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Creatine/Drug Interactions:- AminoglycosidesAminoglycosides: In theory, a combination of aminoglycosides and creatine may increase the risk of nephrotoxicity (119; 147; 15). Renal function should be monitored.
- Antidiabetic agentsAntidiabetic agents: Creatine may alter activities of insulin and other blood glucose lowering agents. In a controlled study, no changes were observed in those taking HMB plus creatine for six weeks (153). Decreased glucose levels in creatine-supplemented animals have been suggested (154). In humans, neither acute nor short-term creatine supplementation influenced glucose tolerance or levels (155; 156; 157). High concentrations of insulin may enhance muscle creatine accumulation (158). This is a result of an insulin-induced transport of creatine from circulation to skeletal muscle (158) vs. creatine delivery (159). Decreased insulin levels in animals have been suggested (154). In humans, neither acute nor short-term creatine supplementation influenced measures of insulin sensitivity (156).
- Anti inflammatory agentsAnti inflammatory agents: In an animal study, the combination of indomethacin with creatine, as measured by the carrageenan-induced paw edema test, showed the drug combination was more effective at reducing inflammation than either drug alone (6). The combination of creatine with nephrotoxic drugs, such as nonsteroidal anti-inflammatory drugs including ibuprofen, indomethacin, naproxen and piroxicam (Feldene®) may adversely affect renal function and be harmful to the kidneys. Renal function should be monitored. NSAIDS reduce renal blood flow (via prostaglandin inhibition) and creatine may be nephrotoxic, so adverse effects may be reciprocal.
- Antilipemic agentsAntilipemic agents: Daily supplementation with creatine can reduce plasma total cholesterol, triacylglycerides and VLDL-cholesterol (7) and thus may potentiate the effects of lipid lowering agents.
- Antineoplastic agentsAntineoplastic agents: Cyclocreatine, an analog of creatine, increased tumor-growth delay in SW2 small-cell lung cancer cells when added with standard anticancer agents including cis-diaminedichloroplatinum(II), cyclophosphamide, adriamycin, or 5-fluorouracil (160). Thus, concomitant use with these or with other antineoplastic agents may potentiate effects or lead to toxicity.
- CaffeineCaffeine: Phosphocreatine resynthesis is possibly inhibited by creatine. In randomized, controlled trials, caffeine antagonizes the ergogenic effects of creatine and counteracts its benefits on intense intermittent exercise performance (3; 4). It is not clear whether caffeine consumption as found in the average cup of coffee or tea also has this effect. A combination of caffeine, ephedra and creatine may increase risk for adverse side effects. In a case series, ischemic stroke was reported in a body builder who consumed ma huang extract (400-600mg caffeine, 40-60mg ephedra, and other supplements) and creatine monohydrate (6g) for six weeks. In one case series, an athlete who consumed 6g creatine monohohydrate, 400-600mg caffeine, and 40-60mg ephedra for six weeks had a stroke (161). A combination of caffeine and creatine may increase risk of dehydration. In humans, caffeine had ergogenic effects after a withdrawal from creatine supplementation (162). In humans, combined use of creatine and caffeine had no effect on caffeine pharmacokinetics. Combined use had no effect on heart rate or blood lactate (163).
- CimetidineCimetidine: Cimetidine competes with creatinine (metabolic product of creatine) for renal tubular secretion and may increase the risk of adverse renal effects (164).
- CNS depressantsCNS depressants: A combination of creatine with this combination of medications may increase the risk of serious adverse effects and may decrease creatine efficacy. Phosphocreatine resynthesis is possibly inhibited by creatine. In randomized, controlled trials, caffeine antagonizes the ergogenic effects of creatine and counteracts its benefits on intense intermittent exercise performance (3; 4). It is not clear whether caffeine consumption as found in the average cup of coffee or tea also has this effect. A combination of caffeine, ephedra and creatine may increase risk for adverse side effects. In a case series, ischemic stroke was reported in a body builder who consumed ma huang extract (400-600mg caffeine, 40-60mg ephedra, and other supplements) and creatine monohydrate (6g) for six weeks. In one case series an athlete who consumed 6g creatine monohydrate, 400-600mg caffeine, and 40-60mg ephedra for six weeks had a stroke (161). A combination of caffeine and creatine may increase risk of dehydration. In humans, caffeine had ergogenic effects after a withdrawal from creatine supplementation (162). In humans, combined use of creatine and caffeine had no effect on caffeine pharmacokinetics. Combined use had no effect on heart rate or blood lactate (163).
- DiureticsDiuretics: Concomitant use with diuretic medications may increase diuretic effects, due to increased diuretic effects with creatine use (6). In a controlled trial, blood electrolytes showed no changes in those taking HMB plus creatine for six weeks (153). No changes in blood electrolytes were observed over 21 months of creatine supplementation in a human study (123).
- Ergot derivativesErgot derivatives: A combination of ergotamine and creatine may increase the risk of adverse effects and decrease creatine efficacy. Phosphocreatine resynthesis is possibly inhibited by creatine. Phosphocreatine resynthesis is possibly inhibited by creatine. In randomized, controlled trials, caffeine antagonizes the ergogenic effects of creatine and counteracts its benefits on intense intermittent exercise performance (3; 4). It is not clear whether caffeine consumption as found in the average cup of coffee or tea also has this effect. A combination of caffeine, ephedra and creatine may increase risk for adverse side effects. In a case series, ischemic stroke was reported in a body builder who consumed ma huang extract (400-600mg caffeine, 40-60mg ephedra, and other supplements) and creatine monohydrate (6g) for six weeks. In one case series, an athlete who consumed 6g creatine monohydrate, 400-600mg caffeine, and 40-60mg ephedra for six weeks had a stroke (161). A combination of caffeine and creatine may increase risk of dehydration. In humans, caffeine had ergogenic effects after a withdrawal from creatine supplementation (162). In humans, combined use of creatine and caffeine had no effect on caffeine pharmacokinetics. Combined use had no effect on heart rate or blood lactate (163).
- Gallium nitrateGallium nitrate: A combination of gallium nitrate and creatine may increase the risk of nephrotoxicity (119; 147; 15). Renal function should be monitored.
- Hepatotoxic agentsHepatotoxic agents: Creatine use may increase liver enzymes. Animal studies indicate that transamidase activity is inhibited during creatine supplementation, but return to normal after removal of endogenous creatine. Similar studies in humans have not been performed (128). In a controlled trial, no changes were observed over 21 months of creatine use (123). In other controlled trials, no changes were observed in hepatic function indices (124; 165; 166). Non-significant increases in liver enzymes have also been noted in a human study (29).
- HydrocodoneHydrocodone: In an animal study, the combination of indomethacin with creatine, as measured by the carrageenan-induced paw edema test, showed the drug combination was more effective at reducing inflammation than either drug alone (6).
- LansoprazoleLansoprazole: In an animal study, the combination of indomethacin with creatine, as measured by the carrageenan-induced paw edema test, showed the drug combination was more effective at reducing inflammation than either drug alone (6).
- Nephrotoxic agentsNephrotoxic agents: In theory, the combination of creatine with nephrotoxic drugs, such as cyclosporin, aminoglycosides (amikacin, gentamicin and tobramycin), gallium nitrate, and tacrolimus, may adversely affect renal function and may be harmful to the kidneys, due to potential for increased nephrotoxic effects (119; 147; 15).
- NifedipineNifedipine: Combined use of nifedipine and creatine may improve stroke and cardiac indices and may be useful for the treatment of myocardial infarction. Like creatine, nifedipine has been shown to have positive effects when added to cardioplegic solution (167).
- OxycodoneOxycodone: In an animal study, the combination of indomethacin with creatine, as measured by the carrageenan-induced paw edema test, showed the drug combination was more effective at reducing inflammation than either drug alone (6).
- ProbenecidProbenecid: In theory, use of creatine with probenecid may increase the levels of creatine in the body, leading to increased side effects (119; 147; 15).
- RenallyeliminateddrugsRenallyeliminateddrugs: In theory, the combination of creatine with renally cleared drugs such as valacyclovir, may impair the renal clearance of the drug and may increase blood levels (119; 147; 15).
- Sodium bicarbonateSodium bicarbonate: In humans, there is a potential for additive effects with creatine for swimming performance (168)
- TacrolimusTacrolimus: Based on secondary sources, a combination of tacrolimus and creatine may increase the risk of nephrotoxicity (119; 147; 15). Renal function should be monitored.
- ValacyclovirValacyclovir: Based on secondary sources, a combination of valacyclovir and creatine may increase the risk of nephrotoxicity (119; 147; 15). Renal function should be monitored. A combination of valacyclovir and creatine may result in increased valacyclovir and acyclovir levels, resulting in increased toxicity if renal function is impaired.
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Creatine/Herb/Supplement Interactions:- Alpha-lipoic acidAlpha-lipoic acid: Addition of alpha-lipoic acid (1,000mg daily) to creatine and sucrose has been found to enhance glucose uptake into skeletal muscle in animal models (169). Muscle total creatine content was increased as compared to creatine alone or creatine with sucrose.
- Anti inflammatory herbsAnti inflammatory herbs: In an animal study, the combination of indomethacin with creatine, as measured by the carrageenan-induced paw edema test, showed the drug combination was more effective at reducing inflammation than either drug alone (6). The combination of creatine with nephrotoxic herbs may adversely affect renal function and be harmful to the kidneys. Renal function should be monitored.
- AntilipemicsAntilipemics: Daily supplementation with creatine can reduce plasma total cholesterol, triacylglycerides and VLDL-cholesterol (7) and thus may potentiate the effects of lipid lowering agents.
- AntineoplasticsAntineoplastics: Cyclocreatine, an analog of creatine, increased tumor-growth delay in SW2 small-cell lung cancer cells when added with standard anticancer agents including cis-diaminedichloroplatinum(II), cyclophosphamide, adriamycin, or 5-fluorouracil (160). Thus, concomitant use with these or with other antineoplastic agents may potentiate effects or lead to toxicity.
- ArginineArginine: In humans, supplementation with creatine, in combination with low arginine, may increase creatine status more dramatically (170).
- CaffeineCaffeine: In randomized, controlled trials, caffeine antagonizes the ergogenic effects of creatine and counteracts its benefits on intense intermittent exercise performance (3; 4). It is not clear whether caffeine consumption as found in the average cup of coffee or tea also has this effect. A combination of caffeine, ephedra, and creatine may increase risk for adverse side effects. In a case series, ischemic stroke was reported in a body builder who consumed ma huang extract (400-600mg caffeine, 40-60mg ephedra, and other supplements) and creatine monohydrate (6g) for six weeks. In one case series, an athlete who consumed 6g creatine monohydrate, 400-600mg caffeine, and 40-60mg ephedra for six weeks had a stroke (161). A combination of caffeine and creatine may increase risk of dehydration. In humans, caffeine had ergogenic effects after a withdrawal from creatine supplementation (162). In humans, combined use of creatine and caffeine had no effect on caffeine pharmacokinetics. Furthermore, combined use had no effect on heart rate or blood lactate (163).
- DiureticsDiuretics: Concomitant use with diuretic herbs and supplements may increase diuretic effects, due to increased diuretic effects with creatine use (6). In a controlled trial, blood electrolytes showed no changes in those taking HMB plus creatine for six weeks (153). No changes in blood electrolytes were observed over 21 months of creatine supplementation in a human study (123).
- EphedraEphedra: A combination of caffeine, ephedra, and creatine may increase risk for adverse side effects. In a case series, ischemic stroke was reported in a body builder who consumed ma huang extract (400-600mg caffeine, 40-60mg ephedra, and other supplements) and creatine monohydrate (6g) for six weeks. In one study an athlete who consumed 6g creatine monohydrate, 400-600mg caffeine, and 40-60mg ephedra for six weeks had a stroke (161).
- Fat soluble vitaminsFat soluble vitamins: In humans, creatine plus vitamin supplements may lower homocysteine to a greater extent than vitamin supplements alone (171). Creatine may lower the effectiveness of vitamins A, D, E and K.
- HydroxymethylbutyrateHydroxymethylbutyrate: In a controlled study, supplementation of hydroxymethylbutyrate (HMB) with creatine had no adverse effects in a clinically controlled study for six weeks (153). HMB and creatine may have additive effects on lean body mass (32) and HMB may antagonize creatine induced increases in creatine phosphokinase (32). However, no additive effects were noted in rugby players (172).
- Hepatotoxic herbs and supplementsHepatotoxic herbs and supplements: Creatine use may increase liver enzymes. Animal studies indicate that transamidase activity is inhibited during creatine supplementation but returns to normal after removal of endogenous creatine. Similar studies in humans have not been performed (128). In a controlled trial, no changes were observed over 21 months of creatine use (123). In other controlled trials, no changes were observed in hepatic function indices (124; 165; 166). Non-significant increases in liver enzymes also have been noted in a human study (29).
- HypoglycemicsHypoglycemics: Creatine may alter activities of insulin and other blood glucose lowering agents. In a controlled study, no changes were observed in those taking HMB plus creatine for six weeks (153). Decreased glucose levels in creatine-supplemented animals have been suggested (154). In humans, neither acute nor short-term creatine supplementation influenced glucose tolerance or levels (155; 156; 157). High concentrations of insulin may enhance muscle creatine accumulation (158). This is a result of an insulin-induced transport of creatine from circulation to skeletal muscle (158) vs. creatine delivery (159). Decreased insulin levels in animals have been suggested (154). In humans, neither acute nor short-term creatine supplementation influenced measures of insulin sensitivity (156).
- MagnesiumMagnesium: In a randomized, controlled study, magnesium and creatine have been used together to increase muscle strength and power (173).
- Nephrotoxic agentsNephrotoxic agents: In theory, the combination of creatine with nephrotoxic herbs, may adversely affect renal function and may be harmful to the kidneys, due to potential for increased nephrotoxic effects (119; 147; 15).
- PyruvatePyruvate: In a randomized, controlled study, creatine in combination with pyruvate has been shown to increase lean body mass and total body mass, as well as bench press and static vertical jump (174).
- Renally eliminated herbs and supplementsRenally eliminated herbs and supplements: In theory, the combination of creatine with renally cleared herbs, may impair the renal clearance of the herb and may increase blood levels (119; 147; 15).
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Creatine/Food Interactions:- CarbohydratesCarbohydrates: In humans, absorption of creatine appears to be enhanced by concurrent carbohydrate ingestion (175; 137; 77; 176). In a randomized, controlled trial, post-exercise supplementation with carbohydrate and creatine results in similar strength gains as protein and carbohydrate (177). In humans, ingesting creatine with carbohydrates augmented glycogen supercompensation in exercised muscle (178).
- Reduced food intakeReduced food intake: In humans, during recovery of body mass loss, creatine does not accelerate body mass restoration (179). In humans, creatine increases muscle total and phosphocreatine with dietary restriction (180). Urinary nitrogen losses were similar to placebo.
- Vegetarian dietVegetarian diet: Anecdotally, lower levels of creatine have been reported in vegetarians.
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Creatine/Lab Interactions:- Adenine nucleotidesAdenine nucleotides: No changes have been reported in muscle (181; 139).
- AlbuminAlbumin: Serum levels remained unchanged with 12mg creatine for four weeks in hemodialysis patients (111) and after approximately one year in patients with amyotrophic lateral sclerosis (126). In a creatine consumer group, there were no differences vs. control for plasma contents and urine excretion rates of albumin (15).
- AmmoniaAmmonia: In controlled trials, creatine lowered serum levels of ammonia during cycling exercises (182; 183; 184). No effects have also been shown (181).
- ASTAST: In humans, significant elevations in AST have been noted with creatine supplementation (185).
- BicarbonateBicarbonate: Blood levels of bicarbonate were significantly decreased in humans taking HMB (153). Thus, use of creatine may yield similar results.
- CortisolCortisol: No changes in cortisol were observed in those taking HMB plus creatine for six weeks (153). However, in another clinical study, cortisol significantly increased after one week of 0.3g/kg creatine (+29%), then returned to baseline at week two (58).
- CreatineCreatine: In humans, serum and urinary creatine increased significantly in those taking supplemental creatine (41; 30; 125; 165; 186; 38; 81). Muscle creatine has been shown to increase in some human studies (187; 182; 188). Early studies reported that radiation-induced creatinuria in rats can be prevented by administration of creatine (189). No differences in creatine status after supplementation were observed in young (24 years) vs. old (70 years) human subjects (190). After supplementation, muscle phosphocreatine increased further in the young subjects. In humans, increased muscle phosphocreatine has been reported by others, even after energy restriction (191; 180). No effect on muscle phosphocreatine has been reported (139). In a clinical trial, vegetarians ingesting creatine (0.25g/kg for seven days, then 0.0625g/kg for 49 days) had a greater increase in total creatine and phosphocreatine than nonvegetarians (46).
- Creatine kinaseCreatine kinase: In a case series, significant elevations in creatine kinase have been noted following creatine supplementation (185).
- Creatinine (serum)Creatinine (serum): Creatine is metabolized to creatinine. Thus creatine supplementation can potentially result in higher than normal serum creatinine levels, despite normal renal function. Higher serum creatinine was noted in at least two randomized, controlled trials (25g daily for seven days and then 5g daily for 11 weeks) (186; 41). However, in a creatine consumer group there were no differences vs. control for plasma contents and urinary excretion rates of creatinine (15).
- Creatinine (urine)Creatinine (urine): Creatine supplementation can also potentially result in higher than normal urine creatinine levels, despite normal renal function. Higher urinary creatinine has been reported in a randomized, controlled trial (81). However, in humans there was no change in urinary creatinine output in 40 athletes ingesting 0.1g/kg daily for seven days (59) of creatine in the heat, and there was no significant alterations in creatinine excretion rates obtained from 24-hour and exercise urine collection periods (80). In a creatine consumer group there were no differences vs. control for plasma contents and urine excretion rates of creatinine (15).
- ElectrolytesElectrolytes: In a controlled trial, blood electrolytes showed no changes in those taking HMB plus creatine for six weeks (153). No changes in blood electrolytes were observed over 21 months of creatine supplementation in a human study (123).
- GlucagonGlucagon: Increased glucagon levels in creatine-supplemented animals have been suggested (154).
- GlucoseGlucose: In a controlled study, no changes were observed in those taking HMB plus creatine for six weeks (153). Decreased glucose levels in creatine-supplemented animals have been suggested (154). In humans, neither acute nor short-term creatine supplementation influenced glucose tolerance or levels (155; 156; 157). High concentrations of insulin may enhance muscle creatine accumulation (158). This is a result of an insulin-induced transport of creatine from circulation to skeletal muscle (158) vs. creatine delivery (159). Decreased insulin levels in animals have been suggested (154). In humans, neither acute nor short-term creatine supplementation influenced measures of insulin sensitivity (156).
- GlycogenGlycogen: In humans, muscle glycogen loading capacity is influenced by its initial levels of creatine (192). In a randomized, controlled trial, neither acute nor short-term creatine supplementation influenced skeletal muscle glycogen content (156).
- Growth hormoneGrowth hormone: In humans, the exercise-induced increase of serum growth hormone was not altered by acute creatine intake (193; 139; 181).
- Guanidino compoundsGuanidino compounds: In humans, plasma guanidinoacetate levels were reduced during creatine loading and maintenance phase (194). Several circulating guanidino compound levels were significantly altered after creatine loading but not during the maintenance phase: homoarginine (+35%), alpha-keto-delta-guanidinovaleric acid (+45%), and argininic acid (+75%) were increased, whereas guanidinosuccinate was reduced (-25%).
- HematocritHematocrit: Hematocrit remained unchanged after supplementation with 12mg creatine for four weeks in hemodialysis patients (111).
- HomocysteineHomocysteine: Creatine supplementation may lower homocysteine levels (195).
- HypoxanthineHypoxanthine: In a randomized, controlled trial, creatine lowered serum levels of hypoxanthine during cycling exercise (182).
- InsulinInsulin: High concentrations of insulin may enhance muscle creatine accumulation (158). This is a result of an insulin-induced transport of creatine from circulation to skeletal muscle (158) vs. creatine delivery (159). Decreased insulin levels in animals have been suggested (154). In humans, neither acute nor short-term creatine supplementation influenced measures of insulin sensitivity (156).
- LactateLactate: In human trials, measured lactate levels were similar between creatine and placebo (85) or had no significant changes (182; 184; 196; 139; 181; 86; 184; 197; 198; 163; 157; 191; 155). In a controlled trial, lactate threshold rose significantly following creatine supplementation (71). Increased lactate has been reported in a controlled trial (186). Decreased lactate has been reported in controlled trials (183; 70).
- LDHLDH: In humans, significant elevations have been noted following creatine supplementation (185).
- LipidsLipids: Daily supplementation with creatine can reduce plasma total cholesterol, triacylglycerides, and VLDL-cholesterol (7). Reduced cholesterol was noted in at least one study (28). Cholesterol, triglycerides, LDL-cholesterol, and cholesterol/HDL ratio levels were significantly reduced with creatine supplementation (15.75g daily for five days followed by 5.25g for 20 days) (199). No changes in lipids were found in humans taking HMB plus creatine for six weeks (153). No changes in lipids were observed after 21 months of creatine use in humans (123). No changes have been observed in other controlled studies (41).
- Liver enzymesLiver enzymes: Creatine use may increase liver enzymes. Animal studies indicated that transamidase activity is inhibited during creatine supplementation but returned to normal after removal of endogenous creatine. Similar studies in humans have not been performed (128). In a controlled trial, no changes were observed over 21 months of creatine use (123). In other controlled trials, no changes were observed in hepatic function indices (124; 165; 166). Non-significant increases in liver enzymes have also been noted in a human study (29).
- LymphocytesLymphocytes: In a controlled trial, lymphocyte counts were within normal limits for those taking HMB plus creatine for six weeks (153). In a controlled trial, no changes were observed over 21 months of creatine use (123).
- MonocytesMonocytes: In a controlled trial, monocyte counts were within normal limits for those taking HMB plus creatine for six weeks (153).
- pHpH: No effect on pH has been noted with creatine use, in a human study (198).
- PotassiumPotassium: In humans, creatine supplementation, in the heat, resulted in no significant alterations in potassium excretion rates obtained from 24 hour and exercise urine collection periods (80).
- SodiumSodium: In humans, creatine supplementation, in the heat, resulted in no significant alterations in sodium, potassium, or creatinine excretion rates obtained from 24-hour and exercise urine collection periods (80).
- TestosteroneTestosterone: In a controlled trial, no changes were observed with HMB plus creatine use over six weeks (153). In humans, the exercise-induced increase of serum testosterone was not altered by acute creatine intake (193).
- UreaUrea: In controlled trials, no changes were observed in those taking HMB plus creatine for six weeks to approximately one year (126; 153). In a creatine consumer group, there were no differences vs. control for plasma contents and urine excretion rates of urea (15).
- Uric acidUric acid: In humans, no effect of creatine supplementation on pre- or post-exercise uric acid has been noted (157). In a controlled trial, increases in urate in urine with high dose creatine have been observed (53). In humans, decreased uric acid at exhaustion following creatine supplementation has been observed (200).
- Other (general)Other (general): In a controlled trial, no changes were observed in metabolic markers, muscle enzymes, and hematological markers over 21 months (123). No changes were observed in hematological indices, renal indices or muscle damage indices in a randomized, controlled trial (124).
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Copyright © 2011 Natural Standard (www.naturalstandard.com)
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The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.
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