Creatine is a well-researched sports supplement. Combined with resistance training, it can increase strength, muscle mass, and post-exercise recovery. Scientists are also investigating if creatine can rev up energy production in the body and protect the heart and brain. Read on to learn about its potential benefits, side effects, and proven supplementation protocols.
What is Creatine?
Introduction
Creatine (α-methyl guanidine-acetic acid) is a substance naturally produced in the body from amino acids. Most of it is stored in muscle cells and released during physical activity. Creatine supplements raise muscle creatine stores, which enhances exercise performance and helps build muscles. Creatine food sources include meat and fish [1, 2].
Most of the body’s creatine is stored in skeletal muscles (95%) as phosphocreatine; the remainder is found in the brain, kidney, and liver. Phosphocreatine is charged with powerful phosphate groups that release a large amount of energy when the muscles need it. The average person uses about 2 g/day of creatine while athletes and bodybuilders have much higher requirements [3].
Creatine has become one of the most widely used nutritional supplements. It’s one of the best-researched supplements for increasing muscle strength and power in athletes. Less known are its benefits beyond athletic performance, which extend to people with various muscle-wasting and neurological diseases [1].
Snapshot
PROs
- Safely increases muscle mass, strength, and exercise performance
- Reduces post-exercise fatigue
- Great for power training
- Protects the brain
CONs
- Doesn’t impact endurance-type or cardio exercise performance
- High doses may cause stomach discomfort or nausea
Power vs. Endurance Training
While almost every athlete has probably tried creatine at least once in their life, not everyone will experience the desired gains. Creatine is a safe and legal sports supplement but it’s not equally effective for all types of exercise. If you’re wondering when or if you should use creatine, have a close look at your exercise regime and your training goals [4].
Creatine will offer significant gains in strength and performance during high-intensity, short-duration, anaerobic training, i.e. high-power bursts aimed at increasing maximal output [4].
Creatine won’t have an effect on endurance-type, aerobic training, such as long-distance running and swimming. You’ll still see improvements in muscle mass and fatigue if you combine strength training alongside endurance-type sports [4].
To determine when to take creatine and how much you need, you should dive deeper to understand exactly what creatine does in your body.
What Does Creatine Do?
The ATP-phosphocreatine system has immense power potential. Muscle stores of phosphocreatine release energy and rapidly boost the production of new ATP energy molecules. The burst of energy needed to sustain exercise with maximal effort normally lasts for only 5 to 10 seconds after which a drop in phosphocreatine causes fatigue [4].
Peaks in strength and exercise capacity during short-term, high-intensity power training depends on two factors:
- ATP levels
- Phosphocreatine stores
Creatine supplementation boosts strength by affecting both: it regenerates ATP supplies during exercise and phosphocreatine supplies after exercise, during recovery [4].
For energy to be released and used, ATP needs to be broken down to ADP (cleaving one of the phosphates in ATP off). ADP is returned to its high-energy state of ATP in different ways during anaerobic exercise (sugar breakdown or glycolysis) vs. aerobic exercise (oxidative phosphorylation).
With high-intensity exercise, muscles rely on the anaerobic system, which uses phosphocreatine and muscle sugar stores (glycogen) as fuels. This is why the degree to which muscles will use creatine directly depends on the intensity and duration of the exercise. Muscles need the most phosphocreatine during the most intense and maximally demanding periods of exercise or sport [4].
For example, a dose of 30 g/day of creatine for 14 days enhanced power during short-term, maximal exercise by increasing ATP production and phosphocreatine availability – going back to the two factors outlined above [4].
Creatine supplements may also “load” muscles by increasing phosphocreatine stores, which in turn increases energy production during explosive, high-intensity exercise bouts [4].
Increasing phosphocreatine stores may also aid in muscle recovery. Higher phosphocreatine levels may help ‘mop up’ the acid-producing exercise byproducts and balance pH levels in the muscles, allowing for continued exercise with minimal fatigue [4].
Creatine is a small molecule that attracts water. These water molecules follow creatine into the cells, which swell as a result. Cell swelling is a so-called anabolic signal that increases the production of proteins, glycogen sugar stores, and DNA while minimizing protein breakdown [5, 6, 4].
Health Benefits of Creatine
Possibly Effective:
1-2) Exercise Performance and Muscle Strength
Creatine supplements increase phosphocreatine stores in muscles, which in turn boost the production of new ATP energy molecules. All cells in your body use ATP as a source of energy but creatine will mainly fuel your muscles and increase your performance during short, high-intensity exercise bouts [1, 2].
Creatine supplementation improves strength and performance during high-intensity, short-duration resistance training according to a large review of 22 studies. According to this review, creatine with resistance training increases [7, 8, 9, 10]:
- Muscle strength by 20% (8% greater than placebo)
- Weightlifting performance (maximal repetitions at a given percent of maximal strength) by 26% (14% greater than placebo)
- Bench press weightlifting performance by up to 43%
Strength/resistance training specifically amplifies its muscle-building benefits. In a study of 32 healthy men during 16 weeks of heavy-resistance training, creatine (6 – 24 g/day) increased muscle growth better than taking 20 g/day of proteins [11].
In a study of 19 men, creatine enhanced free-fat mass, weight-lifting capacity and overall physical performance, and muscle appearance in response to heavy resistance training. The training regime was periodized over 12 weeks and higher creatine doses are given over the first week (25 g/day) followed by a lower maintenance dose (5 g/day) [12].
Creatine loading over five days in 15 college women improved power and delayed muscle fatigue during high-intensity cycling. The loading phase consisted of 20 g/day of creatine and 40 g/day of dextrose [13].
High levels of the protein myostatin can slow or totally block the growth of new muscles. Creatine with resistance training can increase the growth potential of muscles by lowering myostatin. In one study on healthy 27 men, creatine prevented increases in myostatin, which adds to its amplifying effects on muscle-building in power athletes [14].
In rats, creatine supplementation lowered markers of oxidative damage (lipid peroxidation) and enhanced anaerobic performance [15].
Synergies
Fenugreek enhances creatine uptake; combining the two can maximize strength and training adaptation gains.
In a trial of 47 men, creatine (5 g/day) with fenugreek extract (900 mg/day) increased upper body strength and adaptation over an 8-week resistance training program. This combination was as effective as the more classic creatine plus carbohydrates combo, which often involves excessive amounts of simple sugars such as dextrose (70 g/day) [16].
3-4) Muscle Damage and Fatigue
In one study on 14 men, creatine with carbohydrates 5 days before and 2 weeks after a resistance training improved recovery of the knee extensor muscle. Maltodextrin and creatine reduced inflammation after a 30km race in runners, while creatine alone also lowered inflammation markers (TNF-a and CRP) in 24 young sprinters [17, 18, 19].
In 8 Ironman triathletes, creatine with maltodextrin lowered markers of muscle damage better than just maltodextrin [20].
Creatine supplementation reduced leg fatigue after exercising in the heat in a subset of endurance-trained men. Those who responded to creatine supplements had better creatine muscle uptake [21].
In one study on 22 weight-trained men, however, creatine didn’t improve muscle recovery. In this study, creatine was given for 10 days before a single resistance training session. Unlike in most other studies, the participants didn’t receive creatine in the post-exercise recovery phase, which may be a requirement for replenishing phosphocreatine [22].
5) Age-Related Muscle Loss
Creatine supplementation in the elderly may delay muscle wasting, improve endurance, and increase strength [23].
Combined with resistance training, creatine increased lean tissue mass, leg strength, endurance, and power in a trial of 30 older men. Higher creatine doses were used over the first 5 days (loading phase) followed by lower maintenance doses [24].
In two studies of 46 older people, creatine combined with exercise increased muscle strength, weight, fat-free mass, and functional capacity [25, 26].
6) Cognitive Function
The effects of creatine can be extended from its more frequently discussed and evident benefits on muscle fatigue to reducing mental fatigue and improving cognition.
In sleep-deprived rugby players, creatine (20 g/day) improved mood and cognitive skills after supplementing for a week. In another study, creatine improved complex cognitive skills taken for 7 days before sleep deprivation combined with moderate-intensity exercise [27, 28].
These interesting studies suggest that creatine may reverse “brain fog” symptoms caused by stressors such as lack of sleep and circadian rhythm imbalances, which are common in athletes or in people leading a modern, fast lifestyle.
Vegetarian diets lack the main food sources of creatine (meat and fish). Creatine supplements improved processing speed, working memory, and intelligence in 45 vegetarians. Creatine’s vital effect on energy use probably underlies these nootropic effects. By raising brain creatine, supplements increase the brain’s energy capacity and enhance cognitive performance [29, 30].
Preventing a decline in cognition is especially important in the elderly. Creatine (20 g/day) improved cognitive performance and quality of life in one study of 27 elderly people after just 2 weeks [31, 32].
Insufficient Evidence:
No valid clinical evidence supports the use of creatine for any of the conditions in this section. Below is a summary of up-to-date animal studies, cell-based research, or low-quality clinical trials which should spark further investigation. However, you shouldn’t interpret them as supportive of any health benefit.
7) Testosterone Levels
In studies spanning both amateurs and elite athletes, creatine increased testosterone levels. Typical doses were used (around 50 – 100 mg/kg) but the effect was not consistent.
For example, creatine increased testosterone in sprint-swimmers by 14%, had a significant effect in sleep-deprived elite rugby players, but only a barely noticeable effect in healthy college football or rugby players [33, 34, 35, 36, 37, 38].
Further trials should cast more light on the connection between creatine supplementation and testosterone levels.
8) Brain Protection
Creatine supplements (4 g/day) added to SSRI antidepressants improved symptoms in 5 women suffering from depression who previously didn’t respond to therapy. Brain imaging revealed that creatine increased phosphocreatine levels, which explains its mood-enhancing effects [39].
In animals, creatine was used to improve symptoms of Alzheimer’s Disease, stroke, epilepsy, and brain or spinal cord injuries [40, 41, 42, 43].
In brain cells, creatine protected GABA neurons from damage [44].
9) Parkinson’s Disease
Parkinson disease often leads to poor fitness, decreased muscle mass, reduced muscle strength, and fatigue.
Creatine improved upper body strength and enhanced the benefits of resistance training in one study of 20 people with Parkinson’s Disease. Similar to its use in athletes, creatine was loaded in higher doses for 5 days (20 g/day) and then maintained at a lower dose (5 g/day) [45].
In mice, creatine prevented a drop in dopamine levels. Low dopamine and the destruction of dopamine neurons is the hallmark of Parkinson’s Disease that triggers common symptoms [46].
Although promising, larger clinical trials would need to assess if creatine supplements alone may also improve other symptoms in Parkinson’s Disease.
Synergies
In combination with Coenzyme Q10, creatine delayed the cognitive decline in a study of 75 people with mild cognitive impairment and Parkinson’s Disease. This combination was given over a year and a half at a steady dose (10 g/day creatine, 300 mg/day CoQ10). It could also lower plasma phospholipid levels, high levels of which point to poor cognitive function [47, 48].
10) Heart Health
Creatine (20 g/day) lowered high triglycerides, LDL, and cholesterol in one study of 37 people. Healthy blood lipid levels lower the risk of heart attacks and prevent the narrowing of blood vessels [49].
High homocysteine levels increase the risk of heart disease. In one study, creatine added to a multivitamin supplement lowered homocysteine levels in healthy people better than multivitamins alone after 4 weeks. In another trial, however, creatine did not lower homocysteine [50, 51].
More studies are needed to investigate the effects of creatine supplementation on heart health.
11) Blood Sugar Levels
Creatine (10 g/day) along with cardio training reduced blood sugar levels in a trial of 20 healthy men. Creatine does not affect insulin sensitivity or insulin levels [52, 53].
Creatine supplements greatly lowered blood sugars in several studies on animals with diabetes. These findings may not hold true in people with diabetes. So far, no clinical studies of creatine in diabetics have been carried out [53].
Genetics
In rat muscles, creatine increased the expression of the GLUT4 gene. This gene is also activated by exercise and codes for the main insulin-responsive glucose transporter in the body. Increased GLUT4 activity improves insulin sensitivity and may provide benefits for people with diabetes [54, 55].
12) Bone Health
In postmenopausal women, creatine combined with strength training improved the quality of life and reduced symptoms of knee osteoarthritis (such as pain and stiffness). Creatine was loaded at 20 g/day for one week and then maintained at 5 g/day for another 11 weeks [56].
Creatine works together with bone growth factors to increase the activity of bone-building cells. In cell-based studies, it increased mineralization [57].
Possibly Ineffective:
Based on the available clinical evidence, creatine doesn’t seem to help with:
- Amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease) [58, 59]
- Huntington’s disease (a movement disorder) [60, 61]
Creatine Side Effects & Safety
This list does not cover all possible side effects. Contact your doctor or pharmacist if you notice any other side effects. In the US, you may report side effects to the FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch. In Canada, you may report side effects to Health Canada at 1-866-234-2345.
Creatine supplementation is likely safe at doses ranging from 5 – 30 g/day. Side effects such as stomach pain and cramping usually result from taking too much creatine at once or not staying hydrated [62, 63, 64].
To reduce the risk of stomach side effects, the daily dose is usually split up into 3 to 4 equal parts throughout the day, especially during the loading phase.
Creatine also causes water retention in the early stages of supplementation, which is accompanied by weight gain [65].
Does It Damage the Kidneys?
Creatine was safe and posed no risk to the kidneys in short- (5 days), medium- (14 days), and long-term (10 months to 5 years) studies [66].
Most of the public worries stem from a single case study of creatine supplementation in a man with kidney disease [66].
Creatine vs. Creatinine
Creatine is broken down into creatinine, which is normally quickly removed by the kidneys. Creatinine is a marker of kidney disease, as damaged kidneys can’t clear creatinine from the body, leading to its buildup in the blood. If a person with kidney damage takes creatine supplements, their creatinine levels will dramatically increase, as the above-mentioned case demonstrates [66].
In healthy people, only high loading doses of creatine may slightly increase creatinine levels. If you do a creatinine test while taking high creatine doses (~20 g/day), your doctor could pick up this false positive error and assume you have kidney disease if unaware of your supplementation regime [66].
Most athletes have increased creatinine levels, regardless of creatine supplementation. In fact, if creatinine was used as the only measure of kidney function, it would appear as if nearly all athletes are experiencing kidney issues [66].
Pregnancy
Creatine is generally considered safe, but its benefits for pregnant women have not been confirmed. Creatine supplements may help maintain energy levels and acid-base balance during pregnancy. It may also protect babies from birth asphyxia, which occurs when a baby’s brain and other organs lack oxygen and nutrients before, during or right after birth [67].
More research is needed for the safety of creatine during pregnancy to be determined. To stay on the safe side, avoid taking creatine during pregnancy unless prescribed by your doctor.
Supplementing with Creatine
Foods
A typical diet consisting of both meat and plant foods provides about 1 g/day of creatine. Meat (beef, chicken, rabbit) and fish contain the highest amount of creatine. Nonetheless, creatine doses required for most benefits (above 5 g/day) are difficult to achieve without supplements [68, 66, 69, 70, 71].
Supplement Formulations
Creatine supplements have not been approved by the FDA for medical use. In general, regulatory bodies aren’t assuring the quality, safety, and efficacy of supplements. Speak with your doctor before supplementing.
The most common and well-researched form of creatine is creatine monohydrate, used in the majority of studies covered in this article. Creatine monohydrate is absorbed almost completely (close to 100%) and has good bioavailability. As the gold standard, all other forms of creatine are compared to the monohydrate [72].
Other creatine formulations and combined ingredients include [72, 73, 66]:
- Tri-creatine citrate
- Creatine pyruvate
- Creatine phosphate
- Buffered creatine monohydrate (with magnesium-chelate)
- Creatine ethyl ester
- + sodium bicarbonate
- + beta-hydroxy-beta-methylbutyrate (HMB)
- + glycerol
- + glutamine,
- + beta-alanine
- + cinnulin extract
- Effervescent and liquid formulations
The vast number of different creatine forms can be confusing while the manufacturers’ marketing claims are often misleading. Based on the most up-to-date research [74, 66]:
- Beta-alanine with creatine may offer greater effects than creatine monohydrate alone
- Liquid creatine supplements increase peak creatine levels slightly more than solid creatine, which probably has no influence on the overall effects
No other creatine formulations have shown greater benefits than creatine monohydrate.
Dosage
The below doses may not apply to you personally. If your doctor suggests using a creatine supplement, work with them to find the optimal dosage according to your health condition and other factors.
The creatine dosage needed to increase muscle stores depends on your weight and muscle creatine levels prior to supplementation. If you rarely eat meat or fish, your creatine levels are probably lower and will increase more dramatically in response to supplements (20 – 40%). In people with high creatine muscle stores, the increase is less pronounced (10 – 20%) [66].
Exercise performance improvements have been linked to the magnitude of this increase [66].
Note: All dosing information in this section refers to creatine monohydrate.
Loading & Maintenance Protocol
Most clinical studies used a 2-phase (loading + maintenance) supplementation protocol. This is the fastest and most efficient way to maximize muscle creatine stores and strength. It involves taking higher doses for a few days, followed by lower maintenance doses [75, 66].
- The loading phase consists of taking about 20 g/day of creatine (0.3 grams/kg/day) for 5 – 7 days. The daily dose should be spread out into 3 – 4 smaller doses (e.g. 5g taken 4 times throughout the day).
- In the maintenance phase, creatine doses should be maintained at 3 – 5 g/day
According to the research, this protocol increases muscle creatine and phosphocreatine stores by 10 – 40% [66].
Some studies suggest that the loading phase can last only 2 – 3 days, especially if creatine is combined with higher protein and/or carbohydrate intake.
Alternative Protocols
A few studies used supplementation protocols without a loading phase. Skipping the loading phase can still increase creatine stores and muscle strength (e.g. 3 – 6 g/day for 4 – 12 weeks), but the gains are more gradual [66].
Others have suggested cycling strategies, which involve taking loading doses for 3 – 5 days every 3 – 4 weeks. Based on a couple of studies, these cycling protocols are effective at increasing and maintaining muscle creatine levels before they drop to baseline values, which normally occurs at about 4 – 6 weeks [66].
