Everything You Ever Wanted to Know About Magnesium
From The Bible, Stars and Superconductors to Chlorophyll, Muscle Cramps and Catechol-O-Methyltransferase Expression
“The global magnesium supplements market is valued at approximately USD 12.83 billion in 2023 and is projected to reach USD 24.15 billion by 2032, growing at a compound annual growth rate (CAGR) of 8.23% between 2024 and 2032.”
– Vantage Market Research
Clearly, magnesium is a widely used, but seemingly misunderstood mineral. We often know we need it, but we don’t know why / how much / in what form and what to look for. Our deepest insight is, generally, that it can reduce muscular cramping – which it can – but not necessarily.
"A deficiency in magnesium can lead to more than just cramps; it can affect your mood, sleep, and overall health." – Dr. Michael Greger
Some Overview:
Intake is crucial for over 300 biochemical reactions in the body – including energy production, muscle and nerve function, and regulating blood pressure.
It’s been claimed that there would be no life on earth without magnesium – considering it is a vital portion of the chlorophyll molecule – which is responsible for photosynthesis.
In more simple terms: no magnesium = no chlorophyll = no photosynthesis = no plants = no life.
Often, the only time most people think of magnesium is when they’re lying on the ground holding their calf as it spasms and grips — and some helpful soul suggests more magnesium would be a good option. Or possibly the idea is offered up by a friend when we’re not sleeping so well.
So, we buy a bottle labelled something creative like, “Magnesium” or “mega- or ultimate-magnesium”, or similar, at the local supermarket – and give it a go.
Until a few days pass, and our sleep didn’t improve, and we’re not so concerned about cramping anymore – so, of course, it’s added to the pile of pill bottles at the back of the cupboard – one more to the breach.
Re-confirming the long-held, illogical, belief – that supplements just don’t work.
However, maybe we read somewhere that the form of magnesium matters –
So, you turn your Blackmore’s, or whatever, bottle over and find that it’s probably, “magnesium oxide” – which often acts as a laxative prior to replenishing the bodies magnesium stores.
So now what…
Consider the following list of different available forms, their chemical bonding, their relative bioavailability and specific benefits:
FORM BOND BIOAVAILABILITY SPECIFIC BENEFITS
Glycinate Glycine 80-90% Muscle relaxation; sleep quality
Chloride Chloride 50-60% Muscle relaxation and hydration
Threonate L-theanine 25-40% Support cognitive function and memory
Citrate Citric Acid 25-30% Relieves constipation and cramps
Malate Malic Acid 20-30% Energy production and muscle function
Lactate Lactic Acid 20-30% Energy production and muscle function
Taurate Taurine 20-25% Heart health, stress relief
Aspartate Aspartic Acid 20-25% Muscle function, exercise performance
Orotate Oratic Acid 20% Heart health and athletic performance
Sulfate Sulphur 4-20% (oral) Reduce muscle soreness
Oxide Oxygen 4% Relieve constipation and reflux
Hydroxide Oxygen and hydrogen <4% Relieve constipation and heartburn
If that all seems like a jumbled bunch of words, the main take away would be that –
About 90% of magnesium glycinate is absorbed by the body – whereas only about 4% of magnesium oxide is absorbed by the body.
That’s a huge difference.
Also, further to the form, the quality matters:
Understanding Mineral Supplements:
You’ve also probably noticed two numbers on the bottle: Total and Elemental Magnesium.
Total Magnesium
Refers to the total amount of magnesium contained in the supplement, including both the elemental magnesium and any other compounds or ligands – that may be present in the formulation. For example, if a magnesium supplement contains magnesium citrate, the total magnesium would include the weight of the entire magnesium citrate compound (including the citric acid component) — not just the magnesium portion.
Elemental Magnesium
Refers specifically to the actual amount of magnesium available for absorption and use by the body. Elemental magnesium is the pure magnesium content that contributes to the physiological effects and benefits of magnesium. For example, in magnesium citrate, the elemental magnesium is only a portion of the total weight of the compound. For instance, magnesium citrate might contain 16% elemental magnesium by weight (not including the citric acid component).
Importance of the Difference
Dosage and Efficacy: When choosing a magnesium supplement, it's crucial to look at the elemental magnesium content to determine how much magnesium that’s available. A supplement can have a high total magnesium content – but if the elemental magnesium is low, it may not provide the desired effects.
Comparing Supplements: Different forms of magnesium (e.g., magnesium oxide, magnesium citrate, magnesium glycinate) have different percentages of elemental magnesium. Knowing the elemental magnesium helps you compare the efficacy of different supplements.
Determining Quality Claims in Magnesium Glycinate Supplements:
“I know minerals are hard to understand. You’d think a 20% magnesium glycinate is better than a 10%, but it’s actually the reverse. Even though 20% material is higher potency, the absorption/activity is up to 1/3 less.” – Dan Richard, NOW Supplements
In 2022, NOW tested magnesium products from 16 different supplement companies at Eurofins state-of-the-art laboratory. Only one of the products met the label claim when looking at the chelated form of magnesium – suggesting that most brands use non-soluble form of magnesium in place of more expensive chelated form.
“Some brands appear to take advantage of that complexity to obfuscate what they are doing in their formulations so as to induce customers to pay for more than what they’re getting.”
– Dan Richard
Calculating Accurate Magnesium Glycinate Content of Product Claims:
Dividing the molar mass of magnesium by the molar mass of magnesium glycinate will determine the percentage of magnesium glycinate that is elemental magnesium portion.
This calculation should equal just under 14% -- depending on how it’s been weighed by the manufacturer – it can be below 14%, but not above.
So, any product that lists an elemental magnesium amount that exceeds 14% of the total magnesium glycinate amount must be inaccurate – it has been mislabeled, or a cheaper form of magnesium has been blended in without listing it.
‘Buffered’ magnesium glycinate is an example of combining magnesium glycinate with another form, such as magnesium oxide or citrate, however, most don’t list the quantities of each.
For example, if a product claims 100mg of magnesium per serving and 500mg of magnesium glycinate. Divide 100 by 500 and multiply by 100, equals the percentage. In this equation it equals 20% - which exceeds the 14% limit, meaning that the label is inaccurate, or it has other forms of magnesium added.
This example is the first one that came up on a google search –
Vitaceuticals MagZorb Magnesium Glycinate 500mg
"Magnesium is the silent hero of nutrition—essential for over 300 biochemical reactions in the body." – Dr. Mark Hyman
Some Milestones of Magnesium
Ancient Times – “And when they came to Marah, they could not drink of the waters of Marah, for they were bitter: therefore the name of it was called Marah. And the people murmured against Moses, saying, “What shall we drink?” And he cried unto the Lord; and the Lord shewed him a tree, which when he had cast into the waters, the waters were made sweet…” - Exodus 15:23-25 KJV
An explanation proposed was that the main components of wood – cellulose and lignin – reacted to sun exposure and developed “ion-exchange” properties – allowing the wood from the tree to absorb both the magnesium and the sulphate ions, removing the bitterness from the water.
In more “recent” years:
1618 - Magnesium’s earliest recorded use – when a farmer in the town of Epsom, England discovered that water from a local well had a bitter taste and a laxative effect. This water was found to contain magnesium sulfate, which became known as Epsom salt. It was used medicinally as a laxative and for soothing skin conditions. Which is still used today.
1755 – Scottish chemist Joeseph Black, who identified the compound “magnesia alba” (now known as magnesium carbonate) and noted it as differing from lime (calcium oxide).
1808 – British chemist, Humphrey Davy, is credited with isolating pure magnesium metal. Davy used electrolysis to extract it from a mixture of magnesium oxide and mercury oxide, naming it after the ancient Greek region of Magnesia – where large deposits of magnesium-rich minerals were found.
19th Century – Magnesium began to be recognised for its chemical properties, particularly its light weight and flammability. Leading it to be used in pyrotechnics and photography. Magnesium powder was used in flash photography in the mid-19th century to produce bright flashes.
As the industrial revolution developed, magnesium properties were explored for use in alloys, particularly for aviation and military applications due to its strength and lightweight.
During the 18th and 19th centuries, some physicians believed magnesium salts could “cure madness". While there was no scientific basis for the application at the time – modern science has shown that magnesium does play a role in mood regulation and cognitive function.
Early 20th Century – Magnesium became important in both medicine and industry.
Medicinal Uses: Magnesium sulfate (Epsom Salt) continued to be used as a laxative and a treatment for eclampsia in pregnancy. Compounds were also recognised for their role in the nervous system and in muscle function – leading to the development of supplements for deficiency.
Industrial Uses: Magnesium alloys gained widespread use during World War I and World War II within the aerospace industry due to high strength-to-weight ratio. Magnesium was also used in flares, incendiary bombs, and tracer bullets during the wars.
Late 20th Century – Scientists discovered magnesium's essential role in human health. Research into the dietary importance of magnesium grew, linking magnesium deficiency to various health issues such as hypertension, cardiovascular disease, and diabetes. This prompted the addition of magnesium to some fortified foods and increasing the production of dietary supplements.
Modern Day: Today, magnesium is widely used in various industries, from automotive and aerospace applications (in alloys) to electronics (due to its lightweight and conductive properties). In medicine, magnesium is used to treat arrhythmias, severe asthma, and preeclampsia, and is commonly included in supplements to promote muscle and nerve health.
"Magnesium is nature's tranquilizer—helping to ease anxiety and improve sleep quality."
– Dr. Rhonda Patrick
Some Magnesium Roles and Functions Within the Body (Beyond cramps and sleep)
1. Energy Production (ATP Synthesis):
It is essential for converting food into energy by activating adenosine triphosphate (ATP), the energy currency of the cell.
It is a cofactor for enzymes in the glycolysis pathway, Krebs cycle, and oxidative phosphorylation.
Activates hexokinase, an enzyme that catalyses the first step of glycolysis by converting glucose into glucose-6-phosphate.
2. Protein Synthesis:
Is necessary for the synthesis of proteins by stabilizing RNA and ribosomes, which are involved in translating genetic code into proteins.
Involved in the transcription and translation of DNA to RNA, as well as amino acid metabolism.
Facilitates the proper functioning of aminoacyl-tRNA synthetase, which attaches amino acids to their corresponding tRNA during protein translation.
3. Muscle Function:
Regulates muscle contractions by managing calcium uptake in muscle cells. It helps muscles relax after contraction, preventing cramps, spasms and tetany (involuntary muscle contractions).
It also contributes to the production of muscle proteins and the overall maintenance of muscle function.
4. Nerve Function:
Supports proper nerve signalling by regulating neurotransmitters and maintaining nerve cell function.
It plays a role in the release of neurotransmitters such as serotonin and dopamine, essential for mood and cognitive function.
It also helps modulate electrical impulses in neurons, which is crucial for healthy nervous system function.
Modulates the NMDA receptor, preventing excessive calcium influx into neurons, which can lead to excitotoxicity and neural damage.
5. DNA and RNA Synthesis and Repair:
Is involved in the synthesis of DNA and RNA, ensuring proper cell division and growth.
It also assists in the repair of damaged DNA, helping to protect against mutations and maintaining genetic stability.
Acts as a cofactor for DNA polymerase, enabling the addition of nucleotides to the growing DNA strand during replication.
6. Glucose Control and Insulin Sensitivity:
Helps regulate blood sugar levels by improving insulin sensitivity.
It is involved in the uptake and metabolism of glucose, which helps reduce the risk of type 2 diabetes.
Acts as a cofactor for tyrosine kinase, an enzyme critical for insulin receptor signalling and glucose uptake by cells.
7. Bone Health:
Plays a role in the formation of bone by influencing the activity of osteoblasts (bone-building cells) and osteoclasts (bone-resorbing cells).
It contributes to calcium homeostasis, which is essential for bone density and strength, and is a cofactor for enzymes that synthesise collagen.
Enhances the conversion of vitamin D to its active form, calcitriol, which promotes calcium absorption for bone mineralisation.
8. Cardiovascular Health:
Supports the sodium-potassium pump (Na⁺/K⁺-ATPase) in cardiac muscle cells, which maintains the electrical gradient necessary for a stable heartbeat.
Regulates heart rhythm by stabilizing the electrical activity of the heart muscle, reducing the risk of arrhythmias.
It also helps to relax blood vessels, which can lower blood pressure and reduce the risk of hypertension.
It supports lipid metabolism, helping to maintain healthy cholesterol levels.
9. Immune System Support:
Enhances T-cell proliferation by stabilizing ATPase activity in immune cells, ensuring a robust response to infections.
Helps regulate immune responses by influencing the activity of immune cells like macrophages and lymphocytes.
It also reduces inflammation by affecting the production of cytokines and other inflammatory molecules.
10. Electrolyte Balance:
Is critical for maintaining the balance of other electrolytes such as potassium and calcium.
It helps regulate cellular fluid balance, which is crucial for proper hydration and function of cells.
Balances calcium and potassium levels in kidney tubules to maintain proper electrolyte levels and prevent imbalances like hyperkalaemia.
11. Antioxidant Defense:
Is a cofactor for the enzyme superoxide dismutase (SOD), which is part of the body’s antioxidant defence system.
It helps protect cells from oxidative stress and free radical damage.
12. Mitochondrial Function:
Is necessary for maintaining mitochondrial health, the organelles responsible for producing energy in cells.
It supports the integrity of mitochondrial membranes and assists in the regulation of energy metabolism.
13. Hormonal Regulation:
Helps regulate the release and function of hormones such as insulin, thyroid hormones, and estrogen.
It also supports the adrenal glands, playing a role in managing the body’s response to stress.
Supports the production of thyroid hormone by enabling iodination of tyrosine residues in thyroglobulin within the thyroid gland.
14. Mental Health and Cognitive Function:
Helps regulate neurotransmitters like serotonin and GABA, which are involved in mood regulation and stress response.
It plays a role in memory formation, learning, and cognitive performance by supporting synaptic plasticity.
Supports the synthesis of serotonin by stabilizing the enzyme tryptophan hydroxylase, which converts tryptophan into serotonin precursors.
15. Detoxification:
Supports liver function and the detoxification processes by activating enzymes involved in the removal of toxins from the body.
Acts as a cofactor for glutathione S-transferase, an enzyme that conjugates toxins with glutathione for excretion.
16. Sleep Regulation:
Influences the production of melatonin, the hormone that regulates sleep-wake cycles.
It also promotes relaxation by regulating GABA, an inhibitory neurotransmitter involved in calming the nervous system.
17. Digestive Health:
Supports digestive enzyme production and helps maintain smooth muscle function in the gastrointestinal tract.
It acts as a natural laxative, drawing water into the intestines to promote regular bowel movements.
Activates cholecystokinin (CCK), a digestive hormone that stimulates the release of digestive enzymes and bile.
18. Blood Pressure Regulation:
Helps to relax the smooth muscle lining blood vessels, which contributes to vasodilation and can lower blood pressure.
It also interacts with calcium to control the contraction and relaxation of blood vessels.
19. pH Balance:
Is involved in maintaining the body’s acid-base balance, essential for normal cellular functions.
20. Cellular Division and Growth:
Is required for proper cell division and growth, ensuring the creation of new cells during tissue growth or repair.
Facilitates cyclic AMP (cAMP) formation by activating adenylate cyclase, which is critical for transmitting hormonal signals within cells.
21. Enzyme Activation:
Serves as a cofactor for over 300 enzymatic reactions, including those involved in metabolism, synthesis of nucleic acids, and regulation of hormones.
22. Stress Response:
Helps modulate the body's stress response by influencing the hypothalamic-pituitary-adrenal (HPA) axis, which regulates cortisol levels.
23. Skin Health:
Supports collagen synthesis and skin barrier function, contributing to overall skin health and wound healing.
Enhances collagen synthesis by activating prolyl hydroxylase, an enzyme essential for stabilising collagen molecules.
24. Pain Management:
Plays a role in reducing pain sensitivity by influencing NMDA receptors and may help in conditions like migraines and fibromyalgia.
25. Reproductive Health:
Is involved in hormone production that regulates the menstrual cycle, fertility, and pregnancy.
It also supports sperm motility and overall male reproductive health.
Note: The full extent of its biochemical roles spans a wide range of cellular processes essential for maintaining overall health and homeostasis.
"Optimizing your magnesium levels can improve your sleep, reduce stress, and enhance your overall well-being." – Chris Kresser
So, by now we all know we can supplement with magnesium, however utilising whole food / dietary sources of magnesium can be hugely beneficial.
Some Magnesium Whole Food Sources:
FOOD: MAGNESIUM CONTENT PER 100 GRAMS:
1. PUMPKIN SEEDS (PEPITAS) 553mg
2. CHIA SEEDS 392mg
3. SUNFLOWER SEEDS 325mg
4. ALMONDS 270mg
5. CASHEWS 260mg
6. DARK CHOCOLATE (75-80%) 228mg
7. BLACK BEANS (COOKED) 160mg
8. OATMEAL 90mg
9. SPINACH (COOKED) 87mg
10. QUINOA (COOKED) 64mg
11. MACKERAL 30-50mg
12. AVOCADO 29mg
13. BEEF 20-25mg
14. LIVER (BEEF OR CHICKEN) 18-20mg
15. YOGHURT 10-20mg
The current recommended daily intake (RDI) is:
For women – 4mg / kg of bodyweight
For men – 6mg / kg of bodyweight
For example, a 65kg women would, generally, require 260mg per day. So, calculating the quantity obtained from food, plus any supplements / multi-vitamins / electrolyte / mineral water will provide the total intake. Comparing it to the RDI should give you a basic guide of whether you’re consuming enough or not.
Or for a 80kg man = around 480mg per day.
An example of what that would look like in daily eating: Total Magnesium intake: 480 mg
Breakfast: (Subtotal: 112 mg)
Grilled steak (100 g cooked): 24 mg; Sliced banana (1 medium, 120 g): 32 mg; Handful of almonds (20 g, about 16 almonds): 56 mg
Lunch: Subtotal: 176 mg
Grilled salmon (120 g cooked): 35 mg; Steamed spinach (150 g cooked): 118 mg; Avocado (75 g, about 1/2 medium avocado): 23 mg
Snack: (Subtotal: 120 mg)
Pumpkin seeds (15g): 74 mg; Raspberries (100 g): 22 mg
Dinner: (Subtotal: 86 mg)
Grass-fed ground beef patty (120 g cooked): 20 mg; Roasted Brussels sprouts (150 g cooked): 35 mg; Sweet potato (150 g baked, with skin): 31 mg
However, this is the minimum — to avoid disease associated with deficiency – so if we’re stressed, exercising or relatively active, diabetic, have various single nucleotide polymorphisms, suffering GI disorders etc., consider the following:
For both men and women: 10mg / kg of bodyweight.
Some Possible Signs, Symptoms or Diagnosis’s relating to Magnesium Deficiency:
1. Fatigue
2. Weak Bones / Osteoporosis
3. Accelerated Aging
4. Type II Diabetes or Overweight
5. Hypertension & Cardiovascular Disease
6. Muscle Loss & Weakness
7. Stress Tolerance
8. Poor COMT Expression
9. Poor Sleep
10. Poor Digestion or Constipation
"Magnesium acts like a calming mineral, helping to regulate neurotransmitters and promoting a sense of well-being." – Dr. Andrew Weil
Magnesium as Electrolyte
Magnesium, as an ion, is positively charged. In biological systems, magnesium typically exists in its ionic form as (Mg2+), meaning it has lost two electrons and carries a double positive charge.
As magnesium is a metal and, in its elemental state, has two electrons in its outer shell.
To achieve stability, magnesium loses these two electrons, resulting in a positively charged ion (Mg2+).
Electrolyte Role
Its positive charge allows magnesium to interact with negatively charged molecules, such as phosphate groups in ATP or proteins, stabilizing their structures and functions.
Ion Balance
As a positively charged ion, magnesium works alongside other cations (e.g., potassium (K+) and calcium (Ca2+) to maintain the body's electrochemical gradients and cellular homeostasis.
Enzyme Activation
Magnesium's charge facilitates its role as a cofactor in enzymatic reactions, particularly those involving energy metabolism and nucleic acids.
Magnesium as Agonist (Enhancing Actions):
Vitamin D
Magnesium is crucial for the activation of vitamin D in its active form, calcitriol. Magnesium helps convert vitamin D into its active form, which in turn enhances the absorption of calcium. Without adequate magnesium, the body may be less efficient in utilizing vitamin D.
Calcium
Magnesium and calcium work in synergy to maintain muscle function and bone health. Magnesium helps regulate calcium levels by preventing calcium from becoming excessive within cells, especially in muscles and nerves, where it might otherwise cause overstimulation or spasms.
Potassium
Magnesium is required for the proper function of the sodium-potassium pump, which regulates potassium levels inside cells. Adequate magnesium levels help maintain proper potassium balance, supporting nerve function and muscle contraction.
Vitamin B6 (Pyridoxine)
Magnesium is essential for the activation of vitamin B6, and together they play a role in neurotransmitter function, mood regulation, and enzyme activation. Magnesium also helps alleviate symptoms of vitamin B6 deficiency, such as irritability and fatigue.
Vitamin C
Magnesium and vitamin C both support immune function, and adequate magnesium levels can help vitamin C perform its antioxidant and collagen-synthesis roles effectively.
Magnesium as an Antagonist (Inhibiting Actions):
Calcium
Magnesium can act as an antagonist to calcium in certain contexts. For example, magnesium helps regulate calcium flow into cells and prevent excessive calcium buildup, which can contribute to muscle cramps or calcification in tissues. Magnesium also counteracts calcium’s excitatory effects on nerve cells and muscle contraction, helping to prevent overstimulation.
Sodium
Magnesium can help reduce the effects of sodium, particularly in terms of blood pressure regulation. High sodium levels contribute to water retention and increased blood pressure, while magnesium helps relax blood vessels and supports healthy blood pressure.
Phosphorus
Magnesium competes with phosphorus for absorption in the intestines. A high intake of phosphorus (e.g., from processed foods or excess phosphoric acid in soda) can interfere with magnesium absorption, potentially leading to a magnesium deficiency. Conversely, magnesium helps balance the effects of high phosphorus levels in the blood, such as those seen in kidney dysfunction.
Iron
Magnesium can sometimes interfere with the absorption of iron in the intestines. High doses of magnesium supplements, particularly in the form of magnesium oxide, may inhibit iron absorption if taken together. However, this effect is usually more pronounced when magnesium and iron are taken in large quantities or at the same time.
Some Optimal Timings to Consider:
For optimal results, take magnesium supplements at the same time each day.
Some forms of magnesium (like magnesium oxide) can be taken with meals to minimise stomach upset, while others (like magnesium glycinate) can be taken on an empty stomach.
If higher doses are required, consider splitting the dose between morning and evening to improve absorption and minimize potential laxative effects.
Magnesium Glycinate: Evening and before bed
Magnesium glycinate is highly absorbable and well-tolerated, making it ideal for supporting relaxation and improving sleep quality. It also has a calming effect on the nervous system, helping with stress reduction and muscle relaxation before sleep.
2. Magnesium Malate: Morning and throughout the day
Magnesium malate is a combination of magnesium and malic acid, which supports energy production (ATP) within the body. It’s ideal for daytime use, especially for those who experience fatigue or muscle pain (such as in fibromyalgia), as it can help boost energy levels and reduce discomfort.
3. Magnesium Citrate: Morning or afternoon
Magnesium citrate is a more bioavailable form that has a mild laxative effect. It is best taken earlier in the day to avoid any potential disruption to sleep. It is effective for promoting regularity and supporting digestion.
4. Magnesium L-threonate: Evening
Magnesium threonate is known for its ability to cross the blood-brain barrier and support cognitive function and brain health. It is often taken in the evening to support relaxation and improve sleep quality, while also benefiting cognitive function and memory.
5. Magnesium Chloride: Anytime during the day
Magnesium chloride is highly absorbable and can be taken throughout the day. It is often used for muscle relaxation and to support general health. It’s versatile and can be found in topical forms (like oils or lotions) that can be applied directly to the skin as needed.
6. Magnesium Oxide: Morning or afternoon
Magnesium oxide has a lower bioavailability, but it’s commonly used for relieving constipation due to its strong laxative effect. It is best taken earlier in the day, so its effects don’t interfere with sleep.
7. Magnesium Taurate: Evening
Magnesium taurate is a combination of magnesium and taurine, an amino acid that supports cardiovascular health. It is beneficial for lowering blood pressure and supporting heart function, making it ideal for evening use when winding down.
8. Magnesium Aspartate: Morning or afternoon
Magnesium aspartate is a form of magnesium that’s easily absorbed and often used to support general energy levels and muscle function. It can be taken in the morning or afternoon to support daily physical and mental activities.
9. Magnesium Carbonate: Anytime during the day
Magnesium carbonate is less bioavailable but is still effective for supporting overall magnesium levels and digestion. It’s often used for general health and can be taken at any time but taking it after meals can help with digestive support.
Magnesium and Methylation:
Methylation is the addition of a methyl group (CH₃) to DNA, proteins, or other molecules, affecting gene expression and metabolism.
Methylation is involved in DNA repair, gene regulation, and the metabolism of neurotransmitters and hormones.
Magnesium acts as a cofactor for several enzymes involved in the methylation cycle, including methylenetetrahydrofolate reductase (MTHFR), which is crucial for converting homocysteine to methionine.
Magnesium is essential for the synthesis of S-adenosylmethionine (SAMe), the primary methyl donor in the body, facilitating numerous methylation reactions.
Adequate magnesium levels support the conversion of homocysteine to methionine, helping to maintain balanced homocysteine levels, which is important for cardiovascular health.
Methylation affects gene expression and, therefore, magnesium indirectly influences epigenetic mechanisms that can impact health and disease.
Low magnesium levels can impair methylation processes, potentially leading to increased risk of chronic diseases such as cardiovascular disease, certain cancers, and neurodegenerative disorders.
Since methylation is involved in neurotransmitter synthesis, magnesium deficiency may affect mood and cognitive function through disrupted methylation.
Magnesium is integral to the methylation cycle, influencing numerous biochemical pathways and overall health. Maintaining adequate magnesium levels is essential for optimal methylation and the prevention of related chronic diseases.
Magnesium and Catechol-O-Methyltransferase (COMT) Expression
Magnesium is an essential cofactor for many enzymes, including COMT. As a cofactor, magnesium aids in the methylation process, which is a key part of how COMT breaks down catecholamines. The methylation process involves transferring a methyl group (-CH3) to the neurotransmitter molecule, rendering it inactive and helping regulate its effects.
Specifically, magnesium is involved in activating S-adenosylmethionine (SAMe), a molecule that provides the methyl groups needed for this methylation reaction. Without sufficient magnesium, the efficiency of COMT can be reduced, potentially leading to imbalanced levels of neurotransmitters.
It has been shown to have a positive impact on mood regulation. By influencing COMT expression and function, magnesium helps maintain a proper balance of dopamine and other catecholamines, which is crucial for emotional stability. Low magnesium levels can contribute to mood swings, anxiety, and depression — all of which are influenced by neurotransmitter imbalances.
Proper regulation of dopamine and norepinephrine through COMT is essential for cognitive function, focus, and attention. Magnesium supports mental clarity by ensuring that neurotransmitters are properly broken down and balanced. It helps reduce overstimulation or deficiency of certain neurotransmitters that can impair cognitive performance.
Magnesium and the Stress Feedback Loop:
When faced with stress, the body activates the hypothalamic-pituitary-adrenal (HPA) axis, leading to the release of stress hormones and neurotransmitters, like cortisol, epinephrine and norepinephrine.
If this pathway is continually activated – chronic stress can disrupt various bodily systems, affecting mood, sleep, digestion, and overall health.
Magnesium helps regulate cortisol levels and the clearance of catecholamines through COMT.
Considering magnesium acts as buffer against the damaging effects of stress and considering stress depletes magnesium – we can be bound in a vicious feedback loop.
A deficiency in magnesium can increase the body’s sensitivity to stress, potentially triggering an exaggerated response to everyday stressors. Without sufficient magnesium, the HPA axis becomes dysregulated, leading to elevated cortisol levels and increased anxiety, which can further deplete magnesium.
High stress and low magnesium can cause high stress and low magnesium.
So on and so forth.
Some General Contraindications of Magnesium Supplementation:
Kidney Disease - People with severe kidney disease should avoid magnesium supplements.
The kidneys are responsible for excreting excess magnesium. In people with chronic kidney disease or renal impairment, magnesium may not be properly cleared from the body, leading to an increased risk of hypermagnesemia (high magnesium levels in the blood).
High levels of magnesium can lead to muscle weakness, low blood pressure, respiratory depression, heart arrhythmias, or even cardiac arrest.
Heart Block or Certain Cardiac Conditions - People with significant heart disease or conduction issues should consult with their healthcare provider before taking magnesium supplements.
Magnesium can affect heart rhythm by influencing the electrical conduction in the heart. In individuals with heart block or certain other cardiac arrhythmias, high magnesium levels may worsen the condition or interfere with the heart’s normal electrical activity.
Excess magnesium can lead to heart rhythm disturbances such as bradycardia (slow heart rate) or asystole (no heartbeat).
Use of Certain Medications - Some medications may interact with magnesium and either reduce its effectiveness or cause harmful side effects.
Antibiotics (e.g., tetracyclines, quinolones)
Magnesium can bind to these antibiotics in the digestive tract, reducing their absorption and effectiveness.
It’s best to take magnesium supplements several hours apart from antibiotics to avoid this interaction.
Diuretics (e.g., furosemide, thiazides)
Some diuretics can cause increased magnesium excretion in the urine, leading to a potential deficiency. Conversely, potassium-sparing diuretics (e.g., spironolactone) can increase magnesium levels in the blood.
Diuretics can affect magnesium balance, so it’s important to monitor levels when taking magnesium alongside these medications.
Bisphosphonates (e.g., alendronate)
Magnesium can interfere with the absorption of bisphosphonates, medications used to treat osteoporosis.
These medications should be taken at least 2 hours before magnesium supplements.
Proton Pump Inhibitors (PPIs) (e.g., omeprazole)
Long-term use of PPIs can reduce magnesium absorption from the gut, leading to a deficiency.
If on long-term PPI therapy, magnesium levels should be monitored regularly.
Muscle Relaxants and Sedatives (e.g., benzodiazepines)
Both magnesium and these medications can have a sedating effect, potentially leading to excessive drowsiness or respiratory depression when taken together.
Caution should be exercised when combining these substances.
Severe Dehydration - Rehydration should be prioritized before taking magnesium supplements if dehydration is present.
Magnesium supplementation, particularly in forms that have a mild laxative effect (e.g., magnesium citrate), can exacerbate fluid loss in cases of dehydration.
In individuals who are severely dehydrated, supplementation may worsen the condition or lead to an imbalance in electrolytes.
Intestinal Obstruction or Gastrointestinal Disorders - Individuals with significant gastrointestinal issues should avoid magnesium supplements or use them cautiously, under medical supervision.
In conditions like intestinal obstruction, ileus, or severe diarrhea, magnesium can worsen symptoms, especially in the case of supplements that have a laxative effect.
Excessive magnesium can increase the risk of diarrhea, dehydration, or worsening gastrointestinal motility issues.
Hypermagnesemia (High Magnesium Levels) - Regular monitoring of magnesium levels is important in people who are at risk of hypermagnesemia.
Individuals with already elevated magnesium levels (e.g., from kidney dysfunction, excessive supplementation, or other causes) should avoid magnesium supplementation.
Hypermagnesemia can lead to hypotension (low blood pressure), respiratory depression, muscle weakness, and cardiac arrhythmias.
Pregnancy and Breastfeeding (Specific Dosage Considerations) - It is important for pregnant or breastfeeding women to follow healthcare provider recommendations and not exceed the recommended daily dose of magnesium.
While magnesium is important during pregnancy and breastfeeding, excessive magnesium intake can lead to complications.
High doses of magnesium during pregnancy can result in toxicity, leading to low blood pressure, respiratory issues, or foetal harm.
Magnesium Deficiency Statistics
Dietary Surveys: According to the Australian Bureau of Statistics (ABS), data from the Australian Health Survey (AHS) 2011-2012 indicated that about 1 in 3 Australians (or around 33%) were not consuming adequate amounts of magnesium based on recommended dietary intake (RDI) levels. This deficiency was more common in certain age groups, such as adolescents and older adults.
Modern Diets: Diets that are low in magnesium-rich foods, such as whole grains, green leafy vegetables, nuts, and seeds, contribute to this deficiency. The increasing consumption of processed and refined foods, which tend to have lower magnesium content, is a major factor contributing to the deficiency in the population.
At-Risk Groups: Certain groups are more likely to be magnesium deficient in Australia, including:
A) Elderly: Due to decreased magnesium absorption and increased excretion.
B) People with certain health conditions: Those with gastrointestinal diseases, Type 2 diabetes, and those who consume alcohol excessively are at higher risk of magnesium deficiency.
C) Athletes: High levels of physical activity can increase magnesium loss through sweat, putting athletes at a greater risk.
Globally: Magnesium deficiency is not just an Australian issue, but a global one. Studies from other Western countries show that **10% to 30% of the population** may have suboptimal magnesium levels, which aligns with the Australian data.
"Low magnesium levels are linked to chronic diseases such as diabetes, heart disease, and osteoporosis." – Dr. Mark Hyman
Australian research links low magnesium levels to increased risk of chronic diseases:
A new Australian study (Varinderpal S. Dhillon et al., European Journal of Nutrition, Aug 14, 2024) from the University of South Australia, has determined a diet deficient in magnesium increases the risk of DNA damage and chronic degenerative disorders.
Scientists from the University of South Australia measured blood samples from 172 middle aged adults, finding a strong link between low magnesium levels and high amounts of a genotoxic amino acid called homocysteine.
Elevated homocysteine has been associated with damaging the body's genetic enzymatic expression, creating an increased susceptibility to Alzheimer's and Parkinson's disease, gastrointestinal diseases, a range of cancers, and diabetes.
“A low intake of magnesium (less than 300mg per day) can increase the risk of many diseases, but its role in preventing DNA damage has not been fully studied in humans until now.
Our study showed a direct correlation between low magnesium levels in blood (less than 18mg/L) and increased DNA damage, even after adjusting for gender and age.
Blood levels of magnesium, homocysteine (Hcy), folate and vitamin B12 were measured, showing an inverse correlation between magnesium and Hcy and a positive correlation between magnesium, folate and vitamin B12. This indicates that sufficiently high magnesium levels in the blood are essential to protect our genes from toxicity caused by homocysteine, which is increased when folate and vitamin B12 are deficient.”
– Dr. Permal Deo, UniSA molecular biologist
“Chronic magnesium deficiency is likely to disrupt the body's ability to produce energy and power cells, causing accelerated tissue ageing and making people more susceptible to early onset of many diseases.
Magnesium is the fourth most abundant mineral present in the human body. More than 600 enzymes require it as a co-factor and almost 200 require it to activate critical processes in the body.
"The next step is to determine the optimal dietary intake of magnesium, either through food or supplements and how this could impact the onset or progression of cancer and other chronic diseases.”
– Professor Michael Fenech
"Magnesium deficiency is associated with a higher risk of chronic diseases, including cardiovascular disease and metabolic syndrome." – Dr. Andrew Weil
Some Abstract Facts of Magnesium
Magnesium's Role in Earth's Magnetic Field:
Magnesium is a major component of the Earth's mantle, primarily in the form of magnesium silicate minerals. These minerals influence the Earth's magnetic field, as their movement in the molten outer core contributes to the planet's magnetism.
Magnesium Deficiency in Space Travel:
Astronauts are at risk for magnesium deficiency during space missions due to altered calcium and bone metabolism in microgravity, which can impact heart function, muscle coordination, and bone density. Magnesium supplements are crucial for their health during extended stays in space.
Magnesium Can Form a "Memory Alloy":
Magnesium alloys are used in "shape memory alloys" that can return to a pre-set shape when heated. These materials have applications in medical devices, such as stents and bone implants, because of their lightweight and biocompatibility.
"Magnesium Stars":
Some stars, known as magnesium-rich stars, have unusually high levels of magnesium in their atmospheres compared to other elements. These stars provide clues about stellar evolution and the nucleosynthesis of heavy elements in the universe.
Magnesium as a Hydrogen Storage Medium:
Magnesium can absorb large quantities of hydrogen, making it a potential material for hydrogen storage in fuel cells. Magnesium hydrides are being researched as a safer and more efficient way to store hydrogen for renewable energy technologies.
Magnesium Reacts with Carbon Dioxide:
Magnesium can burn in an atmosphere of carbon dioxide, a property that makes it an effective fire-starter even in environments where other materials might not ignite. This is why magnesium is used in emergency fire-starting kits for survival purposes.
It’s One of the Few Metals Found in Biological Systems:
Unlike most metals, which are toxic or inert in biological systems, magnesium is one of the few that plays a vital role in biochemistry.
Magnesium in "Superconductors":
Magnesium diboride (MgB₂) is a superconducting material, meaning it can conduct electricity with zero resistance at relatively high temperatures (for superconductors). This property gives magnesium potential in advanced technologies like magnetic levitation and superconducting power grids.
So now – if you made it this far – hopefully there’s some deeper understanding of a widely used – mostly misunderstood, vital mineral. The body needs it and it needs even more if there is stress, oxidative stress, excessive exercise, toxin exposure, illness, surgery, poor energy and high processed food intake.
The form matters, the quality of supplement matters, the quantity, the timing matters, the dietary intake matters.
All of which are fairly easy to address with the know-how.