In 2024, the New England Journal of Medicine published a review describing the role of magnesium in health maintenance, and as an adjunctive treatment for certain diseases.¹

The title of the review is “Magnesium Disorders.”

This might at first cause people to think it refers to toxicity.

Instead, it describes the delays by conventional medicine in recognizing magnesium’s multiple benefits.

It opens with revelations made around year 1980 in which magnesium was described as a “forgotten
electrolyte” and “nature’s…calcium blocker” in soft tissues.

Reasons given for the under-appreciation of magnesium’s clinical significance include the lack of information regarding the many biological processes that rely on magnesium.

This prestigious review focused on discoveries about how magnesium functions in the body, and on widespread magnesium deficits.

It noted that excess magnesium is rare and occurs primarily in patients with kidney disease receiving magnesium-retaining drugs.

On the next page I provide a summary of this medical publication.

Magnesium is present in all cells in all organisms from plants to higher mammals.

It is indispensable because it is an essential cofactor for cellular energy production.

Magnesium is also a cofactor for hundreds of enzymatic reactions in every cell type.

Magnesium has been shown to help regulate glucose, lipids and protein metabolism. It is involved in the control of neuromuscular function, regulation of cardiac rhythm, modulation of vascular tone, hormone secretion, bone density, and brain functions.

New England Journal of Medicine Review of Magnesium

The journal published an extensive review to educate practicing doctors about magnesium. The 16 bullet points below summarize important data and their clinical significance:

•  Impact on Vascular Health:
  • Magnesium influences vascular health by preventing vascular calcification, maintaining endothelial function, and modulating vascular tone.
•  Essential Cofactor for ATP:
  • Magnesium is crucial as a cofactor for ATP, the primary energy source in cells. Magnesium is involved in over 300 enzymatic reactions including DNA and RNA synthesis.
• Intracellular Regulation:
  • Magnesium regulates cellular processes, including neuromuscular function, cardiac rhythm, vascular tone, hormone secretion, and receptor modulation in the central nervous system.
• Magnesium and Cardiovascular Health:
  • Low magnesium levels are linked to increased cardiovascular risk, including hypertension, arrhythmias, and endothelial dysfunction.
• Associated Disorders:
  • Magnesium deficiency is associated with low potassium and calcium levels, whereas severe deficiency is associated with metabolic disorders, contributing to neuromuscular irritability and cardio-vascular abnormalities.
• Dietary Sources and Absorption:
  • Rich dietary sources include cereals, beans, nuts, and green vegetables, with 30%-40% of dietary magnesium absorbed in the intestine.
• Bone Storage:
  • Bones store 60% of the body’s magnesium, serving as a reservoir to maintain plasma concentration, and influence not only bone health and formation but metabolism, nervous system function, and more.
• Genetic Causes of Low Magnesium:
  • Genetic mutations affecting magnesium transporters can lead to magnesium deficit, which can sometimes be severe.
• Drug-Induced Magnesium Deficits:
  • Drugs like proton-pump inhibitors, immune-suppressing drugs used to manage autoimmune disorders, and certain chemotherapeutics cause low magnesium by inducing renal magnesium wasting.
• Therapeutic Use:
  • Magnesium sulfate is used therapeutically (in IV solutions) for conditions such as ventricular tachycardia, severe asthma exacerbations, and preeclampsia or eclampsia.
• Symptoms of Magnesium Deficiency:
  • Patients with hypomagnesemia often present with nonspecific symptoms, such as lethargy, muscle cramps, or muscle weakness, and thus the diagnosis of magnesium deficiency may be overlooked.
• Role in Bone Health:
  • High magnesium intake increases bone mineral content, reducing the risk of fractures and osteoporosis. It influences bone formation by activating osteoblasts and osteoclasts.
• Non-Drug Causes of Magnesium Loss:
  • Increased loss of magnesium can occur due to gastrointestinal conditions like chronic diarrhea, inflammatory bowel disease, alcohol abuse and chronic kidney diseases.
• Magnesium’s Role in Diabetes:
  • Hypomagnesemia is commonly observed in patients with type II diabetes, linked to insulin resistance and increased urinary excretion.

This 2024 published review concluded with the following:¹

• Hypomagnesemia is common in hospitalized patients and is a risk factor for a prolonged ICU stay.
• Hypomagnesemia should be corrected with magnesium replacement therapy.
• Although there is still much to be learned about magnesium, the field has advanced, and clinicians should be more attuned to the importance of magnesium in clinical medicine.

What the New England Journal of Medicine Did Not Discuss

This review educated physicians about magnesium’s multiple mechanisms, the diseases that it helps treat, and the disorders in which magnesium deficit is a
contributing factor.

Omitted was a strong recommendation for healthy people to ingest enough magnesium to avoid deficiencies.

A significant portion of adult Americans are magnesium deficient. Estimates suggest that around 60% consume less than the recommended amount, and about 45% may have a clinically relevant deficiency.²

Prevalence of magnesium deficits is higher in specific populations such as those with chronic illnesses or those hospitalized. Some data suggest >65% of ICU patients suffer from low magnesium (hypomagnesemia).¹

I wonder how many more people might survive an extended stay in the intensive care unit (ICU) if widespread magnesium optimization were utilized?

The review briefly mentions that “Mild hypo-magnesemia is managed with oral supplements.”

But the review highlights a common side effect, diarrhea, as a challenge that affects some people who consume too much magnesium on an empty stomach.

Instead of recommending most people slowly increase their supplemental magnesium intake, it described pharmaceutical interventions (including magnesium infusions and off-label drugs) to optimize magnesium levels in resistant cases.

We think this impressive NEJM-published review should have featured a public health alert for most people to consider taking a low-cost magnesium supplement. Perhaps the authors made this recommendation, but it was edited out of the final NEJM published copy?

What was Omitted from the NEJM Review?

As comprehensive as the NEJM review was, it omitted a few biological processes as follows:

Magnesium plays a role in the body’s response to stress, influencing adrenal hormone regulation and overall stress resilience.^3-5

Magnesium helps prevent age-related muscle loss. Magnesium deficiency can lead to muscle weakness.⁶

Adequate magnesium levels are essential for maintaining cognitive function and preventing neurodegenerative diseases.⁷

Improving magnesium status can help improve a wide range of persistent disorders.

Validating the Pioneers

In 1980, Dr. Mildred Seelig published extensive research on magnesium, highlighting its cardiovascular benefits and the potential risks associated with its deficiency. Her research and tireless advocacy brought attention to the need for adequate magnesium intake and supplementation.⁸

By the early 2000s, the National Institutes of Health (NIH) began including magnesium supplementation in their dietary guidelines and recommendations,⁹ especially for populations at higher risk of deficiency.

When writing this editorial, I initially overlooked that we wrote about Dr. Seelig’s pioneering work in the early 1980s. I highlight her name “Mildred Seelig” here because she is one of many medical pioneers forgotten with time.

Dr. Seelig’s early research was the genesis for many people supplementing with magnesium today…and more doctors are utilizing it in their medical practice.

I hope Life Extension® readers feel a sense of vindication as research continues to support the value of obtaining enough magnesium in one’s diet and/or supplements. 

For longer life,

William Faloon, Co-Founder
Life Extension

References

1. Touyz RM, de Baaij JHF, Hoenderop JGJ. Magnesium Disorders. N Engl J Med. 2024Jun 6;390(21):1998-2009.
2. Workinger JL, Doyle RP, Bortz J. Challenges in the Diagnosis of Magnesium Status. Nutrients. 2018 Sep 1;10(9).
3. Synapharm Internal Study. Efficiency of a magnesium salt (ATA MG® 770mg) on premenopausal syndrome: a clinical study report. Data on file. 2022.
4. Sartori SB, Whittle N, Hetzenauer A, et al. Magnesium deficiency induces anxiety and HPA axis dysregulation: modulation by therapeutic drug treatment. Neuropharmacology. 2012 Jan;62(1):304-12.
5. Uysal N, Kizildag S, Yuce Z, et al. Timeline (Bioavailability) of Magnesium Compounds in Hours: Which Magnesium Compound Works Best? Biol Trace Elem Res. 2019 Jan;187(1):128-36.
6. Souza ACR, Vasconcelos AR, Dias DD, et al. The Integral Role of Magnesium in Muscle Integrity and Aging: A Comprehensive Review. Nutrients. 2023 Dec 16;15(24).
7. Patel V, Akimbekov NS, Grant WB, et al. Neuroprotective effects of magnesium: implications for neuroinflammation and cognitive decline. Front Endocrinol (Lausanne). 2024;15:1406455.
8. Seelig MS. Magnesium deficiency in the pathogenesis of disease : early roots of cardiovascular, skeletal, and renal abnormalities. New York: Plenum Medical Book Co.; 1980.
9. Costello RB, Elin RJ, Rosanoff A, et al. Perspective: The Case for an Evidence-Based Reference Interval for Serum Magnesium: The Time Has Come. Adv Nutr. 2016 Nov;7(6):977-93.