ARTICLE
Auteur(s) : Dana E
King, Arch G Mainous III, Mark E Geesey, Tina Ellis
Department of Family Medicine, Medical University of South
Carolina, 295 Calhoun Street, Charleston, South Carolina 29425,
USA
Recent evidence strongly supports a significant role for
inflammation in the development of cardiovascular disease in
adults. Higher levels of inflammatory markers such as C-reactive
protein (CRP) indicate increased cardiovascular (CV) risk [1-4].
According to data from the National Health and Nutrition
Examination Survey (NHANES), the median serum CRP is 2.2 mg/L
in adults and 0.4 mg/L in children under age 20 [5, 6]. CRP
levels are highly correlated with cardiovascular risk factors in
children, including blood pressure and BMI [6].Previous research
has indicated that dietary magnesium (Mg) intake may be a key
component in the association between diet and inflammation [7].
Research in the adult population has documented that magnesium
intake is inversely associated with systemic inflammation in
middle-aged and older women [8]. Another study in adults of both
sexes found a significant association between dietary Mg and
likelihood of elevation of CRP that was independent of age, race,
sex, BMI, and smoking [9]. Further, Guerrero-Romero et al. [10]
have shown that low serum magnesium levels are independently
related to elevated CRP concentration in non-diabetic,
non-hypertensive obese subjects.More research is needed to evaluate
the relationship between dietary Mg and serum CRP in children.The
objective of this study was to characterize the association between
Mg intake and CRP in children who are and who are not overweight in
a nationally representative sample of non-institutionalized US
children of both sexes.
Materials and methods
We derived our study sample from the participants in the National
Health and Nutrition Examination Survey 1999-2002 (NHANES 99-02),
the most recent release of this nationally representative, complex,
multistage, probability based survey of the civilian,
non-institutionalized population of the US. Detailed information
about the survey design, questionnaires, laboratory analyses, and
examination methodology can be found on the website for the Centers
for Disease Control, National Center of Health Statistics
(http://www.cdc.gov/nchs/nhanes.htm). We limited our sample for
this analysis to children aged 6-17 years who had valid
measurements for both CRP and dietary intake of magnesium (n =
5007).
High sensitivity C-reactive protein (CRP) was measured as part
of the NHANES 99-02 physical and laboratory examination. Standard
phlebotomy techniques were used to obtain specimens (see website).
The threshold for elevated CRP was defined by American Heart
Association (AHA) guidelines that designate CRP levels ≥
3.0 mg/L as associated with high cardiovascular risk in adults
[4]; no such levels have been established for children.Dietary
intake in the NHANES 99-02 is based on recollection of foods eaten
the previous day by the respondent coupled with known nutritional
content of each of these foods (24 hour recall). The US Office of
Dietary Supplements of the National Institutes of Health
(http://ods.od.nih.gov/index.aspx) and the Institute of Medicine
(IOM) have established Recommended Daily Allowances (RDA) of
magnesium intake based on gender and age (table
1). For each child in the study population we calculated
the percentage of the RDA that they had consumed based on gender
and age. Three groups were established based on magnesium
consumption: less than 75% of the RDA, 75-99% of the RDA, and 100%
or more of the RDA.
Demographic variables (age, race, sex) were included as control
variables because of their known impacts on CRP [11]. Additional
control variables were included that might be linked to eating
behavior or also influence CRP level. We controlled for body weight
(BMI > 85%ile) because of its link to diet and its known
association with CRP [4, 6]. We also controlled for income level
(above or below the poverty level), exercise, fiber intake, and
calorie intake [9, 12]. Because the quantity of magnesium and fiber
consumed may be linked to the total amount of food consumed, total
caloric intake was incorporated as another control variable [5,
13].
Because of this complex sampling design, appropriate weighting
factors (based on statistical stratification and population
estimates) must be taken into account when calculating
population-based frequency estimates. We used SUDAAN (Research
Triangle Institute, Research Triangle, NC), a specialized
statistical program that accounts for the complex weighting of the
NHANES 99-02 sample [14]. Using SUDAAN allowed us to correct for
unequal probabilities of selection and different response rates,
ensuring that the results can be generalized to the
non-institutionalized civilian population of the U.S. Thus the
percentages and odds ratios in this study represent weighted
values. SUDAAN also adjusts the standard errors to account for the
weighting, stratification, and clustering of the complex sampling
design to ensure that expressed p values are valid [15].
Descriptive statistics for the sample were performed to
illustrate the demographic characteristics and dietary magnesium
intake. For each of the demographic variables (age, race, gender,
etc.), the association with the dietary magnesium quartile group
was examined using χ2 analyses.
Magnesium intake then was examined in adjusted multivariate
logistic regression analyses predicting elevated serum CRP
(≥ 3.0 mg/L). The covariates age, race, gender, BMI,
income, exercise, fiber intake, and total caloric intake were
included in the models to control for their effects. Standardized
betas, p-values, odds ratios, and 95% confidence intervals were
obtained from the logistic regression output. Statistical
significance was defined as ≤ 0.05 without correction for
multiple-comparisons, since there was only one mineral examined,
and the specific analyses were planned in advance.
Table 1 US RDA for magnesium based on age and gender
(US Office of Dietary Supplements of the National Institutes of
Health).
|
Age group (years)
|
Boys
|
Girls
|
|
< 9
|
130 mg
|
130 mg
|
|
9-13
|
240 mg
|
240 mg
|
|
> 13
|
410 mg
|
360 mg
|
Results
Of the 5007 children with available laboratory samples, 3236
(58.6%) had magnesium intake below the RDA (table 2) )). Only 38% of overweight children
(> 85%ile) met or exceeded the RDA for Mg intake by age and
gender, compared to 43% of normal weight children
(< 85%ile), although the difference is not statistically
significant (p = 0.07). Children with Mg intake < 75% of the RDA
had a significantly greater median serum CRP (0.38 mg/L)
compared to children above the RDA (0.25 mg/L) (p < 0.05).
In unadjusted analyses, children < 75% RDA were 1.94 times more
likely to have elevated CRP than children above the RDA (p <
0.05).
In logistic regression analyses, controlling for age, race, sex,
income level, exercise, fiber intake, BMI, and total calories,
children with a consumption of < 75% of RDA were 58% more likely
to have elevated CRP (OR 1.58, 95% CI 1.07-∞, table 3). Overweight children with Mg intake below
the RDA were not more likely to have an elevated CRP than children
with Mg intake above the RDA (table
3).
Table 2 Demographics of children ages 6-17 in the US,
according to the presence or absence of elevated serum CRP. Sample
size of 5007 individuals representing a US population estimate of
41,089,564.
|
Total
|
Serum CRP < 3.0 mg/L
|
Serum CRP ≥ 3.0 mg/L
|
χ2 p=
|
|
Dietary Mg intake
|
|
|
|
0.003
|
|
< 75% RDA
|
41.8%
|
85.8%
|
14.2%
|
|
|
75-99% RDA
|
16.9%
|
89.1%
|
10.9%
|
|
|
≥ RDA
|
41.4%
|
92.1%
|
7.9%
|
|
|
Race
|
|
|
|
0.155
|
|
White
|
61.5%
|
90.2%
|
9.8%
|
|
|
Black
|
15.0%
|
88.1%
|
11.9%
|
|
|
Hispanic
|
19.2%
|
86.3%
|
13.7%
|
|
|
Other
|
4.4%
|
86.8%
|
13.2%
|
|
|
Gender
|
|
|
|
0.122
|
|
Male
|
51.4%
|
89.8%
|
10.2%
|
|
|
Female
|
48.6%
|
88.1%
|
11.9%
|
|
|
Household income
|
|
|
|
0.110
|
|
Below poverty
|
22.4%
|
86.7%
|
13.3%
|
|
|
Above poverty
|
77.6%
|
89.6%
|
10.4%
|
|
|
BMI
|
|
|
|
< 0.001
|
|
< 85th percentile
|
68.3%
|
93.9%
|
6.1%
|
|
|
≥ 85th percentile
|
31.7%
|
78.4%
|
21.6%
|
|
|
Exercise
|
|
|
|
0.217
|
|
< 3x/week
|
19.0%
|
87.1%
|
12.9%
|
|
|
≥ 3x/week
|
81.0%
|
89.3%
|
10.7%
|
|
Table 3 Likelihood (odds ratio and 95% confidence
interval) of having elevated serum CRP
(> 3.0 mg/L).
|
All children
|
BMI ≥ 85th Percentile
|
|
Odds ratio
|
95% CI
|
Odds ratio
|
95% CI
|
|
Fiber intake
|
0.982
|
0.956-1.008
|
0.989
|
0.952-1.026
|
|
Caloric intake
|
1.000
|
0.999-1.001
|
1.000
|
0.999-1.001
|
|
Age
|
1.005
|
0.948-1.066
|
1.040
|
0.973-1.112
|
|
Race
|
|
|
|
|
|
White
|
1
|
1
|
1
|
1
|
|
Black
|
0.963
|
0.680-1.364
|
0.983
|
0.595-1.634
|
|
Hispanic
|
1.213
|
0.849-1.732
|
1.063
|
0.695-1.626
|
|
Other
|
0.957
|
0.474-1.935
|
1.083
|
0.411-2.856
|
|
Gender
|
|
|
|
|
|
Male
|
1
|
1
|
1
|
1
|
|
Female
|
1.213
|
0.945-1.558
|
1.424
|
1.049-1.934
|
|
Income
|
|
|
|
|
|
Below poverty
|
1.182
|
0.825-1.695
|
1.238
|
0.869-1.762
|
|
Above poverty
|
1
|
1
|
1
|
1
|
|
Exercise
|
|
|
|
|
|
< 3x/week
|
1
|
1
|
1
|
1
|
|
≥ 3x/week
|
1.032
|
0.717-1.486
|
0.865
|
0.527-1.420
|
|
BMI
|
|
|
|
|
|
< 85th percentile
|
1
|
1
|
|
|
|
≥ 85th percentile
|
3.834
|
2.947-∞
|
|
|
|
Mg Intake
|
|
|
|
|
|
< 75% RDA
|
1.578
|
1.070-∞
|
1.377
|
0.849-∞
|
|
75-99% RDA
|
1.322
|
0.740-2.362
|
1.419
|
0.713-2.824
|
|
≥ RDA
|
1
|
1
|
1
|
1
|
Discussion
The main finding of this study is that children are more likely to
have elevated serum CRP (> 3.0 mg/L) if they
consume less than the RDA of Mg. Overweight children had no greater
likelihood of having elevated CRP. The association between Mg
intake and CRP was maintained after controlling for demographic and
lifestyle factors that could confound the association.
The implications of these findings are that Mg intake may be an
important determinant of levels of inflammation in children and
adolescents as it is in adults. Mg deficiency may play a role in
putting individuals at increased cardiovascular risk at a young
age. The findings also have some implications as to whether
magnesium plays a direct and important role in regulating
inflammation. Magnesium functions in many important metabolic
pathways and is a coenzyme for almost 300 reactions including many
involving muscle contraction. Magnesium has also been found to play
a key role in endothelial metabolism and function [16]. Because
children with elevated CRP frequently also have other accompanying
cardiovascular risk factors, maintaining sufficient magnesium for
important physiologic processes is especially important [6].
Healthier diet habits are needed to assure adequate magnesium
intake in children for these vital metabolic pathways.
Elevated CRP levels are also more common in children with
symptoms of the metabolic syndrome [17]. Children with the
metabolic syndrome were approximately three times more likely to
have an elevated CRP level than children without the metabolic
syndrome [17]. It is unknown whether children with an elevated CRP
level are more likely to experience cardiovascular complications in
the future. However, it will be important to assess the various
cardiovascular risk factors into adulthood.
Previous studies have demonstrated an association between diet
and elevation of serum CRP. Most notably, high dietary fiber intake
has been associated with lower CRP [9, 18, 19]. In those studies,
other nutrients were not found to be associated with CRP levels,
including carbohydrates and saturated fats [9, 18]. However, in
some studies dietary fiber intake was found to be highly correlated
with magnesium intake [9]. The question arises as to whether the
lower levels of CRP are due to the intake of fiber, magnesium, or
some other nutrient in foods that are a common source of both
(e.g., bran). By controlling for fiber intake in the current study,
we were able to test for and confirm an independent association
with magnesium.
The study has some important limitations that should be taken
into account. First, dietary information was obtained from 24-hour
dietary recall, which may not accurately represent an individual’s
intake over the last several weeks or months. Second, participants
may have exaggerated or overestimated their intake of healthy foods
such as vegetables and legumes which are relatively high in
magnesium. However, if true, then population estimates of magnesium
intake are likely to be too low, and the real associations between
Mg and CRP may be stronger than we have illustrated. Third, the
strength of the association between magnesium supplement intake and
CRP is modest, and may be due to other unmeasured factors. Further,
we can make no definitive statement regarding cause and effect in a
cross-sectional analysis.
Conclusion
In conclusion, magnesium intake below the RDA is prevalent and
associated with a higher likelihood of elevated serum CRP in
children. It may be beneficial to consider encouraging more
magnesium intake in children by increasing the intake of
magnesium-rich foods, but at present the scientific evidence does
not support magnesium supplementation for the general population.
Further prospective studies would need to be done to determine
whether increased magnesium intake can lower inflammation and be of
benefit to children’s health.
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|