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Magnesium Absorption and Bioavailability

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May, 2017    |

By Jon-Paul Powers, PHD

    Despite its essential role in human health, many modern diets are deficient in magnesium. As a result, many consumers select magnesium supplements as a convenient way to meet their daily requirements. Supplements contain a variety of inorganic and organic forms of magnesium, the effectiveness of which may depend upon their bioavailability in the body. Magnesium citrate, and other organic magnesium salts, have demonstrated superior bioavailability to inorganic magnesium salts. This makes magnesium citrate an effective source material for oral magnesium supplementation.
    MAGNESIUM AND HUMAN HEALTH

    ROLE AND BENEFITS OF MAGNESIUM

    Magnesium is an essential nutrient for the human body and is known to be involved in more than 300 biochemical reactions; affecting key processes such as energy production, bone development, maintaining electrolyte balance, muscle and heart function, as well as protein, DNA, and RNA synthesis. Magnesium also plays a role in the transport of sodium and potassium ions across cellular membranes. Recently, magnesium has also been demonstrated to improve bowel movement and frequency, thereby reducing functional constipation. More than half of the body’s 20–28g of stored magnesium is present in bones with the remainder residing in the soft tissues and, to a very minor extent (<1%), in the blood.

    DIETARY MAGNESIUM REQUIREMENTS

    Adults require approximately 310–420mg of magnesium daily, and deficiency may lead to irritability, muscle weakness, and irregular heartbeat. Most dietary magnesium typically comes from sources such as fruits, vegetables, leafy greens, seeds and grains. While magnesium is present in food sources, recent Health Canada findings suggest that many adults have an inadequate dietary intake of magnesium. Due to deficiencies in modern diets, many consumers select magnesium supplements as a convenient way to meet their daily requirements.
    MAGNESIUM SUPPLEMENTS
    FORMS OF MAGNESIUM IN SUPPLEMENTS

    Oral magnesium supplements are available in a variety of forms, with powders and capsules being the most common. The magnesium contained in these supplements may be from a variety of source materials or forms, generally grouped as follows:
    • Inorganic magnesium salts (such as oxides, carbonates, chlorides and hydroxides);
    • Organic magnesium salts (such as citrates, lactates, and gluconates); and
    • Magnesium complexes or chelates (such as amino acid chelates).

    From a formulation or manufacturing perspective, the selection of a specific magnesium source material may be chosen for a variety of reasons, including, but not limited to, cost, solubility and available capsule space. From a biological perspective, it should be noted that source material ultimately affects magnesium absorption and bioavailability.
    MAGNESIUM ABSORPTION
    The absorption of magnesium from oral supplementation occurs primarily in the small intestine with the majority of uptake occurring in the distal jejunum and the ileum. Once dissolved in the gastric fluid, magnesium salts dissociate, freeing the ionic magnesium. The majority of the magnesium ions in the intestinal tract are taken up through passive processes mediated by electrochemical gradients and solvent drag, but some uptake occurs via an active transport system. Once absorbed by the intestine, magnesium ions enter the bloodstream for transport to other tissues and organs.

    MEASURING MAGNESIUM ABSORPTION

    There are two common methods used to estimate absorption/bioavailability of ingested magnesium. The most widely available and practical way to determine intestinal magnesium absorption is by measuring blood serum magnesium levels. In serum magnesium analysis, acute changes in the magnesium status of an individual are detected by measuring the concentration of total serum magnesium following magnesium intake. Since serum magnesium does not correlate well with tissue pools of magnesium, this test is considered a poor predictor of intracellular or body magnesium content; however, it remains effective and reliable for measuring rapid extracellular changes in magnesium levels, and to assess intestinal absorption following an oral load of magnesium.

    Urinary analysis is another common method for assessing magnesium absorption. Once magnesium levels exceed a critical threshold in the kidney, the excess magnesium is excreted in the urine. In general, the assumption is that the uptake and release of magnesium are in balance; thus, by determining the concentration of magnesium excreted in the urine, one can estimate the amount of magnesium absorbed by the intestine. Drawbacks to this method of analysis are that test subjects must not be magnesium depleted, and timing of the analysis is critical.

    Other, less common, proxies for magnesium absorption include measuring an increase in salivary or erythrocyte magnesium concentrations. Stable isotopes of magnesium have also been used to track the absorption of magnesium by the body.

    MAGNESIUM CITRATE BIOAVAILABILITY

    The solubility of minerals in the digestive tract is a major factor driving their uptake. Because much of the absorption of magnesium is via passive transport, the greater the solubility of magnesium salt or complex that is in the gut, the greater the potential for magnesium ion dissociation and subsequent availability for uptake into the intestine. Thus, the solubility of the magnesium supplement factors in its overall bioavailability.
    Organic magnesium salts, such as magnesium citrate, are, in general, more soluble than inorganic magnesium salts. The enhanced solubility leads to a greater con- centration of magnesium ions in the intestinal tract. Because of this, supplements containing the highly soluble organic salt forms may be more absorbable by the body (and, therefore, more bioavailable) than inorganic salt forms. Indeed, in vitro and clinical studies have demonstrated the superior solubility and bioavailability of oral organic magnesium salts compared to the representative inorganic form, magnesium oxide. While most studies to date have used urinary magnesium levels as a measure of bioavailability, Wilimzig et al. (1996) further demonstrated that administration of oral magnesium citrate produced a direct increase in plasma magnesium concentrations in healthy volunteers.
    Magnesium citrate is regarded as a highly soluble and readily bioavailable form of magnesium. Studies in simulated gastric fluid demonstrate that magnesium citrate remains in solution even as pH increases. This is an important characteristic since the pH of the intestine increases as it progresses distally. The solubility of magnesium citrate in alkaline environments may enhance bioavailability by increasing the availability of free magnesium ions for passive uptake along the intestinal tract. This means that magnesium ions may remain bioavailable further along the intestinal tract, without the need for additional buffers, allowing more opportunity for transport through cellular membranes. Numerous in vitro studies have demonstrated the superior absorption of organic magnesium salts, including magnesium citrate, in comparison with inorganic salts.
    Furthermore, magnesium citrate was found to be both more soluble in simulated gastric acid, and more intestinally absorbable than magnesium oxide, as determined by urinary magnesium excretion analysis in healthy volunteers. The results of these parallel in vitro and in vivo tests suggest that magnesium citrate’s increased bioavailability relative to magnesium oxide may be a result of its enhanced solubility in the intestinal tract.
    Recently, magnesium in the form of amino acid chelates such as aspartate and bisglycinate (aka diglycinate) have been the focus of advertising campaigns. While these sources have been marketed as being more bioavailable than other common inorganic and organic forms, there is a lack of published data supporting these claims. On the contrary, Schuette et al. demonstrated that magnesium absorption did not differ between oxide or bisglycinate forms in a group of subjects who had undergone ileal resection. Furthermore, a detailed review of the bioavailability and pharmacokinetics of magnesium from a variety of sources suggest there is little, if any, difference between forms generally regarded as bioavailable (e.g. citrate and glycinate).
    In perhaps the best study design to date, the bioavailability of magnesium citrate was found to be superior to both magnesium oxide and a magnesium amino acid chelate. Researchers conducted a parallel intervention study to compare the relative absorbability and bioequivalence of three forms of magnesium (oxide, citrate and amino acid chelate) under acute (24-hour) and chronic (60-day) administration of an oral daily dosage. Subjects were generally healthy and free of conditions or activities known to affect magnesium metabolism and were administered cellulose or sorbitol placebo or 300mg elemental magnesium per day from one of the following sources: magnesium amino acid chelate, magnesium citrate, magnesium oxide.

    Treatment effects were assessed via urinary magnesium excretion, plasma magnesium concentration, erythrocyte magnesium concentration or salivary magnesium con- centration. Chronic supplementation with organic forms of magnesium (magnesium citrate and magnesium amino acid chelate) resulted in a significant increase in urinary magnesium excretion compared to either placebo or magnesium oxide, which is an indirect measure of the increased bioavailability of magnesium citrate.

    As further evidence of the increased bioavailability of magnesium citrate both mean plasma and salivary magnesium concentrations were assayed. Only magnesium citrate was found to produce statistically significant increases compared to all other groups following chronic administration. While this study was designed to determine the differences in magnesium supplementation compared to placebo, it does suggest that supplementation with magnesium citrate may be superior to supplementation with both magnesium oxide and amino acid chelate forms (e.g. bisglycinate, etc.).
    CONCLUSION
    Organic magnesium salts, such as magnesium citrate, are highly soluble in the intestinal tract, which leads to high concentrations of ionic magnesium that can be absorbed by the body. In addition, the enhanced bioavailability of magnesium citrate compared with inorganic magnesium salts (oxides, carbonates, chlorides and hydroxides) is well supported. Furthermore, recent investigations have demonstrated magnesium citrate to be equally or even more bioavailable than amino acid chelates. Therefore, due to its solubility, and its superior bioavailability, magnesium citrate is a highly effective form of magnesium supplementation.
    WHAT’S IN YOUR SALES?
    Not all magnesium supplements are made the same, so knowing what is on your shelves is just as important as selling the product. What you give to your customers and patients reflects your values as a business. With absorption levels ranging from four to 50 per cent, the optimal selling point is that you are offering your clientele the best product on the market. After all, they chose your business over a large corporate chain for a reason. While 50 per cent may not seem all that great, the body does not absorb 100 per cent of anything. The best option is to go for something that is known to have
    a higher absorption level—certain supplements have a better rate due to water solubility. As such, it is imperative to understand what you’re really selling, both for your clients and your bottom line.

    COMMENTARY BY: DAVID FOREMAN, RPH, ND HERBAL PHARMACIST

    Magnesium is one of the supplements that is often overlooked when looking at a patient’s health. Yet, people are actually facing many health issues that have a direct connection to magnesium deficiency being a key-contributing factor. While magnesium deficiency can be tested for, it often is omitted.
    People who are often significantly deficient or at risk of deficiency fall into these conditions or groups:

    ¥ Chronic gastrointestinal issues:
    Crohn’s, Celiac disease, IBS with
    Diarrhea, etc.

    ¥ Alcohol dependency

    ¥ Type 2 diabetics

    ¥ Elderly

    ¥ People with a diet high in refined/processed foods

    Magnesium is a cofactor in biochemical reactions such as; neurotransmitter production, protein synthesis, muscle and nerve production, blood sugar control, blood pressure regulation, nerve impulses, muscle contraction and relaxation, heart rhythm, energy production, DNA and RNA synthesis, glutathione production and of course bone development.

    If we take time to study the true biochemical impact on the body’s physiology that Magnesium possesses, we can see that monitoring levels is important for all patients. Neurologically, it helps with neurotransmitter production and therefore shows promise with ADD, ADHD, depression, and anxiety just to name a few. It has even shown to benefit those with asthma, migraines, chronic fatigue syndrome, fibromyalgia, diabetes, PMS, restless leg syndrome, leg cramps and even hay fever. Modern medicine even uses it in injection form for many conditions such as an irregular heartbeat, post-heart attack, cardiac arrest and seizures.

    The importance of magnesium supplementation should be at the forefront of a practitioner’s thoughts since we now know that the average modern diet is significantly deficient in foods that contain this critical mineral. Excellent food sources of magnesium would be mostly foods high in fibre like nuts, green foods (spinach, kale, broccoli, etc.), beans, avocado, fish (salmon and halibut) and most grains.

    Magnesium dosage tends to be patient-specific, meaning each patient’s requirements for a positive health outcome will vary. Dosingwith magnesium can be challenging depending on which form you are using. Depending on the salt that magnesium is attached to (oxide, orotate, citrate, diglycinate, aspartate, etc.) will impact the bioavailability. Dosing should begin in a lower range per day and slowly increased over days and weeks to a level that either manifests a positive health change or in blood work testing. Side effects from too much magnesium are usually digestive in nature leading to cramping and/or diarrhea.

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