Table 2.

Considerations for combined or repeated use of performance supplements for a sporting event

Question	Potential outcomes	Theoretical examples
What is the interaction between supplements which are used in combination for a single event?	Related mechanisms with additive benefits	Loading strategies for bicarbonate (extracellular buffer) and beta-alanine (intracellular buffer) may combine to increase total buffering capacity and tolerance of acidosis due to high rates of energy production from anaerobic glycolysis. The combination may be better than either product used in isolation due to the greater increase in buffering capacity per se, as well as opportunity to buffer both within the muscle cell as well promote the efflux of H+ from the cell. May be useful for an event/athlete in which substantial drops in muscle pH are experienced
	Related mechanisms with no additive benefits	The benefits of combining bicarbonate and beta-alanine loading protocols may not be evident if the additional buffering capacity provided by either supplement alone is sufficient to address the physiological limitations of the event/athlete
	Independent mechanisms with additive benefits	The benefits of creatine loading (providing additional muscle phosphocreatine substrate) and caffeine (reducing the perception of effort) may combine in a sport involving prolonged repeated efforts. In this case, some other factor is causing fatigue towards the end of the event and caffeine is able to reduce/delay the onset of this effect
	Independent mechanisms with no additive benefits	The benefits of creatine loading (providing additional muscle phosphocreatine substrate) and caffeine (reducing the perception of effort) may not be additive in an event in which fatigue is related to inadequate recovery of phosphocreatine store between sprints. This limitation can be masked by caffeine or addressed by creatine loading. However, once it is addressed, the effect of caffeine is no longer beneficial
	Independent mechanisms with counteractive outcomes (direct)	Nitrate supplementation (nitric oxide production via a separate pathway that can operate in hypoxic and acidic conditions) may enhance the performance of sustained high intensity exercise. However, the addition of bicarbonate loading may reduce the effectiveness of nitrate supplementation by buffering plasma acidosis and removing the conditions where it is valuable
	Independent mechanisms with counteractive outcomes (indirect)	Bicarbonate loading (extracellular buffer) and caffeine (reduced perception of effort) may each enhance the performance of sustained high intensity exercise. However, the co-ingestion of these two supplements may increase the risk of gut side-effects associated with bicarbonate supplementation and may impair performance
What are the potential issues in repeating the use of the same supplement for a subsequent event?	Subsequent use of the supplement might require a different protocol to restore the physiological advantage or to meet the logistical requirements of competition spacing	If the half-life of the supplement is prolonged in relation to the gap between competition events, it may not be necessary to take a complete dose for the subsequent event to achieve its physiological role. For example, smaller doses of bicarbonate, nitrate or caffeine may be suitable as a “top up” for events held 2–4 h apart. Alternately, reorganisation of the recognized protocol may be needed if the gap between events is <2 h (and smaller than the suggested interval for supplement intake for nitrate or bicarbonate)
	Desensitization of physiological systems may render the subsequent use of a supplement less effective	The response to some supplements may be reduced by repeat exposure due to a desensitization effect. For example, it has been suggested (probably erroneously) that the performance effects of caffeine are reduced in habitual users and that its use for competition purposes should follow a caffeine withdrawal
	Residual fatigue left from enhanced performance in the first event may carry over to the subsequent event	It is possible that the greater physiological effort made possible by supplementation in the first event may cause residual fatigue that requires management for the second event. For example, use of caffeine in the first event may mask fatigue and allow a higher intensity/power output that may cause acidosis or greater depletion of fuel substrates