Why loose ions cause big problems in EDS – especially for the kidneys

If you have Ehlers-Danlos Syndrome (EDS), you’ve probably noticed that your body reacts strongly to things that don’t bother other people: a new food, a change in weather, stress, or even just standing up too long. Very often, two hidden problems are teaming up behind the scenes – mast cell activation syndrome (MCAS) and electrolyte (ion) imbalances, especially involving the kidneys.

What Is Mast Cell Activation Syndrome (MCAS) and Why Is It So Common in EDS?

Mast cells are tiny immune cells that act like armed guards throughout your body (skin, gut, blood vessels, nerves). When they sense a threat, they release histamine, prostaglandins, tryptase, and dozens of other chemicals.

In most people, mast cells only fire during real emergencies (bee sting, infection, etc.).

In many people with EDS – estimates range from 50–90% – mast cells are chronically over-reactive.

Why does this happen in EDS?

1. Fragile, stretchy connective tissue constantly irritates mast cells
   Your joints, skin, blood vessels, and gut walls are moving and micro-stretching all day. Mast cells interpret this mechanical stress as “injury” and release chemicals → flushing, hives, swelling, itching.

2. Leaky blood vessels and irritated nerves keep sending “danger” signals.

3. Genetic overlap – some of the same pathways that affect collagen also affect mast-cell stability (TNF-alpha, TGF-beta, KIT receptor, etc.).

The result? A condition now called Mast Cell Activation Syndrome (MCAS) that often travels with hypermobile EDS (hEDS) and sometimes classical or vascular types too.

Common MCAS symptoms in EDS patients:

• Random hives, flushing, or itching

• Sudden food or fragrance sensitivities

• Swelling of face, hands, or ankles

• IBS-like gut issues, reflux, nausea

• Brain fog, anxiety, or feeling “revved up but exhausted”

• Worsening POTS or dizziness spells

How MCAS Causes Electrolyte Problems and Kidney Stress in EDS

When mast cells dump histamine and other mediators, one of the side effects is that your kidneys start wasting magnesium and potassium.

At the same time, EDS itself makes the kidney’s filtering units (glomeruli) more fragile because their basement membrane is built with defective type IV collagen. Stretchier renal blood vessels also cause bigger blood-pressure swings, which further stresses the kidneys.The double hit looks like this:

• Mast cells → histamine surge → kidneys excrete magnesium & potassium → low blood levels

• Weak collagen in kidneys → “sloppy” ion handling and occasional protein leakage

• Result → muscle cramps, heart palpitations, fatigue, constipation, kidney stones, or even long-term kidney injury
  
  

Common electrolyte patterns seen in EDS + MCAS:

• Low magnesium (hypomagnesemia)

• Low potassium (hypokalemia)

• Calcium swings (sometimes kidney stones, sometimes bone pain)

• Sodium dysregulation (worsening POTS symptoms)

Many patients notice dramatic improvement in pain, energy, and stability once magnesium, potassium, salt, and fluids are carefully replaced (always under medical guidance).

The Ratios EDS Patients Need to Watch

Doctors who treat a lot of EDS/MCAS patients focus on these ratios (ask for these labs!):

1. Serum Magnesium is often falsely normal
   → Always request Red Blood Cell (RBC) Magnesium – it’s the real picture.
   Goal: > 5.8 mg/dL (most symptomatic EDS patients sit at 4.2–5.2).

2. Calcium : Magnesium ratio
   Ideal ≈ 2:1 (e.g., Ca 9.5 mg/dL to Mg 4.8–5.2 mg/dL inside cells).
   When magnesium drops, calcium floods into cells → muscle spasms, anxiety, palpitations.

3. Sodium : Potassium ratio
   Goal ≈ 30–35 : 1 (e.g., Na 140 / K 4.2).
   MCAS flares often push potassium down → ratio can hit 40–50:1 → cramps, arrhythmias, constipation.

4. Urinary Magnesium & Potassium wasting check
   After a histamine flare, a 24-hour urine often shows huge magnesium loss (>150 mg/day even when blood levels are low) — proof the kidneys are dumping it.

Low magnesium is the #1 correctable driver of pain, cramps, POTS, and fatigue in EDS.

• Supplement forms that work best: magnesium glycinate, magnesium malate, or slow-release magnesium lactate (400–800 mg elemental spread across the day).

• Pair magnesium repletion with potassium-rich foods or supplements (aim 4,000–4,700 mg potassium daily) and adequate salt (many need 5–10 g sodium/day for POTS).

• Re-check RBC magnesium + serum potassium every 3–6 months once stable.

When the fragile kidneys stop wasting magnesium and potassium (usually after starting MCAS treatment + proper repletion), most people notice:

fewer dislocations and less pain, better energy and sleep, calmer nervous system, more stable blood pressure and heart rate.

The Bottom Line: Two Connected Problems, One Big Opportunity

In EDS, the “thermostat” for ions is broken because of stretchy kidney tubing + mast-cell interference. Fixing MCAS and consciously restoring magnesium, potassium, and the right ratios is one of the highest-leverage things you can do.

• Fragile connective tissue physically triggers mast cells → MCAS

• MCAS + weak kidney scaffolding → rapid loss of magnesium, potassium, and other ions

• Symptoms explode: pain, fatigue, dysautonomia, GI issues, allergies, and more

Recognizing and treating MCAS (with H1/H2 antihistamines, mast-cell stabilizers like cromolyn or ketotifen, trigger avoidance, and targeted supplements) plus supporting electrolyte balance is often the missing piece that helps people with EDS feel 50–80% better.

If you have EDS and any of the symptoms above, talk to your doctor (ideally an EDS-knowledgeable allergist, immunologist, or rheumatologist) about testing for MCAS and checking serum + RBC magnesium, potassium, and urinary electrolytes.

You don’t have to live with the unholy pain  most of the time– understanding the mast cell–kidney–electrolyte connection is often the first step to getting your life back.

Have you noticed flushing, random allergies, or electrolyte issues with your EDS? 

Share your experience in the comments – you’re not alone!