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Study: Managing Cancer Treatment Side Effects with Chinese Herbs

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]

Soy Intake Linked to Improved Survival in Breast Cancer

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 survivalResults 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.

Guiding Patients Through All Stages of The Cancer Journey: The Final Chapter

 

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

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.

anxiety-and-depression

Integrative Resources for Cancer-related Anxiety and Depression

The OutSmart Cancer® System is a WHOLE PERSON approach to supporting the health of cancer patients, survivors and their loved ones.  This includes addressing the psycho-social and spiritual needs of our patients.

Anxiety and depression are common human responses both for patients and loved ones  during every phase of the cancer journey, from diagnosis, active treatment, recovery, living with cancer as a chronic illness or as a cancer survivor long term.  Psychological and spiritual concerns often go untreated.

Most patients require some encouragement to talk about their emotional, psychological and spiritual challenges. It is vital to include thoughtful support and resources to all patients, family members and significant others

ASCO

Cancer is a collective experience and everyone close to the patient is touched by the diagnosis and the suffering.   Everyone is transformed by the depth and intensity of the experience.

“I very much like to frame the cancer journey as an opportunity, as a meaningful and sacred gateway in

 one’s life.  It is a time for reflection and inquiry and for clarifying one’s priorities and core values.  

Many patients and families find the depth and intimate nature of the experience to be ultimately transformational and healing, especially when shared.”

I ask  patients to ponder the questions:

  • What gives me strength?
  • What gives me courage?
  • What are my fears?
  • What are my hopes and dreams?

Patients and families are encouraged to take the opportunity to enter into a new phase of life with new learned self-care and lifestyle tools and resources in alignment with the health focused and proactive principles of my OutSmart Cancer® System.

patients-and-families

The Society for Integrative Oncology(SIO) and ASCO (The American Society of Clinical Oncology) have co-published a resource outlining an integrative approach and research supported resources and recommendations for patients during active treatment as well as post-treatment.

“ I think of post-treatment as the rest of your life, not a finite period of time.”

Recommended Interventions from SIO and ASCO include:

  • Mindfulness based interventions/meditation
  • Yoga
  • Tai Chi/Chi Gung
  • Hypnosis
  • Acupuncture
  • Music/Music Therapy
  • Reflexology (Massage)
  • Aromatherapy: Lavender Essential Oil

SIO and ASCO convened a multi-faceted and diverse expert panel. Their literature search included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2023. This team developed evidence-based guideline recommendations. The literature search identified 110 relevant studies (30 systematic reviews and 80 randomized controlled trials) to inform their guidelines.

I also encourage patients to seek appropriate psychological and spiritual counseling, spend time in nature, engage in creative activities  through art, dance, movement, writing, journaling and poetry as well as the recommendations outlined above.

It is possible to transform challenges and suffering into the pearls of new insights, loving-kindness, compassion and wisdom that can richly inform our inner and outer lives at every phase of the cancer journey.

Additional information is available at www.asco.org/survivorship-guidelines

Reference:

Integrative Oncology Care of Symptoms of Anxiety and Depression in Adults With Cancer: Society for Integrative Oncology–ASCO Guideline

Linda E. Carlson, Nofisat Ismaila, Elizabeth L. Addington, et al

Rhodiola

Rhodiola, Mitochondria and Cancer Chemoprevention

Rhodiola (rosea and crenulata spp.) is a botanical adaptogen with broad application in cancer chemoprevention and mitochondrial support for cancer patients undergoing and recovering from cancer therapies.

Rhodiola is considered an adaptogen. It supports multiple functions that enhance resilience, responsiveness and recovery in the face of stress.

mitochondriaRhodiola came to widespread prominence when it was used by Olympic athletes, high altitude mountain climbers and long distance runners to enhance endurance and sustained energy over 50 years ago.

Rhodiola rosea and its primary active phytochemicals, salidroside and rosavins, have been widely studied for effects on cellular metabolism, energy production, inflammation control, oxidative stress, autophagy and cell death.

Salidroside is known to bind to the cell membrane and enter the cytosol via a membrane transporter where it influences AMPK and improves endothelial function and nitric oxide production, enhances glucose uptake and fatty acid oxidation and inhibit and gluconeogenesis and glycogen synthesis.

AMPK activity is required for cells to respond to stress and changes in energy balance.  It is primarily through this pathway that Rhodiola appears to enhance normal mitochondrial function and energy metabolism.  

Salidroside is water soluble and highly bioavailable via oral administration and its metabolites are excreted in the urine.

Rhodiola has also been shown to inhibit tumor promoting mTOR pathway and reduce angiogenesis and metastasis by down-regulating expression of HIF1a/HIF2a signaling. Reducint mTOR expression is a goal in chemoprevention and in optimizing the tumor microenvironment.

Rhodiola has demonstrated positive synergistic effects when combined with the chemotherapy agent cyclophosphamide.  

Rhodiola metabolites are excreted through the urine and one human study showed that patients with superficial bladder carcinoma who consumed Rhodiola orally reduced the average frequency of recurrence by 50%. 

Murine studies have shown that Rhodiola has Immuno-stimulating properties and increases, CD3 and CD4 T cells, Interferon-g and IL-2 cytokines.

Rhodiola demonstrates anti-inflammatory activity by inhibition of COX2, PLA2, NfkB, TNFa, IL-1B and IL-6 which are all upregulated in the tumor microenvironment. Additionally Rhodiola has inhibits expression of the NLRP3 inflammasome which is activated in the lung epithelia both during viral infections as well as malignancy.  (As a side note, this property of Rhodiola may also enhance vaccine adjuvant effect and maturation of dendritic cells and promote immune response to vaccine innoculation)

rhoRhodiola rosea and Rhodiola crenulata  are available as liquid botanical extract and in capsule form. Rhodiola extracts typically contain 3% salidrosides and 1% rosavins.  A therapeutic dose of Rhodiola is 3000mg/day.

A maintenance dose for cell protection and healthy aging ranges from 200-1000mg per day. Always use professional grade supplements and suppliers.

Rhodiola has a wide range of applications in chronic syndromes, healthy aging, and chemo-prevention and recovery by positively influencing multiple pathways in the cancer terrain and tumor microenvironment.

Selected References

Rhodiola and salidroside in the treatment

of metabolic disorders                                               
Xiang-Li Bai, et al, DOI : 10.2174/1389557519666190903115424

Rhodiola rosea L.: an herb with anti-stress, anti-aging, and immunostimulating properties for cancer chemoprevention

Yonghong Li , et al DOI: 10.1007/s40495-017-0106-1

mTOR, AMPK, and Sirt1: Key Players in Metabolic Stress Management                            
Silvia Cetrullo
, et al DOI: 10.1615/critreveukaryotgeneexpr.2015012975 

KNOW

Knowledge in Integrative Oncology Website

KNOW is a tool that allows access to up-to-date research on natural agents in cancer care.

KNOW: Knowledge in Integrative Oncology Website

https://www.knowintegrativeoncology.org/

Phone & Fax: 1-800-908-5175

Email info@knowoncology.org

KNOWintegrativeoncology.org is dedicated to improving the lives of people with cancer through integrative cancer care.

KNOW shares current best evidence on the use of nutrition and natural health products in oncology. Our goal is to inspire collaboration among healthcare providers, researchers, and advocacy groups to support education, safety, and clinical decision-making.

KNOW is a tool that allows access to up-to-date research on natural agents in cancer care. KNOW systematically searches and presents relevant human studies, including clinical trials, from Medline and EMBASE.

In KNOW, data is searchable by tumor type, natural therapy, conventional treatment, and side effects. You can copy references into professional communications, academic projects or presentations, education materials, curriculum, and websites. KNOW provides convenient links to the publisher for full text review or access.

Key Benefits of KNOW

  • Efficient access to current best evidence
  • Improves clinical outcomes
  • Supports development of educational resources
  • Comprehensive and cost-effective
  • Answers questions about natural therapies in cancer care

KNOW also provides Resources for Patients and Provider Network 

  • COMPETENCY AND SAFETY Articles in KNOW provide important information about safety, tolerability, preparation, dosing, and side effects not readily available to clinicians

How KNOW supports you:

✔ Improved efficiency - Enormous energy is spent to distill current literature.

✔ Stay up-to-date - The volume of research in integrative oncology is ever increasing and it's nearly impossible to stay abreast. Our team keeps the website current with summaries of published studies that the average clinician cannot easily acquire.

✔ Knowledge sharing with providers - KNOW references can be pasted into letters, handouts, presentations, and websites..

✔ Evidence-informed practice - Informed decisions require access to relevant research.

✔ Knowledge base for teaching - A central repository of information supports curriculum for integrative residencies, fellowships, and other training programs.

✔ Collaboration for research and publication projects

Membership to KNOW is subscription-based, providing access for individuals, cancer care teams, research groups, academic project groups, hospitals, and public education organizations.

For more information: https://www.knowintegrativeoncology.org/

bone cancer

Higher Risk of Bone Fracture for Cancer Survivors

Cancer stage, chemotherapy treatment, hormonal treatment, menopause status, physical activity and smoking history increase risk of bone fracture for cancer survivors.

Adult cancer survivors, specifically those who have received chemotherapy, hormonal blockade therapy and/or a diagnosis within five years, are at an increased risk for bone fractures.

bone-fracture

Recent studies published JAMA Oncology, also demonstrated decreased risk for physically active survivors and increased risk for smokers.

“These findings are important as the number of cancer survivors living in the United States is projected to rise to 26.1 million by 2040. Research like this seeks ways for cancer survivors to have a better quality of life after their diagnosis,” said Dr. Erika Rees-Punia, senior principal scientist, behavioral and epidemiology research at the American Cancer Society and lead author of the study, in a press release. “Fractures of the pelvis and vertebrae are more than just broken bones – they are serious and costly.”

Rees-Punia, et al analyzed the association between cancer stage and time of diagnosis with risk of pelvic, radial and vertebral fractures compared to adults without a history of cancer including behavior, lifestyle and type of cancer treatment. 

Among 92,431 participants included in the study, 12,943 experienced a frailty-bone fracture. Cancer survivors who were diagnosed with an advanced cancer stage within five years were at the highest risk for bone fractures compared to those without a history of cancer. Osteoporotic fractures occurred in vertebrae, pelvis and hip.

Additionally, cancer survivors who received chemotherapy had a higher rate of fracture, compared to those who did not receive chemotherapy. 

“We hope our findings will inform clinical guidance on fracture prevention, which could incorporate physical activity with exercise cancer professionals and smoking cessation programs, to improve quality of life after a cancer diagnosis,” Rees-Punia added.

Additional risks related to loss of bone density include malnutrition, persistent stress and elevated cortisol, use of steroid hormones, hyperthyroidism, estrogen and androgen hormone blockade therapies, oophorectomy, menopause, extended convalescence.

While clinicians primarily focus on risk of osteoporosis and bone fracture in women, men can also develop fracture risk and loss of bone mass. Men with low testosterone and androgens as well as men with prostate cancer being treated with androgen deprivation therapy should also be monitored for fracture risk and bone health.

Recommended Patient Guidance and Screening to reduce risk of bone fracture include

  • Bone Mineral Supplements Daily. (Copper free and including bone minerals and co factors)
  • Adequate intake of protein daily 
  • Regular weight bearing and resistance exercise
  • Active vs. Sedentary Lifestyle Support
  • Stop Smoking Support
  • Appropriate Bone Density Scans (DEXA)
  • Appropriate N-Telopeptide Crosslinks Urine Tests to assess rate of turnover of bone minerals
  • Consultation with physician to determine if anti-resorptive or hormonal                   medication may be of benefit to manage bone density and fracture risk

Selected References 

Rees-Punia E, Newton CC, Parsons HM, et al. Fracture Risk Among Older Cancer Survivors Compared With Older Adults Without a History of Cancer. JAMA Oncol. Published online November 03, 2022. doi:10.1001/jamaoncol.2022.5153

Suarez-Almazor ME, Pundole X, Cabanillas G, Lei X, Zhao H, Elting LS, Lopez-Olivo MA, Giordano SH.

Association of Bone Mineral Density Testing With Risk of Major Osteoporotic Fractures Among Older Men Receiving Androgen Deprivation Therapy to Treat Localized or Regional Prostate Cancer.

JAMA Netw Open. 2022 Apr 1;5(4):e225432. doi: 10.1001/jamanetworkopen.2022.5432.

PMID: 35363269 

Daya NR, Fretz A, Martin SS, et al. Association Between Subclinical Thyroid Dysfunction and Fracture Risk. JAMA Netw Open. 2022;5(11):e2240823. doi:10.1001/jamanetworkopen.2022.40823

Bauer DC. Clinical Use of Bone Turnover Markers. JAMA. 2019;322(6):569–570. doi:10.1001/jama.2019.9372

Acupuncture

Acupuncture Provides Long Term Pain Relief for Breast Cancer Patients

Acupuncture Provides Long Term Pain Relief for Joint Pain Caused by Aromatase Inhibitors

In a randomized study conducted in November 2022 by a research team headed by Dr. Dawn Hershman MD,  asked


Does short-term acupuncture confer long-term reduction of joint pain related to aromatase inhibitors among women with breast cancer?

acupuncture-for-breast-cancer

This study demonstrated the benefits and highlights the durability of response to Acupuncture which significantly relieved joint pain caused by aromatase inhibitors in women diagnosed with early-stage, hormone receptor-positive breast cancer for one year.

Patients received 18 acupuncture treatments over 12 weeks.

This is a typical and traditional course of acupuncture applied to achieve a  real pattern change and durable outcome.  Controls included an second set of patients who received sham acupuncture and a third group of patients were told their were on a waiting list and received no treatment.   All patients had been receiving AI therapy for at least 30 days at inception. 


Patients were monitored for another 40 weeks and thus were followed for a full year.

“The study was conducted at 11 academic and community sites within the National Cancer Institute Community Oncology Research Program. Sites were required to have 2 trained acupuncturists for the duration of the trial.” (1)

 

Aromatase Inhibitors (AI) are widely used in the treatment of estrogen receptor positive breast cancers.    AI inhibit the transformation of androgens in the tissue into biologically active estrogens which can bind to the receptors on breast cancer cells sending a growth signal. Aromatase inhibitors are usually prescribed after surgery for five to ten years to reduce risk of recurrence in post-menopausal women.  


Commonly used first line AI include Arimidex (anastrozole), Aromasin (exemestane) and Femara (letrozole).


However a common adverse effect is joint pain and stiffness which contributes to non-compliance with therapy for more than 50% of breast cancer patients.  Many patients do not disclose to their physicians that they have discontinued AI therapy due to poor quality of life and persistent pain.

Researchers concluded that “Acupuncture was associated with a statistically significant decrease in aromatase inhibitor–related joint pain that persisted at 40 weeks after discontinuation of the intervention, suggesting long-term benefits of this therapy.”  

acupuncture-for-breast-cancer

(1) The study showed that a full course of therapeutic acupuncture over three months led to a durable change in perceived pain at 52 weeks compared to controls. This study did not follow women past 52 weeks.

Subsequent systemic reviews and meta-analyses (2, 3) of acupuncture trials have also demonstrated efficacy and long term beneficial effect. 

1.Hershman, D. Et al Comparison of Acupuncture vs Sham Acupuncture or Waiting List Control in the Treatment of Aromatase Inhibitor-Related Joint Pain: A Randomized Clinical Trial. JAMA Netw Open. 2022 Nov 1;5(11):e2241720. doi: 10.1001/jamanetworkopen.2022.41720. PMID: 36367721; PMCID: PMC9652759.

2. Liu X, Lu J, Wang G, et al. . Acupuncture for arthralgia induced by aromatase inhibitors in patients with breast cancer: a systematic review and meta-analysis. Integr Cancer Ther. 2021;20:1534735420980811. doi:10.1177/1534735420980811 - DOI - PMC - PubMed

 

3. MacPherson H, et al. ; Acupuncture Trialists’ Collaboration . The persistence of the effects of acupuncture after a course of treatment: a meta-analysis of patients with chronic pain. Pain. 2017;158(5):784-793. doi:10.1097/j.pain.0000000000000747 - DOI - PMC - PubMed

 

breast-cancer

Melatonin Reduces Radiation Dermatitis in Breast Cancer Patients

Radiation induced dermatitis is a common adverse effect and complication of radiotherapy.  Topical melatonin has proven to be a safe and effective agent in the prevention and treatment of radio-dermatitis in breast cancer patients.   Melatonin protects the skin by acting both as a topical anti-inflammatory and as an antioxidant. (5)

In a randomized placebo controlled trial women undergoing radiotherapy applied topical melatonin gel twice daily and for 2 weeks after completing radiotherapy.  The control group received a placebo gel. In the melatonin group  the occurrence of Grade1/2 radiation dermatitis was 59% vs 90% of the placebo group. “Patients treated with melatonin-containing emulsion experienced significantly reduced radiation dermatitis compared to patients receiving placebo.” (1). 

Topical Melatonin

  • Reduces inflammation and oxidative stress at the site of  irradiation
  • Delays onset of radio-dermatitis
  • Decreases the intensity of radiodermatitis and skin damage
  • Promotes resolution of dermatitis 
  • Promotes healing of skin
  • Improves Quality of Life 

Stress, nervous strain.Sleepless problem.Medicine diffuser.Flat vector

In two double blind randomized placebo controlled trials by the same research team, breast cancer patients applied a low dose melatonin cream twice daily during their course of radiotherapy.  The control group received a placebo cream.  During the first two weeks of therapy there was no difference between the 2 groups. Although there was no statistical difference, the researchers state that melatonin “demonstrated a protective effect”.   They posited that another study with a higher dose of melatonin is warranted. (3)  Researchers reported that melatonin decreased  breast symptoms of radiation dermatitis and improved quality of life for patients in the melatonin group (4)

In a case report a breast cancer patient applied melatonin cream daily and for 3 weeks after completing. radiotherapy treatment.  Radiation dermatitis did not appear at the radiated site until one week after final treatment (a delayed response) and resolved within 3 weeks of continued use of topical melatonin. (2)

There have been no reports of adverse effects with the use of  topical melatonin.

Apply topical melatonin to irradiated skin twice daily during radiotherapy and continuing for 2-3 weeks after completion of course of treatment until the skin is healed.

Melatonin gel or cream can be made by a compounding pharmacist.  Melatonin is also commercially available as a topical cream, as a liposomal solution and as a topical spray. 

References

1 Melatonin for Prevention of Breast Radiation Dermatitis: A Phase II, Prospective, Double-Blind Randomized Trial.

Ben-David MA, Elkayam R, Gelernter I, Pfeffer RM.

Isr Med Assoc J. 2016 Mar-Apr;18(3-4):188-92.

PMID: 27228641 Free article. Clinical Trial. 

2 Compounded Melatonin Cream for the Prevention and Treatment of Radiation Dermatitis: A Case Report.

Garcia-Segura LC, Garcia-Segura JC, Delgado DC, Romero MN, Salgado EC, Llorens LP.

Int J Pharm Compd. 2022 Jan-Feb;26(1):6-8.

PMID: 35081038 

3 Effect of melatonin cream on acute radiation dermatitis in patients with primary breast cancer: A double-blind, randomized, placebo-controlled trial.

Zetner D, Kamby C, Christophersen C, Gülen S, Paulsen CB, Piga E, Hoffmeyer B, Mahmood F, Rosenberg J.

J Pineal Res. 2023 Apr 13:e12873. doi: 10.1111/jpi.12873. Online ahead of print.

PMID: 37055944