Magnesium, Stress, Inflammation, and the Menstrual Cycle

Dr. Liz Bartman

Magnesium is arguably one of the most critical nutrients for cell function. It is used for over 600 enzymatic reactions in our bodies. Yet not even half (48%) of the US population consumes enough magnesium daily. As a mineral, it is used by our mitochondria to produce ATP (the body’s energy currency), by our muscles to regulate skeletal muscle contractions, by our brain to regulate neurotransmitter response and balance, by our bone matrix to support bone strength, by our cardiovascular system to regulate blood pressure, by our cells for protein synthesis and even insulin metabolism, as well as by our liver to aid in daily detox.

When it comes to hormone regulation, magnesium plays a very important role in the activity of COMT (catechol-o-methyltransferase), acting as a substrate for COMT activity. COMT donates methyl groups to the phase 1 catechol-estrogen intermediates (2-OH and 4-OH), helping to reduce excess active estrogen in our tissues. 

When magnesium levels are depleted, COMT can slow down, reducing how efficiently our body can eliminate estrogen. This can increase estrogen dominant symptoms, including heavier and more painful menstrual cycles, headaches, irritability, fibrocystic breast changes, weight changes, and even high blood pressure. In fact, low levels of magnesium are associated with an increased risk for preeclampsia, specifically associated with low 2-methoxy estradiol production (the product of catechol estrogen metabolism dependent on COMT).

 To add insult to injury, stress can significantly deplete our tissue magnesium levels- shifting intracellular magnesium out of our cells and into our bloodstream for rapid use by our nervous system to regulate muscle contractions and catecholamine response from neurotransmitters like Dopamine, Norepinephrine and Epinephrine. Remember, our 2-OH and 4-OH estrogens are catechol estrogens, also requiring COMT for metabolism. As an aside, keep in mind that 16-OH Estrone and Estriol (aka 16-OH Estradiol) are NOT catechol estrogens, and are subject to sulfation and glucuronidation primarily as their phase 2 routes for elimination. 

When our adrenaline is high (stress), we use magnesium to regulate numerous enzymes involved in our HPA stress axis, decreasing NMDA hyper-activity in the brain, regulating CRH and ACTH response, and improving clearance of stress hormones.This significantly limits the activity of COMT (not enough magnesium) and shifts priority of methyl donation to our stress catecholamines and away from estrogen. Now our cells are in a pickle – we have just dumped out all our magnesium in response to stress and are favoring COMT function for adrenaline clearance versus estrogen metabolism. 

Interestingly, 2-Methoxy Estradiol has an important role in VEGF expression and can help regulate blood pressure. When COMT is insufficient at clearing catechol estrogens into the methoxy forms, 2-methoxy Estradiol will decrease. This is the mechanism by which low magnesium is associated with preeclampsia, mentioned above. Poor COMT due to high stress and low magnesium may increase risk for hypertensive changes in non-pregnant women (and men) as well.  

Now we have this perfect storm of chronic stress depleting our magnesium, altering our COMT activity, increasing our blood pressure, and slowing down estrogen metabolism. 

Another depleting factor of magnesium is our degree of inflammation. There can be numerous reasons why a patient may be inflamed, but one important risk is obesity. Adipocytes increase IL-6 and TNF-a production, creating a low-grade, steady state of inflammation. This low-grade chronic inflammatory state significantly decreases magnesium and increases the demand for magnesium in our obese clientele. It is thought that even a mild to moderate depletion in magnesium may further exacerbate the risk for atherosclerosis, hypertension, osteoporosis, type 2 diabetes mellitus and even cancer in our obese patients.

This is why it is so important to factor in our patient’s stress and inflammatory burden when managing hormones. Regardless of gene status for COMT, if a woman is under chronic stress burden, is obese, or is otherwise inflamed, and is not getting enough magnesium to replete her cell activity, she can be at increased risk for poor estrogen detox, increasing risk for PMS symptoms and high blood pressure directly related to estrogen, as well as a host of metabolic diseases characterized by low magnesium.   

Medications can also deplete magnesium and may further compound an already depleted system. Medications include aminoglycosides, Amphotericin B, ACE inhibitors, antipsychotics (neuroleptics), H-2 agonists (Salbutamol, Rimiterol), antibiotics, diuretics, acid-reducing therapy (PPIs, antacids), estrogen (Premarin, Estrace, Prempro), Oral contraceptive pills, oral hypoglycemics (Metformin), diuretics, corticosteroids, opiates, antidepressants, central nervous system stimulants (Adderall, Vyvanse), Albuterol, Digoxin, medroxyprogesterone, SERMs (Raloxifene), and Theophylline. 

Lead can chelate with magnesium and deplete our cellular magnesium stores.

The general daily requirements for magnesium for a non-pregnant woman are around 320 mg per day, while pregnant women should aim for 400 mg daily. Men require 420 mg per day. When stressed or inflamed, research has found that doses up to 500 mg daily should be achieved to help balance our intracellular loss of magnesium. Approximately 30-40% of dietary magnesium is absorbed by the body. 

Foods rich in magnesium include: 

The type of magnesium can make a difference when trying to impact various cellular pathways. 

Our products focus on estrogen detox, adrenal health and energy response primarily, and thus our preferential forms of magnesium are in the glycine and malate forms.

Choosing the right magnesium supplement depends on individual needs and preferences. Magnesium glycinate or magnesium chloride may be suitable for those with digestive sensitivity, while magnesium l-threonate could be preferred for cognitive benefits and migraine support and magnesium taurate could support vascular health.