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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.

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 

 

 

blood-test

What Common Blood Tests Can Detect Early Signs of Cancer

While there is no simple blood test for predicting who will get cancer, there is a lot of information to be gleaned from basic blood work that, taken together, reveals much about an individual’s predispositions for many forms of cancer. By monitoring selected biomarkers routinely measured in primary care, you can learn a lot about physiological patterns that promote carcinogenesis, proliferation, progression, and recurrence long before tumor markers emerge or there are radiological or pathological findings indicating cancer.

The art of assessment lies in part in recognizing the patterns. By learning how to read the multiple biochemical signals that emerge from a pro-carcinogenic “tumor microenvironment,” you can begin to practice real prevention, and give your patients the opportunity for significant improvements in both health-span and lifespan.

The tests included in this article here are ones you are routinely ordering in the integrative and functional medicine setting. While they are not to be misconstrued as diagnostic tests for cancer, they can indicate that a patient is at increased risk, and that further assessment and action is required to identify potential malignancy.

In people who’ve had cancer, these common tests are often prognostic for disease progression and recurrence.

It is vital that primary care practitioners do a better job of recognizing the early signs of recurrence among cancer survivors. According to the American Cancer Society’s 2016-2017 Survivorship Facts and Figures, the population of cancer survivors will increase to 20.3 million by January 1, 2026.

After conventional oncology treatment is finished, these patients typically return to their primary care physicians. They are highly motivated, ripe for change, and in search of clinicians who can support their efforts to restore health and prevent recurrence.

The tests described below will help you fill that role.

Complete Blood Count

One of the most common biomarkers of overall health is the Complete Blood Cell panel, which can be used to monitor hematologic abnormalities caused by solid tumors, hematologic malignancies, as well as the side-effects of the therapies used to treat them.

The following findings are not definitive diagnostic signals, but taken together, they suggest that someone is at greatly increased risk:

  • Elevated White Blood Cells > 11.0 109/L
  • Elevated Platelets > 350 109/L
  • Low Hemoglobin <10.0 g/dL
  • High Neutrophil to Lymphocyte Ratio (NLR)

The latter finding—a high NLR—is especially important.

Neutrophils promote cancer progression, proliferation, and metastasis by increasing vascular endothelial growth factor (VEGF), Hepatocyte growth factors, inflammatory cytokines IL-6, IL-8, matrix metalloproteinases (MMP), and elastase. Neutrophils and macrophages secrete tumor growth promoting factors and contribute to a proliferative tumor microenvironment.

Therefore a high neutrophil count is suggestive of a neoplastic process somewhere in the body.

According to a 2014 metanalysis of 57 studies, an NLR greater than 4.0 was associated with a hazard ratio for overall survival (OS) of 1.81 (95% CI = 1.67 to 1.97; P < .001), an effect observed in all disease subgroups, sites, and stages and that predicts increased risk of mortality (Templeton AJ, et al. JNCI. 2014:106(6).)

Simply put, an NLR over 4 predicts tumor progression and poor overall survival. This is a readily available and inexpensive biomarker with a lot of prognostic value.

Hyperglycemia

A fasting glucose in the range of 100-126 mg/dl is suggestive of cancer risk.

Glucose may have a direct role in cancer development. Tumor cells have increased numbers of receptors for insulin, insulin-like growth factor, and GLUT4. Thus, they transport more glucose into themselves, and this promotes growth and proliferation. It is the main reason for using a low-glycemic, modified ketogenic diet in patients with cancer.

Proliferating tumor cells have up- regulated glucose transporters. Elevated serum glucose is linked to increased risk and progression of many solid cancers, including breast cancer (Haseen SD, et al. Asian Pac J Cancer Prev, 2015:  16, 675-8).

High glucose levels also result in a state of chronic inflammation, which leads to an increase of cytokines, such as interleukin 6 (IL-6), tissue necrosis factor alpha (TNF-α) and vascular endothelial growth factor (VEGF). All of these promote cancer progression, proliferation, and metastasis (Crawley DJ, et al. BMC Cancer, 14(1), 985).

Given the high prevalence of diabetes, metabolic syndrome, and insulin resistance in the US, this is an important indicator to watch.

Serum glucose is a modifiable risk factor. Diet and lifestyle changes that reduce and regulate glucose will also help to reduce risk and progression of cancer.

High Insulin & Low SHBG 

Prolonged hyperinsulinemia leads to reduced hepatic production of sex hormone binding globulin (SHBG). This, in turn, increases risk of steroid hormone driven cancers. Low SHBG results in increased amounts of unbound estrogens and androgens that drive carcinogenesis in breast, endometrial, prostate lung, colorectal and pancreatic tissues.

Free unbound estrogen also exerts immunosuppressive effects in the tumor microenvironment, and has a profound impact on anti-tumor immunity and tumor-promoting inflammation that is completely independent from its direct activity on tumor cells (Svoronos N, et al. Cancer Discovery, 2017: 7(1), 72-85).

Low Serum Albumin

Serum albumin levels have prognostic significance in cancer, and can be used to better define baseline risk in cancer patients. It is generally useful in assessing the nutritional status, disease severity, disease progression, and prognosis.

In a multivariate analysis of 29 studies, Gupta and Lis found, “higher serum albumin levels to be associated with better survival.” (Gupta D, Lis CG. Nutrition Journal, 2010: 9(1), 69).

In the early stages of cancer, there is slight or no hypoalbuminemia. But as the disease progresses, malnutrition and inflammation suppress albumin synthesis, and albumin levels drop significantly.

Albumin levels under 3.5 g/dL are often seen in patients with sarcopenia and cachexia. Malnutrition is a predictor of reduced survival. It is also associated with deteriorating quality of life, decreased response to treatment, increased risk of chemotherapy-induced toxicity, and a reduction in cancer survival.

On the high side, albumin concentrations above 37.5 g/L are predictive of both chemotoxicity and of survival (Srdic D, et al. Supportive Care in Cancer, 2016: 24(11), 4495-4502).

It is also important to look at the Albumin-to-Globulin Ratio.

A ratio of less than 1.66 is a risk factor for cancer incidence and mortality, both short- and long term, in generally healthy screened adults. In people who’ve already developed some form of cancer, a low albumin-to-globulin ratio predicts low overall survival (Suh B, et al. Ann Ocol (2014): 25(11), 2260-2266).

Elevated Ferritin

Ferritin, a strong negative survival predictor, has been associated with the pathological processes of inflammation and infection. High ferritin is suggestive of inflammation, immunosuppression, tumor angiogenesis, and proliferation.

Elevated serum ferritin—indicated by levels over 200 ng/ml in men, and over 150 ng/ml in women–have been seen in people with breast cancer, pancreatic cancer, non-small cell lung cancer, hepatocellular carcinoma, leukemia, colorectal cancer and lymphoma.

High ferritin levels are significantly associated with reduced survival time and increased mortality in cancer patients (Lee S, et al. J Cancer, 2016: 7(8), 957-964)

25-OH Vitamin D Deficiency

Vitamin D has a multi-functional impact on the tumor microenvironment. Increased levels of Vitamin D are associated with reduced occurrence and reduced mortality of different types of cancer, including skin, prostate, breast, colon, ovary, kidney, and bladder.

Vitamin D is involved in a very wide range of physiological processes relevant to cancer development, including: Regulation of Gene Transcription; Growth Arrest; Apoptosis; Cellular Differentiation; DNA Repair; Antioxidant Protection; Immune Modulation; Regulation of Pro-Inflammatory Cytokines; and Control of Angiogenesis & Metastasis.

Low or suboptimal levels of 25-OH Vitamin D are associated not only with increased risk of various forms of cancer, but also with poor prognosis, and more aggressive disease (McDonnell SL, et al. PloS One, 2016: 11(4), e0152441).

This is particularly true in breast cancer. In one study, vitamin D-deficient women with breast cancer typically had more aggressive molecular phenotypes and worse prognostic indicators than those with adequate vitamin D (Williams JD, et al. Endocrinology, 2016: 157(4), 1341-1347).

The Vitamin D Council suggests repletion to 40 to 80 ng/mL, with a target of 50 ng/ml, for optimal health on multiple fronts, including colorectal cancer prevention (Bischoff-Ferrari HA, et al. Am J Clin Nutr, 2006: 84(1), 18-28).

Supplementation to reach mean serum concentrations of 72 nmol/L showed a beneficial effect  against cancer development (Lappe JM, et al. Am J Clin Nutr. 2007: 85(6), 1586-1591).

When assessing patients in the context of cancer risk, the following guidelines are useful:

25 –hydroxy- Vitamin D (ng/ml)

Deficient                                                        < 50

Optimal                                                           50-70

Optimal for Cancer & CVD                70-99

Excess                                                            >100

Elevated Lactic Acid Dehydrogenase

Lactate dehydrogenase (LDH) is an enzyme that catalyzes the reduction of pyruvate to lactate.

Aberrant metabolism and inefficient fuel production is a characteristic of tumor cells, which are dominated by aerobic glycolysis, increased lactate production, and a higher uptake of glucose (the Warburg effect).

Elevated LDH may be a marker of these aberrant metabolic processes in cancer cells.

The normal range for LDH is thought to be 100-333 u/L, with levels greater than 245 u/L considered to be in the upper quartile of normal. Above that 245 u/L mark, it is suggestive of early carcinogenesis, tumor cell proliferation, tumor progression, and poor prognosis.

It is often highly elevated in aggressive forms of cancer and hematological malignancies including: melanoma, lymphoma, acute leukemia, seminoma germ cell, pancreatic, gastric, lung, renal cell, nasopharyngeal, esophageal, cervical, and prostate cancers (Wulaningsih W, et al. Br J Cancer. 2015:113(9). Zhang J, et al. Sci Rep. 2015:5, 9800).

Elevated C-Reactive Protein

C-Reactive Protein (CRP) is a well-established inflammatory marker. It is also a biomarker of cancer survival.

CRP is elevated in patients with solid tumors, and high levels predict poor prognosis, blunted treatment response, as well as tumor recurrence.

As part of the systemic inflammatory response to a tumor, the body releases pro-inflammatory cytokines and growth factors. Interleukin-6, produced by the tumor or surrounding cells, stimulates liver production of acute-phase reaction proteins that increase C-reactive protein (CRP) and fibrinogen.

Elevated CRP correlates with disease stage and increased cancer mortality (Shrotriya S, et al. PloS One. 2015: 10(12), e0143080). Individuals with a high baseline CRP (>3 mg/L) have an 80% greater risk of early death compared with those with low CRP levels (<1 mg/L).  

Patients with invasive breast cancer and CRP levels>3 mg/L at diagnosis have a 1.7 fold increased risk of death compared to those with CRP levels<1 mg/L at diagnosis (Allin KH, et al. Breast Cancer Res. 2011: 13(3), R55).

Converging Signals

No one of the aforementioned test parameters is, in and of itself, an indicator that someone has cancer. But by looking at standard blood test results in a new way, you can start to recognize the patterns of high risk and active cancer physiology. This is crucial to early identification and early intervention.

Clinicians who are aware of the converging signs can meaningfully shift the microenvironment from one that promotes cancer to one that is not supportive of carcinogenesis, proliferation, or progression. In the same way, we can provide meaningful support for the rising tide of underserved cancer survivors and at-risk patients in need of not only a disease plan, but also a health plan.

Prostate-Cancer-Control

Boron and Prostate Cancer Control

Aside from non-melanoma skin cancer, prostate cancer is the most common cancer among men in the United States. It is also one of the leading causes of cancer death among men of all races and Hispanic origin populations.(1)

Dietary Boron intake is inversely correlated with prostate cancer incidence. (5)

Prostate risk is  52% lower in men whose diets contain at least 1.8mg boron daily. Prostate cancer risk reduction is correlated with boron intake.  Recommended optimal daily dose of elemental boron is 3 mg/day for health maintenance.

Mechanisms of Action

Boron-containing compounds interfere with the physiology and reproduction of cancer cells through diverse mechanisms, including inhibition of serine proteases, NAD-dehydrogenases, mRNA splicing and cell division, receptor binding mimicry, and induction of apoptosis. (2) 

normal-prostate

In several studies Barranco et al (7, 8, 9, 10) demonstrate that increased boron intake is associated with lower levels of Prostate Specific Antigen (a biomarker for prostatitis and prostate cancer) as well as modulation of serum estradiol leading to increased expression of ER-beta receptors and decrease of ER-alpha receptors on tumor cells decreasing proliferation and growth signaling.  Furthermore boron supplementation increased regulation of cell cycle arrest, increased apoptosis, decreased cell adhesion, migration and metastatic progression. 

Boron decreases cancer associated inflammatory factors including hs CRP, TNFa, Interleukin-6 all of which are elevated in the tumor microenvironment.   “Elevated hs-CRP is associated with an increased risk for breast cancer, obesity and metabolic syndrome (MetS) in children, atherosclerosis, unstable angina, insulin resistance, type 2 diabetes, nonalcoholic fatty liver disease (NAFLD), metastatic prostate cancer, lung cancer, adult depression, depression in childhood and psychosis in young adult life, coronary heart disease, and stroke." (2)

In  murine study Insulin Like Growth Factor was significantly reduced in the prostate tumor cells in boron dosed animals. The IGF-1 signaling pathway promotes cancer progression and its down regulation is associated with lower risk of prostate cancer. (6)

“Increased intracellular concentration of borate activates borate transporters and leads to growth inhibition and increased apoptosis. “ (2) (3) (11)

Boron may act as a Histone De-acetylase Inhibitor (HDI).  HDI’s act as therapeutic agents for cancer due to their impact on gene expression on growth arrest signaling, cell differentiation and apoptosis in cancer cells. (2)

Boronic Acid has been shown to inhibit hypoxia inducible factor (HIF) which is a physiological stimulus for tumor induced angiogenesis.  Inhibition of HIF leads to inhibition of Vascular Endothelial Growth Factor (VEGF) and the production of capillary blood supply to tumor cells. Angiogenesis leads to exponential tumor growth and to metastatic progression of solid tumors. (11)

Plant foods rich in boron include Avocados, dried apricots, dried prunes, raisins, red kidney beans, lentils, almonds, hazelnuts, brazil nuts, pistachios, cashews and walnuts.

In summary, dietary and supplemental oral boron intake should be optimized to create a tumor microenvironment and cancer terrain that decreases risk of prostate carcinogenesis,proliferation and disease progression through angiogenesis and metastasis. 

 

Selected References

1. American Cancer Society Statistics https://cancerstatisticscenter.cancer.org/

2. Scorei RI, Popa R Jr. Boron-containing compounds as preventive and chemotherapeutic agents for cancer. Anticancer Agents Med Chem. 2010 May;10(4):346-51. doi: 10.2174/187152010791162289. PMID: 19912103.

3. Romulus Ion Scorei and Radu Popa, Sugar-Borate Esters –Potential Chemical Agents in Prostate Cancer Chemoprevention  DOI: 10.2174/18715206113139990124 Volume 13, Issue 6, 2013 Page: [901 - 909]

4. Kiliccioglu I, Konac E, Varol N, Gurocak S, Yucel Bilen C. Apoptotic effects of proteasome and histone deacetylase inhibitors in prostate cancer cell lines. Genet Mol Res. 2014 May 9;13(2):3721-31. doi: 10.4238/2014.May.9.17. PMID: 24854658.

5. Cui Y, Winton MI, Zhang ZF, et al. Dietary boron intake and prostate cancer risk. Oncol Rep. 2004;11(4):887-892.

6. Pizzorno, L.  Review: Nothing boring about boron. Integrative Medicine Vol. 14, No. 4 August 2015

7. Barranco WT, Hudak PF, Eckhert CD. Evaluation of ecological and in vitro

effects of boron on prostate cancer risk (United States). Cancer Causes Control. 2007;18(1):71-77.

8. Barranco WT, Eckhert CD. Boric acid inhibits human prostate cancer cell proliferation. Cancer Lett. 2004;216(1):21-29.

9. Barranco WT, Eckhert CD. Cellular changes in boric acid-treated DU-145 prostate cancer cells. Br J Cancer. 2006;94(6):884-890.

10. Barranco WT, Kim DH, Stella SL Jr, Eckhert CD. Boric acid inhibits stored Ca2+ release in DU-145 prostate cancer cells. Cell Biol Toxicol. 2009;25(4):309-320.

11. Shimizu K, Maruyama M, Yasui Y, Minegishi H, Ban HS, Nakamura H. Boron-containing phenoxyacetanilide derivatives as hypoxia-inducible factor (HIF)-1alpha inhibitors. Bioorg Med Chem Lett. 2010;20(4):1453-1456.

OutSmart-Cancer-Immuno-Therapy

Modulating Extreme Adverse Effects of Immunotherapy Treatments

Today, more and more patients are avoiding toxic chemotherapy in favor of targeted cancer therapies.  Among the many new therapies available are a class of immunotherapy drugs that take the brakes off of the immune system and mobilize T cells against tumor cells.

Because tumor cells have the capacity to disable T cells, this therapy addresses the huge problem of immune resistance in many cancers.  Drugs in the class of PD1 and PDL1 inhibitors were some of the first to be developed.  These drugs bind to PD1 or PDL1 receptors on the tumor surface and unleash the fury of the immune system upon the tumors by removing the inhibitory function of these ligands.

Nature has designed the immune system with both a gas pedal and a brake.  The PD1 and PDL1 inhibitors are the brakes.  Take off the brakes and the immune system is activated.

The best of outcomes with these treatments may result in complete tumor eradication, a truly miraculous outcome for some patients.  I have a patient who came to me with Stage 4 Endometrial Cancer with Lung Metastases some years ago.  After reduction of some of her tumor burden with surgery and rather brutal chemotherapy, her very forward-thinking Gynecologic Oncologist included a course of Keytruda (Pembrolizumab), which was a new immunotherapy treatment at the time. 

The historical prognosis for this patient would have been certain eventual mortality for her metastasized aggressive cancer.  However, she achieved a complete response and has been in remission and designated NED or No Evidence of Disease for many years now.   This is a patient who most likely would not be alive today without the advent of PD1 -PDL-1 inhibitor therapy.

The problem with this class of drugs is that their use is very unskillful and very unpredictable. Some patients will respond with a modicum of mild to moderate systemic autoimmune inflammation while other patients will be disabled by furious, extreme, and damaging autoimmune syndromes.  Some patients may die from extreme autoimmune activity.  I had one patient who developed myocarditis and died within a few days of receiving his first dose.  This was a prostate cancer patient whose sudden death was completely unexpected and not predicted.   

These patients require a health model and safe, effective modulation of extreme auto-immune inflammation not provided by their oncology teams. 

Some patients will have immune activation similar to a nice warm burning ember.  They get the therapeutic benefit without extreme adverse effects.  While other patients will respond with a forest fire of inflammation that must be suppressed aggressively with steroid medications for long periods of time.  The adverse effects of long-term steroid therapy then become part of the clinical picture and challenge for these patients.  In these circumstances, it IS reasonable to ask if the cure is worse than the disease itself? 

My patient developed such severe colitis (a common adverse effect) that she visited the emergency room multiple times for fluid and electrolyte replacement due to extreme persistent watery diarrhea.  Additionally, the nutritional status of this patient was also compromised and she became depleted in both calories and nutrients and developed sarcopenia.

Many cancer patients receiving PD1 and PDL 1 inhibitors are left with lifelong autoimmune disease.   Most common are autoimmune arthritis, colitis, thyroiditis, dermatitis, pneumonitis, and associated loss of normal tissue and organ function.  Some patients suffer ongoing chronic inflammatory pain syndromes.

Less prevalent, but also part of the long list of adverse effects are myocarditis, pericarditis, nephritis, hepatitis, pancreatitis, neuritis, vasculitis. Essentially, any tissue or organ can be impacted with associated loss of function and sequelae.

It is my practice to screen and monitor patients receiving cancer immunotherapies for the development of autoimmune syndromes and intervene early.  If I have a patient with a history of inflammatory or autoimmune disorders I can predict that such patients are more likely to develop adverse effects. 

Additionally, high levels of inflammation not only lead to pain syndromes but are also contributors to ongoing chronic fatigue as well as agitation,  cognitive changes, sleep disruption, anxiety, and depression, and the stress of living not only as a cancer survivor but with a chronic and distressing autoimmune syndrome difficult to control and manage.  It is my firm goal that Quality of Life must be a goal in all treatment plans for cancer patients and survivors.

 If a patient has NO inflammatory adverse effects it is assumed that the patient is not going to benefit from the PD1/PDL1 inhibitor because there is no sign or symptom indicating immune activation.   I always tell patients we should celebrate if they develop a rash or diarrhea because we know the drug is working!   

In fact, it is my observation over many years of following patients who have received these therapies that when the course of immunotherapy treatment is completed those patients who continue to have low levels of inflammation continue to have the therapeutic benefit of tumor control.  This is only an empirical observation on my part.  For example, the endometrial cancer patient described above continues to have mild colitis and has remained in remission.  Before the availability of these therapies, we would expect this patient to have a recurrence and to die of her advanced stage 4 metastatic disease within a few years of her diagnosis.   Patients such as this with lung metastases historically had very poor prognoses and very high mortality rates.  Patients with powerful and manageable responses to PD1 and PDL1 inhibitors may live a long time.  While some patients do recur, some have not.  We have not had decades of time to follow these patients as these treatments are relatively new.  If nothing else, these treatments do extend the life of many patients.

How can we modulate the auto-immune adverse effects of these potentially curative immunotherapy treatments?   I have taken the approach that we employ in Functional and Naturopathic Medicine in the management of auto-immune syndromes to turn down the volume on the immune inflammation just enough to reduce extreme side effects, damage, and loss of function without losing the therapeutic benefit of these immunotherapy treatments.   

While we can rely on studies that have demonstrated that Omega 3 Fatty Acids, Vitamin D3, and Curcumin and a healthy microbiome can modulate auto-immune inflammation, there is a paucity of research on managing autoimmune syndromes related to immunotherapy adverse effects with the exception of steroids. (See selected references below.)

I share with you here my empirical clinical experience.  I have employed this approach with several hundred patients since immunotherapies have come into wider use in oncology.  Clinicians experienced in managing autoimmune syndromes will recognize the basic principles of care.

  • Anti-Inflammatory, Low Antigen Diet
  • Support for the healthy intestinal microbiome 
  • Specific Nutriceutical-Phytochemical Interventions
    • Omega 3 Fatty Acids (EPA DHA)  recommended dose 4-6 grams daily SPMs Specialized ProResolving Mediators can also be considered 1-2grams daily
    • Fat soluble Curcumin recommended dose 2-6 grams daily
    • Vitamin D3 5,000-25,000iu daily  (125mcg-625mcg). 
      • Consider a loading dose of 50,000iu (1.25mg)

I always start at the lower end of the dose range and spread the dosing out into 3-4 doses over the day.  The goal is to MODULATE but not SUPPRESS the therapeutic impact.  It is also important to be mindful of the anticoagulant/platelet aggregation inhibitory effect of such an approach and to determine which patients may NOT be a candidate for high dosing due to thrombocytopenia or anticoagulant pharmaceutical therapies.

This approach has few negative drug-nutrient interactions. I have continued these inflammation-modulating therapies continuously for many years with most patients.  Dosing is highly individualized to each patient towards the goal of supporting and promoting healthy function and quality of life.

For front-line clinicians interested in supporting the health of cancer patients and cancer survivors and learning and implementing my OutSmart Cancer® System developed over 35 years in practice, I encourage you to join our training program, Foundations of Integrative Oncology, self-paced online training with clinical supervision and mentoring.  Go to aiiore.com.  

There is a huge population of patients whose lives have been touched by cancer searching for a health model and skilled and knowledgeable clinicians.

Selected References:

Vitamin D and autoimmune diseases.
Illescas-Montes R, Melguizo-Rodríguez L, et al Life Sci. 2019 Sep 15;233:116744. doi: 10.1016/j.lfs.2019.116744. Epub 2019 Aug 8. PMID: 31401314 

Vitamin D intake is associated with decreased risk of immune checkpoint inhibitor-induced colitis.
Grover S, Dougan M, et al Cancer. 2020 Aug 15;126(16):3758-3767. doi: 10.1002/cncr.32966. Epub 2020 Jun 22. PMID: 32567084

Therapeutic Potential of omega-3 Polyunsaturated Fatty Acids in Human Autoimmune Diseases.
Li X, Bi X, Wang S, Zhang Z, Li F, Zhao AZ.
Front Immunol. 2019 Sep 27;10:2241. doi: 10.3389/fimmu.2019.02241. eCollection 2019.  PMID: 31611873 

Resolvins: Emerging Players in Autoimmune and Inflammatory Diseases.
Abdolmaleki F, Kovanen PT, et al 
Clin Rev Allergy Immunol. 2020 Feb;58(1):82-91. doi: 10.1007/s12016-019-08754-9. PMID: 31267470 

Curcumin in Autoimmune and Rheumatic Diseases.
Yang M, Akbar U, Mohan C.
Nutrients. 2019 May 2;11(5):1004. doi: 10.3390/nu11051004.
PMID: 31052496 

Curcumin and autoimmune disease.
Bright JJ.
Adv Exp Med Biol. 2007;595:425-51. doi: 10.1007/978-0-387-46401-5_19. PMID: 17569223  

Curcumin as an Adjuvant to Cancer Immunotherapy.
Paul S, Sa G.
Front Oncol. 2021 Aug 16;11:675923. doi: 10.3389/fonc.2021.675923. eCollection 2021.
PMID: 34485117 

Gut Bacteria Influence Effectiveness of a Type of Immunotherapy. https://www.cancer.gov/news-events/cancer-currents-blog/2018/gut-bacteria-checkpoint-inhibitors. Feb 2018  NCI Staff