According to the Journal of the American Medical Association, depression afflicts over 322 million people worldwide and is a leading cause of disability and reduced quality of life. The underlying causes are numerous and wide-ranging, but what if, in at least come cases, something as simple as magnesium supplementation could make a dent in this sometimes debilitating condition? Suboptimal magnesium status is a common finding in people with depression. Among younger adults, there may be a small association between low magnesium intake and depression. There’s also an association between higher magnesium intake and lower risk for depression. However, these associations were based on food intake questionnaires, which are not all that reliable—and even when they are reliable, they can only suggest associations and not prove causation. Actually measuring magnesium levels may be a better way to determine magnesium status, but measuring serum magnesium has its shortcomings. 50-60% of the body’s magnesium is stored in the bones and the remainder is in soft tissues, with less than 1% in the blood. Being that 99% of the body’s magnesium is not stored in the blood, the blood level is not always a good reflection of total body status. A healthy body maintains serum levels of minerals within a narrow range and it will remove these minerals from elsewhere in order to accomplish this. A normal blood magnesium does not rule out the possibility of a generalized insufficiency at the tissue level, which could be responsible for signs and symptoms: “The serum Mg can be normal in the presence of intracellular Mg depletion, and the occurrence of a low level usually indicates significant Mg deficiency.” That being said, overt hypomagnesemia was identified in 40% of subjects with depression in one study. Not everyone with depression has low magnesium but compromised magnesium status appears to be more prevalent among people with depression than in those without it. That brings up the question: can magnesium supplementation help ameliorate depression?
In a randomized controlled trial of subjects with magnesium deficiency, 500 mg of magnesium oxide daily for 8 weeks resulted in normal magnesium levels in 85% of subjects compared to 48% of subjects on placebo. The magnesium group and placebo group both experienced improvement in depressive symptoms but the improvement was greater among subjects in the magnesium group. In a different study that used magnesium chloride (which is better absorbed than magnesium oxide), compared to no supplementation, daily use of four 500 mg tablets of magnesium chloride (providing a total 248 mg elemental magnesium) resulted in clinically significant improvements in PHQ-9 scores. Improvement was noted within two weeks and 61% of participants reported that they would use magnesium in the future. The “clinically significant” improvement is noteworthy since a statistical significance doesn’t always translate to results that are relevant to actual humans living with depression.
Truly remarkable real-world relevance was documented in a case series of supplementation with magnesium as glycinate or taurinate resulting rapid and profound improvement (within 7 days) in major depression, post-partum depression, suicidal ideation, anxiety, irritability, insomnia and substance use disorders. Magnesium doses were relatively high—125-300 mg with each meal and at bedtime, for daily totals of 500 – 1200 mg per day. The authors wrote:
“The possibility that magnesium deficiency is the cause of most major depression and related mental health problems including IQ loss and addiction is enormously important to public health and is recommended for immediate further study.”
Magnesium is obviously not a magical fix for all cases of depression and related comorbidities, but it’s possible that in at least some studies evaluating magnesium for depression, the doses used weren’t high enough to elicit a response.
Considering that standard antidepressants fail to have a meaningful impact in as much as 60% of cases, for patients with treatment-resistant depression (TRD) it may be worth trying magnesium supplements, which are inexpensive and readily available. Low cerebral spinal fluid magnesium levels are often found in those with suicidal TRD. Researchers have written:
“We believe that, when taken together, there is more than sufficient evidence to implicate inadequate dietary Mg as contributing to the cause of MD [major depression], and we suggest that physicians prescribe Mg for its prevention and treatment.”
The tolerable upper intake level for magnesium supplementation established by the US Institute of Medicine’s Food and Nutrition Board is 350 mg/day but in some cases higher doses might be needed to achieve a therapeutic benefit. Some researchers propose using 600 – 800 mg/day (of a form other than Mg oxide) as a “universal prevention strategy.”
Even when supplementation is warranted, it may be useful to identify, if possible, the cause for suboptimal magnesium status. Low dietary intake is one potential contributor, but even when someone is consuming adequate magnesium from food, several commonly used medications may increase risk for deficiency, such as proton pump inhibitors, select diuretics, cisplatin, and more. Excessive alcohol intake or abuse may also result in magnesium depletion.