If you’ve ever been stuck in bed at night, feeling like your legs just won’t stop twitching or crawling, you’re not imagining it — and you’re definitely not alone.
Restless Leg Syndrome (RLS) is a surprisingly common condition that disrupts sleep, ruins rest, and leaves millions of people exhausted and frustrated.
Despite how widespread it is, the causes of RLS aren’t always well understood — even by doctors.
Most people assume it’s just about being tired or low on iron.
The truth is, RLS is much more complicated than that.
It’s not just about your bloodwork — it’s about your brain chemistry, your genes, your habits, and even what’s in your medicine cabinet.
Here are 10 lesser-known, research-backed causes of Restless Leg Syndrome that might surprise you — and a few tips on what you can do about them.
1. Low Iron in the Brain
One of the most well-established causes of RLS is iron deficiency — but not the kind that always shows up in standard blood tests.
Even people with normal serum iron levels can experience low iron in the brain, particularly in a region called the substantia nigra, which helps control movement.
This area also plays a key role in dopamine production — and when dopamine signaling is disrupted, RLS symptoms often emerge.
Researchers using MRI scans have repeatedly found iron deficiencies in the brains of RLS patients.
These findings support the theory that it’s not just about how much iron is in your body — it’s about how much your brain can access.
Some doctors now test for ferritin (a more specific iron storage marker) and recommend iron supplements even when blood iron appears normal.
2. Genetic Predisposition
RLS often runs in families, especially when symptoms begin early in life.
Scientists have identified specific genetic markers associated with the condition — most notably in the BTBD9 and MEIS1 genes.
These gene variants are found in a high percentage of people with RLS, although having the gene doesn’t guarantee you’ll experience symptoms.
What’s fascinating is that genetics often interact with other triggers.
Someone may carry a gene that makes them vulnerable to RLS, but not develop the condition until their iron levels drop or a medication interferes with dopamine.
It’s this interaction between genes and environment that makes RLS so tricky to pin down — and why two people in the same family might have completely different experiences with it.
3. Medications That Interfere With Dopamine
Several commonly used medications are known to either trigger or worsen RLS symptoms.
These include certain antidepressants (especially SSRIs and tricyclics), antipsychotic drugs, anti-nausea medications, and sedating antihistamines often found in cold and allergy remedies.
These medications can interfere with dopamine pathways in the brain, making RLS more noticeable — or in some cases, unbearable.
Even blood pressure medications like beta blockers have been implicated.
If you’ve noticed your RLS getting worse after starting a new prescription, it’s worth having a conversation with your healthcare provider about possible alternatives or adjustments.
4. Pregnancy (Especially in the Third Trimester)
Pregnancy brings on a host of hormonal, circulatory, and nutritional changes — and for many women, RLS is an unfortunate side effect.
It’s most common in the third trimester, when iron demands peak and blood volume is at its highest.
The growing uterus can also press on nerves and blood vessels, potentially disrupting normal leg function.
Thankfully, in most cases, RLS symptoms disappear shortly after giving birth.
If the sensations persist, new mothers should be evaluated for lingering iron deficiency or sleep deprivation, which can continue to exacerbate the condition postpartum.
5. ADHD and Dopamine Imbalance
One of the more surprising links in RLS research is its relationship with Attention Deficit Hyperactivity Disorder (ADHD).
Studies have found that up to 44% of people with ADHD also have RLS, and vice versa.
Both conditions appear to involve abnormalities in dopamine signaling — which affects both movement control and emotional regulation.
This overlap means that people with ADHD may be more prone to developing RLS, especially if they are already dealing with stress, sleep deprivation, or nutritional deficiencies.
Some medications used to treat ADHD — especially stimulants — may either help or worsen symptoms, depending on the individual.
6. Underlying Medical Conditions
RLS is frequently secondary to other health issues. Common conditions associated with RLS include diabetes, peripheral neuropathy, kidney disease, thyroid dysfunction, fibromyalgia, and autoimmune disorders like rheumatoid arthritis and celiac disease.
In many cases, the nerve damage or inflammation caused by these diseases contributes to the tingling, crawling sensations associated with RLS.
If you have one of these underlying issues, managing it effectively may reduce or even eliminate your RLS symptoms.
That’s why it’s important to take a holistic view of your health if you’re struggling with restless legs at night.
7. Caffeine and Alcohol
They might seem harmless, but both caffeine and alcohol can disrupt your sleep cycle — and make RLS worse.
Caffeine is a known stimulant that can increase nerve sensitivity and make you more aware of those irritating leg sensations.
Alcohol, meanwhile, tends to fragment sleep and may lower dopamine levels, worsening RLS symptoms in the hours after consumption.
If you’re dealing with restless legs, try cutting out caffeine after midday and limiting alcohol intake, especially in the evening.
Many people notice a significant improvement in symptoms within just a few days of making this change.
8. Withdrawal from Certain Substances
RLS can also be triggered by withdrawal — especially from opioids, sleeping pills (like benzodiazepines), and alcohol.
These substances affect dopamine regulation and the nervous system.
When they’re suddenly removed, your brain and body can react with rebound symptoms, including RLS.
This kind of RLS can be temporary, but it’s often severe.
If you’re planning to stop using any of these substances — especially after long-term use — it’s best to do so under medical supervision to manage any uncomfortable side effects.
9. Physical Injury or Surgery
Believe it or not, injuries and surgeries — especially involving the spine or legs — can trigger RLS in some people.
Nerve irritation, inflammation, or poor circulation following a medical procedure may be enough to activate symptoms.
In some cases, even minor injuries like a twisted ankle have been linked to the onset of RLS.
Researchers still don’t fully understand why this happens, but it’s thought that trauma can sensitize nerves or disrupt normal signaling pathways, making you more prone to experiencing RLS symptoms afterward.
10. Chronic Sleep Deprivation
This one’s a bit of a chicken-and-egg situation.
Poor sleep makes RLS feel worse — but RLS itself causes poor sleep.
Over time, being stuck in this cycle can actually increase your sensitivity to discomfort and worsen your symptoms.
That’s because your body becomes more reactive to even minor signals from your nervous system when it’s sleep-deprived.
Sticking to a consistent bedtime, avoiding screens late at night, and building a calming evening routine can all help break the cycle.
Even an extra 30–60 minutes of sleep per night can make a difference.
Final Thoughts
Restless Leg Syndrome might seem like a simple sleep nuisance, but it’s often a sign of something deeper — whether it’s a nutrient imbalance, a medication issue, or a genetic trait waiting to be triggered.
Understanding the real causes of RLS is the first step toward finding lasting relief.
If you suspect that any of these hidden triggers are affecting you, start by tracking your symptoms and speaking with a healthcare provider.
Remember, the better your sleep, the better your body and brain can function.