseases of global concern [e.g., cardiovascular disease (CVD), type 2 diabetes, metabolic syndrome, and skeletal disorders], as is low vitamin D status. No simple, reliable biomarker for whole-body magnesium status is currently available, which makes clinical assessment and interpretation of human magnesium research difficult. Between 1977 and 2012, US calcium intakes increased at a rate 2-2.5 times that of magnesium intakes, resulting in a dietary calcium to magnesium intake ratio of >3.0. Calcium to magnesium ratios <1.7 and >2.8 can be detrimental, and optimal ratios may be 2.0. Background calcium to magnesium ratios can affect studies of either mineral alone. For example, US studies (background Ca:Mg >3.0) showed benefits of high dietary or supplemental magnesium for CVD, whereas similar Chinese studies (background Ca:Mg <1.7) showed increased risks of CVD. Oral vitamin D is widely recommended in US age-sex groups with low dietary magnesium. Magnesium is a cofactor for vitamin D biosynthesis, transport, and activation; and vitamin D and magnesium studies both showed associations with several of the same chronic diseases. Research on possible magnesium and vitamin D interactions in these human diseases is currently rare. Increasing calcium to magnesium intake ratios, coupled with calcium and vitamin D supplementation coincident with suboptimal magnesium intakes, may have unknown health implications. Interactions of low magnesium status with calcium and vitamin D, especially during supplementation, require further study.


PubMed | Fukushima Medical University, Indiana University, Stanford University, Indiana University Bloomington and 3 more.
Type: Journal Article | Journal: The Journal of nutrition | Year: 2016

Accurate determination of Mg status is important for improving nutritional assessment and clinical risk stratification.We aimed to quantify the overall responsiveness of Mg biomarkers to oral Mg supplementation among adults without severe diseases and their dose- and time responses using available data from randomized controlled trials (RCTs).We identified 48 Mg supplementation trials (n = 2131) through searches of MEDLINE and the Cochrane Library up to November 2014. Random-effects meta-analysis was used to estimate weighted mean differences of biomarker concentrations between intervention and placebo groups. Restricted cubic splines were used to determine the dose- and time responses of Mg biomarkers to supplementation.Among the 35 biomarkers assessed, serum, plasma, and urine Mg were most commonly measured. Elemental Mg supplementation doses ranged from 197 to 994 mg/d. Trials ranged from 3 wk to 5 y (median: 12 wk). Mg supplementation significantly elevated circulating Mg by 0.04 mmol/L (95% CI: 0.02, 0.06) and 24-h urine Mg excretion by 1.52 mmol/24 h (95% CI: 1.20, 1.83) as compared to placebo. Circulating Mg concentrations and 24-h urine Mg excretion responded to Mg supplementation in a dose- and time-dependent manner, gradually reaching a steady state at doses of 300 mg/d and 400 mg/d, or after ~20 wk and 40 wk, respectively (all P-nonlinearity 0.001). The higher the circulating Mg concentration at baseline, the lower the responsiveness of circulating Mg to supplementation, and the higher the urinary excretion (all P-linearity < 0.05). In addition, RBC Mg, fecal Mg, and urine calcium were significantly more elevated by Mg supplementation than by placebo (all P-values < 0.05), but there is insufficient evidence to determine their responses to increasing Mg doses.This meta-analysis of RCTs demonstrated significant dose- and time responses of circulating Mg concentration and 24-h urine Mg excretion to oral Mg supplementation.


Rosanoff A.,Center for Magnesium Education and Research | Capron E.,Center for Magnesium Education and Research | Barak P.,University of Wisconsin - Madison | Mathews B.,University of Hawaii at Hilo | Nielsen F.,U.S. Department of Agriculture
Crop and Pasture Science | Year: 2015

Unlike yield, the plant calcium (Ca):magnesium (Mg) ratio increases at higher soil Ca:Mg and decreases at lower soil Ca:Mg. Edible plant tissue Ca:Mg at various soil ratios has not been robustly studied. Such studies are appropriate because high Ca:Mg dietary ratios may be associated with increased risk of chronic diseases such as cardiovascular disease and diabetes, and human dietary Ca:Mg ratio is rising as populations integrate more processed foods into traditional diets. This review explores whether increasing the soil Ca:Mg ratio is likely to increase edible plant tissue Ca:Mg ratio, a result that could, if substantial, affect human health. A literature search gathered published articles reporting Ca and Mg values for plants grown in soils or nutrient solutions with various Ca:Mg ratios. For each study, soil or solution ratio was plotted against plant ratio, and Pearson's r and 2-tailed P values were calculated. Findings reveal that reporting Ca and Mg content of edible plant tissues is rare in studies assessing the impact of soil Ca:Mg on crop yields, nutrient uptake or crop quality; Ca:Mg of whole plants and most shoots increases as soil Ca:Mg rises; leaf Ca:Mg of some but not all crops increases as soil Ca:Mg rises; Ca:Mg ratios of edible grain, fruit and root tissues are smaller than those of leaves or shoots of the same crop; and Ca:Mg of grain, bean and fruit tissue may not respond to changes in soil Ca:Mg as much as Ca:Mg of plants, shoots and leaves. However, the data are too sparse for conclusions or even speculation. Further measurements of Ca and Mg in edible tissues destined for human consumption are necessary to asses any impact of soil Ca:Mg on the rising dietary Ca:Mg of humans and its health consequences. © CSIRO 2015.


Rosanoff A.,Center for Magnesium Education and Research | Weaver C.M.,Purdue University | Rude R.K.,University of Southern California
Nutrition Reviews | Year: 2012

In comparison with calcium, magnesium is an "orphan nutrient" that has been studied considerably less heavily. Low magnesium intakes and blood levels have been associated with type 2 diabetes, metabolic syndrome, elevated C-reactive protein, hypertension, atherosclerotic vascular disease, sudden cardiac death, osteoporosis, migraine headache, asthma, and colon cancer. Almost half (48%) of the US population consumed less than the required amount of magnesium from food in 2005-2006, and the figure was down from 56% in 2001-2002. Surveys conducted over 30 years indicate rising calcium-to-magnesium food-intake ratios among adults and the elderly in the United States, excluding intake from supplements, which favor calcium over magnesium. The prevalence and incidence of type 2 diabetes in the United States increased sharply between 1994 and 2001 as the ratio of calcium-to-magnesium intake from food rose from <3.0 to >3.0. Dietary Reference Intakes determined by balance studies may be misleading if subjects have chronic latent magnesium deficiency but are assumed to be healthy. Cellular magnesium deficit, perhaps involving TRPM6/7 channels, elicits calcium-activated inflammatory cascades independent of injury or pathogens. Refining the magnesium requirements and understanding how low magnesium status and rising calcium-to-magnesium ratios influence the incidence of type 2 diabetes, metabolic syndrome, osteoporosis, and other inflammation-related disorders are research priorities. © 2012 International Life Sciences Institute.


Rosanoff A.,Center for Magnesium Education and Research | Plesset M.R.,Center for Magnesium Education and Research
Magnesium Research | Year: 2013

Previously, we examined 44 human studies involving oral magnesium (Mg) supplementation for hypertension (HT), sorting them according to HT status, Mg dose and anti-hypertensive medication usage. We found that while some studies reported a significant lowering of blood pressure with Mg supplementation, others did not. We present here our first meta-analysis of a uniform subset from this series of studies. Seven studies, involving 135 hypertensive subjects on anti-hypertensive medication continuously for at least six months, with no more than a two-week washout and with a mean starting systolic blood pressure (SBP) >155 mmHg, demonstrated a mean change of -18.7 mmHg [95% CI = -14.95 to -22.45] p<0.0001 and an effect size test (Cohen's d) = 1.19, i.e. a large and highly significant effect. Meta-analysis of diastolic blood pressure (DBP) for these same seven studies showed a mean change in DBP of -10.9 mmHg [95% CI = -8.73 to -13.1], p<0.0001, with an effect size test (Cohen's d) = 1.19. Other studies from our original collection, approaching, but not meeting the >155mmHgstarting SBP values or not complying as regards anti-hypertensive medication usage, showed mean changes in both SBP and DBP with oral Mg that, while not approaching the high-responder values of the present study, appeared to include some high-responder subjects combined with low- or nonresponder subjects. This uniform subset of seven studies showed a strong effect of Mg treatment in hypertension, which is in stark contrast to results of three other meta-analyses. Using non-uniform sets of studies, the small effects reported in previous metaanalyses may reflect a blending of dissimilar studies, which acted to seriously underestimate the potential of Mg in hypertension in some (but not all) subjects. Within studies, blending of non-, moderate and highresponder subjects in any one study might mask strong effects of Mg treatment in some subjects.


Rosanoff A.,Center for Magnesium Education and Research
Magnesium Research | Year: 2010

USDA food surveys from 1977 through 2007-8 show a rising food Ca:Mg ratio for all USA adult age-gender groups. Food Ca:Mg intake ratios rose from 2.3-2.9 in 1977 to 2.9-3.5 in 2007-8. The % rise in mean Mg intakes compared closely with % rise in mean energy intakes while % rise in mean Ca intakes were substantially higher in all groups, suggesting the rising Ca:Mg comes from higher Ca intakes via food selections, rising food Ca contents or both. Original intake data from these surveys need to be accessed to calculate each individual's Ca:Mg for statistical assessment of this ratio rise. Ca:Mg rose from largely below 3.0 in 1994-5 to generally above or approaching 3.0 after 2000, coinciding with a sharp 2% rise in type 2 diabetes incidence and prevalence in the USA population and a 1994-2005 rise in colorectal cancer incidence among young white, non-Hispanic adult men and women in the USA. The intracellular Ca activation response to low Mg is discussed as a possible mechanism linking metabolic and inflammatory syndromes with low dietary Mg and rising dietary Ca:Mg ratio. Adequacy of both Ca and Mg as well as the Ca:Mg ratio are important in assessing study outcomes. Health consequences should be considered for the USA's 64-67% adults not meeting their Mg requirement from foods, many also consuming below their Ca requirements, and their increasing Ca:Mg ratio from foods.


Rosanoff A.,Center for Magnesium Education and Research
Magnesium Research | Year: 2010

Nutritional magnesium intake from foods in the United States of America (USA) is widely below individual daily requirements [1]. Magnesium in USA has been called the "orphan nutrient" by Robert Heaney due to its lack of attention by the USA nutrition research community during the 20th century - a time of prolific and varied nutrition research progress. USA's Dept. of Agriculture (USDA) first published food values for Ca, P and Fe in 1945; Mg content did not appear regularly in these large food tables until after 1977. Beyond its large study of USA population's serum Mg, 1971-74, NHANES does not measure or make available to researchers any blood or urinary Mg values among its vast array of measurements on a representative sampling of USA humans. Standard medical laboratory assessments do not routinely include serum, red blood cell (RBC) or urinary magnesium.

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