In a recently published paper titled “Use of progestogens and the risk of intracranial meningioma: national case-control study” by Noémie Roland, Anke Neumann et al* the authors assessed the impact of multiple forms of progesterone on the development of brain meningiomas.   The statements in this paper could lead a journalist or patient or anyone not performing a close reading of this study to the false conclusion that all forms of progesterone are linked to brain lesions.  This is not true.

A meningioma is type of lesion is usually noncancerous tumor that arises from the membranes surrounding the brain and spinal cord.  Sixty percent of intracranial meningiomas examined expressed progesterone receptors.  

 The authors investigated multiple forms of progesterone including synthetic progestogens. The forms of progesterone included in the study were progesterone, hydroxyprogesterone, dydrogesterone, medrogestone,medroxyprogesterone acetate, promegestone,dienogest, and intrauterine levonorgestrel.

In naturopathic and integrative medicine bioidentical compounded progesterone is typically used and is labelled “progesterone” and may be used in oral, topical or vaginal forms.

 The study was conducted in France over 10 years from January 2009-December 2018.  The study investigated 108, 366 women who had surgery for meningiomas and these were matched to controls.

The authors concluded that no excess risk of meningioma was associated with the use of progesterone, dydrogesterone, or spironolactone, or the hormonal intrauterine systems used worldwide, regardless of the dose of levonorgestrel they contained.”

Meningiomas may also be associated with age over 65, neurofibromatosis type 2 and exposure to ionizing radiation. Meningiomas are also associated with and may enlarge during pregnancy when progesterone levels are normally elevated in support of the pregnancy.  Furthermore, the authors observed decreasing dosing and withdrawal of  progestogens generally led to a reduction in meningioma volume.

“Prolonged use of medrogestone, medroxyprogesterone acetate, and promegestone was found to be associated with an increased risk of meningioma. Future studies should further clarify the association between the duration of use and risk for the progestogens studied and extend the discussion of meningioma risk to dienogest and hydroxyprogesterone.”

Should you receive questions from concerned patients who are using bio-identical progesterone or levonorgestrel found in many intra-uterine devices on the basis of this study, please do review with them the safety, risks and benefits. 

This is yet another example that in the realm of prescribed hormone replacement therapies that it is vital to be clear about the difference between different forms of  hormones and synthetic hormone mimetic drugs.   Too often these are all labeled progesterone or estrogen in the news and are misunderstood by the general public, our patients.  It is our responsibility to make sure patients are well educated and fully informed and have access to reliable information about their health and medical choices.

 Using any type of hormone therapy is a decision made between a patient and their healthcare provider after carefully weighing the risks and benefits. Bioidentical hormones have been controversial, and many are not FDA-approved, but that doesn't mean a healthcare provider will rule them out as a treatment option.

*Roland N, Neumann A, Hoisnard L, Duranteau L, Froelich S, Zureik M, Weill A. Use of progestogens and the risk of intracranial meningioma: national case-control study. BMJ. 2024 Mar 27;384:e078078. doi: 10.1136/bmj-2023-078078. Erratum in: BMJ. 2024 Mar 28;384:q776. PMID: 38537944; PMCID: PMC10966896.

Historically women diagnosed with breast cancer have received surgery, chemotherapy, targeted therapy, radiotherapy and if estrogen receptor positive, hormonal therapy as standard of care, all of which come with short term and long-term adverse effects.  This approach is now considered to be over-treatment for some patients.  All women should receive thorough assessment to determine if they will or will not benefit from radiotherapy, chemotherapy, hormonal therapy and targeted therapies.  Individualized care plans must become the norm for all women with breast cancer.

In the era of personalized medicine, there are now assessments such as Oncotype DX**, that can determine if chemotherapy or hormonal therapy would provide the most benefit, or no benefit. As a result, many women who previously would have received chemotherapy, no longer suffer exposure to toxic systemic therapy as part of their treatment plan without compromise to survival.

Another study*** has demonstrated that radiotherapy may be unnecessary for some breast cancer patients who are diagnosed at an early stage. After breast conserving surgery a subset of patients who have received neoadjuvant systemic therapy may be able to forgo adjuvant radiotherapy with no impact on long term survival.  This avoids the early and late adverse effects of radiotherapy and contributes to preserving quality of life.

Additionally a recent study* determined that it is feasible and safe to omit axillary lymph node resection surgery in early breast cancer patients who have an excellent response to primary systemic neo-adjuvant therapy. Annemiek Van Hemert, MD, of the Netherlands Cancer Institute in Amsterdam reported that “Breast cancer patients with lymph node positive breast cancer may avoid extensive axillary surgery if they have clear nodes after systemic neoadjuvant chemotherapy.”

 

She further states, “If we are able to predict the response based on the removal of only one lymph node, it means we can safely avoid extensive removal of the lymph nodes if no living tumor cells are left,” Van Hemert said in a statement. “This will avoid serious complications, such as painful swelling in the arm, known as lymphedema.”   This allows effective treatment as well as less harm to patients.

This study was conducted over a period of 8 years from 2014-2021 and is ongoing and there will be more long-term outcomes data in the future.

Patients in this study were both hormone receptor negative and positive.  Patients were both her2neu negative and positive. There were triple negative patients in the study as well.  Patients who had 3 or more axillary nodes were selected to participate in this study.  Node staging was ascertained by PET-CT prior to systemic treatment.  The largest node was marked with radioactive iodine. After systemic treatment this node was excised and evaluated for response to treatment.

Patients who achieved a complete lymph node response to neoadjuvant chemotherapy or targeted treatment (47%) received only radiation therapy and no lymph node dissection.  Patients with residual lymph node disease (53%) received surgical lymph node dissection followed by radiotherapy.

After 44 months, the group with complete lymph node response after neoadjuvant treatment had a Recurrence Rate of 3.2%, Disease Free Survival rate of 85% and and Overall Survival Rate of 93%.   The group with residual disease after neoadjuvant therapy had had similar outcomes of 3.5%. 90% and 82% respectively.

The study concluded that “Surgical removal of axillary nodes can be safely omitted in about 80% of patients treated with primary systemic therapy.”

This is an ongoing study that will continue long-term follow-up.

Dr Fiorita Poulakaki, Head of the Breast surgery Department at Athens Medical Centre Hospital, Greece, and Vice President Europa Donna, the European Breast Cancer Coalition, commented

 “When we treat patients for breast cancer, it is important to ensure that treatment itself causes as little harm to the patients as possible. The results from this study suggest a way to help us avoid side effects that affect the quality of life and can sometimes cause considerable long-term distress to patients. Every day we cure patients, making sure they live long lives, but at the same time we should care also about survivorship issues.”

 As advocates, guides and counselors for our patients, we can educate our patients to initiate a discussion with her oncology team to practice highly individualized decision making so that the most appropriate care plan is put in place for each patient which considers quality of life, life span as well as health span. 

This is fundamental to the OutSmart Cancer® System which includes individualized assessments, consideration of the tumor microenvironment and a whole biosystem approach.  Furthermore, the OutSmart Cancer® provides for a HEALTH PLAN, not just a disease plan for each patient at every stage of their cancer journey.

 

Selected References

*Charles Bankhead, Senior Editor, Study Shows Feasibility, Safety of Omitting Axillary Surgery in Early Breast Cancer. Pathologic CR to guide treatment decisions led to similar 

outcomes in node-positive disease    MedPage Today March 22, 2024

 

van Hemert AKE, van Olmen JP, Boersma LJ, et al. De-ESCAlating RadioTherapy in breast cancer patients with pathologic complete response to neoadjuvant systemic therapy: DESCARTES study. Breast Cancer Research and Treatment. 2023 May;199(1):81-89. DOI: 10.1007/s10549-023-06899-y. PMID: 36892723.

 

**The Oncotype DX Breast Recurrence Score® test https://precisiononcology.exactsciences.com

In January 2023, Memorial Sloan Kettering Cancer Center published a study* demonstrating the safe and effective use of Chinese Herbal Medicines for the management of short-term adverse effects of cancer treatments. The study was a joint effort between the Cancer Center, Pharmacy, Herbal Oncology Program and Integrative Medicine Departments and demonstrates the safe and effective concurrent use of selected Chinese Herbal Formulas to manage and resolve selected adverse effects and promote and restore normal healthy function.

The following Chinese Herbal Formulas were studied in the management of three common adverse effects of cancer treatments:

         Chronic Insomnia: Jia Wei Suan Zao Ren

         Constipation: Ma Zi Ren Wan

         Chronic Diarrhea: Shen Ling Bai Zhu San

These common formulas are readily available from multiple high-quality suppliers and can be found in capsule, tablet and freeze-dried granule forms. **  These formulas can also be compounded by a Chinese Herbal Pharmacy and made into teas.  Chinese Herbal Formulas are typically dosed 2-4x per day taken with warm water or tea and with meals. 

There were 851 outpatients in the study.  84% of participants were undergoing active treatment for multiple cancers.  The Herbal Oncology Program dispensed 1,266 prescriptions over the course of the study to address pain, fatigue, poor appetite, gastrointestinal and mood disorders as well as disrupted sleep related to treatment.   Participants surveyed expressed the need to seek treatment for unmet needs for management of adverse effects and support for health and quality of life. 

The study demonstrated a high level of participant satisfaction and relief while incorporating Chinese Herbs into their care plan with the support of their oncology team.  The formulas selected were of high-quality vetted ingredients, supported by research, and provided excellent symptom management as well as restoration of healthy function, and did not interfere with their oncology treatments.

 

The study team reports that patients requested and received support for acid reflux, bloating and indigestion, dizziness, fatigue inflammation, insomnia, mood, nausea and vomiting, pain, and other unspecified adverse effects.  Additional herbal prescriptions were dispensed for acute cold and flu, cough, as well as for symptoms of fatigue, allergy, dizziness, and hot flashes, but were not part of the study formulations.

 Comments:   

The use of Modern Chinese Herbal medicine is well supported by research and wide clinical use.  

Many Chinese Herbal formulas, such as those used in this study, fall into a “nutritive” category in which tissue repair and normalization and enhancement of structure and function can be achieved without deleterious drug-herb, radiotherapy-herb, immune-therapy or targeted therapy-herb interactions.  

I regularly recommend Chinese Herbal Medicines as well as Acupuncture for management of adverse effects of treatments and for nurturing, promoting, and restoring normal healthy function. This allows patients not only to be able to successfully complete their course of treatments, but also to enjoy and maintain healthy function and quality of life.  This also gives the patient a sense of agency and control and the feeling that they are taking something life giving and non-toxic as well as efficacious.

Symptom management of adverse effects in conventional oncology usually adds more pharmaceuticals to the care plan and rarely results in repair or sustained restoration of healthy function and can come with additional drug toxicities.

This study serves as a prototype for future studies and demonstrates both the safety and efficacy of Chinese Herbal Medicines for managing and resolving common adverse effects of cancer treatments.  This study is also a model of collaborative teams composed of clinicians with diverse skilsl and training working together with mutual respect in service to best outcomes for patients.  

This is inherently the model of the OutSmart Cancer® System which is devoted to multi-disciplinary, multi-faceted, cooperative, and inclusive teams that offer both the best disease care along with a health model for cancer patients and cancer survivors. 

If health is the desired outcome, there must be a plan for HEALTH designed and implemented by health experts on the team. This fills in the missing health side of the cancer equation in conventional oncology care which remains disease focused and is therefore limited and not comprehensive.  

I have been privileged and honored to be able to demonstrate the value of this model over 35 years of clinical practice in concert with leading oncology teams that realize the value of including a multi-faceted integrative approach that contributes a health model for their patients.

 

 *Hou YN, Chimonas S, Gubili J, Deng G, Mao JJ. Integrating herbal medicine into oncology care delivery: development, implementation, and evaluation of a novel program. Support Care Cancer. 2023 Jan 21;31(2):128. doi: 10.1007/s00520-023-07577-x. PMID: 36680628; PMCID: PMC9860233.

**I recommend and have no affiliations with these high quality Chinese Herbal Suppliers: Sun Ten, Blue Poppy, Evergreen, May Way Herbs, TCMZone, to name a few.

Additional Selected References

Yang M, Feng Y, Zhang YL, Smith CM, Hou YN, Wang H, Deng G, Mao JJ. Herbal formula MaZiRenWan (Hemp Seed Pill) for constipation: a systematic review with meta-analysis. Phytomedicine. 2021;82:153459.doi: 10.1016/j.phymed.2021.153459. [PubMed] [CrossRef] [Google Scholar]

 Wang H, Hou YN, Yang M, Feng Y, Zhang YL, Smith CM, Hou W, Mao JJ, Deng G. Herbal formula Shenling Baizhu San for chronic diarrhea in adults: a systematic review and meta-analysis. Integr Cancer Ther. 2022;21:15347354221081214. doi: 10.1177/15347354221081214. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Xiang Y, Guo Z, Zhu P, Chen J, Huang Y. Traditional Chinese medicine as a cancer treatment: modern perspectives of ancient but advanced science. Cancer Med. 2019;8(5):1958–1975. doi: 10.1002/cam4.2108. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Confused about soy isoflavones, soy foods and risk of breast cancer? A recent study concluded that natural phytoestrogens including isoflavone compounds derived from soy and other plants reduce breast cancer recurrence and improve survival.  Results from a study conducted at Johns Hopkins Kimmel Cancer Center, “Phytonutrients and outcomes following breast cancer: a systematic review and meta-analysis of observational studies.” were published in January 2024.

Researchers concluded that soy isoflavones were associated with a 26% reduced risk of breast cancer recurrence among post-menopausal women breast cancer survivors. The most significant results were realized at 60 milligrams per day.

 

Soy contains isoflavone compounds including genistein and daidzein. Isoflavones are phytoestrogens, that have a similar structure to human 17-β estradiol hormone. Phytoestrogens bind to and mildly activate estrogen receptors and act as selective estrogen receptor modulators. Phytoestrogens block the binding of native estrogen and thus block the effects of human estradiol.  Phytoestrogens exert a very mild effect on estrogen activation compared to human estradiol.  Therefore, there is less estrogen activation and signaling in the presence of isoflavone phytoestrogens.

Another review, Soy Isoflavones and Breast Cancer Risk: A Meta-analysis, conducted by Ioannis Boutas, et al in 2022 concluded, “The consumption of soy isoflavones can reduce the risk of breast cancer in pre-menopausal and post-menopausal women.”

A review conducted in 2023, .” Benefits of Soybean in the Era of Precision Medicine: A Review of Clinical Evidence, Jung Hyun Kang, et al, examined the current clinical evidence focusing on the benefits and risks of soybean ingredients and concludes “In breast, prostate, colorectal, ovarian, and lung cancer, epidemiological studies showed an inverse association between soybean food intake and cancer risks. Soybean intake was inversely correlated with risks of type 2 diabetes mellitus (T2DM), and soy isoflavones ameliorated osteoporosis and hot flashes. Notably, soybean was one of the dietary protein sources that may reduce the risk of breast cancer and T2DM.”

Additionally, as early as 2010 Dr. Mary Hardy MD of UCLA Simms Mann Center for Integrative Oncology, Dr. Donald Abrams MD of UC San Francisco Center for Integrative Medicine and Dr. Mark Messina, Ph.D., professor of nutrition a Loma Linda University, CA, co-authored a paper, Can clinicians now assure their breast cancer patients that soyfoods are safe? (Women's Health (2010)6(3), 335–338, addressing the confusion that exists among physicians and patients regarding the health consequences of soy foods and soy isoflavones.  In this paper they identify soy isoflavones as selective estrogen receptor modulators.  They conclude that it is safe for women to include whole, minimally processed soy foods including tofu, soy milk, whole soybeans (like edamame), miso, soy yogurt, and tempeh, in their diets, but that soy foods and soy isoflavones should not be considered as treatment for breast cancer.

 

There is now a clear body of evidence not only demonstrating the safety of phytoestrogens contained in soy and other botanicals, but also their benefits which include the potential reduced risk and reduced recurrence of breast cancer, support for control of menopausal symptoms such as hot flashes and osteoporosis as well as reduced risk of Type 2 Diabetes.

 

Over many decades I have created and honed my OutSmart Cancer® System so that patients have a Health Plan not just a disease plan as well as the tools and knowledge to Create A Body Where Cancer Cannot Thrive.

 

 

My OutSmart Cancer® System includes addressing the unique needs and challenges of five major stages of the Cancer Journey. 

• Just Diagnosed/Shock, Overwhelm, Acceptance/Preparation
• In Treatment/Staying Healthy/Managing Side Effects/Quality of Life
• After Treatment/Recovery/Restoration/Rejuvenation
• Life Beyond Cancer/Remission/Cure/No Evidence of Disease
• Living with Cancer As a Chronic Illness/Living Well, Managing Side    Effects/Quality of Life

There is indeed a Sixth Stage. Some patients will die while under our care. 

We must support them, or refer appropriately so that they can accept that they are facing End of Life and that the cancer is stronger and smarter than the treatments we have available and that it is time to prepare on all levels and in all ways for the dying process and the final exhale.

It is always difficult to begin the conversation, but it is essential that at least ONE of the patient’s care providers be comfortable with a very frank and real and compassionate conversation with the patient, their family and circle of care of what MAY lie ahead.

It is our role to be available for this process and dialogue or to refer appropriately to clinicians who will address their questions and concerns and make sure they have the resources for a peaceful, healing, comfortable and compassionate dying process and final exhale.  If you are not comfortable or trained to do so, please explicitly tell the patient you will refer them to a clinician who can do so.  Make sure you have trusted resources in your community for them.

It is shocking to me HOW MANY oncologists do not have this conversation until the patient is perhaps not even capable of planning for themselves and their loved ones.

It is my personal and professional belief that every person deserves to know what is happening to them and what to expect and that they may indeed be facing their mortality.  But before that final breath, there is a potential to create a healing and integrative journey and a plan for a peaceful and conscious dying process.  

I am thinking now of one particular patient whom I treated for many years for extremely aggressive and recurrent fallopian tube cancer. 

She engaged fully in an integrative approach including OutSmart Cancer diet, lifestyle, supplements, acupuncture, high dose IV Vitamin C and mistletoe therapies. Her very forward thinking and collaborative oncologist offered her many many options, but her cells became resistant quickly after only a month or two of treatment with each try. Eventually she developed malignant ascites, a dire prognostic sign. 

Finally her care providers’ and the patient’s collective decision was to have her enter into compassionate hospice care. The patient accepted this decision with grace as I had started talking with her about her treatment resistance, the aggressive nature of her cancer and what it means prognostically when malignant ascites develops and progresses.  She was well aware that she could die of this cancer with this presentation and history.  I knew that she had not properly prepared fully for her children and that she would have to entangle her business and plan for that transition as well.   And it was time for her to accept and begin to reflect and ponder the end of life and death and dying.   We talked frankly and explicitly about the need to prepare practically, emotionally and spiritually.   

Although she accepted her death, she stated that she was fearful.  She was in a lot of pain which gave her the most anxiety.   This is true of many patients, it is the pain, suffering and anxiety and not having any familiarity with the dying process that makes them most uncomfortable.

Because I made sure she had lead time, she prepared legally, financially and practically for herself and her children.  I encouraged her to work with a therapist to help her to talk with her children.   But she really did not have the tools or the inner development to meet the dying process, contemplate it and find a way to dissipate her fear and have a peaceful transition.

My last conversations with her were about this very process, what to expect, how to plan a peaceful process, how to create the environment and support she wanted to have and to reassure her that hospice physicians and nurses are exceptionally thoughtful and compassionate and attuned human beings who would keep her comfortable, manage her pain and let her know what was unfolding at every step of the way.

Although her oncologist ordered hospice care for her, these most important conversations were not included.   

In person-centered models of medicine, it is the RELATIONSHIP between the patient and the doctor….two tender human beings that matters most at the end.   

I encourage all of you to step into these conversations with your patients.  The only way to become comfortable with them is to practice practice practice.   Start by contemplating your own death and you will find your way.

And so I have realized that there is indeed a Sixth Stage of the Cancer Journey in my OutSmart Cancer® System for some patients and that is the acceptance and conscious, compassionate and potentially healing and transformational journey to the End of Life.

Books I recommend for Patients and Families:

A Beginner’s Guide to The End, Practical Advice for Living Life and Facing Death, BJ Miller 

The Art of Dying Well, A Practical Guide to a Good End of Life, Katy Butler

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.