Magnesium: An Update
During my years in Naturopathic Medicine school and nutrition, I’ve learned about the importance of magnesium and how deficient our modern diet currently is due to monocropping (the practice of growing a single crop year after year on the same land) and other conventional farming methods stripping the soil of valuable nutrients and life-supporting microbiota; the refining and ultra-processing of food stripping away life-supporting nutrients; and, the effect of our modern lifestyles in depleting our stores of magnesium (due to excessive demands. e.g., stress, diet habits, chronic lack of sleep).
Over 300 enzymatic pathways require magnesium. Magnesium is a vital component of detoxification. Magnesium is essential to modulate the stress response (HPA axis activation and the production of stress hormones. Numerous studies have investigated the interaction of magnesium with key mediators of the physiological stress response and demonstrated that magnesium plays an inhibitory key role in the regulation and neurotransmission of the normal stress response. This is because magnesium is a muscle relaxant (calcium support muscle tension and magnesium is required to relax muscle fibres. Without a sufficient pool of magnesium muscle fibres stay contracted and thus lead to muscular tension and cramps). Furthermore, magnesium deficiency has been linked to anxiety and heightened stress response (lowering your resilience and thus making it difficult for you to cope during stressful situations).
Some of the main functions of magnesium in the human body include the maintenance of ionic gradients (keep intracellular sodium and calcium low and potassium high), cellular and tissue integrity, mitochondrial function (ATP production and activation; mitochondria being the energy production factories inside human body cells), and DNA, RNA and protein synthesis and integrity. Any deficiency in magnesium may thus be implicated in activating genetic predispositions (remember that “bad” genes can be activated by bad diet and lifestyle, and chronic stress, including chronic lack of sleep).
Important statistics:
Magnesium is so vital for life, it is the fourth most abundant mineral in the body, required by every cell, and used as a cofactor in over 300 enzyme systems. And yet, studies estimate that as many as 75% of Americans do not get enough and recent data suggest that 1/3 of the global population has subclinical magnesium deficiency based on serum magnesium levels <0.80 mmol/L.[1]
Magnesium deficiency has been found in 84% of postmenopausal women with osteoporosis.[2]
42% (of healthy) university students in Brazil were found to have subnormal magnesium status.[3]
Magnesium depletion has been found in 75% of patients with poorly controlled type 2 diabetes.[4]
A systematic review of 37 studies shows that magnesium deficiency was a possible public health concern for older adults.[5]
In developed countries, the average intake of magnesium is slightly over 4 mg/kg/day. More than a quarter of obese and non-obese youth have inadequate intake of magnesium (27% and 29%, respectively).[6,7]
Since 1940 there has been a tremendous decline in the micronutrient density of foods. In the UK for example, there has been a loss of magnesium in beef (−4 to −8%), bacon (−18%), chicken (−4%), cheddar cheese (−38%), parmesan cheese (−70%), whole milk (−21%) and vegetables (−24%). The loss of magnesium during food refining/processing is significant: white flour (−82%), polished rice (−83%), starch (−97%) and white sugar (−99%). Since 1968 the magnesium content in wheat has dropped almost 20%, which may be due to acidic soil, yield dilution and unbalanced crop fertilisation (high levels of nitrogen, phosphorus and potassium, the latter of which antagonises the absorption of magnesium in plants).[7]
Magnesium deficiency is a widespread problem
Because serum magnesium does not reflect intracellular magnesium, the latter making up more than 99% of total body magnesium, most cases of magnesium deficiency are undiagnosed.
Because of the increased prevalence in chronic diseases, medications (polypharmacy and magnesium-lowering drugs such as Omeprazole), decreases in food crop magnesium contents, and the availability of refined and ultra-processed foods, the vast majority of people in modern societies are at risk for magnesium deficiency.[8]
Certain individuals will need to supplement with magnesium in order to prevent suboptimal magnesium deficiency. Subclinical magnesium deficiency increases the risk of numerous types of cardiovascular disease, costs nations around the world an incalculable amount of healthcare costs, and should be considered a public health crisis.
“Magnesium is the seventh most abundant element in the Earth’s crust by mass or molarity… In vertebrates, magnesium is extremely abundant and it is the second most common intracellular cation (potassium being the first). Extracellular magnesium accounts for only ∼1% of total body magnesium, which is found primarily in serum and red blood cells.[9]”
Again, magnesium (acting as a co-factor) is necessary for the functioning of over 300 enzymes in humans,[10] with 90% of total body magnesium being contained in the muscles and bones (~27% and ~63%, respectively), 90% of which is bound and with only 10% being free.[11]
Additionally, when in the bloodstream, over 1/3 of magnesium is bound to albumin (the most abundant circulating protein in the human body, which is also produced by the liver. Albumin also carries substances such as hormones, medicines, and enzymes throughout your body). 55% of the magnesium in the bloodstream is “free” and for this reason, blood tests cannot reveal the “real” picture and intracellular deficiency.
Overexposure to heavy metals (e.g., tap water, certain teas, drugs/supplements, rice, ultra-processed and refined food products) or heavy metal poisoning may also predispose you to micronutrient deficits.[12] Dietary aluminium may lead to magnesium deficit by reducing the absorption of magnesium by approximately fivefold, reducing magnesium retention by 41% and causing a reduction of magnesium in the bone matrix.[13] And since aluminium is widely prevalent in modern-day society (such as in aluminium cookware, deodorants, over-the-counter and prescription medications, baking powder, baked goods, and others), this could be a major contributor to magnesium deficiency.[7]
What are deficiencies
There are two types of nutrient deficiencies, “frank” deficiencies (such as scurvy from ascorbic acid deficiency) and “subclinical” deficiencies (a clinically silent reduction in physiological, cellular and/or biochemical functions).
It is the latter that is most concerning as it is very difficult to diagnose and predisposes individuals to numerous chronic diseases.
The evidence in the literature suggests that subclinical magnesium deficiency is rampant and one of the leading causes of chronic diseases including cardiovascular disease and early mortality around the globe. This is why magnesium deficiency should be considered a public health crisis.
Since the kidneys are responsible for magnesium balance, excessive consumption of caffeine can contribute to magnesium losses. Intense exercising also leads to greater losses and it is one of the reasons electrolytes are recommended for athletes.
Magnesium and our evolution
Our metabolism is best adapted to a high magnesium intake and has not changed since our bodies (and homeostatic pathways) developed millions of years ago.
Investigations of the macro- and micro-nutrient supply in Palaeolithic nutrition of the former hunter-gatherer societies showed a magnesium uptake with the usual diet of about 600 mg magnesium/day, which is much higher than today.[7,14]
“Even though children may consume an excess of energy, they may not be meeting all of their micronutrient needs.[15]”
What the quote above implies is that children in our modern world are overfed but undernourished.
Researchers have come to the following conclusion:
“Various studies have shown that at least 300 mg magnesium must be supplemented to establish significantly increased serum magnesium concentrations… In other words, most people need an additional 300 mg of magnesium per day in order to lower their risk of developing numerous chronic diseases. So while the recommended daily allowance (RDA) for magnesium (between 300 and 420 mg/day for most people) may prevent frank magnesium deficiency, it is unlikely to provide optimal health and longevity, which should be the ultimate goal.”[7]
Much of the population may not even be meeting the RDA for magnesium and some age groups consume substantially less, which may place them at more risk of chronic diseases by being chronically deficient in magnesium; a problem that is made worse by polypharmacy.
“These intake levels suggest that a substantial number of people may be at risk for Mg deficiency, especially if concomitant disorders and/or medications place the individual at further risk for Mg depletion.[16]”
Increased calcium and phosphorus intake also increases magnesium requirements and may worsen or precipitate magnesium deficiency. This is a pertinent fact to consider when supplementing with calcium without supervision. Excess calcium, phosphorus and vitamin D may also lead to increased magnesium loss increasing magnesium requirements.
Magnesium and anti-nutrients (e.g., lectins, phytic acid)
A common misconception is that consuming phytate-rich foods can lead to nutrient deficiencies particularly magnesium depletion via binding by phytic acid. However, urinary magnesium excretion will drop to compensate for a reduction in bioavailable magnesium. And most high-phytate foods are also good sources of magnesium (grains and beans are good examples). Thus, it is unlikely that consuming foods high in phytate will lead to magnesium depletion.[7]
However, a vitamin B6-deficient diet can lead to a negative magnesium balance via increased magnesium excretion.
Causes of magnesium deficiency
Numerous factors can lead to magnesium deficiency, such as kidney failure, alcohol consumption, digestive (e.g., chronic stress, low stomach acid, use of PPIs such as Omeprazole), pancreatic and malabsorption issues (magnesium is absorbed in the small intestine and in the colon; thus, patients with intestinal or colon damage such as IBD (Crohn’s disease, ulcerative colitis) IBS, coeliac disease, gastroenteritis, idiopathic steatorrhoea, resection of the small intestine, and ileostomy patients may have magnesium deficiency). Renal tubular acidosis, diabetic acidosis, prolonged diuresis, hyperparathyroidism and primary aldosteronism can also lead to magnesium deficiency.
A meta-analysis of 13 studies in almost 5500 patients found that magnesium levels were significantly lower in patients with metabolic syndrome versus controls.
Supplementing with calcium can lead to magnesium deficiency due to competitive inhibition for absorption, and over-supplementing with vitamin D may lead to magnesium deficiency via excessive calcium absorption and hence increase the risk of arterial calcifications.
Use of diuretics and other medications can also lead to magnesium deficiency.
Typical Causes of magnesium deficiency[7,17]
Acetaminophen toxicity
Alcoholism
Aluminium (environmental and dietary)
Aldosteronism
Alcohol
Ageing (hypochlorhydria, ie, decreased acid in the stomach)
Antacids (including ranitidine and famotidine).
Bariatric surgery (small intestinal bypass surgery)
Calcium supplements (or high calcium to magnesium diet).
Caffeine
Cancer
Coeliac disease
Colon removal
Chronic stress
Cisplatin
Crohn’s disease
Ciclosporin
Type 1 and type 2 diabetes (uncontrolled glucose levels).
Diarrhoea
Diets high in fat or sugar
Digoxin (a cardiac stimulant)
Diuretics — non-potassium-sparing diuretics (thiazide and loop diuretics).
Excessive ingestion of poorly absorbable magnesium (such as magnesium oxide), leading to diarrhoea and magnesium loss.
Emotional and/or psychological stress (overactivation of the sympathetic nervous system).
Enzymatic dysfunction (impaired magnesium distribution).
Oestrogen therapy (shifts magnesium to soft and hard tissues lowering serum levels).
Excessive or prolonged lactation
Excessive menstruation
Fasting (or low magnesium intake).
Foscarnet (antiviral medication primarily used to treat viral infections involving the Herpesviridae family)
Gentamicin and tobramycin
Hyperparathyroidism and hypoparathyroidism
Hyperthyroidism
Kidney diseases (glomerulonephritis, pyelonephritis, hydronephrosis, nephrosclerosis and renal tubular acidosis).
Heart failure
Haemodialysis
High phosphorus in the diet (soda, inorganic phosphates contained in many inactive ingredients in processed foods).
Hyperinsulinaemia (and insulin therapy)
Insulin resistance (intracellular magnesium depletion).
Laxatives
Low salt intake
Low selenium intake
Gastrointestinal disorders — malabsorption syndromes (coeliac disease, non-tropical sprue, bowel resection, Crohn’s disease, ulcerative colitis, steatorrhoea), prolonged diarrhoea or vomiting
Liver disease (acute or chronic liver disease, including cirrhosis and NAFLD)
Metabolic acidosis (latent or clinical)
Pancreatitis (acute and chronic)
Parathyroidectomy
Pentamide (antiparasitic drug)
Peritoneal dialysis
Porphyria with the inappropriate secretion of antidiuretic hormone
Pregnancy (increased requirements)
Proton pump inhibitors (PPIs, such as Omeprazole)
Strenuous exercise (increased loss of magnesium via sweat and increased requirements)
Tacrolimus
Vitamin B6 (pyridoxine) deficiency
Vitamin D excess or deficiency (chronic kidney disease and liver disease can prevent the activation of vitamin D).
Potential clinical signs of magnesium deficiency[7,18-20]
Less severe signs
Aggression
Anxiety
Ataxia
Chvostek sign (twitching of the facial muscles in response to tapping over the area of the facial nerve).
Confusion
Cramps (spontaneous carpopedal spasms or painful cramps of the muscles in your hands and feet)
Disorientation
Fasciculations (brief, spontaneous contraction affecting a small number of muscle fibres, often causing a flicker of movement under the skin)
Hyperreflexia
Irritability
Muscular weakness
Neuromuscular irritability
Pain or hyperalgesia (decreases the nociceptive threshold).
Photosensitivity
Spasticity
Tetany (involuntary muscle spasms).
Tinnitus (ringing in the ears).
Tremors
Trousseau sign
Vertigo
Vitamin D resistance
Severe signs
Arrhythmias (caused by overexcitation of the heart)
Calcifications (soft tissue)
Cataracts
Convulsions
Coronary artery disease
Depressed immune response
Depression
Hearing loss
Heart failure
Hypertension
Migraines/headaches
Mitral valve prolapse
Osteoporosis
Parathyroid hormone resistance and impaired parathyroid hormone release/function
Psychotic behaviour
Seizures (overexcitation of the nervous system (nerve cells), which are more likely to fire due to a reduced electric potential difference between the outer and inner surfaces of the cell’s membrane).
Sudden cardiac death
Tachycardia
In conclusion
In order to prevent chronic diseases, we need to change our mindset away from exclusively treating acute illness and instead focus more on treating the underlying causes of chronic diseases, such as magnesium deficiency.
Remember that we are using a healthcare system that is, in fact, a diseased system. We wait for a problem to appear to treat it. There is no prevention. There is nothing based on health but disease. Doctors learn diseases. They do not learn health-supporting avenues like naturopathic medicine, naturopathic nutrition and such movements as Integrative Medicine, Functional Medicine and other medicine focussed on the human body and harmony between all the systems that make the human body whole — not disconnected as preached by the current medical model.
I would like to leave you with some important quotes.
Based on 183 peer-reviewed studies published from 1990 to 2008, one group of authors concluded:
“Hypomagnesemia is a relatively common occurrence in clinical medicine. That it often goes unrecognized is due to the fact that magnesium levels are rarely evaluated since few clinicians are aware of the many clinical states in which deficiency, or excess, of this ion may occur.[5]”
Based on 183 peer-reviewed studies published from 1990 to 2008, one group of authors concluded:
“The perception that ‘normal’ serum magnesium excludes deficiency is common among clinicians. This perception is probably enforced by the common laboratory practice of highlighting only abnormal results. A health warning is therefore warranted regarding potential misuse of ‘normal’ serum magnesium because restoration of magnesium stores in deficient patients is simple, tolerable, inexpensive and can be clinically beneficial.[21]”
Another great quote:
“Although magnesium intakes have been gradually falling since the beginning of the century, there were sharply increased intakes of nutrients that increased its requirements [particularly high vitamin D and phosphorus intakes]…The major source of phosphorus derives from soft drinks that contain phosphoric acid, the consumption of which has been rising markedly in the last quarter of a century.[22]”
References
1. Costello, RB. et al. (2016). Perspective: The case for an evidence-based reference interval for serum magnesium: The time has come. Advances in Nutrition. 7, pp. 977–993. doi:10.3945/an.116.012765
2. Cohen. L. Kitzes, R. (1981). Infrared spectroscopy and magnesium content of bone mineral in osteoporotic women. Israel Medical Association Journal.17, pp. 1123–1125.
3. Hermes Sales, C. et al. (2014). There is chronic latent magnesium deficiency in apparently healthy university students. Nutricion Hospitalaria. 30, pp. 200–204. doi:10.3305/nh.2014.30.1.7510
4. Lima, ML. et al. (2005). Magnesium deficiency and insulin resistance in patients with type 2 diabetes mellitus. Arquivos Brasileiros de Endocrinologia & Metabologia (Archives of Endocrinology and Metabolism). 49, pp. 959–963.
5. Ter Borg, S. et al. (2015). Micronutrient intakes and potential inadequacies of community-dwelling older adults: A systematic review. British Journal of Nutrition. 113, pp. 1195–1206. doi:10.1017/S0007114515000203
6. Durlach, J. (1989). Recommended dietary amounts of magnesium: Mg RDA. Magnesium Research. 2, pp. 195–203.
7. Di Nicolantonio, JJ. O'Keefe, JH. Wilson, W. (2018). Subclinical magnesium deficiency: A principal driver of cardiovascular disease and a public health crisis. Open Heart. 5(1), e000668. doi:10.1136/openhrt-2017-000668. Erratum in: Open Heart. 2018 Apr 5. 5(1), e000668corr1.
8. Louzada, ML. et al. (2015). Impact of ultra-processed foods on micronutrient content in the Brazilian diet. Revista de Saúde Pública. 49, pp. 1–8. doi:10.1590/S0034-8910.2015049006211
9. Kielstein, JT. David, S. (2013). Magnesium: The ‘earth cure’ of AKI? Nephrology Dialysis Transplantation. 28, pp. 785–877. doi:10.1093/ndt/gfs347
10. Martyka, Z. Kotela, I. Blady-Kotela, A. (1996). Clinical use of magnesium. Przeglad Lekarski. 53, pp. 155–158.
11. Vormann, J. (2003). Magnesium: Nutrition and metabolism. Molecular Aspects of Medicine. 24, pp. 27–37. doi:10.1016/S0098-2997(02)00089-4
12. Yasui, M. et al. (1991). Calcium and aluminum deposition in bone in situ. No To Shinkei (Brain and Nerve). 43, pp. 577–582.
13. Neathery, MW. et al. (1990). Effects of dietary aluminum and phosphorus on magnesium metabolism in dairy calves. Journal of Animal Science. 68, pp. 1133–1138. doi:10.2527/1990.6841133x
14. Vormann, J. (2003). Magnesium: Nutrition and metabolism. Molecular Aspects of Medicine. 24, pp. 27–37. doi:10.1016/S0098-2997(02)00089-4
15. Gillis, L. Gillis, A. (2005). Nutrient inadequacy in obese and non-obese youth. Canadian Journal of Dietetic Practice and Research. 66, pp. 237–242. doi:10.3148/66.4.2005.237
16. Rude, RK. Gruber, HE. (2004). Magnesium deficiency and osteoporosis: Animal and human observations. Journal of Nutritional Biochemistry. 15, pp. 710–716. doi:10.1016/j.jnutbio.2004.08.001
17. Wacker, WE. Parisi, AF. (1968). Magnesium metabolism. New England Journal of Medicine. 278, pp. 658–663. doi:10.1056/NEJM196803212781205
18. Shils, ME. (1969). Experimental human magnesium depletion. Medicine. 48, pp. 61–85. doi:10.1097/00005792-196901000-00003
19. Grobin, W. (1960). A New Syndrome, Magnesium-Deficiency Tetany. Canadian Medical Association Journal. 82, pp. 1034–1035.
20. Gerst, PH. Porter, MR. Fishman, RA. (1964). Symptomatic magnesium deficiency in surgical patients. Ann Surg. 159, pp. 402–406.
21. Ismail, Y. Ismail, AA. Ismail, AA. (2010). The underestimated problem of using serum magnesium measurements to exclude magnesium deficiency in adults; a health warning is needed for ‘normal’ results. Clin Chem Lab Med 2010;48:323–7. 10.1515/CCLM.2010.077
22. Seelig, MS. (1980). Magnesium Deficiency in the Pathogenesis of Disease: Early Roots of Cardiovascular, Skeletal, and Renal Abnormalities. Plenum Publishing Corporation. New York. p. 3