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 magnesiums 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, Alzheimers 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 magnesiums role in disease prevention and
overall health. Adv. Nutr. 4: 378S383S, 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 reactions 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
(36). Magnesium also plays a critical role in maintaining normal nerve and muscle function, cardiac excitability (normal

Published in a supplement to Advances in Nutrition. Presented at the Purdue University

Roundtable on White Vegetables: A Forgotten Source of Nutrients held June 1819, 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

heart rhythm), neuromuscular conduction, muscular contraction, vasomotor tone, normal blood pressure, bone integrity,
and glucose and insulin metabolism (316). In this regard,
magnesium deficiency has been associated with a number
of chronic diseases, including migraine headaches, Alzheimers diseases, cerebrovascular accident (stroke), hypertension, cardiovascular disease, and type 2 diabetes
mellitus (1722).
The Dietary Reference Intake for magnesium for adults is
310420 mg/d; magnesium intake is often below these recommendations, 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 (2426).
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 magnesiums role in disease 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 children 13 y of age to 130 mg/d for children 48 y of age.
For older males, the RDA for magnesium ranges from as

2013 American Society for Nutrition. Adv. Nutr. 4: 378S383S, 2013; doi:10.3945/an.112.003483.

low as 240 mg/d (range, 913 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 (913 y of age)
to 360 mg/d for females 1418 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 magnesium deciency 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 insufciency and
not an overt magnesium deciency. It has been reported,
however, that low magnesium status has been associated
with chronic inammatory stress conditions (27).
In humans, decient magnesium intakes are mostly considered marginal to moderate, i.e., between 50% and 90% of
the RDA and may be related to chronic inammatory response conditions (27). This inammatory response could
play a role in obesity in humans because obesity has been
characterized as having a chronic low-grade inammation
component and an increased incidence of a low magnesium
status (27). It is this marginal to moderate magnesium deciency through aggravating chronic inammatory stress that
may be contributing signicantly to the occurrence of atherosclerosis, hypertension, osteoporosis, type 2 diabetes mellitus, 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 unrened (whole) grains, spinach, nuts, legumes, and potatoes
(tubers) (26). Freedman and Keast (25) evaluated the contribution 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 20032006 to establish nutrient 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 magnesium concentrations, ionized magnesium levels, red blood

Table 1. Foods high in magnesium1

Magnesium, mg

Food
1/4 cup of wheat bran (57 g)
1 oz of dry roasted almonds (28.4 g)
1/2 cup of frozen, cooked spinach (14.2 g)
1 oz of mixed, dry roasted nuts (28.4 g)
3/4 cup of bran flakes cereal (170 g)
2 tbsp of smooth peanut butter (32 g)
1 medium baked potato with skin
1/2 cup of cooked pinto beans (113 g)
1/2 cup of brown, long-grained cooked rice
(113 g)
1/2 cup of mature seeds, cooked lentils, (113 g)
1 cup of low-fat chocolate milk (234 mL)
1 medium banana
8 fluid oz of low-fat fruit yogurt (234 mL)
1.5 oz of milk chocolate candy bar (43 g)
1 slice of whole-wheat bread,
commercially prepared
1/2 cup of avocado cubed (113 g)
1

89
80
78
64
64
49
48
43
42
36
33
32
32
28
23
22

Adapted from (26) with permission.

cell magnesium, and urinary magnesium levels using the

magnesium loading test. Of these, serum magnesium concentrations have been shown to be the least sensitive to magnesium status unless there is a severe magnesium deciency
already present (30); although ionized magnesium concentrations 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 continue to use serum magnesium concentrations, but more researchers 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). Migraine headaches more than likely have a genetic basis.
These types of headache disorders stimulate a mechanism
deep in the brain that releases inammatory 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 nonpharmacologic therapies appears to approach that of most
drugs used for the prevention of migraine and tensiontype headaches. Therapies such as magnesium supplementation 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 research articles based on the criteria developed by the U.S.
Magnesium and health 379S

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, Tarighat 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 significant 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 headaches. Longer term trials with a greater number of participants are required to further evaluate the effects of
magnesium on migraine headaches.
Magnesium and Alzheimers disease
Alzheimers disease is the most widespread reason for dementia (35). Alzheimers 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 balance in patients with mild to moderate Alzheimers 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 Alzheimers disease compared with their age-matched controls without Alzheimers
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 ionized magnesium concentrations were significantly related to
cognitive function and not physical function. Individuals
with Alzheimers disease had significantly lower MiniMental 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 between ionized magnesium concentrations and individuals
who have mild to moderate Alzheimers disease (22).
Ozawa et al. (36) examined whether a diet high in potassium, calcium, and magnesium would reduce the risk of dementia 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
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Alzheimers disease. Ozawa et al. (36) reported a significant

inverse association between potassium, calcium, and magnesium intake and all-cause dementia and vascular dementia; the lower the intakes were, the greater the rates of
dementia. This same association was not observed with
Alzheimers disease. The strength of this study was the number 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, inability 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 hypertension. Because of magnesiums 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 association between magnesium intake and stroke risk. The criteria
the researchers chose for their meta-analysis were the following: 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 magnesium 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 qualied
based on their criteria. These studies were published between 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 physical activity (6 studies), diabetes mellitus (6 studies), history of hypertension or measured blood pressure (6 studies),
alcohol consumption (6 studies), and other nutrients (3
studies).
Larsson et al. (37) reported a statistically signicant inverse 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 criteria for the studies included.
Magnesium and hypertension
Magnesium is involved in blood pressure regulation (7). Intracellular magnesium hinders the calcium depolarization

that leads to muscle contraction, leading to vascular relaxation 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 supplementation 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 diastolic 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 magnesium supplementation and controls; however, diastolic
blood pressure was significantly decreased. Dickinson et al.
(38) concluded that [i]n view of the poor quality of included trials and the heterogeneity between trials, the evidence 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 treatment. Larger, longer duration and better quality doubleblind placebo controlled trials are needed to assess the effect
of magnesium supplementation on blood pressure and cardiovascular 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 identied,
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 supplemental 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 effect 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 signicant
decrease in blood pressure; however, combining all trials,
there was a 3- to 4-mm Hg decrease in systolic blood pressure and a 2- to 3-mm Hg decrease in diastolic blood pressure. Based on the results of this single meta-analysis (40),
magnesium supplementation appears to achieve a small,
clinically signicant reduction in blood pressure.
Dickinson et al. (39) did not report signicant 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 criteria 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 deciency
has been shown to accelerate atherosclerosis, but magnesium supplementation has been shown to be preventive.
For humans, it is possible that individuals who consume
more dietary magnesium are more health conscious. Nonetheless, 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
benets of magnesium intake include improvement of glucose and insulin homeostasis or lipid metabolism; its actions
as an antihypertensive, antidysrhythmic, anti-inammatory,
or anticoagulant agent; its antiplatelet effects; its effect on reduced vascular contractility, and/or increasing endotheliumdependent vasodilation. Magnesium might lower blood
pressure by acting as a calcium antagonist on smooth muscle
tone, causing vasorelaxation (4046).
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 signicant role in glucose
and insulin metabolism, mainly through its impact on tyrosine kinase activity, by transferring the phosphate from ATP
to protein. Magnesium may also affect phosphorylase b
kinase activity by releasing glucose-1-phosphate from glycogen. 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
Rodrguez-Morn (16) compared 192 individuals with metabolic syndrome with 384 healthy age- and sex-matched
controls. The researchers reported hypomagnesemia in
126 and 19 individuals with and without the metabolic syndrome, 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 hypertension (OR: 1.9; 95% CI: 1.4, 2.8). The study of magnesiums role in type 2 diabetes mellitus, insulin resistance, and
cardiovascular disease demonstrates magnesiums important
role in health.
In a 3-month prospective trial conducted by GuerreroRomero 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
Magnesium and health 381S

concentrations #0.74 mmol/L (1.8 mg/dL). The researchers

reported a significant increase in serum magnesium concentrations 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 sensitivity, as measured by the homeostasis model assessment of insulin 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 effects of oral magnesium supplementation in overweight individuals with normal serum magnesium levels who had
insulin resistance, but not type 2 diabetes mellitus. Individuals were randomly assigned to receive either magnesium
aspartate hydrochloride supplementation (n = 27) or a placebo (n = 25) for 6 mo. Magnesium supplementation led to
a significant improvement in fasting blood glucose concentrations and some insulin sensitivity measures compared
with the placebo group.
The researchers emphasized the importance of considering 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 inuence
vascular tone and may release nitric oxide, leading to vasodilation, 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 diabetes mellitus (71.1 6 6.1 y of age; 25 men, 25 women)
were assigned to receive either 4.5 g/d of magnesium picolate (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 supplementation 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,
Alzheimers disease, cerebrovascular accident (stroke), hypertension, cardiovascular disease, and type 2 diabetes
mellitus. Although not all researchers have reported improvements 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 magnesiums
effect on health. Longer term, prospective studies using
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similar amounts and types of magnesium supplementation

are also needed to definitively establish a doseresponse effect and the best type of magnesium to use.

Acknowledgments
The sole author had responsibility for all parts of the
manuscript.

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