Creatine loading involves taking a larger amount of creatine for the first few days of supplementation (usually around 0.3 grams per kilogram of bodyweight per day for 5–7 days) before reducing the daily dose to “maintenance” levels (at least 0.03 g/kg of bodyweight). The “alternative” to creatine loading involves simply taking a smaller dose (usually 3–5 g) of creatine every day.

Although both loading and non-loading strategies increase muscle creatine stores, creatine loading saturates muscles with creatine within the first week of supplementation, while non-loading takes around 4 weeks.^[77]

So, in short: no, you do not need to load creatine. However, creatine loading will lead to slightly quicker benefits than non-loading, with the downside being a potentially greater risk of experiencing digestive discomfort during the loading phase.

Several forms of creatine (other than creatine monohydrate) have been investigated, including creatine hydrochloride (creatine HCl), creatine citrate, creatine malate, “buffered” creatine (Kre-Alkalyn), and creatine ethyl ester. However, creatine monohydrate has the most scientific evidence behind it to support its efficacy and safety, and appears to be the cheapest form of creatine to purchase.^[93] For these reasons, creatine monohydrate is currently the best form of creatine.

Supplementation with either creatine or caffeine has consistently been shown to enhance exercise performance in most people, with these improvements thought to occur through separate physiological mechanisms.^[57][94] However, some evidence suggests that caffeine may blunt the performance-enhancing effect of creatine.

For example, one study found that six days of creatine loading increased the amount of torque produced by the quadriceps during a resistance exercise protocol, but adding a single dose of 5 mg of caffeine per kg of bodyweight during the final three days of the six-day creatine-loading protocol resulted in no improvement in exercise performance.^[79] Another study found that supplementation with creatine on 4–5 days per week before performing resistance exercise increased quadriceps muscle thickness, but the same dose of creatine plus 3 mg of caffeine per kg of bodyweight resulted in no increases in quadriceps muscle thickness.^[89] That said, the study was significantly underpowered, limiting its ability to detect small changes over time.

One potential explanation for why caffeine may interfere with creatine’s performance-enhancing properties is the opposing effect the two substances have on muscle relaxation time. More specifically, creatine increases calcium reuptake into the sarcoplasmic reticulum (a structure in muscle cells that stores calcium) and reduces muscle relaxation time, whereas caffeine increases calcium release from the sarcoplasmic reticulum and increases muscle relaxation time.^[81] Theoretically, reduced muscle relaxation time would be conducive to generating high amounts of force quickly and in rapid succession. Another potential explanation is that co-ingestion of creatine and caffeine may cause gastrointestinal distress.^[80][82]

With the above said, some studies have found that after 5–6 days of creatine loading, supplementation with caffeine before an exercise test enhanced exercise performance.^[83][84] Moreover, another study found no differences between supplementation with creatine, creatine plus 300 mg caffeine anhydrous, and creatine plus coffee for changes in strength, muscular endurance, or repeated sprint performance.^[82] That said, although caffeine didn’t appear to blunt creatine’s effects in this study, creatine also didn’t appear to have any beneficial effects to begin with. Additionally, studies that have investigated the acute and chronic effects of supplementation with multi-ingredient preworkout supplements containing both caffeine and creatine have reported enhanced exercise performance and muscular adaptations.^{[85][86][87][88]} However, the preworkout supplements also contained ergogenic ingredients other than creatine and caffeine (e.g., beta-alanine), which may have confounded the results.

Overall, the evidence suggesting that caffeine may blunt creatine’s performance-enhancing effects is weak and observed mainly in studies that implemented a creatine loading protocol or used high (5 mg/kg of bodyweight) doses of caffeine. This implies that this effect — if it exists at all — may not be relevant when creatine loading is not used or when lower doses of caffeine are taken. Until more research is available, it may be best to take caffeine after a creatine loading protocol has been completed, take lower (≤3 mg per kg of bodyweight) doses of caffeine when co-ingested with creatine, or simply take creatine and caffeine separately.

Creatine is found in appreciable quantities in skeletal and cardiac (heart) muscles.^[4][5] Therefore, meat (including poultry and fish) and meat-based products are the main dietary sources of creatine. Here are some examples of (uncooked) meats and their respective creatine content:

• Beef, with minimal visible connective tissue: 4.5 g per kg^[95]
• Chicken: 3.4 g/kg^[5]
• Rabbit: 3.4 g/kg^[5]
• Beef heart: 2.5 g/kg^[5]
• Pork heart: 1.5 g/kg^[4]

According to the NHANES III survey, the average daily consumption of creatine from food sources among Americans aged 19-39 years is around 1.1 g for men and 0.6 g for women.^[96]

Approximately 14.6 mmol of creatinine (creatine’s urinary metabolite) is lost on a daily basis in the average 70 kg healthy young man who has a creatine storage capacity of around 120 g.^[97] This represents a daily creatine loss rate of 1.6%–1.7% (around 2 g),^[98][99] and is the amount of creatine that has to be obtained from the diet or in supplemental form on a daily basis in order to maintain sufficient creatine levels. This value is usually around 20% lower in women and 45% lower in older adults due to lower levels of lean mass in these populations,^[97][100] and higher in individuals with higher than normal levels of lean mass.^[97]

In short, yes. This is because vegetarian diets lack the main dietary source of creatine — meat. With this in mind, and considering that around half of the daily need for creatine is obtained from the diet in omnivores,^[101] it’s no surprise that the muscle creatine content of individuals eating a vegetarian diet tends to be lower compared to individuals eating an omnivorous diet.^[102] Supplementation with creatine appears to close this gap.^[103] It’s worth noting that the levels of creatine in the brain are similar between vegetarians and omnivores.^[104][105]

Creatine monohydrate is the most common form of creatine, and, unless otherwise stated, the default form of creatine used in most studies.^[106] It has high intestinal absorption, with bioavailability of approximately 99% at standard doses of 5–10 g.^[107][108] That said, there is evidence to suggest that high acute doses (greater than 10g) of creatine monohydrate can saturate intestinal uptake, lowering absorption and increasing fecal secretion.^[109]

This basic form of creatine comes in two variants: creatine anhydrous and micronized creatine monohydrate.

Creatine anhydrous (anhydrous coming from the Greek “an-” meaning “without”, and “hydor” meaning “water”) is just creatine without the monohydrate. Creatine anhydrous is converted to creatine monohydrate when exposed to water.^[110][111] Because it does not contain monohydrate, creatine anhydrous is 100% creatine by weight, whereas creatine monohydrate is 88% creatine and 12% monohydrate by weight.

Micronized creatine monohydrate is creatine monohydrate that undergoes a mechanical process that reduces the particle size and increases the water solubility of creatine.

Other creatine formulations include:

• Creatine hydrochloride (Creatine HCl): This form is characterized by the creatine molecules being bound with hydrochloric acid. Creatine HCl is touted to require a lower dosage. However, this claim has not been scientifically proven and seems unlikely, since the stomach has an abundance of HCl anyway, and creatine will separate from HCl in the stomach. Thus, both creatine HCl and creatine monohydrate form free creatine in the stomach.
• Liquid creatine: This form has been found to be less effective than creatine monohydrate.^[112] The reduced effect is likely due to the passive breakdown of creatine over a period of days into creatinine, which occurs when creatine is suspended in solution.^[113] This is not an issue for people preparing a creatine solution at home, since it takes a few days for creatine to start degrading into creatinine.
• Buffered creatine (Kre-Alkalyn): This form of creatine has a higher pH level than creatine monohydrate. This is accomplished by adding alkaline powder to creatine. Buffered creatine is touted to enhance the effects of creatine monohydrate. However, this claim has not been scientifically proven. In fact, a 2012 study comparing buffered creatine to creatine monohydrate in 36 resistance-trained individuals found no significant differences between the two with regard to the accumulation of creatine in muscle tissue, training adaptations, or adverse effects.^[114]
• Creatine ethyl ester: This is an esterified form of creatine monohydrate that has been found to be less effective than creatine monohydrate for increasing muscle creatine levels and enhancing resistance training adaptations.^[115]
• Magnesium-chelated creatine: In this form of creatine, magnesium ions are attached to the creatine molecules. Limited research suggests that this form of creatine may have the same ergogenic effects as creatine monohydrate.^[116]
• Creatine nitrate: In this form of creatine, a nitrate (NO₃⁻) ion is attached to a creatine molecule. Despite creatine nitrate being more soluble in water, it doesn't appear to enhance athletic performance more than creatine monohydrate.^[117]

When you stop taking creatine, your serum levels of creatine will start to drop, returning to baseline levels after around four weeks.^{[119][77][123]} This length of time may vary slightly between individuals.^[124] Assuming a daily creatinine elimination rate of 14.6 mmol/day,^[97][123] the upper limit for serum creatine to return to baseline levels after stopping supplementation should be around six weeks.

The timing of supplementation with creatine for improving training adaptations has only been investigated in a small number of trials.

One 10-week trial looked at the effect of supplementation with creatine together with protein and carbohydrates both before and after resistance training (i.e., in close proximity to the workout) compared to the same supplement taken in the morning and evening (i.e., further away from the workout).^[133] The researchers found that taking the supplement in close proximity to the workout increased lean mass, the cross sectional area of type 2 muscle fibers, strength, and intramuscular creatine and glycogen stores more than taking the supplement further away from the workout. This potential benefit of creatine taken in close proximity to the workout, relative to other times, may be related to an upregulation of creatine transport secondary to muscle contraction.^[120]

A handful of trials have also looked at the effect of supplementation with creatine before compared to after the workout.^{[134][135][136][137][138]} In these trials, no differences were observed between groups for changes in body composition or strength.

In summary, because only one trial examined the effect of taking creatine (together with protein and carbohydrate) in close proximity to, compared to further away from, resistance training sessions, it remains unclear whether there is an optimal time to supplement with creatine. At the very least, it doesn't seem to matter whether creatine is taken before vs. after resistance training sessions.

Supplementation with creatine has been found to improve physical performance (mainly power output) in athletes competing at the elite level in a host of different sports, including soccer,^[47] volleyball,^[48] wrestling,^[16], and swimming.^[49] That said, the beneficial effects of supplemental creatine appear to be less noticeable in elite athletes than in novice athletes.

The evidence is mixed, but the preponderance of the evidence suggests that it’s unlikely that creatine will increase your testosterone levels.

Three randomized controlled trials conducted in healthy young men reported that supplementing with creatine for 1–3 weeks produced small increases in the levels of testosterone or dihydrotestosterone (DHT; a highly active androgen converted from testosterone).^[65][66][67] One of the 3 trials looked at the effect of creatine loading (25 grams/day for 1 week) followed by a maintenance phase (5 grams/day for 2 weeks) on testosterone and DHT in 20 young, healthy rugby players. Although no effect on testosterone was found, creatine increased the levels of DHT by 12 nanograms of DHT per deciliter of blood (ng/dL).^[65] The other 2 trials found that supplementation with creatine for 1 week in healthy, active young men increased the concentrations of testosterone by 57 ng/dL and 150 ng/dL.^[66][67]

Conversely, 10 other trials (involving a total of 218 participants) looking at the effect of supplemental creatine at daily doses of 3–25 grams on testosterone levels for up to 12 weeks have found no statistically significant effect.^{[68][69][70][65][71][72][73][74][75][76]} The participants in the majority of these trials were healthy, active young men. With regard to the form of creatine used, 9 trials administered creatine monohydrate, whereas 1 trial administered creatine malate. It’s worth noting that no trials have looked at the effect of creatine on testosterone in men with abnormally low testosterone levels.

Taken together, the available evidence suggests that supplementing with creatine is unlikely to increase testosterone levels, at least in young healthy men whose testosterone levels are within the normal range.

Research examining the effect of supplementation with creatine on measures associated with exercise-induced muscle damage has provided somewhat paradoxical results.

Two 2021 meta-analyses found that creatine appears to blunt increases in the levels of creatine kinase and lactate dehydrogenase (indirect biomarkers of muscle damage), which suggests that creatine may promote recovery from muscle-damaging exercise.^[139][140] However, a more recent meta-analysis found that, although acute supplementation with creatine blunted increases in the levels of creatine kinase and lactate dehydrogenase following muscle-damaging exercise, chronic supplementation with creatine resulted in larger increases in the levels of these biomarkers of muscle damage.^[141] These findings suggest that creatine may promote the recovery from a single bout of muscle-damaging exercise, but that chronic supplementation may have the opposite effect.

One possible explanation for the findings above could be that, since creatine increases training performance and capacity over time, people who supplement with creatine may work their muscles harder than they otherwise would, which could eventually result in greater cumulative muscle damage.

With the above said, it should be kept in mind that supplementation with creatine doesn’t appear to have a consistent effect on other measures associated with exercise-induced muscle damage, including the recovery of exercise performance and muscle function, inflammatory biomarkers, range of motion, and delayed-onset muscle soreness in the hours following a muscle-damaging exercise bout.^{[139][140][141]}

Although curative therapies for muscle disorders are lacking, supplementation with creatine may improve the symptoms of some muscle disorders. According to a 2013 Cochrane meta-analysis, supplementation with creatine decreased symptom severity, increased muscle strength, and improved activities of daily living in individuals with muscular dystrophies.^[142] However, no effects of creatine were observed in individuals with metabolic myopathies. It’s also worth noting that one trial reported an increase in muscle pain episodes and impairment in activities of daily living with creatine in individuals with glycogen storage disease type V (GSDV, also called McArdle disease).^[143]

Although a 2017 meta-analysis found that supplementation with creatine increased functional independence (as assessed with the Schwab and England Activities of Daily Living Scale), the size of the effect was very small (and potentially clinically irrelevant). Moreover, no effects of creatine were observed on mental health, motor symptoms, or activities of daily living as assessed with the Unified Parkinson's Disease Rating Scale (UPDRS).^[144]

The current body of scientific evidence looking at the effects of creatine on bone health is limited and inconclusive. According to a 2018 meta-analysis, supplementation with creatine alongside resistance training in older adults was no more effective than resistance training alone for improving whole body bone mineral density (BMD) or BMD measured at the lumbar spine, hip, or femoral neck.^[145] That said, a 2023 randomized controlled trial conducted in 237 postmenopausal women found that supplementation with creatine for 2 years alongside resistance training preserved the compressive and bending strength of parts of the femur.^[146]

Limited available evidence from one meta-analysis of five randomized controlled trials involving healthy adults and adults with diabetes found no effect of supplementation with creatine on fasting blood glucose levels or on the degree of insulin resistance.^[147]

The potential links between creatine and cancer are unclear. In general, evidence from in vitro studies and from studies conducted in animals suggests that creatine may have both cancer-suppressive and cancer-promoting properties.^[33]

For example, in mouse models, both creatine and cyclocreatine (a synthetic analog of creatine) have been reported to slow down the rate of growth of subcutaneously implanted tumors.^{[34][35][36][37][38][39]} The potential antitumor effects of cyclocreatine may require the presence of creatine kinase, through which cyclocreatine is converted to phosphocyclocreatine, which, in turn, potentially acts as an energy depleter by trapping ATP that has been released from the cell’s mitochondria or transported into the cell from outside, thereby limiting cancer cell proliferation.^[36] However, because the expression of creatine kinase can vary widely depending on the type of tumor, the potential antitumor effects of cyclocreatine may also vary accordingly.^[40] The potential antitumor properties of supplemental creatine may be related to its effects on cellular acidosis, inflammation, and oxidative stress,^[37][39] as well as on the regulation of antitumor killer T cell immunity.^[41]

On the other hand, findings from some studies suggest that creatine may promote invasion and metastasis of certain types of cancer — including colorectal cancer, breast cancer, and pancreatic cancer — through its energy-buffering properties and modulation of cell signaling.^[42][43][44]

It’s important to highlight that the above findings are from in vitro and animal research, so their applicability to humans is currently unclear.

The limited available research in humans seems to suggest a potential protective role of creatine against cancer. Specifically, according to a 2023 cross-sectional study that was performed using data from 7,344 US adults who participated in the 2017–2020 National Health and Nutrition Examination Survey (NHANES), a higher intake of dietary creatine was associated with a lower risk of cancer or malignancy, with a 1% reduction in cancer risk for every additional milligram of creatine per kilogram of body mass consumed daily.^[45] Moreover, in a 2006 randomized controlled trial, supplementation with creatine in people with colorectal cancer who were undergoing chemotherapy had no effect on muscle mass, muscle function, or quality of life, but improved biomarkers of nutritional status in a subsample of participants that were undergoing less aggressive chemotherapy.^[46]

Overall, the available evidence from in vitro and animal studies suggests that creatine may suppress primary tumor growth, but promote invasion and metastasis of some types of tumor, with limited research in humans linking dietary creatine to a lower risk of cancer as well as to some minor protective effects in people undergoing mild chemotherapy for colorectal cancer.

Creatinine is a byproduct of the breakdown of creatine and phosphocreatine in the body. It is also a commonly used marker of kidney function.

Because supplementing with creatine can increase the blood levels of creatinine, there have been some concerns about a potential negative effect of creatine on kidney function. However, beyond a harmless increase in creatinine levels, scientific reviews on both the long- and short-term safety of supplemental creatine in people with healthy kidneys have consistently found no adverse effects on kidney function with a wide range of doses.^{[50][51][52][53][54][55][56][57]} That said, although doses of >10 g/day have been found not to impair kidney function, fewer long-term trials have assessed the safety of such high chronic daily intakes.

Similar findings have been reported in trials looking at the effect of supplemental creatine in people with kidney disease, with trials reporting no detrimental effects on kidney function.^[58][59][60] That said, long-term trials assessing the safety of supplemental creatine in people with kidney disease are lacking. Also, it’s worth keeping in mind that, because creatine can increase water retention, it could theoretically adversely affect individuals whose kidney disorder is being treated with diuretics, which cause water loss.

Overall, the available evidence suggests that short- and long-term supplementation with creatine is likely safe for people with healthy kidneys, and that short-term supplementation with creatine is likely safe for people with suboptimal kidney function. Less is known about the effects of long-term supplementation with creatine in people with suboptimal kidney function.

Also, it’s worth keeping in mind that, although elevated creatinine levels in response to supplementation with creatine are not indicative of kidney damage, creatine’s ability to raise creatinine levels could potentially mask underlying health issues.

Although plausible, it seems unlikely that supplementing with creatine causes hair loss.

By binding to androgen receptors in susceptible hair follicles, dihydrotestosterone (DHT; a testosterone metabolite) can cause hair follicles to shrink, ultimately leading to hair loss.^[61][62] That said, whether a given hair is more or less likely to fall depends on its location (in male-pattern hair loss, the crown and hairline thin first) and the person’s genetic predisposition to hair loss.^[63][64]

A proposed mechanism behind creatine’s effect on testosterone

The idea that supplemental creatine could be linked to hair loss largely originates from the findings of a 2009 randomized controlled trial.^[65] In this trial, college-aged male rugby players who took creatine monohydrate for 3 weeks experienced a 41% increase in their blood levels of DHT. The baseline DHT concentration was 0.98 nmol/L and the concentration after 3 weeks was 1.26 nmol/L, with both values being well within the normal range.

To date, this has been the only trial testing creatine’s effects on DHT. However, 12 other trials have tested creatine’s effects on testosterone. Of these, only two trials (lasting 6 and 7 days) have reported increases in testosterone levels,^{[66] [67]} while the remaining 10 trials (which ranged in duration from 6 days to 12 weeks) found no effect.^{[68][69][70][65][71][72][73][74][75][76]} Importantly, 5 of these trials specifically tested creatine’s effects on free testosterone, the form of testosterone that gets converted to DHT, and found no significant increases.^{[68][71][73][69][75]}

Lastly, and perhaps most importantly, the effect of supplemental creatine on hair loss hasn’t been directly studied, so all we can do is make educated guesses.

To sum up: (i) Only one trial has reported an increase in DHT levels with supplemental creatine; (ii) although DHT levels increased, they stayed well within the normal range; (iii) no other trials have looked at the effect of supplementing with creatine on DHT levels, but 10 of the 12 trials looking at the effect of supplemental creatine on testosterone, five of which also looked at free testosterone, reported no effect; and (iv) the effect of supplemental creatine on hair loss hasn’t been directly studied.

With the above in mind, we can conclude that, although plausible, it seems unlikely that supplementing with creatine causes hair loss.

No human studies to date have evaluated the safety of supplementation with creatine in women during pregnancy. However, studies in rodents suggest that supplemental creatine may not only be safe, but may also have positive effects on birth outcomes.

For example, in one study conducted in mice, maternal supplementation with creatine from the midpoint of pregnancy until birth increased the creatine content of the placenta (+105%) and of some of the fetal tissues, including the brain (+3.6%), heart (+14%), kidney (+22%), and liver (+37%).^[127] The increased concentration of creatine in the brain of the fetus before birth may protect the fetus from damage associated with low oxygen availability, such as during a Cesarean section.^[128] Protective effects have also been observed in the offspring’s diaphragm (through preserved muscle fiber size),^[129] kidneys,^[130] and neural tissue (due to less oxidation in the brain and less cellular apoptosis).^[131]

Importantly, maternal supplementation with creatine (again, in mice) does not seem to affect the creatine transporter or the enzymes responsible for creatine synthesis in the newborn, which suggests that the capacity for creatine synthesis in the newborn mouse is not altered.^[132]

Supplementation with either creatine or caffeine has consistently been shown to enhance high-intensity exercise performance in most people, and the ingredients are thought to achieve this feat via separate physiological mechanisms. There also doesn’t appear to be any pharmacokinetic interactions when caffeine or creatine are taken together; i.e., neither caffeine nor creatine affects the other’s blood levels.^[78] Caffeine does not influence creatine’s ability to increase muscle phosphocreatine storage^[79], which makes combined supplementation of creatine and caffeine an attractive prospect for athletes and recreational exercisers alike.

However, there is some evidence to suggest that chronic caffeine consumption during creatine loading blunts the ergogenic (i.e., performance-enhancing) effect of creatine.^[80] One notable study found that six days of creatine loading increased the amount of torque produced by the quadriceps during a resistance exercise protocol but adding a single dose of 5 mg of caffeine per kg of body weight during the final three days of the six-day creatine-loading protocol produced no improvement in exercise performance.^[79]

If caffeine does interfere with creatine’s ergogenic effect, it may be a consequence of these supplements having opposing effects on muscle relaxation time. Creatine increases calcium reuptake into the sarcoplasmic reticulum (a structure in muscle cells that stores calcium) and reduces muscle relaxation time, whereas caffeine increases calcium release from the sarcoplasmic reticulum and increases muscle relaxation time.^[81] Theoretically, reduced muscle relaxation time would be conducive to generating high amounts of force quickly and in rapid succession.

Caffeine may also blunt the ergogenic effect of creatine because co-ingestion of these ingredients has been reported to cause gastrointestinal distress in some people.^[80][82]

While these data are thought-provoking, it’s far from clear whether caffeine and creatine should be consumed separately to maximize their ergogenic effects. For instance, despite caffeine potentially diminishing creatine’s ergogenic effect when ingested during creatine loading, other studies found that after five to six days of creatine loading, supplementation with caffeine before an exercise test enhanced performance.^[83][84]

Additionally, studies that investigated the acute and chronic effects of supplementation with a multi-ingredient preworkout supplement containing both caffeine and creatine reported enhanced exercise performance and muscular adaptations.^{[85][86][87][88]} However, these preworkout supplements also contained ergogenic ingredients other than creatine and caffeine (e.g., beta-alanine), which may have confounded the results.

Lastly, and most recently, the results from two studies cast further uncertainty on whether one should refrain from co-ingestion of caffeine and creatine. In the first study, a 2016 randomized controlled trial, 54 physically active men supplemented with a daily loading dose of creatine, creatine plus 300 mg caffeine anhydrous (equivalent to about 3 cups of coffee), creatine plus coffee (containing 300 mg of caffeine), or placebo for five days. No differences between groups were found for changes in upper- or lower-body strength, upper- or lower-body muscular endurance, or repeated sprint performance.^[82] This dose of caffeine didn’t appear to blunt creatine’s effects in this study, but creatine also didn’t appear to have any positive effects to blunt.

In the second study, a small controlled trial published in 2022, 28 resistance-trained adults were randomly assigned to supplement with a non-loading dose of creatine monohydrate (0.1 grams per kg of body weight), caffeine (3 mg per kg of body weight), creatine plus caffeine, or placebo for four to five days per week before performing resistance exercise. After six weeks of training, there were no differences between groups for changes in upper- or lower-body strength, upper- or lower-body muscular endurance, or fat-free mass; however, the group that supplemented with creatine alone, and only that group, experienced an increase in quadriceps muscle thickness compared to baseline.^[89] In this study, the creatine group did see positive effects (albeit in muscle thickness, not performance) that the caffeine + creatine group did not. However, the study was significantly underpowered, limiting its ability to detect small changes over time. The intermittent (as opposed to daily) supplementation protocol may have also influenced the results.

The evidence indicating that co-ingestion of caffeine and creatine blunts creatine’s ergogenic effect is weak, and is seen mainly in studies that implemented a creatine loading protocol, implying that this effect — if it exists at all — may not be relevant when creatine loading is not used. Nonetheless, this level of evidence may be sufficient to lead some people to reconsider their current supplementation practices.

In terms of practical recommendations to mitigate the potentially unfavorable interaction between caffeine and creatine, one option is to supplement caffeine before exercise and creatine after exercise.^[90] If co-ingesting caffeine and creatine, it may be prudent to stick to a lower dose of caffeine (≤ 3 mg per kg of body weight), as the studies that reported a negative interaction had participants supplement with 5 mg per kg of body weight. Additionally, early studies on creatine supplementation, which had participants mix creatine with hot coffee or tea, didn’t find that these beverages inhibited creatine’s ergogenic effect;^[91][92] typical cups of coffee and tea contain far less than 5 mg/kg of caffeine. Further, coffee and tea are not simply “caffeine water” and contain hundreds of other bioactive compounds, which could have influenced the results.

In general, oral supplementation of creatine increases muscle creatine content by 15%–20%, which is more than a 20 millimolar (mM) increase. Individuals who get a response of this magnitude are considered creatine responders.^{[118][77][119][120]} Creatine non-responders are individuals whose muscle creatine content increases by less than 10 mM after prolonged supplementation with creatine,^[121] while creatine quasi-responders are individuals whose muscle creatine content increases by 10–20 mM.^[121]

Non-response to supplemental creatine is thought to explain instances in which not all participants benefit from supplementing with creatine in trials.^[122]

Limited evidence suggests that a single dose of creatine at rest may increase growth hormone secretion in the hours following supplementation, with a high degree of variability between individuals (38%–128%).^[125] On the other hand, creatine loading (but not a lower daily dose to maintain elevated creatine levels) may blunt exercise-induced growth hormone secretion.^[126]