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ABSTRACT Differential analysis of the NHANES 1999 –2000 data set (3)
Background: Current recommendations for magnesium require- indicated that the mean magnesium intake for American women
ments are based on sparse balance data. (white) aged 51–70 y was 238 mg/d (1). For Mexican and African
Objective: To provide new estimates of the average magnesium American women of the same age group, magnesium intakes
requirement for men and women, we pooled magnesium data from were lower: 185 and 169 mg/d, respectively (4). For white, Mex-
27 different tightly controlled balance studies conducted at the US ican, and African women, intakes were lower still for those re-
Am J Clin Nutr 2006;84:843–52. Printed in USA. © 2006 American Society for Nutrition 843
844 HUNT AND JOHNSON
feeding studies conducted at the US Department of Agriculture, (n ҃ 227) with additional participation by blacks (n ҃ 6), Amer-
Agricultural Research Service, Grand Forks Human Nutrition ican Indians or Alaskans (n ҃ 5), Asians (n ҃ 2), Hispanics (n ҃
Research Center, Grand Forks, ND, between 1976 and 2001. The 2), and undeclared ethnicity (n ҃ 1). The ward provided an
studies were designed originally to determine specific outcomes environment for strict control of food consumption, physical
of nutritional challenges on physiologic function. Twenty-seven activity, and data collection. Each subject was provided with a
of 42 studies (13–35) measured magnesium balance and incor- private bedroom with cable television, radio with wake-up alarm,
porated design components, such as a control (nutritionally re- intercom to a 24-h central nurse station, telephone, and a semi-
plete) dietary period, relevant for estimating the magnesium re- private bathroom. Activity areas and the nurse station were ad-
quirement by cross-sectional statistical analysis. A broad range jacent to the private bedrooms. Subjects were allowed to leave
of magnesium intakes were used to estimate the amount of di- the immediate living or dining areas or facility only when ac-
etary magnesium needed to maintain zero magnesium balance in companied by a chaperone to ensure compliance with study
healthy persons. protocols. Meal consumption was observed by specially trained
dietary staff members, and irregularities were recorded. Subjects
agreed to use only personal care products and in the amounts
SUBJECTS AND METHODS approved by the principal investigators and to limit and standard-
Common design characteristics of the 27 individual original ize extraneous chemical exposure. Subjects were not allowed to
metabolic studies used in the present study are summarized be- use tobacco or medicinal marijuana or consume alcohol (except
low. Details about each study are available in the references cited for specified ethanol tolerance tests). For most studies, individ-
in Table 1. ually prescribed physical activity was performed multiple times
per week to maintain initial body composition and physical work
Study no., study design, and reference2 Study period Sex All subjects Qualified subjects3
TABLE 1 (Continued)
Study no., study design, and reference2 Study period Sex All subjects Qualified subjects3
Study no., study design, and reference2 Study period Sex All subjects Qualified subjects3
data from the weight loss experiments collected only during the studies 1-14 and one representative duplicate diet supplying 8.4
initial maintenance dietary periods. MJ (2000 kcal) for all subjects in studies 14-27 were prepared
daily for analysis. For all studies, the daily duplicate diets were
Magnesium supplementation
blended, and aliquots (6% of total weight) of the daily meals were
In most of the studies (studies 1-16, 20, and 24), the basal diet mixed well and made into 6- or 7-d composites before freezing.
was considered magnesium replete and not supplemented with Aliquots of all prescribed dietary supplements, discretionary
magnesium. In the remainder of the studies, the basal diet was foods, and transient medications were measured for mineral con-
supplemented with magnesium as magnesium gluconate (except tent, and the mineral contributions were included as part of the
for one) as needed to meet the magnesium recommended dietary dietary magnesium intake.
allowance (study 17: 57 mg Mg/d; study 21: 171 mg Mg/d; study
23: 114 mg Mg/d) or a specific experimental dietary magnesium Urinary and fecal analyses
value (study 16: 200 mg Mg/d; study 18: 200 mg Mg/d; study 19:
200 mg Mg/d; study 25: 207 mg Mg/d; study 26: 206 or 284 mg Total urine was collected by polypropylene funnels into 4-L
Mg/d; study 27: 100 or 200 mg Mg/d). For study 22, a magnesium polypropylene containers (6 mL of 6N HCl as “Baker Technical”
supplement of 50 mg/d was provided as magnesium citrate dibasic. grade added to prevent bacterial growth; JT Baker Inc, Phillips-
burg, NJ). Fecal output, excluding remains left on toilet paper,
Magnesium balance method was collected directly in plastic bags throughout each study with
precautions to avoid trace mineral contamination. All excreta
Dietary analysis were cooled immediately after collection in a double-doored
Balance data from the last 6 –14 d of each dietary period of refrigerator that provided discreet sample transfer to technical
each study were analyzed. A duplicate diet for each subject in staff. The last 6- or 7-d urine composites of each dietary period
848 HUNT AND JOHNSON
for each volunteer were prepared by combining proportional between preexisting data files and subject was broken by the
aliquots of daily urines and freezing them until analysis. following method. The database for the original studies consisted
Weighed fecal specimens were frozen, lyophilized, and then of multiple data files, each keyed by using a unique individual
combined in toto in a plastic bag to prepare 6- or 7-d composites identification number. A separate file was created that consisted
and were subsequently pulverized by a rolling pin and mixed by only of records with current identification numbers along with
hand shaking for each volunteer. new, randomly generated identification numbers. Subsequently,
the relevant data files in the preexisting database were copied into
Exercise a new database; as the file was copied, the original identification
For all studies, all subjects were required to exercise a mini- number was replaced by the randomly generated identification
mum of 15 min at 50% maximum work capacity on an ergocycle 3 number. Subject names and birth dates were not copied to the
times each week. Additional exercise was prescribed as needed to new database. After the new database was created, the file con-
maintain body weight within 2% of initial weight. Voluntary walk- taining the existing identification numbers and the randomly
ing regimens did not affect mandatory exercise prescriptions. generated identification numbers were deleted permanently. No
hard copy of this file was ever generated. In summary, all linkage
Magnesium balance determination was broken between the preexisting data and the original iden-
tification numbers with no possibility to associate any original
Dietary and fecal sample digestion and analyses data with a specific subject.
Aliquots of the diet and fecal composites were digested with
perchloric and nitric acids in glass beakers. Magnesium content Outliers
of dietary, urinary, and fecal digestates was determined by flame
Data from a specific dietary period for a subject were excluded
lations did not include whole body surface (negligible; 4.1 mg/d
for young men), phlebotomy [negligible; 0.019 mg Mg/mL se- 冘 冉 ⫽ 冊2a ab
ab 2b and eij ⬃ iid N共0,2e 兲 (2)
rum (39)], menstrual [negligible; 2.3 mg/d (range: 6.5-0.3 mg/
d)], or seminal losses. The fixed effects part of the model is ␣ ѿ Xij, whereas the
random-effects part of the model is a*i ѿ b*i Xij ѿ eij. PROC
Data management and statistical analysis MIXED in SAS (version 9.1; SAS Institute, Cary, NC) was used
to fit all models. An unstructured variance-covariance matrix, ⌺,
Confidentiality considerations was specified for the slopes and intercepts. As specified in Equa-
For each original study, a password secure, confidential com- tion 1, both intercepts and slopes are considered random effects.
puter file maintained the linkage between subject name and iden- To test whether random intercepts and slopes were necessary,
tification number, with access limited to select center staff mem- additional models were fit, allowing only random intercepts and
bers. This linkage was separate from research data files and was only random slopes. Akaike’s Information Criteria was used to
kept for several reasons: to provide subjects with individual study compare models. In all cases, the model that resulted in the
results and to provide governmental and institutional auditors smallest Akaike’s Information Criteria value allowed both the
with access as required by law. For the present study, the linkage slopes and intercepts to be random effects.
MAGNESIUM BALANCE AND REQUIREMENT 849
Fixed coefficients were added to the models to allow for sep-
arate intercepts and slopes for men and women to determine
whether sex differences existed in the requirement estimates.
The model used was as follows:
Yij ⫽ ␣ ⫹ 1Xij ⫹ 2Gi ⫹ 3XijGi ⫹ ai* ⫹ bi*Xij ⫹ eij
(3)
where Gi is 1 if subject i was male or 0 if subject i was female. To
test whether there was an age effect on magnesium requirements,
age was added to the model as follows:
Yij ⫽ ␣ ⫹ 1Xij ⫹ 2Ai ⫹ 3Xij Ai ⫹ 4Xij AiGi ⫹ ai* ⫹ bi*Xij
⫹ eij (4)
where Ai is the age of subject i. The men in this study had a
relatively narrow age range compared with the women. There-
FIGURE 1. Relation between magnesium output (fecal ѿ urinary excre-
fore, models that included age as a predictor were also tested by tion) and magnesium intake, both expressed as mg/d, for women [F; n ҃ 150;
using data only from women to assess whether the results ob- weight: 71.6 앐 16.5 kg; age: 51.3 앐 17.4 y (range: 19 –77 y)] and men [E;
tained were simply artifacts of the different age distributions. n ҃ 93; weight: 76.3 앐 12.5 kg; age: 28.1 앐 8.1 y (range: 19 – 65 y)] who
The 95% CIs (41) and 95% prediction intervals (PIs) (42, 43) participated in tightly controlled feeding studies conducted in a metabolic
DISCUSSION
This study expands the magnesium balance data needed to
generate better estimates of the adult magnesium requirement.
As outlined by the FNB (1), the number of magnesium balance
studies that meet minimum design criteria is insufficient. This
study exploited the metabolic data collected from studies in
which only healthy volunteers participated, adequate dietary ad-
aptation (44) was assured by examining only dietary periods
쏜 27 d, magnesium intakes below and near the presumed re-
quired amounts were included, the mineral content of the drink-
ing water was measured, foods and beverages were prepared by
professional staff members for delivery within 1% weighing
FIGURE 3. Relation between magnesium output (fecal ѿ urinary excre- error, duplicate diets were prepared by professional staff mem-
tion) and magnesium intake, both expressed as mg · kcalҀ1 · dҀ1, for women bers, food consumption was quantitative and carried out under
[F; n ҃ 150; weight: 71.6 앐 16.5 kg; age: 51.3 앐 17.4 y (range: 19 –77 y)] visual supervision, fecal and urine collections were continuous to
and men [E; n ҃ 93; weight: 76.3 앐 12.5 kg; age: 28.1 앐 8.1 y (range: 19 – 65 ensure familiarity with the procedure, and samples were ana-
y)] who participated in tightly controlled feeding studies conducted in a
lyzed by state-of-the-art technology. Excluding data when in-
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