Effects of Magnesium on Chronic Fatigue Syndrome (CFS) and Fatigue

March 17, 2025

Nutrition

Magnesium’s Role in Energy and Muscle Function

Magnesium is essential for energy production and muscle function. It is a cofactor in over 300 enzymatic reactions, including the creation of ATP (energy) and proper muscle contraction/relaxation. Every ATP molecule must bind magnesium (as Mg-ATP) to be biologically active. Given this role, it’s not surprising that magnesium deficiency can cause fatigue, weakness, and muscle cramps. Early signs of low magnesium include loss of appetite, fatigue, and weakness, progressing to muscle cramps or abnormalities if not corrected. Conversely, adequate magnesium supports normal energy levels, nerve function, and muscle performance.

For general fatigue or exercise-related fatigue, magnesium may improve outcomes especially if a person is deficient. Studies indicate magnesium supplementation can improve exercise tolerance and delay muscle fatigue by reducing lactate buildup. Athletes with marginal magnesium intake have shown decreased endurance and higher oxygen needs, suggesting optimal magnesium status is important for combating fatigue during physical activity. In some trials, magnesium supplementation has reduced perceived fatigue – for example, a study of women with fatigue showed that 4 weeks of magnesium (400–800 mg/day) significantly reduced fatigue levels. Experts often recommend magnesium for individuals under high stress or athletic training, as stress and heavy exercise can deplete magnesium, potentially creating a vicious cycle of low magnesium and fatigue. Ensuring sufficient magnesium (through diet or supplements) is thus a common expert recommendation to help with low energy and muscle fatigue.

Magnesium and Chronic Fatigue Syndrome (CFS)

People with CFS have been investigated for magnesium deficiencies since magnesium is crucial for mitochondrial energy production. Research findings have been mixed: A notable 1991 study in The Lancet found that CFS patients had significantly lower red blood cell magnesium levels than healthy controls and that intramuscular magnesium injections improved CFS symptoms. In that double-blind trial, six weekly magnesium sulfate injections led to better energy levels, improved emotional state, and reduced pain in 12 of 15 CFS patients, while only 3 of 17 patients on placebo reported improvement. This suggests magnesium played a role in alleviating symptoms for some CFS patients, possibly by correcting an intracellular magnesium deficit. CFS specialists like Dr. Sarah Myhill note that many CFS patients benefit from magnesium (often given by injection) and that low intracellular magnesium could be both a consequence and contributor to the mitochondrial dysfunction seen in CFS. Myhill explains that mitochondria need magnesium to produce ATP, and without enough magnesium, a “vicious cycle” of low energy and poor ion transport may occur in CFS.

However, not all studies have found magnesium deficiencies in CFS. Subsequent research in the 1990s (e.g. Clague 1992; Hinds 1994) did not consistently observe low magnesium levels in CFS patients. These later studies failed to replicate the magnesium deficiency finding, suggesting that not every CFS patient is magnesium-deficient. Despite the inconsistent lab findings, magnesium supplementation is still considered helpful by some experts for a subset of CFS patients, especially given magnesium’s low risk profile. Clinical recommendations often advise ensuring adequate magnesium intake (through diet or supplements) as part of a supportive approach for CFS. The general reasoning is that correcting any possible magnesium insufficiency may improve energy production and muscle function, which could ease fatigue. In practice, magnesium is frequently recommended for CFS patients who show signs of deficiency or have muscle pain and spasms, and some find it improves their sense of well-being. It’s important to note that magnesium alone is not a cure for CFS, but it can be one piece of a comprehensive management strategy, alongside other treatments and lifestyle adjustments.

Different Forms of Magnesium and Their Impact on Fatigue

Magnesium supplements come in various forms, and the form can influence absorption, tolerability, and specific benefits. In general, chelated forms of magnesium (where magnesium is bound to an organic molecule like an amino acid or acid) tend to be better absorbed and gentler on the digestive tract than inorganic salts like magnesium oxide. They can also have added benefits from the ligand they are bound to. Below we explore three forms – Magnesium Chelate, Magnesium Malate, and Magnesium Bisglycinate – and how each may impact energy, muscles, and overall well-being:

Magnesium Chelate: “Chelated magnesium” is a broad term indicating magnesium is bound to one or more amino acids. A common example is magnesium glycinate (magnesium bound to glycine), sometimes simply labeled magnesium chelate. Chelation enhances magnesium’s stability and absorption. Magnesium chelates in general are highly absorbable and are the forms naturally found in foods. By improving magnesium uptake, they ensure more magnesium is bioavailable for cellular processes like ATP production. The glycine component in magnesium glycinate (a type of chelate) has a calming effect on the nervous system, which can promote relaxation and better sleep. Overall, magnesium chelates support energy levels by correcting magnesium deficits without the laxative side effects of some other forms. They also support normal muscle and nerve function broadly.
Magnesium Malate: This is magnesium bound to malic acid, a compound involved in the Krebs cycle (energy generation cycle). Magnesium malate is known as an “energizing” magnesium. Malic acid can help produce ATP, so in theory magnesium malate doubly supports energy metabolism. It has been used in studies on fibromyalgia, a condition with overlapping fatigue and muscle pain, with some evidence that it reduces muscle pain and tenderness (though evidence is mixed and more research is needed). People with fibromyalgia or CFS sometimes report improvements with magnesium malate, potentially due to enhanced muscle energy production. This form is also noted to be gentle on digestion, with less of a laxative effect than forms like citrate. By improving muscle ATP production and reducing muscle fatigue, magnesium malate may improve overall energy and reduce feelings of tiredness, especially in individuals suffering from energy depletion and muscle soreness.
Magnesium Bisglycinate: Also known as magnesium glycinate (the terms are often used interchangeably), this is magnesium chelated to two glycine molecules. It is regarded as one of the most bioavailable and well-tolerated forms of magnesium. Magnesium bisglycinate’s standout feature is that it’s gentle on the digestive system – it typically causes minimal gastrointestinal upset or laxative effect. This makes it ideal for those who get diarrhea with other forms. The glycine component is an amino acid that has calming, inhibitory neurotransmitter properties, so magnesium bisglycinate is often used to promote relaxation, improve sleep quality, and reduce anxiety**. Despite this calming effect, it still effectively raises magnesium levels to support metabolic energy. Users often take bisglycinate in the evening to help with restful sleep and overnight muscle recovery, while still reaping the benefits of magnesium for muscle function (preventing cramps, aiding recovery). This form is well-suited for individuals with high stress or trouble sleeping, as well as those with sensitive stomachs.

Below is a comparison table of Magnesium Chelate vs. Magnesium Malate vs. Magnesium Bisglycinate, highlighting their absorption, typical dosage, benefits, side effects, suited uses, and price/examples:

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Feature	Magnesium Chelate (e.g. glycinate/lysinate chelate)	Magnesium Malate	Magnesium Bisglycinate (magnesium glycinate)
Absorption & Bioavailability	Highly absorbable form. Magnesium bound to amino acids is well-utilized by the body. Note: One study found magnesium chelate had similar absorption to magnesium citrate and better than oxide. Chelates dissolve easily and are designed for high bioavailability.	Very high absorption. Magnesium malate is easily absorbed in the gut, and an animal study found it was absorbed fastest among several forms. Well-tolerated with less laxative effect than some forms.	Excellent bioavailability. Magnesium bisglycinate (two glycine chelate) is one of the most bioavailable forms. It’s absorbed via amino acid pathways, bypassing many of the issues of less soluble salts. Gentle on digestion, so the body can absorb more without diarrhea.
Typical Dosage (Elemental Mg)	Often ~100–200 mg elemental Mg per dose. Many chelate supplements provide 100 mg elemental Mg per tablet (because the rest is the amino acid). A common regimen is 2 tablets (~200 mg) daily, though up to 400 mg/day may be used for deficiency. Always check label for elemental Mg.	Often comes as “di-magnesium malate.” A typical capsule may contain ~140 mg elemental Mg (with the rest being malic acid). For example, 3 capsules = 425 mg elemental Mg in one product. Dosages of 300–500 mg/day elemental Mg (split into 2–3 doses) are common for energy support.	Typically ~100 mg elemental Mg per capsule, since bisglycinate is about 14–15% magnesium by weight. Many products give 200 mg elemental Mg per serving (e.g. 2 capsules of 100 mg each). Because it’s well-tolerated, higher daily doses (300–400+ mg) can be taken if needed, split throughout the day.
Key Benefits	Broad benefits: Replenishes magnesium effectively for overall health – supporting energy production, nerve function, and muscle relaxation. Chelated forms (like glycinate) are less likely to cause diarrhea than Mg oxide. The glycine in many chelates provides a calming effect, aiding sleep and stress reduction. Great for general magnesium supplementation to combat deficiency symptoms (fatigue, muscle twitches, etc.).	Muscle & energy support: Malate may boost physical energy by aiding ATP production (malic acid is a Krebs cycle intermediate). Often reported to reduce muscle pain and tenderness in fibromyalgia. Helps combat exercise-induced fatigue and muscle soreness – some use it to improve stamina and post-workout recovery. Also supports healthy metabolism and may improve mental clarity by reducing fatigue.	Relaxation & recovery: Bisglycinate’s top benefit is promoting relaxation and restful sleep. It can ease anxiety and stress (calming glycine effect). Great for preventing nighttime muscle cramps or twitches. Despite calming properties, it still aids energy indirectly by improving sleep quality and ensuring optimal magnesium for enzymes. Ideal for those who want magnesium’s benefits (preventing fatigue, muscle support) plus a gentle calming supplement.
Potential Side Effects	Very well tolerated. Because it’s highly absorbed, less unabsorbed magnesium stays in the intestines to cause loose stools. High doses may still cause diarrhea – one should increase dose to bowel tolerance. Mild gastrointestinal upset can occur in very sensitive people or if taking on an empty stomach. Overall, minimal side effects; safe for long-term use at recommended doses.	Also well tolerated. Malate typically causes little to no laxative effect at moderate doses. Malic acid is gentle, though a minority of people report slight stomach upset. Taking it with food can help. Because malate delivers a larger Mg dose per pill, taking too many at once could loosen stools – it’s best to spread out doses. No known specific side effects beyond typical magnesium excess (diarrhea).	Extremely well tolerated – designed for sensitive individuals. Does not typically cause diarrhea even at relatively high doses. The most common “side effect” is calmness or drowsiness, which isn’t bad if taken at night (but might relax you if taken in the morning). In rare cases or very high doses, slight softening of stool or stomach upset might occur, but far less often than with other forms.
Best Suited For	CFS patients & general use: Chelated magnesium (especially glycinate) is a good all-around option for anyone with chronic fatigue or magnesium deficiency. Doctors often recommend magnesium glycinate for those who need high doses without GI issues. Also great for athletes or busy individuals to maintain energy and muscle function, and for people who find oxide or citrate upset their stomach. In short, suited to those who want a reliable, well-absorbed magnesium to support overall fatigue reduction, recovery, and health maintenance.	Those with fatigue and muscle pain: Magnesium malate is often favored by individuals with CFS or fibromyalgia due to its potential energy and muscle benefits. It’s also a good choice for athletes or physically active people who want to improve endurance and reduce post-exertion soreness – malate may help muscle cells produce more energy and clear lactate. If you have daytime fatigue or muscle stiffness, malate in the morning might be beneficial (some avoid it late at night due to its energizing nature). Overall, ideal for people looking to boost physical energy and muscle performance while avoiding stomach upset.	Those with stress, sleep issues, or sensitivities: Magnesium bisglycinate is best for people who want magnesium’s benefits without any digestive side effects – for instance, individuals with IBS or sensitive stomach. It’s an excellent option if stress or poor sleep contribute to fatigue, as it has a relaxing effect to improve sleep quality. Also great for athletes for recovery (take at night to relax muscles) and for older adults who may need gentle magnesium for cramps. If you’re magnesium-deficient but can’t tolerate other forms, bisglycinate is often the top recommendation.

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Note: Prices are approximate and can vary by brand and retailer. It’s important to read labels for the elemental magnesium content, since each compound contains different percentages of actual magnesium. Start with the recommended dose on the product, and increase gradually if needed to avoid any laxative effect. Always consult a healthcare provider if you have underlying health conditions or take medications, to ensure magnesium supplements are appropriate for you.

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Authoritative Articles and Sources

For further reading and evidence on magnesium’s effects on fatigue and CFS, see these authoritative sources:

Cox IM, Campbell MJ, Dowson D. (1991). Red blood cell magnesium and chronic fatigue syndrome. Lancet, 337(8744):757-760. – This is the landmark study showing low RBC magnesium in CFS and symptom improvement with magnesium injections.
NIH Office of Dietary Supplements – Magnesium Fact Sheet (Health Professionals). – Comprehensive overview of magnesium, including its role in the body, deficiency symptoms (e.g. fatigue, weakness), and supplement forms.
Mazur A. et al. (2021). “Magnesium Status and Stress: The Vicious Circle Concept Revisited.” Nutrients, 13(1): stress and magnesium review. – A detailed review highlighting how magnesium deficiency and stress (with symptoms like fatigue and irritability) can reinforce each other, and the importance of magnesium in chronic stress and fatigue conditions.
Chen F. et al. (2018). “Can Magnesium Enhance Exercise Performance?” Nutrients, 10(7): 842. – A scientific review discussing magnesium’s impact on exercise, muscle metabolism, and fatigue. Summarizes studies where magnesium supplementation improved muscle performance and delayed fatigue (e.g. by reducing lactate accumulation).
Tardy A-L. et al. (2020). “Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review.” Clinical Nutrition, 39(11): 3062-3078. – An extensive review of micronutrients in energy production. It explains magnesium’s central role in ATP generation and highlights clinical evidence linking magnesium supplementation to reduced fatigue in certain populations.

Each of these sources provides deeper insight into how magnesium affects energy levels, fatigue, and muscle function, as well as evidence from clinical research. They support the conclusion that maintaining adequate magnesium is important for anyone dealing with chronic fatigue or low energy, and they detail the benefits of various magnesium forms in scientific terms. Always refer to such trusted sources or medical professionals when considering supplement strategies for chronic fatigue or any health condition.

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