Creatine

Assessment and Plan: Creatine

• Creatine is available in nutrition stores throughout the country in the form of creatine monohydrate. It has been used in research as an investigational agent in an intravenous form known as creatine phosphate.

• Creatine monhydrate dose:
  • Most research reviewed on use of creatine documented that this supplement is safe, well-tolerated and has with minimal side effects in healthy adult men and women as well as in elderly patients at doses of 3-5 mg per day up to 2 years.
  • Most common for healthy adults: Creatine monohydrate, 20 grams per day in 4 divided doses for 5 days followed by a maintenance dose of 2-5 grams per day for 8-12 weeks (3).
  • Highest dose noted in research was 20 grams by mouth daily for 8 weeks (3), which may be unsafe and is not recommended.
  • The longest duration of creatine dosing studied was 4 grams per day by mouth for 2 years by elderly patients (17).
  • In children and adolescents the safety of creatine is not known (15), therefore creatine use is not advised in this group.

• Creatine and enhancement of athletic performance:
  • Creatine supplementation improves strength in older men: Men at an average age of 70.4 years old significantly increased lean mass compared to placebo (3.3 kg vs 1.3 kg), higher leg press weight (50.1 kg vs 31.3kg), knee extension endurance (21 reps vs 14 reps), and average power output (26.7 watts vs 18 watts) (1). Additional research on 55-82 year olds by Dalbo, VJ et al concluded that creatine be strongly considered as a safe, inexpensive and effective nutritional intervention to help slow the rate of muscle deterioration with age, particularly when consumed in conjunction with a resistance training regimen (5).
  • Creatine use improves strength in both men and women: A short regimen of only 0.35 grams per kg of fat-free mass for 3 days increased body mass, thigh muscle volume, and improved sprint performance with a greater effect for men than women during the first sprint but in later sprints women experienced a greater effect (2).
  • A meta-analysis of 16 studies showed that creatine groups consistently had higher strength than placebo groups in weight lifting tasks but no enhancement of performance was seen in cycling or endurance activities (3). Other research has confirmed these findings (4).
  • Combining whey and creatine monohydrate appears to increase lean tissue mass better than whey protein alone and better than placebo (6), but it is unknown whether whey protein provides greater benefit than creatine monohydrate alone.

• Creatine and bone density: Creatine plus resistance training appeared to increase bone density on dual energy X-ray absorptiometry (Dexa scan) over placebo plus resistance training for 12 weeks. (0.3 grams per kilogram of creatine monohydrate was given for 5 days and then 0.07 grams per kilogram) (7).

• Creatine monohydrate and patients on dialysis: A small 12 mg oral dose of creatine monohydrate for 4 weeks resulted in a 60% reduction the frequency of muscle cramps over placebo without major side effects (9).

• Creatine and chronic heart failure: 20 g of creatine for 5 days increased the amount of exercise subjects could complete before reaching exhaustion while also lowering serum ammonia and lactate levels with use of creatine but not with placebo (10).

• Creatine phosphate in heart surgery: Creatine phosphate given IV perioperatively for coronary bypass surgery appears to show improved heart function (12), reduce ventricular arrhythmias (11,12), and reduce the use of inotropic drugs (12).

• Creatine use in Parkinson’s disease: Patients taking creatine did not appear to reduce the loss of dopaminergic neurons but they did not require as much therapy as placebo for Parkinson’s symptoms (17).

• Creatine and cognition in older patients: Creatine supplementation by elderly subjects at a dose of 5 grams four times a day for 1 week improved random number generation, forward number recall, spatial recall, and long-term memory tasks over placebo but creatine did not improve backward number recall (18).

• Creatine safety concerns, adverse reactions, interactions, and long term use:
  • Creatine safety:
  • Creatine is most likely safe in healthy individuals excluding children and adolescents at doses of 3-5 grams per day and analysis of kidney function prior to creatine supplementation should be considered for safety reasons but in healthy subjects, this appears unnecessary (19).
  • High-dose creatine supplementation of over 3-5 grams per day should not be used by anyone with pre-existing kidney disease or those with a potential risk for renal dysfunction (diabetes, hypertension, reduced glomerular filtration rate). In these patients, creatine should only be considered if kidney function will be evaluated and creatine use will be monitored under a physician’s direction prior to taking.
  • Patients should be advised to report major reactions during use of creatine.
  • Reports have linked creatine to weight gain, cramping, dehydration, diarrhea, dizziness, and may decrease renal function (4).
  • Creatine may be unsafe when combined with other supplements (20).
  • Creatine monohydrate and androgens: Creatine loading for one week plus maintenance dose for 2 weeks did not alter testosterone levels, but dihydrotestosterone (DHT) levels increased by 56% after 7 days of creatine loading and remained 40% above baseline during maintenance which showed that creatine appears to readily convert testosterone to DHT at an increased rate which may be associated with hair loss, benign prostate hypertrophy and prostate cancer (16).
  • Long term use of creatine:
    • Creatine at a dose of 4 grams per day was determined safe in elderly Parkinson’s disease patients with only gastrointestinal complaints, an expected rise in creatinine with breakdown of creatine, normal renal tubular function, and normal glomerular kidney function with monitoring over the duration of 2 years (17).
    • High protein diet plus creatine used by healthy adults at an oral dose of 20 grams per day for 5 days plus 5 grams daily for 12 weeks showed no significant change in markers of renal function including creatinine clearance, urine urea, serum urea, albuminuria, proteinuria, and serum electrolytes between baseline and after 12 weeks compared to controls (21).
  • Case reports
    • A 20-year-old man taking creatine at 20 gm/day for 4 weeks resulted in acute kidney injury (19).
    • An 18-year-old man taking the recommended loading and maintenance doses developed acute tubular necrosis which resolved after 25 days (13).
    • A 24-year-old taking creatine and multiple other supplements for bodybuilding developed acute interstitial nephritis diagnosed by renal biopsy but multiple other supplements may have been the underlying cause (14).
    • A young bodybuilder in good health developed ischemic stroke after taking MaHuang extract (20 mg ephedra alkaloids), 200 mg caffeine, 100 mg L-carnitine, 200 μg chromium, 6000 mg creatine monohydrate, 1000 mg taurine,100 mg inosine, 5 mg coenzyme Q10, and daily use of 40–60 mg ephedra alkaloids, 400–600 mg caffeine, and 6000 mg creatine monohydrate for 6 weeks prior to having the stroke (20).