Using data from a well-characterized, representative sample of older men and women, we found a significant, independent, and strong relation between circulating magnesium and muscle performance, which was consistent across several muscle variables for both men and women. At least 3 mechanisms may explain these findings: 1) the role of magnesium in energetic metabolism, 2) the increased reactive oxygen species production in magnesium deficiency, and 3) the proinflammatory effect of magnesium depletion.
Previous studies conducted in young volunteers found that magnesium status strongly affects muscle performance, probably due to magnesium’s key role in energetic metabolism, trans-membrane transport, and muscle contraction and relaxation (28
). Magnesium depletion causes structural damage to muscle cells through increased oxidative stress and impaired intracellular calcium homeostasis (5
). In one study, magnesium supplementation (up to 8 mg/kg daily) enhanced muscle strength (+20% of peak knee-extension torque) in young untrained individuals (7
). Similarly, physically active young subjects experienced improved endurance performance and decreased oxygen use during sub-maximal exercise after magnesium supplementation (29
). Conversely, postmenopausal women fed 180 versus 320 mg Mg/d had higher heart rate and oxygen consumption during submaximal exercise, probably related to decreased erythrocyte and skeletal muscle magnesium concentrations (6
A large portion of the energy used for physiologic functions in humans is produced by mitochondria through the movement of electrons over the respiratory chain (30
). Magnesium is critical for basic mitochondrial functions, including ATP synthesis, electron transport chain complex subunits, and oxygen detoxification (1
). Inadequate availability of magnesium may lead to reduced mitochondrial efficiency and increased production of reactive oxygen species with consequent structural and functional impairment to proteins (31
), DNA (30
), and other essential molecules. Magnesium in the mitochondria accounts for one-third of total cellular magnesium and is present as a complex with ATP and as a component of membranes and nucleic acids (1
). Studies of magnesium-deficient cultured human cells and animals show evidence of decreased antioxidant capacity (32
), and one study showed mitochondrial swelling and altered ultrastructure in muscle taken from magnesium-deficient animals (5
). Hence, magnesium seems fundamental for the control of oxidative stress and to maintain the normal function of muscle mitochondria.
A state of chronic inflammation has been proposed as one of the main causes of frailty in older persons (34
). Poor magnesium status may trigger the development of a proinflammatory state both by causing excessive production and release of interleukin 1β
and tumor necrosis factor α
) and by elevating circulating concentrations of proinflammatory neuropeptides that trigger activation of low-grade chronic inflammation (36
). On the other hand, it is possible that oxidative mitochondrial decay linked to aging may itself favor hypomagnesemia. A recent study showed that a mutation in a mitochondrial gene results in low circulating magnesium, which became apparent as the affected subjects aged, possibly because magnesium reabsorption at the distal convoluted tubule requires a high amount of ATP (37
Poor muscle strength is a major cause of disability in the elderly (9
). If the findings of the present study are confirmed in other cross-sectional and longitudinal studies, the potential implications are two-fold. First, because measurement of serum magnesium is relatively inexpensive, it should be incorporated as part of a routine physical work-up. Second, the role of magnesium supplementation as a possible intervention for delaying or preventing disability in older adults deserves some consideration.
Defining magnesium deficiency is complex, in part because of the lack of available clinical tests for assessing total-body magnesium content. Currently, the serum magnesium concentration, which normally ranges between 1.8 and 3.0 mg/dL and is tightly maintained within this range (2
), is the most clinically available test for assessing magnesium status. For practical reasons, magnesium deficiency is defined as a serum concentration below the reference interval for the laboratory, which is not necessarily related to a pathophysiologic state of deficiency. Serum concentrations <1.8 mg/dL usually indicate some degree of magnesium depletion (2
), but low intracellular magnesium has been documented even in patients with serum concentrations >1.8 mg/dL (38
). Our results showing a continuous relation between serum magnesium and indexes of muscle performance, not simply driven by subjects with the lowest or highest magnesium concentration, lead us to propose that it is crucial not only to avoid deficiency according to the normal laboratory reference value, but also to obtain optimal magnesium concentrations to attain the best possible muscle performance.
Despite the physiologic importance of magnesium, the multiple problems associated with its deficiency, and the ease of supplementation, inadequate magnesium intake remains highly prevalent in various populations (15
). The typical Western diet high in processed foods and low in whole grains and green vegetables is often deficient in magnesium. Data from the National Health and Nutrition Examination Survey found that daily magnesium intake decreases with age, and older persons are well below the recommended minimal quantity (average of 225 and 166 mg/d compared with the recommended 420 and 320 mg/d for men and women, respectively) (16
). Among US adults, 68% consume less than the recommended daily allowance (RDA) of magnesium, 45% consume <75% of the RDA, and 19% consume <50% of the RDA (15
). The risk of inadequate magnesium intake is particularly high in those affected by chronic conditions and receiving chronic drug treatment (18
). Magnesium supplementation has been shown to be beneficial in several conditions, such as neuropsychiatric disorders, ischemic heart disease and cardiac arrhythmias, asthma, diabetes, and chronic fatigue (39
). Because magnesium supplementation is inexpensive and in general well tolerated, it should be a key consideration in older subjects at particular risk of magnesium deficiency.
Some caveats for the present study should be considered. This analysis used cross-sectional data; longitudinal data are needed to verify whether magnesium deficiency predicts accelerated decline of muscle performance with age. Because serum magnesium may not accurately reflect intracellular magnesium, it is possible that a greater proportion of older persons than those detected with use of circulating concentrations may have intracellular magnesium deficiency.
In conclusion, the results of the present study show an independent concurrent relation between serum magnesium and muscle performance in a large cohort of community-resident older persons. A possible mechanism of this association is the effect of magnesium concentrations on mitochondrial function in muscle, which may be particularly critical in aging muscle.
The limited attention given to suboptimal magnesium status in older populations at higher risk raises several questions that should be the focus of future studies. Some of these are as follows: What mechanisms underlie inadequate magnesium concentrations? What dietary magnesium intake is required in older persons to maintain adequate muscle performance? What is the role of inflammatory cytokines in mediating the adverse effect of magnesium deficiency on muscle? Is low magnesium a component of the frailty syndrome? Can magnesium supplementation influence muscle strength or performance and cytokine concentrations in older persons? The importance of elucidating the role of low magnesium status on the development of sarcopenia cannot be overlooked, because the aging population at risk of related disability continues to grow and contribute to extensive health care costs.