Date of Award


Document Type


Degree Name

Doctor of Philosophy (PhD)


Clinical and Translational Science

First Advisor

Benjamin Littenberg

Second Advisor

Gail Rose


Research has focused extensively on the negative health effects of inadequate Mg intake, but the extent of the problem of deficiency deserves further exploration. The notion that U.S. adults consume an inadequate amount of magnesium, leading to increased risk for chronic diseases such as depression, is plausible. National Health and Nutrition Examination Surveys (NHANES), which are large, cross-sectional, population-based data sets that assess the health and nutritional status of U.S. adults and children, indicate over half the adult population does not consume adequate amounts of magnesium based on the estimated average requirement (EAR) established by the Institute of Medicine. Using 2007 to 2010 NHANES data we found 54% of adults do not meet the EAR, confirming results from earlier surveys. As a result of this finding, a review exploring the factors impacting magnesium consumption over time and the adequacy of current intake in U.S. adults was conducted. Changes in agricultural processes that reduce magnesium levels in crops combined with the increasing consumption of processed foods containing little to no magnesium have led to a decrease in mean daily intake by 200-300 mg per day over the past century. However, population-based studies show a steady and consistent recovery in magnesium intake in U.S. adults over the past several decades. A simple, rapid, accurate test for whole body Mg status is lacking and, although population-based studies have limitations, continued monitoring of Mg consumption is essential to determine whether this positive trend continues. In the meantime, since the health consequences of inadequate magnesium are well established, there are no reported cases of hypermagnesemia from food alone, and magnesium is found in healthy foods adults should consume more often, there are few reasons not to encourage increased magnesium intake.

Cross-sectional and prospective trials in other countries report an association between magnesium intake and symptoms of depression. Depression is a chronic disease affecting a significant portion of the U.S. population. Magnesium plays a role in many of the pathways involved in the pathophysiology of depression and is found in several enzymes, hormones, and neurotransmitters. Depression and magnesium are both associated with systemic inflammation. Current treatment options for depression are limited by efficacy, cost, availability, side effects, and acceptability to patients. As a result of the need for additional treatment options, interest in the role of magnesium in modulating depressive symptoms has grown. We used the NHANES 2007-2010 data to examine this relationship in U.S. adults and found a significant association between very low magnesium intake and symptoms of depression (RR=1.16; 95% confidence interval (CI) 1.06, 1.30; P=0.03). Whether inadequate magnesium leads to increased risk for depression or depression results in poor dietary intake is not known.

To test whether supplementation with over-the-counter magnesium chloride improves symptoms of depression, an open-label, blocked, randomized, cross-over trial was carried out in outpatient primary care clinics on 126 adults (mean age 52; 38% male) diagnosed with, and currently experiencing, mild-to-moderate symptoms. Consumption of magnesium chloride tablets for 6 weeks resulted in a clinically significant net improvement in depression (Patient Health Questionnaire-9) scores of -6.0 points (95% CI -7.9, -4.2; P<0.001) and net improvement in anxiety (Generalized Anxiety Disorders-7) scores of -4.5 points (95% CI -6.6, -2.4; P<0.001). Effects were observed regardless of age, gender, baseline magnesium levels, baseline severity of depression, or use of antidepressant treatments. It worked quickly, was well tolerated, and is much safer and less expensive than conventional treatments with medication. Magnesium supplements are effective for mild-to-moderate depression and are an additional treatment option for patients suffering from depression.



Number of Pages

106 p.