Creatine guide: what is creatine?

Creatine is a tripeptide molecule, with three amino acids (L-arginine, L-glycine, and L- methionine), endogenously produced in the liver and kidneys, or obtained through an omnivore diet, at a rate of 1 gram per day. It is neither a vitamin nor a mineral… nor a steroid! It can be found in foods such as meat, eggs, and fish, with raw beef providing 5g of creatine per 1.1kg.

Creatine is phosphorylated by creatine kinase to form phosphocreatine and transported through the blood to places with great energy demand, such as the skeletal muscle and the brain. While a person has, on average, 120 grams of creatine, about 60% of the total creatine can be found in the form of phosphocreatine, whereas the remaining percentage is free creatine. Since this phosphocreatine increases the muscle ability to form ATP (a molecule that is considered the energy unit of our body), it allows to rapidly produce energy and sustain cell functioning and muscle contraction for longer — if we did not have creatine, muscle contraction would only last a few seconds! 

Creatine supplementation has been increasingly recognised by the scientific community as an essential factor for increasing energy production and lean mass on athletes. It is a widely researched molecule, with more than 200 studies to date, and its efficacy has been more than proven. It is extremely safe for most people, providing a number of health benefits, with neuroprotective and cardioprotective properties.

What are the benefits of creatine?

1 – Musculoskeletal system

When phosphocreatine is transported to the muscle, it is used to provide immediate energy to type IIb muscles fibres (rapid contraction fibres) and to ensure that the muscles are able to do more contractions and not get tired early. Supplementing with creatine makes muscles store more phosphocreatine, leading to even more muscle contractions, more repetitions, endurance, and a higher intensity work, with more strength and muscle gains. In fact, creatine is the reference supplement for improving power, with studies showing a strength increase from 12% to 20% and power from 12% to 26% with creatine monohydrate.

It’s also known that our mitochondrial function and exercise production are going to decrease over time, and some studies have shown that a creatine supplement may prevent and reduce this “deterioration”. This way, there’s a chance that creatine might have beneficial effects in the treatment of sarcopenia (generalised loss of skeletal muscle mass and muscle strength due to ageing), especially when combined with a proper training regime.

Consequently, over the last years, creatine has also been widely researched in other contexts, namely for post-workout muscle regeneration. Studies have shown that, although its protective effect is not very high, it seems indeed to create a level of protection against muscle breakdown, reducing the levels of myostatin, improving cell singling of certain cells, and reducing protein degradation.

After resistance training, which can be extremely tiresome, creatine helps reduce muscle cell damage and inflammation, helping promote a complete recovery.

Moreover, a scientific review comprising more than 150 studies shows that individuals supplementing with creatine can even increase muscle mass by about 2.2% and, consequently, increase total body mass and body volume, as well as decrease fat mass by 3.2%! A study conducted with women has found an increase of up to 60% in muscle mass when compared to a group without supplementation!

Nevertheless, although almost every study suggests that proper creatine supplementation increases body weight approximately 1 to 2 kg, we must keep in mind that muscle is 73% water, and supplementing with creatine will increase water retention within the cells, particularly in an initial phase — if we gain ten kilos while using creatine, about 7.3 kg is water!

Yet, the weight increase with creatine supplementation in the long term seems to be mostly due to an increase in muscle mass. It’s important to highlight, however, that not everyone benefits from creatine supplementation in the same way. Naturally, vegans and vegetarians have slightly lower levels of creatine when compared to people following an omnivore diet, and by adding creatine to their diet, as they are more sensitive to creatine supplementation, they are going to have a slightly higher increase in total creatine and phosphocreatine and a greater overall benefit.

Researchers have also found out that creatine highly increases the levels of alkaline phosphatase (an important bone growth marker), and that it can benefit adjuvant therapy for bone fractures or in the treatment of osteoporosis. Moreover, the fact that creatine provides more energy makes the person move more, and bone tissue needs daily compression strength stimuli to maintain health. So it can be said that creatine may indirectly aid to bone mass preservation and osteoporosis prevention.

2- Neurological system

It has been found that creatine works as a neuroprotective substance, protecting and increasing the survival of nerve cells when subjected to harmful stimuli. An increasing number of studies show that creatine is essential for brain function in congenital disorders related to creatine production and storage, in neurodegenerative disorders, in brain injury and even in a normal brain.

During the processes of the energy-yielding metabolism, there is a production of various reactive oxygen species. These molecules are neurotoxic (responsible for causing damage to cell structures), which could lead to the death of more sensitive cells, found primarily in the heart and the brain.

Supplementing with creatine makes the cells have more energy stored and, consequently, more neuroprotection against these aggressions, helping increase their survival ability to the metabolic and physical trauma associated with these conditions, as well as improve brain function, specifically short-term memory and mental fatigue. In fact, creatine is being currently studied as a possible therapeutical option for Parkinson disease and Amyotrophic Lateral Sclerosis (ALS).

3 – Cardiovascular system

Since the cardiac cells depend on ATP levels to work properly, several studies decided to analyse various cardiac parameters before and after creatine supplementation. It is known that, in people who suffer from heart failure, creatine levels are lower and, as such, the muscle metabolic response to exercise will also be lower. This causes a great limitation to the daily life of people with chronic heart failure, making them have lower muscle resistance and strength, and get tired more easily.

Although supplementing with creatine may not seem to be beneficial for the heart rate or the ejection fraction of the heart (amount of blood present in the left ventricle after diastole and ejected during heart contraction),  it seems to slightly increase performance and anaerobic ability. This happens because, with heart failure, there is a lack of energy components, so supplementing with “energy precursors” like creatine will actually increase the energy levels and improve strength and resistance, resulting in a more functional life for these people.

Even for athletes, there are studies that show the advantages of creatine to increase anaerobic ability in sprinting when compared to placebo. Another aspect is related to homocysteine. This amino acid is an independent risk factor for heart diseases, and high levels of homocysteine are associated with vascular damage and diseases such as arterial hypertension. Creatine has a great influence on the concentrations of homocysteine and supplementing the diet with creatine can decrease about 25% the levels of plasmatic homocysteine, protecting the cells from the vascular damage caused by this molecule, even though more studies are needed to confirm these facts.

4 – Metabolic system

Although there is limited data, some studies suggest that creatine may increase growth hormone levels in a similar way to the response there is when working out in an intense way. In a study where healthy male individuals, while at rest, ingested 20 grams of creatine in a single dose, there were observed, after 6 hours, increased GH levels of up to 83 ± 45%. Nevertheless, a great interindividual variability was also noted in the hours during which the peak of GH occurred and, during exercise, creatine supplementation interestingly suppressed the secretion of the growth hormone by 5-35%. While it is certain that creatine has anabolic properties in the muscle, its influence regarding the effect on growth hormone still needs to be further studied.

Some studies also suggest a peak in testosterone levels, but this situation should be further analysed as well. It is known, however, that one of the mechanisms of creatine to increase anabolism is through the increase of systemic methylation, a fundamental process in the regulation of gene expression and protein synthesis. The SAM Molecule (S-Adenosyl Methionine) is the main agent in the methylation process of the body and supplementing with creatine will cause an increase in methylation and full body anabolism. 

Creatine may also aid in the treatment of diabetes because, although it has no apparent influence on fasting glycaemia, causes a reduction of 11-22% on the postprandial glycaemia, improving tolerance to glucose. Nevertheless, although it is known that there is an increase in the expression of glucose transporters and muscle glycogen availability, the exact mechanism of how this happens still needs to be further studied. As creatine improves symptoms of other pathologies that involve a lack of energy, it has been researched if it can help with chronic fatigue syndrome or in fibromyalgia. 

In these diseases, there are lower levels of phosphocreatine and ATP, comparatively to healthy individuals, and people could potentially improve with the use of creatine supplements. Studies conducted with children and teenagers with post-traumatic brain injuries who supplemented with 400mg/kg/day showed a reduction in fatigue levels from 90% to about 10%! Creatine might also improve symptoms of depression mainly in women, through the increase of serotonin levels. Nonetheless, similar to other cases, more studies are needed to confirm this fact.