Definitions PEA (N-palmitoylethanolamide): An endogenous fatty acid amide synthesized and metabolized by cells that binds to cell receptors. It influences a multitude of physiological functions and has potent anti-inflammatory and pain-relieving properties. Endocannabinoid System: A lipid communication network that has critical physiological functions and serves a vital purpose for our health and well-being through signaling processes, homeostasis and hormone regulation. Lipids and the ECS In 1929, scientists George Oswald Burr and his wife, Mildred Burr, discovered that omega 6 fatty acids were essential for health. This kicked off science’s interest into lipids, and by the 1960s a new age of lipid
Magnesium Hydroxide: This form is often used as an antacid and/or in laxatives. It can be found in over-the-counter products, such as milk of magnesia. Because it has poor bioavailability, it is considered one of the least optimal forms to use as a supplement.
Magnesium Oxide: This form of magnesium is one of the most commonly used in supplements. It is desirable because it is inexpensive and the compound is very small, so large amounts of elemental magnesium can be delivered without taking up much space in a tablet or capsule. Magnesium oxide has long been considered a poor source of magnesium, since it is insoluble in water. At the pH level in the small intestine, it results in a bioavailability of less than 5%.
Several other studies have also confirmed that magnesium oxide is a poor source of magnesium with subjects reporting frequent digestive upset (nausea, loose stools etc.), especially at high doses.
There is only one study showing magnesium oxide having superior intracellular absorption when compared to magnesium citrate, however, it was criticized for poor methodology, such as not having equal dosing for oxide vs citrate, and 50% of subjects that used both forms experienced some digestive side effects. Therefore, a logical solution is to avoid magnesium oxide and favour a form with an amino acid, such as magnesium glycinate.
Magnesium Citrate: A commonly-used form that has been extensively studied for numerous health conditions. As noted above, magnesium citrate appears to have superior bioavailability and intestinal absorption when compared to magnesium oxide.1,2,3,4,5 One noted drawback is that some evidence shows that 65% of the magnesium citrate in an oral dose may form a complex that does not release magnesium.6 This form is found in many supplements and remains a solid option for delivering magnesium into the body, however, since citrate is not actively absorbed (like an amino acid) it can still cause loose stools and digestive upset at higher doses.
Magnesium Aspartate: This unique form of magnesium was originally studied in the 1960s. Researchers found that the combination of magnesium and potassium aspartates had a positive effect on fatigue, and that it could reduce muscle hyper-excitability.1 This makes sense from a physiological perspective, since both magnesium and aspartic acid are critical players in cellular energy production. The main application of this form is when conditions of low energy and chronic fatigue syndrome are observed. According to comparison studies, form also has increased bioavailability compared to oxide and citrate.
Magnesium Glycinate: Magnesium glycinate is one of the most popular supplements on the market. Technically, it is called bis-glycinate, since the compound contains 2 glycine molecules for every 1 magnesium molecule, however, for the sake of convenience, it is usually just referred to as “glycinate”. Glycine is an amino acid known for its calming effect. It also has numerous other benefits in supporting detoxification and cellular function. Because of these characteristics, magnesium glycinate has become an incredibly popular form for magnesium. Clinically, it has been successfully used for chronic pain, anxiety, insomnia, and tight muscles. This combination also has good bioavailability with minimal laxative effects, since glycine is actively transported through the intestinal wall via a cellular transporter.
One drawback to this form is that compared to magnesium oxide, this compound is much bigger and therefore has a much lower amount of elemental magnesium per capsule. Some manufacturers have tried to compensate for this obstacle by coupling magnesium-glycinate with magnesium oxide under the label “chelate”, without fully disclosing this fact to the customer. This poses several ethical and absorption concerns, discussed in more detail in the “FAQ”.
Magnesium Malate: The combination of magnesium and malic acid has been studied with patients suffering from fibromyalgia. Since malate plays a key role in the cellular energy cycle, it can help improve ATP production. There is some preliminary evidence that it may also reduce muscle pain and tender points. Since malate (malic acid) is an amino acid, it is well-absorbed with minimal digestive upset.
Magnesium Orotate: This is a relatively unknown form of magnesium in North America, combined with orotic acid (orotate). This form has good bioavailability, and has been studied specifically for heart health. While not as well-known in North America, it is popular with healthcare practitioners in Europe. The unique aspect of this form is that orotates can easily cross cell membranes, enabling the effective delivery of the magnesium ion to the innermost layers of the cellular mitochondria and nucleus.1 Orotates themselves increase the formation of RNA and DNA, which can help heart cells repair and therefore improve function. In clinical trials, this combination has been shown to improve heart failure, high blood pressure, symptoms of angina, arrhythmias, and exercise performance.2,3 It also helped with conditions of the nervous system, such as tension headaches and dizziness.3 Compared to other forms, magnesium orotate is one of the most well studied (19 randomized trials with over 600 participants) forms making it a favourite with European integrative clinicians for any heart condition.3
Magnesium Taurate: Magnesium and taurine share several similar actions. They both have the ability to improve cardiac function, insulin sensitivity, and have a calming effect on muscles and nerve conduction. They also both have blood pressure-reducing effects, stabilize nerve cells, and improve the contraction of the heart muscle. These complementary actions make it an ideal combination. However, because it is difficult to find a 100% pure, fully-reacted magnesium taurate, a separate taurine supplement is often required in addition to magnesium. Another interesting fact is that low levels of vitamin B6 have been shown to further deplete both magnesium and taurine.
Magnesium Threonate: Emerging animal research has shown that magnesium threonate has the unique ability to cross into the brain to increase magnesium levels in the cerebrospinal fluid. L-theronate can help transport magnesium across the blood brain barrier.1 It has also been shown to increase synapse density, which is correlated to nerve transmission and growth.2,3 In animal studies, this translated into practical improvements in short term and long term memory, and better recall. In 2016, a human study in elderly subjects with early stages of dementia found that cognitive impairment improved after 12 weeks.
Magnesium Sulfate: This form is often used for intravenous (IV) use in clinical and hospital settings, but is not used in oral formulations. It is also found in Epsom bath salts and offers some absorbability through the skin.
|Magnesium Form||% Mg||Description and Summary||Key Clinical Uses|
|Mg oxide||58%||Commonly used in lower quality supplements||Laxative|
|Mg Citrate||11%||Commonly used form – good absorption but still laxative effects||Laxative, general magnesium support|
|Mg (bis)glycinate||11-14%||Amino acid glycine has calming effect on nerves||Insomnia, restless legs, anxiety, muscle spasm|
|Mg malate||11%||Malate increases energy production inside cell||Fibromyalgia, muscle pain|
|Mg aspartate||7%||Aspartate helps transport fats inside the cell||Chronic fatigue|
|Mg taurate||8.8%||Normalizes electrical activity across membranes in heart and brain||Cardiovascular disease Arrhythmia|
|Mg orotate||7.2%||Orotic acid also increases the formation of RNA and DNA, which can help repair damage to heart cells, improve stress tolerance and therefore improve function||Hypertension Congestive Heart Failure Mitral valve prolapse Stable angina Blood vessel elasticity|
|Mg theronate||8.1%||Studied to penetrate past the blood brain barrier||Brain injuries, cognition, memory, focus|
Table 5: Forms and Benefits of Magnesium
The primary goal of this document was to be informative and to raise awareness about the evidence supporting magnesium. We believe that if you have the evidence-based information, you will be able to apply that knowledge for optimal health. You should consider reducing habits that deplete your magnesium and eat foods rich in the mineral. When supplementing, be aware of creative marketing: always look for the most absorbable and 100% pure forms. With this information, you should feel confident when making an informed decision about magnesium.
Magnesium Oxide Magnesium Orotate
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2. Ranade VV, Somberg JC.Bioavailability and pharmacokinetics of magnesium after administration of magnesium salts to humans. Am J Ther. 2001 Sep-Oct;8(5):345-57.
3. Shechter et al. Comparison of magnesium status using X-ray dispersion analysis following magnesium oxide and magnesium citrate treatment of healthy subjects. Magnes Res. 2012 Mar 1;25(1):28-39. doi: 10.1684/mrh.2012.0305.
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2. Firoz M1, Graber M. Bioavailability of US commercial magnesium preparations. Magnes Res. 2001 Dec;14(4):257-62.
3. Ranade VV, Somberg JC.Bioavailability and pharmacokinetics of magnesium after administration of magnesium salts to humans. Am J Ther. 2001 Sep-Oct;8(5):345-57.
4. Kappeler et al. Higher bioavailability of magnesium citrate as compared to magnesium oxide shown by evaluation of urinary excretion and serum levels after single-dose administration in a randomized cross-over study. BMC Nutrition (2017) 3:7
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Lamontagne C, Sewell JA, Vaillancourt R, Kuhzarani C, (2012) Rapid Resolution of Chronic Back Pain with Magnesium Glycinate in a Pediatric Patient. J Pain Relief 1:101.
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McCarty MF. Complementary Vascular-Protective Actions of Magnesium and Taurine: A Rationale for Magnesium Taurate. Medical Hypotheses (1996) 46. 89-100
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2. Lui et al. Efficacy and Safety of MMFS-01, a Synapse Density Enhancer, for Treating Cognitive Impairment in Older Adults: A Randomized, Double-Blind, Placebo-Controlled Trial. Journal of Alzheimer’s Disease 49 (2016) 971–990
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