Science

Magnesium Glycinate & Glycine
This white paper was prepared for Natural Calm by ...
This white paper was prepared for Natural Calm by Dr. Alison Smith to evaluate the benefits of magnesium glycinate and glycine as an amino acid. There are many marketing claims around glycine, however, we wanted to know the facts about how glycine works in the body. Natural Calm products are primarily magnesium citrate. We do incorporate magnesium glycinate together with magnesium citrate in some of the speciality products, including new Calmful Sleep. Learn more about the amino acid, glycine, and how it works in magnesium glycinate.

Magnesium Glycinate and the Amino Acid, Glycine: Absorbability and Bioavailability

By Alison Smith Ph.D., Neuroscience Which magnesium salt is most effective, in terms of absorbability and bioavailability? Research indicates that organic magnesium salts are more absorbable and bioavailable than inorganic salts 1,2. Organic magnesium salts are created in a laboratory by combining an inorganic magnesium salt, derived from earth or rock sources, with either an acid or an amino acid. Magnesium salts combined with amino acids are referred to as amino acid chelates. Magnesium glycinate (also known as magnesium bisglycinate or magnesium diglycinate) is one such organic magnesium salt, or amino acid chelate, that is created by combining inorganic magnesium with an amino acid called glycine. This white paper contains two parts. Part one explores the importance of glycine for human health, and part two investigates the absorbability and bioavailability of magnesium glycinate supplements.

Part I: What is Glycine?

Amino acids are the basic building blocks of proteins, and they are essential not only for a healthy body but for life itself. We simply could not exist without them––they ensure our survival and play an integral role in all cellular processes. Scientists have discovered over 500 different amino acids in nature; however, the human body only requires twenty of them for human cellular function 3. These twenty amino acids are referred to as the standard amino acids 4. The human body can naturally produce half of the standard amino acids––the other half, called the essential amino acids, must be acquired through the diet. Glycine is classified as a non-essential amino acid since the body naturally produces it; however, research shows that the amount of glycine produced by the body is not sufficient enough to keep up with metabolic demands 5; therefore, oral supplementation or eating foods rich in glycine might be warranted. Glycine is the smallest amino acid, so small that it can squeeze through the tiniest spaces 4. It plays a major role in collagen and elastin formation 6, as well as bile acid function. Interestingly, it also acts as a neurotransmitter in the central nervous system 7.  A chronic glycine deficiency can result in impairment of growth, immune and nervous system function, and nutrient metabolism 8.

Glycine: Implications for Health and Nutrition

 Of the total amino acid content in the human body, 11.5% of it is glycine. This amino acid plays a pivotal role in nutrition and metabolism, and for that reason, we require approximately 2 grams of glycine produced by the body or acquired through the diet each day. 80% of the total glycine in the body is used for protein synthesis, and without it, cellular function would suffer 9. The following is a list of health conditions in which glycine plays a critical role: Obesity and Type II Diabetes: There is evidence that plasma concentration of glycine is reduced in obese and type II diabetic patients 10. Oral glycine supplementation may be an effective treatment since it can reduce free fatty acids and triglycerides in the blood and fat cell size within intra-abdominal fat of obese subjects 11. Inflammation: Glycine is anti-inflammatory and immunomodulatory 12. It reduces inflammatory reactions by encouraging an influx of chloride into the cell membrane thus hyperpolarizing the cell, decreasing calcium entry, thus making the cell less active overall. Glycine also reduces the production of proinflammatory cytokines and the expression of adhesion molecules in blood vessels 13, and enhances the activity of macrophages and leukocytes––immune cells that help to clean up injured or infected tissue 14. All of these effects have the potential to reduce atherosclerosis in cardiac patients 15. Sleep: Two separate double-blind studies showed that the administration of 3 grams of glycine, before bedtime, improved quality of sleep, the feeling of fatigue the next day, sleep satisfaction, and time to sleep onset 16,17. No adverse side effects were observed even when subjects ingested up to 9 to 31 grams of glycine per day 18,19. Nervous System Function: Glycine and GABA (gamma-Aminobutyric acid) are the main inhibitory neurotransmitters of the central nervous system. They both activate receptors in the brain and spinal cord that allow an influx of chloride into central nervous system cells––chloride inhibits the cell thus reducing cellular activation 20.  Inhibition is an imperative process in the central nervous system; without it, normal behavioural and motor function would be impossible because inhibition allows precise movements, thoughts, and attention, and the ability to stop or change a neurological response. Defects in inhibition result in psychiatric disorders like ADHD, obsessive-compulsive disorder (OCD), and Tourette’s syndrome 21. There is evidence that glycine supplementation may reduce OCD 22. Glycine has also been shown to improve auditory nerve function in diabetic patients by reducing nerve damage imposed by excessive sugar in the bloodstream 23. Oxidative Stress: Through aerobic metabolism or some pathological processes, the body naturally produces oxidants: harmful substances like free radicals, hydrogen peroxide, and hydroxyl radicals that damage healthy tissues, protein, and DNA––a destructive process referred to as oxidative stress 24. A cell’s ability to defend itself against oxidative stress depends on several antioxidant defence mechanisms including the production of glutathione: a tripeptide synthesized from the amino acids glycine, glutamate, and cysteine; it counteracts the activity of oxidants and reduces oxidative stress 25,26. Two studies by Sekhar et al. 25,27 report that both diabetic and elderly patients have glutathione deficiency and supplementation with glycine and cysteine restores glutathione levels, which in turn reduces oxidative stress, diabetic symptoms, and aging. Glycine supplementation also reduces oxidative stress and blood pressure in patients with metabolic syndrome and might benefit patients with vascular disease or atherosclerosis 15,28. Stroke: Following an ischemic stroke, it is incredibly important to receive treatment as soon as possible––the administration of medication to break down the blood clot in the brain before 4.5 hours post-stroke is ideal 29. There is also preliminary evidence that 1-2 grams of sublingual glycine started within 6-hours post-stroke, and given for 5-days, has neuroprotective effects in ischemic stroke patients: it reduces mortality, the time period of neurological deficits, and the imbalance between excitatory and inhibitory neurotransmitters within the brain 30. Muscle: Research shows that supplemental glycine helps to protect muscle from certain wasting conditions such as cancer cachexia––muscle and fat wasting due to cancer 31,32, sepsis, or reduced caloric intake 33. Cancer: Glycine supplementation has anticancer properties. Evidence shows glycine to inhibit hepatic (liver) and B16 melanoma (skin) cancer cell proliferation and angiogenesis. In the liver, a type of macrophage called Kupffer cells protect the liver against pathogens and toxins; however, in doing so, they produce oxidants––harmful substances that damage liver cells and cause cancer. Glycine supplementation is reported to block oxidant production by Kupffer cells, which in turn reduces liver cancer cell production 9. Glycine also blocks blood vessel formation (angiogenesis) in B16 skin cancer (melanoma) tumours, reducing their size by upwards of 65% 9,34. Connective Tissue Integrity: Glycine is a precursor of collagen production: collagen is an important connective tissue component of skin, tendon, and cartilage; it provides function and structure to the body. Being the smallest amino acid, glycine fits between the tight junctions between larger amino acids that help to form collagen proteins. Glycine is a flexible amino acid, and it gives collagen its pliability and elasticity 9. Liver Toxicity: Glycine plays a protective role against alcohol-induced liver toxicity by shielding liver cell membrane structure from the damaging effects of oxidative stress produced by alcohol in the liver 35. By slowing stomach emptying of alcohol and reducing the by-products of alcohol like acetaldehyde (a type of oxidant), glycine can reduce blood alcohol level and the damaging effects of alcohol 9.

Part II: The Effectiveness of Magnesium Glycinate Supplements

With the vast array of magnesium salts available in capsule, liquid, or powder form, consumers can be left feeling confused by all the choices. Which magnesium supplement should they choose? Which is the most effective? Magnesium glycinate is a popular organic magnesium salt available as a supplement; however, there is very little research on its effectiveness in the human body in terms of absorbability and bioavailability. Here is what the current research can tell us:

Magnesium Glycinate: Absorption and Bioavailability

Organic magnesium salts, like magnesium glycinate, are created in a laboratory by combining an inorganic magnesium salt with either an acid or an amino acid (a protein). For example, magnesium citrate is created by combining an inorganic magnesium with citric acid, and magnesium glycinate is created by combining an inorganic magnesium with the amino acid, glycine. Overall, organic magnesium salts are demonstrably more soluble, absorbable, and bioavailable than inorganic magnesium salts. Magnesium glycinate is a type of organic magnesium salt; therefore, it is considered as a highly absorbable and bioavailable form of magnesium 1,2. In a review article by Coudray et al. 2, magnesium glycinate is listed as a ‘good’ source of magnesium since it is soluble, absorbable, and bioavailable. Schuette et al. 36 report magnesium diglycinate as an absorbable form of magnesium for some patients with intestinal resection.

Magnesium Glycinate in the Treatment of Health Conditions

More research is required to understand how magnesium glycinate helps in the treatment of various health conditions. The current research demonstrates that 300 mg of magnesium bisglycinate, given daily, significantly reduces the frequency and intensity of pregnancy-induced leg cramps 37. The administration of 125-300 mg of magnesium glycinate or taurinate is reported to help in rapid recovery from major depression 38.

Intestinal Absorption of Amino Acid Chelates

How the intestine absorbs magnesium glycinate is not entirely understood. The predominant absorption mechanism described in the literature involves a magnesium salt breaking apart in the gastric juices of the stomach; this process releases ionic magnesium, ready for absorption through the intestine. The ionic magnesium then travels to the distal intestine where it is absorbed through passive diffusion or via facilitated diffusion through ion channels 39,40. There is a theory that amino acid chelates, including magnesium glycinate, are absorbed by a different mechanism; however, it has not been confirmed. The theory states that amino acid chelates remain intact despite exposure to gastric juices in the stomach. The complex, instead, enters the intestine whole and is absorbed by peptide channels in the intestinal wall, opposed to passive diffusion or facilitated diffusion through ion channels 41. Again, this theory has not been proven and more research is required. For more information on the science behind magnesium absorption and how magnesium citrate compares to magnesium glycinate, see the results of a 2017 clinical trial currently under peer review for publication. 

References

  1. Ranade VV, Somberg JC. Bioavailability and pharmacokinetics of magnesium after administration of magnesium salts to humans. American Journal of Therapeutics. 2001;8(5):345.
  2. Coudray C, Rambeau M, Feillet-Coudray C, et al. Study of magnesium bioavailability from ten organic and inorganic mg salts in mg-depleted rats using a stable isotope approach. Magnesium research. 2005;18(4):215.
  3. Cole L, Kramer P. Human physiology, biochemistry and basic medicine. Cambridge, Massachusetts: Academic Press; 2016.
  4. New World Encyclopedia. Amino acid. http://www.newworldencyclopedia.org/p/index.php?title=Amino_acid&oldid=684821. Accessed January, 2018.
  5. Meléndez-Hevia E, de Paz-Lugo P, Cornish-Bowden A, Cárdenas M. A weak link in metabolism: The metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis. J Biosci. 2009;34(6):853-872.
  6. Wu G. Amino acids: Metabolism, functions, and nutrition. Amino Acids. 2009;37(1):1-17.
  7. Rajendra S, Lynch JW, Schofield PR. The glycine receptor. Pharmacology and Therapeutics. 1997;73(2):121-146.
  8. B Matilla, J L Mauriz, J M Culebras, J González-Gallego, P González. Glycine: A cell-protecting anti-oxidant nutrient. Nutrición hospitalaria. 2002;17(1):2-9.
  9. Razak M, Begum P, Viswanath B, Rajagopal S. Multifarious beneficial effect of nonessential amino acid, glycine: A review. Oxidative Medicine and Cellular Longevity. 2017;2017.
  10. Felig P, Marliss E, Cahill GF. Plasma amino acid levels and insulin secretion in obesity. The New England Journal of Medicine. 1969;281(15):811-816.
  11. Perez I, Banos G, El Hafidi M, Zamora J, Soto V, Carvajal-Sandoval G. Glycine intake decreases plasma free fatty acids, adipose cell size, and blood pressure in sucrose-fed rats. The American Journal of Physiology. 2004;287(6):R1387.
  12. Wang W, Wu Z, Dai Z, Yang Y, Wang J, Wu G. Glycine metabolism in animals and humans: Implications for nutrition and health. Amino Acids. 2013;45(3):463-477.
  13. Hasegawa S, Ichiyama T, Sonaka I, et al. Cysteine, histidine and glycine exhibit anti‐inflammatory effects in human coronary arterial endothelial cells. Clinical & Experimental Immunology. 2012;167(2):269-274.
  14. Li P, Yin Y, Li D, Woo Kim S, Wu G. Amino acids and immune function. British Journal of Nutrition. 2007;98(2):237-252.
  15. Díaz-Flores M, Cruz M, Duran-Reyes G, et al. Oral supplementation with glycine reduces oxidative stress in patients with metabolic syndrome, improving their systolic blood pressure. Canadian Journal of Physiology and Pharmacology. 2013;91(10):855-860.
  16. Inagawa K, Hiraoka T, Kohda T, Yamadera W, Takahashi M. Subjective effects of glycine ingestion before bedtime on sleep quality. Sleep Biol Rhythms. 2006;4(1):75-77.
  17. Yamadera W, Inagawa K, Chiba S, Bannai M, Takahashi M, Nakayama K. Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes. Sleep Biol Rhythms. 2007;5(2):126-131.
  18. Kentaro I, Nobuhiro K, Kaori O, Eiji S, Shoji T, Michio T. Assessment of acute adverse events of glycine ingestion at a high dose in human volunteers. Seikatsu Eisei (Journal of Urban Living and Health Association). 2006;50(1):27-32.
  19. Rose W, Wixom R, Lockhart H, Lambert G. The amino acid requirements of man. J Biol Chem. 1995;217:987-996.
  20. O’Brien J, Berger A. Cotransmission of GABA and glycine to brain stem motoneurons. Journal of Neurophysiology. 1999;82(3):1638-1641.
  21. Garavan H, Ross TJ, Stein EA. Right hemispheric dominance of inhibitory control: An event-related functional MRI study. Proceedings of the National Academy of Sciences of the United States of America. 1999;96(14):8301-8306.
  22. Cleveland W, DeLaPaz R, Fawwaz R, Challop R. High-dose glycine treatment of refractory obsessive-compulsive disorder and body dysmorphic disorder in a 5-year period. Neural Plasticity. 2009;2009:1-25.
  23. Muñoz-Carlin MdL, Rodríguez-Moctezuma JR, Gómez Latorre JG, Montes-Castillo ML, Juárez-Adauta S. Effects of glycine on auditory evoked potentials among diabetic patients with auditory pathway neuropathy. Revista médica de Chile. 2010;138(10):1246.
  24. Sies H. Oxidative stress: Oxidants and antioxidants. Experimental Physiology. 1997;82:291-295.
  25. Sekhar RV, McKay SV, Patel SG, et al. Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine. Diabetes care. 2011;34(1):162-167.
  26. Cruz M, Maldonado-Bernal C, Mondragón-Gonzalez R, et al. Glycine treatment decreases proinflammatory cytokines and increases interferon-γ in patients with type 2 diabetes. J Endocrinol Invest. 2008;31(8):694-699.
  27. Sekhar RV, Patel SG, Guthikonda AP, et al. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. The American journal of clinical nutrition. 2011;94(3):847-853.
  28. El Hafidi M, Pérez I, Baños G. Is glycine effective against elevated blood pressure? Current opinion in clinical nutrition and metabolic care. 2006;9(1):26-31.
  29. Schellinger PD, Köhrmann M. 4.5-hour time window for intravenous thrombolysis with recombinant tissue-type plasminogen activator is established firmly. Stroke; a journal of cerebral circulation. 2014;45(3):912-913.
  30. Gusev EI, Skvortsova VI, Dambinova SA, et al. Neuroprotective effects of glycine for therapy of acute ischaemic stroke. Cerebrovascular Diseases. 2000;10(1):49-60.
  31. Bennani-Baiti N, Walsh D. What is cancer anorexia-cachexia syndrome? A historical perspective. The journal of the Royal College of Physicians of Edinburgh. 2009;39(3):257.
  32. Ham DJ, Murphy KT, Chee A, Lynch GS, Koopman R. Glycine administration attenuates skeletal muscle wasting in a mouse model of cancer cachexia. Clinical nutrition (Edinburgh, Scotland). 2014;33(3):448-458.
  33. Koopman R, Caldow M, Ham D, Lynch G. Glycine metabolism in skeletal muscle: Implications for metabolic homeostasis. Current Opinion in Clinical Nutrition & Metabolic Care. 2007;20(4):237-242.
  34. Rose M, Madren J, Bunzendahl H, Thurman G. Dietary glycine inhibits the growth of B16 melanoma tumors in mice. Carcinogenesis. 1999;20(5):793-798.
  35. Yin M, Ikejima K, Arteel G, et al. Glycine accelerates recovery from alcohol-induced liver injury. Journal of Pharmacology and Experimental Therapeutics. 1998;286(2):1014-1019.
  36. Schuette SA, Lashner BA, Janghorbani M. Bioavailability of magnesium diglycinate vs magnesium oxide in patients with ileal resection. Journal of Parenteral and Enteral Nutrition. 1994;18(5):430-435.
  37. Supakatisant C, Phupong V. Oral magnesium for relief in pregnancy-induced leg cramps: A randomised controlled trial. Maternal & Child Nutrition. 2015;11(2):139-145.
  38. Eby KL, Eby GA. Rapid recovery from major depression using magnesium treatment. Medical Hypotheses. 2006;67(2):362-370.
  39. Quamme G. Recent developments in intestinal magnesium absorption. Current Opinion in Gastroenterology. 2008;24(2):230-235.
  40. Roth P, Werner E. Intestinal absorption of magnesium in man. The International Journal Of Applied Radiation And Isotopes. 1979;30(9):523-526.
  41. Olivares M, Pizarro F, Pineda O, Name JJ, Hertrampf E, Walter T. Milk inhibits and ascorbic acid favors ferrous bis-glycine chelate bioavailability in humans. The Journal of nutrition. 1997;127(7):1407.
 
Proven More Absorbable
A randomized, double-blind, placebo-controlled, cr...

A randomized, double-blind, placebo-controlled, crossover trial to compare the bioavailability of magnesium from Natural Calm magnesium with three marketed magnesium supplements.

Background

In 2016, Natural Calm Canada contracted with Nutrasource, a full-service contract research organization (CRO) specializing in clinical trials and product testing for the natural health industry, to compare magnesium absorption from four brands of magnesium supplements. The results were released by Nutrasource in September, 2017, and presented at the Canadian Health Food Association by Dr. Alison Smith.  This summary was prepared by Dr. Smith. A thorough explanation of the study findings can be found on our blog, here.

Methodology

Nutrasource conducted a 10-week, randomized, double-blind, crossover study including 12 healthy, postmenopausal women, randomized into four different treatment sequences. All subjects took 150 mg of the four magnesium brands or a placebo; however, the sequence of treatment varied between subjects. Study Duration: June 2016 - September 2017. Each subject visited the clinic 27 times plus two screening visits. Supplement brands included in the study:
Natural Calm Magnesium carbonate powder with citric acid that converts to magnesium citrate once dissolved in hot water
CanPrev Magnesium bisglycinate powder dissolved in water
Lorna Vanderhaeghe MagSmart ® magnesium bisglycinate powder dissolved in water
Natural Factors Magnesium citrate powder in a capsule
Placebo Hypromellose and rice flour contained in a capsule. One capsule contained an estimated 0.26 mg of magnesium.
Primary Measurement: The concentration of magnesium in the blood serum and urine between 0-8 hours following supplement ingestion. (For information on the rationale for measuring magnesium absorption via blood serum and urine tests, see our White Paper.) Secondary Measurements: The concentration of magnesium in the blood serum and urine between 0-10 hours, 0-12 hours, 0-24 hours (urine only), as well as maximum concentration (Cmax) and time to maximum concentration (Tmax) of magnesium in the blood serum and urine.

Results

10 Subjects completed the study and the following results were found.
  1. For the primary measurement, between 0-8 hours, Natural Calm magnesium citrate significantly increased magnesium concentration in both the blood serum and urine, compared to taking a placebo. The magnesium bisglycinate supplements from CanPrev or Lorna Vanderhaeghe and the magnesium citrate capsule from Natural Factors did not significantly increase magnesium concentration in either the blood serum or urine during this time period.
  1. For the secondary measurement, between 0-12 hours,  Natural Calm magnesium citrate significantly increased magnesium concentration in the urine compared to Lorna Vanderhaeghe’s magnesium bisglycinate supplement.
  1. The maximum concentration of magnesium in the urine (Cmax) was measured after collecting urine over the course of 24 hours. Cmax was a secondary study measure. Results showed the Natural Factors magnesium citrate capsule to significantly increase magnesium concentration in the urine compared to Lorna Vanderhaeghe’s magnesium bisglycinate supplement.

Conclusions

According to the primary measurement, Natural Calm magnesium citrate significantly increases the bioavailability of magnesium in the human body compared to magnesium glycinate competitors. Overall, the statistical tests with a significant result showed that the magnesium citrate supplements from Natural Calm and Natural Factors outperformed both magnesium bisglycinate supplements. Postscript Notes The study is being prepared for peer review and publication in a scientific journal. For the full draft study results, contact info@naturalcalm.ca. We acknowledge that the quality of magnesium glycinate used in the tested products may be a factor, despite that these are two leading magnesium glycinate brands. In 2017, it was revealed that a number of Canadian magnesium glycinate brands contained undisclosed magnesium oxide, a less absorbable form. It is unclear whether CanPrev or Lorna Vanderhaeghe products were implicated in this mislabelling.
Fibromyalgia, Chronic Fatigue Syndrome and Energy
This article expands on our previous articles addr...
This article expands on our previous articles addressing the science on magnesium for fibromyalgia and energy. It was written for submission to the Integrated Health Hub magazine and will be published in the fall of 2017.

Magnesium Supplementation for Fibromyalgia, Chronic Fatigue Syndrome, and Low Energy: Does It Work?

By Anna O’Byrne and Laura Young, Honours B.Sc., Student of the Canadian College of Osteopathy A lack of energy or ‘tiredness’ is one of the most common complaints patients bring to primary care givers (Stadje et al., 2016). Surveys of adults in the US and Europe estimate that 20% to 30% experience significant fatigue (Nicholson, 2012). Fatigue, unfortunately, is often an intractable complaint; across several studies in Canada, the US and Britain, symptoms of fatigue persisted in most patients six months to a year after their initial complaint to a health care provider (Nicholson, 2012). It is not surprising that the demand for energy supplement is on the rise. According to Nutraceuticals World (2017), “…for people who take dietary supplements, energy is now the number two health concern they’re looking to address, with 30% of users citing this need, according to the Council for Responsible Nutrition’s (CRN) 2016 Consumer Survey on Dietary Supplements (Nutraceuticals World, n.d.).” In the quest for more energy, many people have turned to caffeine and other stimulants, natural and synthetic. Some of these have dangerous side effects, including nervousness and sleeplessness (Nutraceuticals World, n.d.). Market watchers have noted a shift in demand for alternatives to energy supplements that are natural, organic and non-stimulating (Nutraceuticals World, n.d.). Magnesium supplements are one such natural, non-stimulating alternative, and the research shows promise for the role of magnesium in increasing energy. According to Dr. Carolyn Dean, M.D., N.D. (2014), “One of the most amazing effects of magnesium on the neuromuscular system is that it provides more energy, even though the mineral generally acts as a relaxant and not a stimulant (pg. 71).” Magnesium activates “enzymes that control digestion, absorption, and the utilization or proteins, fats and carbohydrates (Dean, 2014, p. 15). It’s also important to note that of “the 700-800 magnesium-dependent enzymes, the most important enzyme reaction involves the creation of energy by activating adenosine triphosphate (ATP), the fundamental energy storage molecule of the body (Dean, 2014, p. 15). To better understand the efficacy of magnesium, here we’ll look at the clinical data on magnesium supplementation for fibromyalgia, chronic fatigue syndrome (CFS), and athletics.

Magnesium for Fibromyalgia (FM)

The symptoms of FM include prolonged fatigue and widespread muscular pain. In fact, because of the characteristic fatigue, FM is sometimes confused with CFS and commonly considered comorbid conditions (The New York Times, n.d.). Among those with FM, magnesium is one of the supplements most recommended, according to a recent study (Arranz, Canela, & Rafecas, 2012). Dating back to the 1990s, a number of studies have examined the effects of magnesium supplementation on fatigue and pain associated with FM. One of the earliest studies postulated that FM symptoms are caused by a “deficiency of oxygen and other substances needed for ATP synthesis (Abraham & Flechas, 1992).” In the study, FM patients were administered 1200 to 2400 mg of malate and 300-600 mg of magnesium daily for eight weeks, and the outcomes were compared with placebo tablets. The resultant data supported a “critical role for magnesium and malate in ATP production under aerobic and hypoxic conditions; and indirect evidence for magnesium and malate deficiency” in FM (Abraham & Flechas, 1992). Romano and Stiller (1994), evaluated red blood cell (RBC) and plasma levels to determine whether individuals with FM also present with low magnesium. The study reported that FM patients do, in fact, have significantly lower RBC magnesium levels compared with reference laboratory and the control group. However, there was no significant difference in plasma magnesium levels between the groups (Romano & Stiller, 1994). In 2013, a study published in Rheumatology International demonstrated that magnesium supplementation affected significant improvements in several FM markers (Bagis et al., 2013). Many of the positive outcomes reported were related to pain reduction, but most relevant to this discussion, patients in the magnesium citrate treatment group, receiving 300 mg/day over 8 weeks, saw marked improvements in Beck depression and FM impact questionnaire (FIQ) scores (Bagis et al., 2013). The FIQ is “an instrument that measures physical functioning, work status (missed days of work and job difficulty), depression, anxiety, morning tiredness, pain, stiffness, fatigue, and well-being over the past week (American College of Rheumatology, n.d.).” The authors hypothesized that low magnesium levels may be a factor in the symptoms of FM (Bagis et al., 2013).

Magnesium for Chronic Fatigue Syndrome (CFS)

CFS is notoriously difficult to diagnose and poorly-defined (The New York Times, n.d.). The most distinctive feature is persistent fatigue. CFS patients also experience pain, headache, poor sleep and cognitive symptoms (The New York Times, n.d.). A review published in The Journal of Chronic Fatigue Syndrome examined the relationship between CFS and magnesium (Seelig, 1998). Seelig noted that, “the evidence that Mg deficiency causes a variety of both humoral and cellular defense disturbances, among which are several that have been identified in CFS and FM, is a reason to suspect that either Mg deficiency or its abnormal utilization might be a pathogenic factor in CFS (p. 106).” A 1991 study published in The Lancet essayed to demonstrate that patients with CFS have low magnesium and that symptoms can be improved with supplementation (Cox, Campbell, & Dowson). Twenty CFS patients were tested for red blood cell magnesium concentration and were found to have lower levels than 20 healthy control subjects (Cox et al., 1991). In a double-blind, placebo-controlled clinical study, patients were randomly assigned to either 6 weeks of magnesium sulphate supplementation or placebo. The treatment group was demonstrated to have improved energy, a better emotional state and less pain, as measured by the Nottingham health profile (Cox et al., 1991). In the treatment group, 7 of the patients had a significant change in their energy score, contrasted with 1 patient in the control group (Cox et al., 1991). Unfortunately, no further studies have been published on the topic since these results published over 20 years ago. Clearly, more research is required.

Magnesium and Energy for Athletic Performance

The ceiling on athletic performance is often determined by energy or lack thereof. A 2002 study in The Journal of Nutrition demonstrated that induced magnesium depletion results in an increased need for energy and adversely affects cardiovascular function (Nielsen & Lukaski, 2002). The researchers arrived at this conclusion by supplementing and restricting the magnesium intake of postmenopausal female participants and measuring the effects on exercise (Nielsen & Lukaski, 2002). In 2006 the same authors published an “Update on the relationship between magnesium and exercise (Nielsen & Lukaski, 2006).” Nielsen and Lukaski found that “exercise induces a redistribution of magnesium in the body to accommodate metabolic needs. There is evidence that marginal magnesium deficiency impairs exercise performance and amplifies the negative consequences of strenuous exercise (e.g., oxidative stress) (p.180).” The authors concluded “magnesium supplementation or increased dietary intake of magnesium will have beneficial effects on exercise performance in magnesium deficient individuals (Nielsen & Lukaski, 2006) (p. 180).” In healthy elderly women, a randomized, controlled trial found that magnesium supplementation induced a significant improvement in short physical performance battery (a group of measures that combines the results of the gait speed, chair stand and balance tests) as well as chair stand times and 4 metre walking speeds. The most significant outcomes were observed more notably in subjects whose diets were lower in magnesium (Veronese et al., 2014). Other studies contrasting athletes under magnesium supplementation with control groups have found that “magnesium supplementation positively influences performance (Cinar, Nizamlioglu, Mogulkoc, & Baltaci, 2007)” and that it “improved alactic anaerobic metabolism” even in athletes who were not magnesium-deficient (Setaro et al., 2014).

Is Magnesium an Energy Supplement?

As this paper describes, positive, significant results have been demonstrated among patients with FM, CFS, and healthy individuals during exercise. The research suggests that magnesium supplementation can improve energy and performance, even among those who are not magnesium deficient. Accurate testing of magnesium deficiency is, in any case, not widely available. According to Carolyn Dean, M.D., N.D. (2014), the best method is via Ionized Magnesium Testing, which is not widely available. The Magnesium RBC test is more accessible to the public but less accurate, and serum magnesium testing is less accurate still (p. 217). Whether healthy or presenting with a fatigue related condition, patients should be made aware of the role of magnesium in energy. If a reliable test is not available but symptoms of magnesium deficiency are present, supplementation is a safe, effective option for most.

References

Abraham, G. E., & Flechas, J. D. (1992). Management of Fibromyalgia: Rationale for the use of Magnesium and Malic Acid. Journal of Nutritional Medicine, 3(1). Arranz, L. I., Canela, M. Á., & Rafecas, M. (2012). Dietary aspects in fibromyalgia patients: results of a survey on food awareness, allergies, and nutritional supplementation. Rheumatology International, 32(9), 2615–2621. Bagis, S., Karabiber, M., As, I., Tamer, L., Erdogan, C., & Atalay, A. (2013). Is magnesium citrate treatment effective on pain, clinical parameters and functional status in patients with fibromyalgia? Rheumatology International, 33(1), 167–172. Chronic Fatigue In-Depth Report. (n.d.). In The New York Times online. Retrieved August 15, 2017, from http://www.nytimes.com/health/guides/disease/chronic-fatigue-syndrome/print.html Cinar, V, Nizamlioglu, M., Mogulkoc, R., & Baltaci, A. K. (2007). Effects of magnesium supplementation on blood parameters of athletes at rest and after exercise. Biological Trace Element Research, 115(3), 205–212. Cox, I. M., Campbell, M. J., & Dowson, D. (1991). Red blood cell magnesium and chronic fatigue syndrome. The Lancet, 337(8744), 757–760. Dean, C. (2014). The Magnesium Miracle. New York: Ballantine Books. Energy Trends: The Market Charges On. Brands appeal to a broad audience with natural ingredients that provide sustained benefits (n.d.). In Nutraceuticals World online. Retrieved August 15, 2017, from http://www.nutraceuticalsworld.com/issues/2017-01/view_features/energy-trends-the-market-charges-on/1170 Fibromyalgia Impact Questionnaire (FIQ). (n.d.). In American College of Rheumatology online. Retrieved August 15, 2017, from https://www.rheumatology.org/I-Am-A/Rheumatologist/Research/Clinician-Researchers/Fibromyalgia-Impact-Questionnaire-FIQ Nicholson, K. A. (2012, July). The Symptom of Fatigue in Primary Care: A Comparative Study of Health Care Utilization Patterns Using Electronic Medical Records. Nielsen, F. H., & Lukaski, H. C. (2002). Dietary magnesium depletion affects metabolic responses during submaximal exercise in postmenopausal women. The Journal of Nutrition, 132(5), 930–935. Nielsen, F. H., & Lukaski, H. C. (2006). Update on the relationship between magnesium and exercise. 19(3), 180–189. http://doi.org/10.1684/mrh.2006.0060 Romano, T. J., & Stiller, J. W. (1994). Magnesium Deficiency in Fibromyalgia Syndrome. Journal of Nutritional Medecine, 4(2), 165–167. Seelig, M. (1998). Review and hypothesis: might patients with the chronic fatigue syndrome have latent tetany of magnesium deficiency. Journal of Chronic Fatigue Syndrome, 4(2), 77–108. Setaro, L., Santos-Silva, P. R., Nakano, E. Y., Sales, C. H., Nunes, N., Greve, J., & Colli, C. (2014). Magnesium status and the physical performance of volleyball players: effects of magnesium supplementation. Journal of Sports Sciences, 32(5), 438–445. Stadje, R., Dornieden, K., Baum, E., Becker, A., Biroga, T., Bösner, S., et al. (2016). The differential diagnosis of tiredness: a systematic review. BMC Family Practice, 17(147), 1–11. Veronese, N., Berton, L., Carraro, S., Bolzetta, F., De Rui, M., Perissinotto, E., et al. (2014). Effect of oral magnesium supplementation on physical performance in healthy elderly women involved in a weekly exercise program: a randomized controlled trial. American Journal of Clinical Nutrition, 100(3), 974–981.  
Anxiety and Panic
By Alison Smith Ph.D. A 2013 Global Burden of Dise...
By Alison Smith Ph.D. A 2013 Global Burden of Disease study (Mathers et al., 2001) found mental disorders to be among the primary causes of disability worldwide. According to Baxter et al. (2012), 7.3% of the total global population, that is every one in 14, suffers from an anxiety disorder. In the 2012 Canadian Community Health Survey, Statistics Canada reports 2.4 million Canadians suffer from generalized anxiety disorder alone, with females (3.2%) affected more than males (2.0%) (Pearson et al., 2013). However, only 37% of Canadians with an anxiety disorder actually seek treatment (Roberge et al., 2011), pointing to the need to educate Canadians about effective strategies to treat anxiety and how to access them.

Defining Anxiety and Panic Attacks

Anxiety disorders are those that feature panic and anxiety. Panic is a fear response to imminent danger or a perceived threat, while anxiety is the anticipation of future danger (American Psychiatric Association, 2013). Panic and fear are associated with sympathetic nervous system arousal, the fight-or-flight response, thoughts of imminent threat, and escape behaviours. Anxiety, on the other hand, is associated more with hyper vigilance, muscle tension, and the preparation to flee the scene because of perceived dangers (American Psychiatric Association, 2013). Anxiety disorders include: generalized anxiety disorder, panic disorder, agoraphobia, social anxiety disorder, and phobias (Canadian Mental Health Association, 2013), and treatments include pharmacotherapy and cognitive therapy; nonetheless, natural treatments like magnesium are shown to have anxiolytic effects.

How Magnesium Mediates Anxiety

Magnesium is the second most abundant cation, intracellularly, and the fourth most abundant cation in the whole body (Swaminathan, 2003). It acts as a cofactor in over 300 enzymatic reactions, including the maintenance of healthy brain function and mood (Wester, 1987; Sartori et al., 2012). Studies show magnesium plays a role in keeping anxiety at bay through its modulation of neuronal receptors, neurotransmitters, and hormonal activity within anxiety-related brain regions, in addition to influencing the activity of the hypothalamic-pituitary adrenal (HPA) axis: the main stress response system (Sartori et al., 2012). Brain areas associated with anxiety include: the amygdala, the hippocampus, and the ventromedial prefrontal cortex (Abumaria et al., 2011). The neurophysiological etiology of anxiety is highly complex and not entirely understood; however, rodent experiments have provided some useful details about the role magnesium plays in the pathophysiology of anxiety. For example, under normal, healthy circumstances, N-Methyl-D-Aspartate (NMDA) receptors in brain regions associated with anxiety are typically inhibited by the presence of magnesium in the extracellular fluids. It’s as if magnesium is standing at a gate guarding against NMDA receptor stimulation (Lezhitsa et al., 2011). NMDA receptors are stimulated by the excitatory neurotransmitter, glutamate, which is the main neurotransmitter responsible for healthy and unhealthy nervous system function (Newcomer et al., 2000). An adequate concentration of magnesium in the extracellular fluids is crucial to keep NMDA receptor activation stable. Excessive NMDA receptor activation by glutamate, causes hyperstimulation, excitotoxicity, and neuronal cell death, leading to cognitive and mood disorders like anxiety (Newcomer et al., 2000). Magnesium deficiency resulting in hyperexcitability of NMDA receptors has been linked as one of the physiological origins of anxiety disorders (LeDoux, 2007; Grober et al., 2015; Poleszak et al., 2004). As magnesium inhibits NMDA receptor activation, it also simultaneously promotes gamma-aminobutyric acidA (GABAA) receptor function (Poleszak, 2008). GABAA receptors are stimulated by GABA, an inhibitory neurotransmitter that promotes calm and relaxation. Once GABAA receptors are stimulated, chloride (an inhibitory anion) surges into the neuron thus causing hyperpolarization: a state that helps to prevent neuronal activation (Kandel et al., 2000). In 2008, Poleszak demonstrated that magnesium provides anxiolytic effects not only through NMDA receptor inhibition (Poleszak et al., 2004), but through the potentiation of GABAA receptors as well. Magnesium helps to bind GABA to the GABAA receptor thus helping to prevent excessive neuronal stimulation that can result in anxiety (Moykkynen et al., 2001). In addition to receptor stimulation, magnesium also modulates hormonal activity associated with stress and anxiety. Intense stress and anxiety can trigger the fight-or flight response: a state associated with hypothalamic-pituitary adrenal (HPA) axis activation and the secretion of stress-related hormones (Smith & Vale, 2006). Magnesium suppresses the release of stress hormones like adrenocorticotropin hormone (ACTH) from the pituitary gland and the secretion of cortisol and epinephrine from the adrenal glands — the two main hormones responsible for the physiological cascade of the fight-or-flight response (Sartori et al., 2012). Essentially, when it comes the stress response, magnesium acts like a warmly welcomed chill-pill.

The Cortical Landscape of Anxiety

Brain regions most associated with the state of anxiety include: the amygdala, the hippocampus, and the ventromedial prefrontal cortex (VMPFC). Magnesium plays an important role in the function and modulation of each region.

The Amygdala

The amygdala is an almond-shaped structure located near the centre of the brain, within the medial temporal lobe. There are two amygdalas: one located in each hemisphere. Each amygdala is made up of separate subregions known as nuclei that connect to distinct cortical and subcortical circuitry (LeDoux, 2007; Pittman & Karle, 2015). The amygdala is most associated with the emotional state of fear. In fact, increased activation within the amygdala generates fear responses to non-threatening stimuli (Guyer et al., 2008). During fear conditioning when repeated events trigger a learned fear response, neuronal plasticity occurs within the lateral amygdala thus forming fearful memories (LeDoux, 2007). Plasticity is the neuronal process that underlies learning. It involves rewiring of neuronal connections and synaptic activity to form new functional memories (Kandel et al., 2000). From a basic neurophysiological standpoint, magnesium plays a critical role in plasticity and the learning of new fearful memories within the amygdala (LeDoux, 2007). When a person experiences something that their conscious or subconscious deems as dangerous, this triggers the release of the neurotransmitter glutamate within the lateral amygdala, which then stimulates NMDA receptors, thus exciting neuronal cells through a process called depolarization. Typically, magnesium within the extracellular fluids blocks glutamate and NMDA receptor activation; however, the added shock of the perceived danger causes the magnesium to displace from its blocking position, thus allowing NMDA receptor excitation. If this excitation happens repeatedly, over and over again, plasticity in the lateral amygdala occurs and a new fearful memory is learned (LeDoux, 2007). In essence, the amygdala houses the circuits for learned fear responses and drives the behavioural reactions to that fear (Abumaria et al., 2011). Developing fearful memories and their related safety behaviours is crucial for survival. As humans we need to recognize dangers and react to them — an ability that is definitely an evolutionary advantage (Abumaria et al., 2011). Our cavemen ancestors needed to recognize and escape from predatory animals and to spot poisonous plants. Without the amygdala and the ability to form fearful, yet informative, memories and reactions, survival would only become precarious. If you remove the amygdala, the fear response disappears along with thoughts of self-protection (LeDoux, 2007). However, experiencing excessive fear associated with objects or situations that are not innately dangerous can develop into a chronic anxiety disorder that can be resistant or remitting to pharmacological treatment or cognitive therapy (Abumaria et al., 2011).

The Hippocampus

The hippocampus is a part of the hippocampal formation located within the medial temporal lobe in the same vicinity as the amygdala. And, just like the amygdala, there are two hippocampal formations within each hemisphere (Andersen, 2011). Among its many functions, the hippocampus helps us to form fearful memories within the amygdala by providing spatial and temporal information about the stimulus that is deemed dangerous. The hippocampus also plays a supportive role in the process of learning new, healthy memories that inhibit the fearful memories stored in the lateral amygdala — this process is known as extinction. In terms of extinction, the amygdala generates and houses fearful memories, while the hippocampus and VMPFC form new memories that govern the expression of the fear response associated with the fearful memories (Abumaria et al., 2011). Slutsky et al. (2010) reported that increasing magnesium concentration within the brain by administering magnesium L-threonate (MgT) to rodents enhanced learning-related plasticity within the hippocampus. Since the hippocampus plays a role in the extinction of fearful memories, supplementing with magnesium might be a useful strategy to aid extinction, enhance memory, and prevent age-related cognitive and memory decline (Slutsky et al., 2010).

The Prefrontal Cortex

The prefrontal cortex (PFC), unlike the amygdala and hippocampus, is located within the anterior portion of bilateral frontal lobes on the surface of the brain. It governs highly complex goal-directed behaviours, frequently classified as ‘executive functions’ (Funahashi & Andreau, 2013). The VMPFC has direct connections with the amygdala, and dysfunction within this connection can cause an anxiety disorder (Guyer et al., 2008). Since the VMPFC, with the aid of the hippocampus, creates new learned memories that can extinguish fearful memories housed within the amygdala, finding a way to stimulate learning-related plasticity within these regions would be an advantage and potentially helpful to those suffering from an anxiety disorder (Abumaria et al., 2011). From a natural medicine perspective, preliminary research in the rodent model shows administering oral magnesium supplementation, in the form of magnesium Lthreonate (MgT), can enhance the formation of extinction memories not only within the hippocampus (Slutsky et al., 2008), but the VMPFC as well (Abumaria et al., 2011; Fitzgerald et al., 2013). Abumaria and colleagues (2011) demonstrated that administering MgT improved working memory, learning ability, and short and long-term memory in the rodent model. Is it then possible for MgT to enhance memory production and extinction in the VMPFC and hippocampus of humans to hasten anxiety disorder treatment and recovery? That is a question that still needs to be explored.

Anxiety and Magnesium Deficiency

Despite the critical role that minerals play in healthy brain function, most Canadian diets are sorely deficient in essential minerals, thus predisposing a significant portion of the population to anxiety related disorders, not to mention other mental health issues (Health Canada, 2013). According to Health Canada, 45% of Canadians fail to consume the minimum daily requirement of 250 mg of magnesium (Health Canada, 2013; Canadian Food Inspection Agency, 2016). That’s a shocking 10.4 million Canadians at risk of developing magnesium deficiency and subsequent anxiety disorders. To make matters worse, Canadians who are chronically magnesium deficient cannot simply add additional magnesium rich foods to their diet hoping to solve their hypomagnesemia. In the last 100 years, mineral concentration in agricultural soil has significantly decreased, making it difficult for people to consume adequate amounts of minerals like magnesium from harvested food (Marler & Wallin, 2006). Therefore, in moderate to severe cases of magnesium deficiency, supplementation is the only course of treatment (Durlach et al., 1994). Inadequate blood magnesium concentration triggers symptoms such as anxiety, nervousness, agitation, low stress tolerance, weakness, and depression (Grober et al., 2015). In rodent experiments, brain and blood plasma levels of magnesium are significantly correlated with anxiety behaviours (Laarakker et al., 2011), and magnesium supplementation has been shown to have anxiolytic and antidepressant effects by acting as an NMDA receptor antagonist, as long as magnesium blood serum concentration was raised by at least 58% (Poleszak et al., 2004).

Treating Anxiety with Magnesium

Taking all of the information discussed into consideration, it is scientifically evident that magnesium supplementation has the potential to reduce anxiety by: (1) inhibiting NMDA receptor activation (Lezhitsa et al., 2011), (2) potentiating GABAA receptor activation (Moykkynen et al., 2001), (3) reducing the secretion of ACTH, cortisol, and epinephrine from the pituitary and adrenal glands respectively (Sartori et al., 2012), and (4) enhancing neuronal plasticity for new extinction memories within the hippocampus and VMPFC (Poleszak, 2004 & 2008). To date, cognitive behavioural therapy is considered the most effective form of treatment for anxiety disorders (Rector et al., 2016). Pharmacotherapy treatments for clinical anxiety (antidepressants, serotonin-specific reuptake inhibitors (SSRIs), and benzodiazepines) are available, but they can come with a host of negative side effects like decreased alertness, dependency, sexual dysfunction, and even suicidal thoughts (Lakhan & Vieira, 2010). For some, pharmacotherapy simply is not an option: they would prefer a more natural solution. Therefore, studying the efficacy of natural treatments like magnesium has great clinical significance (Boyle et al., 2017). Several human studies have investigated the effects of magnesium in combination with zinc, calcium, or plant extracts, demonstrating that combined therapy is effective to reduce anxiety (Carroll et al., 2000; De Souza et al., 2000; Hanus et al., 2004). However, to get a real sense of the effectiveness of magnesium, it would be prudent for researchers to focus on the mono-mineral rather than in combination. Experiments in the rodent population have shown significant anxiolytic effects using the following magnesium derivations: mg-aspartate, mg-chloride, mg-L-threonate, mg-lactate, mg-oxide, or mg-pyroglutamate (Abumaria et al., 2011; Lezhitsa et al., 2011); however, there are no studies to date that have definitively determined which form of magnesium is the best to reduce anxiety.

References

Abumaria, N., Yin, B., Zhang, L., Li, X. Y., Chen, T., Descalzi, G., ... & Zhuo, M. (2011). Effects of elevation of brain magnesium on fear conditioning, fear extinction, and synaptic plasticity in the infralimbic prefrontal cortex and lateral amygdala. Journal of Neuroscience, 31(42), 14871-14881. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC: Author. Andersen, P. (Ed.). (2007). The hippocampus book. Oxford University Press. Baxter, A. J., Scott, K. M., Vos, T., & Whiteford, H. A. (2013). Global prevalence of anxiety disorders: a systematic review and meta-regression. Psychological medicine, 43(5), 897-910. Boyle, N. B., Lawton, C., & Dye, L. (2017). The Effects of Magnesium Supplementation on Subjective Anxiety and Stress—A Systematic Review. Nutrients, 9(5), 429. Canadian Food Inspection Agency. (2016 January 12). Information within the nutrition facts table: Daily intake. Retrieved from: http://www.inspection.gc.ca/food/labelling/food-labelling-for-industry/nutritionlabelling/information-within-the-nutrition-factstable/eng/1389198568400/1389198597278?chap=6 Canadian Mental Health Association. (2013 September). Anxiety disorders. Retrieved from: http://www.cmha.ca/mental_health/understanding-anxietydisorders/#.WXjhJ__ysy4 Carroll, D., Ring, C., Suter, M., & Willemsen, G. (2000). The effects of an oral multivitamin combination with calcium, magnesium, and zinc on psychological wellbeing in healthy young male volunteers: a double-blind placebo-controlled trial. Psychopharmacology, 150(2), 220-225. De Souza, M. C., Walker, A. F., Robinson, P. A., & Bolland, K. (2000). A synergistic effect of a daily supplement for 1 month of 200 mg magnesium plus 50 mg vitamin B6 for the relief of anxiety-related premenstrual symptoms: a randomized, double-blind, crossover study. Journal of women's health & gender-based medicine, 9(2), 131-139. Durlach, J., Durlach, V., Bac, P., Bara, M., & Guiet-Bara, A. (1994). Magnesium and therapeutics. Magnesium research, 7(3-4), 313-328. Fitzgerald, P. J., Seemann, J. R., & Maren, S. (2014). Can fear extinction be enhanced? A review of pharmacological and behavioral findings. Brain research bulletin, 105, 46-60. Funahashi, S., & Andreau, J. M. (2013). Prefrontal cortex and neural mechanisms of executive function. Journal of Physiology-Paris, 107(6), 471-482. Gröber, U., Schmidt, J., & Kisters, K. (2015). Magnesium in prevention and therapy. Nutrients, 7(9), 8199-8226. Guyer, A. E., Lau, J. Y., McClure-Tone, E. B., Parrish, J., Shiffrin, N. D., Reynolds, R. C., ... & Ernst, M. (2008). Amygdala and ventrolateral prefrontal cortex function during anticipated peer evaluation in pediatric social anxiety. Archives of general psychiatry, 65(11), 1303-1312. Hanus, M., Lafon, J., & Mathieu, M. (2004). Double-blind, randomised, placebo controlled study to evaluate the efficacy and safety of a fixed combination containing two plant extracts (Crataegus oxyacantha and Eschscholtzia californica) and magnesium in mild-to-moderate anxiety disorders. Current medical research and opinion, 20(1), 63-71. Health Canada. (2013 June 24). Percentage of adults with a usual intake of magnesium below the estimated average requirement (EAR) in Canada. Retrieved from: http://www.hc-sc.gc.ca/fn-an/surveill/atlas/map-carte/adult_magnesium-eng.php Kandel, E.R., Schwartz, J.H., & Jessell, T.M. (2000). Principles of Neural Science (4th ed.). New York, NY: McGraw-Hill. Laarakker, M. C., van Lith, H. A., & Ohl, F. (2011). Behavioral characterization of A/J and C57BL/6J mice using a multidimensional test: association between blood plasma and brain magnesium-ion concentration with anxiety. Physiology & behavior, 102(2), 205-219. Lakhan, S. E., & Vieira, K. F. (2010). Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review. Nutrition Journal, 9(1), 42. LeDoux, J. (2007). The amygdala. Current biology, 17(20), R868-R874. Lezhitsa, I. N., Spasov, A. A., Kharitonova, M. V., & Kravchenko, M. S. (2011). Effect of magnesium chloride on psychomotor activity, emotional status, and acute behavioural responses to clonidine, d-amphetamine, arecoline, nicotine, apomorphine, and L-5-hydroxytryptophan. Nutritional neuroscience, 14(1), 10-24. Marler, J. B. & Wallin, J. R. (2006). Human health, the nutritional quality of harvested food and sustainable farming systems. Nutrition Security Institute, USA. Mathers, C. D., Lopez, A. D., & Murray, C. J. (2006). The burden of disease and mortality by condition: data, methods and results for 2001. Global burden of disease and risk factors, 45, 88. Möykkynen, T., Uusi-Oukari, M., Heikkilä, J., Lovinger, D. M., Lüddens, H., & Korpi, E. R. (2001). Magnesium potentiation of the function of native and recombinant GABAA receptors. Neuroreport, 12(10), 2175-2179. Newcomer, J.W., Farber, N.B., & Olney, J.W. (2000). NMDA receptor function, memory, and brain aging. Dialogues in clinical neuroscience, 2(3), 219. Pearson, C., Janz, T. & Ali, J. (2013). Mental and substance use disorders in Canada. Health at a Glance. September. Statistics Canada Catalogue no. 82-624-X. Pittman, C. M., & Karle, E. M. (2015). Rewire Your Anxious Brain: How to Use the Neuroscience of Fear to End Anxiety, Panic, and Worry. New Harbinger Publications. Poleszak, E., Szewczyk, B., Kędzierska, E., Wlaź, P., Pilc, A., & Nowak, G. (2004). Antidepressant-and anxiolytic-like activity of magnesium in mice. Pharmacology Biochemistry and Behavior, 78(1), 7-12. Poleszak, E. (2008). Benzodiazepine/GABAA receptors are involved in magnesium-induced anxiolytic-like behavior in mice. Pharmacological Reports, 60(4), 483. Rector, N. A., Laposa, J. M., Kitchen, K., Bourdeau, D., & Joseph-Massiah, L. (2016). Anxiety disorders: An information guide. Centre for Addiction and Mental Health. Roberge, P., Fournier, L., Duhoux, A., Nguyen, C. T., & Smolders, M. (2011). Mental health service use and treatment adequacy for anxiety disorders in Canada. Social psychiatry and psychiatric epidemiology, 46(4), 321-330. Sartori, S. B., Whittle, N., Hetzenauer, A. & Singewald, N. (2012). Magnesium deficiency induces anxiety and HPA axis dysregulation: modulation by therapeutic drug treatment. Neuropharmacology, 62(1), 304-312. Slutsky, I., Abumaria, N., Wu, L. J., Huang, C., Zhang, L., Li, B., ... & Tonegawa, S. (2010). Enhancement of learning and memory by elevating brain magnesium. Neuron, 65(2), 165-177. Swaminathan, R. (2003). Magnesium metabolism and its disorders. The Clinical Biochemist Reviews, 24(2), 47. Smith, S. M., & Vale, W. W. (2006). The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues in clinical neuroscience, 8(4), 383. Wester, P. (1987). Magnesium. American Journal of Clinical Nutrition, 45, 1305–1312
Supplements for Insomnia and Sleep Disorders
4 Natural Solutions that Promote Calmful Sleep By ...

4 Natural Solutions that Promote Calmful Sleep

By Anna O'Byrne and Laura Young, clinical research expert, Honours B.Sc., student of the Canadian College of Osteopathy According to 2011 research conducted at Université Laval, sleep disorders affect 40% of adult Canadians (Science Daily, 2011). While only 13.4% of those surveyed displayed all symptoms required to diagnose insomnia, the full 40% experienced symptoms of insomnia at least three times a week (Science Daily, 2011).

What is Insomnia?  

Insomnia is characterized by sleep onset delay and difficulty with sleep maintenance, including nocturnal wakefulness and waking earlier than planned (Science Daily, 2011). The causes of insomnia are varied and include: poor sleep hygiene; existing psychiatric or medical conditions; certain substances; stress; and sleep disorders (Sleep Foundation, n.d.). A number of sleep disorders are caused by circadian rhythm disruptions. The more common of these include: delayed sleep-wake phase disorder, shift work disturbances and travel-related jetlag (Sleep Education, 2017). What is now deemed ‘social jet lag’ occurs with “self-selected modifications to the natural light/dark cycle” and resultant variations between sleep time on weekdays and weekends (Swaminathan, Klerman, & Phillips, 2017).

Insomnia Effects and Treatment Options

Poor sleep and lack of sleep is associated with a range of psychological, psychiatric and medical conditions. Insomnia affects cognitive, emotional and social functioning (Misra & Sharma, 2017). A vast body of research exists investigating the relationship between poor sleep and health-related quality of life (Brevik et al., 2017). Pharmacological treatments are considered less than ideal (Misra & Sharma, 2017). Most sleep inducers are sedatives and are often associated with addiction and other side effects (Rao, Ozeki, & Juneja, 2015). Non-pharmacological treatments include, “stimulus control therapy, sleep restriction, relaxation, sleep hygiene and cognitive therapy” (Misra & Sharma, 2017). In the quest for safer, more effective insomnia solutions, we also look to alternative medicine.

Natural Supplements for Extra Sleep Support

Magnesium

Magnesium “plays a critical role in nerve transmission, cardiac excitability, neuromuscular conduction, muscular contraction, vasomotor tone, blood pressure” and more (Volpe, 2013). As early as 1980, researchers demonstrated the effects of magnesium on sleep. In a polygraphic study of newborns, sleep behaviour positively correlated to serum magnesium levels. An increase in magnesium resulted in an increase of quiet sleep and a decrease in active sleep (Dralle & Bodeker, 1980). More recently, Abbasi et al. (Abbasi et al., 2012) reported in a double-blind, randomized, placebo-controlled study of older patients with insomnia, that daily magnesium supplementation induced statistically significant increases in sleep time and sleep efficiency. A significant decrease in insomnia severity scores and sleep onset latency, among other positive indicators were further reported (Abbasi et al., 2012). Magnesium is a GABA agonist (more on which, below) and plays “a key role in the regulation of sleep and endocrine systems” (Held et al., 2002). Held et al. investigated the effect of magnesium supplementation on age-related neuroendocrine and sleep EEG changes in a placebo-controlled, randomized cross-over study (Held et al., 2002). The results demonstrated that magnesium supplementation led to a significant increase in slow wave sleep and the results suggest that magnesium partially reverses sleep EEG and nocturnal neuroendocrine changes occurring during aging (Held et al., 2002).

L-theanine

“L-theanine (γ-glutamylethylamide) is an amino acid found primarily in the green tea plant” (White et al., 2016). A 2016 study published in the journal, Nutrients, reported, “subjective stress response to a multitasking cognitive stressor, was significantly reduced one hour after administration of the L-theanine drink when compared to placebo” (White et al., 2016). In a 2017 review of acute psychoactive effects, L-theanine taken alone was found to improve self-reported relaxation, tension and calmness (Dietz & Dekker, 2017). As a treatment for sleep disorders, according to a review published in the Journal of the American College of Nutrition in 2015, L-theanine is a “safe natural sleep aid” (Rao et al., 2015). It has been found to “promote relaxation without drowsiness,” and “unlike conventional sleep inducers, L-theanine is not a sedative but promotes good quality of sleep through anxiolysis.” (Rao et al., 2015). Melatonin Melatonin (N-acetyl-5-methoxy-tryptamine) is a chief secretory product of the pineal gland with a well-established relationship to sleep (Zhang et al., 2017). The production of melatonin is triggered by low-light conditions, and higher levels in the bloodstream encourage sleep (Sleep Foundation, n.d.). Circadian rhythms of melatonin are significantly delayed through exposure to artificial light at night (Cuesta, Boudreau, Cermakian, & Boivin, 2017). Strategically-timed melatonin administration is indicated for the treatment of intrinsic circadian rhythm sleep-wake disorders (American Academy of Sleep Medicine et al., 2015). Melatonin, aside from phase-shifting these rhythms, “may have direct soporific effects, particularly at higher doses” (American Academy of Sleep Medicine et al., 2015). Studies suggest that timing of melatonin for these disorders is more important than dosing, at least insofar as the phase-shifting effects are concerned (American Academy of Sleep Medicine et al., 2015). Randomized, double-blind clinical trials have demonstrated positive results with the use of melatonin for patients with primary insomnia aged ≥55 years (Lyseng-Williamson, 2012). Melatonin treatment demonstrated significant improvements relative to placebo in many sleep and daytime parameters, including: sleep quality and latency, morning alertness and health-related quality of life. Over the short and long-term, melatonin treatment was not associated with dependence, tolerance, rebound insomnia or withdrawal symptoms (Lyseng-Williamson, 2012). Similar positive results and positive carryover effects were reported in a study which investigated patients with insomnia related to chronic use of beta-blocker medications, which may suppress melatonin (Scheer et al., 2012). Age is a consideration in use of melatonin, and as a supplement, it is currently indicated for ages 18 – 80 (Wade et al., 2011). Wade et al. evaluated the age limit for use of melatonin. The randomized, double-blind, placebo-controlled study revealed short and long-term efficacy of melatonin for patients aged 18-80 years who experienced insomnia, with particularly strong results for those aged 55 and over (Wade et al., 2011). In all age cohorts, sleep improvements were maintained over the long-term, with no signs of tolerance, no withdrawal symptoms or rebound insomnia. Most adverse events were mild with no significant differences in safety outcomes between the melatonin and placebo groups (Wade et al., 2011). The use of melatonin for those under age 18 could be considered controversial, however, it may be indicated for individuals with certain conditions.  Cortesi et al. (Cortesi, Giannoti, Sebastiani, Panunzi, & Valente, 2012) investigated melatonin and cognitive behavioural therapy for persistent insomnia presenting in children with autism. The study reported that melatonin was found to elicit significant improvements across all outcome measures including: sleep latency, total sleep time, wake after sleep onset and number of awakenings. Melatonin therapy reduced insomnia symptoms and was most effective in combination with cognitive-behavioural therapy (Cortesi et al., 2012).

 Gamma-aminobutyric Acid (GABA)

GABA is the chief inhibitory neurotransmitter in the brain (Watanabe, Maemura, Kanbara, Tamayama, & Hayasaki, 2002). It is synthesized in the brain via a process that converts glutamate, an excitatory neurotransmitter, into an inhibitory neurotransmitter (Petroff, 2002; Schousboe & Waagepetersen, 2007). Marketed as an amino acid supplement, GABA is purported to relax the nervous system and reduce anxiety. The research on GABA for sleep is preliminary but promising. Studies have reported a close association between sleep and the GABAergic system (Held et al., 2002). Two studies published in the journal, Biofactors, demonstrated the natural relaxant and anti-anxiety effects on humans of orally administrated γ-Aminobutyric acid (GABA). The first study evaluated the effect of GABA intake via electroencephalograms (EEG), and showed that GABA significantly increased alpha waves and decreased beta waves compared to water or L-theanine. The researchers concluded GABA not only induces relaxation but also reduces anxiety (Abdou et al., 2006). Meverhoff et al. (Meverhoff, Mon, Metzler, & Neylan, 2014) investigated cortical GABA and glutamate in posttraumatic stress disorder (PTSD). Self-reported sleep quality revealed a correlation between poor sleep quality and GABA levels. Those with PTSD had lower cortical GABA levels, higher depressive, anxiety and insomnia scores (Meverhoff et al., 2014).

Conclusions

Studies suggest that non-pharmacological products may significantly reduce symptoms of insomnia, with high levels of safety. Various clinical studies have demonstrated the efficacy of magnesium, l-theanine, melatonin and GABA in improving sleep quality.

Resources

Abbasi, B., Kimiagar, M., Sadeghniiat, K., Shirazi, M., Hedayati, M., & Rashidkhani, B. (2012). The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial. The Official Journal of Isfahan University of Medical Sciences, 17(12), 1161–1169. Abdou, M. A., Higashiguchi, S., Horie, K., Kim, M., Hatta, H., & Yokogoshi, H. (2006). Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans. BioFactors, 201–208. American Academy of Sleep Medicine, Auger, R. R., Burgess, H. J., Emens, J. S., Deriy, L. V., Thomas, S. M., & Sharkey, K. M. (2015). Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD). An Update for 2015. Journal of Clinical Sleep Medicine, 11(10), 1199–1236. http://doi.org/10.5664/jcsm.5100 Brevik, E. J., Lundervold, A. J., Halmøy, A., Posserud, M. B., Instanes, J. T., Bjorvatn, B., & Haavik, J. (2017). Prevalence and clinical correlates of insomnia in adults with attention-deficit hyperactivity disorder. Acta Psychiatrica Scandinavica. http://doi.org/doi: 10.1111/acps.12756 Cortesi, F., Giannotti, F., Sebastiani, T., Panunzi, S., & Valente, D. (2012). Controlled-release melatonin, singly and combined with cognitive behavioural therapy, for persistent insomnia in children with autism spectrum disorders: a randomized placebo-controlled trial. Journal of Sleep Research, 21(6), 700–709. http://doi.org/10.1111/j.1365-2869.2012.01021.x Cuesta, M., Boudreau, P., Cermakian, N., & Boivin, D. B. (2017). Skin Temperature Rhythms in Humans Respond to Changes in the Timing of Sleep and Light. Journal of Biological Rhythms. Dietz, C., & Dekker, M. (2017). Effect of Green Tea Phytochemicals on Mood and Cognition. Current Pharmaceutical Design. Dralle, D., & Bodeker, R. H. (1980). Serum magnesium level and sleep behavior of newborn infants. European Journal of Pediatrics, 134(3), 239–243. Held, K., Antonijevic, I. A., Kunzel, H., Uhr, M., Wetter, T. C., Golly, I. C., et al. (2002). Oral Mg(2+) supplementation reverses age-related neuroendocrine and sleep EEG changes in humans. Pharmacosychiatry, 35(4), 135–143. Lyseng-Williamson, K. A. (2012). Melatonin prolonged release: in the treatment of insomnia in patients aged ≥55 yrs. Drugs & Aging, 29(11), 911–923. Meverhoff, D., Mon, A., Metzler, T., & Neylan, T. C. (2014). Cortical gamma-aminobutyric acid and glutamate in posttraumatic stress disorder and their relationships to self-reported sleep quality. Sleep, 37(5), 893–900. Misra, A., & Sharma, P. K. (2017). Pharmacotherapy of Insomnia and Current Updates. J Assoc Physicians India, 65(4), 43–47. Petroff, O. A. (2002). GABA and glutamate in the human brain. Neuroscientist, 8(6), 562–573. Rao, T. P., Ozeki, M., & Juneja, L. R. (2015). In Search of a Safe Natural Sleep Aid. The Journal of the American College of Nutrition, 34(5), 436–437. Scheer, F. A. J. L., Morris, C. J., Garcia, J. I., Smales, C., Kelly, E. E., Marks, J., et al. (2012). Repeated Melatonin Supplementation Improves Sleep in Hypertensive Patients Treated with Beta-Blockers: A Randomized Controlled Trial. Sleep, 35(10), 1395–1402. http://doi.org/10.5665/sleep.2122 Schousboe, A., & Waagepetersen, H. (2007). GABA: homeostatic and pharmacological aspects. Progress in Brain Research, 9–19. Sleep Foundation: Sleep Disorders. (n.d.). www.sleepfoundation.org. Retrieved June 7, 2017. Science Daily: Sleep disorders affect 40 percent of Canadians. (2011, September 8). www.sciencedaily.com. Retrieved June 9, 2017. Sleep Education: Delayed Sleep-Wake Phase – Overview & Facts. (2017). www.sleepeducation.org. Retrieved June 7, 2017. Swaminathan, K., Klerman, E. B., & Phillips, A. (2017). Are Individual Differences in Sleep and Circadian Timing Amplified by Use of Artificial Light Sources? Journal of Biolo, 32(2), 165–176. http://doi.org/doi: 10.1177/0748730417699310 Volpe, S. L. (2013). Magnesium in disease prevention and overall health. Advanced Nutrition, 4(3), 378S–83S. Wade, A. G., Crawford, G., Ford, I., McConnachie, A., Nir, T., Laudon, M., & Zisapel, N. (2011). Prolonged release melatonin in the treatment of primary insomnia: evaluation of the age cut-off for short- and long-term response. Current Medical Research and Opinion, 27(1), 87–98. Watanabe, M., Maemura, K., Kanbara, K., Tamayama, T., & Hayasaki, H. (2002). GABA and GABA receptors in the central nervous system and other organs. International Review of Cytology, 213, 1–47. White, D. J., de Klerk, S., Woods, W., Gondalia, S., Noonan, C., & Scholey, A. B. (2016). Anti-Stress, Behavioural and Magnetoencephalography Effects of an L-Theanine-Based Nutrient Drink: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial. Nutrients, 8(1). Zhang, L., Guo, H. L., Zhang, H. Q., Xu, T. Q., He, B., Wang, Z. H., et al. (2017). Melatonin prevents sleep deprivation-associated anxiety-like behavior in rats: role of oxidative stress and balance between GABAergic and glutamatergic transmission. American Journa of Translation Research, 9(5), 2231–2242.    
A Complete Magnesium Primer?
Recently, Natural Calm Canada published a white pa...
Recently, Natural Calm Canada published a white paper on magnesium absorption - an arm's length review of the peer-reviewed literature, by a PhD in microbiology, Dr. Jon-Paul Powers. The white paper discredited certain claims in the natural health industry, particularly by marketers of magnesium glycinate - a good form of magnesium, but not one that has been proven superior. Dr. Powers' research made it clear that no credible studies have been published to date comparing magnesium glycinate with citrate. What research does exist suggests that the two are comparable, or that magnesium citrate may be more absorbable. Shortly after, a leading magnesium glycinate brand released a document entitled "Magnesium Bis-Glycinate: Redefined. Redesigned." and later, "Magnesium a Complete Primer". The papers came to our attention when we were asked to account for a study therein comparing magnesium glycinate to magnesium citrate. The study, however, was not available on PubMed, suggesting it had not been published or peer-reviewed. Again, we outsourced the scientific analysis to experts: this time, to Dr. Alison Smith, PhD. The following is her critique of the primer and the study cited therein. We also append a critical review of "Magnesium Bis-Glycinate: Redefined. Redesigned."

Review of the White Paper: "Magnesium a Complete Primer"

By: Alison Smith, Ph.D General Comments:
  • Magnesium a Complete Primer is a 68-page white paper released in May 2017 by a Canadian magnesium glycinate company. It contains information pertaining to magnesium function, dietary sources, deficiency, absorption, and the brand's magnesium products. The current analysis will focus on the topic of magnesium absorption on pages 35-40.
  • The document contains some references (pg. 50); however, most of the information pertaining to magnesium absorption is not referenced. The one reference used to support their claim is misleading and does not meet appropriate scientific standards.
Specific Comments:
  1. Pg. 36.“...the further away you travel from the stomach, the less acidic the environment becomes. The less acidic the environment, the harder it is for magnesium ions to remain soluble.” This information is not referenced and is therefore misleading. The author uses this statement to build toward their claim that magnesium amino acid chelates (like magnesium bis-glycinate) are superior to magnesium salts (like magnesium citrate etc.); however, there are no studies to support that claim.
  2. Pg. 37. “Magnesium amino acid complexes (or chelates) behave differently than magnesium salts...they use other transport sites called dipeptide channels.” Unreferenced claim. Even if chelates can use different channels than dissociated magnesium salts, where is the evidence that this possibility results in superior absorption of chelates?
  3. Pg. 37. “Mineral amino acid complexes are actually quite common in nature and a natural way we get magnesium from our diet.” This claim is unreferenced. It misleads consumers into believing amino acid complexes are the best type of magnesium supplement to take.
  4. Pg. 39. “...we can reliably investigate how well different magnesium types are absorbed through the intestinal walls.” This statement is misleading, unreferenced, and contradictory. The author argues in the previous paragraphs -- leading up to this statement -- that it is difficult to measure magnesium levels in the blood serum, blood cells, and urine. Since these are the only methods to measure absorption of magnesium in humans, this statement is completely contradictory.
  5. Pg. 39-40. Starting on page 39, the author describes an experiment performed by Albion Laboratories Inc., written by Hartle, Morgan, and Poulsen (2016). This study used an artificial experimental method of predicting intestinal absorption of various types of magnesium by using a simulated intestine model. The simulated model placed intestinal cells on a welled plate. Magnesium of varying types was then placed into the liquid of the model. The author of the white paper argues that the movement of the different types of magnesium through the simulated membrane predicts how well those types of magnesium will absorb in the human intestine. The experiment tested the difference in absorbability between: Mg bis-glycinate, Mg bis-glycinate with Mg oxide, Mg citrate, Dimagnesium malate, Mg oxide, and a control. The authors, however, do not reference any studies that attest to the validity of this method. In a 2012 PubMed listed article by Etcheverry et al. (2012) the validity of in vitro models of intestinal absorption (like the model used in the Albion Minerals experiment) are evaluated. The authors point out that, “in vitro models of intestinal absorption cannot make any assumptions about the bioavailability of the nutrients used in a study” and “None of the methods currently used to assess magnesium bioaccessibility/bioavailability have been validated against human absorption studies, and no method has been used extensively.” Therefore, simulating intestinal cells on cultured plates cannot possibly substitute the human intestine, and it cannot be used to claim which form of magnesium is the most effective.
  6. Pg. 40. The authors use an abstract by Albion Laboratories Inc. written by Hartle et al. (2016) to support their claim that Mg bis-glycinate and buffered Mg bis-glycinate are more absorbable than Mg citrate or Mg oxide. You can read the abstract by Hartle et al. here: http://www.fasebj.org/content/30/1_Supplement/128.6.short
  7. Pg. 40 of the white paper...“The chelated magnesium bis-glycinate and buffered magnesium bis-glycinate...were much better absorbed than other forms of magnesium like magnesium citrate and magnesium oxide on its own.” There are several issues with this claim: (i) It is misleading. The experiment by Hartle et al. (2016) is not published as an article. The abstract was presented at the Experimental Biology 2016 Meeting (conference), but this does not mean that the results are valid, since abstracts are not peer-reviewed as published articles are. Abstracts cannot be used to support a claim because the data may not pass inspection during the peer-review process. Please see note about how scientific articles are published in point #8. (ii) Albion Minerals supplied the magnesium glycinate brand with the data for the graph on page 40. Using experimental results from their vendor, Albion Minerals is a serious conflict of interest.
(iii) The graph on Pg. 40 does not indicate which magnesium types are significantly different from each other. There is an ANOVA result listed, but what does it pertain to? In published scientific data, there would be asterisks above the bars that are statistically different from each other. The abstract by Albion is also unclear about which tests were significantly different from each other. (iv) The authors are misleading readers into believing that an artificial intestine model on a welled plate can reliably show which form of magnesium is best absorbed. The current scientific literature states that this method cannot reliably support this type of claim. 8. Note about publishing a scientific article: Publishing a scientific article is quite difficult. An article is submitted to a journal and evaluated by the editor-in-chief in addition to at least three different, independent, academic, peer-reviewers who are unknown to the author. The reviews’ job is to tear the paper apart, spot errors, suggest changes, demand more data and novelty...in essence, their job is to prevent publication. Scientific journals only want high calibre articles, so this process makes sense. There are two types of abstracts: those that accompany published articles, and those that accompany posters presented at a scientific conference. The abstract by Hartle et al. (2016) from Albion, is an abstract that was presented at a conference. This type of abstract is not peer-reviewed. It’s just a way to show the community your latest work. A conference abstract cannot be used to support any type of argument because the results and data are not peer-reviewed.

Review of "Magnesium Bis-Glycinate: Redefined. Redesigned."

By: Laura Young, Clinical Research Expert To earn respect in the scientific community, a paper requires peer-reviewed references. The authors of this paper have neglected to include references to support the claims stated in this paper. Further, a clinical research study must be performed and documented to demonstrate the behaviour of a product in the human body.  Several statements in this paper have not been proven by results from clinical research.  These include:
  • “Each blend employs the best mix of salts and complexes to maximize the supply of magnesium while maximizing the use of all the absorption channels.” (p. 5)
  • “But there is also free glycine. Mimicking your natural digestion process, glycine can form complexes with the magnesium ions in your gut. Once formed, they too can use the abundant dipeptide channels.” (p. 5)
  • “Compact molecules react faster and diffuse across cell membranes more rapidly than larger ones. Many molecules in pharmaceutical drugs are designed to be small for this very reason."
  • “As a magnesium complex, it is more quickly absorbed in the intestine.” (p. 5)
  • “The strong configuration of bonds in magnesium glycine complexes protect the mineral from unwanted reactions with these agents.” (p. 5)
  • “As a pH buffer, Glycine can help keep pH lower for longer down the intestinal tract. This allows for the better absorption of magnesium ions.” (p. 5)
Glysine is a non-essential amino acid. It is synthesized by the body in addition to obtaining some sources from the diet. The language used in this paper leads the reader to believe that supplementation with glysine is beneficial, which is not supported by references. Finally, the authors claim Magnesium oxide as a “great source of magnesium once it's combined with glycine” (p. 5), which contradicts the research.
  • Walker et al. (2003) demonstrated superiority of organic forms of Magnesium in terms of bioavailability over Magnesium oxide. Walker et al. further reported the bioavailability of magnesium oxide relative to placebo. The authors state, “A small amount of magnesium oxide can be a great source of magnesium once it’s combined with glycine.” (p. 5)
  • Walker et al. (2003) demonstrated the superiority of organic forms of Magnesium in terms of bioavailability over Magnesium oxide. Walker et al. further reported the bioavailability of magnesium oxide relative to placebo.
Fallingborg, J. 1999. Intraluminal pH of the human gastrointestinal tract. Danish Medical Bulletin. 46(3), 183-96. Walker, A.F., Marakis, G., Christie, S., Byng, M. 2003. Mg citrate found more bioavailable than other Mg preparations in a randomized, double-blind study. Magnesium Research. 16(3), 183-91.
Magnesium Citrate and Ceruloplasmin
Prepared for Natural Vitality by the Think Healthy...
Prepared for Natural Vitality by the Think Healthy Group in Collaboration with the Center for Magnesium Education & Research, LLC. Republished here with the permission of Dr. Rosanoff. For the original post, please go to http://www.magnesiumeducation.com/consumer-education-research-on-magnesium-issues

Facts About Ceruloplasmin

  • Ceruloplasmin is the major copper-carrying protein in the blood and plays an active role in the metabolism of iron.
  • Ceruloplasmin binds free copper and iron thus inhibits their ability to start free radical information.
  • There is a theory that the free copper and iron-binding activity of ceruloplasmin decreases lipidoxidation (i.e., is an antioxidant) and the development of atherosclerosis (based on cell studies). Human studies have not confirmed this theory.

Citrate and Ceruloplasmin

  • It is well known that adequate magnesium status conveys antioxidant capability to a human body.
  • Most studies on citrate and ceruloplasmin are over 25 years old and out of date. Many are from the 1960s.
  • One 8-ounce glass of orange juice contains about the same amount of citrate as one serving (2 tsp) of Natural Vitality’s Natural Calm.
Some cell and animal studies suggest that either citrate or ascorbic acid can inhibit the activity of ceruloplasmin. For example, Lovstad (1996) suggested that 10-mM concentrations of citrate can inhibit the ferroxidase activity of ceruloplasmin in a cell study. There are three problems with cell and/or animal studies such as Lovstad (1996):
  1. Normal human plasma concentrations of citrate range between 0.05 mM and 0.3 mM.
  2. 10-mM plasma concentrations (30 to 200 times normal) are likely only achieved through intravenous administration of citrate for medical purposes and not through a typical recommended dose of a magnesium citrate supplement.
  3. Humans and other mammals filter and excrete citrate much more efficiently than rats and other test animals.Human intervention studies have not been able to reproduce these findings reported in cells and/or animals.To theoretically inhibit the activity of ceruloplasmin, a human would need to consume levels of either citrate and/or vitamin C (ascorbic acid) that are not possible through food intake. One would need to consume at least an entire 8-ounce container (56 servings) of Natural Vitality’s Natural Calm magnesium citrate supplement in one serving to get this effect.
Doctors have been using high-dose vitamin C for decades without any difficulties. There is no credible scientific evidence that taking magnesium citrate at levels recommended on supplement labels has any effect on ceruloplasmin.

Overview: The Effect of Magnesium Citrate on Ceruloplasmin

Scope of Work

The Center for Magnesium Education and Research is providing this scientific mini-review of how magnesium citrate affects ceruloplasmin based on the current peer-reviewed scientific literature to date. Consumer education on how magnesium citrate affects ceruloplasmin was developed based on the mini-review of the scientific literature.

Methodology

PubMed Search 1: (magnesium) AND ceruloplasmin PubMed Search 2: (citrate) AND ceruloplasmin Exclusion criteria: non-English studies 64 articles were identified and their abstracts were reviewed. 13 articles were identified as relevant and were reviewed in full-text.

Results and Conclusions

Ceruloplasmin is the major copper-carrying protein in the blood and plays an active role in the metabolism of iron. Lower ceruloplasmin levels may indicate either a copper and/or zinc deficiency or a vitamin C overload (using amounts far greater than typical human consumption). Ceruloplasmin has been proposed as an important factor in cellular iron efflux and has been suggested to be downregulated in atherosclerotic plaques.3 Ceruloplasmin functions as an antioxidant. Free copper and iron are powerful catalysts of free radical damage. Ceruloplasmin binds free copper ions and prevents free radical–induced oxidative damage.4 In a similar manner, ceruloplasmin facilitates iron loading onto its transport protein (i.e., transferrin) and prevents free ferrous (Fe+2) from participating in free radical–generating reactions.4 The interaction of copper and ascorbate (i.e., vitamin C) has been described since the early 1960s. Dietary ascorbate has been suggested to interfere with copper absorption in several animal and human studies at high levels.5 Since ascorbate seems to influence the free metal, and since 90–95% of copper found in the serum is bound to ceruloplasmin, some scientists have hypothesized that ascorbate (or citrate) may have an influence on this protein. The oxidase activity (i.e., the ability to bind free copper and iron) of ceruloplasmin has been suggested to be lower in the presence of ascorbate in vitro and in animal models.4 Contrary to this hypothesis, a small human intervention by Jacob et al.6 found that while ceruloplasmin’s oxidase activity was lower in young men fed a high level of vitamin C, it did not depress intestinal copper absorption or overall body copper status. Higher serum vitamin C levels did not result in a decrease in ceruloplasmin levels or its enzymatic activity.6 This is consistent with another small human intervention study that reported that 1500 mg/d supplementation with vitamin C had no effect on copper balance or blood levels of copper in young women.7 In humans, normal citrate concentrations in the plasma range between 0.05 and 0.3 mM.8,3

References

1.Kumar A, Archana E, Pai A, Gayathry N, Shenoy RP, Rao A. Serum mineral status and climacteric symptoms in perimenopausal women before and after yoga therapy, an ongoing study. J MidlifeHealth. 2013;4(4):225–229. 2.Osaki S, McDermott JA, Frieden E. Proof for the ascorbate oxidase activity of ceruloplasmin. J BiolChem. 1964;239(1):3570–3575. 3.Wang Q, Ji J, Hao S, Zhang M, Li K, Qiao T. Iron together with lipid downregulates protein levels of ceruloplasmin in macrophages associated with rapid foam cell formation. J Atheroscler Thromb.2016;23(10):1201–1211. 4.Johnson MA, Fischer JG, Kays SE. Is copper an antioxidant nutrient? Crit Rev Food Sci Nutr.1992;32(1):1–31. 5.Percival SS, Harris ED. Ascorbate enhances copper transport from ceruloplasmin into human K562cells. J Nutr. 1989;119(5):779–784. 6.Jacob RA, Skala JH, Omaye ST, Turnlund JR. Effect of varying ascorbic acid intakes on copper absorption and ceruloplasmin levels in young men. J Nutr. 1987;117(12):2109–2115. 7.Milne DB, Klevay LM, Hunt JR. Effects of copper (Cu) intake and vitamin C supplements on copper and iron nutrition in women (Abstract 3448). Fed Proc. 1987;46(3):908. 8.Koushanpour E, Kriz W. Tubular resorption and secretion: classification based on overall clearance measures. In: Renal physiology: principals, structure, and function, 2nd ed. New York, NY: Springer-Verlag; 1986. pp. 214–239. Other Helpful References 1.Wang Q, Ji J, Hao S, Zhang M, Li K, Qiao T. Iron together with lipid downregulated protein levels of ceruloplasmin in macrophages associated with rapid foam cell formation. J Atheroscler Thromb.2016;23(10):1201–1211. 2.Lovstad RA. On the mechanism of citrate inhibition of ceruloplasmin ferroxidase activity. Biometals.1996;9(3):273–275. 3.Lovstad RA. A kinetic study of the coupled iron-ceruloplasmin catalyzed oxidation of ascorbate in the presence of albumin. Biometals. 1995;8(4):328–331. 4.Kassouny ME, Coen CH, Bebok ST. Influence of vitamin C and magnesium on calcium, magnesium and copper contents of guinea pig tissues. Int J Vitam Nutr Res. 1985;55(3):295–300. 5.Klenner FR. Observations on the dose and administration of ascorbic acid when employed beyond the range of a vitamin in human pathology. J Orthomolecular Med. 1998;13(4):198–210.
Magnesium Myths vs. Science
In this series of short videos, Dr Alison Smith, P...
In this series of short videos, Dr Alison Smith, PhD (Neuroscience) and award-winning health blogger, debunks myths associated with magnesium. She takes on marketing claims that are unfounded in science and shares what the clinical research really says about the types of magnesium that are most absorbable. It's amazing how marketing claims can skew the science. Now you know that there is no research supporting claims that magnesium glycinate, bisglycinate, or any other chelate is a more absorbable form. If anything the research suggests that magnesium citrate has the advantage. But remember: there is no published clinical research comparing these two popular forms - magnesium citrate and magnesium glycinate.  If anyone tells you otherwise, you can point them here or check out our white paper. At Natural Calm, we're committed to truth in marketing. If you ever have questions about health statements we make, contact us. We want to support a fair, fact-based playing field and make it easier for Canadians to choose supplements based on credible research
Magnesium Absorption (White Paper)
How Does Magnesium Citrate Compare to Other Forms ...

How Does Magnesium Citrate Compare to Other Forms of Magnesium?

Dr. Jon-Paul Powers, PhD, Microbiology, Partner and Scientific Advisor, Gowling GWL 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, whose effectiveness 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.(1,2) Magnesium also plays a role in the transport of sodium and potassium ions across cellular membranes.(3) Recently, magnesium has also been demonstrated to improve bowel movement and frequency thereby reducing functional constipation.(4,5) More than half of the body’s 20-28 g magnesium store is present in bones with the remainder residing in the soft tissues and, to a very minor extent (<1%), in the blood.(6,7)

Dietary magnesium requirements

Adults require approximately 310-420 mg of magnesium daily, and deficiency may lead to irritability, muscle weakness, and irregular heartbeat.(8) Most dietary magnesium typically comes from sources such as fruits, vegetables, leafy greens, and 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.(9) Due to deficiencies in modern diets, many consumers select magnesium supplements as a convenient way to meet their daily requirements.

Magnesium Supplements

Oral magnesium supplements are available in a variety of formats 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 due to 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.(10,11) 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.(12,13) 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.(14,15) 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.(16) In general, the assumption is that the uptake and release of magnesium are in balance;(17) 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.(18) Stable isotopes of magnesium have also been used to track the absorption of magnesium by the body.(19)

Magnesium Bioavailability

The solubility of minerals in the digestive tract is a major factor driving their uptake.(20) 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.(21) The enhanced solubility leads to a greater concentration 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.(22,23,24) 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.(25) Magnesium citrate is regarded as a highly soluble and readily bioavailable form of magnesium.(26) Studies in simulated gastric fluid demonstrate that magnesium citrate remains in solution even as pH increases.(27) 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.(28) 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.(29) 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.(30) 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).(31) 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. Walker et al. (2003) 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 h) and chronic (60 days) administration of an oral daily dosage.(32) Subjects were generally healthy and free of conditions or activities known to affect magnesium metabolism and were administered cellulose or sorbitol placebo or 300 mg 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 concentration. 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.(33) 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.(34) 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 like bisglycinates. Therefore, due to its solubility, and its superior bioavailability, magnesium citrate is a highly effective form of magnesium supplementation. See also our blog post on the topic: Are You Being Misled About Magnesium?

Sources

1 World Health Organization, available at: http://www.fao.org/DoCREP/004/Y2809E/y2809e0k.htm 2 Health Canada, available at: http://webprod.hc-sc.gc.ca/nhpid-bdipsn/atReq.do?atid=multi_vitmin_suppl&lang=eng 3 Bara et al. Magnesium Res 1993;6(2):167-177 4 Dupont et al. Clin Gastroenterol Hepatol 2014;12(8):1280-7 5 Bothe et al. Eur J Nutr 2015;Nov.18 ahead of print. 6 Schaafsma. Eur J Clin Nutr 1997;51(1):13-16 7 Benech and Grognet. Magnesium Res 1995;8(3):277-284 8 Mayo Clinic, available at: http://www.mayoclinic.org/drugs-supplements/magnesium-supplement-oral-route-parenteral-route/description/drg-200707309 Health Canada, available at: http://www.hc-sc.gc.ca/fn-an/surveill/nutrition/commun/art-nutr-adult-eng.php 9 Health Canada, available at: http://www.hc-sc.gc.ca/fn-an/surveill/nutrition/commun/art-nutr-adult-eng.php 10 Coudray et al. Magnesium Res 2005;18(4):215-23 11 Ranade and Somberg. Am J Therapeutics 2001;8:345-357 12 Ranade and Somberg. Am J Therapeutics 2001;8:345-357 13 Johen-Dechent and Ketteler. Clin Kidney 2012;5(1):i3-i14 14 Johen-Dechent and Ketteler. Clin Kidney 2012;5(1):i3-i14 15 Elin. Dis Mon 1988;34(4):161-218 16 Ranade and Somberg. Am J Therapeutics 2001;8:345-357 17 Bohmer et al. Magnesium Trace Elem 1990;9:272-278 18 Walker et al. Magnes Res 2003;6(3):183-91 19 Schuette et al. JPEN J Parenter Enteral Nutr 1994;18(5):430-435 20 Coudray et al. Magnesium Research 2005;18(4):215-23 21 Siebrecht, S. OM & Ernährung 2013;144:2-16 22 Lindberg et al. J Amer Col of Nutrition 1990;9(1):48-55 23 Firoz and Graber. Magnesium Research 2001;14(4):257-262 24 Coudray et al. Magnesium Research 2005;18(4):215-23 25 Wilimzig et al. Euro J Clin Pharmacol 1996;49:317-323 26 Ranade and Somberg. Am J Ther 2001;8:345-357 27 Lindberg et al. J Amer Col Nutr 1990;9(1):48-5528 28 Couday et al. Magnesium Res 2005;18(4):215-23 29 Lindberg et al. J Amer Col Nutr 1990;9(1):48-55 30 Schuette et al. J Parenter Enteral Nutr 1994;18:430-435 31 Ranade and Somberg. Am J Ther 2001;8:345-357 32 Walker et al. Magnes Res 2003;6(3):183-91 33 Walker et al. Magnes Res 2003;6(3):183-91 34 Walker et al. Magnes Res 2003;6(3):183-91
Why Magnesium
The hardest-working mineral in the body does more ...

The hardest-working mineral in the body does more than you know!

Very few people give a moment’s thought to what goes on at the cellular level in our bodies. We have trillions and trillions of cells in our bodies, each one less than a nanogram, each one performing enzymatic reactions, energy transfers every millisecond. Magnesium is a pivotal part of this dance in and around our cells.

The Multi-Tasking Mineral

Every cell in our bodies relies on magnesium. It’s known as the ‘the spark of life’ because without magnesium, the very process by which our cells derive energy ceases to function. Magnesium is critical for the success of hundreds of biochemical or enzymatic reactions across all bodily systems: for our nerves, brain, muscles, bones, organs and hormones, magnesium is essential. There are only 7 macro-minerals in the body, and magnesium is ranked 4th in terms of abundance. Magnesium’s multi-tasking properties are linked to the way it partners with other nutrients. Magnesium is a cooperative mineral, aligning itself with other nutrients to help them perform their functions.

Magnesium and Calcium

Magnesium lives in the centre of the cell, and with adequate levels, keeps calcium on the outside of the cell where it belongs – until the body calls for energy and then calcium floods the cell. Too much calcium and not enough magnesium creates an unhealthy balance, allowing calcium to seep into the cell. Calcium in the centre of the cell puts the body in a perpetual state of excitement. There is ample evidence that tension-based conditions such as migraines, restless legs, muscle cramps, PMS and even day-to-day stress can be attributed to the troubling imbalance of too little magnesium and too much calcium.

Health Benefits of Magnesium

Every muscle and nerve in your body relies upon magnesium to maintain normal function. This includes the biggest muscle of them all – your heart – and magnesium also has a direct connection to the electrical system of your heart, keeping heart rhythm steady. Magnesium supports a healthy immune system, in part through its work with omega-3s. It has a crucial, yet little-known role in maintaining strong bones and teeth. Magnesium is the mineral that activates the vitamin D that assimilates calcium into your bones to help keep them strong. This critical mineral also regulates blood sugar levels, promotes normal blood pressure, and is known to be involved in energy metabolism and protein synthesis. Protein synthesis is an enormously complicated process that utilizes DNA, RNA, amino acids and ATP (energy) to form proteins at the rate of hundreds of proteins per second in a healthy cell. Magnesium’s multi-tasking properties are so diverse that deficiency is thought to be a key contributor to the diseases described as Metabolic Syndrome. “Metabolic” refers to the chemical processes of an organism. Metabolic Syndrome is so named because the diseases of Metabolic Syndrome - specifically Heart Disease and Diabetes - show similar deficiencies at the cellular level. Magnesium is also instrumental for temperature regulation, electrolyte balance, and activating nutrients including the vitamin B group and Omega 3s, as well as crucial hormones such as melatonin and serotonin.

How Much Magnesium Do You Need?

According to Dr. Carolyn Dean, M.D., N.D. and bestselling author of The Magnesium Miracle, most North Americans aren’t getting enough magnesium. Dean recommends 500 mg daily as a healthy starting place, in line with the intake common for adults 100 years ago. Health Canada sets a lower bar, suggesting 350 mg/day as an adequate intake. Even based on this modest figure, up to 65% of us fall short. Today, many Canadian adults are getting only 200 mg/day. Unlike many nutrients, magnesium is depleted every twelve hours. It must be constantly replenished. As a supplement, it’s non-toxic; any excess is safely eliminated. While too much magnesium is almost never a problem, too little can be a health disaster.

Who Is Deficient and Why

"Both our current diet and tendency to over-supplement with calcium…makes getting enough magnesium almost impossible.”

- Carolyn Dean, M.D., N.D. Author of The Magnesium Miracle

We just aren’t getting enough magnesium through food. Lifestyle, processed foods, and modern agriculture’s depleted soils are to blame. What magnesium we do ingest is often poorly absorbed or depleted by medication, caffeine, sugar, alcohol, excess calcium and stress. Low magnesium is even more dangerous given Canadians’ high intake of calcium through dairy, fortified foods and supplements. Calcium and magnesium need to be in balance for the chemistry of our cells to function properly. When calcium is in excess, we may experience symptoms of magnesium deficiency.

Common Symptoms of Deficiency

Magnesium deficiency can manifest as a number of symptoms because magnesium is such a wide-ranging, multi-tasking mineral. These include:

Conditions Associated with Low Magnesium

In addition to everyday symptoms, there are a number of conditions with strong links to low magnesium. These include: Research shows that supplementation with an effective, absorbable magnesium can help.

If There's Just One Thing You Add to Change Your Health, Make it Magnesium

Many of our customers aren’t the type to use supplements. We frequently hear that Natural Calm is the only natural health product many rely on daily. It’s so simple, yet so effective. Why? Because Natural Calm is the better magnesium. Here’s what people love:
  • Our proprietary magnesium citrate is highly absorbable, delivering fast relief from symptoms of deficiency
  • The great tasting flavours are organic and sweetened with organic stevia
  • Natural Calm is non-GMO, vegan, gluten-free, certified C.L.E.A.N. and R.A.W.
Natural Calm is the top-selling magnesium in North America, supported by thousands of five-star reviews on Amazon.com and on our website. It's the winner of dozens of natural health product awards, and we're so confident in our product, we offer a 100% money-back guarantee.

Is Natural Calm Right for You?

Magnesium is a safe and effective supplement for most people. If you have kidney failure, myasthenia gravis, excessively slow heart rate or bowel obstruction, consult your healthcare practitioner before using any supplements. It’s easy to find the level of supplementation that’s right for you. Take Natural Calm to the point at which bowel movements are comfortably loose. If you experience diarrhea, take smaller, more frequent doses, or decrease total daily dosage. Our transdermal magnesium gel, magnesium liquid and spray completely bypass the digestive tract. For those who wish to avoid any laxative effect, topical magnesium is a wonderful alternative.
Stroke
Strokes are one of the leading causes of mortality...
Strokes are one of the leading causes of mortality in Canada. It is estimated that every seven minutes a Canadian dies of heart disease or stroke, accounting for 7% of all deaths. An ischemic stroke occurs when clots form in blood vessels and travel to the brain, blocking blood flow to the neuronal tissue. A hemorrhagic stroke occurs when blood vessels break, and blood seeps into the brain tissue. Up to 50% of these episodes can be prevented and many of the risks factors can be effectively managed.

Magnesium for stroke prevention

Magnesium supports the whole cardiovascular system in a number of ways. High intake of magnesium and other minerals can reduce risks of cardiovascular disease (1). Magnesium helps to lower blood pressure and prevents the buildup of cholesterol and calcium on the wall of the artery, which otherwise may lead to blockages or thrombosis (blood clots). Magnesium also acts as a healthy, natural blood thinner that helps keep the blood flowing smoothly. Generations ago, doctors prescribed magnesium chloride or magnesium sulphate intravenously when heart attack or stroke patients arrived at emergency rooms. When magnesium was given within 3 hours of the onset of stroke or heart attack, magnesium reduced the incidence of death by 50% (2). Other studies indicate that in addition to guarding against stroke, magnesium also helps regulate blood sugar, and is linked with lower levels of inflammation, a risk factor for Other studies indicate that in addition to guarding against stroke, magnesium also helps regulate blood sugar, and is linked with lower levels of inflammation, a risk factor for diabetes and cardiovascular disease (3).

Other Important Preventative Measures

While high blood pressure can damage and weaken the arteries, the risk can be reduced by eating a healthy diet, lowering sodium levels and exercising. It's also critical to control cholesterol, unhealthy levels of which can accumulate on vessels and reduce blood flow and oxygen supply to the brain.

Sources

1. Prospective Study of Calcium, Potassium, and Magnesium Intake and Risk of Stroke in Women. Hiroyasu Iso, Meir J. Stampfer, JoAnn E. Manson, Kathryn Rexrode, Charles H. Hennekens, Graham A. Colditz, Frank E. Speizer and Walter C. Willett. 1999, Stroke, Vol. 30, págs. 1772-1779. 2. Associations of dietary magnesium intake with mortality from cardiovascular disease: The JACC study. Wen Zhange, Hiroyasu Iso, Tetsuya Ohira, Chigusa Date, Akiko Tamakoshi, JACC Study Group. 2, Atherosclerosis , Vol. 221, pp. 587-595. 3. To lower your stroke risk, pay attention to this mineral. BECK, LESLIE. January 17, 2012.
Cholesterol
When we talk about cholesterol, we have to differe...
When we talk about cholesterol, we have to differentiate between 'good' and 'bad' types. Low-density lipoprotein, LDL, is harmful because it carries cholesterol into the bloodstream, promoting the buildup of cholesterol plaque on the arterial walls. High-density lipoprotein, HDL, is considered beneficial to the body. It helps remove cholesterol from blood vessel walls and the blood itself, bringing it to the liver for processing and excretion. Hypercholesterolemia, or dyslipidemia, is the presence of high levels of cholesterol in the blood, and it is one of the main factors contributing to the development of atherosclerosis and ischemic heart disease (1). According to a recent Canada-wide health survey, 45% of Canadian men and 43% of Canadian women have unhealthy total cholesterol levels.

Risk Factors

Current Canadian guidelines recommend that doctors test for high cholesterol levels for the following, high-risk groups:
  • Men over the age of 40
  • Women over the age of 50 or who have gone through menopause
  • Smokers
  • People with diabetes or high blood pressure
  • Those with a parent, brother or sister who had heart disease at an early age
  • Anyone with a BMI in the obesity range
  • Children with a family history of high cholesterol
It should come as no surprise that 'bad cholesterol' or LDL is not normally found in natural foods, nor produced in our bodies. It comes from processed foods, fried foods, fast foods. 'Junk food' is cluttering our bloodstream and wreaking havoc with our health.

Magnesium for Cholesterol Levels

Studies indicate that high levels of magnesium in the diet could be inversely related to diseases like hypertension and type 2 diabetes mellitus. The higher intake of magnesium can lead to a substantial decrease in blood triglycerides and an increase of HDL cholesterol levels (2). Magnesium acts like a natural statin which helps block the specific enzyme (HMG-CoA reductase) in the liver that produces cholesterol. When that enzyme is blocked cholesterol levels are lowered, but when magnesium levels are low cholesterol continues being produced leading to a risk of coronary hearth disease. There is also evidence suggesting a relation between magnesium levels and obesity linked to high cholesterol levels. This mineral may have an antiobesity effect because of the way in which it interacts with fatty acids in the intestine, reducing the digestible energy content (think: calories) of the diet (3). Magnesium-rich foods like whole grains, nuts, fruits and vegetables help to reduce body weight and maintain healthy cholesterol levels. Sources 1. Magnesium dietary intake modulates blood lipid levels and atherogenesis. BELLA T. ALTURA, MANFRED BRUST, SHERMAN BLOOM, RANDALL L. BARBOUR, JEROME G. STEMPAK, AND BURTON M. ALTURA. March de 1990, Proc. Natl. Acad. Sci, Vol. 87, págs. 1840-1844. 2. Low magnesium and atherosclerosis: an evidence-based link. Maier, Jeanette A.M. 2003, Molecular Aspects of Medicine, Vol. 24, págs. 137-146. 3. Magnesium Intake and Incidence of Metabolic Syndrome Among Young Adults. Ka He, Kiang Liu, Martha L. Daviglus, Steven J. Morris, Catherine M. Loria, Linda Van Horn, David R. Jacobs and Peter J. Savage. 2006, Circulation, Vol. 113, págs. 167-1682.
Blocked Arteries
Most people associate blocked or clogged arteries ...
Most people associate blocked or clogged arteries with the heart, but an artery can be blocked anywhere in the body:
  • Coronary Artery Disease occurs when plaque builds up in the arteries that carry blood to the heart. If left unchecked, it will result in heart attack or stroke. Coronary Artery Disease is one of the leading causes of death in Canada and the United States.
  • Carotid Artery Disease refers to the carotid arteries located along the sides of the neck. These arteries deliver rich nutrients to the brain. Blockages here can lead to stroke.
  • Peripheral Artery Disease is when the vessels that carry blood to the legs are restricted. Reduced blood flow to the legs and feet can result in pain and numbness, and at worst, serious infection.

How Arteries Become Blocked

When plaque hardens and permanently narrows the artery walls in any of these three cardiovascular disease states, the condition is called Atherosclerosis. With stable plaque build-up in the heart, angina – or chest pain – may occur upon extreme exertion, but generally, there are no symptoms. Should plaque build-up become unstable – like a bump on an artery wall – it can burst or rupture, permanently damaging the heart muscle and causing a heart attack or myocardial infarction.

Causes

There are many environmental risk factors for the development of atherosclerosis. These include smoking, diet, lack of exercise or infections. Genetic factors like diabetes, hyperlipemia, hypertension, obesity play a role, and men are more likely to develop this disease. However, elevated levels of serum cholesterol are enough to develop atherosclerosis, even in the absence of these other risk factors (1).

Magnesium for Preventing Atherosclerosis

Epidemiological research has indicated a direct relation between atherosclerosis and magnesium levels.
  • Low plasma concentrations of magnesium are the cause of some inflammation states and atherosclerosis is an inflammatory disease.
  • Low plasma magnesium could potentiate the negative effects of several risk factors and induces dysfunction of the intern walls of the vessels.
  • Hypomagnesemia is frequently associated with hypertension, diabetes, and aging, which are risk factors for atherosclerosis (2).

The Relationship Between Calcium and Magnesium in Blocked Arteries

Calcium and magnesium act antagonistically - they have opposite effects. Excess levels of calcium act along with fatty acids and cholesterol cause the formation of plaques in veins and arteries. Magnesium helps prevent calcification and it plays an important role in diverting calcium to the bones, away from arteries (3).

Prevention and Treatment

Atherosclerosis is treatable when diagnosed, and though it is progressive, it is also preventable. A low-fat diet is highly recommended and unsaturated oils should be preferred. High intake of magnesium, smart food and drink choices, and exercise also help to reduce the risk. It is also critical to maintain healthy blood pressure and cholesterol levels.

Sources

1. Low magnesium and atherosclerosis: an evidence-based link. Maier, Jeanette A.M. 2003, Molecular Aspects of Medicine, Vol. 24, págs. 137-146. 2. Associations of serum and dietary magnesium with cardiovascular disease, hypertension, diabetes, insulin, and carotid arterial wall thickness: the ARIC study. Atherosclerosis Risk in Communities Study. Ma J, Folsom AR, Melnick SL, Eckfeldt JH, Sharrett AR, Nabulsi AA, Hutchinson RG, Metcalf PA. 7, 1995, J Clin Epidemiol, Vol. 48, págs. 927-940. 3. The role of calcium and magnesium in the development of atherosclerosis. Experimental and clinical evidence. Orimo H, Ouchi Y. 1990, Ann N Y Acad Sci., Vol. 598.
Hypertension
High Blood Pressure (HBP) or hypertension is also ...
High Blood Pressure (HBP) or hypertension is also known as 'the silent killer'. With no discernible symptoms, and the potential to shut down the heart if left untreated, hypertension is a life-threatening condition. 1 in 3 Canadian adults have HBP, yet, sadly, many are unaware until a cardiac episode reveals the story of their heart’s true condition. Hypertension is measured by the force of the blood pushing against the artery walls as it pumps, known as systolic pressure, and diastolic pressure measured between beats when the heart is at rest. If blood pressure rises and stays consistently high, it causes damage to the heart, blood vessels and even the kidneys.

Magnesium for High Blood Pressure

Magnesium deficiency, or hypomagnesemia, is common especially in women and elderly groups. It has been suggested that this condition contributes to the development of hypertension and cardiovascular disease. tudies that have demonstrated how magnesium participates in the regulation of vascular tone, endothelial function, vascular inflammation, and glucose and lipid metabolism (1). Magnesium acts as a natural calcium blocker in the cells, improving dysfunction of the inner lining of blood vessels in hypertensive and diabetic patients (2). Studies have demonstrated that magnesium participates in the regulation of vascular tone, endothelial function, vascular inflammation, and glucose and lipid metabolism (1). Magnesium acts as a natural calcium blocker in the cells, improving dysfunction of the inner lining of blood vessels in hypertensive and diabetic patients (2). Magnesium also acts as a natural diuretic, ridding the body of excess water and sodium that can cause high blood pressure. A magnesium intake of 500 to 1000 mg per day may reduce blood pressure as much as 5.6 ⁄ 2.8 mm Hg. Many experts believe that magnesium supplementation should be the first line of defense against hypertension prior to initiating any prescription drug regimen. A combination of increased levels of magnesium and potassium along with reduced sodium in the diet has been proven more effective in reducing blood pressure than antihypertensive drugs alone (3).

Lifestyle Changes

In the U.S., application of the DASH (Dietary Approaches to Stop Hypertension) Diet was shown to lower blood pressure in patients with stage 1 hypertension and high-normal blood pressure. The DASH diet, which emphasizes the consumption of fruits, vegetables, high fiber, and low-fat dairy products, also includes large amounts of magnesium, potassium, calcium, dietary fiber, and protein. In a study conducted by the DASH research group, it was shown that the combination of a low sodium intake and the proposed diet had greater effects on lowering blood pressure than either intervention alone (4). Exercise is also an excellent way to reduce blood pressure levels. It is recommended to include routines of yoga or meditation in your daily life to lower stress levels that contribute to hypertension. Through diet, adequate magnesium intake and physical activity, hypertension can be prevented.

Sources

1. LACK OF ASSOCIATION BETWEEN SERUM MAGNESIUM AND THE RISKS OF HYPERTENSION AND CARDIOVASCULAR DISEASE. Abigail May Khan, MD, Lisa Sullivan, PhD, Elizabeth McCabe, MS, ScM, Daniel Levy, MD, Ramachandran S. Vasan, MD, and Thomas J. Wang, MD. 4, 2010, Am Heart J., Vol. 160, pp. 715-720. 2. Complementary vascular-protective actions of magnesium and taurine: a rationale for magnesium taurate. McCarty, M.F. 2, Med Hypotheses, Vol. 46, pp. 89-100. 3. The Role of Magnesium in Hypertension and Cardiovascular Disease. Houston, Mark. 11, The Journal of Clinical Hypertension, Vol. 13. 4. EFFECTS ON BLOOD PRESSURE OF REDUCED DIETARY SODIUM AND THE. The DASH–SODIUM Collaborative Research Group. 1, 2001, The New England Journal of Medicine, Vol. 344.
Magnesium and Children
Magnesium is vital for 700 – 800 enzymatic proce...
Magnesium is vital for 700 – 800 enzymatic processes throughout the body and it may be the hardest-working, most essential nutrient for total health. Children need magnesium for:

Symptoms of Magnesium Deficiency in Children

Universally, two of the most common symptoms of magnesium deficiency are poor sleep and constipation, and these are also two of parents’ most common concerns when it comes to children’s health. Just as with adults, when we see these two symptoms – individually, but particularly when together – we should immediately suspect a magnesium deficiency. Other common childhood concerns can often be linked to low dietary magnesium. Often, these symptoms are considered normal, including growing pains and cramps, erratic energy, moodiness, headaches, insomnia and frequent waking. The fact is, these are only ‘normal’ because so many children aren’t eating a magnesium-rich diet. A simple magnesium deficiency can sometimes look like a more serious condition, or exacerbate an existing condition, like migraines, ADD, ADHD, autism, and asthma. Some researchers believe that low magnesium is linked to learning disabilities because of its role in protecting cells, including DNA, from heavy metals including aluminum, mercury, lead, cadmium, beryllium and nickel. Certainly low energy and poor concentration can be associated with insufficient magnesium. Under stress, children may exhibit more of the symptoms of magnesium deficiency, because the body uses up magnesium to deal with the stress response. So, it is not unusual to see a peak or a sudden onset of magnesium deficiency symptoms in a child whose diet has not changed but who is experiencing a new form of stress. Since magnesium levels cannot be accurately measured through a routine blood test, the best way to recognize magnesium deficiency is by identifying symptoms, together with an understanding of how diet and lifestyle choices affect health. Parents should become familiar with the symptoms of magnesium deficiency.

Why Children are Magnesium Deficient

Health Canada data shows that approximately 40 - 75% of Canadian adults aren’t getting the minimum requirements for magnesium. And of course, many health experts believe that the minimum requirements are too low. North Americans are falling short on magnesium primarily because of diet. Magnesium is found primarily in unprocessed whole grains, legumes, seeds, nuts and dark leafy greens. Most adults don’t eat enough of these foods to meet their magnesium requirements, and this is no less true for children. Consider the top magnesium food sources: • Pumpkin seeds 307mg per ¼ cup • Brazil nuts or sunflower seeds 130 mg per ¼ cup • Black-eyed peas at 121mg of magnesium per ¾ cup • Spinach, cooked at 157mg per 1 cup Very few children eat enough of these foods to meet their magnesium requirements. Beyond measuring intake, it’s important to look at dietary and lifestyle factors that deplete magnesium. Anyone who eats a diet high in calcium, sugar and even animal protein (typical of many kids) is depleting what magnesium they do get because these foods act as magnesium leeches.

How Much Magnesium Do Kids Need?

Even with a healthy diet, it’s hard to get enough magnesium every day. According to Health Canada, children ages:
  • 1-3 need 80mg of magnesium per day
  • 4-8 need 130mg per day
  • 9-13 need 240mg per day
In the teen years, boys need more than girls based on a body weight calculation:
  • Girls ages 14 – 18 need 360mg per day
  • Boys ages 14 – 18 need 410mg per day
Other experts recommend a higher intake daily. For example, Dr. Carolyn Dean suggests that children consume 4 - 5 mg of magnesium per pound of body weight. A 50 lb 7-year-old child could thus need up to 250mg of magnesium a day. The best way to judge whether a child is getting sufficient magnesium is again, to look at symptoms.

Addressing Childhood Magnesium Deficiencies

Although it is difficult to get enough magnesium through diet, the overall health benefits are substantial because magnesium-rich foods are among the world’s healthiest. Try to increase your child’s intake of magnesium-rich foods.
  • One surprising source of magnesium is cocoa powder, or better, raw cacao. Try adding it to smoothies and sugar-free desserts
  • Increase whole grains
  • Add seeds, nuts and legumes
Beware of ‘magnesium myths’. You’ll often hear that avocado, bananas, yogurt and other foods are good sources of magnesium. Compare the actual magnesium content of these foods with your child’s daily needs (see above). You’ll often discover that these ‘good sources’ aren’t very substantial sources of magnesium. Decrease magnesium-leeching foods:
  • Cut back on sugary foods and refined carbohydrates
  • Limit dairy
  • Substitute plant proteins for animal proteins
  • If applicable, cut caffeine
The next step is choosing a good supplement – and eliminating those supplements that can exacerbate a magnesium deficiency. If you routinely supplement your child’s diet with a multivitamin, check the label for calcium content. The calcium in a supplement should never be greater than the magnesium content. If your child’s supplement has more calcium than magnesium, beware. Excess calcium can symptoms of magnesium deficiency. Too much vitamin D can also cause symptoms of magnesium deficiency. However, research on the optimal intake of vitamin D is controversial at this point. The best advice is to get sun exposure every day and to avoid high doses of vitamin D. It’s rare to find a child’s multivitamin that has enough magnesium without too much calcium or vitamin D. And remember that minerals in tablet form tend to be less efficiently absorbed. Some experts suggest that only 10% of the minerals in a tablet are available to the body. Natural Calm’s Kid’s Calm is a highly absorbable magnesium drink, identical to our best-selling adult formula but with easy-to-follow dosing on the label for kids from 1 - 18.

Magnesium Safety for Children

Magnesium is a very safe supplement. Unlike many nutrients, magnesium is eliminated from the body daily - in fact, it needs to be replaced about every 12 hours. The body has a built-in failsafe mechanism: when there is too much magnesium, it is excreted through the bowels, which is why many people experience diarrhea when they take too much magnesium at one time. The kidneys play a key role in excreting excess magnesium. For this reason, anyone with existing or suspected kidney health issues should consult a physician prior to beginning magnesium supplementation. Parents of children who have a pre-existing medical condition or who are on medication should also check with their health care practitioners.

Sources

Health Canada (2012). Do Canadian Adults Meet Their Nutrient Requirements Through Food Intake Alone? Health Canada (2005). Reference Values for Elements – Dietary Reference Intakes Tables. Ottawa: Government of Canada.
Kidney Health
Kidneys are like the master chemists and master cl...
Kidneys are like the master chemists and master cleansers of the body
The kidneys remove waste from the body, such as urea and creatinine; regulate and purge excess minerals such as magnesium, sodium and potassium; control the body's water levels and blood pressure.

Kidney Disease and Magnesium

When the kidneys are under stress, certain diseases, such as high blood pressure and diabetes occur. Existing diabetes can cause kidney deterioration and ultimately, total failure. Magnesium can protect the kidneys from disease.  If, however, kidney damage has already occurred, magnesium supplementation is not recommended except under the care of a healthcare professional.

Kidney Stones

Kidney stones are hard, crystallized mineral deposits that start small and grow in the kidney. Men are four times more likely to develop kidney stones than women. The prostate gland in men enlarges as they age leading a condition called BPH (Benign Prostate Hypertrophy). This can result in difficulty emptying the bladder. The restricted flow allows chemicals and toxins to accumulate, forming crystals and stones. Both genders agree that the passing of a kidney stone is a very painful experience.

Magnesium for Kidney Stones

Magnesium is a vital mineral partner to Vitamin B6. Together they play a crucial role in preventing the formation of kidney stones. When animals deficient in vitamin B6 were given high levels of magnesium, they continued to show oxalic acid in the urine but they no longer converted this acid into kidney stones. Magnesium improved the utilization of calcium, having the effect of a solvent - preventing the caking and crusting, like lime in a kettle, of unassimilated calcium. An excerpt from Dr. Whitaker’s website, “America’s most trusted wellness doctor” features a testimony from a patient: "I used to get kidney stones regularly. Then, almost 25 years ago, I heard about taking magnesium. I’ve been taking it ever since and haven’t had a kidney stone." —H.M., Odessa, TX Dr. Whitaker goes on to share that Harvard researchers found that taking 180 mg of magnesium along with 10 mg of vitamin B6 daily reduced stone formation by 92.3 percent per year. Another study showed about a 90 percent reduction with magnesium alone (500 mg daily).

Magnesium Citrate is Especially Beneficial for Kidney Stones from Calcium

People who develop calcium stones in their kidneys not only have excess calcium in their urine and kidneys, they also have low levels of citrate. Citrate is a form of citric acid that inhibits calcium stone formation. You can increase citrate levels by adding lemon juice to water. Researchers from the University of California found that drinking four ounces of lemon juice per day, diluted in water, dramatically reduced kidney stone formation. Or, when supplementing with magnesium, choose Natural Calm’s magnesium citrate powder, which combines the benefits of magnesium plus citrate to keep your kidney functioning at its best.
Diabetes
There is more understood today about the relations...
There is more understood today about the relationship between magnesium and diabetes than ever before – and it is leading healthcare professionals to concur: if you are at risk for diabetes, magnesium is absolutely essential for prevention. Magnesium deficiencies have been observed both inside the cell and outside the cell in pre-diabetes, type 2 diabetes, stable diabetes and chronic diabetes (type 1). Prolonged magnesium deficiency is also directly related to increased incidences of heart disease typically associated with poorly managed diabetes.

Understanding Insulin Resistance

Insulin is a hormone produced by the pancreas to carry the blood sugar (glucose) to our cells for energy production. Insulin resistance or insulin sensitivity refers to the challenge the pancreas is having in producing enough insulin to process the glucose in the blood. The more difficulty the cells have metabolizing glucose, the more insulin the pancreas wants to produce. The metabolic process of people with diabetes is no different than the metabolisms of people without diabetes. The only difference is in the volume of insulin produced, or the body’s ability to utilize the insulin that is produced. When there is too much glucose in the blood, two problems result. 1) The pancreas will try to keep up by producing more and more insulin, and 2) excess glucose will be turned into saturated fat. It can become a vicious cycle of producing more and more insulin, while the tired cells are less and less able to use this excess insulin Eventually, the body becomes somewhat immune to the insulin, and it is no longer able to metabolize the glucose at all. But all the non-functioning insulin in the blood – known as hyperinsulinemia – is linked to damaged blood cells, high blood pressure, heart disease, obesity and even osteoporosis.

Magnesium, Insulin and Diabetes

A characteristic of insulin resistance – where the body needs to produce higher volumes of insulin - is that little to no magnesium is found in the centre of the blood cells. This is referred to as intracellular magnesium. We know there is a direct correlation between magnesium and insulin. Magnesium is the one mineral that ‘twins’ with almost every other nutrient in one metabolic process or another, and the hormone insulin is no different. Insulin plays a role in moving magnesium across the cell wall – inside and outside the cell. When found When found inside the cell, magnesium contributes to improving “insulin-mediated glucose uptake” which is a fancy way of saying magnesium helps insulin do its’ job. Conversely, the absence of intracellular magnesium impairs insulin action and exacerbates insulin resistance.

Clinical Implications of Low Magnesium Levels

  • Insulin resistance is known to be directly related to magnesium deficiency
  • Loss of magnesium increases in periods of high levels of blood glucose
  • Diabetes-related diseases such as atherosclerosis (narrowed heart vessels that inhibit blood flow, usually as a result of high blood pressure and/or high cholesterol) and retinopathy (damage to the blood vessels of the eye) have an increased likelihood of progression when there are low levels of intracellular magnesium

How Magnesium Supplementation Helps

  • Corrects the deficit in intracellular magnesium levels
  • Decreases platelet reactivity
  • Improves insulin sensitivity
  • Has a role in the release and activity of insulin transport in the blood
  • May protect against diabetes and its complications
  • Plays a role in carbohydrate metabolism
Individuals with poorly-controlled diabetes may benefit from magnesium supplements because of increased magnesium loss in urine associated with hyperglycemia (high blood sugar)
Metabolic Syndrome
There is a cluster of risk factors that together a...
There is a cluster of risk factors that together are known as Metabolic Syndrome. When present together, these risk factors increase the likelihood of Coronary Artery Disease, Stroke and Type 2 Diabetes - and each of these risk factors is related to magnesium deficiency.

Metabolic Syndrome risk factors include:

  • ‘Central obesity’ or ‘apple-shaped’ weight distribution, with extra weight around the middle and upper parts of the body
  • Insulin resistance. The body uses insulin less effectively than normal and as a result, blood sugar and fat levels rise
  • High cholesterol
  • High blood pressure, or hypertension
  • Aging
  • Genetic history of any of the factors
  • Hormone changes
  • Lack of exercise
People who have Metabolic Syndrome often have two other problems that can either cause the condition or make it worse:
  • Excess blood clotting
  • Increased levels of blood substances that are a sign of inflammation throughout the body

Magnesium and Prevention of Metabolic Syndrome

It is no coincidence that each of these factors represents a process in the body dependent upon magnesium. Multi-tasking magnesium is the mineral that addresses each of these factors. Magnesium:
  • Is responsible for the production, function and transport of insulin by the cells
  • Activates cell membrane to help balance glucose levels
  • Is a natural blood thinner
  • Helps prevent and treat insulin resistance for Type 1 and 2 diabetes
  • Can reduce high cholesterol
Magnesium is closely bound up with metabolic processes throughout the body – it plays a role in 700 – 800 enzymatic processes at the cellular level. It is not surprising that magnesium, when sufficient, will minimize Metabolic Syndrome risk factors and prevent the onset of conditions such as heart disease and diabetes.
Stress Management
The body’s stress reactions were meant to protec...
The body’s stress reactions were meant to protect us, but a perpetual state of stress can take an enormous toll on human health. When the body is in a state of alarm, the adrenal glands release hormone surges, such as cortisol and adrenaline. Cortisol affects the digestive system, reproductive system, and too much cortisol can affect normal growth processes. Long-term activation of stressors in the body will disrupt almost all the body’s usual functions, including metabolism, which is why stress can promote weight gain.

Symptoms of Stress

There are no shortages of symptoms that can suggest stress. The American Institute of Stress publishes 50 Common signs and symptoms of stress and the Top 10 are: 1. Frequent headaches, jaw clenching or pain 2. Gritting, grinding teeth 3. Stuttering or Stammering 4. Tremors, trembling of lips and hands 5. Neck ache, back pain, muscle spasms 6. Lightheadedness, faintness, dizziness 7. Ringing, buzzing or popping sounds 8. Frequent blushing, sweating 9. Cold, sweaty hands and feet 10. Dry mouth, problems swallowing Interestingly, all of these symptoms of stress are also symptoms of magnesium deficiency, which will make more sense as you read on.

The Risks of Magnesium Deficiency Under Stress

Under stress, our body takes action:

  • Heart rate and blood pressure soar, increasing the flow of blood to the brain to improve decision-making
  • Blood sugar rises to furnish more fuel for energy as the result of the breakdown of glycogen, fat, and protein stores caused by adrenalin surging
  • Blood is shunted away from the gut, where it is not immediately needed for digestion, to the large muscles of the arms and legs to provide more strength in combat, or greater speed in fleeing a scene of potential peril
  • Clotting occurs more quickly to prevent blood loss from lacerations or internal hemorrhage

Without enough magnesium, our body can't cope with stress:

• When blood pressure soars, the smooth muscles in the walls of your blood vessels can go into spasm if you are magnesium deficient. This can cause chronic hypertension • When blood sugar rises, magnesium is responsible for insulin opening up cell membranes to allow sugar into the cells. If you are magnesium-deficient, blood sugar continues to rise and cells do not receive glucose • If the large muscles of the arms and legs are magnesium-deficient, increased circulation can cause muscle cramping, irritability, and restless leg syndrome • Without enough magnesium, blood clotting can become enhanced leading to leg, lung, and brain clots.

The Two-Way Relationship Between Magnesium and Stress

Magnesium is known as the anti-stress mineral. But the relationship between magnesium and stress works in two directions: stress depletes magnesium, but magnesium counteracts stress. Any stress, whether mental or physical, will deplete magnesium from the body. The body uses up magnesium stores in reacting to stress. And a body without enough magnesium will exhibit more of the symptoms of stress. In addition to the functions listed above, the body needs magnesium to:
  • downgrade the cortisol response and cleanse cortisol from the cells
  • keep calcium outside the cells where it belongs. Excess calcium in the cells has been shown to cause rigidity and tension in the cell
  • balance the nervous system gets and relax muscles, to prevent mental stress associated with physical tension
So, magnesium is essential for two facets of stress management: it helps to prevent the physical tension that leads to stress, and magnesium downgrades our physical response to stressful situations. But magnesium can only do its job as the ‘anti-stress mineral’ if we have an adequate intake.
Bone Health
North Americans consume the most calcium in the wo...

North Americans consume the most calcium in the world and yet have the weakest bones in the world. How can that be?

The countries that consume the most dairy products (USA, Canada, Sweden and Finland) have the highest incidence of osteoporosis and poorer bone health, despite a major focus on osteoporosis prevention and treatment. Hip fractures in elderly Japanese women occur at less than half the rate of those experienced by women in high dairy-consuming western countries. The western world’s fascination with calcium to build bone is, sadly, untrue. It’s true that the bone is largely composed of calcium, however, calcium depends on other nutrients to do its work, especially its twin mineral, magnesium. Simply increasing calcium without regard for nutrient balance is now known to cause more harm than good. The standard advice for women with low bone density is to supplement with calcium and sometimes vitamin D, but inevitably, without adequate magnesium, annual Bone Mineral Density (BMD) tests show no improvement whatsoever. There are two clear reasons for this: 1) Insufficient magnesium to convert the Vitamin D to promote calcium absorption, and 2) High-sugar, high-fat food and drink, so loved by North Americans will cause a literal ‘fat barrier’ that prevents calcium from being absorbed.

The Key Minerals and Vitamins for Bone Health

Clearly, more calcium does not equal stronger bones. The real equation for optimal bone health is magnesium + vitamin D + calcium. Magnesium activates vitamin D, which in turn metabolizes the calcium. In addition to these three major players in skeletal health, there are many others – but the imbalance of calcium and magnesium is perhaps the biggest reason for bone decay in North America. When we have magnesium deficiency at the cellular level, calcium can’t do its job in the bone. Calcium alone is useless and potentially harmful. Without magnesium, the body will blindly deposit calcium into muscle and organ tissue, causing health issues such as calcium deposits and/or calcification of muscle tissues – dangerous when you consider calcification of the heart. To be clear: taking more magnesium will not fix a calcium deficiency, which in any case is rare in the western population. Instead, magnesium enables the best use of calcium in the body, dissolving any excess calcium, while helping any needed calcium to assimilate. Without enough magnesium, calcium turns from a nutrient into a pollutant. It can cause heart disease, arthritis, osteoporosis and calcification of organs and tissues. Excess calcium combined with low magnesium is a lethal combination indeed. Excess magnesium, on the other hand, is not typically a concern. Unlike calcium, magnesium is safely eliminated from the body by healthy kidneys every 12 hours.

Magnesium, Hormones and Bone Health

Magnesium also activates a particular hormone, calcitonin, that helps to preserve bone structure and draws calcium out of the blood and soft tissues back into the bones, preventing some forms of arthritis and kidney stones. Calcitonin needs to be guided, if you will, or activated by magnesium to deposit correctly into the bone for continued growth. It is a popular but untrue belief that bones can’t grow after a certain age. They can certainly continue to replenish themselves as long as the right nutrient balance is present. Magnesium suppresses another bone hormone called PHT (parathyroid), preventing it from breaking down bone. When we are magnesium deficient, the balance between PTH and calcitonin tilts too far toward PTH, which results in excessive stimulation of osteoclasts and net bone loss. The imbalance of the hormones DHEA and cortisol may also result in bone loss. Under stress, the body produces a stress hormone called cortisol. Cortisol will pull calcium from your bones. Cortisol and DHEA balance each other out; if one is high the other is low. Magnesium helps regulate the cortisol response to stress. It’s also important to note that low hormone levels, in general, can lead to loss of bones, which is why many women start to lose bone density after menopause.

pH Balance and Bone Health

The body needs to maintain a pH of 7 in the bloodstream in the same way it needs to maintain 98°F body temperature. The Standard American Diet (SAD) diet is mostly an acidic diet. Protein, dairy (even though it is high in calcium) bread, soda, sugar and pastas are examples of acidic foods. When we consume acidic foods, our body becomes more and more acidic. Acidic foods and drink throw the pH out of balance, and alkaline foods restore the pH. Magnesium and calcium, as minerals, are alkaline. To compensate for the acidic diet, the PHT hormone will draw minerals from the bones to neutralize the acid in the bloodstream. An acidic diet thus depletes the bones of precious minerals. You can check your pH balance yourself at home. Ask your local pharmacists for a litmus test paper.

High Fat, High Sugar Diets and Bone Health

The HFS diet (HighFatSugar) diet remains the diet of choice, despite an overwhelming mountain of evidence that junk food is directly linked to chronic diseases such as cardiovascular disease and diabetes, to say nothing of the obesity crisis. But the HFS diet also has implications for bone health. HFS food leads to weight gain, adding pressure on the skeleton, while at the same time a HFS diet deprives the body of the nutrients it needs to build strong bones. Magnesium, in particular, is glaringly absent from a HFS diet, and in fact prevents the body from making use of what magnesium is acquired through such a poor diet.

The Science of Bone Building & Osteoporosis Prevention

Osteoporosis is not an inevitable part of aging. It is simply the body’s attempt to compensate for factors that are interfering with normal biochemical balance and bone formation. Some of these factors include:
  • poor nutrition – particularly a perpetual state of magnesium deficiency – and highly acidic diets, which is to say an emphasis on animal proteins, dairy and processed foods
  • lack of sunlight exposure, resulting in low Vitamin D
  • high caffeine and/or alcohol intake
  • lack of exercise
  • inflammation
  • chronic stress
  • some prescription medications – yes even those prescribed to arrest bone loss

Menopause and Osteoporosis

Along with lower estrogen in menopausal years, there are also findings of lower magnesium in menopausal women. Some health care professionals wisely suggest that menopausal women take magnesium – usually to help with absorption of calcium in the gastrointestinal tract. However, few medical professionals realize the importance of magnesium in its own right and the risks of too much calcium.

Prescription Drugs for Bone Building

Fosamax is part of a class of osteoporosis medications known as anti-resorptive drugs. These medications dramatically reduce bone loss, but in a disturbing way. The drug leads to premature death to osteoclasts, the cells that break down and recycle old, worn-out segments of bone. Bone breakdown and bone build-up, however, are tightly coupled, so that just as bone breakdown is dramatically reduced by Fosamax, so too is new bone formation. In fact, studies show that the bone-forming surface of bone is suppressed by 60–90% with the usual dose of bisphosphonates. It is far more accurate to call these prescription medicines 'bone hardeners', not bone builders. The results show up in bone density tests as “improved”, when they have so altered the fundamental composition of the bone that it eventually leads to higher risk of fracture. These are the outcomes currently under review as the class of drugs is relatively new.

Supplements for Osteoporosis

Dr. Carolyn Dean suggests a nutritional alternative to prescription drugs for bone building. The following list is excerpted from her bestselling book, The Magnesium Miracle.
  • Calcium: 500 mg per day
  • Magnesium: 300 mg twice a day
  • Boron: 2 mg daily (involved in Vitamin D conversion)
  • Copper: 1-3 mg daily (for collagen cross-linking)
  • Manganese: 5- 10 mg per day
  • Zinc: 10 mg daily (important for bone matrix)
  • Vitamin A: 20,000 IU daily (forms bone matrix)
  • Vitamin B6 : 50 mg per day
  • Folic Acid: 800 mcg daily
  • Vitamin B complex: 50 mg per day
  • Vitamin C: 1,000 mg per day
  • Vitamin D 1,000 IU per day or 20 minutes in the sun daily
  • Progesterone for postmenopausal women under the advice of your octor and after hormonal saliva testing to determine deficiency of progesterone
Heart Health
Magnesium for the Heart Magnesium is essential for...

Magnesium for the Heart

Magnesium is essential for the functional and structural integrity of the heart’s cells and blood pressure regulation. Here’s what you should know:
  • Magnesium works along with potassium to stimulate muscle contractions. Deficiencies in either or both nutrients can result in an irregular heartbeat
  • Magnesium’s work in the bloodstream as an anti-toxin, blood thinner, insulin transporter, plaque-buster and electrolyte helps reduce the risks for the development of cardiovascular diseases
  • Cellular loss of magnesium may be a basic biochemical mechanism in the evolution of myocardial lesions

Magnesium Deficiency and Cardiovascular Diseases

Magnesium in the typical western diet is inadequate to meet individual needs, and studies show that average magnesium intakes are insufficient to protect against cardiovascular disease. People living in areas with low-magnesium water have high rates of heart attack and stroke death, higher than people living in areas of high-magnesium water. Consumption of drinking water even moderately high in magnesium can be expected to reduce cardiovascular mortality by 30–35%. The relation between magnesium deficiency and coronary artery disease has been studied intensively. Patients with coronary artery disease frequently suffer from magnesium deficiency. Myocardial tissue magnesium concentration has been negatively linked with mortality in many studies. Hence, low magnesium levels seem to play a role in the formation of coronary artery disease. Deficiency of magnesium in the diet and abnormalities in magnesium metabolism play important roles in different types of heart diseases such as ischemic heart disease, congestive heart failure, sudden cardiac death, atherosclerosis, a number of cardiac arrhythmias and ventricular complications in diabetes. Magnesium deficiency results in damage to the coronary vessels, leading to a marked reduction in oxygen and nutrient delivery to the heart cells. The incidence of magnesium deficiency in chronic heart failure has been reported at more than 30% and is accompanied by muscular magnesium deficiency.

High Calcium, Low Magnesium and Heart Disease

Calcium and magnesium have reciprocal effects in a wide variety of functions. Their imbalance can induce dysfunctions and disease. The most important risk factor for impending heart disease is a low magnesium-to-calcium ratio in the cells. All the usual factors, such as high cholesterol, active type 2 diabetes (insulin resistance) and hypertension (high blood pressure) can be the result of a low magnesium status.

Magnesium Supplementation

In vascular medicine, magnesium supplementation relaxes blood vessels and lowers blood pressure by acting as a mild physiological calcium blocker. It works as a natural blood thinner, whereas calcium thickens blood. Magnesium has been shown to reduce the risk of coronary heart disease and relieve symptoms in roughly 85 percent of mitral valve prolapsed patients. Increased magnesium outside the cell decreases amounts of calcium inside the cell, which can lower blood pressure. Magnesium also inhibits the action of the enzyme that synthetizes cholesterol, lowering triglycerides and raising high-density lipoprotein or “good cholesterol” levels. Oral magnesium supplementation has been shown to improve resting heart function and exercise performance.

Sources

Barbagallo, and others. 2003, Molecular Aspects of Medicine, Vol. 24, pp. 39-52. Epidemiologic Data on Magnesium Deficiency-associated Cardiovascular Disease and Osteoporosis: Consideration of Risks of Current Recommendations for High Calcium Intakes. Seelig, Mildred. 2001, Advances in Magnesium Research: Nutrition and Health, pp. 177-190. The high heart health value of drinking-water magnesium. Rosanoff, Andrea. 81, 2013, Medical Hypotheses, pp. 1063-1065. Seelig, Mildred S. Interrelations Between Magnesium and Calcium. Guy Berthon. Handbook of Metal-ligand Interactions in Biological fluids . New York : Dekker, 1995, pp. 914-934. Magnesium in Cardiovascular Disease. Stühlinger, H. G. 2002, Journal of Clinical and Basic Cardiology, Vol. 5, pp. 55-59. Protective role of magnesium in cardiovascular diseases: A review. Sajal Chakraborti, Tapati Chakraborti, Malay Mandal, Amritlal Mandal, Sudip Das, Samardendranath Ghosh. 1, 2002, Molecular and Cellular Biochemistry, Vol. 238. Chronic heart failure and micronutrients. Klaus K.A. Witte, Andrew L. Clark, John G.F. Cleland,. 7, 2001, Journal of the American College of Cardiology, Vol. 37. Magnesium: Novel Applications in Cardiovascular Disease – A Review of the Literature. Kupetsky-Rincon, E.A. y Uitto, J. 2, 2012, Annals of Nutrition and Metabolism, Vol. 61, pp. 102-110. Oral magnesium therapy, exercise heart rate, exercise tolerance, and myocardial function in coronary artery disease patients. R Pokan, P Hofmann, S P von Duvillard, G Smekal, M Wonisch, K Lettner, P Schmid, M Shechter, B Silver, N Bachl. 2006, Br J Sports Med, Vol. 40, pp. 773-778. Rising Ca:Mg intake ratio from food in USA Adults: a concern? Rosanoff, Andrea. 4, 2010, Magnesium Research, Vol. 23, pp. S181-93.
Muscle Health
The Magnesium-Calcium Relationship and Why it Matt...

The Magnesium-Calcium Relationship and Why it Matters for Muscle Health

Magnesium is a key mineral for muscle health and performance. It aids in relaxation of tensed muscles, protein synthesis for muscle recovery and repair, and it helps to prevent lactic acid buildup. Magnesium works in a constant interplay with calcium, magnesium’s mineral opposite. Calcium’s functions to tense and excite muscle and nerves. Magnesium does the opposite, and it helps to push high levels of calcium out of the cells. In the muscle, magnesium prevents the build-up of calcium and even re-absorbs calcification that has already taken place. Calcium to magnesium ratios in the body should be 1:1 for optimum health. But because magnesium is excreted every 12 hours, and the body is unable to excrete excess calcium, the ratio very easily becomes imbalanced. Excess calcium os often stored in the muscles, causing tension, tightness, cramping, and spasm. Unfortunately, this is true even when it comes to our body’s most important muscle, the heart. You should never take calcium without magnesium. Magnesium, on the other hand, can be taken daily even without a calcium supplement.

Magnesium, Muscle Cramps and Spasms

Cramps and spasms in the muscles are likely a direct result of excess calcium. That’s because cramping of the muscles is often caused by calcification or a build-up of calcium in the muscle and soft tissues. Without sufficient magnesium to balance calcium, calcium will rush into the cell and flood it – causing a constant state of tension and rigidity. This manifests as muscle cramps, spasms and pain. Without sufficient magnesium to balance calcium, calcium will rush into the cell and flood it – causing a constant state of tension and rigidity. This manifests as muscle cramps, spasms and pain.

Magnesium, Exercise and Muscle Health

For serious athletes who train hard every day, intense workout sessions should be followed with specific nutrients. This post-workout refuelling is known as recovery – recovering the nutrients the body loses during daily, aggressive exercise. Magnesium should be part of this recovery plan. Too much calcium and not enough magnesium can significantly affect performance levels. Magnesium is excreted through sweat, and endurance athletes sweat 1 to 1.5 litres per hour. Muscle cramping and spasm, shortness of breath, rapid pulse and even a feeling that your heart ‘skips a beat’ during workouts are all signs of magnesium deficiency. The good news is that magnesium is easy to replenish with Natural Calm magnesium citrate, so you can return to peak performance by the next session Many athletes add Natural Calm Magnesium Chloride (our transdermal product line) to their recovery regime. Applying liquid magnesium topically to stressed muscles after a workout is a fast and effective way to replenish magnesium.
Foods that Deplete Magnesium
Excerpted with adaptations from Kimberly J Brown, ...
Excerpted with adaptations from Kimberly J Brown, MS, RD, Sports Nutritionist Dietary intake of protein, carbohydrate and fat can affect magnesium balance. Besides the negative effect high-protein diets have on hydration status, cardiovascular health and bone health, excessive protein intake also contributes to increased urinary loss of magnesium. Furthermore, the fat content in high-protein foods is often sufficient to reduce the absorption of magnesium. Diets high in refined foods, processed foods or sugars have inherently low magnesium content. Those who favour protein, fat or refined products are encouraged to transform their plate to include fruits, vegetables and whole grains with moderate amounts of lean protein. This will help promote a correct balance of magnesium, calcium and phosphorous within the body. To compound the problem of low reported dietary intakes of magnesium and consequent risk for a magnesium deficiency, there are several food nutrients that hinder the absorption rate of magnesium.
  • Dietary fibre, despite its pronounced health benefits, slightly lowers the absorption rate of magnesium.
  • In addition, beverages containing phosphoric acid (pop or soda, diet pop), and aspartame will prevent absorption of magnesium.
  • Additionally, the consumption of large amounts of calcium, vitamin D and zinc all decrease magnesium absorption.
Anyone favouring the intake of any of these food nutrients is encouraged to bump up their magnesium intake to compensate for reduced absorption. 1) Lukaski, H.C., Bolonchuk, W.W., Klevay, L.M., Milne, D.B., Sandstead, H.H. (2001). Interactions among dietary fat, mineral status and performance of endurance athletes: A Case Study. Int J Spor Nutr Exerc Metab. 11(2): 186-198
Energy
It's a little-known fact that magnesium - consider...
It's a little-known fact that magnesium - considered the sleep mineral and the anti-stress mineral - is actually essential for energy production. "One of the most amazing effects of magnesium on the neuromuscular system is that it provides more energy, even though the mineral generally acts as a relaxant and not a stimulant." (Dr. Carolyn Dean, The Magnesium Miracle, p. 71)

Magnesium Creates Energy in the Cells

Cells draw on energy packets called ATP (adenoside triphosphate). The ATP required at the cellular level for physical activity depends on enzymes called ATPases. During strenuous activity, these magnesium-dependent enzymatic processes rely heavily on an extraordinarily fast-paced rate of ATP turnover. This is only possible when sufficient magnesium levels are present in the body. In fact, ATP must be bound to magnesium in order to be biologically available to the muscle. Sometimes described as the furnace of the cells, the energy-producing ATP needs magnesium to do the job it needs to do well. Without sufficient magnesium, energy production declines, energy levels fall and you start to feel fatigued. According to Dr. Dean, "Some of the first studies showing the relationship between magnesium and physical exercise were done on animals and found that decreased exercise capacity can be an early sign of magnesium deficiency. When the animals were given magnesium dissolved in water, their endurance was restored. Most human studies also confirm that both brief and extended exercise depletes magnesium." (p. 70)

Magnesium, Energy and Exercise Performance

In a very tightly controlled, three-month study in the U.S., the effects of magnesium depletion on exercise performance in 10 women was observed. In months 1 and 3, the women received a magnesium-deficient diet of 112mgs per day, and a magnesium supplement of 200mgs per day to reach the Recommended Dietary Allowance per day. In month 2, the supplement was withdrawn to intentionally result in a magnesium-deficient diet. At the end of each month, the women were asked to cycle at increasing intensity until they reached 80% of their maximum heart rate, at which time they were subjected to a battery of tests. The results clearly established that when magnesium was deficient, metabolic efficiency was reduced as both heart rate and oxygen intake increased, in essence making the body work much harder to perform the same task. Source:  J Nutr 132:930-935 (2002)
Women’s Health
It would be fair to say, given the challenges of e...
It would be fair to say, given the challenges of estrogen, stress, autoimmune disorders, Chronic Fatigue Syndrome, migraine, insomnia, bone health, and thyroid - to name just a few - that women need magnesium more than men. Yet women get just 70% of their minimum requirements for magnesium while men get 80%. Pound for pound, women have less magnesium circulating throughout their bodies. And because of magnesium’s effect on hormones, women can suffer more noticeably from magnesium deficiencies during pregnancy, breastfeeding and with PMS. Here’s a partial list of how magnesium particularly benefits women:
  • Helps balance the entire hormone system, reducing complications with menstruation, fertility, pregnancy and menopause
  • Builds strong bones, preventing osteoporosis
  • Reduces anxiety by balancing the output of adrenaline and cortisol
  • Activates B vitamins, essential for reducing stress
  • Facilitates production, storage and transport of energy
  • Helps stabilize RNA and DNA synthesis (stabilizing the genetic blueprint)
  • Activates Omega 3s, supporting mood, brain health and reducing inflammation
  • Relaxes muscles and nerves, reducing muscle pain, menstrual cramps, nervous anxiety and headaches
  • Prevents thickening and clotting of the blood, which contributes to PMS, migraines, and stroke
  • Reduces hypertension, preventing pregnancy complications (preeclampsia) and heart attack
How much? Women should aim for 6 - 8 mg of magnesium per kilogram of weight, daily (3 - 4.5 mg/lb). A 150 lb woman should get 450 - 675 mg a day through diet and supplements. During pregnancy, periods of intense exercise and stress, strive for the higher end of the intake spectrum. Source: Dean, Carolyn, M.D., N.D. The Magnesium Miracle, Revised and Updated. Ballantine Books, 2007.
Sleep Disorders
"A good laugh and a long sleep are the best cures ...
"A good laugh and a long sleep are the best cures in the doctor’s book," so says an Irish proverb, and if there's truth in it, most of us could use more of the medicine of sleep. It is estimated that almost 1 out of every 3 adults have difficulty falling asleep or staying asleep. There are of course hundreds of reasons that can disrupt sleep once it starts, or prevent you from falling asleep in the first place. Physiologically, one of the key contributors can be a lack of magnesium or melatonin – or both. Among Canadians who have learned first-hand the benefits of magnesium, a great night’s sleep is cited as the most appreciated. In hundreds of Natural Calm testimonies, the restoration of a good night’s sleep is the most frequently cited benefit. Insomnia can be the most noticeable symptom of magnesium deficiency. Lack of magnesium can result in over-excitement and nervousness, keeping the electrical signals in your brain firing, causing you to wake up prematurely, or preventing sleep in the first place. The most prevalent sleep disorders can all be related to magnesium deficiency, including:
  • difficulty falling asleep
  • abrupt awakening from sleep
  • jerking and other disruptive
  • talking in your sleep
  • Restless Leg Syndrome (RLS)
A nutrition research project at the United States Department of Agriculture found that “a diet inadequate in magnesium caused changes in brain waves--electrical activity in the brain” when subjects were at rest. These findings build on a growing body of evidence pointing to magnesium deficiency as a cause of sleep disturbances, including agitated sleep and frequent waking. Magnesium helps relax muscles and nerves to support a deep, restful sleep. Common leg cramps and RLS, characterized by jumpy, twitchy, overactive limbs can be treated by calming magnesium. The same goes for tension headaches, the result of a tightening of the muscles in the neck and scalp, and migraines, triggered by the exaggerated firing of nerves. And that’s not all: magnesium activates melatonin, a sleep-inducing hormone. Without enough magnesium, your body won't get those natural cues to wind down and slip into restorative sleep.

The Calcium Connection

Typically, North American diets are heavily skewed in favour of calcium. Not only do many opt for dairy products over magnesium-rich plant sources, increasingly people consume calcium-fortified products. As a result, the average North American consumes five to ten times more calcium than magnesium. There’s certain logic behind the warm glass of milk theory, and it’s instructive as a starting point for understanding the mechanisms of nutrients and sleep. Milk contains tryptophan, a precursor to melatonin commonly associated with turkey dinners. Milk’s calcium aids in the uptake of tryptophan, speeding relaxation. However, without enough magnesium, high calcium creates an imbalance; that imbalance can set of the tension that prevents sound sleep. According to Darcy Sutherland, a Registered Nutritional Consultant Practitioner (RNCP) practicing in Toronto, “magnesium has, in recent years, taken a back seat to calcium. There’s been an emphasis on the importance of calcium and vitamin D for bone health, but taking these supplements on their own can throw off the body's balance.” Without magnesium, the signals to relax are impeded. More calcium, for most, is not the answer. Better absorption of calcium through an adequate supply of magnesium is a better solution. Magnesium supplementation has been a proven natural sleep aid both by helping you stay asleep and to fall asleep faster

When Magnesium Supplementation Isn’t Enough

If you have tried Natural Calm at bedtime for several nights in a row and have been one of the few who has not experienced an improved night’s sleep, it could be that your body is not producing enough melatonin. Melatonin is sometimes referred to as the Dracula hormone because its release is brought on naturally by darkness. As such it regulates our internal clocks, increasing when we should feel sleepy and dropping with morning light. Artifical light – including television sets in the bedroom – are enough to inhibit the production of melatonin. And as we age, our natural production of melatonin declines. After the age of 40, this decrease can be significant. Should you continue to experience difficulties sleeping even in dark rooms, you may want to add a few drops of Heavenly Sleep liquid melatonin to your night-time Natural Calm magnesium drink. So remember Heavenly Sleep along with Natural Calm magnesium is the ultimate sleep solution.
Restless Leg Syndrome (RLS)
RLS is a disorder of the part of the nervous syste...
RLS is a disorder of the part of the nervous system that affects movements of the legs. For most, it occurs most at nighttime, so RLS is considered a sleep disorder. RLS sufferers have strange sensations in their legs and an irresistible urge to move their legs to relieve the sensations. RLS sufferers describe “jumpy” “twitchy” or "creepy crawly" feeling deep in the legs. The severity of these symptoms can range from mild to intolerable. At its extreme, RLS makes it difficult to fall asleep and stay asleep. For about 60% of people with RLS, both the frequency and the intensity can worsen over time.

The Magnesium Solution

Many physicians suggest lifestyle changes or prescription drugs. Some of the suggested Rx ‘solutions’ for RLS include benzodiazepines, opiods – heavy duty narcotics designed for pain relief, anti-epileptics, and dopamine agonists. Testimonies from Natural Calm users suggest without a doubt that RLS can be ameliorated by addressing magnesium deficiency. Hundreds of fans have written to say that their RLS symptoms were completely eliminated when they discovered Natural Calm. And scientific studies on the efficiency of sleep (decreased episodes of awakening and increased sleep time) showed significant improvement when magnesium supplementation was introduced, especially for people reporting episodes of RLS. RLS is one of the leading conditions for which magnesium has proven to be a literal overnight cure for even the most severe cases. Some of our most enthusiastic testimonials come from Natural Calm fans who use our magnesium citrate drink and apply our transdermal magnesium chloride to their legs before bed. Magnesium applied topically - to the skin - absorbs quickly, and it completely bypasses the gut. For those with sensitive digestive systems and RLS, Natural Calm transdermal magnesium is the perfect solution.
Inflammation
Inflammation is the activation of the immune syste...
Inflammation is the activation of the immune system as a result of infection, irritation or injury. Inflammation triggers include excessive insulin, emotional stress, free-radical damage, viral, bacterial, fungal and other pathogenic infections, obesity, overconsumption of hydrogenated oils, periodontal disease, smoking, some prescription drugs, environmental toxins and radiation. As an example of inflammation in action, take an ankle sprain. This acute injury will prompt the immune system to create and send a protein called a Circulating Immune Complex (CIC) to the affected area. The CIC travels down to the injured ankle and causes pain and swelling. This action helps prevent further injury and irritation. CIC also supports fresh blood, antibodies and vital cells flooding the area, so that repair and healing can begin. Next, the proteolytic enzymes are produced and sent down to the affected area to help counteract the inflammation. These enzymes are mediated by magnesium, meaning they perform better when adequate levels of magnesium are present in the blood cells.

Inflammation, Enzymes and Magnesium

When science states that magnesium is responsible for 700 - 800 enzymatic processes in the body, the production of proteolytic enzymes is just one of them. If magnesium levels are too low, the activities of these crucial magnesium-sensitive enzymes will not work as they should. Properly-functioning enzymes are essential for so many reasons:
  • Enzymes break down scar tissue, including fibrosis. Fibrosis is scar tissue that builds up in the body and over time creates so much restriction and strain on the organs that they can no longer function properly.
  • Enzymes clean the blood of excess fibrin that causes the blood to thicken, which causes blood clots, leading to heart attack or stroke.
  • Enzymes take some of the strain off of the liver by keeping the blood clean.
Enzymes are central to inflammation and the fundamental supporter of enzymes is magnesium.

When Magnesium is Low

Researchers have found that when magnesium levels are too low, there is a profound increase of inflammatory cytokines, along with increased levels of histamine. Problems with insulin metabolism results in the inability to properly store magnesium, causing blood vessels to constrict, elevated blood pressure, and coronary arterial spasm, all of which can result in a heart attack. The presence of inflammation will itself deplete magnesium levels, so supplementation when the body is battling and inflamed is crucial. If there is not enough magnesium present at this time, excess calcium will precipitate around the area of inflammation which will cause rigidity and blockage of blood flow. Magnesium is at the core of the inflammatory process. Deficiency in magnesium should be considered the first cause, yet magnesium is seldom considered. Increases in extracellular magnesium concentration cause a decrease in the inflammatory response while reduction in the extracellular magnesium results in inflammation.
Fibromyalgia
Fibromyalgia is a condition of unknown origin that...
Fibromyalgia is a condition of unknown origin that causes widespread, long-term pain, stiffness and tenderness in muscles and ligaments. The vast majority of sufferers are women in their mid-20s to late-50s. There is no known cause for fibromyalgia making a definitive diagnosis difficult.  Healthcare professionals instead look at the symptoms. In addition to muscle stiffness and pain, fibromyalgia can also cause wider-ranging symptoms, such as sleep problems, general fatigue, depression, headaches, numbness or tingling, Irritable Bowel Syndrome, and an inability to think clearly.

Fibromyalgia and Sleep

Many times Chronic Fatigue Syndrome (CFS) and fibromyalgia are closely related. Some researchers subscribe to the theory that fibromyalgia may be caused by a lack of deep sleep. Our muscles recover from the day’s activities during stage 4 sleep, during which the body truly can refresh itself. People with fibromyalgia never truly enter stage 4 sleep. Instead of sinking into the deep sleep enjoyed by most people, they remain in a lighter form of sleep. One of magnesium’s leading benefits is a marked improvement in sleep.

Fibromyalgia and Magnesium

Magnesium deficiency is common in chronic fatigue syndrome and fibromyalgia sufferers. And since we know the ideal calcium/magnesium balance is crucial to muscle health, anyone with symptoms of fibromyalgia would benefit from increased magnesium intake. Dr. Carolyn Dean, M.D., N.D. argues that magnesium is an important treatment for fibromyalgia because this key mineral ameliorates fatigue and muscle pain and helps to combat chronic fatigue syndrome by ensuring a deeper REM sleep as well as activating the ATP energy bundles in the cells. Note that if there is no discernible improvement in sleep after introducing a high-quality magnesium supplement, such as Natural Calm, a melatonin deficiency may be underlying the chronic sleep issues. Magnesium activates melatonin. Some individuals don’t produce enough melatonin for the magnesium to activate, in which case we recommend using Natural Calm’s Heavenly Sleep liquid melatonin together with Natural Calm’s magnesium citrate at bedtime.
Migraines and Headaches
Migraines and headaches can be debilitating. Days ...
Migraines and headaches can be debilitating. Days spent in dark rooms, not moving. Social events missed. Too many medications.

Migraine Causes

  • A confirmed cause of migraines continues to elude researchers and scientists, but many believe they are a result of sudden, dramatic changes in the blood vessels.   These 'vascular changes' are such that they interfere with the flow of blood and/or oxygen to the brain.
  • The triggers or causes of these changes to the blood vessels, or vascular change are as varied as the individuals who suffer from migraines.
  • A widely-held theory is that serotonin levels drop, causing inflammation and pain.  Because serotonin, also known as 5-HT or 5-HTP is also known to regulate mood and a general feeling of well-being, many prescription drugs for depression, designed to elevate serotonin levels,  may be prescribed for migraine sufferers.   Many patients are disappointed with the efficacy of these medications in reducing the frequency or severity of their migraines.

The Magnesium-Migraine Connection

Magnesium – when present in adequate amounts in the blood vessels – helps with the enzymatic conversion of tryptophan – the biochemical fore-runner to serotonin.  Magnesium therefore directly affects the amount of serotonin found in the blood. Not enough magnesium =  not enough serotonin. Any migraine sufferer would do well to replenish their magnesium levels every day. Other fascinating facts:
  • 66% of migraine sufferers have low magnesium
  • Magnesium helps reduce the frequency, intensity, and duration of migraines
  • Magnesium deficiency will cause irritation and inflammation in the smooth muscles around the neck and scalp
  • Magnesium acts as a natural blood thinner, helping prevent thickened blood and tiny clots that can cause blood vessel spasm and pain
  • Magnesium relaxes the blood vessels and allows them to dilate, reducing the spasms and constrictions that can cause migraines
  • Magnesium regulates the action of brain neurotransmitters (such as serotonin) and inflammatory substances, which may play a role in migraines when unbalanced
  • Magnesium relaxes muscles and prevents the buildup of lactic acid, which, along with muscle tension, can worsen head pain.

Research on the Magnesium-Migraine Link

In a 1996 published study, researchers gave 81 migraine sufferers either 600 milligrams of magnesium or a placebo pill once daily for three months. After four weeks, 42% of the group taking magnesium reported a reduction in the number of migraine occurrences.  As well, the duration of migraine drug use significantly decreased among people who took magnesium supplements. 20 years later, there is growing support in the physician community that some of the most severe cases of migraines may actually be directly related to an imbalance of key minerals such as magnesium and calcium.
Chronic Pain
Chronic Pain is One of Canada’s Most Common Medi...

Chronic Pain is One of Canada’s Most Common Medical Conditions and the Least Understood

Pain is a result of an excessive stimulation of a chemical in the brain called “NMDA.” Magnesium works to settle NMDA without the toxicity of over-the-counter (OTC) pain medications. It has been found to lessen pain caused by severe pancreatic cancer and chronic pain problems such as fibromyalgia. Magnesium helps to dramatically reduce pain by relaxing muscles and driving excess calcium out of the cells. It also helps by reducing spasms and by relaxing blood vessels in the extremities that are often associated with Raynaud’s Syndrome. There are so many syndromes today that can be described as tension-based. Magnesium’s job in the body is to calm and relax the cells, easing stress at the cellular level and reducing tension. North American love of calcium, which can lead to tension, is also a contributing factor in pain and pain management. It is essential to maintain balanced levels of calcium and magnesium, as too much calcium may cause pain, as will too little magnesium. Dr. Linda Rapson, who specializes in treating chronic pain and has a focus on nutrition as it relates to pain, believes that the majority of her patients who complain of muscle pain, cramps and fatigue have signs of magnesium deficiency. “Virtually all of them improve when I put them on magnesium,” says Rapson, who runs a busy Toronto pain clinic. Dr. Rapson has been treating patients for more than 30 years and has seen magnesium work in those with migraines, fibromyalgia and constipation. “The scientific community should take a good hard look at this.”