Have an iPhone? Click here to listen in iTunes
About Andrew Koutnik, BS, PhD(c)
Andrew Koutnik received his Bachelor’s degree with Honors in Exercise Science from Florida State University. While at Florida State, Andrew was involved in 10 publications exploring how exercise, nutrition, supplementation, psychological status, and genetic defects in cardiac tissue impact both
the cardiovascular and autonomic systems. Andrew received a Presidential Fellowship awards to join the Metabolic Therapeutic laboratory at USF College of Medicine to study wasting conditions in cancer. His current research revolves around cancer cachexia and potential therapeutic intervention to mitigate or attenuate this condition.
Connect with Andrew
Books and Products Discussed in this Episode
02:10 Prevalence of Cachexia: Cachexia is tied to COPD, chronic heart failure, kidney failure and AIDS to name a few. It is more prevalent in cancer, Andrew’s area of study. 20% of all patients who have cancer do not die from cancer. They die from cachexia. It is understudies and undertreated. It occurs at a rate of 30% to 80% of all cancer patients. In advanced metastatic cancer, the range is 60% to 80%.
03:37 What is Cachexia? It is a multifactorial syndrome. Weight loss, one of the symptoms, is notorious for worse outcomes and poor quality of life. Anorexia is a component of cachexia. Inflammation is one of the most important aspects of the condition and it ties into the other aspects mentioned above. Inflammation is the focus of many current therapies. Research is being devoted to pro-inflammatory cytokines, IL6 and TNF-Alpha. Both are commonly reported in cachexia. Another symptom, a result of inflammation, is metabolic derangement, where a patient becomes insulin or ghrelin resistant.
07:04 Stages of Cachexia: The first stage, pre-cachexia, begins with initial weight loss and loss of appetite and some metabolic derangement. When you are cachexic, you have reduced food intake, you have lost at least 5% of your body weight and/or greater than 2% of your body weight with a BMI of less than 20 kg/m2, or you have been diagnosed with sarcopenia. In the final stages, refractory cachexia, involves varying degrees of wasting of over 5%. You are resistant to antineoplastics and resistant to any treatment of cachexia. This is usually in the last 3 months of life and is viewed as irreversible. A certain subset of patients, who have stable disease, can gain weight during refractory cachexia.
10:05 Anemia: Anemia is another symptom of cachexia. Biomarkers would be low hemoglobin, low hematocrit, and lower blood cell count. This can lead to functional impairment.
10:15 Loss of Muscle Tone: The most important aspect of cachexia is the loss of muscle tissue. Cachexia is defined as a multifactorial syndrome with a loss of muscle and/or fat. Muscles communicate to the rest of the body. Pro-inflammatory cytokines can go to the muscle and induce catabolism and reduce synthesis of the muscle. Muscle loss may also impact cancer treatments, by decreasing tolerance to antineoplastic treatment. Muscle is its own organ system that plays in integrative role to many other aspects of the body. Cross talk occurs between brain and muscle, brown fat and muscle, white fat and muscle, liver and muscle, as well as pancreas and muscle. Interaction with other systems is one reason it is important to go from cell culture testing to using animal models.
19:07 Diet Impact upon Muscle/Fat Loss: Someone who has been on a ketogenic diet for an extended period of time may lose higher proportions of fat than a diet without the high levels of fat. Your body adapts to the foods we eat. Cachexia is a unique form of weight loss, unlike that from caloric restriction, increased activity or fasting. However, chronic infection seems to replicate many of the facets of cachexia.
24:45 Developing Effective Therapies: There have been about 100 clinical trials with cachexia, but there is no standard of care for it. Progesterone stimulates appetite and has been approved for AIDS cachexia, but not cancer cachexia. SARMS (Selective Androgen Receptor Modulators) is an interesting anabolic agent initially used by some extreme body builders. Because SARMS is specific to muscle tissue, you get the benefits of testosterone, without the side effects. In cachexia patients, SARMS has passed phase 2 trials.
27:11 Sarcopenia: Sarcopenia does not have all of the facets of cachexia. In both you typically lose muscle tissue and body weight. You can have sarcopenia or cachexia, but be obese. Inflammation can play a role in sarcopenia.
29:42 Chronic Stressors: Exercise, not done in the extreme) is a short duration stressor. These appear to be good for you. Chronic stressors are not associated with health. If you inhibit the pro-inflammatory process of exercise (as in taking antioxidants prior to exercise), you reduce the ability for your body to adapt to the process. Chronic stress, even healthy things in excess, start to create negative consequences.
35:52 Beneficial Growth Signals: Acute elevation in certain growth hormones, scare people in the context of treating cancer. Many of those same signals stimulate cancer growth. Benefit to the muscle, may increase tumor growth. Insulin is a potent growth stimulator in cancer.
36:59 Categories Therapies for Cancer Cachexia: These include nutritional therapies and appetite stimulators, like anti-anorexics. Other categories include anti-inflammatories and anabolic agents.
37:24 Nutritional Therapies: The goal of nutritional therapies and appetite stimulators is to eat more calories. Generally, you are not salvaging the muscle, nor are you growing muscle. When you over-consume food in a cachexic (or normal) state, you grow a disproportionate amount of adipose tissue. You can still lose muscle while putting on fat. A higher protein diet is one nutritional strategy. Protein is the substrate for building muscle. There is no evidence that this is effective.
39:03 Anti-Anorexic Therapies: The most studied drug category is progestin. Progesterones are derivatives of this. Megace, the most popular, has been approved for treating AIDS cachexia. It effectively stimulates hunger and is added to other therapies. In cachexia, monotherapies do not work. Ghrelin mimetics stimulate appetite. There is not enough evidence to prompt proscribing them, especially when there may be ghrelin resistance. Corticosteroids stimulate appetite, but there are many side effects.
40:52 Anti-Inflammatory Therapies: Corticosteroids are immune modulating, having a positive impact upon appetite and improve quality of life. The side effect of elevating blood sugar may have an impact upon the tumor. NSAIDs are also used, but there is little evidence of efficacy. Omega 3s are being studied in Andrew’s lab as one of the non-toxic therapies. Omega 3s have anti-inflammatory properties, anti-catabolic properties and may have anti-tumor properties. It could be an integrative component in multimodal therapies. Many omega 3s in the OTC pill form are not necessarily bioavailable.
44:41 Anabolic Agents: Leucine is a nutritional anabolic agent which can stimulate muscle protein synthesis. BCAs over periods of time can induce muscle growth. Stimulating muscle protein synthesis, the synthesis of new muscle, may have an anabolic role. However, if you have an inflammatory state, their ability to be effective may be blocked. There is evidence a ketogenic diet having anti-inflammatory properties and may lower TNF-Alpha, IL6 and C – reactive protein. The ketogenic diet also downregulates a lot of growth signaling. It is worth exploring. In testing, testosterone has been found to reduce fatigue, but it had no effect upon attenuated muscle loss or fat loss. Insulin was tested as well. If you inhibit myostatin, you may have some growth process. This may affect the heart. In cancer patients, myostatin is upregulated, which can exaggerate muscle loss. It appears to be independent of the tumor aspect. Pre-clinical evidence is supportive.
53:00 Caloric Restriction: Caloric restriction has its place in potential anti-cancer therapies, but cachexia can cause death and is a co-morbidity. Only calorically restrict to a level of body weight that is healthy and maintainable. You may have an initial drop in tumor. There is a theory that chemotherapy can knock out all but a chemo-resistant subsection of a heterogeneous tumor, leaving room and nutrition for the tumor to grow.
56:20 SARMs for Hypertrophy: Andrew hesitates to recommend, since it has not gone through phase three trials. It is context dependent.
59:59 Low Carb vs Keto: Andrew is a type 1 diabetic and a low carb approach helps him to manage his blood sugar levels. Carbs have a place in performance. Andrew does powerlifting and has made personal records using both dietary approaches. Do what helps you to effectively maintain blood sugar levels. Find out what works for you. Lack of sleep, being sick, exercise intensity and duration, effects insulin sensitivity. Andrew has been taught many valuable lessons about being sensitive to his body and lessons for his work in the lab. Blood sugar metabolism is being found to impact many serious conditions.
01:13:51 Andrew’s Elevator Speech: Exercise and nutrition are medicine, but not considered so in the medical field. More initiatives should be made on things that do not involve drug intervention.