Magnesium is the fourth most abundant mineral and the second most abundant intracellular divalent cation and has been recognized as a cofactor for >300 metabolic reactions in the body. Some of the processes in which magnesium is a cofactor include, but are not limited to, protein synthesis, cellular energy production and storage, reproduction, DNA and RNA synthesis, and stabilizing mitochondrial membranes. Magnesium also plays a critical role in nerve transmission, cardiac excitability, neuromuscular conduction, muscular contraction, vasomotor tone, blood pressure, and glucose and insulin metabolism. Because of magnesium's many functions within the body, it plays a major role in disease prevention and overall health. Low levels of magnesium have been associated with a number of chronic diseases including migraine headaches, Alzheimer's disease, cerebrovascular accident (stroke), hypertension, cardiovascular disease, and type 2 diabetes mellitus. Good food sources of magnesium include unrefined (whole) grains, spinach, nuts, legumes, and white potatoes (tubers). This review presents recent research in the areas of magnesium and chronic disease, with the goal of emphasizing magnesium's role in disease prevention and overall health.

1. SUPPLEMENT
White Vegetables: A Forgotten Source of Nutrients
Magnesium in Disease Prevention
and Overall Health1,2
Stella Lucia Volpe*
Department of Nutrition Sciences, Center for Integrated Nutrition & Performance College of Nursing and Health Professions Drexel University,
Philadelphia, PA
ABSTRACT
Magnesium is the fourth most abundant mineral and the second most abundant intracellular divalent cation and has been recognized as a
cofactor for >300 metabolic reactions in the body. Some of the processes in which magnesium is a cofactor include, but are not limited to,
protein synthesis, cellular energy production and storage, reproduction, DNA and RNA synthesis, and stabilizing mitochondrial membranes.
Magnesium also plays a critical role in nerve transmission, cardiac excitability, neuromuscular conduction, muscular contraction, vasomotor
tone, blood pressure, and glucose and insulin metabolism. Because of magnesium’s many functions within the body, it plays a major role in
disease prevention and overall health. Low levels of magnesium have been associated with a number of chronic diseases including
migraine headaches, Alzheimer’s disease, cerebrovascular accident (stroke), hypertension, cardiovascular disease, and type 2 diabetes
mellitus. Good food sources of magnesium include unrefined (whole) grains, spinach, nuts, legumes, and white potatoes (tubers). This review
presents recent research in the areas of magnesium and chronic disease, with the goal of emphasizing magnesium’s role in disease prevention and
overall health. Adv. Nutr. 4: 378S–383S, 2013.
Introduction
Magnesium is the fourth most abundant mineral and the
second most abundant intracellular divalent cation and
has been recognized as a cofactor for >300 metabolic reac-
tions in the body (1,2). Approximately 50% of magnesium
is in the bone, 50% is in the tissues and organs, and 1% is in
the blood (1,2). Some of the processes in which magnesium
is a cofactor include, but are not limited to, protein synthesis,
cellular energy production and storage, reproduction, DNA
and RNA synthesis, and stabilizing mitochondrial membranes
(3–6). Magnesium also plays a critical role in maintaining nor-
mal nerve and muscle function, cardiac excitability (normal
heart rhythm), neuromuscular conduction, muscular contrac-
tion, vasomotor tone, normal blood pressure, bone integrity,
and glucose and insulin metabolism (3–16). In this regard,
magnesium deficiency has been associated with a number
of chronic diseases, including migraine headaches, Alz-
heimer’s diseases, cerebrovascular accident (stroke), hy-
pertension, cardiovascular disease, and type 2 diabetes
mellitus (17–22).
The Dietary Reference Intake for magnesium for adults is
310–420 mg/d; magnesium intake is often below these rec-
ommendations, particularly as people age (23). Although
magnesium content is high in whole grains and dark, leafy
green vegetables, magnesium is also high in white vegetables
such as white potatoes (24–26).
The purpose of this review is to present research in the
area of magnesium and disease. The goal of this paper is
to demonstrate the importance of magnesium’s role in dis-
ease prevention and overall health.
Current status of knowledge
Dietary Reference Intakes for magnesium
The Dietary Reference Intakes for magnesium has been
established as the RDA. They range from 80 mg/d for chil-
dren 1–3 y of age to 130 mg/d for children 4–8 y of age.
For older males, the RDA for magnesium ranges from as
1
Published in a supplement to Advances in Nutrition. Presented at the Purdue University
Roundtable on “White Vegetables: A Forgotten Source of Nutrients” held June 18–19, 2012
in Chicago, IL. The roundtable was sponsored by Purdue University. The roundtable and
supplement publication were supported by an unrestricted grant from the Alliance for
Potato Research and Education. All roundtable speakers received travel funding and an
honorarium for participation in the meeting and manuscript preparation. The views
expressed are those of the authors. The supplement coordinator was Catherine Nnoka, a
paid consultant to the Alliance for Potato Research and Education. Guest editor Connie
Weaver received compensation from the Alliance for Potato Research and Education for
travel expenses, manuscript preparation, and editorial services for the supplement
publication. Guest editor Cheryl Anderson received compensation from the Alliance for
Potato Research and Education for editorial services.
2
Author disclosures: S. L. Volpe, no conflicts of interest.
* To whom correspondence should be addressed. E-mail: Stella.L.Volpe@drexel.edu
378 S ã2013 American Society for Nutrition. Adv. Nutr. 4: 378S–383S, 2013; doi:10.3945/an.112.003483.
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2. low as 240 mg/d (range, 9–13 y of age) and increases to 420
mg/d for males 31 to 70 y of age and older. For females, the
RDA for magnesium ranges from 240 mg/d (9–13 y of age)
to 360 mg/d for females 14–18 y of age. The RDA for females
31 to 70 y of age and older is 320 mg/d (23).
It has been reported that ~60% of adults in the United
States do not consume the RDA for magnesium (27). The
lower intake of magnesium from a larger proportion of the
U.S. population may be related to the increased rate of chronic
disease. Nonetheless, increased diseases attributed to magne-
sium deficiency have not yet been reported, perhaps because
they have not been explored in the medical community and/or
because they may be related to a magnesium insufficiency and
not an overt magnesium deficiency. It has been reported,
however, that low magnesium status has been associated
with chronic inflammatory stress conditions (27).
In humans, deficient magnesium intakes are mostly con-
sidered marginal to moderate, i.e., between 50% and 90% of
the RDA and may be related to chronic inflammatory re-
sponse conditions (27). This inflammatory response could
play a role in obesity in humans because obesity has been
characterized as having a chronic low-grade inflammation
component and an increased incidence of a low magnesium
status (27). It is this marginal to moderate magnesium defi-
ciency through aggravating chronic inflammatory stress that
may be contributing significantly to the occurrence of ather-
osclerosis, hypertension, osteoporosis, type 2 diabetes melli-
tus, and certain types of cancer (27). Furthermore, certain
medications prescribed for such diseases, such as loop and
thiazide diuretics (often prescribed for hypertension and/or
congestive heart failure), can further exacerbate magnesium
loss, typically through the urine (28).
Food sources of magnesium
Although magnesium is a rather ubiquitous mineral, there is
no major food that provides an extremely high amount of
magnesium. The foods highest in magnesium include unre-
fined (whole) grains, spinach, nuts, legumes, and potatoes
(tubers) (26). Freedman and Keast (25) evaluated the contri-
bution of white potatoes, oven-baked potatoes, and French
fries to the nutrient needs in children and adolescents.
They reported that these vegetables provided at least 5%
of the magnesium intake. Thus, white vegetables that are
prepared healthfully need to be taken into consideration
when educating individuals on healthy nutrition options
for magnesium intake. Table 1 provides examples of the
amount of magnesium in some foods.
More recently, Freedman and Keast (29) evaluated 24-h
dietary recall data from NHANES 2003–2006 to establish nu-
trient contributions from white potatoes. They reported that,
among all groups of consumers, white potatoes (prepared in
various ways) contributed to w10% of the total daily intake
of various vitamins and minerals, including magnesium (29).
Magnesium status
Magnesium status can be measured via serum total magne-
sium concentrations, ionized magnesium levels, red blood
cell magnesium, and urinary magnesium levels using the
magnesium loading test. Of these, serum magnesium con-
centrations have been shown to be the least sensitive to mag-
nesium status unless there is a severe magnesium deficiency
already present (30); although ionized magnesium concen-
trations and the magnesium loading test have been shown
to be more accurate, there is still debate among researchers.
Although the magnesium loading test is still considered the
gold standard, it cannot be used in individuals with kidney
disease (30). Despite the fact that serum magnesium levels
are not sensitive to magnesium status, most researchers con-
tinue to use serum magnesium concentrations, but more re-
searchers are using ionized magnesium concentrations. If
possible, researchers should consider using 2 markers of
magnesium status to ensure reliable results.
Magnesium and migraine headaches
It has been reported that magnesium may be an effective
complementary treatment for migraine headaches (31). Mi-
graine headaches more than likely have a genetic basis.
These types of headache disorders stimulate a mechanism
deep in the brain that releases inflammatory products in the
region of the blood vessels and nerves of the brain. Migraines
can last anywhere from hours to days, with many individuals
unable to function normally during an attack. Attacks can be
as infrequent as once a year to as frequent as once a week, with
nausea being the most common symptom.
Although the cause of migraine headaches is unknown
(31). Mauskop (32) stated that the “efficacy of some non-
pharmacologic therapies appears to approach that of most
drugs used for the prevention of migraine and tension-
type headaches.” Therapies such as magnesium supplemen-
tation result in minimal to no side effects and are generally
low in cost (32).
In a comprehensive search strategy, Pringsheim et al. (33)
evaluated randomized, double-blind, controlled trials of
treatments for migraine prophylaxis. They graded the re-
search articles based on the criteria developed by the U.S.
Table 1. Foods high in magnesium1
Food Magnesium, mg
1/4 cup of wheat bran (57 g) 89
1 oz of dry roasted almonds (28.4 g) 80
1/2 cup of frozen, cooked spinach (14.2 g) 78
1 oz of mixed, dry roasted nuts (28.4 g) 64
3/4 cup of bran flakes cereal (170 g) 64
2 tbsp of smooth peanut butter (32 g) 49
1 medium baked potato with skin 48
1/2 cup of cooked pinto beans (113 g) 43
1/2 cup of brown, long-grained cooked rice
(113 g)
42
1/2 cup of mature seeds, cooked lentils, (113 g) 36
1 cup of low-fat chocolate milk (234 mL) 33
1 medium banana 32
8 fluid oz of low-fat fruit yogurt (234 mL) 32
1.5 oz of milk chocolate candy bar (43 g) 28
1 slice of whole-wheat bread,
commercially prepared
23
1/2 cup of avocado cubed (113 g) 22
1
Adapted from (26) with permission.
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3. Preventive Services Task Force. Based on the research that
they evaluated, Pringsheim et al. (33) strongly recommended
magnesium citrate, among a number of other medications
and supplements, for use as prophylaxis for migraines.
Nonetheless, they stated that prophylactic drug selection
should be based on a variety of issues, including migraine
clinical characteristics, other disorders/diseases, side effects,
and effectiveness.
In a randomized, placebo-controlled clinical trial, Tar-
ighat Esfaniani et al. (34) evaluated the effects of magnesium
on migraine symptoms. A total of 133 patients, with history
of migraine headaches, were randomly assigned to 1 of 4
groups: 1) 500 mg/d of magnesium oxide, 2) 500 mg/d of
L-carnitine, 3) 500 mg/d of magnesium oxide plus 500
mg/d of L-carnitine, 4) control group. Participants remained
on this regimen for 12 wk. The migraine indicators used
were number of attacks per month, number of days per
month, and headache severity. Although there was a signif-
icant decrease in migraine indicators in all groups, it was
found that magnesium supplementation had a significant
effect on all migraine indicators (34).
Data from trials conducted for as long as 12 wk suggest
that magnesium is an effective therapy for migraine head-
aches. Longer term trials with a greater number of partici-
pants are required to further evaluate the effects of
magnesium on migraine headaches.
Magnesium and Alzheimer’s disease
Alzheimer’s disease is the most widespread reason for de-
mentia (35). Alzheimer’s disease is the sixth leading cause
of death in the United States, with >79,000 deaths per
year (35). Barbagallo et al. (22) examined magnesium bal-
ance in patients with mild to moderate Alzheimer’s disease.
Their study population included 101 older patients (73.4 6
0.8 y of age; 42 men, 59 women) who were evaluated for
both serum total magnesium and serum ionized magnesium
concentrations and were administered the Mini-Mental
State Examination. Ionized magnesium concentrations were
significantly lower in the group with Alzheimer’s disease com-
pared with their age-matched controls without Alzheimer’s
disease (0.50 6 0.01 mmol/L vs. 0.53 6 0.01 mmol/L; P <
0.01); no significant differences existed between groups
with respect to serum magnesium concentrations. The ion-
ized magnesium concentrations were significantly related to
cognitive function and not physical function. Individuals
with Alzheimer’s disease had significantly lower Mini-
Mental State Examination scores (20.5 6 0.7 vs. 27.9 6
0.2; P < 0.001) and significantly lower scores for the physical
function tests. This study demonstrates an association be-
tween ionized magnesium concentrations and individuals
who have mild to moderate Alzheimer’s disease (22).
Ozawa et al. (36) examined whether a diet high in potas-
sium, calcium, and magnesium would reduce the risk of de-
mentia in 1081 community-dwelling Japanese men and
women, 60 y of age and older who did not have diagnosed
dementia. At the 17-y follow-up, 303 participants had a
diagnosis of dementia, 98 vascular dementia, and 166
Alzheimer’s disease. Ozawa et al. (36) reported a significant
inverse association between potassium, calcium, and mag-
nesium intake and all-cause dementia and vascular demen-
tia; the lower the intakes were, the greater the rates of
dementia. This same association was not observed with
Alzheimer’s disease. The strength of this study was the num-
ber of participants and the length of follow-up; however, no
causal effect can be determined for magnesium alone or any
of the other minerals because it was an observational study
and other confounding factors could have played a role.
Magnesium and cerebrovascular accident (stroke)
Cerebrovascular accidents (strokes) can lead to paralysis, in-
ability to speak and/or swallow normally (and thus lead to
malnutrition), or death. Strokes are the fourth leading cause
of death in the United States, with >128,000 deaths per year
(35). Strokes are typically a result of uncontrolled hyperten-
sion. Because of magnesium’s role in blood pressure control,
it has also been studied in relation to strokes. Larsson et al.
(37) conducted a meta-analysis to summarize the associa-
tion between magnesium intake and stroke risk. The criteria
the researchers chose for their meta-analysis were the fol-
lowing: 1) the study had to be a prospective design, 2) the
exposure of interest was magnesium intake, 3) the main
outcome measure was stroke, 4) the researchers reported
RRs with 95% CIs for 3 quantitative categories of magne-
sium intake, and 5) the RRs had to be adjusted for age
and sex (37).
Of the 163 peer-reviewed journal articles screened,
Larsson et al. (37) found that 7 prospective studies qualified
based on their criteria. These studies were published be-
tween 1998 and 2011. There were 6477 cases of stroke and
241,378 participants. Four of the studies were conducted
in the United States, 2 were conducted in Europe, and
1 was conducted in Taiwan. The median magnesium intakes
were 242 mg/d in men and women in the United States and
471 mg/d in Finnish men (37).
The 7 prospective studies reviewed by Larsson et al. (37)
provided risk estimates that were adjusted for age, smoking,
and BMI. Most researchers controlled or adjusted for phys-
ical activity (6 studies), diabetes mellitus (6 studies), his-
tory of hypertension or measured blood pressure (6 studies),
alcohol consumption (6 studies), and other nutrients (3
studies).
Larsson et al. (37) reported a statistically significant in-
verse association between magnesium intake and risk of
stroke. They found that an intake increment of 100 mg/d
of magnesium was associated with an 8% reduction in the
risk of stroke. Magnesium intake was inversely associated
with the risk of ischemic stroke, not hemorrhagic stroke.
Once again, a causal relationship was not reported, although
the strength of this meta-analysis was the strict inclusion cri-
teria for the studies included.
Magnesium and hypertension
Magnesium is involved in blood pressure regulation (7). In-
tracellular magnesium hinders the calcium depolarization
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4. that leads to muscle contraction, leading to vascular relaxa-
tion and thus decreased blood pressure (7).
Dickinson et al. (38) evaluated the effects of magnesium
supplementation for the treatment of hypertension. This
was a meta-analysis using the following inclusion criteria
for studies: 1) randomized, controlled trials of a parallel or
crossover design that compared oral magnesium supple-
mentation with usual care, placebo, or no treatment; 2)
the treatment and follow-up had to be $8 wk in duration,
3) the participants in the studies had to be at least 18 y of
age with a systolic blood pressure $140 mm Hg, and 4)
the researchers had to have reported both systolic and dia-
stolic blood pressure at the end of the follow-up period
(38). The researchers found 12 randomized, controlled trials
that met their criteria, with a total sample size of 545
participants. When all trials were combined, there was no
significant decrease in systolic blood pressure between mag-
nesium supplementation and controls; however, diastolic
blood pressure was significantly decreased. Dickinson et al.
(38) concluded that “[i]n view of the poor quality of in-
cluded trials and the heterogeneity between trials, the evi-
dence in favor of a causal association between magnesium
supplementation and blood pressure reduction is weak
and is probably due to bias. This is because poor quality
studies generally tend to over-estimate the effects of treat-
ment. Larger, longer duration and better quality double-
blind placebo controlled trials are needed to assess the effect
of magnesium supplementation on blood pressure and car-
diovascular outcomes.”
More recently, Kass et al. (39) conducted a meta-analysis
to assess effect of magnesium supplementation on blood
pressure. They also wanted to establish the characteristics
of trials showing the largest effect size. The primary outcome
measures were systolic blood pressure and diastolic blood
pressure. Of the 141 peer-reviewed articles they identified,
22 trials with 23 sets of data and a total sample size of
1173 were used. The studies ranged from 3 to 24 wk of
follow-up, and all were published before July 2010. The sup-
plemental magnesium dose ranged from 120 to 973 mg/d,
with a mean dose of 410 mg/d used.
When Kass et al. (39) combined their data, the overall ef-
fect was 0.32 for systolic blood pressure (95% CI: 0.23, 0.41)
and 0.36 for diastolic blood pressure (95% CI: 0.27, 0.44). A
greater effect was found for interventions in crossover trials:
0.51 for systolic blood pressure and 0.47 for diastolic blood
pressure (39).
In general, Kass et al. (39) reported that higher doses of
magnesium led to greater reductions in blood pressure.
Not all trials that they examined demonstrated a significant
decrease in blood pressure; however, combining all trials,
there was a 3- to 4-mm Hg decrease in systolic blood pres-
sure and a 2- to 3-mm Hg decrease in diastolic blood pres-
sure. Based on the results of this single meta-analysis (40),
magnesium supplementation appears to achieve a small,
clinically significant reduction in blood pressure.
Dickinson et al. (39) did not report significant effects of
magnesium on blood pressure, perhaps because their study
was published in 2006, and Kass et al. (40) reported their
study in 2012 and included larger trials. However, the crite-
ria that each group of researchers used to include in their
meta-analyses were different, which ultimately could have
caused the differences in results.
Cardiovascular disease
Cardiovascular disease is a chronic disease that remains the
leading cause of death, with ~599,413 deaths per year in the
United States (35). In animal studies, magnesium deficiency
has been shown to accelerate atherosclerosis, but magne-
sium supplementation has been shown to be preventive.
For humans, it is possible that individuals who consume
more dietary magnesium are more health conscious. None-
theless, the daily dietary intake of magnesium has decreased
from w500 mg/d in the 1900s to w175 mg/d. This is likely a
result of an increased consumption of processed foods
(40,41).
The mechanisms proposed for potential cardiovascular
benefits of magnesium intake include improvement of glu-
cose and insulin homeostasis or lipid metabolism; its actions
as an antihypertensive, antidysrhythmic, anti-inflammatory,
or anticoagulant agent; its antiplatelet effects; its effect on re-
duced vascular contractility, and/or increasing endothelium-
dependent vasodilation. Magnesium might lower blood
pressure by acting as a calcium antagonist on smooth muscle
tone, causing vasorelaxation (40–46).
Magnesium and type 2 diabetes mellitus
Perhaps the most studied chronic disease with respect to
magnesium is type 2 diabetes mellitus (and the metabolic
syndrome). Magnesium plays a significant role in glucose
and insulin metabolism, mainly through its impact on tyro-
sine kinase activity, by transferring the phosphate from ATP
to protein. Magnesium may also affect phosphorylase b
kinase activity by releasing glucose-1-phosphate from glyco-
gen. In addition, magnesium may directly affect glucose
transporter protein activity 4 (GLUT4), and help to regulate
glucose translocation into the cell.
In a cross-sectional design, Guerrero-Romero and
Rodríguez-Morán (16) compared 192 individuals with met-
abolic syndrome with 384 healthy age- and sex-matched
controls. The researchers reported hypomagnesemia in
126 and 19 individuals with and without the metabolic syn-
drome, respectively (P < 0.00001). Of all of the metabolic
syndrome symptoms, hypomagnesemia was most closely
related with dyslipidemia (OR: 2.8; 95% CI: 1.3, 2.9) and hy-
pertension (OR: 1.9; 95% CI: 1.4, 2.8). The study of magne-
sium’s role in type 2 diabetes mellitus, insulin resistance, and
cardiovascular disease demonstrates magnesium’s important
role in health.
In a 3-month prospective trial conducted by Guerrero-
Romero et al. (47), 60 participants were randomly assigned
in a double-blind fashion to either 300 mg/d of magnesium
chloride or a placebo. Insulin resistance (homeostasis model
assessment of insulin resistance index $3.0) was the major
outcome. Hypomagnesemia was defined as serum magnesium
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5. concentrations #0.74 mmol/L (1.8 mg/dL). The researchers
reported a significant increase in serum magnesium concen-
trations from baseline to the end of intervention (P <
0.0001), with no change in the placebo group (P = 0.063).
The researchers also reported significant improvements in
insulin sensitivity in the magnesium-supplemented group
from baseline to the end of the study (P < 0.0001), with
no change in the placebo group (P = 0.087). Insulin sensitiv-
ity, as measured by the homeostasis model assessment of in-
sulin resistance index, was >4.0 at baseline and was <3.0 at
the end of the study (47).
If magnesium supplementation affects insulin sensitivity
in participants with diabetes mellitus, it may also improve
insulin sensitivity in obese individuals who are at risk of
type 2 diabetes mellitus. Mooren et al. (48) examined the ef-
fects of oral magnesium supplementation in overweight in-
dividuals with normal serum magnesium levels who had
insulin resistance, but not type 2 diabetes mellitus. Individ-
uals were randomly assigned to receive either magnesium
aspartate hydrochloride supplementation (n = 27) or a pla-
cebo (n = 25) for 6 mo. Magnesium supplementation led to
a significant improvement in fasting blood glucose concen-
trations and some insulin sensitivity measures compared
with the placebo group.
The researchers emphasized the importance of consider-
ing the use of magnesium supplementation to prevent type 2
diabetes mellitus in those individuals who are at risk (e.g.,
overweight individuals with insulin resistance) (48).
It has been well established that cardiovascular disease,
hypertension, and type 2 diabetes mellitus are interrelated.
Because magnesium has been shown to directly influence
vascular tone and may release nitric oxide, leading to vaso-
dilation, Barbagallo et al. (49) evaluated if oral magnesium
would improve vascular function in older patients with
type 2 diabetes mellitus. Sixty participants with type 2 dia-
betes mellitus (71.1 6 6.1 y of age; 25 men, 25 women)
were assigned to receive either 4.5 g/d of magnesium pico-
late (368 mg/d of magnesium ion) (n = 30) or a placebo
(n = 30). Patients’ usual diabetes mellitus and hypertension
care was not altered during the 1-mo trial. Magnesium sup-
plementation significantly improved vascular tone, from
3.3% to 8.4% (measured using noninvasive flow-mediated
dilation of the brachial artery) with no changes reported
in the control group. By improving vascular tone, blood
flow will improve, and blood pressure could be decreased.
Conclusions
This review highlights areas where magnesium has been
shown to improve symptoms of migraine headaches,
Alzheimer’s disease, cerebrovascular accident (stroke), hy-
pertension, cardiovascular disease, and type 2 diabetes
mellitus. Although not all researchers have reported im-
provements or cause-and-effect relationships. there is good
evidence to support the positive influence that magnesium
has on overall health. More research is required, however,
with larger sample sizes to further elucidate magnesium’s
effect on health. Longer term, prospective studies using
similar amounts and types of magnesium supplementation
are also needed to definitively establish a dose–response ef-
fect and the best type of magnesium to use.
Acknowledgments
The sole author had responsibility for all parts of the
manuscript.
Literature Cited
1. Elin RJ. Magnesium: the fifth but forgotten electrolyte. Am J Clin
Pathol. 1994;102:616–22.
2. Takaya J, Higashino H, Kobayashi Y. Intracellular magnesium and insu-
lin resistance. Magnes Res. 2004;17:126–36.
3. Newhouse IJ, Finstad EW. The effects of magnesium supplementation
on exercise performance. Clin J Sport Med. 2000;10:195–200.
4. Bohl CH, Volpe SL. Magnesium and exercise. Crit Rev Food Sci Nutr.
2002;42:533–63.
5. Shils ME. Magnesium. In: Shils ME, Olson JA, Shike M, Ross AC, eds.
Modern nutrition in health and disease. 9th ed. Baltimore, MD:
Lippincott Williams & Wilkins; 1999. p. 169–92.
6. Chubanov V, Gudermann T, Schlingmann KP. Essential role for
TRPM6 in epithelial magnesium transport and body magnesium ho-
meostasis. Pflugers Arch. 2005;451:228–34.
7. Paolisso G, Barbagallo M. Hypertension, diabetes mellitus, and insulin
resistance: the role of intracellular magnesium. Am J Hypertens. 1997;
10:346–55.
8. Barbagallo M, Dominguez LJ, Galioto A, Ferlisi A, Cani C, Malfa L,
Pineo A, Busardo’ A, Paolisso G. Role of magnesium in insulin action,
diabetes and cardio-metabolic syndrome X. Mol Aspects Med. 2003;24:
39–52.
9. He K, Liu K, Daviglus ML, Morris SJ, Loria CM, Van Horn L, Jacobs
DR Jr, Savage PJ. Magnesium intake and incidence of metabolic syn-
drome among young adults. Circulation. 2006;113:1675–82.
10. Murakami K, Okubo H, Sasaki S. Effect of dietary factors on incidence
of type 2 diabetes: a systematic review of cohort studies. J Nutr Sci
Vitaminol (Tokyo). 2005;51:292–310.
11. Guerrero-Romero F, Rodriguez-Moran M. Hypomagnesemia is linked
to low serum HDL-cholesterol irrespective of serum glucose values.
J Diabetes Complications. 2000;14:272–6.
12. Gropper SS, Smith JL, Groff JL. Magnesium. Advanced nutrition and
human metabolism. 4th ed. Belmont, CA: Thomson and Wadsworth;
2005.
13. Soltani N, Keshavarz M, Minaii B, Mirershadi F, Asl SZ, Dehpour AR.
Effects of administration of oral magnesium on plasma glucose and
pathological changes in the aorta and pancreas of diabetic rats. Clin
Exp Pharmacol Physiol. 2005;32:604–10.
14. McCarty MF. Magnesium may mediate the favorable impact of whole
grains on insulin sensitivity by acting as a mild calcium antagonist.
Med Hypotheses. 2005;64:619–27.
15. Lopez-Ridaura R, Willett WC, Rimm EB, Liu S, Stampfer MJ, Manson
JE, Hu FB. Magnesium intake and risk of type 2 diabetes in men and
women. Diabetes Care. 2004;27:134–40.
16. Guerrero-Romero F, Rodríguez-Morán M. Low serum magnesium
levels and metabolic syndrome. Acta Diabetol. 2002;39:209–13.
17. Kanbay M, Yilmaz MI, Apetrii M, Saglam M, Yaman H, Unal HU,
Gok M, Caglar K, Oguz Y, Yenicesu M, et al. Relationship between
serum magnesium levels and cardiovascular events in chronic kidney
disease patients. Am J Nephrol. 2012;36:228–37.
18. Kupetsky-Rincon EA, Uitto J. Magnesium: novel applications in cardi-
ovascular disease. A review of the literature. Ann Nutr Metab. 2012;61:
102–10.
19. Kupetsky-Rincon EA, Li Q, Uitto J. Magnesium reduces carotid intima-
media thickness in a mouse model of pseudoxanthoma elasticum: a
novel treatment biomarker. Clin Transl Sci. 2012;5:259–64.
20. Reed BN, Zhang S, Marron JS, Montague D. Comparison of intrave-
nous and oral magnesium replacement in hospitalized patients with
cardiovascular disease. Am J Health Syst Pharm. 2012;69:1212–7.
382S Supplement
byguestonJune14,2016advances.nutrition.orgDownloadedfrom

6. 21. Abbasi IU, Salim-ul-Haque, Kausar MW, Karira KA, Zubaris NA. Cor-
relation of divalent cat ions (Ca++, Mg++) and serum renin in patients
of essential hypertension. J Pak Med Assoc. 2012;62:134–8.
22. Barbagallo M, Belvedere M, Di Bella G, Dominguez LJ. Altered ionized
magnesium levels in mild-to-moderate Alzheimer’s disease. Magnes
Res. 2011;24:S115–21.
23. Food and Nutrition Board, Institute of Medicine. Dietary Reference In-
takes for calcium, phosphorus, magnesium, vitamin D, and fluoride.
Washington, DC: National Academies Press; 1997.
24. Subramanian NK, White PJ, Broadley MR, Ramsay G. The three-
dimensional distribution of minerals in potato tubers. Ann Bot. 2011;
107:681–91.
25. Freedman MR, Keast DR. White potatoes, including French fries, con-
tribute shortfall nutrients to children’s and adolescents’ diets. Nutr Res.
2011;31:270–7.
26. U.S. Department of Agriculture, Agricultural Research Service. 2011.
USDA National Nutrient Database for Standard Reference, Release
24. Nutrient Data Laboratory Home Page, http://www.ars.usda.gov/
ba/bhnrc/ndl, retrieved September 16, 2012.
27. Nielsen FH. Magnesium, inflammation, and obesity in chronic disease.
Nutr Rev. 2010;68:333–40.
28. Office of Dietary Supplements. Dietary Supplement Fact Sheet: Magne-
sium. http://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/,
retrieved September 16, 2012
29. Freedman MR, Keast DR. Potatoes, including French fries, contribute
key nutrients to diets of U.S. adults: NHANES 2003–2006. J Nutr
Ther. 2012;1:1–11.
30. Arnaud MJ. Update on the assessment of magnesium status. Br J Nutr.
2008;99(Suppl 3):S24–36.
31. World Health Organization. Headache disorders. Fact Sheet #277. http:
//www.who.int/mediacentre/factsheets/fs277/en/, retrieved September
16, 2012.
32. Mauskop A. Nonmedication, alternative, and complementary treat-
ments for migraine. Continuum (Minneap Minn). 2012;18:796–806.
33. Pringsheim T, Davenport W, Mackie G, Worthington I, Aubé M, Christie
SN, Gladstone J, Becker WJ; Canadian Headache Society Prophylactic
Guidelines Development Group. Canadian Headache Society guideline
for migraine prophylaxis. Can J Neurol Sci. 2012; 39(2, Suppl 2)S1–59.
34. Tarighat Esfanjani A, Mahdavi R, Ebrahimi Mameghani M, Talebi M,
Nikniaz Z, Safaiyan A. The effects of magnesium, L-carnitine, and con-
current magnesium-L-carnitine supplementation in migraine prophy-
laxis. Biol Trace Elem Res. 2012;150:42–8.
35. Centers for Disease Control and Prevention. FastStats. http://www.cdc.
gov/nchs/fastats/lcod.htm/, retrieved September 16, 2012.
36. Ozawa M, Ninomiya T, Ohara T, Hirakawa Y, Doi Y, Hata J, Uchida K,
Shirota T, Kitazono T, Kiyohara Y. Self-reported dietary intake of
potassium, calcium, and magnesium and risk of dementia in the
Japanese: The Hisayama study. J Am Geriatr Soc. 2012;60:1515–20.
37. Larsson SC, Orsini N, Wolk A. Dietary magnesium intake and risk of
stroke: a meta-analysis of prospective studies. Am J Clin Nutr. 2012;
95:362–6.
38. Dickinson HO, Nicolson DJ, Campbell F, Cook JV, Beyer FR, Ford GA,
Mason J. Magnesium supplementation for the management of essen-
tial hypertension in adults. Cochrane Database Syst Rev. 2006; (3):
CD004640.
39. Kass L, Weekes J, Carpenter L. Effect of magnesium supplementation
on blood pressure: a meta-analysis. Eur J Clin Nutr. 2012;66:411–8.
40. Bo S, Pisu E. Role of dietary magnesium in cardiovascular disease pre-
vention, insulin sensitivity and diabetes. Curr Opin Lipidol. 2008;19:
50–6.
41. Ma J, Folsom AR, Melnick SL, Eckfeldt JH, Sharrett AR, Nabulsi AA,
Hutchinson RG, Metcalf PA. Associations of serum and dietary
magnesium with cardiovascular disease, hypertension, diabetes, in-
sulin, and carotid arterial wall thickness: the ARIC study. Athero-
sclerosis Risk in Communities Study. J Clin Epidemiol. 1995;48:
927–40.
42. Altura BT, Brust M, Bloom S, Barbour RL, Stempak JG, Altura BM.
Magnesium dietary intake modulates blood lipid levels and atherogen-
esis. Proc Natl Acad Sci U S A. 1990;87:1840–4.
43. Orimo H, Ouchi Y. The role of calcium and magnesium in the devel-
opment of atherosclerosis. Experimental and clinical evidence. Ann
N Y Acad Sci. 1990;598:444–57.
44. Song Y, Manson JE, Cook NR, Albert CM, Buring JE, Liu S. Dietary
magnesium intake and risk of cardiovascular disease among women.
Am J Cardiol. 2005;96:1135–41.
45. Chakraborti S, Chakraborti T, Mandal M, Mandal A, Das S, Ghosh S.
Protective role of magnesium in cardiovascular diseases: a review. Mol
Cell Biochem. 2002;238:163–79.
46. Houston M. The role of magnesium in hypertension and cardiovascu-
lar disease. J Clin Hypertens (Greenwich). 2011;13:843–7.
47. Guerrero-Romero F, Tamez-Perez HE, González-González G, Salinas-
Martínez AM, Montes-Villarreal J, Treviño-Ortiz JH, Rodríguez-Morán
M. Oral magnesium supplementation improves insulin sensitivity in
non-diabetic subjects with insulin resistance. A double-blind placebo-
controlled randomized trial. Diabetes Metab. 2004;30:253–8.
48. Mooren FC, Krüger K, Völker K, Golf SW, Wadepuhl M, Kraus A. Oral
magnesium supplementation reduces insulin resistance in non-diabetic
subjects - a double-blind, placebo-controlled, randomized trial. Diabe-
tes Obes Metab. 2011;13:281–4.
49. Barbagallo M, Dominguez LJ, Galioto A, Pineo A, Belvedere M. Oral
magnesium supplementation improves vascular function in elderly
diabetic patients. Magnes Res. 2010;23:131–7.
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