Current treatment options for depression are limited by efficacy, cost, availability, side effects, and acceptability to patients. Several studies have looked at the association between magnesium and depression, yet its role in symptom management is unclear. The objective of this trial was 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 with Patient Health Questionnaire-9 (PHQ-9) scores of 5–19. The intervention was 6 weeks of active treatment (248 mg of elemental magnesium per day) compared to 6 weeks of control (no treatment). Assessments of depression symptoms were completed at bi-weekly phone calls. The primary outcome was the net difference in the change in depression symptoms from baseline to the end of each treatment period. Secondary outcomes included changes in anxiety symptoms as well as adherence to the supplement regimen, appearance of adverse effects, and intention to use magnesium supplements in the future. Between June 2015 and May 2016, 112 participants provided analyzable data. Consumption of magnesium chloride for 6 weeks resulted in a clinically significant net improvement in PHQ-9 scores of -6.0 points (CI -7.9, -4.2; P<0.001) and net improvement in Generalized Anxiety Disorders-7 scores of -4.5 points (CI -6.6, -2.4; P<0.001). Average adherence was 83% by pill count. The supplements were well tolerated and 61% of participants reported they would use magnesium in the future. Similar effects were observed regardless of age, gender, baseline severity of depression, baseline magnesium level, or use of antidepressant treatments. Effects were observed within two weeks. Magnesium is effective for mild-to-moderate depression in adults. It works quickly and is well tolerated without the need for close monitoring for toxicity.

Background: Depression is a common and often disabling disorder. Magnesium supplementation has been linked to improvement in depressive symptoms, but consensus on the relationship between magnesium and depression has not been reached.Methods: The purpose of this study was to test the existence of an association between dietary magnesium intake and depression in the adult US population. A cross-sectional, population-based data set (National Health and Nutrition Examination Survey) was used to explore the relationship of magnesium intake and depression in 8894 US adults (mean age, 46.1 years; 47.4% men) from 2007 to 2010. Using logistic regression to model the relationship between the presence of depression (Patient Health Questionnaire score >5) and low magnesium intake (<184 mg/day), we examined the risk ratio (RR) of magnesium intake and its 95% confidence interval.Results: After adjusting for all potential confounders, the strength of the association of very low magnesium intake with depression was statistically significant (RR ‫؍‬ 1.16; 95% CI, 1.06 -1.30). Adjusting for all other covariates, low magnesium intake was associated with depression in subjects younger than age 65 (RR, 1.22; 95% CI, 1.06 -1.40; P ‫؍‬ .007) but seemed to be protective in seniors (RR, 0.75; 95% CI, 0.56 -0.98; P ‫؍‬ .032).Conclusions: We found a significant association between very low magnesium intake and depression, especially in younger adults. The finding of the potential protective effect of low magnesium intake in older adults is surprising and warrants further investigation. (J Am Board Fam Med 2015;28:249 -256.)

We recently reported that lowering the high, habitual palmitic acid (PA) intake in ovulating women improved insulin sensitivity and both inflammatory and oxidative stress. In vitro studies indicate that PA can activate both cell membrane toll-like receptor-4 and the intracellular Nucleotide Oligomerization Domain (Nod)-Like Receptor protein, NLRP3. To gain further insight into the relevance to human metabolic disease of dietary PA, we studied healthy, lean and obese adults, enrolled in a randomized, cross-over trial comparing 3-week, high PA (HPA) and low PA/high oleic acid (HOA) diets. After each diet, both hepatic and peripheral insulin sensitivity were measured, and we assessed cytokine concentrations in plasma and in supernatants derived from LPS-stimulated peripheral blood mononuclear cells (PBMCs) as well as pro-inflammatory gene expression in skeletal muscle. Insulin sensitivity was unaffected by diet. Plasma concentration of tumor necrosis factor-α was higher during the HPA diet. Lowering the habitually high PA intake by feeding the HOA diet resulted in lower secretion of interleukin (IL)-1β, IL-18, IL-10, and tumor necrosis factor-α by PBMCs, as well as lower relative mRNA expression of cJun and NLRP3 in muscle. Principal components analysis of 156 total variables coupled to analysis of covariance indicated that the mechanistic pathway for the differential dietary effects on PBMCs involved changes in the PA/OA ratio of tissue lipids. Our results indicate that lowering the dietary and tissue lipid PA/OA ratio resulted in lower leukocyte production of pro-inflammatory cytokines and muscle expression of redox-sensitive genes, but the relevance to diabetes risk is uncertain.

Background Previous literature suggests that a higher ratio of palmitic acid (PA)/oleic acid (OA) in the diet induces inflammation, which may result in deficient brain insulin signaling, and, secondarily, impaired physical activity, sleep efficiency, and cognitive functioning. Objective We hypothesized that lowering the typical dietary PA/OA would affect the activation of relevant brain networks during a working memory task and would also lower secretion of pro-inflammatory cytokines. Design In 12 female subjects participating in a randomized, cross-over trial comparing 3-week high PA diet (HPA) and low PA and a high OA diet (HOA), we evaluated functional magnetic resonance imaging (fMRI) using an N-back test of working memory, cytokine secretion by lipopolysaccharide(LPS)-stimulated peripheral blood mononuclear cells (PBMC), and plasma cytokine concentrations. Results Brain activation during the HPA diet compared to the HOA diet was increased in regions of the basal ganglia including the caudate and putamen (p<0.005). In addition, compared to the HOA diet, during the HPA diet, the plasma concentrations of IL-6 (p= 0.04) and IL-1β (p= 0.05) were higher, and there was a higher secretion of IL-18 (p=0.015) and a trend for higher IL-1β secretion (p=.066) from LPS-stimulated PBMCs. Conclusions The HPA diet resulted in increased brain activation in the basal ganglia compared to the HOA diet as well as increased secretion of pro-inflammatory cytokines. These data provide evidence that short-term (2 week) diet interventions impact brain network activation during a working memory task and that these effects are reversible since the order of the study diets was randomized. These data are consistent with the hypothesis that lowering the dietary PA content via substitution with OA also could affect cognition.

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