Magnesium supplementation overcomes “all-cause mortality” resulting from low serum magnesium

Magnesium supplementation overcomes “all-cause mortality” resulting from low serum magnesium

Low serum magnesium is a predictor of “all-cause mortality” including cardiovascular diseases – heart failure, arrythmia, atherosclerosis, and stroke. Cardiovascular diseases are the number one cause of death in Western nations. Magnesium supplementation assists in the prevention of cardiovascular diseases. In a vast range of diseases, increased magnesium intake suppresses pathology associated with an inflammatory response.

Magnesium deficiency has been linked to inflammation and chronic inflammation for decades 1. In magnesium deficiency, the inflammation is sustained with an increase in all-cause mortality and higher cardiovascular mortality 2. In addition to all-cause mortality and cardiovascular mortality, low dietary magnesium increases the risk of mortality from cancer 3. Very low serum magnesium leads to an increase in mortality in most diseases studied 4.

In a vast range of diseases, increased magnesium intake suppresses pathology associated with an inflammatory response. It has been found that extra dietary magnesium of about 100 mg per day is associated with a five percent lower risk of cancer mortality 3. There is a significant inverse association between dietary magnesium intake and mortality from all causes and mortality from cancer.

Benefits of magnesium supplementation have been reported in multiple studies. In heart failure patients, there are improvements in arrythmias, diastolic and systolic function, inflammation, and myocardial infarction rate 1. In one study, magnesium treatment significantly decreased the hospital mortality rate from ischemic heart disease by 21 percent and all-cause mortality by 16 percent. Oral magnesium citrate appears to decrease heart rate variability in heart failure patients. Magnesium citrate appears to be especially advantageous as it contains both the magnesium ion and citrate entity (see note on magnesium citrate at the end of this article).

Magnesium regulation of insulin signalling links magnesium deficiency to metabolic diseases, diabetes and obesity. Magnesium deficiency is found in diabetes and obesity, both of which are high risk factors for cardiovascular diseases. Magnesium supplementation improves insulin resistance, reduces plasma glucose levels, increases high-density lipoprotein cholesterol levels and improves outcomes for hypertension and stroke 1.

Magnesium modulates calcium effects. Experiments demonstrate that intracellular magnesium is regulated, at least in part, by extracellular magnesium 7. This finding has health significance for controlling inflammation and disease because intracellular magnesium is considered to modulate pro-inflammatory pathways stimulated by calcium. Intracellular free calcium is a critical event in the commencement of inflammatory processes. Indeed, the concentration of calcium ions outside of body cells is 10,000 (ten thousand) times the concentration of calcium inside body cells. Intracellular magnesium appears to modulate the inflammatory pathways stimulated by calcium entering the cell.

Importantly, magnesium is considered to dampen inflammation and inflammatory responses by acting as an intracellular antagonist to calcium and modulating the opening of intracellular calcium channels involved with inflammation responses. Low magnesium levels are implicated in inflammation and endothelial disfunction resulting in cytokine exaggerated responses. Chronic inflammation is correlated so strongly to ageing that the term “inflammageing” has become synonymous with senescence.

As identified in multiple clinical trials, extensive medical literature confirms that magnesium acts as a “brake” on parathyroid hormone (PTH) release from the parathyroid glands. That is, magnesium is an agonist of calcium for calcium-sensing receptors of the parathyroid glands (in other words, a calcium antagonist).

The parathyroid glands produce parathyroid hormone (PTH). PTH regulates serum/plasma calcium concentration. The primary cellular signal that inhibits the secretion of PTH is an increase in serum calcium concentration. The parathyroid glands secrete PTH when the calcium level is low. It is considered that low levels of blood magnesium can also stimulate the secretion of PTH.

Diseases correlated with elevated levels of PTH are associated with increased incidence of cardiovascular diseases and mortality 5. Multiple lines of evidence from experimental and clinical studies suggest that PTH could be causally involved in pathological processes leading to cardiovascular diseases.

Plasma PTH is a strong risk marker for cardiovascular mortality independent of other clinical risk factors. Research has identified that PTH is involved in vascular calcification and is involved in cardiac calcification, cardiac fibrosis and ventricular hypertrophy. PTH is involved in raising classical inflammation markers.

Higher plasma PTH is associated with a higher risk for cardiovascular mortality even in individuals without signs of any disturbed mineral metabolism. In a TGA (Australia) registered clinical trial in relatively healthy women at a prestigious Australian medical teaching hospital, it was found that the consumption of soluble bioavailable magnesium significantly stabilised the serum concentration of PTH. See figure 3 in scientific article – How to achieve a long healthy lifespan.

That is, magnesium acts as a Brake on PTH release. Pathology from high PTH levels may be averted.

References:

1 Magnesium, Oxidative Stress, Inflammation, and Cardiovascular Disease: Antioxidants, October, 2020.

2 Low serum magnesium concentrations predict cardiovascular and all-cause mortality. Atherosclerosis, Nov 2011.

3 Total Dietary, and supplemental magnesium intakes and risk of all-cause, cardiovascular, and cancer mortality. A systematic review and dose-response meta-analysis of prospective cohort studies. Adv. Nutr, July 2021.

4 Serum magnesium concentrations and all-cause cardiovascular, and cancer mortality among US adults. Results from the NHANES 1 epidemiologic-follow up study. Cling. Nutr. Oct 2018.

5 Plasma parathyroid hormone and the risk of cardiovascular mortality in the community. Circulation. 2009.

7 Mg regulates cytotoxic functions of NK and CD8T cells in chronic EBV infection through NKG2D. Science. July 2013.

What are the best forms of magnesium to consume?

The best forms of magnesium to consume are those forms of magnesium that dissolve in water. The USA Department of Health (NIH) states that: “The best forms of magnesium to consume are those forms that are soluble (dissolves in water) and more completely absorbed from the intestines”.

Possibly, magnesium citrate dissolved in water is preferred because the citrate also has multiple benefits in addition to the magnesium. Citrate helps regulate metabolic flux in body cells and directs nutrients to the pentose phosphate pathway which helps to produce the body’s main antioxidant, glutathione, and is essential to produce all RNA and DNA. Citrate also is rapidly metabolised to alkaline bicarbonate in body cells which buffers body cells against excess acidity.

Any registered compounding pharmacist can prepare and dispense soluble magnesium citrate. In Australia, magnesium citrate is available as a cordial called Magna Aqua and can be purchased online.

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