Subclinical magnesium deficiency: a principal driver of cardiovascular disease and a public health crisis

Jan 13, 2018 | Research | 0 comments

Published: 13th January, 2018
Authors: James J DiNicolantonio, James H O’Keefe, and William Wilson

In Summary:

  • Magnesium could be essential in the prevention (and treatment) of chronic disease
  • If deficient magnesium “can be pulled from the bone (as well as muscles and internal organs) in order to maintain normal” levels
  • We’re evolved from hunter gathers with a magnesium uptake of 600mg magnesium a day, “much higher than today”
  • “Most people need an additional 300 mg of magnesium per day in order to lower their risk of developing numerous chronic diseases”
  • Autoimmune diseases can cause increased magnesium deficiency
  • “One group of authors concluded: ‘When magnesium substitution is started, the minimum dose to be applied is 600 mg magnesium per day”

Quick Summary:

Magnesium is a mineral that’s vital for our health.

It helps our muscles and nerves work properly and hearts stay healthy. However, many people don’t get enough magnesium in their diet. This can lead to a condition called “subclinical magnesium deficiency.”

Subclinical magnesium deficiency means you don’t have enough magnesium in your body to cause obvious symptoms, but you still have low levels of magnesium in your blood.

One of the reasons this is becoming such a problem is that many people don’t realise they have it.

They may not feel any symptoms, but their body is still not getting enough magnesium. It’s important to eat foods that are high in magnesium, like nuts, seeds, and leafy green vegetables and/or supplement where necessary.

Magnesium deficiency can increase the risk of developing diseases like heart disease and diabetes and a range of autoimmune diseases.

Autoimmune diseases are where your immune system attacks your own body by mistake. This can cause damage to your organs and tissues. Some examples of autoimmune diseases include rheumatoid arthritis (such as ankylosing spondylitis), lupus, and multiple sclerosis.

Studies have shown that low magnesium levels can increases this risk of developing autoimmune diseases. That’s because magnesium helps regulate the immune system. When you don’t have enough magnesium, your immune system can become overactive and start attacking your own body.

The authors of this study believe that magnesium deficiency is becoming a public health crisis because most people are not getting enough magnesium in their diet. In fact, one study found that over half of the US population does not meet the recommended daily intake for magnesium.

Getting enough magnesium in your diet and/or via supplementation can help protect your heart and reduce your risk of developing autoimmune diseases. Good sources include:

  • Nuts and seeds (such as almonds)
  • Leafy green vegetables (such as spinach and kale)
  • Fish (such as salmon and halibut)
  • Magnesium supplements


“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.

Furthermore, because of chronic diseases, medications, decreases in food crop magnesium contents, and the availability of refined and processed foods, the vast majority of people in modern societies are at risk for magnesium deficiency.

Certain individuals will need to supplement with magnesium in order to prevent suboptimal magnesium deficiency, especially if trying to obtain an optimal magnesium status to prevent chronic disease.

Subclinical magnesium deficiency increases the risk of numerous types of cardiovascular disease, costs nations around the world an incalculable amount of healthcare costs and suffering, and should be considered a public health crisis.

That an easy, cost-effective strategy exists to prevent and treat subclinical magnesium deficiency should provide an urgent call to action.”

Magnesium in human biology

“… The human body contains around 25 g of magnesium.

Magnesium is necessary for the functioning of over 300 enzymes in human, 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. In the serum, 32% of magnesium is bound to albumin, whereas 55% is free…

The elimination of magnesium is mainly controlled by the kidneys, increasing in the urine when there is magnesium surplus and falling to just 1 mEq of magnesium (~12 mg) during deficits.

However, despite renal conservation, magnesium can be pulled from the bone (as well as muscles and internal organs) in order to maintain normal serum magnesium levels when intakes are low.

Thus, a normal serum magnesium level does not rule out magnesium deficiency, which predisposes to osteopaenia, osteoporosis and fractures.

An excess of heavy metals due to soil contamination and a lack of minerals due to soil erosion also may predispose to micronutrient deficits.

The importance of the mineral content of soil and water, once greatly appreciated, think low iodine levels in soil and the increased prevalence of goitre, has all but been forgotten.

Furthermore, refined foods are depleted of magnesium during their processing.

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…

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, and should be considered a public health crisis.”

Magnesium intake

“The homeostatic mechanisms to regulate magnesium balance were developed millions of years ago.

Investigations of the macro- and micro-nutrient supply in Paleolithic nutrition of the former hunter/gatherer societies showed a magnesium uptake with the usual diet of about 600 mg magnesium/day, much higher than today’.

Our homeostatic mechanisms and genome are still the same as with our ancestors in the Stone Age. This means our metabolism is best adapted to a high magnesium intake…

One expert has argued that a typical Western diet may provide enough magnesium to avoid frank magnesium deficiency, but it is unlikely to maintain high-normal magnesium levels and provide optimal risk reduction from coronary artery disease and osteoporosis.

That is, ‘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…

… around half (48%) of the US population consumes less than the recommended amount of magnesium from food.

The US Department of Agriculture states that the average magnesium intake in women and men is 228 mg/day and 323 mg/day, respectively.

Based on these data, one group of authors noted: ‘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’.

The most recent published review on magnesium concluded: ‘Approximately 50% of Americans consume less than the Estimated Average Requirement (EAR) for magnesium, and some age groups consume substantially less’…

Another long-term study lasting 50 weeks found that somewhere between 180 mg and 320 mg of magnesium/day is required in order to maintain positive magnesium balance.22 And since many individuals may be consuming below 320 mg/day of magnesium, this poses a major public health threat…

The authors also found a correlation between the low magnesium consumption in food and the prevalence of risk factors for ischaemic heart disease, such as hyperlipoproteinaemia, arterial hypertension and body weight.

In 2004, Durlach concluded: ‘About 20% of the population consumes less than two-thirds of the RDA for Mg. Women, particularly, have low intakes.

For example, in France, 23% of women and 18% of men have inadequate intakes. Mg deficiency during pregnancy can induce maternal, fetal, and pediatric consequences that might last throughout life’.

The median magnesium intake in an elderly population (832 subjects aged 70 years or older) in Southern France was also found to be below the RDA.26 Another French study on 2373 subjects (4–82 years of age) noted that 71.7% of men and 82.5% of women had an inadequate magnesium intake…

Magnesium deficiency has been found in 84% of postmenopausal women with osteoporosis diagnosed by low magnesium trabecular bone content and Thoren’s magnesium load test.33 Among apparently healthy university students in Brazil, 42% were found to have subnormal magnesium status (based on plasma or erythrocyte magnesium levels).13 The average magnesium intake was only around 215 mg/day. Magnesium depletion has been found in 75% and 30.8% of patients with poorly controlled type 2 diabetes based on serum and intracellular magnesium status, respectively.34

Magnesium deficiency can be present despite normal serum magnesium levels.6 Approximately 20% of 381 unselected elderly men and women (most of them in their 80s) were found to have low erythrocyte potassium and magnesium levels. The authors of the study concluded:

‘This study underlines the large prevalence of magnesium and potassium deficiencies in the elderly’.

Another study concluded: ‘The commonly designated low limit of the normal range… is below levels that exist in patients with marginal deficiencies that can predispose to development of pathologic findings, so that the prevalence and importance of this disease is insufficiently considered…

It is a statistical error to use the confidence limits of the normal population as the exclusion limit for those with abnormal Mg status’.

In other words, our normal range of serum magnesium is inaccurate and that serum magnesium levels at the lower end of normal likely suggest marginal magnesium deficiency.

Indeed, ‘The magnesium content of the plasma is an unreliable guide to body stores: muscle is a more accurate guide to the body content of this intracellular cation’…

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’.

One study found that 10 out of 11 apparently healthy women were magnesium-deficient based on the oral magnesium load test.

The authors concluded: ‘The results showed there are more frequent deficiencies of magnesium in organisms than it is generally assumed’.

Another study showed that 37.6% of patients with type 2 diabetes and 10.9% of age-matched and sex-matched healthy controls have low plasma magnesium levels.

Dietary factors affecting magnesium status

“Since 1940 there has been a tremendous decline in the micronutrient density of foods. In the UK for example, there has been 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).

One review paper concluded: ‘Magnesium deficiency in plants is becoming an increasingly severe problem with the development of industry and agriculture and the increase in human population’.

Processed foods, fat, refined flour and sugars are all devoid of magnesium, and thus our Western diet predisposes us to magnesium deficiency. Good dietary sources of magnesium include nuts, dark chocolate and unrefined whole grains.

Increased calcium and phosphorus intake also increases magnesium requirements and may worsen or precipitate magnesium deficiency.

Dairy, especially cheese, has a very high phosphorus to magnesium (Mg) ratio. For example, cheddar cheese has a phosphorus:magnesium ratio of ~18 and a calcium:magnesium ratio of ~26, whereas pumpkin seeds have a phosphorus:magnesium ratio of 0.35 and a calcium:magnesium ratio of 0.21. Some have argued that the optimal dietary calcium:magnesium ratio is close to 2:1….

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.

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.

Magnesium balance

“… young women may be in negative magnesium balance despite consuming 350 mg of magnesium per day. However, one double-blind metabolic balance study in postmenopausal Caucasian women showed that 318 mg of magnesium per day was enough to remain in positive balance, but 118 mg/day was inadequate.

A more recent balance study in postmenopausal women found that while a diet containing 399 mg of magnesium per 2000 kcal was able to produce a positive magnesium balance, a diet containing ~100 mg of magnesium per 2000 kcal was inadequate.

Other data have found negative magnesium balance in men with osteoporosis or psychoneurosis consuming 240 mg/day of magnesium.

Another study noted negative magnesium balance (−122 mg) in those consuming 322 mg/day of magnesium on top of a high-fibre diet.

In other words, context matters (overall dietary pattern, patient population and background medication).”

Causes of magnesium deficiency

“Numerous factors can lead to magnesium deficiency, such as kidney failure, alcohol consumption and malabsorption issues (magnesium is absorbed in the small intestine and in the colon; thus, patients with intestinal or colon damage such as Crohn’s disease, irritable bowel syndrome, coeliac disease, gastroenteritis, idiopathic steatorrhoea, ulcerative colitis, resection of the small intestine, ileostomy patients or patients with ulcerative colitis may have magnesium deficiency).

Renal tubular acidosis, diabetic acidosis, prolonged diuresis, acute pancreatitis, hyperparathyroidism and primary aldosteronism can also lead to magnesium deficiency.”

Clinical signs of magnesium deficiency

“Among the most common laboratory signs of magnesium deficiency are low potassium and calcium levels, as well as low urine and/or faecal magnesium.

… Other signs of magnesium deficiency included tremor, fasciculations (‘a brief spontaneous contraction that affects a small number of muscle fibres.’), spontaneous carpopedal spasm (painful cramps of the muscles in your hands and feet) and generalised spasticity.

Other clinical features of magnesium deficiency include mental disturbances such as depression, confusion, agitation, hallucinations, weakness, neuromuscular irritability (tremor), athetoid movements and convulsive seizures.”

Treatment of magnesium deficiency

“One group of authors concluded: ‘When magnesium substitution is started, the minimum dose to be applied is 600 mg magnesium per day.

The therapy should proceed for more than one month, and then continue with a dose that holds the serum value not lower than 0.9 mmol/L magnesium’.

The authors noted that using a cut-off of 0.75 mmol/L for magnesium deficiency misses 50% of those with true magnesium deficiency.”

Coronary artery disease

“‘…low heart muscle magnesium may contribute to sudden death after myocardial infarction.

Western diets are probably often low in magnesium, so that the magnesium in hard drinking water may help to protect its consumers from ischemic heart disease…Increasing the magnesium content of the diet may help to prevent ischemic heart disease, and there is already evidence that magnesium salts can have beneficial effects on established heart disease’.

… Chipperfield noted: ‘Magnesium-deficient diets…predispose animals to the development of myocardial fiber necrosis.

Administration of magnesium salts has been shown to reverse many of the changes in animal models of heart disease…There is also good evidence from some animal studies that pretreatment with magnesium salts protects against many of the changes in the heart caused by anoxia…’

In other words, consuming a diet high in magnesium may prevent the harms from an acute ischaemic events.

Just 42–64 days on a diet low in magnesium (~101 mg/day) produced atrial fibrillation and flutter in three of five postmenopausal women (ages 47–75 years).

Moreover, the arrhythmias responded quickly to magnesium supplementation. During the low-magnesium diet, glucose levels increased and red blood cell superoxide dismutase decreased.

The authors of the study concluded: ‘A dietary intake of about 4.12 mmol (~101 mg/day, my insertion) Mg/8.4 MJ is inadequate for healthy adults and may result in compromised cardiovascular health and glycemic control in postmenopausal women’.

In a randomised, double-blind, placebo controlled study on 350 patients with acute myocardial infarction, intravenous magnesium sulfate given immediately after completion of thrombolytic therapy significantly reduced all-cause mortality (3.5% vs 9.9%, P<0.01) and ventricular arrhythmias (13% vs 48.6%, P=0.00001). There was also a numerical reduction in reinfarction (8.8% vs 12.7%, P value not significant).


“Subclinical magnesium deficiency is a common and under-recognised problem throughout the world. Importantly, subclinical magnesium deficiency does not manifest as clinically apparent symptoms and thus is not easily recognised by the clinician.

Despite this fact, subclinical magnesium deficiency likely leads to hypertension, arrhythmias, arterial calcifications, atherosclerosis, heart failure and an increased risk for thrombosis.

This suggests that subclinical magnesium deficiency is a principal, yet under-recognised, driver of cardiovascular disease.

A greater public health effort is needed to inform both the patient and clinician about the prevalence, harms and diagnosis of subclinical magnesium deficiency.”

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