Magnesium research is a field that is currently both very exciting and very frustrating. It is exciting because there is a possibility that many people can benefit their health by increasing their magnesium intake. This excitement is reflected by the existence of journals solely or mostly dedicated to magnesium research. On the other hand, magnesium research can be frustrating for two reasons: funding for nutrition-related magnesium research has not been a high priority, and in many areas, conclusions are hard to draw due to seemingly contradictory results. This chapter was particularly difficult to write because hardly any issue is clear cut, including the relative bioavailabilities of different supplement forms.
The need for more research on magnesium is evident, considering that many reports contend that marginal magnesium deficiency is not uncommon. Additionally, a number of health applications are backed by some evidence but require more research for a definitive judgment.
Overview of Function
Magnesium affects a multitude of physiological processes, which can be categorized as follows:
• Cofactor for Enzymes: Magnesium is needed as a cofactor for a large number of enzyme-catalyzed reactions, especially those that require ATP for energy. These ATP-requiring enzymes include those that add phosphate to other enzymes (enzyme phosphorylation) and those involved in the formation of cyclic adenosine monophosphate (cAMP), both of which regulate many processes within cells.
• Physiological Modulator: Intracellular free magnesium ions act as a physiological modulator. These modulations include competing with calcium for entrance into cells via cell membrane channel passage. This competition between calcium and magnesium for cell membrane channels seems to keep many cellular processes in balance. This balancing act may also occur outside cells where magnesium is thought to antagonize calcium’s promotion of blood clotting.
• Potassium Modulation: Besides affecting calcium function, magnesium also modulates potassium function. One action of magnesium on potassium is to block channels where potassium can leave cells, which helps maintain the unequal distribution of intracellular and extracellular potassium. Magnesium also influences this potassium distribution through its necessity for the enzyme Na,K-ATPase, which pumps sodium out of cells and potassium in. These relationships are manifest in severe magnesium deficiency, leading to body potassium depletion and low serum potassium readings.
• Indirect Antioxidant Functions: Magnesium has indirect antioxidant functions, likely mediated by its other biochemical roles. Magnesium-deficient animals show signs of a pro-oxidant state, including high sensitivity of lipoproteins to oxidation, above-normal serum values for molecules associated with a pro-inflammatory state, high values for lipid peroxides, low plasma values for radical scavenging capacity, and poor myocardial tolerance to oxidant stress. Magnesium deficiency in cultured cells can also increase the production of free radicals and hydrogen peroxide. The exact biochemical mechanisms are complex, potentially involving magnesium’s influence on cell membrane stability and lipid composition, or its role in regulating processes that control pro-oxidant and antioxidant molecules, possibly mediated by the pro-inflammatory molecule substance P.
• Role in Bone Health: About two-thirds of the body’s magnesium is found in bone, suggesting a role in bone health. This includes magnesium affecting hydroxyapatite crystal structure and controlling bone cell proliferation. Magnesium’s antioxidant effects could also restrict bone resorption. Furthermore, magnesium affects the secretion of parathyroid hormone (PTH) and insulin-like growth factor, both of which influence bone metabolism. The effects of magnesium deficiency on PTH are unusual, as serum PTH levels can rise or fall at different times, and during a rise, there can be poor receptor reactivity to the hormone.
Overview of Metabolism
Magnesium absorption occurs by both a saturable carrier-mediated process and simple diffusion. Absorption does not appear to be regulated in the same way as occurs for minerals such as calcium. While there is some evidence that vitamin D status affects magnesium absorption, in most circumstances, magnesium absorption appears to occur largely independent of vitamin D hormone influence. Any increase in magnesium absorption due to vitamin D hormones may often be largely balanced by increased urinary excretion.
Nutritional Status Assessment
• Serum Total Magnesium: By far, this is the most common means of assessing magnesium status. Serum is generally preferred over plasma due to possible magnesium contamination and assay interferences. Serum magnesium is influenced by dietary magnesium and short-term changes in renal magnesium losses. However, serum magnesium values do not always reflect intracellular or total-body magnesium content. Low tissue magnesium can occur despite normal serum values, and short-term changes are not always reflected. Factors like fluctuations in albumin or pH can affect it. Values under 0.7 mM usually mean that substantial magnesium depletion has taken place. The normal range is 0.70 to 1.05 mM, reflecting that homeostatic mechanisms work against big changes in serum values as stores drop.
• Muscle Biopsy Magnesium: This would seem appropriate since over a fourth of the body’s magnesium is typically found in muscle. The main limitations are that sample collection is uncomfortable for subjects and requires skill.
• Mononuclear Blood Cell (MNC) Total Magnesium: These contents appear to reflect magnesium status in some, but not all, circumstances. Results vary, and the utility of MNC magnesium for status assessment is still debatable, potentially due to technical considerations in sample preparation and the effects of illness on cell composition and size.
• Erythrocyte-Ionized Magnesium: This seems to be a very good indicator of magnesium status, with existing work generally supportive. It is most directly measured by an NMR technique, but this has drawbacks: most labs are not fluent in it, and a substantial amount of blood is needed. Alternatives include fluorescent probes (with procedural pitfalls) and zero-point titration, which has compared favorably with NMR for relative results.
• Serum-Ionized Magnesium: Shows considerable promise in assessing magnesium status, typically measured by a magnesium-specific electrode. However, some researchers question how often it diagnoses marginal magnesium deficiency not detected by total serum magnesium. Technical problems include electrode quality, need for rapid sample centrifugation and analysis, and circadian rhythms (recommending blood collection between 6 and 10 AM). An alternative uses ultrafiltration followed by total magnesium reading in the low molecular weight fraction, but it has technical pitfalls such as pH changes affecting magnesium partitioning.
• Urinary Total Magnesium: Also used for assessing magnesium status, especially after an acute parenteral magnesium load (a tolerance test). Without an acute load, in healthy subjects, it can be directly proportional to dietary intake and magnesium stores. However, this is not always true, as high urinary magnesium can occur with excessive renal losses.
Bioavailability from Foods and Supplements
• Absorption Rates: An absorption of about 40 to 50% is often viewed as normal for children and young adults with Western diets. Magnesium is generally absorbed better than minerals like iron, and absorption from various sources is somewhat similar. For a high-magnesium mineral water, absorption can jump from 46% on an empty stomach to over 52% with a meal.
• Factors Affecting Absorption:
◦ Phytates and Oxalates: These can negatively affect magnesium absorption, though their actual impact varies. Spinach, high in oxalates, can provide well-absorbed magnesium, possibly because spinach magnesium is often in chlorophyll, not predominantly bound to oxalates. High phytate intakes can have a substantial effect.
◦ Calcium: Often stated to negatively affect magnesium absorption, but a major effect for most human circumstances is unconfirmed.
◦ Zinc: High-dose zinc supplements may be an underappreciated cause of poor magnesium absorption.
• Magnesium Supplement Forms: Many different complexes are available and can impact magnesium status, though differences in bioactivity can occur. The general attitude is that organic magnesium supplements are better absorbed than inorganic versions, in part due to better water solubility. However, this idea is not clear-cut, as results are often conflicting, partly due to a lack of precise tools for measuring acute bioavailability. Stable isotope studies are needed for better answers.
◦ GI Tract Side Effects: These may differ between supplement types, but this is not wellnesium Sulfate**: Used for intramuscular/intravenous administration and as a laxative (Epsom Salts). Little study on oral efficacy for supplementation; recommended against due to possible low absorption, supported by rat studies.
◦ Magnesium Hydroxide: Also an antacid and laxative (e.g., Maalox). Poor water solubility. One human study found similar acute effects on urinary magnesium to organic forms. Showed beneficial effects on bone density in one study, but questions exist. Long-term use may increase cardiac event risk in certain subjects. Can influence drug solubility and absorption. Author suggests choosing another complex if the goal is picolinate, pidolate, glycinate, other amino acid chelates, taurate, gluconate, and orotate.
▪ Magnesium Lactate: May have good absorption due to very high water solubility, but caution is needed in interpreting existing reports.
▪ Magnesium Citrate: Considered a well-absorbed complex; one study showed it was absorbed 4.5 times as well as magnesium oxide.
▪ Magnesium Taurate: Has theoretical appeal, and animal studies suggest specialized bioactivity.
▪ Magnesium Pidolate: Animal)**: Magnesium diglycinate chelate and magnesium aspartate appear to have good GI tolerability. Slow-release preparations are designed to be less irritating. Published comparisons for incidence of diarrhea between different forms are limited.
Typical Intakes Versus Needs
There are no commonly eaten foods that have extremely large percentages of the adult RDAs for magnesium. Nuts and seeds are the most concentrated per unit weight among commonly eaten foods. Other relatively good sources are whole grains and dark green leafy vegetables (due to chlorophyll content). Milk, dairy, legumes, and some other vegetables and fruits also contribute.
The exact consequences of this could affect blood pressure via multiple mechanisms, including its effects on the sodium-potassium pump, calcium ion flow (influencing vascular tone, reactivity, and dilation), antioxidant actions (as oxidant stress contributes to hypertension), and hormone secretion. Magnesium deficiency can promote hypertension in animals. Human epidemiological studies show correlations between magnesium intake and blood pressure, but these relationships may reflect other positive aspects of high-magnesium diets.
Studies of magnesium supplementation and blood pressure have yielded inconsistent results, often due to small sample sizes or the instability of blood pressure as an endpoint. It is possible that magnesium impacts blood pressure only under specific conditions:
• Subjects initially have at least a marginal magnesium deficiency.
• The deficiency is corrected by the supplement.
• Subjects initially have high blood pressure, but not so advanced that magnesium cannot make an impact.
• The high blood pressure is due to a specific process that responds to magnesium, such as the renin-angiotensin-aldosterone system or changes in intraerythrocyte sodium.
This scenario is supported by observations that magnesium supplementation shows: no effect in people with normal blood pressure; an effect in responders who recently acquired hypertension; no effect on blood pressure when it also has no effect on magnesium status markers; and improvements in blood pressure correlating with increases in serum/plasma magnesium. Positive studies often use well-absorbed forms or above-RDA doses. Some normotensive individuals with marginal deficiency might still respond, and a good magnesium intake may help prevent future hypertension.
Expected blood pressure changes can be small, though some studies show double-digit systolic changes. Maximal blood pressure control is achieved by multiple interventions. The author recommends starting with the biggest known influences on blood pressure before considering magnesium.
At present, it is difficult to say definitively who can benefit. Eating a diet high in magnesium is probably a good idea from multiple health perspectives. For those at high risk for low magnesium intake or with high needs, consultation with a physician and dietitian is advised. If serum magnesium is low, a low-dose supplement with high bioavailability and low GI side effects is likely safe and potentially helpful. Even with normal serum values, a moderately high magnesium diet is encouraged.
Serum Lipids in Non-Diabetic Subjects
Animal studies suggest that moderately high magnesium intake can beneficially affect serum or tissue lipid compositions, potentially through binding to lipids and bile salts in the GI tract, reducing their absorption, or by correcting a marginal deficiency. Some human studies show inverse correlations between magnesium status and certain serum lipid values. Diet interventions increasing magnesium intake from 400 mg/day to 1000 mg in about 400 subjects resulted in approximately a 10% decrease in serum, LDL, and triglyceride cholesterol. However, it’s hard to attribute these effects solely to magnesium. HDL cholesterol only increased in subjects with initially low serum magnesium. One study with high-dose magnesium oxide did not lower serum cholesterol, while another found magnesium supplementation (500 mg) combined with a low-calorie, low-cholesterol diet lowered serum triglycerides but not cholesterol. A study of 1000 mg magnesium oxide in hyperlipidemic subjects actually slightly increased serum cholesterol (due to LDL) which returned to pretreatment levels after washout.
In summary, there is not yet conclusive evidence that high doses of magnesium can consistently produce beneficial effects on serum lipids, though this remains a possibility. This action may or may not require correction of a marginal magnesium deficiency.
Prevention of Cardiovascular Disease in Non-Diabetic Subjects
Magnesium’s potential relationship to serum lipids and blood pressure, along with its antioxidant and anti-inflammatory actions, could impact cardiovascular disease risk. Magnesium-deficient rats show lipoproteins highly susceptible to atherosclerosis-related oxidation. Magnesium also affects cardiac muscle integrity and can restrict calcium movements, influencing heart beat, vasospasm, platelet aggregation, and vasodilation. A controversial idea suggests magnesium plays a role in preischemia conditioning.
Epidemiological studies have found correlations between magnesium intake or blood magnesium status and risk of certain cardiovascular diseases, including stroke and ischemic heart disease. Autopsy studies also show lower myocardial and skeletal magnesium in individuals dying from ischemic heart disease. However, these studies do not distinguish direct magnesium effects from other beneficial dietary factors. Animal studies directly show low magnesium intake can enhance atherosclerosis.
Direct supplementation studies for preventing cardiac events in healthy people are scarce due to the need for large subject numbers and long durations. Studies focusing on survivors of cardiovascular events, however, provide some insights:
• Magnesium citrate supplementation (at RDA levels) improved exercise tolerance, exercise-induced chest pain, and quality of life in patients with coronary artery disease.
• Magnesium orotate improved left ventricular function and exercise tolerance.
• Magnesium supplementation plus aspirin improved brachial artery endothelial function and exercise tolerance.
• Magnesium oxide (800-1200 mg/day) inhibited platelet-dependent thrombosis.
• Enteric-coated magnesium chloride supplementation in patients with congestive heart failure raised serum magnesium, decreased blood pressure, vascular resistance, and reduced the frequency of ventricular premature complexes.
It is unclear if these benefits depend on correcting a marginal magnesium deficiency. Some studies showed benefits without low initial serum magnesium or without increasing serum magnesium. In contrast, one study using magnesium hydroxide in acute myocardial infarction survivors showed a trend towards higher cardiac events in the magnesium group (by one statistical analysis), though this may be related to the antacid effects of magnesium hydroxide.
In summary, for subjects with cardiovascular disease, magnesium supplementation produces apparent benefits in several studies, which are promising but need more bolstering evidence. Some physicians may consider modest doses, while others may be cautious, especially regarding magnesium hydroxide. It is not yet clear what these studies imply for preventing a first cardiac episode. One 10-year study in 400 high-risk individuals showed less complications, sudden deaths, and total mortality with a magnesium-rich diet, but this is not a definitive last word. A magnesium-rich diet is recommended for multiple health benefits.
Diabetes
Marginal magnesium deficiency appears to be common in many diabetic subjects (Type 1 and Type 2), with reports of low serum, erythrocyte-ionized, and muscle magnesium values. This is attributed to high renal magnesium loss and magnesium redistribution. Inverse correlations exist between serum magnesium and markers relevant to diabetes, such as fasting glucose and HbA1c, possibly linked to magnesium’s role in insulin sensitivity.
These observations suggest that many diabetic people could benefit from increased magnesium intake. Supplementation studies have shown some benefits, but are often small, lack placebo controls, or have conflicting results. Magnesium supplementation can also improve insulin responses and actions in elderly subjects without diabetes.
There is doubt about the exact benefits, the specific diabetic population that would benefit most, and the ideal treatment (dose, complex, duration). This requires large, multi-center trials. Speculations for conflicting results include:
• Lipid effects may involve two mechanisms: correction of marginal deficiency requiring sufficient treatment time, or decreased absorption of lipids and bile salts from high oral magnesium intake.
• The specific magnesium complex used may be important, with magnesium pidolate showing better effects on serum lipids in one study, possibly due to better bioavailability or specialized effects.
• For metabolic control, magnesium status improvement is not the only factor, as some studies showed improved status without metabolic control changes.
The American Diabetes Association’s 1992 statement recommended adequate dietary magnesium and only assessing/repleting hypomagnesemia in high-risk patients. The author suggests that anyone with diabetes can have their serum magnesium checked. If low, a low-dose supplement with high bioavailability and low GI side effects is likely safe and possibly helpful. If serum values are normal, a moderately high magnesium diet is still recommended, with supplementation being a decision to be made in consultation with a physician and dietitian.
Stress
Magnesium has strong theoretical ties to inhibiting responses to psychological stress. Magnesium deficiency is characterized by neural and neuromuscular hyperexcitability, and magnesium influences blood vessel dilation/constriction and systems involved in depression pathophysiology (e.g., hippocampal kindling, ACTH). Functional overlaps with lithium (an anti-depression drug) suggest magnesium’s role as a mood stabilizer.
Magnesium interacts with stress-related catecholamine hormones (epinephrine and norepinephrine) in three possible ways:
1. Epinephrine may increase magnesium needs: Low serum magnesium is reported during physiological stress with high catecholamine levels (e.g., myocardial infarction, cardiac surgery, insulin-induced hypoglycemia, emotional stress). Epinephrine infusion decreases serum magnesium. The mechanism is not fully confirmed, but may involve fat breakdown and magnesium binding. It is not known if this leads to a functional magnesium deficit.
2. Magnesium may inhibit catecholamine secretion during stress: Supported by animal and human studies. For example, magnesium supplementation can decrease urinary norepinephrine and epinephrine in people with mitral valve prolapse, and magnesium sulfate infusion suppresses cardiac norepinephrine release during stress. This suggests that above-adequate magnesium intakes might counteract some stress effects.
3. Magnesium may limit detrimental effects caused by catecholamine hormones during stress: Well-supported by animal work. Magnesium deficiency increases aortic sensitivity to norepinephrine, and high magnesium intake reduces pulmonary vascular reactivity. This indicates magnesium may have effects beyond correcting a deficiency.
Human supplementation studies in this area are limited. One study in elderly subjects showed magnesium supplementation partially reversed aging-related neuroendocrine and sleep EEG changes, resembling lithium’s effects. Magnesium pidolate did not affect blood pressure during sympathetic neuro-stimulation in another study, despite raising serum magnesium. Noise-induced hearing-loss studies also suggest a link between magnesium and protection against stress, though mechanisms may be ear-specific.
In conclusion, a connection between magnesium and resistance to the ill effects of psychological stress has a strong mechanistic basis, but insufficient human intervention studies exist for definitive value.
Exercise
Since a great deal of the body’s non-bone magnesium is found in muscle, studies on magnesium supplementation relevant to exercise are expected. However, such studies yield differing results, partly due to the many variables in exercise study design. It is uncertain how severe marginal magnesium deficiency needs to be to see an effect, or how often it occurs. Dietary surveys show varied magnesium intake among athletes. It is also unsettled whether dietary magnesium-induced improvement in exercise performance could go beyond correcting a marginal deficiency.
Ten representative studies (5 negative, 5 positive) on magnesium supplementation and exercise performance, all using placebo controls, highlight the conflicting picture:
• Negative results often report minimal impact on urine or serum magnesium, suggesting magnesium status may not have improved.
• Positive results sometimes involve other active ingredients (like orotate or potassium) or use magnesium oxide, which doesn’t always show good bioavailability but can affect training-induced strength.
Many studies have questions about their interpretation, such as lacking before-intervention testing or including both genders with small numbers. The author concludes that there are many questions about the studies of magnesium supplementation and exercise, and thus, no conclusions can be reached yet.
A popular supplement for exercisers is “ZMA” (zinc, magnesium, and vitamin B6). One meeting abstract reported some benefits, but detailed full-length papers are needed to evaluate these findings. Claims are often based on general zinc or magnesium research, not specific to ZMA.
Osteoporosis Prevention or Restriction
Given that a high portion of the body’s magnesium resides in bone and that magnesium has possible mechanistic ties with bone health (supported by animal studies), it makes sense that magnesium intake could affect osteoporosis. However, human intervention studies are very limited. One study in postmenopausal women with osteoporosis reported an increase in trabecular bone density after one year of magnesium supplementation, but this finding is unusual for the timeframe, the effect was not sustained for all subjects, and there was no placebo group for comparison. Another study in healthy young adult females showed no effect on bone turnover markers, but also no change in serum magnesium, suggesting a deficiency might not have existed or been corrected. Other studies have limitations such as low subject numbers or design problems.
At present, though magnesium protection against osteoporosis is theoretically very possible, it is not known if increased magnesium intake would help osteoporosis prevention or restriction to a large degree in many people.
Chronic Fatigue
Magnesium status in subjects with chronic fatigue syndrome (CFS) does not seem consistent. Some studies report low erythrocyte magnesium, while others report normal serum total and ionized magnesium. One study found evidence of magnesium deficiency in just under half of CFS patients. Magnesium supplementation studies have shown some subjective symptom improvements in a portion of subjects, or improvements in antioxidant defense parameters in those with “subclinical” magnesium deficiency.
In conclusion, it is hard to reach a conclusion on the value of magnesium supplementation in chronic fatigue syndrome due to inconsistent findings on magnesium status, very limited testing of symptom improvement, and the mixing of different fatigue classifications in studies.
Asthma
Many Internet sites tout magnesium supplements for asthma patients. While parenteral magnesium has been tried pharmacologically in asthmatic subjects for acute stress, this does not necessarily indicate that oral supplements would be effective. One short-term crossover intervention study showed magnesium supplementation improved subjective, but not objective, asthma symptoms. There are some epidemiological links between magnesium intake and asthmatic symptoms.
Therefore, at present, there is no direct, strong evidence that oral magnesium supplements would help asthma.
Beta-Thalassemia/Sickle Cell Anemia
People with sickle cell anemia are reported to have high urinary magnesium excretion and low plasma or serum magnesium. Small human studies show beneficial effects of magnesium pidolate supplementation on erythrocytes, indicative of better cell hydration. In a mouse model, low magnesium worsened the condition, and high magnesium improved it. An unblinded study strongly decreased painful days in sickle cell patients. Similar magnesium metabolism abnormalities are found in beta-thalassemia, with magnesium supplementation affecting erythrocyte hydration.
These results are certainly interesting, and the next step would be large, placebo-controlled trials, with attention given to the particular magnesium complex used.
Kidney Stones
Magnesium-potassium citrate is used to prevent kidney stones, primarily for citrate delivery, but magnesium itself may help inhibit stone formation, particularly for calcium oxalate stones. Several theoretical mechanisms include:
• Inhibiting calcium oxalate crystal formation.
• Influencing body citrate metabolism, which increases urinary citrate and inhibits stone formation.
• Non-citrate-related alkali effects in the urine, which reduce stone development (especially with antacid magnesium complexes like magnesium hydroxide).
• Binding to oxalate in the GI tract to prevent oxalate absorption.
• Repressing internal oxalate production, though this may be relevant only for severe magnesium deficiency.
Some studies suggest marginal magnesium deficiency in chronic stone formers, but this is not overly compelling. It’s possible that magnesium intake could be useful for kidney stone prevention, whether as an antacid, a corrector of marginal deficiency, or through actions beyond these.
Studies on magnesium supplementation for stone formation or risk factors are inconsistent, often due to small subject numbers, problematic endpoints, lack of specific complex details, or absence of placebo controls (which can reveal strong placebo effects in these studies). For example, magnesium oxide treatment has shown mixed results, and even when positive effects are reported, interpretation is often clouded by study design. Magnesium hydroxide has also been studied, with one placebo-controlled study showing improvement that was not statistically significant compared to placebo. One study found magnesium nearly as effective as calcium in reducing oxalate absorption and urinary excretion after an oxalate load, strengthening one proposed mechanism.
Considering the mixed results, if one adopts a “it may help and it probably won’t hurt” approach, a moderately high magnesium intake is appropriate. This can be achieved through diet, or conveniently with supplements, especially for those who need to avoid oxalate-rich foods. The author personally takes 320 mg of an organic compound (e.g., magnesium bisglycinate or lactate) daily for kidney stone prevention, noting these have not been directly tested in humans for this purpose but are likely safe and well-absorbed.
Pregnancy: Premature/Low Birth Weight Outcomes
One line of evidence supports a connection, with an inverse relationship between very-low-birth-weight outcomes and magnesium levels in drinking water in Taiwan, and lower serum magnesium in women in preterm labor. However, other studies find no correlation.
Studies on magnesium supplement effects in pregnancy have been criticized for their design. A meta-analysis reported that oral magnesium treatment from before the 25th week of gestation was associated with a lower frequency of preterm birth, but this effect disappeared upon excluding a cluster trial. The author notes that poor design can bias results toward favoring supplementation.
Thus, although oral magnesium supplementation may help prevent premature and low-birth-weight pregnancy outcomes, this hypothesis has not yet been adequately tested.
Premenstrual Syndrome (PMS)
Three studies explored magnesium supplementation for PMS:
• One crossover, placebo-controlled study showed 200 mg magnesium oxide/day reduced mild premenstrual symptoms related to fluid retention in the second menstrual cycle (not the first). Urinary magnesium increased slightly.
• Another crossover, placebo-controlled study with the same dose and complex, plus vitamin B6, found a significant effect of the magnesium-vitamin B6 combination on anxiety-related PMS symptoms by one statistical analysis. The authors noted modest effects and poor absorption from magnesium oxide.
• A double-blind, randomized study with magnesium pyrrolidone carboxylic acid found a significant impact on the total Menstrual Distress Questionnaire score and the “negative effect” cluster in the second month of supplementation. Lymphocyte and polymorphonuclear cell magnesium increased, but not plasma or erythrocyte magnesium.
Based on these studies, it cannot be said that magnesium supplements can provide major PMS symptom relief, but there may be a modest effect on some symptoms. The relationship of increased magnesium intake to PMS symptoms may not have yet been tested in an ideal design.
Mitral Valve Prolapse (MVP)
Magnesium could affect MVP symptoms through direct effects on neurological function and by restricting catecholamine rises in the blood. Three studies report magnesium improving symptoms in subjects with MVP:
• One study found low serum magnesium in 60% of symptomatic MVP patients. Magnesium carbonate supplementation reduced symptoms and urinary epinephrine/norepinephrine more than placebo. However, the form used (magnesium carbonate) is an antacid, which can relieve some MVP symptoms, so not all effects may be due to magnesium status changes.
• Another study showed magnesium orotate supplementation partially or completely reduced various symptoms in over half of MVP patients.
• A third study found magnesium lactate supplementation improved a number of symptoms, including the disappearance of Trousseau’s sign.
In conclusion, these studies raise the possibility that increased magnesium intake can help with some MVP symptoms in at least some people with symptomatic MVP. More research is needed, especially placebo-controlled studies that thoroughly characterize magnesium status and link changes to symptom improvement.
Other Applications
Many other health applications have been proposed for magnesium supplements based on abnormal blood or urinary magnesium values, mechanistic ties, or a few studies. As evident from the preceding sections, these lines of reasoning do not guarantee a clear demonstration of efficacy, especially if supplementation studies have design flaws. At this point, many claims for magnesium supplementation could be true, but are not yet confirmed.
Toxicity
The adult Upper Level (UL) for magnesium is 350 mg from supplements (not total intake from food plus supplements). This UL is based on gastrointestinal tract distress such as diarrhea, rather than a toxic magnesium build-up. The actual intake that causes GI tract symptoms likely depends on the specific magnesium complex(es) ingested, whether the daily dose is taken at once or spread out, and whether the supplement is taken with food; however, these suppositions are not extensively researched.
Typical supplement doses are considered safe for people with good kidney function, except for potential GI symptoms. Magnesium toxicity symptoms, beyond diarrhea and nausea, include mental abnormalities, cardiac problems, reduced reflexes, and breathing difficulties.
Magnesium Supplements at a Glance
• Adult RDA: 420 mg (male), 320 mg (female)
• Typical dose in supplement studies: 300–600 mg (optimal doses for each application are not well characterized)
• Best supplement complex: Organics are generally considered more active than inorganics, except chloride liquid; however, actual data is conflicting, possibly due to limitations in methodology. Data is also conflicting for comparisons among organics. Amino acid chelates and lactate are among the best for GI tolerance. Certain magnesium complexes may work best for specialized applications.
• Applications:
◦ Use is established for treating substantial hypomagnesemia.
◦ Many other uses have some rationale, but are unconfirmed.
◦ The best supported of the unconfirmed uses are:
▪ Producing various benefits in diabetic subjects with low serum magnesium.
▪ Modest lowering of blood pressure in certain types of people.
▪ Giving various benefits in cardiac rehabilitation patients (though one study may show a use risk).
▪ Treatment of sickle cell anemia (though supplementation has been studied in just a few people).
• Upper Level: 350 mg from supplements (based on GI tract symptoms). People may be able to exceed the UL without symptoms with magnesium from foods, with certain types of supplements, and possibly by spacing out daily doses.
• Safety issues: Typical supplement doses are considered safe for people with good kidney function except for GI symptoms, especially diarrhea.
Summary and Conclusions
Despite mounds of study on magnesium in general and on supplementation in particular, very little can be said definitively about the efficacy of magnesium supplements. The only established use for supplementation is for treatment of substantial hypomagnesemia due to “classical reasons,” such as the use of certain diuretic drugs. Many other applications may be useful, but this cannot be confirmed because so many studies are too small, too conflicting in results, too hard to interpret, too poorly designed, or simply require more follow-up.