When an athlete wonders whether a prescription drug could boost endurance, the first name that pops up is acetazolamide. It’s a carbonic anhydrase inhibitor most known for treating glaucoma and altitude sickness, but its impact on exercise physiology is a hot topic among coaches and sports physicians.

Acetazolamide is a synthetic sulfonamide that inhibits the enzyme carbonic anhydrase, leading to increased renal excretion of bicarbonate and a mild metabolic acidosis. The drug is typically prescribed at 250‑500 mg daily for altitude prophylaxis, but athletes sometimes experiment with lower doses to manipulate blood pH during training.

How Acetazolamide Works in the Body

Understanding the mechanism is key before you decide to add the pill to a training regimen. The enzyme Carbonic Anhydrase catalyzes the reversible conversion of carbon dioxide and water into carbonic acid, which quickly dissociates into bicarbonate and hydrogen ions. By blocking this enzyme, acetazolamide forces kidneys to dump bicarbonate, lowering plasma pH and creating a controlled metabolic acidosis.

This shift has two main effects for an exercising athlete:

1. It stimulates ventilation - the body tries to expel excess CO₂, which can improve oxygen uptake during high‑altitude exposure.
2. It enhances the Bohr effect - lower pH causes hemoglobin to release oxygen more readily to working muscles.

Both pathways sound promising for endurance, but the reality depends on dose, timing, and individual tolerance.

Acetazolamide and Altitude Training

Altitude training-living or training at elevations above 2,000 m-relies on hypoxia to trigger erythropoietin (EPO) production and boost red‑cell mass. The problem is that altitude also depresses VO₂ max, especially during the first few days. Athletes sometimes use acetazolamide to speed up acclimatization.

A 2023 field study of 24 elite cyclists showed that a 250 mg dose taken twice daily for 48 hours before ascent reduced the drop in VO₂ max from 12 % to 5 % compared with a placebo group. The same study noted a modest increase in ventilation rate (by 8‑10 %) and a quicker return to sea‑level performance after a 10‑day high‑altitude camp.

While these results are encouraging, they come with a caveat: the study participants were all medically screened and monitored for electrolyte balance. Unsupervised use can backfire.

Dosage Guidelines for Athletes

There is no one‑size‑fits‑all regimen, but most sports physicians recommend the following protocol for a short‑term altitude exposure:

• Loading phase: 250 mg orally every 12 hours for 2‑3 days prior to ascent.
• Maintenance phase: 125‑250 mg every 12 hours while at altitude.
• Stop‑date: Discontinue 24 hours before returning to sea level to allow plasma bicarbonate to normalize.

For sea‑level training, the dosing is usually lower (125 mg once daily) and only considered when an athlete is trying to induce a mild acidosis to stimulate buffering capacity. However, this off‑label use is rarely endorsed without a medical prescription.

Potential Side Effects and Health Risks

Because acetazolamide forces the kidneys to lose bicarbonate, it can lead to:

• Electrolyte disturbances - especially low potassium and sodium.
• Kidney stone formation - due to increased urinary calcium.
• Gastrointestinal upset - nausea, metallic taste, and occasional vomiting.
• Neurological symptoms - tingling in the fingers and toes (paresthesia) or mild headache.

Most athletes who stick to the recommended dose report only mild tingling that resolves when the drug is stopped. The bigger danger lies in combining acetazolamide with other diuretics or high‑dose NSAIDs, which can precipitate severe dehydration and renal injury.

WADA, Doping Regulations, and Ethical Considerations

The World Anti‑Doping Agency (WADA) does not list acetazolamide as a prohibited substance, but it appears on the Doping Regulations monitoring list. This means athletes must disclose therapeutic use through a TUE (Therapeutic Use Exemption) if the drug is taken in a sport that has strict blood‑parameter limits.

Key points for compliance:

1. Obtain a written prescription from a qualified physician.
2. File a TUE with the relevant national anti‑doping organization before competition.
3. Maintain a log of dosage, timing, and any side effects for audit purposes.

Failure to disclose can result in a violation, even though the compound itself is not banned.

Practical Checklist for Athletes Considering Acetazolamide

• Consult a sports medicine doctor and discuss altitude goals.
• Get baseline blood chemistry - focus on bicarbonate, potassium, and creatinine.
• Plan dosing schedule at least 48 hours before ascent.
• Hydrate well; aim for at least 2‑3 L of fluid per day.
• Monitor for tingling, nausea, or excessive fatigue; stop the drug if symptoms worsen.
• Document everything for a potential TUE submission.

Comparison Table: Acetazolamide vs Placebo in Altitude Training

Frequently Asked Questions