We all want to supercharge our gym gains in one way or another.
As natural lifters, creatine is one of the few supplements that will give us the most results. Thus we want to make sure we use the best creatine supplement.
For a long time, creatine monohydrate has ruled as the king.
Many other creatine supplements (different forms) have come and challenged the king, but have lost.
- Creatine hydrochloride (HCL)
- Creatine ethyl ester
- Creatine nitrate
- Creatine citrate
- Creatine pyruvate
Creatine monohydrate (regular creatine) still rules as king…until now?
CreGAAtine is his new challenger. Let’s see if CreGAAtine will become the next king.
What is creatine
Creatine is a compound created naturally in the body. It’s created from the amino acids arginine, glycine and methionine in the kidneys and liver.
First, the 2 amino acids arginine and glycine are combined by the enzyme l-arginine:glycine amidinotransferase (AGAT), which produces guanidinoacetate acid (GAA). Then the enzyme guanidinoacetate methyltransferase (GAMT) converts GAA to creatine with the help of a methyl donor.
GAA (also known as glycocyamine or betacyamine) has been investigated as an energy-boosting dietary supplement in humans for more than 70 years. It’s only recently that GAA and creatine have been used together in research.
How does creatine work
Once newly formed creatine is released from the liver into the blood, about 95% of creatine is stored in muscle (taken up by the creatine transporter (CRT)). The remaining amount is found in other tissues, like the heart, brain, and testes.
Of this, about 2/3 of creatine is bound with inorganic phosphate (Pi) and stored as phosphocreatine (PCr) with the remainder stored as free creatine.
Phosphocreatine is used to rapidly recycle ATP in the body, thus allowing for great sustained energy output.
As you can see, in times of need when ATP drops and ADP increases, creatine phosphate is used to add a phosphate to ADP to create ATP.
Low ATP in the body leads to muscle fatigue (general fatigue) and impaired muscle contraction. ATP is the most important energy substrate in the body. Low ATP will lead to all kinds of problems.
Rapid creatine phosphate usage occurs mostly during the most explosive parts of a movement. For example, creatine phosphate helps to recycle ATP during a 100m sprint and then drops off quickly after that.
After a few seconds, the body relies more heavily on glycolysis for ATP (quick breakdown of ATP). This can last a couple of minutes. Once muscle glycogen is depleted, the body will start relying mostly on fat for fuel.
People with a defect of the creatine transporter in the brain tend to suffer from mental retardation, brain degeneration and fatigue.
Who needs creatine the most
Our bodies can create 1-2g of creatine daily. The rest of our creatine we get from the diet.
In 2011, Wallimann found that creatine stores are not fully saturated on vegan or normal omnivore diets that generally provide 0 or 0.75–1.5 g/day of creatine. And that daily dietary creatine needs may be in the order of 2–4 g/person/day to promote general health (R).
Meaning, on average we don’t create enough creatine or consume enough through our diet for optimal health.
Vegetarians have been reported to have muscle creatine and phosphocreatine stores about 20–30% lower than non-vegetarians. Vegetarians are the ones that will benefit the most from creatine supplementation.
Furthermore, the body breaks down about 1–2% of creatine in the muscle per day into creatinine which is excreted in the urine. Degradation of creatine to creatinine is greater in individuals with larger muscle mass and individuals with higher physical activity levels.
Therefore, a normal-sized individual may need to consume 2–3 g/day of creatine to maintain normal creatine stores. Someone with a lot of muscle mass and that exercise a lot might need 5g+ creatine daily to keep his levels topped off.
Benefits of creatine
Creatine supplementation has been shown to:
- Help lower cholesterol, triglycerides and/or manage blood lipid levels
- Reduce the accumulation of fat in the liver
- Decrease homocysteine thereby reducing risk of heart disease
- Serve as an antioxidant
- Enhance glycemic control
- Have anti-inflammatory and immunomodulating effects
- Reduce the progress of some forms of certain cancers
- Increase strength and muscle mass
- Minimize bone loss in some studies
- Has a performance-enhancing effect
- Improve functional capacity in osteoarthritic and fibromyalgia patients
- Enhance cognitive function and mental performance, particularly in older populations
- Improve the efficacy of some anti-depressant medications (R)
- Improve functional capacity in patients with chronic fatigue-related syndromes such as post-viral fatigue syndrome (PFS) and myalgic encephalomyelitis (ME).
- Support reproductive health.
- Support skin health.
- Help with energy levels
It’s truly a must-have compound with lots of health benefits.
What is CreGAAtine
CreGAAtine is a unique creatine proprietary blend that contains creatine monohydrate and the creatine precursor, GAA. CreGAAtine is an evidence based nutraceutical, safe, patented and doping-free verified. It’s been heavily studied by European Society for Clinical Nutrition and Metabolism (ESPEN).
They are not magically connected to each other in a lab, but just 2 powders thrown together in a supplement, usually in a 1:1 ratio.
The reason for this is because GAA has various benefits that creatine doesn’t have.
Benefits of GAA
The main upside is that it can be taken up by cells via 4 different pathways instead of 1 (that’s 3 additional pathways).
GAA is taken up via:
- The creatine transporter (it has 10 times less affinity than creatine for this transporter, so it doesn’t really compete with creatine here) (R)
- Taurine transporter (SLC6A6)
- Gamma-aminobutyric acid transporter (GAT2)
- Passive diffusion (R)
Thus if someone has a defect in the creatine transporter, they can still absorb GAA just fine.
The second upside to GAA is that it seems to be slightly better than creatine itself at increasing creatine levels in certain areas of the body.
Side effects of GAA
The biggest downside of GAA is that it requires methyl donors to be converted to creatine. If a lot of GAA is taken, it can start to increase homocysteine and even contribute to hyperhomocysteinemia. Homocysteine is inflammatory, causes vascular inflammation, increases the risk of blood clots and even contributes to erectile dysfunction.
Reduced methyl donors can lead to low dopamine, nitric oxide and impaired detoxification as of other things.
Animal studies reported that GAA accumulation is neurotoxic and has pro-oxidant effects (R). However, this is more likely due to a defect in GAA conversion to creatine instead of GAA supplementation.
CreGAAtine vs creatine monohydrate
A few studies have found that combining creatine monohydrate with GAA might result in higher concentrations of creatine in the muscle and brain.
Thus far, this 4 weeks study is the only study that compared CreGAAtine with creatine monohydrate on muscle and brain creatine. Here are their results:
“Creatine-GAA mixture was superior to creatine alone to increase mean creatine levels in skeletal muscle (16.9 ± 20.2 vs. 2.0 ± 6.0%; P = 0.02) and grey matter (5.8 ± 5.3% vs. 1.5 ± 3.2%; P = 0.02), also for bench press performance (6.0% vs. 5.1%; P < 0.01). Compared with creatine administration alone, combined GAA and creatine resulted in less weight gain (1.6 ± 0.2 kg vs. 0.7 ± 0.2 kg; P < 0.01).” (R)
This is where the following absurd statements:
- CreGAAtine is 8.5 times more powerful than creatine monohydrate
- CreGAAtine provides 3.9x more creatine in gray matter and 1.9x in white matter.
8.5 fold better sounds like a massive benefit. But look at it this way.
CreGAAtine vs creatine monohydrate on brain creatine levels
Let’s say you had 10g of creatine in your brain for simplicity reasons. Creatine levels would increase to 10.58g (5.8%) vs 10.15g (1.5%) for CreGAAtine vs monohydrate respectively. That’s a meager 0.43g difference. Doesn’t sound so great anymore now does it?
Other studies have found that creatine monohydrate supplementation can increase brain phosphocreatine content by 5–15% (which is a lot more than the 1.5% found in the study above) (R).
CreGAAtine vs creatine monohydrate on muscle creatine levels
In terms of muscle creatine, let’s say you have 100g of creatine in your muscles. According to the study above, supplementing 4g CreGAAtine and creatine monohydrate would increase muscle creatine stored to 116.9g (16.9%) and 102g (2%) creatine. That might seem like a more significant difference. But check this out.
Other studies have shown that creatine monohydrate increases muscle creatine by 20-40%, not a meager 2% (R). So if creatine monohydrate increases muscle creatine by 20-40%, and CreGAAtine only by 16.9%, now it doesn’t seem so great anymore, right?
8.5X More Effective Than Creatine Monohydrate
As mentioned above, this statement is due to the study above showing that CreGAAtine increased muscle creatine 8.5 times more than creatine monohydrate (16.9% vs 2%).
However, as I pointed out creatine monohydrate can increase muscle creatine by 20-40%, not 2%.
CreGAAtine is better for small, weaker muscle groups
The above study found that bench press performance increased by 6.1% for CreGAAtine and only 5% for creatine monohydrate. That’s a 20% improvement!!!
That 1.1% difference is too small to make any conclusions just from 1 study. Besides, if creatine increased muscle creatine by 20%, the bench press performance would have increased the same in both groups.
CreGAAtine provides 3.9x more creatine in gray matter and 1.9x in white matter
This study found that CreGAAtine increased grey matter creatine by 5.8 ± 5.3% (vs. 1.5%) and white matter creatine by 6.6% more compared to creatine monohydrate (R).
However, this study found that creatine loading for 30 days increases creatine in gray matter (4.7%), white matter (11.5%), cerebellum (5.4%) and thalamus (14.6%) (R).
It would rather seem to me that they are equally effective.
However, CreGAAtine will definitely be superior for people with a creatine transporter defect.
CreGAAtine is taken up in 4 different ways and not just 1
A “problem” with creatine monohydrate is that it’s only taken up by 1 transporter, whereas GAA can enter a cell 4 different ways.
Supposedly, the creatine transporter can become saturated with continuous creatine supplementation, resulting in a lower capacity to transport creatine into the cell.
This limitation seems to hamper its optimal uptake in tissue with high energy requirements. Taking GAA with creatine can bypass this limitation (R).
However, taking 5g creatine monohydrate for at least 30 days leads to muscle creatine saturation, unless someone has a creatine transporter defect.
Studies show that creatine supplementation in doses of 5–20 g/day for >5 days can increase intramuscular creatine and phosphocreatine to the point of saturation (R).
No need to add GAA to bypass this saturation “problem”.
CreGAAtine has less non-responders
Because CreGAAtine has 4 ways to be taken up by cells, it’s highly unlikely that there will be non-responders, right?
A non-responder is someone that doesn’t get more than a 5% increase in intramuscular creatine from supplementation.
This study found that 13.3% of participants were categorized as nonresponders to GAA, whereas 6.6% as quasi‐responders, and 80.0% as responders after 4 weeks of supplementing 3g GAA (R).
The main (hypothesized) reason why some people are non-responders to creatine is that they already have high levels of creatine in their muscles (R). Creatine influx into a cell is proportional to the deficiency. The less creatine you have, the more will be taken up. If you eat a lot of creatine-rich food such as meat, you’re more likely to be a creatine non-responder.
Based on this fact, it’s impossible for CreGAAtine to have less non-responders than creatine monohydrate, because if a muscle doesn’t need more creatine, it just doesn’t need more. Regardless of how much GAA is in a cell.
CreGAAtine doesn’t cause water retention
A common misconception is that people think creatine causes water retention giving your muscles a balloon-like appearance.
Not gaining extra water weight is especially important in sports disciplines where body mass is an important category.
The reasoning for this is that approximately two sodium molecules and one chloride molecule are necessary for creatine transport. Meaning, as you pull creatine into the muscle, you’ll also pull sodium in. Sodium attracts water, which will give you a poofy look. However, the sodium and creatine are pulled into the muscle, not under the skin. So this will actually make you look pumped, and not poofy.
But this whole water retention myth is not backed up by science.
Some studies have found that in the short term (3 days), creatine supplementation increases water retention, primarily attributed to increases in intracellular volume.
However, longer-term studies (4+ weeks) showed that creatine didn’t alter total body water (intra or extracellular) relative to muscle mass (R).
The main reason why CreGAAtine “doesn’t” cause water retention is because they’re using less overall creatine (2g vs 4g). Less creatine = less intramuscular hydration (in the short term).
CreGAAtine comes in sachets so that the creatine doesn’t degrade
The reason for this is that creatine is a hygroscopic substance, which means that creatine powder tends to absorb moisture from the air. Thus, over time, creatine turns to its inactive form, creatinine, which does not have an ergogenic effect as creatine.
This is BS since creatine monohydrate powder is very stable showing no signs of degradation into creatinine over years, even at elevated storage temperatures (R). However, if you mix it with water or some liquid, it will degrade over time. Don’t mix and store. Mix and consume.
GAA is also very stable, so no need to put any of them in sachets either.
CreGAAtine minimizes the side effects of GAA
Since GAA has a few possible side effects, such as depleting methyl donors and increasing homocysteine, taking CreGAAtine can bypass this. The reason for this is that the dose of GAA in CreGAAtine is much less than when you’d take it by itself. Thus minimizing side effects.
Plus, creatine spares methyl donors and lowers homocysteine. So they basically cancel each other out (R).
How to enhance the effects of creatine
There are 2 main ways to get more creatine into your cells.
Take your creatine with:
Green et al. first reported that the combination of creatine supplementation with carbohydrates substantially increased muscle creatine uptake by 60%. This was beyond the point that acute creatine loading alone could do (R, R, R).
Fenugreek has also been shown to enhance the uptake of creatine, to the same extent as carbs (R). The uptake of creatine is via a creatine transporter-independent pathway.
If you’re afraid that Fenugreek might increase prolactin and lower DHT, check out this vid where I debunk it.
Do I need to load creatine?
The most effective and rapid way to increase muscle creatine stores is to ingest 5 g of creatine monohydrate four times daily for 5–7 days. This will top your levels off in 5-7 days.
However, you’ll get the same amount of muscle saturation if you take 2–3 g/day of creatine for 30 days.
So basically, a creatine loading phase is not necessary. If you’re planning on taking creatine for years, speeding up muscle saturation by 3 weeks isn’t going to make a difference at all in the long term.
But regardless, large doses of creatine are very safe. Dietary supplementation of 20–30 g/day of creatine monohydrate for up to 5 years has also been studied in some clinical populations and shown no side effects.
Creatine and muscle growth (what to expect)
We all know that creatine promotes muscle mass gains. It’s the most potent natural supplement on the market!
But by how much?
This 2022 meta-analysis found that creatine helped men gain on average 1.46 kg of lean body mass (R).
The point I’m trying to make is that you’ll never get steroid-like gains from creatine or any natural supplement for that matter. Chances are you won’t even notice a difference in your physique after 30 days or 365 days, whether it’s creatine monohydrate or CreGAAtine.
What will have the biggest effect on your muscle mass gains is eating the right diet:
- Adequate protein (1.6-2g of protein per kg of body weight)
- Carbs to fuel your workout (100-400g daily; depending on what you feel best on)
- Fat for testosterone optimization and synthesis of new cells (15-45% of total calories)
The “supplement” that has made the biggest difference for me in the gym in terms of performance is liver. Each morning I eat 100g of raw liver and since doing that, my muscles as able to work much harder. More than any other supplement has done for me.
Price comparison of CreGAAtine and creatine monohydrate
Optimum Nutrition Micronized Creatine Monohydrate Powder:
- 5g per serving
- 120 servings
= $0.3 per serving
- 30 servings
- 4g per serving (2g GAA + 2g creatine monohydrate)
= $0.96 per serving
CreGAAtine is 3 times more expensive than creatine monohydrate for zero upsides.
CreGAAtine is solving problems that don’t exist. It’s heavily understudied and only one study shows that CreGAAtine is superior to creatine monohydrate. And I’ve debunked those claims.
The only real potential reason to use CreGAAtine is when someone has a neurodegenerative condition and doesn’t respond to creatine alone.
IMO, creatine monohydrate is still the best type of creatine. Heck, even CreGAAtine is 50% creatine monohydrate. They just added GAA.
I’m not trying to tell you what to buy, I’m just showing you the science. I know that I’m going to keep on buying creatine monohydrate.
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