Can You Become Immune To Creatine? What You Need To Know

As an experiment some months into I had been using creatine to boost my muscle strength, it suddenly happened to me one day whether it is possible that my body can become immune to creatine.

I wanted to find an answer to this (as I didn’t want all that creatine I had been consuming every day to go to naught!) and subsequently did some research to find out some solid, research-backed answers to the question of creatine resistance.

So, can we become immune to creatine? From what conclusive evidence exists on this subject, the answer appears to be, No. Creatine is a naturally produced molecule—an amino acid derivative made in the liver and the kidneys at a rate of about 1-2g a day and then gets stores up in our muscles and brain. 

But unlike, say caffeine, you can never store up more than a limited amount since the molecule also routinely gets degraded into creatinine, and our body gets rid of this through urine at a rate of about 2g a day.

This also explains why frontloading (more on that later) or consuming higher doses of creatine is useless for our purposes. It is a bit surprising that creatine, despite being a fairly well-researched substance (especially in comparison with some highly touted supplements), is still a subject of a good number of myths and misconceptions.

However, a studied look into the ways creatine works (and helps in our bodybuilding efforts) will be hopefully able to dispel a lot of these commonly circulating myths.

Why Can We Not Develop Resistance to Creatine?

The answer to this question can be very well illustrated by comparing creatine to another commonly used substance, namely caffeine, and by showing their differences in nature and the way they work on our system. As to creatine, you might already hear that it improves your strength, muscle gains, and recovery, especially when you are engaged in powerlifting exercises.

Now, the way creatine does it is by way of faster regeneration of ATPs or adenosine triphosphates that act as the primary energy source for our muscles during high-intensity workouts.

Creatine here plays the role of a backup generator, so when the ATP store in our muscles gets depleted during heavy lifting exercises, creatine helps supply some additional ATPs. This helps us perform one or two extra reps and also facilitates faster recovery.

This much is more or less common knowledge. What is less commonly known, though, is the fact that creatine can only turn ADP or adenosine diphosphates into ATPs once it gets phosphorylated by creatine kinase which is an enzyme.

This means that the efficacy of your creatine depends entirely on how much of it is getting phosphorylated by the above-mentioned enzyme. Now, the key thing to realize here that this enzyme creatine kinase can get saturated with creatine which is a substrate. In biochemistry, this saturation point will be called ‘the binding curve.’

So, once the stored creatine level in your body reaches this point, there is no room for any excess creatine to get bound to creatine phosphate and thus turn into ATPs.

Now, researches have shown that this maximum exists around 3-5g a day for most people (for others, 2-3 g per day). So, all excess creatine that you may store in your body (normally, by way of taking creatine supplements) is bound to go to waste.

Now, let’s for a moment compare this to caffeine. We all know how that occasional cup of coffee provides increased energy, motivation, alertness and also acts as a source of positive feelings, and in some cases, even of euphoria.

We also know that the substance caffeine, basically a stimulant of—to get a bit technical here—the methylxanthine class, is responsible for those effects.

However, any regular drinker of coffee knows that the more frequent is your use of caffeine, the lesser the effects. So, basically, you’ll have to drink more and more to continue experiencing the same kind of feelings.

In other words, at the same time your body develops tolerance to caffeine, it also becomes, to a degree, dependant on the substance.

Now, this is what happens in case of caffeine tolerance. Caffeine primarily works by offsetting the effect of the substance adenosine that builds up in the body during hours of fatigue and then gets dissolved when we sleep.

However, when we drink coffee, the molecules of caffeine, that have a somewhat identical chemical structure to adenosine, bind themselves to those same brain receptors normally used by adenosine.

This is why you’ll feel more wakeful and alert after gulping a cup of strong coffee. Also, caffeine also affects an increase in the production of the hormones dopamine and adrenaline, thus giving rise to positive feelings and raised alertness.

However, as you start drinking coffee more regularly, your brain also starts producing more adenosine which means that you’ll need to go on increasing your caffeine intake to offset that increase in the production of adenosine.

The process is more or less the same for all substances to which our body is prone to form dependence. Creatine, on the other hand, is a natural substance produced in our own body and is also found in a small number of food items, most abundantly in beef and other red meats but also in certain fruits and vegetables, albeit in a very small amount.

So, when you are taking a creatine supplement with a view to increasing your muscle gain and overall strength, you are only providing your body greater storage of creatine than what is produced by the body itself plus any amount that can enter your system through foodstuff. However, one must keep in mind that the advantages gained by using a creatine supplement are not huge.

According to one source, regular use of creatine supplement will increase one’s overall strength endurance by 14% and his one rep maximum strength by 5% (information gathered by reviewing 22 separate studies).

In light of this fact, it is not surprising to see why this question of becoming immune to creatine arises in the first place. Let’s now look at some concrete facts as well as some common myths surrounding the substance creatine since this may help us to better understand our subject at hand.

The Creatine Hype

Scientists had discovered the beneficial aspects of creatine as far back as in 1912. However, it was only after the 1992 Barcelona Olympics that creatine became a subject of popular discussion.

In that edition of the multisport event, as many as three British athletes (namely, Colin Jackson, Sally Gunnell and most notably, Linford Christie) had used creatine, which was (and still is) a legal substance, to boost their performance. All of the three athletes had also clinched the top spot in their respective events.

In the wake of this, the sport nutrition companies began selling and advertising the compound. As we can expect, in many instances, the promotion used rather aggressive tactics and helped propagate information which was not in keeping with the facts.

The supplement has however remained popular ever since, both with professional athletes, as well as casual gym-goers, powerlifters, et al.

And yet, even after all these decades, many misconceptions continue to surround creatine. Some of these are: creatine is not natural; creatine is a steroid; creatine is meant for bodybuilders only; creatine will help in muscle gain even without adequate exercise; as well as a few more egregious ones!

A Slight Benefit

However, as I mentioned already, creatine use will only give you a slight benefit during high-intensity exercises. You’ll be able to perform an extra rep or two; your body will recover quickly, and so on.

The benefits are well worth the effort since creatine is a safe (yes, it is, but more on that later) and a legal substance. However, the users must not expect any miraculous results from creatine.

If you are in a non-clinical setting, it is often difficult at first to tell whether or not the use of creatine is making any difference to your performance at all. For this reason, I suggest that you monitor your weight changes for the first few months since you start using a creatine supplement.

Studies show that, due to creatine’s water retention properties in the muscle tissues, users will notice weight gains once they start using creatine. So, if you notice any considerable gain in weight after starting supplementation, you may conclude that your body is responding to creatine.

This also takes us straight to the question of creatine response. Since research also show that not everybody is responsive to creatine.

Creatine: Responders vs. Non-responders

According to the studies conducted, most people respond well to creatine while there are others who do not respond at all. Again, according to available literature, the number of people who are naturally resistant to creatine no matter how much they stuff it in lies at an estimated 20 to 30%.

It has been found that normally people with a high percentage of type 2 muscle fibers respond well to creatine while non-responders typically has a low percentage of the same fiber.

More importantly for our purpose, the studies also tell that most non-responders already have a high initial muscle creatine content while with responders, the contrary is the case.

This again supports the theory that there is an upper ceiling to muscle creatine level and its effects. So, if your muscle tissues already contain an adequate level of creatine, it is most likely that additional supplementation of creatine will be of little use to you.

Loading or Cycling?

People who take creatine in supplement form normally follow one of the 3 following procedures:

They load or front-load: This involves taking a high dose of creatine (around 20g a day) for the first week or so and then sticking with a routine of 3-5g a day.
Cycling: Taking creatine for 3 weeks and then giving one week off; and after that, continuing with this on/off protocol.
I am taking a small but adequate amount of creatine (3-5g a day) from the very start.

Now, as mentioned earlier, there is little benefit to be had by front-loading. In terms of raising creatine content in muscle tissues, procedure 1 and 3 effects in much the same way. However, some believe that loading helps raise muscle creatine content faster. There is a possibility that this might be the case, however not enough research exists to back up this claim.

It is possible that frontloading may help in faster creatine retention in the muscles and creatine storage. But the benefit is, at best, a slight one. Taking creatine in small doses (as in procedure 3) will provide you results fairly quickly, too—normally, in 2 to 3 weeks from when you start taking creatine.

And finally, cycling creatine, it can be conclusively said, does not provide any advantage over the other two methods. This research shows here that the natural creatine store of our body neither depletes nor experiences any increase by long-term creatine supplementation. This again provides an answer to our basic question of whether or not our body can become immune to creatine.

The study also states that long-term supplementation of the compound also does not affect the user’s health in any significant manner—at least when the user is a professional athlete undergoing high-intensity training regularly (the study in question only involved professional/semi-professional athletes as its subjects). If you would like to try good quality creatine just check this link on Amazon.

Is Creatine Safe: Potential Side Effects of Creatine

It is only natural that, in addition to the question of creatine tolerance, many creatine users, especially those who are using the supplement for some considerable time, will have some concern regarding the potential side effects of creatine. And here also we bump against a good number of misconceptions that have little back up by way of scientific research. Some of these creatine scare stories include:

1. Creatine can cause stomach cramp, diarrhea.
2. It can lead to gastrointestinal discomfort, kidney problems, long-term muscle injury as well as a muscle cramp.
3. Creatine can potentially cause or heighten the risk of testicular cancer.
4. Creatine may lead to hair loss.
5. You will gain excessive weight due to creatine’s water retention properties.
6. Creatine causes increased anger, shortening of temper, etc.

Now, let’s look at each of these allegations separately.

  • Creatine and stomach cramp & diarrhea

Some studies have noted that stomach cramping or diarrhea or both can be experienced by some individuals who are on creatine supplementation, especially in the initial phases of creatine use. However, these cases are rare and are normally caused as a result of using creatine in an improper manner.

For example, if you take your supplement without sufficient water or if the compound is not well dissolved in the water when you take it, this may lead to some mild stomach cramp.

This happens primarily because if the compound is taken without adequate water, then it will draw the rest of the required water from the body and this may cause some cramp in the stomach. This is why it is important that you consume the supplement properly as described below.

As to diarrhea, this may happen if someone takes too much creatine at once. So, if you’re loading, you must always phase out your daily intake. But if you face this problem even when you are taking a normal dose (3-5g a day), consider dividing your daily intake into two.

  • Creatine and muscle cramp & muscle injury

There is absolutely no evidence at all that creatine causes muscle cramps, injuries or illness in an athlete. Two recent studies that involved 61 athletes in a training camp found that creatine is in no way involved with muscle cramps or injuries in these athletes.

Significantly enough, these athletes were consuming as much as 15-25g a day of creatine during the loading phase and 5g a day after that. These numbers are considered as upper ceilings of creatine intake, and even so, not a single case of muscle cramp or discomfort was reported.

  • Creatine causes kidney damage

Another purely anecdotal report was unsupported by any research at all. The fact of the matter is that the rumor spread courtesy one case report according to which an athlete who was trying to dehydrate and cut weight while taking high doses of creatine, unfortunately, fell victim to renal failure.

Save this one case; there is no evidence at all in the existing literature on the subject that creatine use is in any way associated with kidney damage, failure, etc.

  • Creatine and testicular cancer

Again, studies that exist so far have not been able to find any link between creatine and testicular cancer. Some athletes who have suffered from this ailment are known to have been using high doses of other supplements, including banned steroids, along with normal does of creatine.

And it is most likely that the condition had been caused in them by the banned substances many of which may have had hidden steroids included within those supplements.

  • Creatine and short temper

More of those anecdotal reports associate creatine use with a short temper, increased anger, aggression, etc. No research confirms these reports. On the contrary, one recent study mentions that using 5g a day of creatine is known to increase the efficacy of antidepressant medication.

More and more studies from recent times are finding, on top of its already acknowledged advantages, further additional benefits of using creatine. We’ll briefly discuss that in a later section.

  • Creatine and Hair Loss

This is another big concern with creatine users that the supplement will lead to premature hair loss. This whole concept had generated from a study performed back in 2009 that had found that long-term creatine use increases the DHT hormone levels in users. And since DHT is known to speed up hair loss in men with a history of male pattern baldness, it was presumed that creatine might be responsible for hair loss.

However, the point to note here is that this whole concept is based solely on a single study and one that didn’t concern itself directly with the question of baldness either. Additionally, no further research on the subject of the link between creatine supplementation and an increase in DHT hormone levels have been done as of yet.

Still, l suggest that if the condition of male pattern baldness runs in your family, you might like to consider this or/and seek professional advice from a qualified physician. On the other hand, it can be safely said that those without any history of male pattern baldness may consume creatine without any concern.

  • Creatine and Weight Gain

Now, the only consistently reported adverse side effect in over 1,000 studies conducted on the subject of creatine supplementation is weight gain, especially in long-term creatine users (those who’ve been using creatine for 5 years or more). Studies tell that part of this gain is due to the water retention in muscles while the rest results from fat-free muscle gain.

However, even this has been put to question by a recent placebo-controlled, double bind study conducted in the US. This study had found that test subjects did not show any significant uptick in the water amount in their bodies. On the other hand, those on creatine showed healthy gains in total body mass and more significantly, in fat-free mass.

In conclusion, most side effects stories associated with creatine use are anecdotal and are not backed by any conclusive evidence. Even so, if you’ve any doubts in mind or if you are on any medication, it is best, for reasons of safety, to consult your physician before you begin supplementation.

But How Good Is Creatine to Our Immune System?

I had been talking about whether it is possible for our body to become immune to creatine. In the meantime, however, some reports suggest that creatine may not be all that good for our immune system.

One group of researchers had found for instance that the most popular form of creatine supplement, the creatine monohydrate, may potentially be sensed by our body as a foreign substance and this may subsequently slow down the regular functions of the receptor molecules.

In the light of this, the study states in conclusion that creatine, especially when used over long periods, may harm the immune system and the body’s usual ability to locate and eliminate viruses and bacteria.

However, this is mostly the finding of a single study (which also in some way contradicts findings from other studies), and until further research appears with more conclusive evidence, it will be unfair to deduct anything concrete on this subject from this one study alone.

Is there any other potential downside? Not anything that we know. However, some suggest that since creatine does not provide any great benefit in terms of muscle gain and strength, it may not be a bad idea to stay away from it altogether.

One such advocate of this view is Jim King, MD, a renowned sports physician. According to Dr. King, if creatine shows only some minimal improvement but comes with potential risk, it is best to avoid it. Now, it’s not that we fully agree with the opinion, but to provide you with some perspective!

Not all Creatine Supplements Are the Same

Normally, the question of becoming immune to the effects of creatine will arise in someone when that person is not receiving or feels that he is not receiving expected benefits from his supplementation.

Now, as I already mentioned that you could only gain a slight advantage by using creatine and it will be unreal to expect any magical results. That said, if you start to feel that your body has all of a sudden stopped responding to creatine, one reason for this may be the supplement you are using.

I mentioned the phenomenon of creatine hype earlier in the article. There is a lot of marketing gimmick surrounding creatine, and many sellers try to dish out the unfounded fact that different forms of creatine supplement are more effective than the standard creatine monohydrate. Some of these different supplement forms include Creatine Citrate, Creatine HCL, Buffered Creatine, Creatine Ethyl Ester, etc.

Often claims are made on the part of the sellers of these different creatine supplement forms that a particular form of creatine results in a higher uptake in muscles compared to creatine monohydrate or does not degrade as much as the monohydrate version and so on.

Simply stated, the statements are untrue and are not backed by any scientific research at all. And still, it is not uncommon for an average and not too informed user to fall victim to these marketing gimmicks.

Accordingly, he may change from creatine monohydrate to another form of the supplement, and this may often result in a non-response. As you can expect, these other versions are often more expensive than creatine monohydrate.

So, I suggest is that you stick with monohydrate until any conclusive evidence turns in that a different form of supplement is superior to it. Except that, the only time l suggest that you experiment with a buffered form is if you are experiencing any particular discomfort while using monohydrate (such as diarrhea, stomach cramp, etc.).

There is only one exception to what I said in the above paragraph. There is a creatine supplement called Polyethylene Glycosylate that has been found by at least one study to be more effective than creatine monohydrate in that the said supplement can provide similar effects in terms of muscle gain, etc., but with a 75% less dosage.

However, this is still just one study, and unless you find more proof in support of the claim, I would suggest that you stick with the much more well-known, well-researched, and the safe and effective creatine monohydrate. Also, the polyethylene glycosylated form is way more expensive than the standard monohydrate. Another reason for your sticking with the latter!

What Do You Take It With and When?

This is another crucial topic when it comes to the question of responding to creatine. Many people tend to think that it does not matter much what you take your creatine with and will normally mix the powder with water before consuming.

However, existing literature tells us that creatine absorption by muscles occurs to a much higher degree when it is taken with high amounts of carb and ideally, with some good amount of protein put in as well.

One study, for example, tells us that creatine retention gets fairly enhanced when the supplement is taken with about 50g of carbohydrates and 47g of protein. So, you must aim to take your supplement with a full meal with the supplement mixed in a glass of heavy milkshake.

If adding with water: If, however, you mix the powder in a glass of water (instead of in a milkshake) it is highly essential to make sure that all of the powder is thoroughly mixed in the water.

There shouldn’t be any visible specks floating in the water. All parts of the compound that are not adequately absorbed in a fluid will draw water from your body, and this may result in conditions like stomach cramps or other gastrointestinal discomforts.

Somewhat of less importance is when you take your creatine. However, most sports nutritionists concur on the point that it is best to take your creatine supplement post-workout. One reason for this is that we normally take some full meal or a heavy glass of milkshake anyway after a workout session, so it is much more convenient for you’re your creatine at this point.

According to one sports nutritionist, namely Nikhil Rao, taking creatine pre-workout may potentially have some adverse effects, too. Rao maintains that since the compound is hygroscopic if we take creatine before the workout, it may pull water from adjacent muscle tissues into our bloodstream and our gastrointestinal tract. And this may result in conditions such as muscle cramps, bloated feeling and so on.

Related Questions

  • Does creatine have any other benefits?

Creatine is often used to treat a variety of conditions in older adults. It is known to slow down brain deterioration in patients with neurologic conditions (such as those with Parkinson’s disease). Creatine is also administered to chronic heart failure patients since it is known to improve the pumping function of the heart.

Creatine, when mixed with some amount of whey protein, can often increase overall strength in adults over 65 years of age, and this without needing to perform any physical exercise.

Perhaps, more pertinent for our purpose is the fact that creatine supplementation, when combined with resistance training, can potentially increase our bone density.

I had mentioned earlier that creatine is also stored in our brain and it is backed by research that during intense and long bouts of mental activity, creatine phosphate is used by our brain to improve mental/cerebral performance.

Finally, a recent Louisiana State University study suggests that creatine supplementation can have potential benefits for endurance training since the compound comes with the ability to increase glycogen levels when we carb-load.

  • Is it okay for teens to use creatine?

Although little research has been done on this subject, most experts believe that it is best that teenage people under 18 avoid this supplement. Since teens, as opposed to adults, are still in a growing phase, creatine may have some adverse effects on their growing bones and muscles.

The truth is we don’t know exactly what will or may happen, so it is strongly recommended that all middle and high-schoolers stay away from it.

Please read my next article about “What Accessories Should I Use In Weightlifting?”

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Can You Become Immune To Creatine? What You Need To Know


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Tomasz Faber

HI, MY NAME IS TOMASZ, and welcome to my site I’m a weightlifter, and I’m very much interested in health and fitness subjects. Throughout a few years of my weightlifting training, and diet experience, I managed to make my body much, much stronger, as well as build endurance and athletic figure. I live in London, UK, where I enjoy my weightlifting more...

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