Hypermobility/EDS, POTS and Chronic Fatigue: Connecting the Dots

Written by Chelsea Lee

If you have flexible joints, get dizzy when you stand up, and feel wiped out by things other people seem to manage easily, you're not imagining a pattern. Hypermobility, POTS and chronic fatigue come together far more often than chance would predict.

This post steps back and looks at the whole picture: what each condition is, why they seem to come together, and what that means for feeling better.

First, what are these conditions?

Hypermobile EDS (hEDS) and hypermobility spectrum disorder (HSD).

Ehlers-Danlos syndromes are a group of 13 inherited connective tissue conditions. Hypermobile EDS (hEDS) is by far the most common, making up roughly 80–90% of cases, and it's the only type without a known gene or genetic test (Frontiers in Neurology, 2024). People with symptomatic hypermobility who don't meet the strict hEDS criteria are diagnosed with HSD. For day-to-day care, the two are treated much the same.

POTS (postural orthostatic tachycardia syndrome).

Your heart rate jumps by 30 or more beats per minute within 10 minutes of standing, without your blood pressure dropping. It often comes with light-headedness, palpitations, brain fog, shakiness, nausea and fatigue. Lying down usually helps.

ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome).

This is more than just being tired. The hallmark is post-exertional malaise is a crash in symptoms after physical, mental or emotional effort, often delayed by a day or two and lasting days or weeks. Unrefreshing sleep, brain fog and feeling worse when upright are also common.

Other conditions often join the cluster, including mast cell activation syndrome (MCAS), gut problems, persistent pain, headaches and, more recently, long COVID.

Why do they cluster?

The short answer: connective tissue is everywhere, and when it behaves differently, it can affect far more than your joints. Researchers have proposed several overlapping explanations. Most people probably have a mix.

1. Stretchy blood vessels and blood pooling

Collagen doesn't just hold joints together. It's also in the walls of your veins. One leading theory is that more compliant veins don't tighten properly when you stand, so blood pools in the legs and belly (Ehlers-Danlos Society). Less blood gets back to the heart and brain, so the heart speeds up to compensate. That's POTS in a nutshell.

2. Less blood flow to the brain

A Dutch study of 200 women with ME/CFS looked at blood flow to the brain during tilt-table testing. The team expected the drop in flow to be larger in people who were also hypermobile (Van Campen et al., 2021). Reduced brain blood flow when upright may help explain brain fog and fatigue across all three conditions. Low blood volume has also been found in both POTS and ME/CFS (National Academies, 2022).

3. The nervous system

The autonomic nervous system runs everything you don't think about: heart rate, blood pressure, digestion, temperature. Nerve changes, including small fibre neuropathy, are thought to play a part in how blood vessels behave in hEDS, though the exact mechanism isn't settled (Ehlers-Danlos Society). Persistent pain also tends to make the whole nervous system more sensitive, which can amplify every other symptom.

4. Mast cells and inflammation

Mast cells are immune cells that release histamine and other chemicals. Histamine widens blood vessels and raises heart rate, which can worsen POTS-type symptoms. Some researchers suggest the link may run both ways: ongoing inflammation and high adrenaline levels might weaken connective tissue over time, worsening or even triggering hypermobility (Frontiers in Neurology, 2024). (This is still a hypothesis).

5. The knock-on cycle

When standing makes you feel awful and effort causes crashes, it's natural to do less. Deconditioning then reduces blood volume and muscle pump strength, which makes POTS worse. Unstable, painful joints add to the load. None of this means it's "all deconditioning". It just means each problem can feed the others.

What the research shows (and what it doesn't)

The overlap is real and well documented. Joint hypermobility has been found in up to 57% of people with POTS and 49% of people with ME/CFS, compared with roughly 10–20% of the general population (Frontiers in Neurology, 2024).

It isn't new, either. A 2002 Johns Hopkins study found that 60% of children with chronic fatigue syndrome were hypermobile, compared with 24% of healthy children (Johns Hopkins, via Newswise). More recently, a study of 815 adults in an ME/CFS registry found the hypermobile group was more likely to report EDS and POTS, and had more pain, gut, headache and autonomic symptoms and lower quality of life (Mudie et al., 2024). The authors suggest hypermobile people may be a distinct subgroup of ME/CFS.

A few important caveats:

  • Being flexible doesn't mean you'll become unwell. About 1 in 5 healthy teenagers is hypermobile, and most never develop ME/CFS (Johns Hopkins, via Newswise).

  • The numbers vary a lot. Estimates depend on who's studied and how hypermobility is measured. Many studies rely on self-report, and the precise rate of hEDS in POTS is still unknown (Miller et al.).

  • We don't yet know the cause. The mechanisms above are strong leads, not necessarily proven explanations. New research means our explanation is always changing!

What this means for you

Ask about the whole picture

If you have one of these conditions, it's worth being checked for the others. A thorough POTS assessment should include a hypermobility screen, and an EDS or HSD assessment should include heart rate and blood pressure lying and standing. Your GP is the place to start. They can do a simple stand test and refer you on to a cardiologist, rheumatologist or other specialist if needed.

The basics for POTS

Non-drug strategies are usually tried first (Dysautonomia International):

  • Fluids and salt to boost blood volume. Check with your GP before adding salt, as it isn't right for everyone.

  • Compression. Waist-high garments or an abdominal binder tend to work better than knee-high socks.

  • Reclined exercise such as swimming, rowing or a recumbent bike, plus leg and core strengthening.

  • Muscle pumps before standing. Before you get up, spend 20–30 seconds pumping your ankles, marching your feet and squeezing your thigh and buttock muscles. This helps push pooled blood back towards your heart, so standing is less of a shock. Crossing your legs and clenching those muscles can also help if you have to stand still.

  • Small habits like getting up slowly, avoiding long periods of standing still, and raising the head of the bed slightly.

Respect your energy limits

Here's where the overlap gets tricky. Exercise is a cornerstone of POTS care. But if you have ME/CFS, pushing through with fixed weekly increases can make you worse. The UK's NICE guideline no longer recommends graded exercise therapy for ME/CFS and recommends energy management, or pacing, instead (NICE).

In practice, that means:

  • Start well below what you think you can do, often lying or sitting.

  • Track how you feel 24–48 hours after activity, not just during it.

  • Build up only when you're stable, and pull back after a crash rather than pushing on.

  • Count mental and emotional effort too. A stressful meeting can cost as much as a walk.

Where physio fits

A good physio can help with the pieces that often get missed:

  • Pain and joint care. Hands-on treatment, plus gentle work on joint control and stability for hypermobile joints.

  • Headaches and neck pain, which are very common in this group.

  • Calming the nervous system. Slow breathing and gentle movement can take the edge off a system stuck on high alert.

  • A paced plan. Activity matched to your energy, then a referral to an exercise physiologist when you're ready to build.

  • Joining the dots. Recognising when symptoms point to something your GP should look at.

The takeaway

If your body seems to have a dozen unrelated problems, they may not be unrelated at all. Hypermobility, POTS and chronic fatigue often share roots in connective tissue, blood flow and the nervous system. Seeing them as one connected picture usually leads to better, gentler care.

Sources

Chelsea Lee
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Physiotherapy for Hypermobility