The Complex Relationship Between Creatine and Cancer

In this article, we will take a close look at the complex relationship between creatine supplementation and cancer. We will explore the potential benefits of creatine for muscle strength and performance, as well as the potential risks, including a possible link to cancer. This article aims to provide a comprehensive overview of the current scientific discourse on this topic.
Jakub Hantabal

Jakub Hantabal

Postgraduate student of Precision Cancer Medicine at the University of Oxford, and a data scientist.

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The Relationship Between Creatine Supplementation and Cancer

What is creatine and why do people take it?

Creatine is a molecule that occurs naturally in the human muskuloskeletal system. It is synthesised in the liver, pancreas and kidneys, and plays a role in energy production, especially during high-intensity exercise. Creatine is stored in skeletal muscles as phosphocreatine, which is then broken down to creatine during activity to provide energy for muscle contractions [1, 2].

Creatine can also be obtained through the diet, and it is abundant in red meat and fish. In addition to diet, creatine supplementation is nowadays very popular in the fitness community. Supplements are available in multiple forms, including powders, liquids, and tablets [1].

The primary motivation for creatine supplementation is to increase muscle mass and improve athletic performance. Supplementation increases the availability of creatine in muscles, potentially enabling them to generate more energy, leading to increased strength, enhanced exercise capacity, and faster muscle growth [3, 4]. Additionally, creatine increases water retention in the muscle, leading to a larger muscle mass. Creatine supplementation may also provide additional benefits such as enhanced post-exercise recovery, aid in injury prevention and rehabilitation, and even offer potential neurological benefits, including improvements in cognition, communication, positive behavioural changes, and reductions in headaches, dizziness, and fatigue [3]. Furthermore, creatine has been shown to have antioxidant properties, and may have protective effects against neurodegeneration [5].

What are the risks of taking creatine?

While the safety profile of creatine is very good, it can cause side effects in certain individuals. These can vary from person to person. Following the change in water retention into the muscle, some people may experience an increase in body weight [6, 7, 8]. It is however important to note that this weight gain may be a result of correct supplementation resulting in muscle gain. Another common reported side effect is muscle cramping. This could be due to dehydration or an imbalance of electrolytes in the body [7, 9]. Correct hydration is important when taking creatine supplements. Dehydration, leading to increased strain on the kidneys can occur when not enough water is taken while supplementing creatine [7]. Digestive symptoms such as diarrhoea and stomach irritation can occur, particularly during the loading phase of creatine supplementation or when taking large doses at once [10, 8].

In very rare cases, more serious side effects may occur, particularly at higher dosages or in individuals with certain underlying health conditions. These can include liver damage, kidney damage, kidney stones, compartment syndrome, and rhabdomyolysis [7]. However, it's important to acknowledge that robust clinical trials have not established a causal relationship between creatine supplementation and these severe side effects [11].

Does creatine supplementation cause cancer?

The relationship between creatine supplementation and development of cancer is complex and not fully understood, as is the case with MK 677 and cancer or TB 500 and cancer . There is a large discourse in the scientific literature; some studies suggest that creatine might have a role in cancer development, while others indicate that it could potentially be protective against cancer. Interestingly, creatine content has been reported to be low in several types of malignant cells [12].

Some studies found a link in increased invasiveness and potential to metastise in pancreatic, colorectal and breast cancers in mice that received creatine supplementation [13]. Another study investigated whether creatine supplementation increases the presence of carcinogenic heterocyclic amines, chemicals that have a mutagenic effect on the DNA thus increasing the chance of the cell to undergo malignant transformation (becoming cancerous). These are often found in red meats, particularily those cooked to higher temperatures or grilled. However, the study did not find an association between creatine supplementation and increased presence of heterocyclic amines [14].

Can creatine prevent cancer?

Contrastingly to the previously mentioned studies, some research also indicates that creatine supplementation can also help combat cancer.

Creatine supplementation has been shown to inhibit the growth of subcutaneous cancer in some studies [15]. In a study on rats, creatine supplementation was found to slow tumor growth by approximately 30% compared to a placebo. However, the overall survival rate was not affected positively (longer survival) or negatively (shorter survival). As creatine has antioxidant properties, the anti-tumour effect can be attributed to reduction of oxidative stress, which is an imbalance between antioxidants and reactive oxygen species (molecules with an oxygen atom which are harmful to the cell). More specifically, the effect was attributed to the improved function of the creatine kinase (CK)-creatine system in cancer cells, leading to a reduction in acidosis, inflammation, and oxidative stress [16].

Creatine could be potentially used in combination with other therapeutics in cancer treatment. In combination with methylglyoxal, a compound investigated as novel cancer treatment with cytotoxic effect on cancer cells, creatine reduced tumour size and improved overall survival in a mouse model of sarcoma, a cancer of connective tissue [17].

However, in human patients in a study of colorectal cancer, patients treated with chemotherapy did not benefit from creatine supplementation. There was no improvement in muscle mass or overall physical function of the patients, however it is worth noting that some predictors of poor outcomes were improved [18].

The relationship between creatine usage and cancer incidence is complex and requires a large amount of further research. It's important to note that while some studies suggest potential benefits or harms, these findings are not definitive and should not be used as a basis for clinical decisions without further research. Additionally, most studies to date are conducted on mouse models, which do not accurately capture the complexity of cancer in human patients. Cancer is a very complex disease, and it is important to note that there is not a single causative, or protective agent to cancer.

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Jakub Hantabal

Jakub Hantabal

Jakub is a postgraduate student of Precision Cancer Medicine at the University of Oxford, and a data scientist. His research focuses on the impact of hypoxia on genetic and proteomic changes in cancer. Jakub also consults and collaborates with multiple institutions in the United Kingdom and Slovakia supporting research groups with advanced data analysis, and he also co-founded an NGO organising educational events in data science.