Magnesium is an essential mineral involved in brain, heart, and skeletal muscle function. It is estimated that over 50% of the population is magnesium-deficient. Only 30% of ingested magnesium from the diet is absorbed by the intestines. Magnesium supplementation is necessary for many; however, not all supplements are created equal. The form of magnesium and its bioavailability are important for repletion.
For supplemental magnesium to be absorbed in the intestines and delivered into the body and brain, it must be chelated or bound to a substrate. Magnesium supplements come in a variety of forms, such as inorganic salts (oxide, sulfate, etc.), and organic salts (citrate, glycinate, malate, glycerophosphate, etc.). Studies on bioavailability show that organic salts are more bioavailable than inorganic salts.
For example, the glycerophosphate form is bound to a glycerol molecule and a phosphate group. These molecules are naturally present in the body (as phospholipids), which ensures optimal assimilation and transport into the cells. Cell membrane phospholipids are especially abundant in the nervous system. Therefore, this form of magnesium may be helpful for brain health.
The Studies
Two recent reviews assessed the therapeutic applications of magnesium in cognitive health. A systematic review and meta-analysis concluded with moderate confidence that serum magnesium has a U-shaped association with dementia and cognitive impairment. Another review stated that maintaining adequate magnesium levels is preventive of dementia and Alzheimer’s disease, especially in older adults and individuals with metabolic risk factors. The studies analyzed in these reviews were heterogeneous regarding supplementation, and conclusions could not be drawn about the best supplement. This may be due to differences in forms and doses used, which affect bioavailability.
COVID-19 is associated with neuropsychiatric symptoms. 111 older adults with confirmed infection in the 6 months prior were enrolled in a prospective cohort study. Several factors were evaluated, including cognitive function via Mini-Mental Status Exam, depression (PHQ-9), anxiety (Geriatric Anxiety Inventory), functional status, and labs. Among the participants, 18.8% developed cognitive impairment within 6 months, and low serum magnesium and depression were independently associated with a higher risk. Study authors noted that, in addition to magnesium, other trace elements such as phosphorus may play a role in the metabolic imbalances observed in COVID-19 patients.
A systematic review on the bioavailability of magnesium supplements concluded that all magnesium supplements can maintain physiological levels in healthy participants. It is unknown whether specific forms help in older patients, patients with illnesses, or those with low levels. The authors do mention that the tissue distribution of magnesium differs depending on the salts used. For example, magnesium taurate increases brain magnesium in animals more than other forms.
Another in vitro and human randomized study comparing the bioavailability of 15 commercial magnesium formulations showed the best bioavailability for glycerophosphate, citrate, and glycinate forms.
More studies are needed to compare all forms of magnesium. There is no standardized protocol for studying the bioavailability of minerals, which is likely why studies conflict.
Conclusions
These studies highlight the importance of magnesium for cognitive health. However, reviews are inconclusive on the optimal form and dose. Magnesium glycerophosphate has higher bioavailability compared to other forms and, because of its structure, may support brain health. Clinical trials studying magnesium glycerophosphate are needed to confirm potential neurocognitive benefits.
