Magnesium, Methylation, and the MTHFR Gene

Magnesium is essential for the proper functioning of numerous processes within the body. As a cofactor for more than 300 enzymatic reactions, it is involved in muscle contraction, neuromuscular pathways, glucose maintenance, heart contraction, and blood pressure regulation.

Magnesium is also essential for energy production, nucleic acid synthesis, bone development, and the active transmembrane transport of other ions (i.e., the movement of molecules across cell membranes using ATP).

Above all, magnesium is a vital cofactor in the methylation cycle, and its deficiency may contribute to other MTHFR-related symptoms.

This article will discuss the body’s needs for magnesium and its role in methylation. We will explain how to identify and correct a magnesium deficiency and why this is so important for those with an MTHFR gene mutation.

Magnesium plays a pivotal role in synthesizing ATP (adenosine triphosphate). ATP is critical for numerous bodily processes, including healthy metabolism, muscle contraction and relaxation, glucose utilization, normal neurological function, and the release of neurotransmitters.

Magnesium’s many benefits include:

Methylation is an important biochemical process that “turns on” the biological switches that govern many bodily systems.

The methylation cycle requires one carbon atom and three hydrogen atoms (CH3) to be transferred from one component to another. CH3 is provided by SAMe (S-adenosylmethionine), the body’s primary methyl donor.

To produce SAMe, however, the body requires methylfolate. A mutation on the MTHFR gene impairs the body’s ability to create methylfolate, which then impairs the methylation process, causing numerous dysfunctions and subsequent health conditions.

Magnesium is a cofactor in methionine adenosyltransferase 1A (MAT1A), an enzyme that controls the production of SAMe.

Magnesium is also required for the proper function of catechol-O-methyltransferase (COMT), the enzyme responsible for metabolizing catecholamines (neurohormones released in response to stress). Impaired activity has been linked to cardiovascular diseases, particularly hypertension.

Another critical enzyme with a high magnesium requirement is glutamine synthetase, which drives glutathione synthesis.

Severe magnesium deficiency (hypomagnesemia) can result from chronic disease, excess alcohol intake, gastrointestinal disorders that affect uptake and absorption, and increased renal loss. Redistribution and intracellular shifts can occur in acute pancreatitis and pregnancy.

Other causes of low magnesium include low dietary intake (due to low magnesium content in food and high intake of refined/processed foods), chronic diarrhea, chronic stress, and medications such as antacids, proton pump inhibitors, diuretics, and some antibiotics.

Symptoms of a magnesium deficiency may include muscle weakness, muscle cramps, and nervous system excitability (causing tremors or muscle spasms).

Other symptoms may include:

Chronic magnesium deficiency can lead to numerous health conditions, including:

Researchers have stated that, along with increasing the risk of various diseases and costing incalculable amounts in healthcare and suffering, subclinical magnesium deficiency “should be considered a public health crisis.”

Around 10%–30% of a given population has a subclinical magnesium deficiency. Approximately 50% of Americans consume less than their required daily intake of magnesium, with some age groups consuming substantially less. This is primarily due to food processing decreases in food crop magnesium content.

Some researchers have argued that a typical Western diet cannot maintain sufficient magnesium levels nor reduce the risk of coronary artery disease and osteoporosis. It has also been suggested that the “normal range” of serum magnesium is inaccurate and that serum magnesium levels at the lower end of normal are closer to marginal magnesium deficiency.

Supplementation may be a much more effective and convenient way to restore and support magnesium levels.

Supplementation may help prevent and treat many common health conditions, including metabolic syndrome, migraines, diabetes, preeclampsia, premenstrual syndrome, hyperlipidemia, and some cardiac arrhythmias.

It may also be used as an adjunct or treatment for depression and as a therapeutic intervention for many other health conditions. Clinicians recommend optimizing magnesium status through supplementation as safe, useful, and well-documented.

Magnesium supplementation for depression is shown to be as effective as imipramine. Supplementation has also shown significant therapeutic effects in heart failure and cardiovascular disease.

The Recommended Dietary Allowance (RDA) of magnesium for adults is 400-420 mg daily for men and 310-320 mg for women, while the tolerable upper-level intake from supplements is 350 mg.

As most people are already subclinically deficient, they would need at least 300 mg of magnesium/day to maintain magnesium levels, lower their risk of chronic diseases, and support optimal health.

Supplementation of 500 mg of Mg has been associated with significant improvement in the insomnia severity index, sleep time, sleep efficiency, sleep onset latency, serum cortisol concentration, serum renin, and melatonin.

Diabetic patients treated with 600mg magnesium for 12 weeks showed a significant reduction in total cholesterol and LDL with an increase in HDL.

Supplementation should be increased slowly, as taking large amounts at once can cause gastrointestinal issues. We recommend consulting a health practitioner before starting a supplement regime.

The best forms of magnesium are those with some form of delivery mechanism. Studies have shown magnesium is more bioavailable when bound to other compounds (chelated).

Some studies have suggested that organic magnesium compounds are more bioavailable than inorganic magnesium oxide. Other research has noted systemic differences in the studies, meaning this is not a reliable conclusion.

Many different forms of magnesium supplements are available, including:

For those with MTHFR gene mutations, magnesium supplementation is especially important.

Magnesium supplementation may help reduce the risk of stroke and heart failure, both of which may be higher in those with MTHFR due to low folate status and increased levels of homocysteine.

Magnesium is also shown to prevent and treat migraines and headaches, another common symptom of MTHFR.

MTHFR C677T is also linked to an increased risk of developing type 2 diabetes. Magnesium supplementation has improved glucose levels and insulin sensitivity in those with diabetes.

Depression is also a common feature of MTHFR. However, supplementation with magnesium may be beneficial in treating depression.

There is no specific evidence regarding which form of magnesium is “best” for treating MTHFR-related symptoms. However, benefits are more likely to be obtained from a highly bioavailable form that is easily absorbed and utilized in the body.

Those with MTHFR are advised to supplement with folate and vitamin B12 to assist with methylation. However, a magnesium supplement may help relieve other MTHFR-related symptoms such as muscle cramps, headaches, and depression.

Magnesium’s many roles in the body make it one of our most critical nutrients. Deficient levels are both pervasive and problematic, suggesting that supplementation is necessary for most of the adult population.

Those with MTHFR are especially likely to benefit from magnesium supplementation to support cardiovascular and neurological health.

Although a wide range of magnesium supplements are available online and in stores, it is advisable to choose a product with clinically proven high bioavailability—such as that from Methyl-Life’s® magnesium product range.

Designed specifically for those with MTHFR gene mutations, the Methyl-Life® range includes two highly-rated magnesium products: Sucrosomial Magnesium and Magtein L-Threonate. Each form is backed by scientific research for its excellent bioavailability and efficacy. They can be taken alongside other MTHFR supplements to optimize health and wellbeing.