Vitamin Mineral Research

Magnesium Deficiency and the Brain

The importance of magnesium for memory, mood, migraines, and fibromyalgia

Magnesium is essential for the healthy functioning of every organ in the human body.[1],[2],[3],[4] Unfortunately, nationwide surveys have shown that two-thirds of all adults, and up to 90% of the elderly, are not achieving the recommended dietary allowance (RDA) for this mineral.[5],[6] Magnesium insufficiency is exacerbated not only by inadequate diets, exercise, and stress, but also by medications such as antibiotics, antacids, and anti-hypertensive drugs, which can interfere with magnesium absorption.[7],[8],[9]

In addition to its importance for metabolic health and musculoskeletal function, magnesium is particularly important for the brain. Among its many functions, magnesium forms active complexes with adenosine triphosphate (ATP), the primary energy source for brain neurons.[10] Remarkably, a single neuron in the gray matter of the brain utilizes approximately 4.7 billion ATP molecules per second, even at rest.[11] This relentless demand for ATP helps explain why magnesium is so critical for brain health.[12]

Low magnesium levels have been linked to conditions such as depression, anxiety, pain (fibromyalgia and migraine), premenstrual syndrome, and age-related memory loss, as discussed below.[1],[2],[9],[13],[14],[15],[16]

Magnesium for your brain

Magnesium may help support cognitive function in older adults, and the effect may be greater among subjects with sufficient vitamin D.

In addition to serving as a cofactor for ATP-dependent enzymes, magnesium is important for the regulation of the NMDA receptor,[17] a neurotransmitter receptor that is implicated in learning, memory, mood, and pain responses.[18],[19],[20],[21] Abnormal NMDA receptor activity has been shown in individuals with Alzheimer’s disease (AD), Parkinson’s disease, depression, and/or anxiety.[20],[22],[23],[24]

The hippocampus is part of the brain known as the limbic system, and it plays important roles in consolidating information from short-term memory to long-term memory, and in spatial memory that enables navigation. In animals, magnesium deficiency has been shown to impair hippocampus-dependent memory formation.[18] Conversely, magnesium supplementation has been shown to improve several of these functions, including learning and memory, in aged rats.[25] Moreover, in an animal model of AD, magnesium was shown to prevent neuron loss and to reverse the cognitive deficits associated with AD.[26]

In human studies, low magnesium levels have been found in the cerebrospinal fluid and brains of individuals with Alzheimer’s disease (AD).[2],[27],[28] Moreover, AD patients with lower serum magnesium levels were more likely to have more severe symptoms.[29] In a study of more than 1000 older individuals who were followed for 17 years, those with higher intakes of calcium, magnesium, and potassium had a lower risk of developing dementia.[30] Magnesium (and multimineral) supplementation may even be indicated for individuals with mild cognitive impairment,[31],[32] as a fraction of this population goes on to develop AD.

There is a synergistic relationship between magnesium and vitamin D.[33],[34] Vitamin D deficiency, which is extremely common in adults and especially in the elderly,[35] reduces the absorption of dietary magnesium.[36] Conversely, magnesium assists in the metabolism and activation of vitamin D.[37],[38] In a placebo-controlled study of women between 44–76 years of age, in which over 80% of the subjects were deficient in vitamin D, magnesium supplementation (500 mg/day for eight weeks) significantly increased vitamin D levels compared with the placebo group.[39]

Some diseases, including AD and mood disorders, are associated with deficiencies of both vitamin D and magnesium.[40],[41] In a study of 2466 participants over the age of 60 who completed a cognitive function test, those with greater magnesium intake and higher serum 25(OH)D levels scored higher on measures of cognition.[42] Taken together, these findings suggest that magnesium may help support cognitive function in older adults, and the effect may be greater among subjects with sufficient vitamin D. For these reasons, co-supplementation of magnesium and vitamin D is often recommended.

Magnesium for migraines

A meta-analysis of randomized, controlled trials concluded that oral magnesium supplementation alleviated the frequency and intensity of migraines by 80% and 73%, respectively.

Research has found significantly lower levels of magnesium in the serum, saliva, and cerebrospinal fluid of individuals with migraine headaches – both during and between migraine attacks.[43],[44],[45] In a matched case-control study of patients regularly having migraine headaches versus healthy individuals, those experiencing migraines had significantly lower serum magnesium levels than the controls, both during and between migraine attacks.[46] Those with low levels of magnesium were shown to be 35 times more likely to have acute migraine attacks.

A meta-analysis of randomized, controlled trials (RCTs) concluded that oral magnesium supplementation alleviated the frequency and intensity of migraines by 80% and 73%, respectively.[47] The average magnesium dose used in the studies was 420 mg per day. Importantly, another study showed that magnesium supplementation (500 mg daily) was effective in preventing migraines.[48] As mentioned above, magnesium is capable of blocking the NMDA receptor,[49] a receptor that contributes to pain transmission.[50] This may be one mechanism by which magnesium may reduce migraines, as well as fibromyalgia,[51] discussed below.

Magnesium for fibromyalgia

Lower serum and red blood cell magnesium levels correlated with more severe FM symptoms.

Fibromyalgia (FM) is a neurological condition characterized by intense widespread pain and tenderness coupled with severe fatigue, headache, and sleep problems. Women with FM were found to have lower dietary intakes of magnesium and calcium than a control group of healthy women.[52] The researchers also showed that lower dietary intakes of magnesium and calcium were correlated with an increased number of tender points and a decreased pain thresholds in women with FM.[52]  A separate study found that lower serum and red blood cell magnesium levels correlated with more severe FM symptoms, and that supplementation with magnesium citrate (300 mg daily) and amitriptyline (10 mg daily; a standard drug treatment) helped decreased pain scores in women with FM.[53]

Magnesium for mood

Lower dietary intakes of magnesium are associated with a greater risk of depression.

Numerous studies have shown that lower dietary intakes of magnesium are associated with a greater risk of depression.[54] Plasma levels of magnesium are often lower among individuals with depression as compared with healthy controls.[55],[56],[57] Unfortunately, the use of medications to treat depression may further contribute to low magnesium levels.[56]

Several mechanisms are thought to explain the link between magnesium levels and mood. First, magnesium is required to convert tryptophan to serotonin,[58] a neurotransmitter that is a major determinant of mental health and mood.[59] Second, magnesium was shown to normalize the stress-induced changes in NMDA receptors in animal models.[19] In addition to contributing to pain transmission, the NMDA receptor is a target for classical antidepressant drugs.[60],[61] Third, magnesium has been shown to increase levels of brain-derived neurotrophic factor (BDNF), a growth factor that supports brain plasticity, the brain’s ability to change and adapt as a result of experiences.[62] In humans, depression is often associated with low BDNF levels.[63]

To assess the effects of magnesium supplementation, an open-label, randomized, cross-over trial was done with 126 adults who had been diagnosed with mild-to-moderate symptoms of depression.[64] Supplementation with magnesium chloride (248 mg/day for 6 weeks) led to a clinically significant improvement in mood and anxiety scores. The supplement was well tolerated, and 61% of participants reported they would use magnesium in the future.

In a placebo-controlled trial, 60 patients diagnosed with depression who also had low serum magnesium levels were randomized to receive either magnesium (250 mg/day) or a placebo for eight weeks. Based on a 21-item scoring system known as the Beck Depression Inventory-II, the symptoms of depression were significantly improved in the magnesium group as compared to the placebo group.[65]

Taken together, the evidence suggests that individuals with depression often have low magnesium levels, and that magnesium supplementation may be helpful in such cases.

Magnesium and PMS

Last but not least, estrogen and progesterone affect magnesium levels, and magnesium levels influence premenstrual syndrome (PMS).[1] In a study of women with PMS, more than one-third were found to have low serum magnesium levels.[66] Supplementing with magnesium (200-250 mg daily) together with vitamin B6 (40-50 mg daily) was shown to reduce symptoms of PMS, including nervous tension, headaches, and mood swings.[67],[68],[69] Supplementation with vitamin D and calcium may also be helpful for PMS.[70]

In closing

Adequate magnesium levels are essential for good health, but many adults are not getting enough of this nutrient. Major dietary sources of magnesium include whole grains, nuts, and green leafy vegetables, but many scientists advise supplementing with magnesium to ensure adequate cellular stores. Organic forms of magnesium, such as magnesium citrate, are more bioavailable than magnesium oxide, and may thus be more effective.[71] The RDA for magnesium for adults is 310-420 mg per day, depending on age and gender.[72]

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