Also, provide a title for this work . Be specific, don't fill with irrelevant information. Be advanced, not basic generalized answers. Identify the key information needed to answer the question you selected before starting to write. Be systematic, precise, and succinct. The information and analysis must use the sources provided below which msut be cited as in text citations (the sources are provided below). All the sources must be used and cited as in text ciations. 
3) You are not allowed to use figures of styles. Avoid using adverbs
 4) DO NOT USE enumeration. This act or process of making or stating a list of things one after another not allowed. This is very important; enumerations are not allowed at all, so make sure the work does not contain enumerations 
5) Ensure a diversity of length and sentence structure between sentences in order to imitate a human style of writing. When it comes to writing content, two factors are crucial, "perplexity" and "burstiness." Perplexity measures the complexity of text. Separately, burstiness compares the variations of sentences. Humans tend to write with greater burstiness, for example, with some longer or complex sentences alongside shorter ones. AI sentences tend to be more uniform. Therefore, when writing the following content I am going to ask you to create, I need it to have a good amount of perplexity and burstiness 

Don’t forget to not be shorter than 100 words per each element requested  and use all the headings and answer as below.
The electrolye chosen is: Magnesium 

In the table below, include the following information for the electrolyte you selected.
•	Normal range of the lab value 
•	Causes of excess (hyper) and deficiency (hypo)
•	Signs and symptoms of excess (hyper) and deficiency (hypo)


Article 1:
NIH. (2024). Office of Dietary Supplements—Magnesium. https://ods.od.nih.gov/factsheets/magnesium-healthprofessional/

Introduction
Magnesium, an abundant mineral in the body, is naturally present in many foods, added to other food products, available as a dietary supplement, and present in some medicines (such as antacids and laxatives). Magnesium is a cofactor in more than 300 enzyme systems that regulate diverse biochemical reactions in the body, including protein synthesis, muscle and nerve function, blood glucose control, and blood pressure regulation [1-3]. Magnesium is required for energy production, oxidative phosphorylation, and glycolysis. It contributes to the structural development of bone and is required for the synthesis of DNA, RNA, and the antioxidant glutathione. Magnesium also plays a role in the active transport of calcium and potassium ions across cell membranes, a process that is important to nerve impulse conduction, muscle contraction, and normal heart rhythm [3].
An adult body contains approximately 25 g magnesium, with 50% to 60% present in the bones and most of the rest in soft tissues [4]. Less than 1% of total magnesium is in blood serum, and these levels are kept under tight control. Normal serum magnesium concentrations range between 0.75 and 0.95 millimoles (mmol)/L [1,5]. Hypomagnesemia is defined as a serum magnesium level less than 0.75 mmol/L [6]. Magnesium homeostasis is largely controlled by the kidney, which typically excretes about 120 mg magnesium into the urine each day [2]. Urinary excretion is reduced when magnesium status is low [1].
Assessing magnesium status is difficult because most magnesium is inside cells or in bone [3]. The most commonly used and readily available method for assessing magnesium status is measurement of serum magnesium concentration, even though serum levels have little correlation with total body magnesium levels or concentrations in specific tissues [6]. Other methods for assessing magnesium status include measuring magnesium concentrations in erythrocytes, saliva, and urine; measuring ionized magnesium concentrations in blood, plasma, or serum; and conducting a magnesium-loading (or tolerance) test. No single method is considered satisfactory [7]. Some experts [4] but not others [3] consider the tolerance test (in which urinary magnesium is measured after parenteral infusion of a dose of magnesium) to be the best method to assess magnesium status in adults. To comprehensively evaluate magnesium status, both laboratory tests and a clinical assessment might be required [6].
Recommended Intakes
Intake recommendations for magnesium and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the Food and Nutrition Board (FNB) at the Institute of Medicine of the National Academies (formerly National Academy of Sciences) [1]. DRI is the general term for a set of reference values used to plan and assess nutrient intakes of healthy people. These values, which vary by age and sex, include the following:
•	Recommended Dietary Allowance (RDA): Average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals; often used to plan nutritionally adequate diets for individuals
•	Adequate Intake (AI): Intake at this level is assumed to ensure nutritional adequacy; established when evidence is insufficient to develop an RDA
•	Estimated Average Requirement (EAR): Average daily level of intake estimated to meet the requirements of 50% of healthy individuals; usually used to assess the nutrient intakes of groups of people and to plan nutritionally adequate diets for them; can also be used to assess the nutrient intakes of individuals
•	Tolerable Upper Intake Level (UL): Maximum daily intake unlikely to cause adverse health effects
Table 1 lists the current RDAs for magnesium [1]. For infants from birth to 12 months, the FNB established an AI for magnesium that is equivalent to the mean intake of magnesium in healthy, breastfed infants, with added solid foods for ages 7–12 months.
Table 1: Recommended Dietary Allowances (RDAs) for Magnesium [1]

Age	Male	Female	Pregnancy	Lactation
Birth to 6 months	30 mg*	30 mg*		
7–12 months	75 mg*	75 mg*		
1–3 years	80 mg	80 mg		
4–8 years	130 mg	130 mg		
9–13 years	240 mg	240 mg		
14–18 years	410 mg	360 mg	400 mg	360 mg
19–30 years	400 mg	310 mg	350 mg	310 mg
31–50 years	420 mg	320 mg	360 mg	320 mg
51+ years	420 mg	320 mg		
*Adequate Intake (AI)
Sources of Magnesium
Food
Magnesium is widely distributed in plant and animal foods and in beverages. Green leafy vegetables, such as spinach, legumes, nuts, seeds, and whole grains, are good sources [1,3]. In general, foods containing dietary fiber provide magnesium. Magnesium is also added to some breakfast cereals and other fortified foods. Some types of food processing, such as refining grains in ways that remove the nutrient-rich germ and bran, lower magnesium content substantially [1]. Selected food sources of magnesium are listed in Table 2.
Tap, mineral, and bottled waters can also be sources of magnesium, but the amount of magnesium in water varies by source and brand (ranging from 1 mg/L to more than 120 mg/L) [8].
Approximately 30% to 40% of the dietary magnesium consumed is typically absorbed by the body [2,9].
Table 2: Magnesium Content of Selected Foods [10]

Food	Milligrams
(mg) per
serving	Percent
DV*
Pumpkin seeds, roasted, 1 ounce	156	37
Chia seeds, 1 ounce	111	26
Almonds, dry roasted, 1 ounce	80	19
Spinach, boiled, ½ cup	78	19
Cashews, dry roasted, 1 ounce	74	18
Peanuts, oil roasted, ¼ cup	63	15
Cereal, shredded wheat, 2 large biscuits	61	15
Soymilk, plain or vanilla, 1 cup	61	15
Black beans, cooked, ½ cup	60	14
Edamame, shelled, cooked, ½ cup	50	12
Peanut butter, smooth, 2 tablespoons	49	12
Potato, baked with skin, 3.5 ounces	43	10
Rice, brown, cooked, ½ cup	42	10
Yogurt, plain, low fat, 8 ounces	42	10
Breakfast cereals, fortified with 10% of the DV for magnesium, 1 serving	42	10
Oatmeal, instant, 1 packet	36	9
Kidney beans, canned, ½ cup	35	8
Banana, 1 medium	32	8
Salmon, Atlantic, farmed, cooked, 3 ounces	26	6
Milk, 1 cup	24–27	6
Halibut, cooked, 3 ounces	24	6
Raisins, ½ cup	23	5
Bread, whole wheat, 1 slice	23	5
Avocado, cubed, ½ cup	22	5
Chicken breast, roasted, 3 ounces	22	5
Beef, ground, 90% lean, pan broiled, 3 ounces	20	5
Broccoli, chopped and cooked, ½ cup	12	3
Rice, white, cooked, ½ cup	10	2
Apple, 1 medium	9	2
Carrot, raw, 1 medium	7	2
*DV = Daily Value. The U.S. Food and Drug Administration (FDA) developed DVs to help consumers compare the nutrient contents of foods and dietary supplements within the context of a total diet. The DV for magnesium is 420 mg for adults and children age 4 years and older [11]. FDA does not require food labels to list magnesium content unless magnesium has been added to the food. Foods providing 20% or more of the DV are considered to be high sources of a nutrient, but foods providing lower percentages of the DV also contribute to a healthful diet.
The U.S. Department of Agriculture’s (USDA’s) FoodData Central  [10] lists the nutrient content of many foods and provides comprehensive list of foods containing magnesium arranged by nutrient content and by food name.
Dietary supplements
Magnesium supplements are available in a variety of forms, including magnesium oxide, citrate, and chloride [2,3]. The Supplement Facts panel on a dietary supplement label declares the amount of elemental magnesium in the product, not the weight of the entire magnesium-containing compound.
Absorption of magnesium from different kinds of magnesium supplements varies. Forms of magnesium that dissolve well in liquid are more completely absorbed in the gut than less soluble forms [2,12]. Small studies have found that magnesium in the aspartate, citrate, lactate, and chloride forms is absorbed more completely and is more bioavailable than magnesium oxide and magnesium sulfate [12-16]. One study found that very high doses of zinc from supplements (142 mg/day) can interfere with magnesium absorption and disrupt the magnesium balance in the body [17].
Medicines
Magnesium is a primary ingredient in some laxatives [18]. Phillips’ Milk of Magnesia, for example, provides 500 mg elemental magnesium (as magnesium hydroxide) per tablespoon; the directions advise taking up to 4 tablespoons/day for adolescents and adults [19]. (Although such a dose of magnesium is well above the safe upper level, some of the magnesium is not absorbed because of the medication’s laxative effect.) Magnesium is also included in some remedies for heartburn and upset stomach due to acid indigestion [18]. Extra-strength Rolaids, for example, provides 55 mg elemental magnesium (as magnesium hydroxide) per tablet [20], although Tums is magnesium free [21].
Magnesium Intakes and Status
Dietary surveys of people in the United States consistently show that many people consume less than recommended amounts of magnesium. An analysis of data from the National Health and Nutrition Examination Survey (NHANES) of 2013–2016 found that 48% of Americans of all ages ingest less magnesium from food and beverages than their respective EARs; adult men age 71 years and older and adolescent males and females are most likely to have low intakes [22]. In a study using data from NHANES 2003–2006 to assess mineral intakes among adults, average intakes of magnesium from food alone were higher among users of dietary supplements (350 mg for men and 267 mg for women, equal to or slightly exceeding their respective EARs) than among nonusers (268 mg for men and 234 for women) [23]. When supplements were included, average total intakes of magnesium were 449 mg for men and 387 mg for women, well above EAR levels.
No current data on magnesium status in the United States are available. Determining dietary intake of magnesium is the usual proxy for assessing magnesium status. NHANES has not determined serum magnesium levels in its participants since 1974 [24], and magnesium is not evaluated in routine electrolyte testing in hospitals and clinics [2].
Magnesium Deficiency
Symptomatic magnesium deficiency due to low dietary intake in otherwise-healthy people is uncommon because the kidneys limit urinary excretion of this mineral [3]. However, habitually low intakes or excessive losses of magnesium due to certain health conditions, chronic alcoholism, and/or the use of certain medications can lead to magnesium deficiency.
Early signs of magnesium deficiency include loss of appetite, nausea, vomiting, fatigue, and weakness. As magnesium deficiency worsens, numbness, tingling, muscle contractions and cramps, seizures, personality changes, abnormal heart rhythms, and coronary spasms can occur [1,2]. Severe magnesium deficiency can result in hypocalcemia or hypokalemia (low serum calcium or potassium levels, respectively) because mineral homeostasis is disrupted [2].
Groups at Risk of Magnesium Inadequacy
Magnesium inadequacy can occur when intakes fall below the RDA but are above the amount required to prevent overt deficiency. The following groups are more likely than others to be at risk of magnesium inadequacy because they typically consume insufficient amounts or they have medical conditions (or take medications) that reduce magnesium absorption from the gut or increase losses from the body.
People with gastrointestinal diseases
The chronic diarrhea and fat malabsorption resulting from Crohn’s disease, gluten-sensitive enteropathy (celiac disease), and regional enteritis can lead to magnesium depletion over time [2]. Resection or bypass of the small intestine, especially the ileum, typically leads to malabsorption and magnesium loss [2].
People with type 2 diabetes
Magnesium deficits and increased urinary magnesium excretion can occur in people with insulin resistance and/or type 2 diabetes [25,26]. The magnesium loss appears to be secondary to higher concentrations of glucose in the kidney that increase urine output [2].
People with alcohol dependence
Magnesium deficiency is common in people with chronic alcoholism [2]. In these individuals, poor dietary intake and nutritional status; gastrointestinal problems, including vomiting, diarrhea, and steatorrhea (fatty stools) resulting from pancreatitis; renal dysfunction with excess excretion of magnesium into the urine; phosphate depletion; vitamin D deficiency; acute alcoholic ketoacidosis; and hyperaldosteronism secondary to liver disease can all contribute to decreased magnesium status [2,27].
Older adults
Older adults have lower dietary intakes of magnesium than younger adults [21,28]. In addition, magnesium absorption from the gut decreases and renal magnesium excretion increases with age [29]. Older adults are also more likely to have chronic diseases or take medications that alter magnesium status, which can increase their risk of magnesium depletion [1,30].
Magnesium and Health
Habitually low intakes of magnesium induce changes in biochemical pathways that can increase the risk of illness over time. This section focuses on four diseases and disorders in which magnesium might be involved: hypertension and cardiovascular disease, type 2 diabetes, osteoporosis, and migraine headaches.
Hypertension and cardiovascular disease
Hypertension is a major risk factor for heart disease and stroke. Studies to date, however, have found that magnesium supplementation lowers blood pressure, at best, to only a small extent. A meta-analysis of 12 clinical trials found that magnesium supplementation for 8–26 weeks in 545 hypertensive participants resulted in only a small reduction (2.2 mmHg) in diastolic blood pressure [31]. The dose of magnesium ranged from approximately 243 to 973 mg/day. The authors of another meta-analysis of 22 studies with 1,173 normotensive and hypertensive adults concluded that magnesium supplementation for 3–24 weeks decreased systolic blood pressure by 3–4 mmHg and diastolic blood pressure by 2–3 mmHg [32]. The effects were somewhat larger when supplemental magnesium intakes of the participants in the nine crossover-design trials exceeded 370 mg/day. A diet containing more magnesium because of added fruits and vegetables, more low-fat or nonfat dairy products, and less fat overall was shown to lower systolic and diastolic blood pressure by an average of 5.5 and 3.0 mmHg, respectively [33]. However, this Dietary Approaches to Stop Hypertension (DASH) diet also increases intakes of other nutrients, such as potassium and calcium, that are associated with reductions in blood pressure, so any independent contribution of magnesium cannot be determined.
In 2022, FDA approved a qualified health claim for conventional foods and dietary supplements that contain magnesium [34]. One example of this claim states, “Consuming diets with adequate magnesium may reduce the risk of high blood pressure (hypertension). However, FDA has concluded that the evidence is inconsistent and inconclusive.” FDA also specifies that foods and dietary supplements carrying this claim on their labels must provide at least 84 mg of magnesium per serving and, for dietary supplements, no more than 350 mg.
Several prospective studies have examined associations between magnesium intakes and heart disease. The Atherosclerosis Risk in Communities study assessed heart disease risk factors and levels of serum magnesium in a cohort of 14,232 White and African-American men and women age 45 to 64 years at baseline [35]. Over an average of 12 years of follow-up, individuals in the highest quartile of the normal physiologic range of serum magnesium (at least 0.88 mmol/L) had a 38% reduced risk of sudden cardiac death compared with individuals in the lowest quartile (0.75 mmol/L or less). However, dietary magnesium intakes had no association with risk of sudden cardiac death. Another prospective study tracked 88,375 female nurses in the United States to determine whether serum magnesium levels measured early in the study and magnesium intakes from food and supplements assessed every 2 to 4 years were associated with sudden cardiac death over 26 years of follow-up [36]. Women in the highest compared with the lowest quartile of ingested and plasma magnesium concentrations had a 34% and 77% lower risk of sudden cardiac death, respectively. Another prospective population study of 7,664 adults age 20 to 75 years in the Netherlands who did not have cardiovascular disease found that low urinary magnesium excretion levels (a marker for low dietary magnesium intake) were associated with a higher risk of ischemic heart disease over a median follow-up period of 10.5 years. Plasma magnesium concentrations were not associated with risk of ischemic heart disease [37]. A systematic review and meta-analysis of prospective studies found that higher serum levels of magnesium were significantly associated with a lower risk of cardiovascular disease, and higher dietary magnesium intakes (up to approximately 250 mg/day) were associated with a significantly lower risk of ischemic heart disease caused by a reduced blood supply to the heart muscle [38].
Higher magnesium intakes might reduce the risk of stroke. In a meta-analysis of seven prospective trials with a total of 241,378 participants, an additional 100 mg/day magnesium in the diet was associated with an 8% decreased risk of total stroke, especially ischemic rather than hemorrhagic stroke [39]. One limitation of such observational studies, however, is the possibility of confounding with other nutrients or dietary components that could also affect the risk of stroke.
A large, well-designed clinical trial is needed to better understand the contributions of magnesium from food and dietary supplements to heart health and the primary prevention of cardiovascular disease [40].
Type 2 diabetes
Diets with higher amounts of magnesium are associated with a significantly lower risk of diabetes, possibly because of the important role of magnesium in glucose metabolism [41,42]. Hypomagnesemia might worsen insulin resistance, a condition that often precedes diabetes, or it might be a consequence of insulin resistance [43]. Diabetes leads to increased urinary losses of magnesium, and the subsequent magnesium inadequacy might impair insulin secretion and action, thereby worsening diabetes control [3].
Most investigations of magnesium intake and risk of type 2 diabetes have been prospective cohort studies. A meta-analysis of seven of these studies, which included 286,668 patients and 10,912 cases of diabetes over 6 to 17 years of follow-up, found that a 100 mg/day increase in total magnesium intake decreased the risk of diabetes by a statistically significant 15% [41]. Another meta-analysis of eight prospective cohort studies that followed 271,869 men and women over 4 to 18 years found a significant inverse association between magnesium intake from food and risk of type 2 diabetes; the relative risk reduction was 23% when the highest to lowest intakes were compared [44].
A 2011 meta-analysis of prospective cohort studies of the association between magnesium intake and risk of type 2 diabetes included 13 studies with a total of 536,318 participants and 24,516 cases of diabetes [45]. The mean length of follow-up ranged from 4 to 20 years. Investigators found an inverse association between magnesium intake and risk of type 2 diabetes in a dose-responsive fashion, but this association achieved statistical significance only in individuals who were overweight (body mass index [BMI] 25 or higher) but not in normal-weight individuals (BMI less than 25). Again, a limitation of these observational studies is the possibility of confounding with other dietary components or lifestyle or environmental variables that are correlated with magnesium intake.
Only a few small, short-term clinical trials have examined the potential effects of supplemental magnesium on control of type 2 diabetes and the results are conflicting [42,46]. For example, 128 patients with poorly controlled diabetes in a Brazilian clinical trial received a placebo or a supplement containing either 500 mg/day or 1,000 mg/day magnesium oxide (providing 300 or 600 mg elemental magnesium, respectively) [47]. After 30 days of supplementation, plasma, cellular, and urine magnesium levels increased in participants receiving the larger dose of the supplement, and their glycemic control improved. In another small trial in Mexico, participants with type 2 diabetes and hypomagnesemia who received a liquid supplement of magnesium chloride (providing 300 mg/day elemental magnesium) for 16 weeks showed significant reductions in fasting glucose and glycosylated hemoglobin concentrations compared with participants receiving a placebo, and their serum magnesium levels became normal [48]. In contrast, neither a supplement of magnesium aspartate (providing 369 mg/day elemental magnesium) nor a placebo taken for 3 months had any effect on glycemic control in 50 patients with type 2 diabetes who were taking insulin [49].
The American Diabetes Association states that there is insufficient evidence to support the routine use of magnesium to improve glycemic control in people with diabetes [46]. It further notes that there is no clear scientific evidence that vitamin and mineral supplementation benefits people with diabetes who do not have underlying nutritional deficiencies.
Osteoporosis
Magnesium is involved in bone formation and influences the activities of osteoblasts and osteoclasts [50]. Magnesium also affects the concentrations of both parathyroid hormone and the active form of vitamin D, which are major regulators of bone homeostasis. Several population-based studies have found positive associations between magnesium intake and bone mineral density in both men and women [51]. Other research has found that women with osteoporosis have lower serum magnesium levels than women with osteopenia and those who do not have osteoporosis or osteopenia [52]. These and other findings indicate that magnesium deficiency might be a risk factor for osteoporosis [50].
Although limited in number, studies suggest that increasing magnesium intakes from food or supplements might increase bone mineral density in postmenopausal and elderly women [1]. For example, one short-term study found that 290 mg/day elemental magnesium (as magnesium citrate) for 30 days in 20 postmenopausal women with osteoporosis suppressed bone turnover compared with placebo, suggesting that bone loss decreased [53].
Diets that provide recommended levels of magnesium enhance bone health, but further research is needed to elucidate the role of magnesium in the prevention and management of osteoporosis.
Migraine headaches
Magnesium deficiency is related to factors that promote headaches, including neurotransmitter release and vasoconstriction [54]. People who experience migraine headaches have lower levels of serum and tissue magnesium than those who do not.
However, research on the use of magnesium supplements to prevent or reduce symptoms of migraine headaches is limited. Three of four small, short-term, placebo-controlled trials found modest reductions in the frequency of migraines in patients given up to 600 mg/day magnesium [54]. The authors of a review on migraine prophylaxis suggested that taking 300 mg magnesium twice a day, either alone or in combination with medication, can prevent migraines [55].
In their evidence-based guideline update, the American Academy of Neurology and the American Headache Society concluded that magnesium therapy is probably effective for migraine prevention [56]. Because the typical dose of magnesium used for migraine prevention exceeds the UL, this treatment should be used only under the direction and supervision of a health care provider.
Health Risks from Excessive Magnesium
Too much magnesium from food does not pose a health risk in healthy individuals because the kidneys eliminate excess amounts in the urine [29]. However, high doses of magnesium from dietary supplements or medications often result in diarrhea that can be accompanied by nausea and abdominal cramping [1]. Forms of magnesium most commonly reported to cause diarrhea include magnesium carbonate, chloride, gluconate, and oxide [12]. The diarrhea and laxative effects of magnesium salts are due to the osmotic activity of unabsorbed salts in the intestine and colon and the stimulation of gastric motility [57].
Very large doses of magnesium-containing laxatives and antacids (typically providing more than 5,000 mg/day magnesium) have been associated with magnesium toxicity [58], including fatal hypermagnesemia in a 28-month-old boy [59] and an elderly man [60]. Symptoms of magnesium toxicity, which usually develop after serum concentrations exceed 1.74–2.61 mmol/L, can include hypotension, nausea, vomiting, facial flushing, retention of urine, ileus, depression, and lethargy before progressing to muscle weakness, difficulty breathing, extreme hypotension, irregular heartbeat, and cardiac arrest [29]. The risk of magnesium toxicity increases with impaired renal function or kidney failure because the ability to remove excess magnesium is reduced or lost [1,29].
The FNB has established ULs for supplemental magnesium for healthy infants, children, and adults (see Table 3) [1]. For many age groups, the UL appears to be lower than the RDA. This occurs because the RDAs include magnesium from all sources—food, beverages, dietary supplements, and medications. The ULs include magnesium from only dietary supplements and medications; they do not include magnesium found naturally in food and beverages.
Table 3: Tolerable Upper Intake Levels (ULs) for Supplemental Magnesium [1]

Age	Male	Female	Pregnant	Lactating
Birth to 12 months	None established	None established		
1–3 years	65 mg	65 mg		
4–8 years	110 mg	110 mg		
9–18 years	350 mg	350 mg	350 mg	350 mg
19+ years	350 mg	350 mg	350 mg	350 mg
 
Interactions with Medications
Several types of medications have the potential to interact with magnesium supplements or affect magnesium status. A few examples are provided below. People taking these and other medications on a regular basis should discuss their magnesium intakes with their health care providers.
Bisphosphonates
Magnesium-rich supplements or medications can decrease the absorption of oral bisphosphonates, such as alendronate (Fosamax), used to treat osteoporosis [61]. Use of magnesium-rich supplements or medications and oral bisphosphonates should be separated by at least 2 hours [57].
Antibiotics
Magnesium can form insoluble complexes with tetracyclines, such as demeclocycline (Declomycin) and doxycycline (Vibramycin) as well as quinolone antibiotics, such as ciprofloxacin (Cipro) and levofloxacin (Levaquin). These antibiotics should be taken at least 2 hours before or 4–6 hours after a magnesium-containing supplement [57,62].
Diuretics
Chronic treatment with loop diuretics, such as furosemide (Lasix) and bumetanide (Bumex), and thiazide diuretics, such as hydrochlorothiazide (Aquazide H) and ethacrynic acid (Edecrin), can increase the loss of magnesium in urine and lead to magnesium depletion [63]. In contrast, potassium-sparing diuretics, such as amiloride (Midamor) and spironolactone (Aldactone), reduce magnesium excretion [63].
Proton pump inhibitors
Prescription proton pump inhibitor (PPI) drugs, such as esomeprazole magnesium (Nexium) and lansoprazole (Prevacid), when taken for prolonged periods (typically more than a year) can cause hypomagnesemia [64]. In cases that FDA reviewed, magnesium supplements often raised the low serum magnesium levels caused by PPIs. However, in 25% of the cases, supplements did not raise magnesium levels and the patients had to discontinue the PPI. FDA advises health care professionals to consider measuring patients’ serum magnesium levels prior to initiating long-term PPI treatment and to check magnesium levels in these patients periodically [64].
Magnesium and Healthful Diets
The federal government’s 2020–2025 Dietary Guidelines for Americans notes that “Because foods provide an array of nutrients and other components that have benefits for health, nutritional needs should be met primarily through foods. … In some cases, fortified foods and dietary supplements are useful when it is not possible otherwise to meet needs for one or more nutrients (e.g., during specific life stages such as pregnancy).”
For more information about building a healthy dietary pattern, refer to the Dietary Guidelines for Americans  and the USDA’s MyPlate. 
The Dietary Guidelines for Americans describes a healthy dietary pattern as one that
•	Includes a variety of vegetables; fruits; grains (at least half whole grains); fat-free and low-fat milk, yogurt, and cheese; and oils.
o	Whole grains and dark-green, leafy vegetables are good sources of magnesium. Low-fat milk and yogurt contain magnesium as well. Some ready-to-eat breakfast cereals are fortified with magnesium.
•	Includes a variety of protein foods such as lean meats; poultry; eggs; seafood; beans, peas, and lentils; nuts and seeds; and soy products.
o	Dried beans and legumes (such as soybeans, baked beans, lentils, and peanuts) and nuts (such as almonds and cashews) provide magnesium.
•	Limits foods and beverages higher in added sugars, saturated fat, and sodium.
•	Limits alcoholic beverages.
•	Stays within your daily calorie needs.

Article 2:
Allen, M. J., & Sharma, S. (2024). Magnesium. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK519036/
Magnesium
Mary J. Allen; Sandeep Sharma.
Author Information and Affiliations
Last Update: February 20, 2023.
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Continuing Education Activity
Magnesium use is indicated for a variety of diseases. This is due to the variety of effects magnesium has within the body. Administration of magnesium can be divided into FDA versus non-FDA approved. Also, magnesium is commonly used in over-the-counter products. This activity will highlight the mechanism of action, adverse event profile, pharmacology, monitoring, and relevant interactions of magnesium, pertinent for interprofessional team members in treating patients with conditions where magnesium is indicated.
Objectives:
•	Identify the physiological processes in which magnesium is involved.
•	Summarize the indications for endogenously administered magnesium therapy.
•	Explain the contraindications and toxicity of magnesium therapy.
•	Describe some interprofessional team strategies for improving care coordination and communication to properly use magnesium to improve patient outcomes in the varied scenarios where magnesium is effective.
Access free multiple choice questions on this topic.
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Indications
Magnesium use is indicated for a variety of diseases. This is due to the variety of effects magnesium has within the body. Administration of magnesium can be divided into FDA versus non-FDA approved. Also, magnesium is commonly used in over-the-counter products.[1][2][3][4] Normal serum blood magnesium levels are between 1.8 and 2.2 mg/dL.
Hypomagnesemia: Magnesium Concentration of Less Than 1.8 mg/dL
•	Magnesium depletion can result from inadequate intake, decreased renal absorption, or impaired gastrointestinal (GI) absorption.
•	Risk factors for hypomagnesemia include those with GI disease, chronic diarrhea, proton pump inhibitor therapy, alcohol use disorder, and diuretic use, both loop and thiazide. It is common to see hypomagnesemia along with low levels of other electrolytes, such as hypokalemia and hypocalcemia. In patients with refractory hypokalemia or hypocalcemia, hypomagnesemia may be the reason. It is difficult to correct these electrolyte imbalances without first treating the magnesium imbalance.[5]
•	Symptoms of hypomagnesemia correlate with the development of concurrent hypocalcemia. The signs include Trousseau sign, Chvostek sign, hyperreflexia, tremor, and muscle fasciculations. Patients may also experience vague symptoms such as nausea, vomiting, lethargy, and weakness. Severe hypomagnesemia, less than 1.25 mg/dL, can result in generalized tonic-clonic seizures.[5]
Eclampsia or Severe Pre-Eclampsia
•	Magnesium is given to those with severe pre-eclampsia to prevent seizures and those with eclampsia to control seizures.[6]
Constipation
•	Over-the-counter laxatives, such as Milk of Magnesia, commonly contain magnesium.
Pre-Term Labor (Off-Label Use)
•	Magnesium can be given as a tocolytic to stop the progression of pre-term labor.[5]
Arrhythmias (Off-Label Use)
•	Administration of magnesium is recommended in certain arrhythmias such as torsades de pointes, digoxin-associated arrhythmia, ventricular arrhythmias like ventricular fibrillation, and ventricular tachycardia.[7]
Asthma: Acute Severe Exacerbation (Off-Label Use)
•	Magnesium is recommended as adjunctive therapy for patients with severe, life-threatening exacerbation or refractory cases after 1 hour of intensive conventional therapy. Magnesium allows bronchial smooth muscle relaxation, which aids in patients with status asthmatics.
Migraines: Over the Counter Supplementation 
•	The use of magnesium in migraines is limited at this moment. Hypomagnesemia has been found in patients with migraines. Supplemental magnesium is considered an inexpensive, simple preventive treatment option for some. However, the dosage required is above the daily requirement, thus potentially leading to hypermagnesemia. The American Academy of Neurology and the American Headache Society have stated that magnesium therapy is “probably effective” for migraine prevention.[8]
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Mechanism of Action
As with other electrolytes, magnesium's role in the body is diverse and complex. The mechanism of action of magnesium is dependent on which organ system is involved and the formulation used.Physiology of Magnesium
•	Magnesium is the fourth most common cation in the body. The majority of magnesium is intracellular; it is the second most common intracellular cation following potassium. Magnesium plays a vital role in over 300 reactions involving metabolism. It is involved with hormone receptor binding, muscle contraction, neural activity, neurotransmitter release, vasomotor tone, and cardiac excitability. It is necessary for the active transport of potassium and calcium across the cell membrane. ATP is dependent on magnesium for proper functioning.[5]
Effects of Magnesium
Gastrointestinal
•	Oral magnesium promotes defecation via osmotic retention of fluids. It is also used in over-the-counter antacids.[5]
Cardiovascular
•	Magnesium acts as a natural calcium channel blocker, and it is a cofactor of the Na-K-ATP pump. Magnesium helps control atrioventricular node conduction. Therefore, hypomagnesemia can cause myocardial excitability resulting in arrhythmias such as ventricular tachycardia and torsades de pointes.[5]
Neurological System
•	Magnesium depresses the central nervous system (CNS) while producing anticonvulsant effects. At neuromuscular junctions, it inhibits the release of acetylcholine, thus blocking peripheral neuromuscular transmission.[5]
Reproductive System
•	Magnesium is used as a tocolytic during pre-term labor. Magnesium stimulates calcium reuptake by the sarcoplasmic reticulum, which promotes relaxation of muscle and vasodilation. For pre-term labor, magnesium decreases the calcium within the uterine muscle.[5]
Musculoskeletal System
•	Magnesium is a cofactor of parathyroid hormone (PTH) synthesis. With hypomagnesemia, concurrent hypoparathyroidism will ensue. Hypoparathyroidism can lead to decreased calcium and eventually lead to osteopenia or osteoporosis.[5]
Respiratory System
•	Magnesium administration can cause bronchial smooth muscle relaxation. The cause of smooth muscle relaxation is unclear. It is thought to be either by inhibiting calcium, histamine, or acetylcholine release. There may also be a synergist effect with the concurrent use of beta-agonists.[5]
Hemostasis of Magnesium
•	Roughly 50% of magnesium is located within the bone, 25% is within the muscle, and the remainder is in soft tissue, serum, and red blood cells (RBC). Like other electrolytes, it can be classified as ionized, protein-bound, or bound to anions. Ionized magnesium is the most biological activity.
•	The intestine, bone, and kidney maintain magnesium homeostasis. Similar to calcium, magnesium is absorbed via the intestine, stored in the bone, excreted via the kidneys. The absorption of magnesium is inversely proportional to the concentration within the body; if there are low magnesium levels within the body, more magnesium will be absorbed.
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Administration
Administration of magnesium can occur in various ways. Dietary intake is the primary source of magnesium for a healthy individual. The recommended daily intake varies with gender and age. Green leafy vegetables, fish, legumes, and whole grains are good sources of magnesium.
Magnesium comes in various salts and forms, including magnesium oxide, magnesium citrate, magnesium sulfate, magnesium hydroxide, and magnesium gluconate.
•	Treatment can be via oral magnesium salts or intravenous (IV) or intramuscular (IM) magnesium sulfate. IV or IM magnesium sulfate is given for severe hypomagnesemia or those unable to tolerate or adhere to oral therapy.
•	Patients with alcohol use disorder are treated empirically to avoid hypomagnesemia. For patients with renal insufficiency, the clinician must increase the dose to adjust for the increase in renal loss.[5]
•	The clinician must also address concurrent hypokalemia or hypocalcemia.
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Adverse Effects
Adverse reactions are associated with magnesium’s effect on the neuromuscular and cardiovascular systems and can vary depending on the exact formulation. Effects can include the following:
•	Serious adverse events:
o	Cardiovascular collapse
o	Respiratory depression or paralysis
o	Hypothermia
o	Depressed cardiac function
o	Pulmonary edema
•	Common adverse events:
o	Flushing
o	Hypotension
o	Vasodilation
o	Impaired reflexes
o	Abdominal pain
o	Diarrhea
o	Flatulence
o	Nausea/vomiting
o	Respiratory depression
o	Electrolyte disorders (hypocalcemia, hyperkalemia)
o	Hypermagnesemia[9] 
Hypermagnesemia can be a serious adverse event, particularly as it pertains to cardiology effects; see the Toxicity section for more information. 
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Contraindications
For contraindications, factors to consider are renal function, pregnancy, and neuromuscular disease.
•	It is crucial to assess renal function before giving magnesium. Renal failure can cause decreased magnesium excretion leading to toxicity. Closely monitor magnesium levels in patients with reduced renal function.[2]
•	Patients with neuromuscular disease, such as myasthenia gravis need to be closely monitored if they are given magnesium. Magnesium inhibits the release of acetylcholine which can cause deterioration.
•	Magnesium is considered class D for pregnancy. Skeletal demineralization, hypocalcemia, and hypermagnesemia are seen with long-term use, more than 5 to 7 days, of magnesium, which is necessary for pre-term labor treatment.
•	There are no contraindications for magnesium supplements with other prescriptions. However, various drugs increase or decrease the concentration of either magnesium or the prescribed medication.
•	Magnesium may be used in pregnancy and lactation; there is no expected risk of fetal or infant harm based on limited data in humans.
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Monitoring
Hypermagnesemia may occur from overdose. Monitoring magnesium level is necessary while administering magnesium. Monitoring can be done on serum magnesium levels, as well as other electrolytes such as calcium and potassium.
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Toxicity
Hypermagnesemia: Serum Magnesium Concentration Greater Than 2.6 mg/dL
•	Hypermagnesemia is a potential effect of administering magnesium. If too much magnesium is administered too quickly, hypermagnesemia may ensue.
•	Symptoms include vasodilation causing flushing, hypotension, hyporeflexia, and respiratory depression. With a magnesium concentration above 6 mg/dL, ECG changes can consist of PR prolongation, widening of QRS, and peaked T waves. Cardiac arrest occurs whenever levels are above 15 mg/dL.[7][9][5]
•	Hypermagnesemia is less common than hypomagnesemia. The most significant cause of hypermagnesemia is renal failure causing increased retention of magnesium. It can also occur in the overuse of magnesium-containing laxatives and antacids.[2]
•	Treatment for hypermagnesemia includes calcium gluconate, diuresis, or dialysis. It is important to maintain circulatory and respiratory support for those with severe hypermagnesemia. IV furosemide is the diuretic of choice, as it increases magnesium excretion.[10][5]
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Enhancing Healthcare Team Outcomes
Magnesium is a vital mineral for many bodily functions. However, unless patients are diagnosed with hypomagnesemia, this mineral should not be empirically recommended by the prescribing clinicians, including MDs, DOs, NPs, and PAs. These days many people consume magnesium supplements because of a false understanding of correcting the condition. Excessive magnesium intake is not safe either, as it can lead to hypotension, hyporeflexia, and respiratory depression. With a magnesium concentration of above 6 mg/dL, ECG changes can include PR prolongation, widening of QRS, and peaked T waves. Cardiac arrest occurs whenever levels are above 15 mg/dL. When IV magnesium is administered, the nurse should constantly monitor the vital signs, especially blood pressure.[10] 
While magnesium is generally safe, given the potential for severe issues in specific cases, the entire interprofessional team needs to be aware of the patient's intake of supplemental magnesium and record such in the patient's health record. This way, the whole team can make medical decisions based on complete and accurate data. It is incumbent on each interprofessional team member to provide input based on their area of expertise and counsel the patient on the appropriate use of the drug. Pharmacists need to examine the possibility of drug-drug interactions and report to the prescriber as appropriate. An interprofessional approach involving clinicians, mid-level practitioners, pharmacists, and nursing staff, collaborating the activities, and openly sharing case information will provide the safest and most successful patient care. [Level 5]