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Maintaining and Increasing Muscle Mass in Cancer Patients

Sarcopenia (loss of muscle mass) is an integral and deleterious component of cancer physiology. The metabolism of the tumor microenvironment is catabolic even at the earliest stages of cancer, long before the patient or care provider can see that muscle mass is declining. It is therefore my practice to include a plan for preserving and maintaining muscle mass in all patients.   For those patients who have already lost significant muscle mass it is very challenging.  When a patient has already suffered abnormal weight loss it is still possible to at least stop the decline and at best produce weight gain as muscle.

Tumor burden drives catabolism along with physiologic and behavioral contributors that include adverse effects of cancer treatments, nausea, loss of appetite, pain, changes in digestive function along with the emotional and traumatic stressors of the cancer experience that impact self care and eating behaviors.

Additionally, as the age demographic for cancer patients is typically patients over 50 years of age, the physiology of aging itself is already contributing to the loss of muscle mass that becomes more catabolic each year.   The increased catabolic state that accompanies tumor burden compounds the fact of loss of muscle mass.

 

The guideline for optimized protein intake for older patients is about 1 gram of protein per pound of body weight.  I therefore recommend that patients include 30 grams of protein three times daily from food at a minimum.   And an additional 20-30 grams on top of that.  The supplement can come in the form of free form amino acids or a serving of protein powder in water which are very easy for patients to implement.  

Leucine is a primary branch chain amino acid that is the anabolic signal to skeletal muscle. 

Leucine is abundant primarily in animal proteins.  I recommend vegans consider a branch chain amino acid supplement that supplies 2.5-3 grams of leucine per serving.  A person who eats 30 grams of animal protein will be getting a sufficient dose of leucine and does not need to supplement their meals.

Here is my general recommendation for supplements in addition to 30 grams of protein from food 3 times daily for retaining and building muscle mass:

Branch Chain Amino Acids 1 serving in water twice daily on empty stomach (containing 2.5-3.0g leucine per serving)

Some BCAA products also contain L-glutamine which also contributes to and is the most abundant amino acid in skeletal muscle tissue.

The use of L-Glutamine in cancer patients is controversial as some cancer cells change their metabolism to glutaminolysis using glutamine as the preferred fuel to product ATP (rather than glucose).  However, oral glutamine supplementation is unlikely to amplify glutaminolysis as there is plenty of glutamine available in the large muscle depot at all times.

L-Carnitine 1.5-2.0 grams per day

If patients are having a difficult time eating sufficient protein with meals I will also include a serving of an Complete Essential Amino Acids Formulation along with the BCAA supplementation noted above.

Omega 3 Fatty Acids have also shown anabolic potential.  They are already included in my OutSmart Cancer® Plans due to their multi-faceted contributions to healthy cell and mitochondrial membranes,  inflammation control, reduction of thrombus risk and tumor cell adhesion so important in the tumor microenvironment.  I recommend 2-6 grams daily of EPA-DHA in triglyceride form.

I also recommend that patients use Bone Broth which contains 10grams of protein per cup and often contains electrolytes as well depending upon how it is prepared.  Bone broth contains glutamine which is very healing to the intestinal epithelium and is considered a therapeutic food for cancer patients experiencing intestinal inflammation secondary to their cancer treatments.  Glutamine is one of the primary fuels for the colonocytes and has been in wide use for repair and to restore normal barrier function even in the hospital setting.  The primary protein in bone broth is collagen derived and is not very high in leucine. Collagen is not the best form of protein for muscle mass, but it is still a complete protein and an easy source for patients who may drink 2-4 cups a day as part of their daily fluid intake.  2-4 cups of bone broth daily would provide an additional 20-40 grams of protein.

I also prescribe protein shakes  with 20-30 grams of protein per shake.  This is very effective as many cancer patients become uninterested in food and food preparation, lose their appetite, become nauseous or suffer poor self care due the exhaustion and overwhelm of cancer and cancer treatments.   A protein shake can be designed to be a meal replacement or a supplement to calories and macronutrients.   Whey protein has been shown to be an excellent form for building muscle mass.

Muscle mass is also a function of muscle use and weight bearing.  Therefore an exercise program should also be in place, not only for healthy muscle mass but also because regular exercise has been shown to increase survival and reduce not only cancer related, but all cause mortality and of course is good for stress management and emotional well being.  The statistics on including a minimum of 30 minutes of exercise daily are compelling.   I ask my patients to engage in four 15 minute walks daily to accumulate one hour of walking.  Almost all patients can accomplish this.

Additionally, patients must include strength training with resistance.

Strength Training can be done with weights, whole body weight or resistance bands at least twice per week.  There are many excellent videos to be found only for every age group and level of fitness. No matter how inexperienced or out of shape, anyone can begin.   This makes a huge difference in strength vs frailty in cancer patients and elderly patients and should be part of standard of care within a health model.

I also want to highly recommend the work of Dr. Gabrielle Lyon DO who has devoted herself to the what she calls “Muscle-Centric Medicine”.  Her book, Forever Strong: A New Science Based Strategy for Aging Well” written for the general audience. She clearly explains the science and provides concrete and clear guidelines for eating and exercise to preserve and build muscle at every stage of life.  She also has additional resources for clinicians.

Selected References

Exercise and Cancer Survivorship (book) 2010 ISBN : 978-1-4419-1172-8 https://link.springer.com/book/10.1007/978-1-4419-1173-5

Matei B, Winters-Stone KM, Raber J. Examining the Mechanisms behind Exercise's Multifaceted Impacts on Body Composition, Cognition, and the Gut Microbiome in Cancer Survivors: Exploring the Links to Oxidative Stress and Inflammation. Antioxidants (Basel). 2023 Jul 14;12(7):1423. doi: 10.3390/antiox12071423. PMID: 37507961; PMCID: PMC10376047.

Anjanappa M, Corden M, Green A, Roberts D, Hoskin P, McWilliam A, Choudhury A. Sarcopenia in cancer: Risking more than muscle loss. Tech Innov Patient Support Radiat Oncol. 2020 Nov 9;16:50-57. doi: 10.1016/j.tipsro.2020.10.001. PMID: 33385074; PMCID: PMC7769854.

Williams GR, Dunne RF, Giri S, Shachar SS, Caan BJ. Sarcopenia in the Older Adult With Cancer. J Clin Oncol. 2021 Jul 1;39(19):2068-2078. doi: 10.1200/JCO.21.00102. Epub 2021 May 27. PMID: 34043430; PMCID: PMC8260902.

Larsson L, Degens H, Li M, Salviati L, Lee YI, Thompson W, Kirkland JL, Sandri M. Sarcopenia: Aging-Related Loss of Muscle Mass and Function. Physiol Rev. 2019 Jan 1;99(1):427-511. doi: 10.1152/physrev.00061.2017. PMID: 30427277; PMCID: PMC6442923.

D'Hulst G, Masschelein E, De Bock K. Resistance exercise enhances long-term mTORC1 sensitivity to leucine. Mol Metab. 2022 Dec;66:101615. doi: 10.1016/j.molmet.2022.101615. Epub 2022 Oct 14. PMID: 36252815; PMCID: PMC9626937.

Melone MAB, Valentino A, Margarucci S, Galderisi U, Giordano A, Peluso G. The carnitine system and cancer metabolic plasticity. Cell Death Dis. 2018 Feb 14;9(2):228. doi: 10.1038/s41419-018-0313-7. PMID: 29445084; PMCID: PMC5833840.

Takagi A, Hawke P, Tokuda S, Toda T, Higashizono K, Nagai E, Watanabe M, Nakatani E, Kanemoto H, Oba N. Serum carnitine as a biomarker of sarcopenia and nutritional status in preoperative gastrointestinal cancer patients. J Cachexia Sarcopenia Muscle. 2022 Feb;13(1):287-295. doi: 10.1002/jcsm.12906. Epub 2021 Dec 22. Erratum in: J Cachexia Sarcopenia Muscle. 2023 Apr;14(2):1142. PMID: 34939358; PMCID: PMC8818668.

Reidy PT, Rasmussen BB. Role of Ingested Amino Acids and Protein in the Promotion of Resistance Exercise-Induced Muscle Protein Anabolism. J Nutr. 2016 Feb;146(2):155-83. doi: 10.3945/jn.114.203208. Epub 2016 Jan 13. PMID: 26764320; PMCID: PMC4725426.

Moro T, Brightwell CR, Velarde B, Fry CS, Nakayama K, Sanbongi C, Volpi E, Rasmussen BB. Whey Protein Hydrolysate Increases Amino Acid Uptake, mTORC1 Signaling, and Protein Synthesis in Skeletal Muscle of Healthy Young Men in a Randomized Crossover Trial. J Nutr. 2019 Jul 1;149(7):1149-1158. doi: 10.1093/jn/nxz053. PMID: 31095313; PMCID: PMC7443767.

breast-bone-cancer

The Link between Bone Density and Breast Cancer Risk

Understanding and Monitoring Risk Factors

Bone density, or bone mineral density ( BMD ), is the amount of bone mineral in bone tissue.  Bone mineral density (BMD) is a lifetime marker of estrogen exposure in a woman's body and has been associated with increased breast cancer risk. Estrogen is a crucial factor in maintaining bone density and gradually decreases over age. While there are many factors that influence bone density and bone health, the presence of estrogen contributes to the capacity of bone to continuously remodel and maintain the dynamic balance between bone resorption and bone formation.  A woman’s exposure to estrogen over the life cycle may contribute to her risk of breast cancer.

breast-cancer

Bone density measurement is used in clinical medicine as an indirect indicator of osteoporosis and fracture risk.  There is a clear association between poor bone density and a higher probability of fracture.  There is a clear association between poor bone density and low estrogen levels.  Conversely, there is a clear association between increased and healthy bone density and higher estrogen levels.

pink-ribbonScreening for risk of breast cancer should ALSO include assessment of estrogen levels and bone density along with well-recognized risk factors which include first degree relatives, obesity, increased visceral fat, smoking, alcoholism, early menarche, late menopause, sedentary lifestyle, hormone replacement therapy, and prolonged estrogen exposure, increased density of breast tissue. 

I would also add exposure to environmental endocrine disruptors and imbalances in the intestinal microbiome influencing estrogen metabolism.  

Breast density and bone density are related to endogenous and exogenous estrogen exposure in a woman’s body.  There is a correlation between estrogen exposure, high breast density, high bone density, and increased risk of breast cancer.

Bone is living metabolically active tissue. “Bone remodeling is the process by which bone is renewed to maintain bone strength and mineral homeostasis. Remodeling involves continuous removal of discrete packets of old bone, replacement of these packets with newly synthesized proteinaceous matrix, and subsequent mineralization of the matrix to form new bone begins before birth and continues until death.  Bone remodeling increases in perimenopausal and early postmenopausal women and then slows with further aging, but continues at a faster rate than in premenopausal women. Bone remodeling is thought to increase mildly in aging men.”  Normal Bone Anatomy and Physiology 10.2215/CJN.04151206

Engaging in a health model for all patients includes assessing and managing bone health to promote healthy bone over the life cycle. A health model for cancer patients, due to the typically older age demographics will inherently include a large population of patients already at risk for loss of bone mass, osteopenia and osteoporosis. Screening for bone mineral density and managing bone health should be part of whole-person, whole health care. Taking a thorough history that includes family history, bone health and bone mineral density can bring attention to patients at higher risk for low bone density and fracture as well as patients with a higher risk of estrogen driven breast cancers.

Bone density measurement is used in clinical medicine as an indirect indicator of osteoporosis and fracture risk.  There is a clear association between poor bone density and higher probability of fracture.  There is a clear association between poor bone density and low estrogen levels.  Conversely there is a clear association between increased and healthy bone density and higher estrogen levels.

The Most Common Risk Factors for Low Bone Density and Primary Considerations for a Bone Density Test include:

bone-density 

  • Females age 65 or older
  • Males aged 70 or older
  • People over age 50 with
    • previous bone fracture from minor trauma
    • rheumatoid arthritis
    • low body weight
    • a parent with a hip fracture
  • Individuals with vertebral abnormalities
  • Individuals receiving, or planning to receive, long-term glucocorticoid therapy
  • Individuals with primary hyperparathyroidism
  • Individuals being monitored to assess the response or efficacy of an approved osteoporosis drug therapy
  • Individuals receiving androgen deprivation therapy 
  • Individuals with a history of eating disorders

Additional factors that are related to the risk of low bone density and the need for assessment include smoking, alcohol intake, long-term use of corticosteroid drugs, sedentary or convalescent lifestyle, protein status, mineral status, digestion, and absorption function, chronic inflammation and vitamin D status.  

For cancer patients and survivors also consider periods of poor nutrition, calorie, protein status, convalescence, lack of exercise, effect of hormonal therapies, oophorectomy, orchiectomy, chemotherapy, immunotherapy, treatment induced thyroiditis, gastritis, enteritis and colitis,  chronic pain impacting appetite, digestive and absorptive dysfunction, surgical loss of gastrointestinal organs and function as contributors to risk of loss of bone density and as well as multiple and varied adverse effects of cancer physiology and cancer treatments upon nutritional status and active lifestyle.

Selected References 

Clarke B. Normal bone anatomy and physiology. Clin J Am Soc Nephrol. 2008 Nov;3 Suppl 3(Suppl 3):S131-9. doi: 10.2215/CJN.04151206. PMID: 18988698; PMCID: PMC3152283.

Fraenkel M, Novack V, Mizrakli Y, Koretz M, Siris E, Norton L, Shafat T, Geffen DB. Bone mineral density in women newly diagnosed with breast cancer: a prospective cohort study. NPJ Breast Cancer. 2022 Feb 17;8(1):21. doi: 10.1038/s41523-022-00388-z. PMID: 35177701; PMCID: PMC8854387.

Zain NM, Seriramulu VP, Chelliah KK. Bone Mineral Density and Breast Cancer Risk Factors among Premenopausal and Postmenopausal Women A Systematic Review. Asian Pac J Cancer Prev. 2016;17(7):3229-34. PMID: 27509955.