Amino Acids and Protein Nutrition for Cancer Cachexia - Dr. Amino

Amino Acids and Protein Nutrition for Cancer Cachexia

Virtually all forms of cancer induce a condition called cachexia, a weakening and wasting away of the body during serious illness. The effects of cancer cachexia have become recognized as a major factor in determining the effectiveness of cancer therapy and ultimately mortality. Amino acids are an important nutritional therapy for combating cancer cachexia.

There are many forms of cancer, each with specific and unique characteristics. However, virtually all forms of cancer induce a condition called cachexia, a weakening and wasting away of the body during serious illness. The effects of cachexia have become recognized as a major factor in determining the effectiveness of cancer therapy and ultimately mortality.

What Is Cachexia?

A consensus of experts defined cachexia as follows: “Cachexia is a complex metabolic syndrome associated with underlying illness and characterized by loss of muscle with or without loss of fat mass.”

Cachexia has two components:

  1. A loss of appetite that reduces food intake.
  2. Metabolic changes in the body that render normal nutrition ineffective.

The result is malnutrition and loss of lean tissue, which is mostly muscle. Malnutrition and loss of lean muscle tissue in cancer patients has a number of detrimental effects:

Virtually all forms of cancer induce a condition called cachexia, a weakening and wasting away of the body during serious illness. The effects of cancer cachexia have become recognized as a major factor in determining the effectiveness of cancer therapy and ultimately mortality. Amino acids are an important nutritional therapy for combating cancer cachexia.

Every single one of these consequences can impair a patient’s ability to recover from cancer. A study published in 2013 in the Journal of Clinical Oncology sought to determine the degree to which muscle loss contributes to cancer mortality. Results showed that regardless of weight, patients who were cachexic (with involuntary weight loss, muscle depletion, and low muscle attenuation) had a “poor prognosis.” Patients who maintained more lean muscle mass survived lived nearly two years longer.

A 2017 study determined that low muscle mass and muscle attenuation contribute to a poor outcome for metastatic breast cancer patients. Is it possible to do anything about the devastating effects of cancer cachexia on muscle?

To determine the treatment, we must first understand what causes the onset of cachexia. Unfortunately, at a molecular level, scientists don’t know fully understand the precise mechanisms. However, we do understand that at the physiological level, nutritional therapy is the key to tackling cancer cachexia.

The Stress Response in Cancer

Cancer places the body under physiological stress. As a result, appetite is reduced and food intake falls. During the stress response there is a greater need than ever for amino acid nutrition. Amino acids are needed to produce new proteins that can help battle cancer, such as proteins involved with immune function, as well as proteins in tissues and organs such as the liver and brain whose uninterrupted function is necessary for survival.

Nonessential amino acids can be produced in the body, but the nine essential amino acids cannot be produced in the body. Since there is no reservoir of amino acids in the body, muscle protein starts to break down at an accelerated rate to maintain a steady supply of both nonessential and essential amino acids for the other tissues and organs.

Muscle is the primary tissue that can afford to lose some of its protein mass without affecting normal physiology. However, the stress response is adaptive for only a few days—continued loss of muscle protein for longer than that will begin to adversely affect many normal physiological responses. Thus, the continued loss of muscle protein at an accelerated rate is the physiological basis for the development of cancer cachexia.

What Is the Conventional Treatment for Cancer Cachexia?

Cancer scientists have been searching for a treatment for cancer cachexia for many years but have yet to produce a successful solution. The most current recommendations for treatment of cancer cachexia come from the European Society of Parenteral and Enteral Nutrition (ESPEN). These recommendations focus on the early diagnosis of nutritional risk. They also recommend the use of a variety of nutritional interventions, decreasing inflammation, and increasing physical activity.

Unfortunately, there may be significant problems to implementing the ESPEN recommendations. Increased activity is the most effective way to reverse muscle protein breakdown, but the cancer patient usually does not feel like doing a lot of activity. Reducing inflammation with nutrients such as omega-3 fatty acids is useful for mild cases, but the level of systemic inflammation in cancer cachexia is so great that dietary approaches often have little impact. Further, suppression of appetite in cancer cachexia limits how much adequate nutrition can actually be consumed. It is often necessary to provide nutritional support via tube feeding or even providing nutrition intravenously. In addition, the normal effectiveness of dietary protein in reversing the breakdown of muscle protein is limited in cancer cachexia.

Anabolic Resistance and Cancer Cachexia

Anabolic refers to building up muscle. Normally dietary protein is anabolic, because it stimulates the production of new muscle protein. In cancer cachexia the muscle is resistant to the normal anabolic effect of dietary protein (a condition called anabolic resistance). For example, a study published in Clinical Nutrition showed that feeding a normal nutritional supplement containing protein, carbohydrate, and fat designed specifically for cancer cachexia was completely ineffective in stimulating the production of new muscle protein.

The problem in anabolic resistance is that the molecular machinery in the muscle that must be activated to initiate the process of protein synthesis is in an inactive state and cannot be activated by normal nutrition. A high dose of the amino acid leucine, on the other hand, can activate these intracellular factors. When a high dose of the essential amino acid leucine was added to the nutritional supplement in the study described above, the nutritional supplement became an active stimulator of muscle protein synthesis.

Essential Amino Acids and Muscle Protein Synthesis

The effectiveness of a nutritional supplement for cancer cachexia spiked with leucine can be further enhanced by using a balanced mixture of essential amino acids to stimulate muscle protein synthesis. A balanced mixture of essential amino acids with a relatively high proportion of leucine not only activates the initiation of muscle protein synthesis, but also provides all the amino acids necessary for synthesis of muscle protein, since there are ample nonessential amino acids available already. Essential amino acids have the great advantage in this circumstance of being effective in a very small amount. A dose of essential amino acids as small as 3 grams can effectively stimulate muscle protein synthesis, thereby reversing the loss of muscle protein.

Do Essential Amino Acids Stimulate Tumor Growth?

The notion that providing nutrition to cancer patients feeds the tumor and accelerates growth has been kicked around for more than 40 years. Studies done on mice support this perspective, as feeding mice specific amino acids can stimulate tumor growth. However, one must be extremely cautious extrapolating results from mice to humans. Experimental cancer in mice usually involves the implantation of tumors that become much larger, relative to body weight, than any tumor in humans. Further, mice have very little muscle. Thus, a big tumor without much muscle means that the tumor is not getting all the amino acids it needs from muscle protein breakdown for optimal growth.

Therefore, dietary amino acids can stimulate tumor growth in mice. Mice don’t accurately reflect the response in humans. In humans, muscle mass is large relative to tumor load, so muscle protein breakdown provides the tumor with all the amino acids necessary for rapid growth. Consequently, dietary protein will not stimulate tumor growth (the tumor is already getting all the amino acids it needs), but rather the absorbed amino acids will start to replete the muscle protein that has been lost due to the cachexia response.

Essential Amino Acid Supplementation for Cancer Patients

The rapid loss of muscle mass in cancer cachexia contributes directly to mortality and should be treated nutritionally. Because of anabolic resistance and decreased appetite, normal dietary intake is generally insufficient to combat the rapid loss of muscle. Consuming dietary supplements containing essential amino acids, including a relatively high dose of leucine, is a reasonable approach to slowing the rate of muscle protein loss.

Dr. Robert Wolfe

Robert R. Wolfe, PhD, has researched amino acid and protein metabolism for more than 40 years. His work has been continuously funded by the National Institutes of Health since 1975. He has published more than 550 scientific articles and 5 books that have been cited more than 60,000 times according to Google Scholar.

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