MAGNESIUM
Magnesium is an essential mineral that plays a vital role in numerous functions throughout the body, including the regulation of nerve and muscle function, blood pressure, and blood sugar levels. Despite its importance, studies show that many people do not consume adequate amounts of magnesium through their diet alone. This is where magnesium supplementation comes in.
Magnesium supplementation has gained popularity in recent years as a way to potentially improve various aspects of health, including ADHD, sleep, depression, stress, blood pressure, diabetes, performance, cramping, and hormone balance. While not a cure-all, research has shown promising results in many of these areas, and there is growing interest in the potential benefits of magnesium.
In this article, we will explore the potential benefits of magnesium supplementation in depth. We will examine the latest research on magnesium and its impact on ADHD, sleep, depression, stress, blood pressure, diabetes, performance, cramping, and hormone balance. We will also discuss safe levels of magnesium supplementation, potential side effects, and recommendations for incorporating magnesium into a healthy lifestyle. By the end of this article, you will have a better understanding of the potential benefits of magnesium supplementation and how it may contribute to your overall health and well-being.
Table of Contents
- Sources
- Recommendations & Dietary Availability
- Biological Significance
- Deficiency
- Measurement
- Bioavailability & Intestinal Absorption
- Neurology & The Brain
- The Blood Brain Barrier
- ADHD
- Sleep
- Depression
- Stress
- Learning
- Migraines
- Cardiac Function
- Blood Pressure
- Triglycerides
- Glucose Metabolism
- Type I Diabetes
- Fat Absorption
- Muscle & Exercise
- Performance
- Cramping
- Interaction with Testosterone
- Interaction with Thyroid Hormones
- Magnesium & Cancer
- Teeth
- Forms of Magnesium Supplementation
- Summary
Sources
Magnesium can be found in a variety of foods that are commonly consumed in a healthy diet. Some of the best dietary sources of magnesium include leafy green vegetables, nuts, legumes and beans, and animal tissue.
There are some dietary supplements available that may contain magnesium in the form of herbs or food products. Examples of such supplements include:
- Basella Alba (Indian Spinach) at 114+/-1mg/100g
- King Oyster (Mushroom) at 740+/-230mcg/g
- Seeds of Mucuna Pruriens
- Seeds of Irvingia Gabonensis (African Mango) at 429+/-0.3ppm dry weight
- Royal Jelly at 217.493mg/kg
- Schisandra Chinensis at trace levels
Recommendations & Dietary Availability
In 1999, the Recommended Dietary Allowance (RDA) for magnesium was established in the US to be within the range of 310-420mg. This amount is considered to meet the needs of 97-98% of the population.
The RDA for magnesium intake varies based on age and gender. For individuals aged 14-18, the RDA for magnesium is between 360-410mg per day, with higher values for males. In the 18-30 age bracket, the RDA is attenuated to 310-400mg daily. For those 31 years or older, the RDA is slightly increased to 320-420mg per day. During pregnancy, females require an additional 30-40mg of magnesium daily, with no alterations during lactation.
Based on this RDA, approximately 68% of adults do not meet the RDA for magnesium, and 19% of adults consume less than half of the recommended amount.
These results are slightly more promising than the United States NHANES 2005-2006 survey, 60% of adults in the US consumed less than the Estimated Average Requirement (EAR) for magnesium, which is set at 255-265mg depending on age group.
Main Takeaway: Magnesium deficiency, at least to a minor degree, appears to affect a large percentage of adults.
Biological Significance
Magnesium is a crucial mineral in the body, serving primarily as an electrolyte and mineral cofactor for enzymes. In its role as an electrolyte, magnesium helps to maintain fluid balance, while its role as a cofactor is critical to the function of over 300 enzyme systems in the body. These enzyme systems include ATP, Adenyl Cyclase, and the enzymes involved in glycolysis. Additionally, magnesium is required for the activation of creatine kinase, which plays an important role in energy metabolism.
The human body typically stores between 21-28g of magnesium, with about half of this amount deposited in bone tissue. The majority of the remaining magnesium is found inside of cells. Non-bone and extracellular magnesium stores account for only 0.3% of overall body magnesium stores, and are made up of 55% free form magnesium, 33% bound to proteins such as enzymes, and 12% in anion complexes.
Typical serum levels of magnesium range from 1.7-2.5mg/dL.
Deficiency
Obesity has been linked to magnesium deficiency, which can be addressed through Vitamin D injections. However, it is important to note that the deficiency may be a symptom of abnormalities in Vitamin D metabolism, rather than a standalone issue.
Individuals with Type II diabetes have a higher risk of magnesium deficiency compared to the general population, with an estimated 25-38% of diabetic individuals experiencing deficiency.
Measurement
While magnesium levels can be measured in serum obtained from blood samples, this method of measurement may not accurately reflect the body’s magnesium ion stores.
More reliable methods for measuring magnesium levels include analyzing magnesium content in red blood cells and white blood cells, with the latter being particularly useful for assessing intramuscular magnesium stores. In some cases, direct measurement of magnesium levels in muscle tissue through biopsy may also be performed. [1]
Bioavailability & Intestinal Absorption
When consumed orally, magnesium is absorbed in the intestines through both paracellular (between intestinal cells) and transcellular (via intestinal cells) absorption. However, up to 90% of magnesium absorption occurs through the paracellular route.
The permeability of the paracellular route, which is responsible for the majority of magnesium absorption, is influenced by the tight junction proteins that regulate the width of gaps between intestinal cells. Dysfunction of these proteins can lead to a condition known as “leaky gut”.
The body regulates magnesium absorption in response to levels of magnesium in the serum and body stores. Magnesium absorption increases during periods of deficiency and decreases during periods of sufficiency. The concentration gradient between the lumen (1-5 mM) and blood (0.5-0.7 mM) suggests that regulation of magnesium absorption in the paracellular route may also occur. The mechanism of regulation at the level of tight junctions is currently unexplored, but it is thought to play a role in magnesium absorption.
When it comes to transcellular absorption, which accounts for the remaining 10% of magnesium absorption, two transporters from the transient receptor potential melastatin family, TRPM6 and TRPM7, are primarily responsible. [1, 2]
TRPM6 and TRPM7 are also known as chanzymes due to the presence of a Thr/Ser kinase, which classifies them as eukaryotic α-kinases.
TRPM7 is known to be negatively regulated by the Magnesium ion. which supports the decreased bioavailability from the lumen to the blood during Magnesium sufficiency; interestingly, TRPM7 exists in most cells in the body whereas TRPM6 is mostly limited to the intestines but expressed in the kidneys, lung, and testes. [1]
A genetic flaw in TRPM6 has been found to cause a rare condition called hypomagnesemia with secondary hypocalcemia, highlighting the critical role of TRPM6 in dietary magnesium intake.
Furthermore, in cases of dietary Magnesium deficiency, the mRNA levels of TRPM6 tend to increase, suggesting a potential feedback mechanism to enhance absorption of Magnesium. Vitamin D does not appear to influence TRPM6, at least in the kidneys.
TRPM6 and TRPM7 are also known to respond to other divalent cations such as Calcium, Zinc, Manganese, and Cobalt. Nickel is a substrate of both transporters but has been shown to preferentially use TRPM6. [1, 2]
Main Takeaway: The absorption of Magnesium in the intestines occurs through two mechanisms: paracellular (between intestinal cells, also known as enterocytes) and transcellular (via enterocytes). Both of these mechanisms are regulated by the body’s Magnesium levels. When Magnesium levels are sufficient, absorption is reduced, and when there is a deficiency, absorption increases.
When consumed through the diet (assuming varied), total magnesium bioavailability appears to be in the 20-30% range. [1, 2] Some bioactives also present in the diet, such as dietary inulin (a fiber), may enhance absorption rates while dietary phytic acid may reduce magnesium absorption by 60% due to binding to Magnesium and oxalate may reduce magnesium absorption as well, but to a lower extent than phytic acid. Leafy vegetables appear to have slightly higher Magnesium absorption rates in the 40-60% range and is slightly more bioavailable than Magnesium Sulfate, with the higher range being those lower in oxalate content.
Main Takeaway: The absorption of Magnesium from the diet is affected by the presence of various factors, such as phytates and oxalates. Phytates, which are found in whole grains and legumes, can impair Magnesium absorption, whereas oxalates, which are found in some vegetables, have less of an impact on Magnesium absorption. When considering the percentage of Magnesium absorbed, leafy green vegetables are a better source than grains. A mixed diet typically has a 20-30% bioavailability of Magnesium, but this can be increased if the diet is rich in vegetables rather than grains.
A study found that after consuming 500mg of elemental Magnesium daily for one month, 43% of participants who had low blood magnesium at the beginning of the study no longer had hypomagnesia. However, after stopping the supplement for four weeks, the same number of participants became deficient in magnesium again, indicating that full elimination of the supplement occurs within a month of cessation.
Neurology & The Brain
Magnesium ions in the brain act as an inhibitory ion to counteract calcium at NMDA receptors (excitatory receptors involved in long-term learning and excitation), which is the main neuronal mechanism of Magnesium ions. [1]
Magnesium is an endogenous calcium channel blocker and plays a regulatory role in calcium metabolism. [1]
Low Magnesium levels are associated with neuronal hyperexcitation and random firing, and secondary to higher activation of NMDA receptors more calcium appears to be released.
At resting membrane potential, magnesium ions bind to NMDA receptors, which prevents the influx of calcium ions into the neurons, and as a result, prevents neuronal firing, [1] while activation of neurons intentionally displaces magnesium. At typical concentrations, Magnesium serves as a placeholder in ion channels and does not necessarily have inhibitory effects. However, when Magnesium is present in high concentrations, it can exert antagonistic effects. [1]
Memantine and Ketamine are drugs that do not undergo displacement during neuronal activation and act as NMDA blockers, effectively inhibiting the activation of neurons.
Acute regulation of Magnesium is highly regulated both by sets of ionic pumps on neurons and the choroid plexus, which acts in concert with the blood brain barrier to establish a constant concentration of Magnesium. [1, 2] Decreases in cerebral Magnesium stores are only seen over prolonged periods of inadequate Magnesium ingestion.
Main Takeaway: Adequate levels of magnesium in the brain are crucial for maintaining normal neuronal function during periods of neuronal inactivity. When there is a deficiency of magnesium in the brain, which usually happens due to chronic dietary deprivation, neurons can become excessively activated during periods of inactivity.
Excitotoxicity occurs when excessive activation of neurons leads to toxic effects, mediated by calcium-dependent enzymes triggered by excessive calcium influx. [1]
Magnesium can block this influx and may have a greater effect when levels are not deficient.
There is some evidence that preservation of Magnesium after neural injury (where Magnesium can decline) can preserve neuronal function by attenuating toxicity indirectly by excessive NDMA firing; although this study used injections and may not be applicable to supplementatal Magnesium.
Main Takeaway: Long-term overstimulation of NMDA receptors or acute excessive activation can lead to neurotoxic effects that are mediated by calcium-dependent mechanisms. Magnesium can mitigate this toxicity primarily during periods of neuronal inactivity. However, it is worth noting that these neurotoxic effects are not applicable to calcium supplements as calcium is tightly regulated in the body like magnesium.
Optimal and high levels of Magnesium in the brain (achieved through oral administration of Magnesium L-Threonate in rats) may enhance excitatory function during periods of activation, as there is an upregulation of excitatory receptors during periods of rest.
The Blood Brain Barrier
Magnesium concentration in the brain is higher than that of serum, with a homeostatic balance achieved at the blood-brain barrier maintained by active transport. Studies have suggested that there is a limit to the amount of magnesium that can be loaded into the brain, with absorption rates ranging from 11-18%. [1]
Low-dose supplementation with Magnesium L-Threonate (50mg magnesium, 604mg total) has been shown to mimic this effect.
ADHD
A deficiency of Magnesium has been observed to be more prevalent in children who have been diagnosed with ADHD, according to research. In one study that involved 116 children, it was found that 95% of the children with ADHD had a Magnesium deficiency. Another study found that children with ADHD had a lower Magnesium content in their saliva compared to control children. The control group had a Magnesium concentration of 0.70+/-0.2mmol/L while the ADHD group had a concentration of 0.23+/-0.06mmol/L. In a study that divided children into subgroups of ADD and ADHD, Magnesium deficiency was found only in the hyperactive subgroup and not in the inattentive group or control.
After identifying 50 children aged 7-12 years with ADHD and dietary magnesium deficiency, an intervention study was conducted where the children were given 200mg of magnesium daily for 6 months. The results showed a significant improvement in hyperactivity, as measured by two rating scales, compared to their baseline scores.
One study found that fish oil omega-3 fatty acids may enhance the benefits of Magnesium supplementation in children with ADHD. The study followed 810 children for 12 weeks and found improvements in symptoms as assessed by the SNAP-IV rating scale.
Main Takeaway: The available evidence suggests that Magnesium may be helpful for children with ADHD due to a possible association between ADHD and Magnesium deficiency. However, the exact efficacy of Magnesium in treating ADHD remains uncertain. It is possible that Magnesium could be used as a complementary therapy alongside standard drug treatments for ADHD.
Sleep
Magnesium appears to have some role in sleep by exerting sedative-like effects. Furthermore, there seems to be a weak but significant correlation between magnesium levels and the timing of sleep, regardless of dietary energy intake. Specifically, the group with the lowest magnesium levels had the most delayed midpoint of sleep. This may be more of an effect than a cause, as intentional sleep deprivation (sleeping 80% of normal length) for 4 weeks has been shown to reduce erythrocytic Magnesium levels by 3.5%.
A study conducted on 12 healthy elderly participants showed that effervescent Magnesium (10mmol, gradually increasing to 30mmol) over a period of 20 days resulted in a 63.3% increase in slow-wave sleep and reduced levels of cortisol during sleep, which helped to normalize age-related changes in sleep patterns.
There is evidence that consuming less than the Estimated Average Requirement (EAR) for magnesium through diet (265-350mg) may negatively affect sleep. In a study on individuals aged 59+/-8 years with magnesium intake below the EAR, supplementing with 320mg of Magnesium Citrate over 7 weeks led to improved sleep quality and some reduction in inflammatory markers.
Interestingly, magnesium supplementation did not increase serum magnesium levels more than placebo in the general population. However, when looking specifically at magnesium-deficient individuals, supplementation was effective in increasing serum magnesium levels.
Depression
There is an association between magnesium and depression, as people with depression tend to have lower levels of magnesium in their erythrocytes compared to healthy individuals, with levels ranging from 75-77% of controls in major depression. Some antidepressants, such as amitriptyline and sertraline, have been shown to increase magnesium stores in erythrocytes.
It should be noted that the correlation between Magnesium and depression is not always consistent, and there seems to be little correlation between serum Magnesium levels and depression. [1, 2] Elimination of magnesium from the diet of rats has been linked to symptoms of anxiety and depression.
Studies have shown an inverse relationship between dietary Magnesium intake and depressive symptoms in people with depression. When controlling for socioeconomic and lifestyle factors, this relationship was still statistically significant, although the odds ratio decreased from 0.70 to 0.86.
According to a hypothesis presented in a review, chronic activation of NDMA receptors due to magnesium deficiency may cause a form of neuronal injury that is misdiagnosed as treatment-resistant depression based on the phenotype.
A study conducted on elderly diabetic individuals with newly diagnosed depression and low serum magnesium levels (less than 1.8mg/dL) showed that a 12-week intervention with 450mg of Elemental Magnesium (in the form of Magnesium Chloride) was as effective as 50mg of imipramine (an antidepressant) in reducing depressive symptoms.
It’s been showed that magnesium is effective for mild-to-moderate depression in adults. It works quickly and is well tolerated without the need for close monitoring for toxicity.
Stress
Learning
An elevation in Magnesium levels from 0.8mM to 1.2mM has been shown to decrease the amplitude of NMDA receptor currents at the resting membrane potential by as much as 50%, without affecting currents during depolarization. This was hypothesized to be due to Magnesium blocking NMDA at resting potential but being expelled during activation of the neuron.
Over an extended period, an elevated concentration of magnesium at 1.2mM is linked with a rise in the strength of NMDA currents. This suggests that there may be a compensatory increase in the number of NMDA receptors to maintain optimal neuronal activity.
Studies conducted on rats showed that a diet containing 604mg/kg Magnesium-L-Threonate for a month resulted in a 60% increase in the NB2M subunit, observed in the prefrontal cortex and hippocampus, but not in the amygdala. This upregulation was also found to enhance signaling by increasing BDNF levels by 36% (55% in the prefrontal cortex in other studies), which is downstream of CREB activation that was increased by 57%, a result of NMDAR activation. The NB2M subunit and NMDAR signaling are involved in synaptic plasticity and memory function, with genetic overexpression of NB2M causing increased associative memory formation in young and old rats. The NR2A subunit does not appear to be affected.
Neurons from rats that received oral treatment with Magnesium-L-Threonate exhibited an increase in sensitivity to ifenprodil, which is an NB2M selective agonist. This increased sensitivity was observed through the enhancement of excitatory post-synaptic currents (EPSCs) of NMDA, which increased from 8.8+/-3.1% to 24.1+/-3.6%, representing a 273% increase in sensitivity. Moreover, this increased sensitivity was particularly evident in response to neuronal bursts, rather than single action potentials. Increased hippocampal frequency has been noted previously, although this study did not elaborate as much on mechanisms.
In male rats, a daily dose of Magnesium (L-Threonate) at 604mg/kg (which included 50mg/kg of elemental Magnesium in addition to the 0.15% already present in food pellets) was found to be the minimum effective dose in increasing brain Magnesium levels. After a month of treatment, brain Magnesium levels increased by 7% relative to baseline. However, the in vivo measurement technique may have underestimated the actual increase, which could have been up to 15%. In aged rats, the 604mg/kg daily dose of Magnesium (L-Threonate) was linked to improvements in short-term and long-term spatial memory, memory recall, and short-term working memory. In young rats, spatial memory appeared to be improved, but not other parameters. However, the positive effects on learning in young rats disappeared after the treatment was discontinued, while the benefits persisted for up to 12 days in older rats.
Main Takeaway: Magnesium has been shown to potentially increase NMDA transmission potential without affecting the resting potential. This suggests a possible hormetic role for magnesium, which may have synergistic effects when combined with NMDAR agonists like D-Aspartic Acid to enhance cognitive function. This effect has been observed with Magnesium L-Threonate and may also apply to superloaded magnesium. Additionally, in vivo supplementation with Magnesium-L-Threonate has been found to be effective in enhancing memory in both young and old rats, with greater efficacy observed in older rats.
Migraines
There seems to be a correlation between a lower magnesium level and migraines in people who experience migraines, similar to other health conditions. [1]
In a group of individuals who experienced migraines without auras for at least two years and had 2-5 attacks per month, supplementing with 600mg elemental magnesium (in the form of magnesium citrate) per day for three months resulted in reduced migraine severity compared to the placebo group (although the frequency of migraines was reduced in both groups). The Visual Analogue Score (VAS) decreased from 7.57+/-0.86 to 4.00+/-1.53, indicating a nearly 50% reduction in severity.
Cardiac Function
Lower levels of magnesium in the blood, which can indicate a deficiency, have been associated with heart arrhythmia and hypertension, among other health problems. In rats, intentionally depriving them of magnesium over a prolonged period of time has been shown to lead to cardiac apoptosis. There is a rough correlation between low levels of Magnesium and increased risk of heart disease and related ailments. [1] Supplemental magnesium has been shown to reduce the risk of coronary heart disease and other cardiovascular conditions in individuals who are deficient in magnesium. The cardiovascular benefits of magnesium are not consistently observed in individuals who are not deficient in this mineral.
Blood Pressure
Serum magnesium levels have been found to be a predictor of blood pressure complications, independent of obesity status.
In a study on diabetic adults, supplementation with 360mg Magnesium for 3 months did not show any effects on glucose or lipid metabolism. However, it was found that serum Magnesium levels were associated with a reduction in diastolic blood pressure, which is a different benefit of Magnesium compared to other effects that may require increased muscular stores.
A study that investigated individuals with normal blood pressure but low magnesium status found that normalization of magnesium levels (using 2.5g Magnesium Chloride for 3 months to increase levels from 0.66mM to 0.78mM) resulted in a 7.1% reduction in systolic blood pressure and a 4.7% reduction in diastolic blood pressure. Another study that supplemented 336mg Magnesium (as Lactate) in females with low dietary intake (239+/-79mg) also reported a decrease in blood pressure, but the findings did not reach statistical significance.
Main Takeaway: When individuals have a deficiency in Magnesium, taking Magnesium supplements may have a moderate effect in reducing blood pressure. However, not all studies have observed significant reductions in blood pressure.
A 12-week study in people with newly diagnosed hypertension showed that supplementing with 600mg of Magnesium pidolate daily, in addition to standard intervention, resulted in a significant reduction in 24-hour systolic (-5.6+/-2.7mmHg) and diastolic (-2.8+/-1.8mmHg) blood pressure compared to a placebo group that received standard intervention only. The decrease in blood pressure may be related to a decrease in intracellular calcium and sodium, which was observed only in the Magnesium-supplemented group. Additionally, the serum Magnesium levels increased from 2.3mg/dL to 2.44mg/dL in the Magnesium-supplemented group.
A study using 480mg Magnesium (as Oxide) measured the 24-hour blood pressure and observed reductions in systolic blood pressure ranging from 2-3.7mmHg and 1.4-1.7mmHg for diastolic blood pressure. The reduction was more effective in individuals with higher baseline blood pressure.
Although some studies have reported no significant effects of Magnesium supplementation on blood pressure, some have found significance in subgroups with elevated blood pressure. For instance, one study showed significant reductions in blood pressure in people with systolic blood pressure higher than 140mmHg.
Main Takeaway: Magnesium supplementation may lead to a small reduction in blood pressure in individuals with hypertension, regardless of their baseline magnesium levels.
There is currently insufficient evidence to support the idea that Magnesium supplementation reduces blood pressure in individuals with normal blood pressure and no Magnesium deficiency or inadequate dietary intake. [1]
Triglycerides
An acute intervention in healthy individuals with an average age of 41.5 years, where 500mg of Magnesium Chloride was administered with a meal (a bread roll with butter), resulted in a significant decrease in the post-meal elevation of triglycerides and non-esterified fatty acids (NEFA). The reduction in absorption was attributed to the delayed peak concentration of chylomicron-TAG, which was observed to be at 6 hours instead of 3 hours post-meal, and a decrease in its Cmax from 5.8-fold higher than baseline to 3.6-fold. The changes were independent of alterations in calcium and cholesterol metabolism, which were similar between groups.
Studies in both animals [1] and humans have found that intake of divalent minerals, such as Magnesium and Calcium, can lead to an increase in fecal lipid content. This effect is thought to be due to the formation of insoluble salt complexes with fatty acids. [1]
Long term studies have failed to demonstrate reductions in triglycerides following 450mg elemental magnesium for 4 months in deficient hypertensive adults. The improvement in triglyceride levels from magnesium supplementation may be due to an improvement in glucose metabolism.
Glucose Metabolism
To address abnormalities and insulin resistance caused by Magnesium deficiency, restoring Magnesium levels to normal appears to be effective.
Type I Diabetes
Type I diabetics (insulin-dependent; more commonly genetic or immune-related rather than diet-related) appear to have higher rates of Magnesium deficiency, which can be seen at up to 25% [1] while a correlation exists between lower erythrocyte Magnesium content (more indicative of Magnesium status than serum) and more polyneuropathic symptoms.
In type II diabetics as well, subsamples of persons with more diabetic neuropathy appear to be at even greater risk of Magnesium deficiency (intracellular) relative to diabetics without symptoms of neuropathy; with diabetics (Type I and II) in general being at greater risk than healthy controls.
Magnesium supplementation at a dose of 300mg in insulin-dependent diabetes (Type I) appears to reduce the rate of disease-related decline in nerve function (diabetic polyneuropathy). While 69% of control had a worsening of neuropathy and 31% stasis, Magnesium supplementation had 12% of its sample worsen and 49% of patients in stasis. The amount of improvement was 8% in placebo and 39% in Magnesium.
Main Takeaway: Magnesium supplementation potentially has a role as adjuvant in reducing the negative effects of the diabetic state on nerve health, thus being protective against Diabetic Neuropathy
Fat Absorption
Magnesium supplementation may have the ability to hinder fat absorption.
Muscle & Exercise
Skeletal Muscle appears to store approximately 35% of the body’s total Magnesium stores, where it can act as an endogenous calcium channel blocker and help regulate muscle contraction.
Severe depletions of Magnesium (in a clinical setting) are known to induce cramping and severe muscular pain. [1]
During muscle contraction, cytosolic levels of Magnesium appear to increase in correlation to decreasing pH (an increase in acidity turning exponential any lower than pH 6.5). This relationship appears to be causal as it does not exist in a contracting muscle without increases in pH.
One study in persons with alcoholic liver disease (a condition where muscular strength is reduced and magnesium deficiency exists) failed to note any increased muscular stores of Magnesium in response to oral and intravenous magnesium oxide treatment for 6 weeks.
Performance
Restoring a Magnesium deficiency does not appear to significantly improve anaerobic or aerobic physical performance.
A single study in Triathletes suggests remarkable effects from high dose Magnesium supplement and appears to be structured well, but it has not been replicated.
Cramping
Magnesium is thought to be related to muscle cramping mainly due to correlations between a higher rate of muscle cramping coinciding with reduced serum magnesium levels which applies to pregnant women (as a decline in Magnesium levels in the serum of the mother during pregnancy correlates with the appearance of cramps) [1] and some persons experiencing night cramps in the calf muscle. Furthermore, severe hypomagnesia (low serum magnesium) has been noted to be associated with severe muscle cramping and muscle pain.
Magnesium supplementation for the purpose of reducing leg cramps has mixed evidence; even the evidence suggesting it is useful is relatively low powered and likely not clinically relevant.
When it comes to Pregnancy-related cramping there’s mixed evidence. It appears to be more beneficial than placebo (which is, in and of itself, beneficial to leg cramps) but the degree it is better than placebo is sometimes insignificant and sometimes clinically relevant. [1]
Same motifs appear to be carried over into noctural cramps. [1] There appears to be benefit to both placebo and Magnesium Intervention, with the degree that Magnesium is better than placebo being small enough to many times be deemed statistically insignificant.
Interaction with Testosterone
Magnesium has the possibility to either increase or normalize testosterone levels, but the evidence on Magnesium and testosterone is minimal. When increases in testosterone are seen, they are minimal.
Interaction with Thyroid Hormones
Supplementation of Magnesium Sulfate (10mg/kg bodyweight) was associated with a lesser reduction of thyroid hormones (free T3, total T3 and T4) that occurs during exercise. [1]
Magnesium & Cancer
There appears to be an association between higher dietary magnesium and lower colorectal cancer risk. This protective effect is linked to foods containing magnesium rather than supplements (which has not yet been investigated).
Teeth
Low magnesium levels in serum and perhaps a low magnesium:calcium ratio are associated with an increased risk of periodontal diseases and lesser tooth integrity.
Forms of Magnesium Supplementation
Magnesium oxide has lower absorption than most magnesium salts, [1, 2] but more elemental magnesium. It may not be a bad choice for increasing magnesium levels, but its low absorption can cause gastrintestinal upset and a strong laxative effect. Note that Magnesium Oxide is sometimes paired with Calcium supplement to mitigate the pro-constipative effects of Calcium.
Magnesium Hydroxide (MgOH2) is commonly used for laxatative purposes. It may possess antacid effects, but is not suited for nutritional supplementation.
Magnesium Citrate is the most commonly used form of Magnesium supplementation, due to its high water solubility and possible usage in liquids, as well as due to its low cost. It appears to have a higher bioavailability at around 25-30%, probably due to its increased water solubility relative to oxide chelations (as it is hypothesized that small molecular weight acids hold this potential). [1] It has a three-fold higher bioavailability relative to oxide, although still a relatively small absorption percentage.
Magnesium L-Aspartate show increased bioavailability relative to Oxide but tend to be lesser than Citrate. One exception is Magnesium Monoaspartate, which has been found to have bioavailability of 42% relative to citrate’s 30%.
Magnesium glycinate, also known as magnesium diglycinate or magnesium bisglycinate has inceased bioavailability relative to Oxide, and is absorbed in different areas of the gut than traditional magnesium supplementation.
Magnesium Orotate (Orotic acid) appears to have favorable kinetics when in systemic circulation and a large safety profile, but gastrointestinal uptake rate is not known.
Magnesium L-Threonate has begun to be looked into for specifically increasing brain magnesium levels and learning. [1] Some data suggest that Magnesium L-Threonate and Magnesium Gluconate dissolved in milk have higher bioavailabilities than Citrate, Glycinate, Oxalate, and Gluconate by itself. [1]
Summary
Tldr; Magnesium can be found in a variety of foods that are commonly consumed in a healthy diet. Magnesium deficiency, at least to a minor degree, appears to affect a large percentage of adults.
Magnesium is a crucial mineral in the body, serving primarily as an electrolyte and mineral cofactor for enzymes. In its role as an electrolyte, magnesium helps to maintain fluid balance, while its role as a cofactor is critical to the function of over 300 enzyme systems in the body. These enzyme systems include ATP, Adenyl Cyclase, and the enzymes involved in glycolysis. Additionally, magnesium is required for the activation of creatine kinase, which plays an important role in energy metabolism.
The human body typically stores between 21-28g of magnesium, with about half of this amount deposited in bone tissue. The majority of the remaining magnesium is found inside of cells.
Typical serum levels of magnesium range from 1.7-2.5mg/dL.
Individuals with Type II diabetes have a higher risk of magnesium deficiency compared to the general population, with an estimated 25-38% of diabetic individuals experiencing deficiency.
The absorption of Magnesium in the intestines occurs through two mechanisms: paracellular (between intestinal cells, also known as enterocytes) and transcellular (via enterocytes). Both of these mechanisms are regulated by the body’s Magnesium levels. When Magnesium levels are sufficient, absorption is reduced, and when there is a deficiency, absorption increases.
The absorption of Magnesium from the diet is affected by the presence of various factors, such as phytates and oxalates. Phytates, which are found in whole grains and legumes, can impair Magnesium absorption, whereas oxalates, which are found in some vegetables, have less of an impact on Magnesium absorption. When considering the percentage of Magnesium absorbed, leafy green vegetables are a better source than grains. A mixed diet typically has a 20-30% bioavailability of Magnesium, but this can be increased if the diet is rich in vegetables rather than grains.
Adequate levels of magnesium in the brain are crucial for maintaining normal neuronal function during periods of neuronal inactivity. When there is a deficiency of magnesium in the brain, which usually happens due to chronic dietary deprivation, neurons can become excessively activated during periods of inactivity.
Long-term overstimulation of NMDA receptors or acute excessive activation can lead to neurotoxic effects that are mediated by calcium-dependent mechanisms. Magnesium can mitigate this toxicity primarily during periods of neuronal inactivity. However, it is worth noting that these neurotoxic effects are not applicable to calcium supplements as calcium is tightly regulated in the body like magnesium.
The available evidence suggests that Magnesium may be helpful for children with ADHD due to a possible association between ADHD and Magnesium deficiency. However, the exact efficacy of Magnesium in treating ADHD remains uncertain. It is possible that Magnesium could be used as a complementary therapy alongside standard drug treatments for ADHD.
Magnesium appears to have some role in sleep by exerting sedative-like effects. Furthermore, there seems to be a weak but significant correlation between magnesium levels and the timing of sleep, regardless of dietary energy intake.
It’s been showed that magnesium is effective for mild-to-moderate depression in adults. It works quickly and is well tolerated without the need for close monitoring for toxicity.
Magnesium has been shown to potentially increase NMDA transmission potential without affecting the resting potential. This suggests a possible hormetic role for magnesium, which may have synergistic effects when combined with NMDAR agonists like D-Aspartic Acid to enhance cognitive function. This effect has been observed with Magnesium L-Threonate and may also apply to superloaded magnesium. Additionally, in vivo supplementation with Magnesium-L-Threonate has been found to be effective in enhancing memory in both young and old rats, with greater efficacy observed in older rats.
There is a rough correlation between low levels of Magnesium and increased risk of heart disease and related ailments. Supplemental magnesium has been shown to reduce the risk of coronary heart disease and other cardiovascular conditions in individuals who are deficient in magnesium. The cardiovascular benefits of magnesium are not consistently observed in individuals who are not deficient in this mineral.
When individuals have a deficiency in Magnesium, taking Magnesium supplements may have a moderate effect in reducing blood pressure. However, not all studies have observed significant reductions in blood pressure. Magnesium supplementation may lead to a small reduction in blood pressure in individuals with hypertension, regardless of their baseline magnesium levels.
To address abnormalities and insulin resistance caused by Magnesium deficiency, restoring Magnesium levels to normal appears to be effective.
Magnesium supplementation potentially has a role as adjuvant in reducing the negative effects of the diabetic state on nerve health, thus being protective against Diabetic Neuropathy
Magnesium supplementation may have the ability to hinder fat absorption.
Skeletal Muscle appears to store approximately 35% of the body’s total Magnesium stores, where it can act as an endogenous calcium channel blocker and help regulate muscle contraction.
Severe depletions of Magnesium (in a clinical setting) are known to induce cramping and severe muscular pain.
Restoring a Magnesium deficiency does not appear to significantly improve anaerobic or aerobic physical performance.
Magnesium supplementation for the purpose of reducing leg, pregnancy-related and noctural cramps has mixed evidence; even the evidence suggesting it is useful is relatively low powered and likely not clinically relevant.
Has the possibility to either increase or normalize testosterone levels, but the evidence on Magnesium and testosterone is minimal. When increases in testosterone are seen, they are minimal. Supplementation of Magnesium Sulfate (10mg/kg bodyweight) was associated with a lesser reduction of thyroid hormones (free T3, total T3 and T4) that occurs during exercise.
There appears to be an association between higher dietary magnesium and lower colorectal cancer risk. This protective effect is linked to foods containing magnesium rather than supplements.
Low magnesium levels in serum and perhaps a low magnesium:calcium ratio are associated with an increased risk of periodontal diseases and lesser tooth integrity.
