The Hidden Risks of Everyday Medication in Ultrarunning

At 110 kilometres into a 100 miler, a couple of painkillers can sound like a perfectly reasonable idea. Your legs hurt, you have been moving for most of a day, and the next checkpoint is still a long way away.

In everyday life, reaching for ibuprofen, paracetamol or a cold and flu tablet might barely warrant a second thought. During an ultramarathon, the situation is different. Heat, prolonged exertion, changes in kidney blood flow, an unhappy stomach, limited sleep and inconsistent food intake can all affect how your body handles medication.

That does not mean every tablet is dangerous, or that runners should abandon medically necessary treatment. It means the usual assumptions about familiar medicines deserve a closer look.

This is a Track3D research guide based on a structured review of published studies and Australian medication and anti-doping information, not medical advice or a ranking of which painkiller to take. Where the studies disagree or do not answer a 24–48-hour question, we will say so.

The same medicine, a very different environment

A 100-mile race is not a normal day with a lot more walking. Exercise changes how blood is distributed, especially between working muscles, skin, the gut and the kidneys. Temperature, hydration, energy availability and the amount of time spent moving can change substantially between the first morning and the second night.

Then add the things that make ultrarunning an ultra: running downhill on tired legs, eating for hours when your stomach does not want food, keeping warm overnight and trying to make sensible decisions with very little sleep.

Those are plausible mechanisms for additional risk, but the important qualifier is that a lot of medication research involves short cycling tests, healthy volunteers or ordinary clinical use. Very few studies examine repeated medication exposure during a continuous 30- to 40-hour mountain race.

The everyday medicine picture

These are not interchangeable products, and legal availability is not the same as sporting permission or medical suitability.

NSAIDs: why a painkiller might create another problem

NSAIDs are non-steroidal anti-inflammatory drugs. Ibuprofen, naproxen and diclofenac are familiar examples. They reduce pain and inflammation partly by inhibiting enzymes involved in prostaglandin production.

Prostaglandins do more than contribute to discomfort. They can also help maintain blood flow through the kidneys when the circulation is under stress. During prolonged exercise, especially with heat or fluid loss, that protective role can become more important. Blocking it is one reason clinicians are cautious about NSAID use in endurance events.

There are also gastrointestinal concerns. NSAIDs can irritate and damage the digestive tract, and endurance exercise introduces its own gut stress.

NSAIDs are not generally prohibited by WADA. That does not make taking them during a race medically advisable. The current Ultra-Trail Kosciuszko medical guidance explicitly advises runners against their use.

What the ultramarathon ibuprofen trial actually found

In a 2017 randomised trial, researchers compared ibuprofen with placebo during an 80 km stage of multi-day ultramarathon events. Kidney outcomes were available for 89 participants.

That is an observed difference of about 18 percentage points. It is concerning, but the statistical uncertainty was large: the published 95% confidence interval for the difference ranged from 4 points lower to 41 points higher with ibuprofen. The study did not establish a statistically conclusive increase under the conventional superiority test, nor did it establish the planned non-inferiority claim.

There is another distinction that matters. The outcome was defined using a change in a blood marker called creatinine, relative to an estimated baseline. Creatinine-defined acute kidney injury is a recognised research and clinical classification, but the trial did not demonstrate permanent kidney damage in those runners.

A 2024 scoping review covering 30 publications found mixed and methodologically limited evidence across kidney, electrolyte and other outcomes. A negative result in one observational study does not prove safety, just as one concerning trial does not settle every clinical question.

Gut injury and low sodium are separate questions

In a small controlled study of nine trained men, ibuprofen combined with brief cycling produced greater measured intestinal injury and permeability markers than exercise alone. Those measurements support concern about the gut barrier, but they are not the same as diagnosed gastrointestinal bleeding or a known risk of hospitalisation during a 100 miler.

There is also discussion about NSAIDs and exercise-associated hyponatraemia, where blood sodium becomes abnormally low. Studies disagree about the size or existence of a specific NSAID contribution, and some published figures require correction or further verification.

It is important not to confuse hyponatraemia with dehydration. Both can occur around endurance events, their symptoms can overlap, and the correct response is not always simply to drink more fluid.

Paracetamol is not an NSAID, but it is not a free pass

Paracetamol (Panadol is a familiar Australian brand) relieves pain through different mechanisms from NSAIDs. It does not produce the same prostaglandin-related kidney effects as a typical NSAID, but that does not make it a universally safe substitute for race pain.

Excess paracetamol can cause serious liver injury. A less obvious risk is accidentally taking it twice: one product for pain and another cold and flu product may contain the same active ingredient. The TGA's practitioner information explains the clinical toxicity concerns.

Could pain relief help athletic performance? Some small cycling experiments found task-specific effects. However, a 2021 review of ten studies involving 141 participants found no significant overall endurance or time-trial improvement. Its time-to-exhaustion subgroup showed a positive finding, which is not the same as a demonstrated improvement in ultra race time.

We also do not have adequate evidence that repeated therapeutic paracetamol use during a 30-hour race is harmless under all nutritional and medical circumstances. Severe clinical malnutrition has specific medical implications; skipping a few feeds during an ultra is not automatically the same condition.

Caffeine is a genuine performance enhancer, and it is permitted

Here is the interesting contrast. Caffeine has credible evidence for improving some endurance tasks and reducing perceived effort. The Australian Institute of Sport places caffeine among its Group A supplements, which have strong evidence for specific sporting applications.

Caffeine is also completely ordinary in ultrarunning: coffee before the start, caffeinated gels, cola at an aid station and perhaps an energy drink in the second night.

But those sources add up. Caffeine can also contribute to sleep difficulty, anxiety, a racing heartbeat or gastrointestinal discomfort, with considerable individual variation. A 2026 synthesis of acute side effects examined these concerns in athletes.

A separate body of sleep-deprivation research suggests caffeine can temporarily support some measures of vigilance. It does not restore a rested brain, and the relevant 48-hour experiments were not conducted while people were running technical trails.

There is no well-validated cumulative caffeine safety ceiling specifically for a 24–48-hour ultra that can be extracted from these studies.

Cold, flu and allergy tablets: check what is actually in the packet

Brand names are not enough. A cold and flu product might contain paracetamol, a decongestant, a sedating antihistamine, or a combination. Another product with a similar name may contain different ingredients.

Pseudoephedrine is a good example of why availability and anti-doping status must be considered separately. Some legitimate Australian pharmacy products contain it, yet WADA prohibits pseudoephedrine in competition above a specified urinary threshold. That is not proof of a meaningful endurance benefit, and the research on healthy-athlete performance is inconsistent.

Some older antihistamines, such as promethazine and doxylamine, can cause drowsiness and impaired coordination. Prescription sleep medicines may have additional next-day effects. None of those effects becomes less relevant because you are trying to navigate a rocky descent after a long night.

For an event using WADA rules, check the exact medicine through Sport Integrity Australia and Global DRO, including its ingredient, formulation and administration route. A legitimate prescription or pharmacist sale does not automatically provide anti-doping clearance.

Prescription treatment and performance enhancement are not the same thing

Asthma is a useful example. An inhaler can be medically important for someone with asthma, yet controlled studies in healthy people have not consistently demonstrated an endurance benefit from inhaled salbutamol. WADA has conditional allowances for certain inhaled beta-2 agonists, so both the medication and its route matter.

Systemic corticosteroids, including prednisone and prednisolone, can affect inflammation and physiology, and certain administration routes are prohibited in competition. Tramadol is prohibited in competition and, like other opioids, has important potential adverse effects. Neither observation means someone should stop prescribed or emergency treatment because they are entered in a race.

If you have a legitimate medical condition, medication decisions belong with your treating clinician. Anti-doping compliance is an additional question, not a substitute for medical care.

Questions worth settling before race day

There is no one medication rule that covers every runner, every prescription and every race. What is useful is removing ambiguity while you are still rested and capable of reading the small print.

• Know the active ingredients. Check combination products rather than relying on a brand name.
• Discuss existing medicines with a qualified clinician. Include relevant kidney, liver, heart, asthma or other medical history, and the expected duration of the event.
• Check interactions. Consider overlapping painkillers, multiple products containing paracetamol, stimulant combinations and sedating medicines.
• Check the actual event rules. Organiser medical recommendations, WADA classifications and individual Therapeutic Use Exemption requirements are different things.
• Do not assume a good training response settles ultra safety. A two-hour training run does not replicate a second night on the course.
• Know when to seek medical help. Severe or worsening symptoms, confusion, collapse, persistent vomiting, markedly reduced urine output or other unusual illness are not problems to mask with another tablet.

This checklist is not a dosing strategy or an individual treatment plan. Seek medical assessment when symptoms suggest illness or injury, and follow race medical instructions where appropriate.

What the research still cannot tell us

There are credible studies involving ultramarathon runners, but much of the wider evidence comes from cycling time trials, laboratory heat experiments, small crossover studies or clinical medicine. The same study can report a measurable change in a blood marker without demonstrating a difference in illness, hospitalisation or finishing time.

Our review also found reporting inconsistencies in some published tables, incomplete access to certain original papers and important questions about repeated exposure over 24–48 hours. Rather than fill those gaps with assumptions, we have kept the uncertain findings qualified or excluded disputed numerical claims.

We cannot derive a universal injury rate, a ranking of the safest race painkillers, or a reliable individual risk prediction from the available evidence. The gaps are even larger for runners with existing medical conditions, different ages, different medication combinations and very long exposure to heat, altitude or sleep deprivation.

Common questions

Related Track3D Guides: When Your Stomach Stops Cooperating in an Ultra and How to Plan Your Race Day for a 100K or 100 Mile Ultramarathon.

Research notes and primary sources

Research snapshot: 12 October 2026. This article is an educational summary of a structured Track3D evidence review, not a formal systematic review, clinical advice, a medical safety clearance or an individual anti-doping ruling. Scientific findings and Australian sport rules may change. Where original full texts or corrections could not be verified, we have restricted or omitted the affected claims. Publication requires separate medical and regulatory review.