196 Introduction to Human Nutrition
positive fi ndings may refl ect the lack of sensitive and
reliable tools for assessing magnesium status, the
failure to account for magnesium intake from water
(in dietary studies), or the diffi culty in attributing
causality to a single nutrient owing to the apparent
heterogeneity of causes arising from epidemiological
data relating to most chronic diseases. The fact that
in 1997 the US RDA for magnesium was raised for
most groups is a refl ection that nutrition scientists
believe that there is a negative consequence to sub-
optimal magnesium intake. Additional research is
needed to justify this concern.
Toxicity
Magnesium, when ingested as a naturally occurring
substance in foods, has not been demonstrated to
exert any adverse effects in people with normal renal
function. However, adverse effects of excess magne-
sium intake (e.g., diarrhea, nausea, abdominal cramp-
ing) have been observed with intakes from nonfood
sources such as various magnesium salts used for
pharmacological purposes. For this reason the US
Food and Nutrition Board established the tolerable
UL for adolescents and adults as 350 mg of nonfood
magnesium.
Genetic diseases
Several disease states are associated with magnesium
defi ciency, some of which have genetic roots, for
example hypomagnesemia with secondary hypocal-
cemia, primary hypomagnesemia with hypercalciuria,
renal hypomagnesemia 2, Bartter’s syndrome, and
Gitelman’s syndrome.
Primary hypomagnesemia with hypercalciuria is
caused by a mutation in the paracellin-1 (PCLN1)
gene on chromosome 3. PCLN1 is a component of the
tight junction complex in nephrons and, therefore,
has a role in renal magnesium ion reabsorption.
Hypomagnesemia with secondary hypocalcemia is an
autosomal recessive disorder and is determined by a
mutation in a gene located on 9q12–q22.2.
Renal hypomagnesemia 2 is believed to be due to
an autosomal dominant isolated renal magnesium
loss, which is caused by misrouting of the Na+/K(+)-
ATPase gamma-subunit. This small, type I membrane
protein is localized on the basolateral membranes of
nephron epithelial cells and is expressed in the distal
convoluted tubule, the main site of active renal mag-
nesium reabsorption.
It has been proposed that Bartter’s syndrome is
a heterogeneous entity with at least two subsets,
Gitelman’s syndrome and “true” Bartter’s syndrome.
True Bartter’s syndrome, a hypokalemic alkalosis with
hypercalciuria, is caused by mutation in the NaK 2 Cl
cotransporter gene SLC12A1 on chromosome 15.
Bartter’s syndrome is also caused by mutations in the
K(+) channel gene ROMK on chromosome 11. Gitel-
man’s syndrome, a hypokalemic alkalosis with hypo-
calciuria and hypomagnesemia, is caused by mutations
in the thiazibesensitive NaCl cotransporter gene on
16q13.Assessing status
Estimating magnesium requirements and establish-
ing magnesium–disease relationships depend on
accurate and specifi c indicators of magnesium status.
Several such indicators have been described. All of
these are based on measurement of the magnesium
content in various body pools. Analysis of total mag-
nesium in serum is often used as an indicator of mag-
nesium status, although only about 1% of total body
magnesium is present in ECF. It has been suggested
that the concentration of ionized magnesium in
serum may be a more reliable and relevant determi-
nant of magnesium defi ciency. In addition, intracel-
lular magnesium concentration (usually measured in
accessible tissues such as erythrocytes and lympho-
cytes) provides a more accurate assessment of body
magnesium status than does the concentration of
magnesium in serum. The dietary balance approach
is considered to be the best available method for
estimating magnesium requirements. Although this
method is a powerful research tool for the study of
magnesium homeostasis, it is time, resource, and
labor intensive, and these limit its application to large
populations. None of the currently available proce-
dures is perfect for all circumstances.Requirements and dietary sources
In 1997, the US RDA [the nutrient intake value that
is suffi cient to meet the requirement of nearly all
(97–98%) individuals in a life-stage and sex group]
for magnesium was revised upwards for most groups.
The current RDA for adult women is now 320 mg/day
and for adult men is 420 mg/day. An additional value
is now part of the US Food and Nutrition Board’s
dietary reference intakes, the estimated average
requirement (EAR; the nutrient intake value that is