Herb-Drug Interactions: Creatine


Types, sources and related compounds

Creatine monohydrate. Creatine phosphate is also used.

Use and indications

Creatine supplements are taken most often to improve exercise performance and increase muscle mass. They are also used for the treatment of cardiac disorders and have possible uses for motor neurone disease, muscular dystrophies, Huntington’s disease and Parkinson’s disease.

Creatine is found in foods, most abundantly in meat and fish, and is also synthesised endogenously

Excessive intake of creatine, by the use of supplements, has, very rarely, been reported to cause acute renal impairment.


Creatine is distributed throughout the body, with the majority being found in skeletal muscle. Creatine is degraded to creatinine, and both creatine and creatinine are excreted via the kidneys. Absorption of creatine is likely to be an active process, and may follow nonlinear kinetics with the ingestion of high doses because of saturation of skeletal muscle stores, although this has not been confirmed experimentally. The maximum plasma level of creatine is reached less than 2 hours after the ingestion of doses of under 10 g, but after more than 3 hours for doses over 10 g, and may vary with the ingestion of carbohydrate, see food. Clearance of creatine would appear to be dependent on both skeletal muscle and renal function.

Interactions overview

There are no established interactions with creatine, but there is some evidence that caffeine might counteract its beneficial effects, and a high carbohydrate intake might increase its retention. There is an isolated report of stroke in a patient taking a creatine supplement with caffeine plus ephedra, although the role of creatine in this case is uncertain. There is a possibility that creatine supplements might complicate interpretation of serum creatinine measurement.

Creatine + Caffeine

Limited evidence suggests that the performance-enhancing effects of creatine may be reduced by caffeine.

Clinical evidence

Nine healthy subjects given a creatine supplement 500mg/kg daily for 6 days, and caffeine capsules 5 mg/kg daily for 3 days beginning on the fourth day, experienced a lack of performance-enhancing effects of creatine during knee extension exercises, when compared with creatine given alone. One subject experienced some gastrointestinal discomfort during concurrent use.

These findings were replicated in a later study in 9 healthy subjects. Caffeine 5 mg/kg reduced phosphocreatine resynthesis during rest from a period of exercise when given with creatine 25 g daily for 2 or 5 days.

Experimental evidence

No relevant data found.


Caffeine appears to inhibit the resynthesis of endogenous phosphocreatine during recovery from a period of strenuous exercise, which, in turn, delays the formation of the energy source, ATP.

Importance and management

These studies are preliminary and there seem to be no further reports of an interaction. However, those taking creatine supplements to enhance exercise performance should perhaps reduce caffeine intake from beverages and other sources. Note that caffeine is also present in a number of herbal medicines, consider also caffeine-containing herbs.

Creatine + Food

Limited evidence suggests that a high carbohydrate intake may increase creatine retention.

Clinical evidence

In a study, 22 healthy male subjects were given 5 g creatine alone, or with 500 mL Lucozade (which provided a source of glucose and simple sugars) every 4 to 5 hours, giving a total dose of creatine of 20 g daily for 2 days. Subjects who received creatine alone continued their normal diet, whereas those receiving creatine with Lucozade received a high-carbohydrate diet. The peak plasma concentration and AUC of creatine was higher in those who had not received the glucose load (as Lucozade), but this group also demonstrated the highest urinary creatine excretion. In a similar study, the effect of about 50 g of protein plus 50 g of carbohydrate on the retention of creatine from supplements was similar to that of high carbohydrate (100 g carbohydrate).

Experimental evidence

No relevant data found.


The authors suggested that their findings indicate that the ingestion of carbohydrate with creatine led to an increase in insulin secretion, resulting in an increased uptake of creatine by skeletal muscle, and that protein/carbohydrate might have a similar effect.

Importance and management

These studies suggest that patients who are taking creatine to improve their muscle creatine stores might experience better results if the creatine is taken at the same time as high amounts of carbohydrates or protein/carbohydrates. However, this requires further study.

Creatine + Herbal medicines; Ephedra with Caffeine

There is an isolated report of stroke in a patient taking a creatine supplement with ephedra plus caffeine, although the role of creatine in this case is uncertain.

Evidence, mechanism, importance and management

A 33-year-old fit man with no vascular risk factors had a stroke 6 weeks after starting to take two supplements to aid body building. The first contained ephedra alkaloids (from ma huang), caffeine, levocarnitine and chromium, and the second contained creatine, taurine, inosine and coenzyme Q10. His daily consumption was estimated to be 40 to 60 mg of ephedra alkaloids, 400 to 600 mg of caffeine and 6 g of creatine. Note that serious adverse events such as stroke have been reported with caffeine and dietary supplements containing ephedra alkaloids, and ephedra is banned in some countries. See Ephedra + Caffeine. Therefore, this case could be attributed to this supplement alone, and the role of creatine is unclear.

Note that caffeine might counteract some beneficial effects of creatine. Consider caffeine, above.

Creatine + Laboratory tests

There is a possibility that creatine supplements might complicate the interpretation of serum creatinine measurement.

Evidence, mechanism, importance and management

Creatinine is produced in muscles from the breakdown of creatine, and is excreted by the kidneys. Blood levels of creatinine are therefore used as one measure to estimate renal function.

It is possible that dietary supplementation with creatine could lead to increased serum levels of creatinine, and this might be particularly so in patients with impaired renal function and with long-term use.Note that, it has been suggested that the long-term, high-dose use of creatine supplements might actually contribute to worsening renal function, although further study is needed to establish this.

It would be sensible for individuals taking creatine supplements to tell their health provider this fact, if they need to have renal function tests.