Taking food supplements based on BCAAs is an approach popular with athletes to improve their performance and reduce muscle aches. However, data raises concern: as these compounds are used by cancer cells to grow, could they promote the occurrence of this disease? Here are some answers.
An Upset Metabolism In The Case Of Cancer
Cancer cells proliferate and have increased metabolic needs compared to healthy cells. They draw different nutrients from their environment to satisfy them. Among the resources used, branched amino acids (BCAA) feature in a good position. These are valine, leucine, and isoleucine, essential amino acids that our body is not able to synthesize independently.
Protein Synthesis And Energy Production
Within cancer cells, BCAAs constitute essential building blocks for the production of new proteins. They also activate the mTORC1 signaling pathway, which triggers their production. They also provide nitrogen for the formation of nucleic acids (DNA, RNA). BCAAs are also degraded within the mitochondria into compounds with high energy potential, such as acetyl-CoA, which participates in the formation of ATP. In this way, they provide energy to cancer cells to support their intense activities.
Overproduction Of Transporters And Enzymes
If the role of BCAAs is not fundamentally different within a healthy cell or a cancerous cell, there is a significant difference between these two situations. In cancer, there is a reprogramming of BCAA metabolism, which supports the progression of the disease. First, cancer cells can produce the transporters that allow BCAAs to be transported from the environment in increased quantities, as seen in pancreatic ductal carcinoma, a form of pancreatic cancer. Most of them also overexpress the enzymes involved in the first step in the use of BCAAs, branched-chain amino acid transaminases (BCAT). There are two types: BCAT1, located in the cytoplasm, and BCAT2, present in the mitochondria.
Activation Of Proliferation
For example, a study carried out on glioblastoma cells, the most common brain cancer in adults, highlighted this increased enzymatic activity. Analyzes carried out in vitro revealed a higher than usual quantity of BCAT1. Its neutralization made it possible to reduce the proliferation of cancer cells and alter their invasion capacity, highlighting the fundamental role of the dysregulation of this enzyme in the process of malignant transformation.
In animals carrying this type of tumor, inhibition of BCAT1 slowed the development of cancer. This overexpression of BCAT1 affects many forms of the disease, such as leukemia, ovarian cancer, liver cancer, or breast cancer. For the latter, these high levels of the enzyme are associated with therapeutic resistance to tamoxifen, an anti-hormonal drug often prescribed in this context, and with reduced patient survival.
Dietary Intake And Cancer Risk
In view of the close links between cancer and BCAA metabolism, numerous studies have been carried out on population samples to try to determine whether dietary intake of these compounds could have an impact on cancer risk. The results obtained are very different depending on the forms of the disease.
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No Link With Breast Cancer
A large-scale study analyzed data collected from 196,161 American women from the Nurses’ Health Study and Nurses’ Health Study II cohorts followed for around twenty years. She did not find any link between the dietary intake of total BCAAs or for each of them considered individually and the occurrence of breast cancer.
Optimization of anti-tumor immunity
The results of work carried out in mice suggest possible benefits of a diet rich in BCAA once the disease has been declared. Animals benefiting from increased dietary intake of these amino acids exhibit slowed tumor growth, with limited formation of metastases in the lungs. However, neither the proliferation of cancer cells nor the vascularization of tumors was modified. On the other hand, the increase in BCCA levels leads to a rise in a particular type of cellular defense in the spleen, the NK (Natural Killer), capable of destroying cancer cells. At the same time, they reduce the formation of N-cadherin, a protein that facilitates the mobility and invasion of tumor cells into other tissues.
Increased risk of pancreatic cancer
A study carried out in Italy among 326 people with pancreatic cancer and 652 healthy participants, however, established a link between the level of dietary BCAA intake and the risk of developing this disease. Participants consuming the highest quantities had a twofold risk of developing the disease . Experiments carried out in mice have confirmed the negative influence of a diet rich in BCAAs, which accelerates the progression of pancreatic ductal adenocarcinoma.
Reduced risk of colon cancer
The same team of Italian researchers had previously looked at the eating habits of 1,953 people who have colorectal cancer and 4,154 healthy subjects. The results in this case were the opposite of previous results: high BCAA intakes proved to be slightly beneficial against this disease, with a 10% reduction in the risk of developing it. Protection was more marked for one of its particular forms affecting the terminal part of the digestive tract, sigmoid colon cancer, reaching 51%.
Multi-Faceted Protection
Several avenues could explain this protective effect. Obesity and associated metabolic disorders (insulin resistance, type 2 diabetes) represent a clearly identified risk factor for colorectal cancer. A study in obese mice showed that BCAA supplementation blocks the development of precancerous lesions in the colon, possibly by alleviating insulin resistance.
Furthermore, isoleucine attenuates the production of vascular endothelial growth factor and could thereby counteract the angiogenesis necessary to fuel tumors. Finally, BCAAs stimulate the synthesis of glutamine, a compound that protects the intestinal wall from inflammation and oxidative stress.
Is High Blood Levels a Risk Factor For Cancer?
Other work has explored the link between BCAA blood levels and the risk of developing cancer. For example, one study showed an increase in the risk of pancreatic cancer by almost 2.5 in people with the highest levels compared to those with the lowest. A team carried out a study based on a statistical approach, Mendelian randomization, to establish a possible causal link between the blood level of BCAA and nine different cancers. The only positive association was obtained for squamous cell lung cancer, which represents approximately a quarter of lung cancers.
The Indicator Of An Unbalanced Diet
However, the BCAA blood level could be a better reflection of the dietary intake of these compounds. They are mainly present in meat, fish, legumes, dairy products, and eggs and represent 15 to 25% of total dietary protein intake. Researchers have, in fact, shown that a high BCAA blood concentration is instead a sign of an unbalanced diet, too rich in animal foods, poor in vegetable proteins and fiber, with an unfavorable fatty acid composition. This dietary profile is conducive to the onset of many chronic pathologies, including cancer.
The Effects Of Supplementation
Some clinical trials are being conducted to explore the potential effects of amino acid supplementation, including branched-chain amino acids (BCAAs), in the field of cancer.
Benefits In Case Of Liver Cancer
Most studies carried out in humans concern liver cancer. One study was conducted on patients undergoing surgery to remove hepatocellular carcinoma using a radiofrequency ablation procedure. Some of the recruited volunteers benefited from BCAA supplementation initiated two weeks before the intervention. The group was then followed for almost four years.
Supplementation improved event-free survival, which is the length of time no disease-related adverse events occur, and reduced the relapse rate compared to placebo. A meta-analysis involving 16 studies and nearly 1,600 patients concluded that BCAA supplementation improves blood albumin levels. This indicator is often used in cases of liver cancer because it reflects the proper functioning of this organ.
Reduce Surgical Consequences
Another meta-analysis compiled the results of 13 clinical trials and six observational studies devoted to the effects of supplementation in cancer patients treated with surgery. It reveals a reduction in the risk of postoperative infection by 38% thanks to BCAAs. In addition, taking these amino acids is beneficial against ascites, an abnormal accumulation of fluid in the abdominal cavity, for maintaining body weight and limiting the length of hospitalization.
Possible Support Against Cachexia
Cachexia, which corresponds to involuntary weight loss and muscle wasting, is common in people with cancer. Amino acid supplementation is one way to stop this phenomenon. In this context, leucine has notably been the subject of preclinical studies, which indicate that it can effectively contain it. There needs to be more data in humans. A study was conducted in patients with advanced cancer.
For 12 weeks, 27 of them benefited from an intervention based on a physical exercise and nutrition program coupled with leucine supplementation, while 25 formed a control group. At the end of this period, grip strength improved in the treatment group, suggesting an improvement in physical abilities. However, concerns persist about the possible doping effect of the approach on tumor development. A very recent study carried out in mice suffering from cachexia linked to colorectal cancer showed that leucine supplementation reduced the survival rate of males without providing the slightest positive effect on the reconstruction of muscle tissue.
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