Central Journal of Human Nutrition & Food Science

Cite this article: Papanikolaou Y, Brooks J, Reider C, Fulgoni VL (2014) Dietary Magnesium Usual Intake is Associated with Favorable Diabetes-Related Physiological Outcomes and Reduced Risk of Metabolic Syndrome: An NHANES 2001-2010 Analysis. J Hum Nutr Food Sci 2(3): 1038.

*Corresponding authorYanni Papanikolaou, Nutritional Strategies Inc., 59 Marriott Place, Paris, ON N3L 0A3, Canada, Tel: +1-519-504-9252; Email:

Submitted: 25 February 2014

Accepted: 12 October 2014

Published: 15 October 2014

ISSN: 2333-6706

Copyright© 2014 Papanikolaou et al.

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Dietary Magnesium Usual Intake is Associated with Favorable Diabetes-Related Physiological Outcomes and Reduced Risk of Metabolic Syndrome: An NHANES 2001-2010 AnalysisYanni Papanikolaou1*, James Brooks2, Carroll Reider2 and Victor L. Fulgoni3

1Nutritional Strategies, Inc. Canada2Pharmavite, LLC, USA3Nutrition Impact, LLC, 9725 D Drive North, Battle Creek, MI 49014, USA

INTRODUCTIONType 2 diabetes mellitus prevalence remains an increasingly

important burden to public health worldwide. In 2010, total diabetes (i.e., diagnosed and undiagnosed diabetes) among U.S. individuals aged 20 years or older was 25.6 million or 11.3% of the population [1]. An estimated 79 million Americans 20-years-old and greater have pre-diabetes [1]. People with pre-diabetes present blood glucose levels that are higher than normal, however, not high enough to be diagnosed as diabetes. Nonetheless, individuals with pre-diabetes are at an elevated risk for developing type 2 diabetes, heart disease and stroke [2]. While these statistics include type 1 diabetes mellitus, type 2 diabetes accounts for about 95% of diagnosed diabetes in adults [2]. If current trends continue, it is predicted that the

prevalence of total diabetes in the U.S. will increase from the 2010 level of about 1 in 10 adults to between 1 in 5 and 1 in 3 adults in 2050 [3].Currently, diabetes is a major cause of heart disease and cerebrovascular complications (i.e., stroke) and is the seventh leading cause of death in the U.S. [1]. Average medical expenditures among people with diagnosed diabetes have been reported to be 2.3 times greater relative to what expenditures would be in the absence of diabetes with estimated direct and indirect costs at $174 billion [1].

The etiology of type 2 diabetes is multifaceted, however, environmental factors, including the American diet are key contributors to development and progression of type 2 diabetes.Several studies have shown that dietary strategieshelp improve characteristics associated with type 2 diabetes, including

Abstract

Type 2 diabetes mellitus (DM2) has been a growing public health concern and diet is widely believed to play an important role in its development. Magnesium has received considerable interest for its potential in improving insulin sensitivity, glucose control and thus influencing diabetes risk. We examined the relationship between dietary magnesium intake from food and food combined with supplements and diabetes and other related health factors in adults ≥20 years of age using data from the National Health and Nutrition Examination survey from 2001-2010. Usual intakes from foods alone and from foods plus dietary supplements were determined using the methods from the National Cancer Institute.Adults with adequate intake of magnesium from food had significantly different HOMA-IR (7.14%, p=0.0204); systolic blood pressure (-0.54%, p=0.0279) and HDL-cholesterol (2.29%, p=0.001) compared to adults with inadequate intake of magnesium from food. Adequate intake of magnesium from food plus supplement had significant differences in waist circumference (-0.86%, p=0.0043), systolic blood pressure (-0.56%, p=0.0297) and HDL-cholesterol (3.35%, p<0.0001) compared to adults with inadequate intake of magnesium from food plus supplements. Higher dietary intake of magnesium from food plus supplements was associated with significantly reduced odds ratios for elevated glycohemoglobin, metabolic syndrome, obesity, overweight or obesity, elevated waist circumference, elevated systolic blood pressure, reduced HDL and elevated C-reactive protein. Thus, there is a beneficial relationship between dietary magnesium intake and diabetes-related physiological outcomes in U.S. adults.

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improvement in insulin sensitivity, blood glucose concentrations, glycemic control, inflammatory markers, oxidative stress and lipid profiles [4-7]. Of interest, dietary minerals may also factor in a contributing profile. Magnesium acts as a cofactor in enzymescontributing to carbohydrate metabolism [8] and has garnered attention for its potential in improving insulin sensitivity and glucose control [9], which may potentially lend protection against type 2 diabetes development. Prospective evidence has identified a modest inverse association between dietary magnesium consumption and risk of developing type 2 diabetes among middle aged, overweight women [10]. Similar findings were seen in a Japanese population, such that adults in the highest quartile had a 36% risk reduction for type 2 diabetes [11]. A recent meta-analysis provided further substantiation to support an inverse association between magnesium intake and risk of type 2 diabetes, consistent with a dose-response relationship [12].

As evidence continues to build, we conducted an analysis in U.S. adults ≥20 years of age to determine the relationship between magnesium intake and diabetes and other related health factors as found in the National Health and Nutrition Examination Survey (NHANES) 2001-2010.

MATERIALS AND METHODSThe NHANES is a nationally representative, cross-sectional

survey of non-institutionalized, civilian U.S. residents, collected by the National Center for Health Statistics of the Centers for Disease Control and Prevention [13]. Written informed consent was obtained for all participants or proxies, and the survey protocol was approved by the Research Ethics Review Board at the National Center for Health Statistics. Data from five NHANES datasets(2001-2002, 2003-2004, 2005-2006, 2007-2008, 2009-2010) were combined for these analyses [14, 15]. The nutrient intakes for NHANES 2001-2008 are from the USDA Food and Nutrient Database for Dietary Studies 3.0 [16]. The combined sample included 14,338 participants, aged ≥19 years of age, who had complete 24-h dietary intake data from What We Eat in America [17].

Statistical methods

Magnesium intake from food was estimated as individual usual intake using the National Cancer Institute (NCI) method [18]. Intake from supplements was taken from NHANES supplement intake data, and intake from food plus supplements was calculated as individual usual intake with supplement intake being added to daily individual intake from food. Quartiles of dietary intake of magnesium (both with and without supplements) were created from their distributions determined using the sampling weights. Covariates used in the NCI model were survey day (one or two) and a weekend day flag (i.e., Friday/Saturday/Sunday vs. others). Complete details of the NCI method are shown elsewhere [19], and the SUDAAN/SAS macros (SAS, version 9; SAS Institute Inc) necessary to fit this model and to perform the estimation of usual intake distributions are available on the NCI website [18].Estimated average requirement (EAR) values were used to assess adequacy of dietary magnesium intake. The EAR is the

appropriate value to be used for assessing adequacy of intake (i.e., determining the proportion of individuals whose usual intake is less than the EAR [20].

NHANES 2001-2010 data were analyzed examining the relationship between diabetes and related health factors with the intake of magnesium from food and magnesium from food plus supplements. SAS (version 9.2; SAS Institute Inc.) and SUDAAN (version 11, Research Triangle Park, NC) are used with NHANES day 1 dietary data and survey parameters including weights and variance estimation adjusting for primary sampling units and strata. Data are presented as means ± standard errors and a p-value of <0.05 was set to establish significance.

Analyses were limited to men and non-pregnant/non-lactating women ≥ 20 years of age. Additionally, those with unreliable dietary records as assessed by the USDA were excluded. Plasma glucose, glycohemoglobin, insulin, HOMA-IR, body mass index (BMI), waist circumference, blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides and C-reactive protein were analyzed. The glucose and insulin values reported

Risk Factors Criteria used for determination

Diabetes Diabetes diagnosed or insulin medications or glucose control medications

Diabetes (Informed by Doctor) Diabetes diagnosed

Elevated Glucose Glucose control medications or Plasma Glucose ≥ 100 mg/dl

Elevated Glycohemoglobin > 5.7% for age >19

Elevated Insulin Glucose control medications or Plasma insulin ≥ 15 µU/ml

Elevated HOMA-IR Glucose control medications or ≥ 4Taking diabetic meds to lower blood sugar Yes

Metabolic Syndrome

At least 3 of following: elevated waist circumference, elevated glucose, elevated triglycerides, elevated blood pressure, reduced HDL

Obese BMI ≥ 30

Overweight BMI ≥ 25 <30

Overweight or Obese BMI ≥ 25

Elevated Waist Circumference Male ≥ 102 cm or female ≥ 88 cm

Elevated Blood Pressure Hypertension medications or DBP ≥ 85 mm or SBP ≥ 130 mm

Elevated Systolic BP (SBP) Hypertension medications or SBP ≥ 130 mm

Elevated Diastolic BP (DBP Hypertension medications or DBP ≥ 85 mm

Elevated LDL Lipid lowering medications or ≥ 100 mg/dl

Reduced HDL Male < 40 mg/dl or female < 50 mg/dl

Elevated Triglycerides Lipid lowering medications or ≥ 150 mg/dl

Elevated C-reactive Protein ≥ 3 mg/l

Table 1: Criteria for determining the presence of diabetes or other heath risk factors.

The data for metabolic syndrome, BMI, waist circumference, overweight and obesity factors was adjusted for age, gender, ethnicity, poverty income ratio, physical activity level and alcohol; and data for all other factors was adjusted for BMI, age, gender, ethnicity, poverty income ratio, physical activity level and alcohol.

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in the present study are from fasted samples. The presence of diabetes and other health risk factors were determined and using the criteria presented in Table 1.

RESULTSMagnesium Intakes From Foods and Dietary Supplements

and Comparison of Diabetes-Related Outcome Factors in U.S. Adults ≥ 20 Years of Age.

Adults with adequate intake (i.e., adults meeting EAR) of magnesium from food had significantly different HOMA-IR (7.14%, p=0.0204); systolic blood pressure (-0.54%, p=0.0279) and HDL-cholesterol (2.29%, P=0.001) compared to adults with inadequate intake (i.e., adults not meeting EAR) of magnesium from food (Table 2). However, the difference in systolic blood pressure between adults with adequate magnesium intake and

adults with inadequate magnesium intake was less than 1% (Table 2). No significant difference was noted for plasma glucose, glycohemoglobin, insulin, BMI, waist circumference, diastolic blood pressure, LDL-cholesterol, triglycerides and C-reactive protein among adults with adequate and inadequate intake of magnesium from foods (Table 2).

Adults with adequate intake of magnesium from food plus supplement had significant differences in waist circumference (-0.86%, p=0.0043), systolic blood pressure (-0.56%, p=0.0297) and HDL-cholesterol (3.35%, p<0.0001) compared to adults with inadequate intake of magnesium from food plus supplements (Table 3).Similar to findings in the food data, the difference in waist circumference and systolic blood pressure between adults with adequate magnesium intake and adults with inadequate magnesium intake was less than 1% (Table 3).No significant

Adults with Inadequate Intake of Mg from Food

(Do not meet EAR)

Adults with Adequate Intake of Mg from Food

(Meet EAR)P Value for Difference

Plasma Glucose* (mg/dL) 103.20±0.41 103.15±0.53 0.9313

Glycohemoglobin (%) 5.53±0.01 5.53±0.01 0.5196

Insulin* (µU/mL) 11.67±0.18 11.86±0.19 0.3703

HOMA-IR 3.33±0.06 3.57±0.09 0.0204

Body Mass Index (kg/m2) 28.50±0.09 28.48±0.13 0.9014

Waist Circumference (cm) 97.78±0.21 97.42±0.30 0.2232

BP Systolic (mm Hg) 122.96±0.25 122.30±0.26 0.0279

BP Diastolic (mm Hg) 71.21±0.24 71.63±0.24 0.0718

LDL-cholesterol (mg/dL) 117.77±0.60 116.35±0.82 0.1487

HDL-cholesterol (mg/dL) 52.99±0.24 54.21±0.28 0.0001

Triglyceride (mg/dL) 141.98±2.30 138.14±2.85 0.2630

C-reactive protein (mg/dL) 0.42±0.01 0.39±0.02 0.1780

Table 2: Comparison of diabetes-related outcome factors in US adults aged ≥ 20 years with adequate and inadequate dietary intakes of magnesium from food (excluding supplements), NHANES 2001-2010. Data are presented as mean±SE.

*represents fasting values

Adults with Inadequate Intake of Mg from Food plus Supplement

(Do not meet EAR)

Adults with Adequate Intake of Mg from Food plus Supplements

(Meet EAR)

P Value for Difference

Plasma Glucose* (mg/dL) 103.38±0.48 102.96±0.47 0.5278

Glycohemoglobin (%) 5.53±0.01 5.52±0.01 0.3129

Insulin* (µU/mL) 11.88±0.20 11.64±0.16 0.2607

HOMA-IR 3.39±0.07 3.44±0.08 0.6326

Body Mass Index (kg/m2) 28.60±0.09 28.40±0.12 0.1267

Waist Circumference (cm) 98.09±0.22 97.25±0.27 0.0043

BP Systolic (mm Hg) 123.07±0.27 122.38±0.25 0.0297

BP Diastolic (mm Hg) 71.33±0.26 71.43±0.23 0.6621

LDL-cholesterol (mg/dL) 117.95±0.74 116.61±0.71 0.2019

HDL-cholesterol (mg/dL) 52.53±0.25 54.29±0.26 <0.0001

Triglyceride (mg/dL) 141.57±3.02 139.39±2.52 0.5856

C-reactive protein(mg/dL) 0.44±0.02 0.39±0.01 0.0674

Table 3: Comparison of diabetes-related outcome factors in US adults aged ≥ 20 years with adequate and inadequate dietary intakes of magnesium from food plus supplements, NHANES 2001-2010. Data is presented as mean±SE.

*represents fasting values

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difference was noted for plasma glucose, glycohemoglobin, insulin, HOMA-IR, BMI, diastolic blood pressure, LDL-cholesterol, triglycerides and C-reactive protein among adults with adequate and inadequate intake of magnesium from foodplus supplements (Table 3).

Quartiles of Dietary Magnesium Intakes From Foods and Dietary Supplements and Comparison of Diabetes-Related Outcome Factors in U.S. Adults ≥ 20 Years of Age

As the magnesium intake from food increased, the values for systolic blood pressure and C-reactive protein decreased while values for HOMA-IR, diastolic blood pressure and HDL-cholesterol increased significantly (Table 4). However the difference in systolic or diastolic blood pressure from lowest to highest quartile was 2% or less (Table 4). Mean values for plasma glucose, glycohemoglobin, insulin, BMI, waist circumference,

LDL-cholesterol and triglycerides did not change significantly with increase in magnesium intake from food (Table 4).

As the magnesium intake from foodplus supplements increased, the values for insulin, BMI, waist circumference, systolic blood pressure and C-reactive protein decreased while values for diastolic blood pressure and HDL-cholesterol increased significantly (Table 5). However the difference in BMI, waist circumference and systolic & diastolic blood pressure from lowest to highest quartile of magnesium intake was less than 2% (Table 5). Values for plasma glucose, glycohemoglobin, HOMA-IR, LDL-cholesterol and triglycerides did not change significantly with increase in magnesium intake from food plus supplements (Table 5).

Odds Ratios of Diabetes-Related Outcome Measures in U.S. Adults ≥ 20 Years of Age with Adequate and Inadequate Dietary Intake of Magnesium from Food and Dietary Supplements

Quartiles of Magnesium Intake from Food (mg/day)P Value for TrendQ1

(<238.8)Q2

(238.8–286.9)Q3

(286.9-341.3)Q4

(>341.3)Plasma Glucose* (mg/dL) 103.31±0.63 101.87±0.52 104.01±0.65 103.57±0.78 0.3850

Glycohemoglobin (%) 5.51±0.02 5.52±0.01 5.54±0.01 5.53±0.02 0.2949

Insulin* (µU/mL) 11.73±0.23 11.77±0.28 11.74±0.21 11.74±0.23 0.9888

HOMA-IR 3.32±0.10 3.34±0.10 3.43±0.10 3.61±0.14 0.0461

Body Mass Index (kg/m2) 28.47±0.13 28.46±0.13 28.36±0.14 28.67±0.16 0.4398

Waist Circumference (cm) 97.79±0.28 97.60±0.32 97.28±0.35 97.87±0.37 0.9763

BP Systolic (mm Hg) 123.82±0.38 122.71±0.36 121.91±0.31 122.37±0.38 0.0074

BP Diastolic (mm Hg) 70.85±0.30 71.15±0.31 71.24±0.27 72.26±0.30 0.0009

LDL-cholesterol (mg/dL) 117.77±1.05 116.81±0.82 117.83±0.89 116.36±1.14 0.5574

HDL-cholesterol (mg/dL) 51.98±0.41 53.39±0.31 53.89±0.30 54.60±0.35 <0.0001

Triglyceride (mg/dL) 137.53±3.01 138.67±2.29 147.79±5.22 137.44±3.54 0.6261

C-reactive protein(mg/dL) 0.47±0.02 0.44±0.03 0.38±0.02 0.36±0.02 0.0032

Table 4: Diabetes-related outcome factors by quartiles of dietary intake of magnesium from food (excluding supplements) among U.S. adults ≥ 20 Years, NHANES 2001-2010. Data is presented as mean±SE.

*represents fasting values

Quartiles of Magnesium Intake from Food plus Supplements (mg/day) P Value for

TrendQ1(<255.4)

Q2(255.4-314.3)

Q3(314.3-382.1)

Q4(>382.1)

Plasma Glucose* (mg/dL) 103.70±0.64 103.11±0.53 103.44±0.64 102.37±0.71 0.2163Glycohemoglobin (%) 5.54±0.01 5.53±0.01 5.54±0.02 5.50±0.02 0.0731Insulin* (µU/mL) 12.27±0.32 11.78±0.20 11.84±0.25 11.13±0.21 0.0030HOMA-IR 3.53±0.11 3.35±0.08 3.48±0.11 3.33±0.14 0.4292Body Mass Index (kg/m2) 28.72±0.11 28.45±0.12 28.57±0.16 28.23±0.16 0.0292Waist Circumference (cm) 98.43±0.25 97.82±0.29 97.61±0.35 96.71±0.40 0.0003BP Systolic (mm Hg) 123.61±0.40 122.51±0.31 122.62±0.32 122.04±0.33 0.0029BP Diastolic (mm Hg) 71.14±0.34 70.91±0.27 71.57±0.26 71.88±0.30 0.0168LDL-cholesterol (mg/dL) 117.41±1.01 117.44±0.98 117.90±0.95 116.11±1.15 0.4828HDL-cholesterol (mg/dL) 51.63±0.39 53.26±0.29 53.85±0.31 55.15±0.36 <0.0001Triglyceride (mg/dL) 137.76±2.84 139.60±2.63 149.09±4.98 134.82±2.84 0.9204C-reactive protein(mg/dL) 0.48±0.03 0.43±0.02 0.40±0.02 0.34±0.02 0.0003

Table 5: Diabetes-related outcome factors by quartiles of dietary intake of magnesium from food plus supplements among U.S. adults ≥ 20 Years, NHANES 2001-2010. Data are presented as mean±SE

*represents fasting values

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Odds Ratio (95% CI)P Value for Difference

Adults with Inadequate Intake of Mg from Food

(Do not meet EAR)

Adults with Adequate Intake of Mg from Food

(Meet EAR)Diabetes 1.00 0.99 (0.86, 1.15) 0.9201Diabetes (Informed by Doctor) 1.00 0.97 (0.84, 1.13) 0.7286Elevated Glucose 1.00 1.04 (0.92, 1.17) 0.5418Elevated Glycohemoglobin 1.00 0.97 (0.88, 1.07) 0.5778Elevated Insulin 1.00 1.01 (0.86, 1.19) 0.9089Elevated HOMA-IR 1.00 1.04 (0.90, 1.21) 0.5536Taking diabetic meds to lower blood sugar 1.00 1.02 (0.88, 1.18) 0.8391Metabolic Syndrome 1.00 0.88 (0.79, 0.98) 0.0166Obesity 1.00 0.95 (0.87, 1.04) 0.2629Overweight 1.00 0.97 (0.90, 1.06) 0.5009Overweight or Obesity 1.00 0.91 (0.84, 0.99) 0.0305Elevated Waist Circumference 1.00 0.92 (0.85, 1.01) 0.0729Elevated BP 1.00 0.88 (0.80, 0.98) 0.0205Elevated Systolic BP 1.00 0.87 (0.78, 0.96) 0.0070Elevated Diastolic BP 1.00 0.94 (0.85, 1.03) 0.1781Elevated LDL 1.00 0.94 (0.83, 1.07) 0.3550Reduced HDL 1.00 0.84 (0.75, 0.94) 0.0039Elevated Triglycerides 1.00 0.91 (0.80, 1.02) 0.1152Elevated C-reactive Protein 1.00 0.90 (0.56, 1.45) 0.6540

Table 6: Odds Ratios for diabetes and related outcome measures in US adults aged ≥ 20 years with adequate and inadequate dietary intakes of magnesium from food (excluding supplements), NHANES 2001-2010.

Odds Ratio (95% CI)

P value for difference

Adults with Inadequate Intake of Mg from Food plus

Supplements(Do not meet EAR)

Adults with Adequate Intake of Mg from Food plus

Supplements(Meet EAR)

Diabetes 1.00 1.01 (0.90, 1.13) 0.8787Diabetes (Informed by Doctor) 1.00 0.99 (0.89, 1.10) 0.8389Elevated Glucose 1.00 1.01 (0.89, 1.14) 0.8855Elevated Glycohemoglobin 1.00 0.88 (0.81, 0.96) 0.0046Elevated Insulin 1.00 1.01 (0.87, 1.17) 0.8816Elevated HOMA-IR 1.00 1.03 (0.90, 1.18) 0.6739Taking diabetic meds to lower blood sugar 1.00 0.99 (0.88, 1.12) 0.8708Metabolic Syndrome 1.00 0.92 (0.82, 1.03) 0.1419Obesity 1.00 0.92 (0.85, 1.00) 0.0378Overweight 1.00 0.95 (0.88, 1.03) 0.2305Overweight or Obesity 1.00 0.86 (0.79, 0.94) 0.0011Elevated Waist Circumference 1.00 0.88 (0.81, 0.96) 0.0057Elevated BP 1.00 0.92 (0.83, 1.03) 0.1461Elevated Systolic BP 1.00 0.90 (0.81, 1.01) 0.0659Elevated Diastolic BP 1.00 0.99 (0.89, 1.09) 0.7840Elevated LDL 1.00 0.94 (0.81, 1.09) 0.3983Reduced HDL 1.00 0.81 (0.71, 0.93) 0.0034Elevated Triglycerides 1.00 0.96 (0.85, 1.10) 0.5778Elevated C-reactive Protein 1.00 0.80 (0.52, 1.24) 0.3153

Table 7: Odds Ratios for diabetes and related outcome measures in US adults aged ≥ 20 years with adequate (meet EAR) and inadequate (do not meet EAR) dietary intakes of magnesium from food plus supplements, NHANES 2001-2010.

The odds ratios for metabolic syndrome, overweight or obesity, elevated blood pressure, elevated systolic blood pressure and reduced HDL were significantly lowered in adults with adequate intake of magnesium from food and compared to adults withinadequate intake of magnesium from food (Table 6).

No significant difference in odds ratios for any other outcomes measured was observed.

Magnesium intake from food in combination with dietary supplements was associated with reduced risk for several

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diabetes-related measures. The odds ratios for elevated glycohemoglobin, obesity, overweight or obesity, elevated waist circumference and reduced HDL were significantly lowered in adults with adequate intake of magnesium from food plus supplements compared to adults with inadequate intake of magnesium from food plus supplements (Table 7). There was no significant difference in odds ratios for any other outcomes measured.

Odds Ratios of Diabetes-Related Outcome Measures in U.S. Adults ≥ 20 Years of Age Quartiles of Dietary Intake of Magnesium from Food and Dietary Supplements.

Higher dietary intake of magnesium from foods was associated with significantly reduced odds ratios for elevated blood pressure, elevated systolic blood pressure and reduced HDL (Table 8). There was no significant association between

dietary intake of magnesium from foods and other outcome measures (Table 8).

Higher dietary intake of magnesium from food plus supplements was associated with significantly reduced odds ratios for elevated glycohemoglobin, metabolic syndrome, obesity, overweight or obesity, elevated waist circumference, elevated systolic blood pressure, reduced HDLand elevated C-reactive protein (Table 9). There was no significant association between dietary intake of magnesium from food and supplements and other outcome measures (Table 9).

DISCUSSIONThe present secondary analysis identified several beneficial

physiological outcomes associated with dietary magnesium consumption.Dietary intake of magnesium from foods or from

Odds Ratios (95% CI) forQuartiles of Mg Intake from Food (mg/day)

P for trendQ1

(<238.8)Q2

(238.8–286.9)Q3

(286.9-341.3)Q4

(>341.3)

Diabetes 1.00 0.95(0.81, 1.10)

1.03(0.89, 1.20)

0.95(0.77, 1.17) 0.8506

Diabetes (Informed by Doctor) 1.00 0.94(0.81, 1.11)

1.00(0.85, 1.17)

0.92(0.75, 1.12) 0.5122

Elevated Glucose 1.00 1.03(0.88, 1.20)

1.01(0.82, 1.25)

1.07(0.88, 1.31) 0.5794

Elevated Glycohemoglobin 1.00 1.14(0.99, 1.32)

1.14(0.96, 1.36)

0.95(0.80, 1.13) 0.6650

Elevated Insulin 1.00 0.95(0.80, 1.12)

1.01(0.79, 1.28)

0.99(0.80, 1.23) 0.8942

Elevated HOMA-IR 1.00 0.90(0.77, 1.05)

0.99(0.79, 1.25)

1.07(0.86, 1.33) 0.3958

Taking diabetic meds to lower blood sugar 1.00 1.00

(0.83, 1.21)1.14

(0.95, 1.37)1.00

(0.8, 1.26) 0.6060

Metabolic Syndrome 1.00 0.90(0.77, 1.05)

0.86(0.73, 1.03)

0.85(0.71, 1.07) 0.0655

Obesity 1.00 1.01(0.91, 1.14)

0.94(0.82, 1.06)

0.99(0.87, 1.13) 0.6309

Overweight 1.00 0.92(0.83, 1.02)

0.98(0.87, 1.10)

0.98(0.87, 1.11) 0.9241

Overweight or Obesity 1.00 0.93(0.82, 1.05)

0.90(0.79, 1.02)

0.95(0.82, 1.09) 0.3840

Elevated Waist Circumference 1.00 0.98(0.85, 1.12)

0.88(0.77, 1.00)

0.96(0.83, 1.10) 0.3195

Elevated BP 1.00 0.88(0.76, 1.03)

0.71(0.60, 0.83)

0.77(0.64, 0.93) 0.0030

Elevated Systolic BP 1.00 0.87(0.75, 1.03)

0.70(0.59, 0.83)

0.77(0.65, 0.93) 0.0017

Elevated Diastolic BP 1.00 0.97(0.85, 1.11)

0.82(0.71, 0.94)

0.95(0.80, 1.12) 0.2580

Elevated LDL 1.00 0.97(0.82, 1.14)

1.05(0.86, 1.28)

0.84(0.67, 1.04) 0.1895

Reduced HDL 1.00 0.80(0.71, 0.91)

0.72(0.60, 0.87)

0.73(0.60, 0.88) 0.0013

Elevated Triglycerides 1.00 0.97(0.81, 1.17)

0.86(0.70, 1.05)

0.86(0.70, 1.04) 0.0721

Elevated C-reactive Protein 1.00 0.64(0.41, 1.01)

0.38(0.17, 0.87)

0.42(0.16, 1.13) 0.0632

Table 8: Odds ratios for diabetes and related outcome measures by quartiles of dietary intake of magnesium from food (excluding supplements) among U.S. adults ≥ 20 Years, NHANES 2001-2010.

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Odds Ratios (95% CI) for Quartiles of Mg Intake from Food plus Supplements (mg/day)

P for trendQ1

(<255.4)Q2

(255.4-314.3)Q3

(314.3-382.1)Q4

(>382.1)

Diabetes 1.00 1.00(0.87, 1.15)

0.94(0.79, 1.13)

0.99(0.83, 1.18) 0.7800

Diabetes (Informed by Doctor) 1.00 0.96(0.84, 1.11)

0.93(0.78, 1.10)

0.96(0.80, 1.15) 0.5526

Elevated Glucose 1.00 1.09(0.93, 1.28)

0.98(0.82, 1.17)

0.98(0.82, 1.17) 0.4823

Elevated Glycohemoglobin 1.00 1.08(0.94, 1.24)

0.92(0.79, 1.06)

0.81(0.69, 0.95) 0.0027

Elevated Insulin 1.00 0.97(0.79, 1.20)

0.97(0.80, 1.18)

0.88(0.71, 1.09) 0.2206

Elevated HOMA-IR 1.00 1.03(0.84, 1.26)

0.98(0.80, 1.21)

0.90(0.74, 1.11) 0.2331

Taking diabetic meds to lower blood sugar 1.00 0.98

(0.81, 1.20)1.04

(0.83, 1.29)0.97

(0.79, 1.19) 0.9138

Metabolic Syndrome 1.00 0.97(0.84, 1.12)

0.84(0.71, 0.98)

0.77(0.64, 0.92) 0.0009

Obesity 1.00 0.98(0.88, 1.08)

1.01(0.90, 1.15)

0.85(0.75, 0.98) 0.0359

Overweight 1.00 0.91(0.80, 1.03)

0.86(0.75, 0.99)

0.94(0.83, 1.07) 0.3689

Overweight or Obesity 1.00 0.88(0.77, 0.99)

0.85(0.73, 0.98)

0.79(0.69, 0.89) 0.0008

Elevated Waist Circumference 1.00 0.91(0.82, 1.01)

0.87(0.78, 0.98)

0.80(0.69, 0.91) 0.0013

Elevated BP 1.00 0.81(0.70, 0.95)

0.81(0.71, 0.92)

0.83(0.70, 0.99) 0.0673

Elevated Systolic BP 1.00 0.82(0.70, 0.96)

0.82(0.72, 0.93)

0.81(0.68, 0.97) 0.0298

Elevated Diastolic BP 1.00 0.91(0.79, 1.05)

0.96(0.86, 1.09)

0.95(0.80, 1.13) 0.7520

Elevated LDL 1.00 1.08(0.89, 1.32)

1.05(0.85, 1.29)

0.93(0.74, 1.16) 0.4523

Reduced HDL 1.00 0.83(0.72, 0.95)

0.76(0.65, 0.90)

0.66(0.53, 0.82) 0.0002

Elevated Triglycerides 1.00 1.04(0.89, 1.22)

0.96(0.80, 1.15)

0.90(0.76, 1.06) 0.1096

Elevated C-reactive Protein 1.00 0.58(0.32, 1.05)

0.47(0.24, 0.92)

0.35(0.14, 0.91) 0.0183

Table 9: Odds ratios for diabetes and related outcome measures by quartiles of dietary intake of magnesium from food plus supplements among U.S. adults ≥ 20 Years, NHANES 2001-2010.

foods plus supplements are associated with several favorable diabetes-related outcome measures, including higher HDL-cholesterol and lower C-reactive protein. While dietary intake of magnesium from food plus supplement (but not from food excluding supplements) was associated with lower insulin, dietary intake of magnesium from foods alone (but not from food plus supplements) was associated with higher HOMA-IR.Dietary intake of magnesium from foods or from food plus supplements was associated with reduced risk for metabolic syndrome, obesity or overweight, elevated blood pressure, and reduced HDL-cholesterol. Additionally,a risk reduction was associated with dietary intake of magnesiumfrom foods and dietary supplements for elevated glycohemoglobin, elevated waist circumference & elevated C-reactive protein.

Magnesium is an essential nutrient representing the

fourth most abundant mineral and the second most abundant intracellular divalent cation and acts as a cofactor in more than 300 metabolic reactions in the human body [21]. Magnesium is fundamental in numerous physiological functions, which include glucose and insulin metabolism [21]. The 2010 Dietary Guidelines Advisory Committee Report (DGAC) identified magnesium, as well as other nutrients, as shortfall nutrients for children and most notably adolescents (a high prevalence of inadequate dietary intake of a nutrient among any segment of the population constitutes a shortfall nutrient) [22]. Our previous work has reported the percentage of individuals aged ≥2 years with total usual nutrient intake, including that from foods and dietary supplements, falling below the EAR was considerable for magnesium, such that 45% of this population reporting inadequate magnesium consumption [23]. The dairy

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J Hum Nutr Food Sci 2(4): 1038 (2014) 8/9

category has been identified as a key source of magnesium, with the dairy food group contributing 13% of the magnesium in the diet for individuals ≥2 years [24]. The 2010 Dietary Guidelines for Americans (DGA) recommends 3 daily servings of low-fat or fat-free milk and milk products for people ages 9 and older, 2.5 servings for 4-8 year olds and 2 servings for children ages 2-3 [25]. The reality is Americans on average are consuming about 1.7 servings of dairy foods daily [26]. Similarly, the American population is not meeting recommendations for other nutrient-dense foods that also contribute to dietary magnesium intake, including fruits, vegetables and whole grains, which collectively represent major contributors of dietary magnesium [22]. Thus, current dietary patterns that provide inadequate dietary magnesium, in collaboration with environmental factors (i.e., lack of physical activity), may be promoting a physiological milieu that favors progression of diabetes and diabetes-related outcomes. Low levels of magnesium have been associated with numerous chronic diseases, including cardiovascular disease and type 2 diabetes [21]. For the latter, several epidemiological studies suggest a protective role, such that greater magnesium intake is associated with a reduced risk for type 2 diabetes [10-12,28]. Multicenter, prospective data from the large CARDIA study cohort found that magnesium consumption was inversely associated with incidence of diabetes. Further, magnesium intake was also inversely associated with c-reactive protein, IL-6, fibrinogen levels and HOMA-IR and serum magnesium levels were significantly inversely correlated with c-reactive protein and HOMA-IR following adjustment for potential confounders. In contrast, a recent animal intervention showed that magnesium supplementation delays diabetes development under excessive food intake conditions [29].

An important finding in the present work, given the relationship of blood glucose and insulin with HOMA-IR, was that statistically non-significant findings were seen with plasma glucose and insulin values, while changes in HOMA-IR were statistically significant. HOMA-IR is calculated as fasting plasma insulin (mU/L) X fasting plasma glucose (mmol/L)/22.5and as such represents a completely different variable than fasting blood glucose or insulin when considered individually. It appears that the formula impacts glucose and insulin values in a way that allows for detection of differences. For example, combining these values in a multiplication formula creates a broader distribution of values, which then allowed us to see significant differences among our groups.

A limitation of this analysis is that the estimates relied on self-reported dietary data for intake of dietary magnesiumfrom both foods and dietary supplements. The models that were applied also relied on assumptions that reported nutrient intakes from food sources on 24-h recalls were unbiased, and the self-reported dietary supplement intake reflected the true long-term supplement intake. The data presented in the manuscript demonstrate associations and not cause and effect due to the observational nature of NHANES.

Our current observational findings demonstrate several beneficial relationships between dietary magnesium intake and diabetes-related outcome measurements in U.S. adults 20 years of age and older.Importantly, dietary intake of magnesium from

foods or from food plus supplements was associated with a decreased risk for metabolic syndrome, obesity or overweight, elevated blood pressure, and reduced HDL-cholesterol, with lower odds ratios identified with dietary intake of magnesium from foods and dietary supplements for elevated glycohemoglobin, elevated waist circumference & elevated C-reactive protein. As magnesium has been identified as a shortfall nutrient by the 2010 DGAC report, and Americans continue to struggle with meeting nutrient and food group recommendations, dietary magnesium supplementation coupled with appropriate food choicesoffer an evidence-based option to meet authoritative recommendations and potentially reduce the risk of diabetes and diabetes-related outcomes.

ACKNOWLEDGMENTSV.L.F. designed research, conducted analyses and provided

interpretation: Y.P. collaborated on the interpretation and drafted the manuscript: C.R. and J.B. contributed to the manuscript; all authors read and approved the final manuscript.

The present research was funded by Pharmavite, LLC. Y. Papanikolaou, and V. Fulgoni: no conflicts interest. J. Brooks and C. Reider are employees of Pharmavite, LLC.

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