Quinine

• Quinine is a bitter alkaloid sourced from the bark of the cinchona tree1 and has a long history of use in traditional medicine such as a treatment for malaria², where doses of 1 g of quinine sulphate were administered before the acute phase.³
• Quinine carries a strong bitter taste⁴ and is used in tonic water as a flavouring agent.¹ Its concentration in commercial beverages varies greatly and such products typically lack nutritional information detailing the amount of quinine used. The concentration of quinine in tonic water is much lower than that used for medical purposes.
• Quinine is one of the latest emerging acute nutritional strategies that purportedly activate brain areas to reduce perception of effort and subsequent pacing decisions, in both research and practical settings.⁵
• Ingestion of Quinine activates the bitter taste receptors in the oral cavity and upper gastrointestinal tract to increase corticomotor excitability and stimulate neural excitability.⁴ Changes in the autonomic nervous system (ANS)^6,7 provide a potential mechanism to enhance performance in high effort, short duration activities.
• Unlike the case for carbohydrate mouth rinsing, the quinine solution needs to be swallowed for it to prove effective⁴ and to ensure that it has contact with specific receptors that are concentrated in the back of the mouth and throat.
• Benefits of quinine ingestion as a sensory-driven tastant include increased 30 second cycling sprint performance by 2.5-4%⁸ and increased cycling performance (~6%) during initial stages of a 3 to 4-minute cycling effort.⁹
• Since the effects of quinine ingestion are seen immediately after the ingestion of quinine, the ergogenic effect has been attributed to central activation by afferent taste.
• To date, studies that have reported benefits of quinine ingestion have involved exercise protocols undertaken on cycle ergometers. It is unclear if this translates to real world cycling (e.g. track cycling) and whether other sprint events in running or swimming would benefit from pre-event quinine ingestion.
• It is unclear whether other factors might inhibit or diminish sensory-driven pathways when ingesting quinine. For example, bitter tasting medications are often masked by manipulations involving salt.¹⁰ Therefore, it might be possible to counter-act an unpleasant and persistent bitter taste after the event by ingesting a salty snack. However, whether salt intake prior to or around the pre-event quinine ingestion interferes with any ergogenic effect is unknown.
• It is also relevant to explore ways to amplify sensitivity to the bitter taste prior to ingesting quinine to magnify performance benefits without needing to increase the actual dose.

The manufacturer’s guidelines should be followed in regards to the shelf-life of the quinine powder (Quinine Hydrochloride Dihydrate). Once the solution is prepared it should be consumed as soon as possible given the lack of information about the shelf-life and biological effectiveness.

• A single dose of quinine solution is prepared by mixing 0.02 g of Quinine Hydrochloride Dihydrate in 25 ml of deionised water (or 0.08 g per 100ml of deionised water). Such a solution is considered safe to use. However, quinine powder (Quinine Hydrochloride Dihydrate) is considered hazardous and requires careful handling.
• It is necessary to swirl the quinine solution in the mouth and then swallow it to achieve a beneficial effect.¹¹
• Such a protocol (10-20 seconds prior to the sprint) has been found to improve a maximal 30 second cycling effort⁸ and the initial 80 seconds of a 3 to 4-minute cycling time-trial.⁹
• However, quinine ingestion during the last 90 second of a 4-minute maximal cycling effort has failed to improve performance.¹²
• Ingesting the directed single dose of quinine solution triggers an extremely bitter sensation in the mouth, which can be counteracted, postevent and after benefitting from the ergogenic effect of the tastant, by ingesting a salty snack (e.g. Salt and Balsamic vinegar flavoured rice cakes) or equivalent.

Limited evidence for dose-response

• No adverse effects have been reported when quinine is used in low doses (0.02 g of quinine in a 25 ml solution) prior or during exercise, and a single dose of quinine solution as described above is considered safe for use. It is unclear if concentrations higher than 2mM of quinine would trigger a higher sensory-driven response for even greater performance benefits – or, in contrast to this, induce detrimental effects.
• Currently, there is insufficient evidence to consider individual responsiveness to quinine ingestion in the sporting setting. However, ingestion of strong-tasting nutrients alongside or prior to quinine ingestion could interfere with its performance effects if it counteracts the bitter taste or sensory response triggered.

Careful handling required

• Quinine powder (Quinine Hydrochloride Dihydrate, S1125, Sigma-Aldrich Pty Ltd, Australia) is considered a hazardous chemical and requires careful handling when preparing the solution.
• Although not classed as a dangerous chemical, inappropriate handling or accidental inhaling of quinine powder can cause acute oral toxicity, impaired respiration and skin sensitisation.

Evidence for benefits still lacks certainty

Benefits might be specific to certain scenarios and short-term duration of effort. Further research is needed before more information can be provided around specific protocols, including targeted sprint events, potential uses in training and different modes of ingestion (e.g. gels or solid forms) that might be more practical to achieve in competition scenarios.

Supplement safety information and batch tested product list www.sportintegrity.gov.au/what-we-do/anti-doping/supplements-sport, opens in a new tab

1. Brasic, J. R. (1999). Should people with nocturnal leg cramps drink tonic water and bitter lemon? PR, 84(2), 355-367.
2. Permin, H., Norn, S., Kruse, E., & Kruse, P. R. (2016). On the history of Cinchona bark in the treatment of Malaria. DMA, 44, 9-30.
3. Marchoux, E. (1933). Les traitements du paludisme [Treatments of malaria]. Malaria Commission CH/Malaria/193.
4. Gam, S., Guelfi, K. J., Hammond, G., & Fournier, P. A. (2015a). Mouth rinsing and ingestion of a bitter-tasting solution increases corticomotor excitability in male competitive cyclists. EJAP, 115(10), 2199-2204.
5. Best, R., McDonald, K., Hurst, P., & Pickering, C. (2021). Can taste be ergogenic? EJN, 1, 45-54.
6. Kelley, A. E., Baldo, B. A., Pratt, W. E., & Will, M. J. (2005). Corticostriatal-hypothalamic circuitry and food motivation: integration of energy, action and reward. PB, 86(5), 773-795.
7. Robin, O., Rousmans, S., Dittmar, A., & Vernet-Maury, E. (2003). Gender influence on emotional responses to primary tastes. PB, 78(3), 385-393.
8. Gam, S., Guelfi, K. J., & Fournier, P. A. (2014). Mouth rinsing and ingesting a bitter solution improves sprint cycling performance. MSSE, 46(8), 1648-1657.
9. Etxebarria, N., Ross, M. L., Clark, B., & Burke, L. M. (2019). Ingesting a Bitter Solution: The Sweet Touch to Increasing Short-Term Cycling Performance. IJSPP, 14(6), 727-732.
10. Rahman, Z., Siddiqui, A., & Khan, M. A. (2013). Orally disintegrating tablet of novel salt of antiepileptic drug: formulation strategy and evaluation. EJPB, 85(3 Pt B), 1300-1309.
11. Gam, S., Tan, M., Guelfi, K. J., & Fournier, P. A. (2015b). Mouth rinsing with a bitter solution without ingestion does not improve sprint cyclingperformance. EJAP, 115(1), 129-138.
12. Etxebarria, N., Clark, B., Ross, M., Hui, T., Goecke, R., Rattray, B., & Burke, L. (2020). Quinine ingestion during the latter stages of a 3000 m time trial fails to improve cycling performance. IJSNEM, ahead of print.