Magnesium for menstrual pain and endometriosis: benefits and scientific evidence

A clear review of how magnesium intervenes in muscle contraction, pain signaling, and the functioning of the nervous system, and what current scientific evidence says about its role in dysmenorrhea and endometriosis.

1. Endometriosis: muscle contraction, nervous system, and pain amplification

If you live with endometriosis, adenomyosis, or very painful periods, you probably know that menstrual pain does not depend solely on inflammation. Uterine contractility, muscle tension, and nervous system sensitization can also contribute to the intensity and persistence of symptoms.

During menstruation, the endometrium releases prostaglandins, especially PGF2α and PGE2, which are involved in regulating uterine contractions. When their production is elevated, they can promote intense contractions, a temporary decrease in uterine blood flow, and pain.
In endometriosis, in addition, persistent inflammation and the activation of pain nerve pathways can contribute to the development of peripheral and central sensitization, making stimuli that would normally be mildly painful perceived with greater intensity.

This may be compounded by increased tension in the pelvic floor muscles, which in some women appears as a sustained response to pain.
These three dimensions—muscle contractility, pain transmission, and nervous system regulation— constitute relevant targets in the comprehensive management of menstrual and pelvic pain.

2. What is magnesium bisglycinate and why is it of interest in endometriosis

Magnesium is an essential mineral that participates in hundreds of enzymatic reactions related to energy metabolism, muscle function, and nerve transmission.

In EndoRestore™ we use magnesium bisglycinate, a chelated form in which magnesium is bound to glycine molecules, selected for its absorption profile and digestive tolerance.
Magnesium plays particularly interesting roles in the context of menstrual pain:

• It regulates muscle contraction and relaxation. Magnesium acts as a physiological antagonist to calcium, a mineral essential for muscle contraction. By intervening in the regulation of intracellular calcium, it contributes to the normal functioning of the muscles and to muscle relaxation mechanisms.

• It participates in the regulation of neuronal excitability. Magnesium is involved in pain sensitization processes. Adequate magnesium availability contributes to the balance of nerve signaling.

• It intervenes in energy metabolism. Magnesium is necessary for numerous ATP-dependent reactions, ATP being the main energy molecule in cells. Therefore, it is essential for the normal functioning of the muscles and the nervous system.

• It participates in the stress response. Magnesium is involved in neuroendocrine mechanisms related to the stress response and neuronal excitability, processes that can influence pain perception.
  
  

This set of functions makes magnesium a nutrient of interest in situations where menstrual pain, muscle tension, and neuromuscular regulation alterations coincide, although its physiological functions do not necessarily mean that supplementation improves these symptoms in all women.

3. Clinical evidence in menstrual pain

Research on magnesium in menstrual health has focused mainly on primary dysmenorrhea and premenstrual syndrome.

Primary dysmenorrhea

Some clinical trials have evaluated magnesium supplementation to reduce menstrual pain.
The results of certain studies suggest possible improvements in symptom intensity, although the available evidence has limitations related to sample size, the doses used, and the heterogeneity of the protocols.
Its possible usefulness has been related to the regulation of uterine contractility and magnesium's role in mechanisms linked to pain signaling and the modulation of neuromuscular excitability.

Premenstrual syndrome (PMS)

Magnesium has also been investigated for its possible influence on symptoms such as irritability, emotional tension, and certain premenstrual physical discomforts.
Some studies have observed improvements with its supplementation, especially when combined with vitamin B6.

Endometriosis and adenomyosis

In these conditions, the interest in magnesium is based mainly on its neuromuscular functions and pain sensitization mechanisms.
Therefore, its inclusion should be understood as a possible nutritional support, especially when there is insufficient magnesium intake, and not as a specific treatment for these diseases.

4. Experimental evidence: what mechanisms it modulates

Beyond clinical results, magnesium's physiological mechanisms help explain why this mineral is of interest in the context of menstrual pain.

Calcium regulation and muscle contractility

Calcium plays a central role in the contraction of smooth muscle cells, including those in the uterus. Magnesium participates in regulating the entry and intracellular availability of calcium, contributing to the balance between contraction and relaxation. This mechanism provides a physiological basis for investigating its possible role in situations of elevated uterine contractility.

NMDA receptors and pain sensitization

NMDA receptors participate in excitatory transmission in the nervous system and in central sensitization mechanisms. Magnesium exerts a voltage-dependent physiological block on these receptors, helping to regulate their activity. This function is particularly interesting in persistent pelvic pain, where nerve sensitization can amplify pain perception. However, the fact that magnesium intervenes in these mechanisms does not mean that its supplementation can reverse central sensitization.

Energy metabolism and neuromuscular function

Magnesium is necessary for the activity of numerous enzymes that use ATP.
Its role in energy metabolism helps maintain essential functions such as nerve impulse transmission, muscle functioning, and electrolyte balance. Together, these mechanisms position magnesium as a fundamental nutrient for neuromuscular regulation and nerve signaling, two relevant processes in the pathophysiology of menstrual pain.

5. Magnesium bisglycinate within an integrative approach

Not all forms of magnesium have the same solubility, absorption, and digestive tolerance characteristics. The magnesium bisglycinate is a chelated form that usually presents good gastrointestinal tolerance and constitutes an interesting alternative for supplementation. Its chemical structure allows it to provide magnesium bound to glycine.

In the management of endometriosis, magnesium can be part of an individualized nutritional strategy, along with a proper diet, adapted physical activity, pelvic floor physical therapy when indicated, and medical treatment. Its interest is especially relevant when diet does not allow meeting the requirements for this mineral or when there are circumstances that increase the risk of insufficient intake.

5. The synergies of EndoRestore

In EndoRestore™, magnesium bisglycinate is combined with B vitamins and other bioactive compounds, with the goal of bringing together nutrients that intervene in complementary physiological processes.

Vitamin B6 (P-5-P)

Vitamin B6, in its active form pyridoxal-5-phosphate (P-5-P), participates as a cofactor in numerous reactions in amino acid metabolism and neurotransmitter synthesis. Among them, GABA and serotonin stand out, involved in the regulation of neuronal excitability, mood, and various processes related to pain perception. For its part, magnesium participates in neuromuscular functioning and the regulation of excitatory receptor activity, such as NMDA. The combination of both nutrients allows action on two complementary physiological functions:

• Magnesium: regulation of neuronal excitability, muscle function, and energy metabolism.

• Vitamin B6: participation in neurotransmitter synthesis and regulation of hormonal activity.

Some clinical trials have investigated the combination of magnesium and vitamin B6 in women with premenstrual syndrome, with favorable preliminary results regarding certain emotional symptoms.

Vitamin B12 and folate (B9)

Vitamin B12 contributes to the normal functioning of the nervous system, while folate participates in normal psychological functions and homocysteine metabolism. In combination with magnesium and vitamin B6, these nutrients provide complementary nutritional support for cellular metabolism and neurological functions.

7. Conclusion

Magnesium is an essential mineral for the functioning of the muscles, nervous system, and energy metabolism. Its role in the regulation of intracellular calcium, neuronal excitability, and NMDA receptors provides a relevant physiological basis for investigating its role in menstrual and pelvic pain. Although some studies suggest possible benefits of magnesium supplementation in dysmenorrhea and premenstrual syndrome, clinical evidence remains limited, especially in women with endometriosis or adenomyosis.

In EndoRestore™, magnesium bisglycinate is integrated together with vitamin B6, vitamin B12, folate, and different bioactive compounds to provide a complementary nutritional support in processes related to neuromuscular functioning, cellular metabolism, and the response to oxidative stress. Its use should be part of an individualized approach and does not replace the medical treatments indicated for the control of pain or the disease.

8. Bibliographic references

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2. Seifert B, Wagler P, Dartsch S, Schmidt U, Nieder J. Magnesium—a new therapeutic alternative in primary dysmenorrhea. Zentralbl Gynakol. 1989;111(11):755–760.
3. De Souza MC, Walker AF, Robinson PA, Bolland K. A synergistic effect of a daily supplement for 1 month of 200 mg magnesium plus 50 mg vitamin B6 for the relief of anxiety-related premenstrual symptoms: a randomized, double-blind, crossover study. J Womens Health Gend Based Med. 2000;9(2):131–139. DOI: 10.1089/152460900318623.
4. Kirkland AE, Sarlo GL, Holton KF. The role of magnesium in neurological disorders. Nutrients. 2018;10(6):730. DOI: 10.3390/nu10060730.
5. Yalçın Bahat P, Ayhan I, Üreyen Özdemir E, İnceboz Ü, Oral E. Dietary supplements for treatment of endometriosis: a review. Acta Biomed. 2022;93(1):e2022159.