Introduction

Magnesium is an essential dietary mineral. It plays critical roles in myriad physiological processes, serving as a cofactor to more than 300 enzymes in the human body and maintaining the integrity of cellular structures and DNA. Magnesium deficiency is widespread, affecting more than half of people in the U.S. and increasing the risk of many chronic conditions, including cancer, metabolic disorders, and neurodegenerative diseases.

At a glance, magnesium participates in:

• Enzymatic reactions, serving as a cofactor for more than 300 enzymes involved in various physiological processes, including protein synthesis, muscle and nerve function, and blood glucose control.^[1]
• Brain health, preserving brain volume and cognitive function in aging.^[2]
• Stress and mood regulation, mediating the body's stress response and influencing synapse formation. ^[3]
• Chronic disease protection, supporting DNA repair^[4] and ameliorating oxidative stress.^[5]
• Cardiovascular health, enhancing vasodilation and assisting in blood pressure regulation.[ ^[6]
• Metabolic health, activating enzymes involved in glucose homeostasis and insulin sensitivity.^{[7] [8]}
• Athletic performance, supporting energy production, electrolyte balance, and increasing oxygen uptake and total work output.^[9]
• Bone homeostasis, serving as a magnesium reservoir and contributing to the structural development of bone.^[10]
• Vitamin D synthesis, serving as a cofactor for enzymes involved in vitamin D synthesis and degradation, maintaining healthy vitamin D levels.^[11]

This overview identifies magnesium's many roles in the human body, describes the consequences of magnesium deficiency, and highlights the importance of maintaining adequate levels of this nutrient through dietary or supplemental intake.

Magnesium in the diet: Recommendations and sources

Table 1. RDAs and AIs for Magnesium

*Adequate intake; Mg = milligrams

Recommended dietary allowance for magnesium

The recommended dietary allowance (RDA) for magnesium, intended to meet the needs of most people, varies according to one's age, sex, and lifestyle. Men need 400 to 420 milligrams daily, and women require 310 to 320 milligrams daily. Pregnant and lactating women have slightly higher requirements to support fetal and neonatal development. However, lifestyle factors influence magnesium needs considerably. In particular, athletes, regular sauna users, or people who engage in vigorous recreational or professional activities may have increased magnesium needs due to muscle demands and sweat losses. Nutrition experts have yet to establish RDAs for infants and recommend an adequate intake (AI) level instead. See Table 1 for the RDAs and AIs for magnesium.

Dietary sources of magnesium

Magnesium is ubiquitous in the human diet and is present in many plant-based foods. Many magnesium-rich foods provide other essential nutrients, which may work synergistically with magnesium to promote health. In general, fiber-rich foods are typically magnesium-rich, too. Food processing techniques often remove magnesium.^[12] Good dietary sources of magnesium include:

• Dark leafy greens, such as spinach, kale, and Swiss chard
• Legumes, such as beans, lentils, and chickpeas
• Nuts and seeds, such as pumpkin seeds, chia seeds, or almonds
• Whole grains, such as brown rice, oats, or whole wheat products

Multiple factors influence magnesium bioavailability

Several factors inhibit magnesium bioavailability, diminishing the mineral's absorption and utilization. For example, phytates (found in whole grains and legumes) and oxalates (found in spinach and chard) can form complexes with magnesium, reducing the mineral's bioavailability. Similarly, excessive dietary fiber intake can interfere with the absorption of many minerals, including magnesium, albeit to a lesser extent.^[13] High zinc or calcium intake from supplements can promote competitive inhibition, a phenomenon in which nutrients compete for absorption in the gut, potentially creating a relative deficit. Because magnesium plays a crucial role in vitamin D metabolism, high doses of vitamin D can deplete magnesium levels, making magnesium supplementation a vital component of vitamin D therapy.^[14]

See our vitamin D overview article for more information about the interdependence of vitamin D and magnesium.

Evidence suggests that proton-pump inhibitors (drugs that reduce stomach acid) impair magnesium absorption by inhibiting the action of magnesium transporters in the gut.^[15] Conversely, magnesium interferes with the uptake and action of many drugs, including those used to treat osteoporosis, heart failure, and others.^[16] People who take prescription drugs should discuss magnesium supplementation with their healthcare provider.

Dietary and lifestyle strategies can maximize magnesium bioavailability

Dietary and lifestyle strategies that mitigate the effects of factors that impair magnesium bioavailability include avoiding excessive dietary fiber intake, soaking grains and legumes before cooking to reduce phytate content,^[17] and diversifying magnesium sources in the diet to minimize oxalates. Maintaining a balanced and appropriate intake of other minerals and vitamins, particularly calcium, zinc, and vitamin D, can reduce the risk of competitive absorption or depletion issues.

Interestingly, peptides in calcium-rich dairy products may promote magnesium absorption,^[18] working synergistically to promote bone health. Taking multiple small magnesium doses throughout the day rather than a single large dose can increase absorption.^[19]

Magnesium deficiency and health implications

Despite magnesium's presence in many commonly consumed foods, roughly half of people in the United States do not consume enough of this essential nutrient, primarily due to low intake of foods richest in the mineral.^[20] Data from the National Health and Nutrition Examination Survey indicate that magnesium intake in the United States. is low, with most people consuming approximately 70 to 75 percent of the recommended amounts. These data take on greater significance when considering that the RDAs are intended to prevent serious illness rather than optimize healthy cell, tissue, and organ function.

Other factors influencing magnesium intake stem from agricultural practices (such as using phosphate-based fertilizers) that deprive the soil of magnesium, diminishing the mineral's availability for uptake into plants. Evidence suggests that the magnesium content of vegetables grown in the United States and the United Kingdom is 80 to 90 percent lower than a century ago. Furthermore, current federal nutrient databases have not been updated to reflect changes in the magnesium content of foods.^{[21] [22]}

Symptoms and consequences of magnesium deficiency and inadequate intake

Assessing magnesium levels and determining deficiency present challenges. The human body stores approximately 60 percent of its magnesium in the bones, which serve as the mineral's primary reservoir. In times of low intake, the body draws on these stores to maintain healthy plasma concentrations (0.7 to 1 mmol/L) to support normal physiological needs.^[23] In addition, the kidneys limit urinary excretion of magnesium.

Therefore, several factors may influence plasma magnesium levels, including dietary or supplemental intake, albumin levels, urinary excretion variability (which can fluctuate daily or hourly), and circadian rhythmicity.^[24] Consequently, plasma magnesium levels may not reflect true magnesium status. Some evidence suggests that red blood cells, which have slightly higher magnesium content than plasma, are more desirable for assessing magnesium status. However, this claim has been called into question due to the studies' poor designs and lack of validation.^[25]

Despite the body's readily available magnesium reservoir, true magnesium deficiency can occur, particularly in people with chronically low intake or those with impaired gut absorption, heavy alcohol intake, and users of certain medications, such as proton pump inhibitors and diuretics.^{[15] [26]} Early symptoms of magnesium deficiency, which are vague and often overlap with other medical conditions, include loss of appetite, nausea, vomiting, fatigue, and weakness. Later symptoms include numbness, tingling, muscle contractions and cramps, seizures, personality changes, abnormal heart rhythms, and dangerously low potassium or calcium levels due to altered mineral homeostasis.

A large population-based study found that people with plasma magnesium levels below 0.7 mmol/L were 32 percent more likely to die prematurely from all causes. This finding is particularly relevant because plasma magnesium levels indicate severe deficiencies rather than optimal levels. While normal plasma magnesium levels help identify severe deficiencies, they may not necessarily reveal the optimal magnesium level for overall health.^[27]

Magnesium supplementation trials and challenges

Randomized controlled trials in nutrition encounter specific challenges not found in drug trials, chiefly due to variability in participants' baseline nutrient levels. In drug trials, the absence of the drug at the start negates the need for pre-trial drug-level assessments. However, nutrition studies must take a different approach. For example, in a trial examining the effects of magnesium supplementation, only those participants who are deficient in magnesium at the outset may see benefits. Without initial measurements of magnesium levels, identifying who benefits from the supplementation may lead to incorrect conclusions. Failing to incorporate these considerations can lead to inconclusive and potentially misleading research findings.^[28]

Supplemental forms of magnesium

Magnesium is a naturally occurring mineral that readily forms complexes with other compounds. These complexes influence magnesium supplement bioavailability, therapeutic uses, and potential synergistic effects.

Supplemental forms of magnesium include:

• Magnesium aspartate: Highly bioavailable; may improve insulin sensitivity in people without type 2 diabetes.^[29]
• Magnesium chloride: Highly bioavailable; can be used topically or orally; may be beneficial in treating peripheral neuropathy associated with kidney disease.^[30]
  
• Magnesium citrate: Highly bioavailable; popular for its laxative effect; often used for constipation relief and to improve mood; may be beneficial in preventing or treating neurological disorders.^[31]
• Magnesium glycinate: Highly bioavailable and less likely to cause laxative effects; often recommended to improve sleep or reduce anxiety; may treat migraines in children.
  
• Magnesium hydroxide/oxide: Less bioavailable than other forms; may benefit constipation and heartburn.^[32]
  
• Magnesium lactate: May be gentler on the stomach; suitable for long-term use at moderate doses; may reduce mental stress; may be cardioprotective.^[33]
• Magnesium malate: May improve symptoms associated with fibromyalgia.^[34]
  
• Magnesium orotate: May work synergistically with vitamins K2 and D to manage type 2 diabetes and dyslipidemia. May modulate the gut-brain axis to promote mental health.^[35]
  
• Magnesium pidolate (picolinate): May be beneficial against osteoporosis.^[36]
  
• Magnesium sulfate: Commonly known as Epsom salts, used in baths for muscle relaxation and minor aches; low oral bioavailability. Little evidence suggests magnesium sulfate is absorbed via the skin.^[37]
  
• Magnesium taurate: May reduce blood pressure and protect the heart.^[38]
  
• Magnesium threonate: Noted for its ability to cross the blood-brain barrier, potentially improving cognitive function and reducing anxiety. See "Magnesium threonate" below.

Each form varies in its bioavailability and exerts different effects on the body. For example, in a rodent study comparing the absorption of magnesium oxide, chloride, sulfate, carbonate, acetate, pidolate, citrate, gluconate, lactate, and aspartate, bioavailability ranged from 50 to 67 percent. Organic forms (magnesium aspartate, citrate, glycinate, lactate, malate, orotate, pidolate/picolinate, taurate, and threonate) demonstrated slightly higher bioavailability than inorganic forms, but all were equally effective at restoring plasma and red blood cell magnesium levels.

High dietary magnesium intake poses no risk to human health because excess is excreted in urine. However, high-dose supplemental intake may cause nausea, intestinal cramping, diarrhea, and mineral imbalances. The tolerable upper limits (UL) for magnesium are presented in Table 2. Note: The ULs for magnesium are lower than the RDAs because the ULs are for supplemental magnesium intake, not dietary intake. No evidence suggests that exceeding the RDA for (dietary) magnesium is harmful; conversely, abundant evidence suggests that doing so may be beneficial.^{[39] [40]}

Table 2. Tolerable upper limits for supplemental magnesium intake

Mg = milligrams

Magnesium threonate

Magnesium threonate may influence brain function because it can cross the blood-brain barrier. However, evidence to support this claim is lacking.

Magnesium transport into the brain

Typically, only a small fraction of ingested magnesium reaches the brain due to intricate active transport systems that regulate the delivery of magnesium from the digestive tract into the bloodstream and then the cerebrospinal fluid.^{[41] [42] [43]}

The body establishes and manages a concentration gradient that creates higher magnesium levels in the blood than in the cerebrospinal fluid, ensuring a controlled quantity of magnesium transport into the brain. Consequently, even a 300 percent increase in blood magnesium causes less than a 19 percent change in cerebrospinal fluid magnesium content,^[42] highlighting the crucial role of physiological processes in maintaining magnesium balance and influencing brain health and function.^{[43] [31]}.

Some animal evidence suggests that magnesium threonate readily crosses the blood-brain barrier and, at human-equivalent doses of 8.1 milligrams per kilogram body weight (roughly 662 milligrams for a 180-pound person), can improve cognition and decrease amyloid plaques in the brain.^{[44] [45]}

Magnesium threonate's molecular structure facilitates transport into the brain.

Magnesium threonate is chelated to threonic acid, a metabolite of vitamin C. This molecular structure facilitates magnesium threonate's passage through the blood-brain barrier, increasing magnesium concentration in the brain more effectively than other forms.

Clinical trials investigating magnesium threonate's effects

Few studies have explored the effects of magnesium threonate in humans. Notably, these studies were industry-funded, raising concerns about potential conflicts of interest.

In one study, 44 participants took 1,500 to 2,000 milligrams of magnesium threonate or a placebo daily for 12 weeks and underwent cognitive testing before and after the intervention. The treatment group achieved a marginal increase in plasma magnesium levels, with no increase noted in red blood cell magnesium levels compared to those who took a placebo. However, a marked increase in the participants' urinary magnesium suggested that most of the supplemented magnesium was excreted. When each test was considered in isolation, participants exhibited no improvements in cognitive performance compared to the placebo group. Only when the results of the four tests were analyzed collectively did the data reflect notable improvement, suggesting a degree of statistical uncertainty in the study's conclusions.^[46]

In a separate study, 102 participants took a combination supplement providing 400 milligrams of magnesium threonate, vitamins C, D, and B6, and phosphatidylserine (a phospholipid found in brain cell membranes) or a placebo. They underwent cognitive testing before and after the intervention. The investigators did not evaluate serum or brain magnesium levels. Although the treatment group did exhibit better cognitive test performance than the placebo group, this study raises questions about causation and whether the observed benefits were attributable to magnesium threonate, the vitamins, phosphatidylserine, or a blend of these components.^[47]

Note: Magnesium threonate may not be optimal for meeting the RDA because it contains little elemental magnesium. Consequently, people considering supplemental magnesium threonate for its possible brain health benefits should not count it toward their RDA goal. To ensure adequate magnesium intake, especially if one's dietary intake does not meet or exceed the RDA, supplementing with an alternate form of organic magnesium with a higher elemental magnesium content, such as magnesium glycinate, is advised.

Magnesium in neurological health, sleep, stress management, and mood

A growing body of evidence identifies associations between dietary magnesium intake and brain function, influencing neurological health, sleep, stress management, and mood.

Cognitive function in aging

In an observational study of more than 6,000 people aged 40 to 73, high dietary magnesium intake (~550 milligrams daily) correlated with larger gray matter and hippocampal volumes than average intake (~350 milligrams daily), particularly in women. These increases in brain volume translated to roughly one year of reduced brain aging.^[2]

However, this was an observational study based on self-reported dietary intake. Factors such as overall dietary patterns, lifestyle habits, or other health conditions could influence brain volume. Nevertheless, lower magnesium has been linked to the development and progression of various age-related brain disorders.^{[48] [43] [31]} Conversely, higher cerebral magnesium levels may decrease oxidative stress and inflammation, improve synaptic plasticity, and counteract other mechanisms that drive neurodegeneration.^[48]

An analysis of 21 studies involving more than 1,100 people with Alzheimer's disease and 1,000 people who were healthy revealed that those with Alzheimer's exhibited markedly lower plasma and serum magnesium levels than those who were healthy. However, a subset analysis of 284 people with Alzheimer's versus 117 who were healthy revealed that magnesium levels in cerebrospinal fluid were also low relative to those in healthy people, but the difference was not statistically significant.^[49]

In a study that followed more than 1,000 middle-aged adults for 17 years, researchers found that those who consumed the most dietary magnesium daily (at least 196 milligrams) were 37 percent less likely to develop dementia in old age than those who consumed the least (174 milligrams or less daily).^[50] Another study in people aged 60 and older without dementia found that consuming higher dietary magnesium (at least 434 milligrams) reduced the risk of developing mild cognitive impairment, a stage before dementia, by 7 percent.^[51]

However, a study involving more than 2,500 mentally healthy older adults found that a higher daily dietary magnesium intake (at least 407 milligrams) was linked to better overall brain function, primarily among non-Hispanic white females with adequate vitamin D status, underscoring the interdependence of the two nutrients.^[52]

Notably, these studies are observational, meaning they can show associations but cannot prove that higher magnesium intake directly causes these health benefits. More research that includes controlled trials may establish a definitive link.

Mechanisms driving magnesium's brain effects

Magnesium's effects on the brain may be related to its role as a coenzyme for the myriad enzymes necessary for brain function. Some of these enzymes include:

• Adenosine triphosphatases (ATPases), a broad class of enzymes that hydrolyze ATP. Examples of ATPases include Na+/K+-ATPase and Ca2+-ATPase, which establish the electrochemical gradient across cellular membranes to facilitate effective neuronal function.^[53]
• Creatine kinase, an enzyme that participates in a bidirectional reaction involving creatine. In one direction, ATP phosphorylates creatine, yielding creatine phosphate and adenosine diphosphate. In the reverse direction, creatine phosphate donates its phosphate group to ADP, regenerating creatine and ATP, supporting the high energy demands of neuronal activity and signaling.^[54]
• Glutamine synthetase, an enzyme that maintains the brain's balance of glutamate and glutamine. Preserving this balance is crucial in protecting neurons from glutamate-induced excitotoxicity and subsequent neuronal damage.^[55]

Migraine

Migraine is a neurological disorder commonly manifested as severe headache pain accompanied by nausea, vomiting, and light sensitivity. Approximately 15 percent of people worldwide experience migraine, with women reporting migraine more often than men. Emerging evidence suggests that magnesium supplementation may prevent migraines.^{[56] [57] [56]} While these findings are based on a limited number of trials, their clinical significance is noteworthy due to the widespread prevalence of migraines.

A common feature of migraine is cortical spreading depression, a wave of brain activity that promotes the visual and sensory changes often associated with migraine auras.^[58] Evidence suggests magnesium supplementation prevents these waves.^[59] Additionally, magnesium may decrease the release of chemicals involved in pain signaling in the brain, such as substance P and glutamate, potentially lessening the pain associated with migraines. Furthermore, magnesium may prevent the narrowing of brain blood vessels caused by serotonin, a neurotransmitter implicated in migraine.

Evidence suggests the effective dose for preventing migraine is approximately 600 milligrams (as magnesium citrate) daily,^[57] roughly double the tolerable upper limit for supplemental magnesium. Dividing the dose into smaller amounts, such as 200 milligrams taken three times throughout the day, may reduce digestive upset while still providing an effective dose for migraine management.

Sleep

Interest in magnesium's effects on sleep is growing, and multiple mechanisms have been implicated in its role in sleep regulation.

For example, evidence suggests that magnesium is an antagonist to N-methyl-D-aspartate (NMDA) and an agonist to γ-aminobutyric acid (GABA). These compounds play critical roles in maintaining aspects of sleep architecture, particularly slow-wave sleep, which relies heavily on the glutamatergic and GABAergic systems.^{[60] [61] [62]} Additionally, magnesium serves as an endogenous inhibitor of the NMDA receptor, promoting the cellular influx of potassium ions and enhancing sleep quality.^[63] Magnesium also enhances the activity of serotonin N-acetyltransferase, an enzyme required for melatonin synthesis,^[64] potentially improving sleep.^{[60] [61] [65]} Interestingly, sleep deprivation markedly depletes magnesium levels,^[66] but whether these alterations create a vicious cycle of sleep impairments is unclear.

Evidence supporting the role of magnesium in sleep is mixed. An analysis of observational data from one cohort study and three cross-sectional studies involving more than 8,000 participants found that higher magnesium intake was associated with better sleep quality.^[67] However, observational studies may be subject to "healthy user bias," a form of bias in studies related to participants' behaviors or underlying characteristics. For example, participants with higher magnesium intake may engage in other healthy habits that contribute to better sleep. The same analysis found that five randomized controlled trials investigating the effects of supplemental magnesium on sleep showed mixed results, with magnesium improving some aspects of sleep quality but not others,^[67] highlighting the need for more nuanced research in this field.

Interestingly, sleep and stress are intricately linked, and teasing out the effects of magnesium on the two presents challenges. Findings from a study in which investigators assessed the effects of short-term (one day) and long-term (one month) sleep deprivation on magnesium levels in healthy men demonstrated that long-term sleep deprivation caused a robust reduction in magnesium in red blood cells and increased participants' risk for coronary arterial spasm and clot formation.^[66]

Stress, anxiety, and depression

Stress and anxiety

A complex interplay of nervous, hormonal, and immune mechanisms mediates the body's response to stress. Because magnesium is critical in the stress response, sustained or chronic stress may deplete magnesium stores. Interestingly, several symptoms of magnesium deficiency, such as fatigue, irritability, and mild anxiety, mirror those of stress.^[3]

Part of the body's stress response involves mobilizing magnesium to facilitate energy production and utilization in the form of ATP. The body rapidly extracts magnesium from its stores, temporarily increasing serum magnesium levels. As stress continues, the body excretes the extracted magnesium in urine, gradually depleting overall magnesium stores.^[68]

In addition, elevated levels of cortisol, the body's primary stress hormone, signal the kidneys to increase magnesium excretion, further reducing the body's total magnesium supply. Stress triggers the release of other hormones that disrupt magnesium homeostasis in the body, promoting decreased magnesium uptake in the gut and increased excretion via the kidneys, driving chronic magnesium depletion.^[69] Interestingly, correcting magnesium deficiency lowers cortisol levels, indicating a bidirectional relationship. When adults with obesity took 350 milligrams of magnesium citrate daily for 24 weeks, their serum cortisol levels dropped approximately 15 percent (after adjusting for sex differences).^[70]

In a study in which eight healthy adults received infusions of adrenaline (a stress hormone), the participants' plasma magnesium levels fell considerably during the infusion and remained low for one hour afterward.^[71] Other studies have demonstrated that stress exposure can influence magnesium levels in blood and urine. For example, young adults undergoing intermittent or persistent stress (such as experiencing political intolerance or involvement in a military conflict) experienced substantial decreases in their plasma magnesium concentrations. They also exhibited substantial increases in oxidative stress.^[72]

In a study of university students during exam time, investigators noted an increase in anxiety levels and a corresponding increase in urinary magnesium excretion.^[73] In a related study conducted over the subsequent four weeks post-exams, the students exhibited reduced red blood cell magnesium concentrations.^[74]

A study that examined the effects of noise exposure (a potent stressor) on catecholamine and magnesium levels in healthy men found that the timeframe for these alterations varied, with blood magnesium levels rising a few hours post-noise exposure and urinary excretion peaking after a few hours and continuing for up to two days.^[75]

Interestingly, acute (short-term) stress can induce a brief spike in blood magnesium levels, known as transient hypermagnesemia. Researchers have observed hypermagnesemia after short, intense exercise sessions lasting around 20 minutes, suggesting that the body attempts to rally magnesium resources to aid in energy production and other vital functions.^[76] However, following prolonged physical activity sessions (approximately one hour), hypermagnesemia does not occur, suggesting a time threshold exists beyond which the body does not respond in the same manner.^[76] It is noteworthy that after both short and extended physical activities, magnesium levels fall below baseline resting values, indicating that exercise depletes magnesium.^[76]

Depression and mood regulation

Magnesium mediates the flow of calcium ions in neuronal calcium channels, regulating neuronal nitric oxide production. It ultimately influences synapse formation, brain function, and mood. In the setting of magnesium deficiency, neurons may not meet their magnesium requirements, potentially driving neuronal damage that could manifest as depression.^[77]

An analysis of more than 3,600 adults' medical records found that lower serum magnesium levels were associated with depressive symptoms, suggesting that supplemental magnesium may help treat depression.^[78] A study investigated this possibility, providing 2,000 milligrams of supplemental magnesium daily in 112 adults with depression. Participants' depressive symptoms improved while receiving magnesium, an effect noted within just two weeks of treatment initiation, regardless of whether participants were taking antidepressant medications.^[79] In addition, case histories demonstrate that 125 to 300 milligrams of supplemental magnesium glycinate and taurinate elicited rapid recovery from major depression in less than one week.^[77]

Chronic disease prevention

Cancer

Magnesium's crucial role in DNA repair and its potential implications for cancer prevention are profound.^[4] DNA sustains daily damage due to internal exposures (such as those arising from metabolic processes) and external exposures (such as ultraviolet radiation and pollution).^[80] Magnesium facilitates the function of DNA repair enzymes, but because the body's natural capacity for DNA repair diminishes with age, low magnesium status can exacerbate the risk of DNA damage over time.^[81]

The high frequency of cell division in the human body, particularly in tissues with rapid turnover, such as the skin and gut epithelium, underscores the necessity of DNA replication for new cell formation.^{[82] [4]} Magnesium is vital for the proper function of DNA polymerases, the enzymes that facilitate cell division, and insufficient magnesium can impair these processes, potentially causing errors and mutations in the DNA.

Magnesium also participates in the activity of matrix metalloproteinases (MMPs), a broad class of enzymes involved in extracellular matrix breakdown, tissue remodeling, and wound healing.^[83] A magnesium deficiency can disrupt MMP activity, facilitating cancer cell invasion and progression. This crucial role for magnesium underscores its broad role in cellular health and cancer prevention, highlighting its importance in maintaining genetic integrity and preventing malignancies.^[84]

An observational study within the VITamins And Lifestyle (VITAL) cohort that tracked the health of more than 66,000 for eight years revealed that magnesium intakes of 75 to 99 percent of the RDA increased the risk for pancreatic cancer by 42 percent; intakes of less than 75 percent of the RDA increased the risk by 76 percent. Each 100 milligram per day decrement in magnesium intake correlated with a 24 percent rise in pancreatic cancer risk.^[85] Interestingly, magnesium supplementation (either through multivitamins or individual supplements) demonstrated an inverse association with pancreatic cancer risk. While these findings provide a correlation, they do not establish causation. However, age, gender, body mass index, and non-steroidal anti-inflammatory drug use did not modify this association, suggesting a consistent link across different populations.^[85]

Additional evidence from the Paris Prospective Study 2, which followed more than 4,000 men over 18 years, showed that higher magnesium levels were associated with a 40 percent decrease in the risk of premature death from all causes and a 50 percent decrease in deaths from cancer.^[86]

A meta-analysis examining the effects of dietary and supplemental magnesium intake on cancer risk found that dietary magnesium intake was associated with reduced risks of all causes of premature and cancer-related deaths. For every additional 100 milligrams per day of dietary magnesium, the risk of death from all causes decreased by 6 percent and from cancer by 5 percent. These benefits were specifically linked to magnesium from dietary sources rather than supplements. Interestingly, supplemental magnesium intake demonstrated a slight positive association with cancer-related death risk. These inconsistencies highlight the need for cautious interpretation of such data due to heterogeneity between studies.^[40]

Hypertension

Hypertension (high blood pressure) is a major public health concern, affecting nearly half of all U.S. adults, including roughly 20 percent of young adults aged 18 to 39.^{[87] [88]} Awareness of blood pressure levels is crucial from a young age, as elevated blood pressure increases the risk for cardiovascular diseases.^[89] High blood pressure is also one of the principal risk factors for dementia due to its damaging effects on the brain's small vessels, impairing cognitive function in later years. Early monitoring and management of blood pressure are imperative for reducing these risks.^{[90] [91] [92]}

Magnesium contributes to blood pressure regulation by enhancing the production of vasodilators such as prostacyclin and nitric oxide, which relax blood vessels and improve cardiac function. Magnesium's vasodilatory effect facilitates blood flow, thus lowering blood pressure and easing cardiac workload. Additionally, its anti-inflammatory properties and ability to prevent vascular damage bolster heart health, illustrating magnesium’s essential role in cardiovascular wellness.^[6]

A comprehensive meta-analysis involving 34 trials and more than 2,000 participants found that magnesium supplementation, at an average dose of 368 milligrams daily, reduced systolic and diastolic blood pressures. This effect was time- and dose-dependent, pointing to a causal relationship between magnesium supplementation and blood pressure reduction.^[93] Further laboratory studies corroborate these findings, demonstrating magnesium's capacity to modulate vascular smooth muscle function, decrease vascular resistance, and prevent vasoconstriction – key elements in combating hypertension.^[5]

Oxidative stress

Oxidative stress arises when excess reactive oxygen species overwhelm the body's capacity to mount an effective antioxidant response. It damages cellular components, such as lipids, proteins, mitochondria, and DNA, and is implicated in the pathogenesis of many chronic conditions, including cardiovascular disease, neurodegenerative disorders, type 2 diabetes, obesity, kidney dysfunction, and others. Evidence suggests that magnesium’s antioxidant properties protect against oxidative stress.^[5]

In stroke-prone hypertensive rats, magnesium deficiency increased the number of neutrophils (immune cells that produce reactive oxygen species), raised systolic blood pressure, impaired endothelial function, and heightened oxidative stress markers, including interleukin-6. However, increasing magnesium levels in an ex-vivo setting reduced neutrophil activity, suggesting that higher magnesium mitigates the anti-inflammatory effects of deficiency.^[94] In rat heart tissue, magnesium deficiency exacerbates myocytes' response to oxidative stress, impairing heart muscle contraction and promoting tissue damage in ischemia-reperfusion injury.^[95] In a rat model of type 2 diabetes, magnesium deficiency increased levels of plasma malondialdehyde, a marker of oxidative stress, and decreased expression of superoxide dismutase and glutathione S-transferase – key antioxidant enzymes. However, magnesium supplementation restored antioxidant enzyme activity.

Glutathione S-transferase facilitates the activity of glutathione, a potent antioxidant compound produced in the body's tissues, particularly those vulnerable to oxidative stress, such as the eyes, liver, and brain. Glutathione scavenges harmful reactive oxygen species, thereby preventing damage from oxidative stress. Magnesium is a cofactor for enzymes involved in glutathione synthesis, and magnesium deficiency is associated with profound reductions in glutathione levels.^{[96] [97] [98]}

Metabolic health

Magnesium influences metabolic processes via its pivotal role in forming magnesium-ATP complexes. These complexes activate enzymes involved in phosphorylation and dephosphorylation reactions, including those that drive glycolysis and insulin receptor activation.^{[7] [8]} In this way, magnesium regulates both glucose homeostasis and insulin sensitivity, underscoring magnesium's integral role in glucose metabolism and overall metabolic health.^[99]

Evidence suggests that magnesium influences the risk of developing diabetes and participates in the disease's pathophysiological progression. Disorders that reduce cellular ATP content (such as diabetes) increase cellular magnesium losses, and people with type 1 or type 2 diabetes often present with low magnesium levels.^[100] However, treatment with pioglitazone (an anti-diabetes drug) restores magnesium levels, pointing to the bidirectional relationship between magnesium and diabetes.^[101]

Athletic performance

Magnesium may enhance athletic performance via its roles in energy production, muscle function, electrolyte balance, and blood glucose homeostasis. (See "Magnesium and metabolic health" above.)

Energy production

Magnesium influences anaerobic and aerobic energy production through its role in ATP metabolism. However, low magnesium may facilitate partial uncoupling of the mitochondrial respiratory chain, increasing the oxygen required for ATP production.^[96] In addition, low magnesium may increase energy costs and oxygen consumption during exercise by impairing muscle relaxation, especially in high-demand activities like cycling.^[102]

Evidence suggests that magnesium supplementation bolsters energy production, enhancing athletic performance. For example, male athletes who took 390 milligrams of magnesium daily for 25 days experienced improved peak oxygen uptake and total work output.^[9] Similarly, adolescents who took 8 milligrams of magnesium per kilogram of body weight daily saw increases in endurance and reduced oxygen consumption during submaximal exercise.^[103]

Muscle function

Magnesium is vital for muscle function and strength. A study involving more than 1,400 adults found that higher blood magnesium levels correlated with better muscle function, including grip strength and leg muscle power.^[104] Another study revealed that magnesium supplementation (8 milligrams per kilogram body weight) combined with strength training three times a week boosted strength. The investigators posited that these gains were related to enhanced muscle protein synthesis.^[105] Interestingly, physically active people with normal magnesium levels do not appear to experience functional or performance benefits from supplementation.^[106]

Electrolyte balance and muscle cramps

Magnesium regulates the body's electrolyte balance, which is essential for nerve transmission, muscle contraction, and heart rhythm stability. Deficiencies in magnesium, particularly in athletes with high electrolyte turnover due to increased sweat losses, can disrupt this balance, leading to dehydration and potential complications, including muscle cramps.

Evidence suggests magnesium prevents and treats muscle cramps.^[107] Swimmers who took supplemental magnesium reported an 86 percent reduction in muscle cramps after three days.^[104] However, although some research has identified benefits, particularly in pregnant women, the findings are inconsistent and often influenced by study participants' initial magnesium status.^{[108] [109]}

The effectiveness of Epsom salt (magnesium sulfate) baths for muscle cramps is questionable.^[37] While some evidence indicates that some magnesium absorption occurs via the skin, the extent and clinical relevance of such absorption are still under investigation. Despite anecdotal claims about Epsom salts' benefits for muscle cramps and skin health, robust scientific proof is limited.

Bone health

Magnesium is crucial for mineral and bone homeostasis, bone cell function, and the growth and formation of hydroxyapatite crystals – a key contributor to bone hardness. Roughly 60 percent of the body's magnesium is stored in the bones, acting as a dynamic reservoir for this essential mineral. However, bone magnesium losses occur with aging as the body strives to maintain its narrow, stable range of plasma magnesium levels.^[110] When dietary magnesium intake is insufficient, the body compensates by pulling magnesium from the bones. Chronic low intake can decrease bone magnesium content, particularly in older adults, whose magnesium stores may be as low as 10 percent.^{[111] [112]} Some evidence suggests magnesium loss contributes to osteoporosis.^[113]

Adequate magnesium intake in early life influences long-term bone health and mediates the risk for osteoporosis. For example, a study in young adult women found that magnesium-rich diets during pre-adolescence markedly improved heel bone density.^[10] In addition, a study found that prepubertal girls who received 300 milligrams of elemental magnesium daily for one year exhibited greater hip bone mass than those who took a placebo. These findings highlight magnesium's crucial role in strengthening bones and preventing osteoporosis.

Vitamin D production

Vitamin D is a steroid hormone produced in the body. Its synthesis occurs via a multistep process that relies on the activity of six enzymes. Each of these enzymes is magnesium-dependent, and evidence suggests that magnesium deficiency impairs vitamin D metabolism.^{[11] [114] [115]}

Population-based data indicate that high magnesium intake, whether from the diet, supplements, or both, is linked to higher vitamin D levels. Statistical analysis revealed an interaction between magnesium and vitamin D intakes, influencing the risk of vitamin D deficiency and insufficiency. For example, adequate magnesium intake can enhance the body's ability to maintain healthy levels of vitamin D. Conversely, low magnesium intake may hinder the body's ability to utilize vitamin D effectively, even if vitamin D intake is sufficient. The study found that the benefits of having higher vitamin D levels in reducing the risk of early death, especially from cardiovascular disease and colorectal cancer, were greater in people with above-average magnesium intake.^[116]

Findings from a randomized controlled trial in which participants received customized doses of magnesium or placebo demonstrated how supplementation influences vitamin D status. Participants with vitamin D deficiency who received magnesium exhibited increased levels of 25-hydroxyvitamin D [25(OH)D], an intermediate form of vitamin D. However, participants with sufficient vitamin D who received magnesium exhibited increased levels of 1α,25-dihydroxyvitamin D [1,25(OH)2D], the final, active form of the steroid hormone. These findings suggest that magnesium's influence on vitamin D status varies based on existing vitamin D levels, playing a critical role in either helping to stabilize vitamin D in the body or activating it, depending on individual needs.^[11]

Aging

Aging refers to the collective physiological, functional, and mental changes that accrue in a biological organism over time. It is the primary risk factor for many chronic diseases in humans, including cancer, Alzheimer's disease, and cardiovascular disease. Nutritional status profoundly influences the rate at which a person ages.

As an essential nutrient, magnesium plays a vital role in both immediate survival mechanisms and long-term health maintenance. Evidence suggests that in conditions where magnesium is scarce, the body prioritizes its allocation to critical short-term survival functions, such as energy production. This prioritization – a theoretical phenomenon known as triaging – often occurs at the expense of long-term health processes, such as DNA repair. Consequently, while the body may maintain enough magnesium to avoid acute deficiencies, it may divert magnesium from less immediate critical functions, such as bone maintenance, thereby increasing the risk of long-term conditions like osteoporosis.^[117]

Sufficient magnesium intake is crucial for preventing the gradual accumulation of cellular damage that can drive adverse health effects over time. Adequate magnesium levels ensure the proper function of DNA repair and replication processes, preventing mutations that could lead to cancer-causing transformations and cellular dysfunction. This proper functioning is essential for mitigating the aging process and reducing the risk of chronic diseases such as cancer. Therefore, maintaining adequate magnesium levels through diet or supplementation can play a critical role in promoting longevity and healthy aging by supporting essential cellular processes and preventing chronic health issues.

Learn more about triage theory in this clip featuring Dr. Bruce Ames.

Conclusion

Magnesium is an essential mineral. It participates in myriad physiological processes, serving as a cofactor for more than 300 enzymes in the human body, including those involved in DNA repair, bone homeostasis, and vitamin D synthesis. Poor magnesium status is likely widespread, especially among people who don't eat magnesium-rich foods, athletes, and those who incur extensive sweat losses, such as sauna users. Magnesium readily forms complexes with other compounds, influencing its bioavailability, therapeutic uses, and potential synergistic effects. Evidence suggests magnesium preserves cognitive function in aging, improves mood, decreases anxiety, prevents migraines, and reduces the risk of many chronic diseases, including cancer, hypertension, type 2 diabetes, and osteoporosis. Magnesium may enhance athletic performance via its roles in energy production, muscle function, electrolyte balance, and blood glucose homeostasis. Maintaining adequate magnesium status is crucial for health and longevity.