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Author: Chopel Lhamu

Vitamin-D

Higher Vitamin D Intake Reduces Risk of Colorectal Cancer

In a recent (2021) study* investigators concluded that higher total vitamin D intake is associated with decreased risks of
young-onset colorectal cancer and precursors (polyps).

colorectal-cancer
Colorectal Cancer (CRC) infographic for education
Colorectal Cancer (CRC) infographic for education illustration


Excluding skin cancers, colorectal cancer is the third most common cancer diagnosed in both men and women in the United States. The rate of people being diagnosed with colon or rectal cancer each year has dropped overall since the mid-1980s, mainly because more people are getting
screened (colonoscopy) and changing their lifestyle-related risk factors (healthy BMI, decreasing red meats, refined foods, and increasing fiber and phytochemicals from fruits and vegetables and whole grains).

From 2013 to 2017, incidence rates dropped by about 1% each year. But this downward trend is mostly in older adults and masks rising incidence among younger adults since at least the mid-1990s. From 2012 through 2016, it increased every year by 2% in people younger than 50 and 1% in people 50 to 64. 
https://www.cancer.org/cancer/colon-rectal-cancer/about/key-statistics.html

During the period from 1991 to 2015 the researchers* documented 111 cases of young-onset colorectal cancer and 3,317 colorectal polyps. Analysis showed that higher total vitamin D intake was associated with a significantly reduced risk of early-onset colorectal cancer. The same link was found between higher vitamin D intake and risk of colon polyps detected before age 50.

According to principal researcher K Ng, “Our results further support that vitamin D may be important in younger adults for health and possibly colorectal cancer prevention,

Understanding risk factors that are associated with young-onset colorectal cancer leads to informed recommendations about diet and lifestyle, as well as identifying high-risk individuals to target for earlier screening.

Many cancers, including colorectal and ovarian cancers, that were historically prevalent in older age groups are increasingly being seen in younger patients. Therefore, frontline, primary care providers, particularly in a health-focused setting such as functional, integrative, naturopathic, nutritional, and oriental medicine clinics MUST include patient teaching and appropriate screening in patients under 50.

Vitamin D is both a prognostic and predictive biomarker for both well patients and patients with a diagnosis or history of cancer. It is an important modulator of immunity and cancer biology in multiple histological types of cancer including skin, prostate, breast, ovary, colon, bladder, and kidney malignancies.

With regard to the functions of Vitamin D in the tumor microenvironment, Vitamin D

  • Regulates Gene Transcription
  • Induces Growth Arrest
  • Induces Apoptosis
  • Enhances DNA Repair
  • Enhances Antioxidant Protection
  • Enhances Immune Modulation
  • Enhances Differentiation
  • Decreases Pro-Inflammatory Cytokines
  • Decreases Invasion into the Extracellular matrix
  • Decreases Angiogenesis & Metastasis

I recommend including Serum 25-OH Vitamin D assays for ALL patients. Aim for Optimized Serum 25-OH Vitamin D levels of 60-80 ng/ml for promoting a robust cancer terrain that is inhospitable to the development, progression, and spread of cancer. Oral Vitamin D should be administered as Vitamin D3 cholecalciferol (not ergocalciferol, Vitamin D2).

*Reference: Hanseul Kim, Marla Lipsyc-Sharf, Xiaoyu Zong, Xiaoyan Wang, Jinhee Hur, Mingyang Song, Molin Wang, Stephanie A. Smith-Warner, Charles Fuchs, Shuji Ogino, Kana Wu, Andrew T. Chan, Yin Cao, Kimmie Ng, Edward L. Giovannucci.Total Vitamin D Intake and Risks of Early-Onset Colorectal Cancer and Precursors. Gastroenterology, 2021; DOI: 10.1053/j.gastro.2021.07.002

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  • Confidently obtain a detailed cancer history
  • Address the unique needs of your patients whose lives have been touched by cancer
  • Create care plans focused on the post-treatment concerns of cancer survivors
  • Become the long-term health partner that patients in your community are seeking 
blood-test

Selected Prognostic Cancer Biomarkers from Common Blood Tests

What Can You Learn About Cancer Survival from a CBC?

Common Biomarkers, Cancer Progression and Survival

tumor microenvironment

An excellent paper "Inflammatory markers in cancer: Potential resources * is a thorough and detailed discussion of routinely measured Cancer Biomarkers found in the inflamed tumor microenvironment that are indicative of immune capacity and prognosis. Clinicians will typically have access to a current CBC (Complete Blood Count) with differential and can readily calculate the lymphocyte ratios below

The presence of inflammatory markers is linked to both risks of cancer development and cancer survival.  Cancer-related inflammation is associated with tumorigenesis and tumor progression. Increased levels of multiple biomarkers are present in the tumor microenvironment.

A thorough evaluation will include Cytokines, Leukocytes, Acute-phase proteins (ferritin, ceruloplasmin, CRP).     

Although not routinely measured, prostaglandins, cyclooxygenases, lipoxygenases, transcription factors, and LDH may be elevated. 

Cancer Related Inflammation Promotes

  • Tumor Growth
  • Proliferation
  • Progression
  • Angiogenesis  
  • Metastasis
  • Thrombus Formation
  • Immune Suppression
  • Cancer Related Fatigue  
  • Depression
  • Pain

Selected Prognostic Cancer Biomarkers from the CBC and CMP

  • Neutrophil: Lymphocyte Ratio
  • Lymphocyte: Monocyte Ratio
  • Platelet: Lymphocyte Ratio
  • CRP: Albumin Ratio
  • Hypoalbuminemia

Neutrophil / Lymphocyte Ratio (NLR)

  • Neutrophyl LymphocytesThe neutrophils act as tumor-promoting leukocytes, capable of suppressing anti-tumor immune response; are effectors of angiogenesis; promote leakage of tumor cells and endothelial cells into the circulation, therefore contributing to participate in the metastatic cascade. Therefore, an elevated neutrophil count can stimulate tumor angiogenesis and contribute to disease progression, thus leading to a negative correlation between neutrophil density and patient survival. 
  • On the other hand, lymphocytes are a part of the host’s antitumor response the presence of lymphocytes in the tumor is associated with better responses to chemotherapy and better prognosis. 
  • Thus, the NLR can reflect the balance between the activation of the inflammatory pathway and the antitumor immune function. 
  • The division of neutrophil count by lymphocyte count is defined as NLR. 
  • An increase in NLR has been reported to correlate with poor prognosis in cancer patients.
  • A cut-off value between 2-4 has been reported in cancer patients.

Faria, S. S., Fernandes, P. C., Silva, M. J., Lima, V. C., Fontes, W., Freitas-Junior, R., Eterovic, A. K., Forget, P. The neutrophil-to-lymphocyte ratio: a narrative review. Ecancermedicalscience, 10, 702 (2016) DOI:10.3332/ecancer.2016.702 

Lymphocyte/Monocyte Ratio (LMR) 

  • Lymphocytopenia has been associated with increased tumor burden and poor prognosis. The probable cause could be the destruction of lymphocytes by tumor cells which decreases the body’s anti-tumor response.
  • Monocytosis has also been found to be associated with poor prognosis as they Tumor-associated macrophages, which are an important mediator of cancer progression and metastases. 
  • The division of lymphocyte count by monocyte count is defined as LMR. 
  • A low LMR as a simple biomarker of the host immune system has been suggested to be related to poor prognosis in various cancers. 
  • The median cut-off value for LMR has been reported to be 3.0.

Nishijima TF, Muss HB, Shachar SS, Tamura K, Takamatsu Y Prognostic value of the lymphocyte-to-monocyte ratio in patients with solid tumors: a systematic review and meta-analysis. Cancer Treat Rev 41(10) 971-8 (2015) DOI: 10.1016/j.ctrv.2015.10.003 

Platelet/Lymphocyte Ratio (PLR)

  • Platelet/ LymphocytePlatelets are another important tumor-promoting leukocyte. They secrete vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), hepatocyte growth factor (HGF), insulin-like growth factor (IGF), transforming growth factor β (TGFβ), and many cytokines which promote epithelial to mesenchymal transition (EMT) and promote metastasis.
  • Lymphocytes, as we know, are part of the host's defense against tumors. 
  • The division of platelet count by lymphocyte count is defined as PLR. 
  • The cutoff value estimated for PLR is 160. 
  • A high PLR value correlates with a poor response to therapy and a bad prognosis.

Templeton AJ, Ace O, McNamara MG, Al-Mubarak M, Vera-Badillo FE, Hermanns T, Seruga B, Ocaña A, Tannock IF, Amir E. Prognostic role of platelet to lymphocyte ratio in solid tumors: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev 23(7) 1204–12 (2014)  DOI: 10.1158/1055-9965.EPI-14-0146 

CRP/Albumin Ratio (GPS_Glasgow Prognostic Score)

  • Albumin-300x281-1A combination of Albumin and C-reactive protein (CRP) measurements into a 3level predictive score. 
  • Patients who had both a serum elevation of CRP (>1.0 mg/dL) and hypoalbuminemia (<3.5 g/dL) were allocated a GPS of 2. 
  • Patients with only one of the abnormal values were allocated a GPS of 1, and 
  • Patients who had neither were allocated a GPS of 0. 
  • Survival decreases with increasing score

McMillan DC, Crozier JE, Canna K, Angerson WJ, McArdle CS. Evaluation of an inflammation-based prognostic score (GPS) in patients undergoing resection for colon and rectal cancer. Int J Colorectal Dis. 22(8):881–886 9 (2007) DOI: 10.1007/s00384-006-0259-6 

Hypoalbuminemia (mGPS mGlasgow Prognostic Score)

  • Patients who had both a serum elevation of CRP (>1.0 mg/dL) and hypoalbuminemia (<3.5 g/dL) were allocated a GPS of 2. 
  • Patients who had only serum elevation of CRP but not hypoalbuminemia were allocated an mGPS of 1, and 
  • Patients who had neither or only hypoalbuminemia were allocated a mGPS of 0. 
  • Survival decreases with increasing scores.

Similar to GPS but hypoalbuminemia = score 0
Proctor MJ, Morrison DS, Talwar D, Balmer SM, O'Reilly DS, Foulis AK, et al. An inflammation-based prognostic score (mGPS) predicts cancer survival independent of tumor site: a Glasgow Inflammation Outcome Study. Br J Cancer. 104(4):726–734 (2011) DOI: 10.1038/sj.bjc.6606087 
*Richa Chauhan, Vinita Trivedi, Inflammatory markers in cancer: Potential resources 
Frontiers in Bioscience, Scholar, 12, 1-24, Jan 1, 2020

Biomarker Lactic Acid Dehydrogenase Predicts Cancer Progression and Overall Survival

Aberrant metabolism and inefficient fuel production are characteristic of tumor cells, which are dominated by aerobic glycolysis, increased lactate production, and a higher uptake of glucose (the Warburg effect). Elevated LDH is a marker of these aberrant metabolic processes in cancer cells. High serum LDH levels are associated with poor prognosis in patients with cancer and predict progression and overall survival.

Aerobic glycolysis was described for the first time about a century ago by Otto H. Warburg who showed that cancer cells metabolize glucose differently than normal cells (Warburg effect) and that tumors derive energy mainly from the conversion of glucose to lactic acid and minimally via cellular respiration involving oxygen. Tumors produce massive amounts of the aerobic glycolysis waste product, lactic acid. This is evidence of deregulated metabolism, hence the understanding of cancer as “disorder of cellular metabolism”.  Lactic Acid itself may promote the growth and spread of cancer cells, especially at high concentrations by changing the tumor microenvironment.

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

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

LDH 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.

The OutSmart Cancer System® recognizes cancer as a metabolic syndrome and leverages the abnormal metabolism of tumor cells to exert influence over the tumor microenvironment and the behavior of tumor cells. Attending to the Cancer Terrain is a fundamental approach for influencing cancer cell metabolism.  

EGCG, a catechin found in Green Tea (H. Camellia sinensis) has been identified as an agent which inhibits LDH activity in normal and low oxygen environments by influencing the conversion of pyruvate to lactate at the end of the glycolytic pathway.  This may deprive cancer cells of their preferred fuel, glucose, and metabolites, including lactate that produces a favorable environment for malignant proliferation, growth, and progression. Recommended Therapeutic Dose 1-3 grams daily.

Monitoring trends in LDH is a method of both identifying abnormal cellular metabolism found in many solid and hematologic malignancies and is also of value in identifying early signs of recurrence as well as disease progression.

For patients achieving remission, during the first two years after completion of cancer treatment, LDH and other biomarkers of the Cancer Terrain are monitored every 3 months.  Thereafter, every six months for 3-10 more years to track and identify early signs of recurrence.  

For patients living with cancer as a chronic illness, LDH and biomarkers of the Cancer Terrain are monitored every 3 months to track evidence of recurrence and treatment resistance.

 

Learn more about monitoring the Cancer Terrain and the Tumor Microenvironment.
Receive training in Dr. Nalini’s OUTSMART CANCER SYSTEM ®.
www.aiiore.com

By using biomarkers of the Cancer Terrain and cellular metabolism, it is possible to identify trends that allow for early intervention. LDH is one of the most valuable and reliable biomarkers reflecting the active presence of the aberrant physiology of tumor cells and is prognostic and predictive of progression and overall survival in cancer patients.

 

Selected References:

Oral Cancer AIIORE Blog

Phytochemicals in Oral Cancer Prevention and Therapy

Oral cancers originate in the oral cavity and may spread to the neck and throat and local lymph nodes and can metastasize. These cancers are most commonly squamous cell carcinomas and are often very aggressive.

Cancers of the oral cavity, head, and neck are linked to drinking alcohol, smoking tobacco, betel nut chewing, human papillomavirus infection, and nutritional deficiencies.

Phytochemicals are a useful adjunct therapy for both prevention and therapy.

The continuous increase in cancer cases, the failure of conventional chemotherapies, and the excessive toxicity of chemotherapies demand alternative cancer treatments.

Phytochemicals can inhibit or antagonize factors, which are dysregulated in cancer cells and may enhance the effects of conventional therapy or could be developed into a stand-alone therapy*

Phytochemicals may exert their chemopreventive properties by blocking the critical events of tumor initiation and promotion, thereby reversing the premalignant stage. Phytochemicals may also prevent tumorigenesis by inhibiting or slowing tumor progression or promoting cell differentiation. Furthermore, phytochemicals can enhance innate immune surveillance and improve the elimination of transformed cells.”**

Phytochemicals that impact multiple pathways active in the development, growth, progression, and spread of oral cancers include

Phytochemicals in Oral Cancer
  • Black Raspberry anthocyanins
  • Green Tea Catechins (EGCG, EGC, ECG)
  • Curcuma longa (curcuminoids) (tumeric)
  • Alliums: Garlic and Onions (allicin, s-allylcysteine)
  • Resveratrol 3,4’,5-trihydroxy-trans-stilbene
  • Lycopene carotenoid (tomatoes, red bell peppers)
  • Astaxaxanthin and Canthaxanthin  carotenoid xanthophylls  (green leafy vegetables)
  • Bromelain cysteine protease (pineapple)

For a detailed and thorough discussion of risk factors, etiologies, signs and symptoms, histopathology, molecular mechanisms and therapeutic interventions in oral, head, and neck cancers see: 

*Tzu-Ying Lee , Yu-Hsin Tseng Review : Biomolecules  The Potential of Phytochemicals in Oral Cancer Prevention and Therapy: A Review of the Evidence 2020 Aug 6;10(8):1150. doi: 10.3390/biom10081150

** Kotecha R., Takami A., Espinoza J.L. Dietary phytochemicals and cancer chemoprevention: A review of the clinical evidence. Oncotarget. 2016;7:52517–52529. doi: 10.18632/oncotarget.9593.


 

The Connection Between Breast Cancer and The Environment

Breast Cancer is the most commonly diagnosed malignancy in women.

Image Credit - Ribbon vector created by pikisuperstar - www.freepik.com

There is a continually expanding and compelling volume of data linking breast cancer to exposure to environmental toxins, radiation and endocrine disrupters lead to increased incidence of breast cancers.

When taking a thorough history of our patients we must include a review of their “Exposome”

Genetic and Genomic factors, Reproductive history, lifestyle factors such as weight, alcohol consumption, smoking and lack of physical exercise all contribute to increased risk profiles. Socioeconomic status as well as psychological health and resilience, all influence outcomes. Racial and ethnic minorities are often exposed to a disproportionately higher level of environmental toxins in the US. Immigrants may have lived in areas where there are no environmental regulations or controls.

Exposures to common chemicals found in products used every day contribute to a lifetime burden of toxic chemicals. The greatest rise in the incidence of breast cancers occurred in the decades after World War II when there were exponential increases in the use of herbicides, pesticides, plastics, cosmetics and body care products.

Cancer is often a perfect storm of genetics and environment. While studies are done on single agents, the reality is that we are living in a toxic chemical soup in modern life exposing us to a myriad of chemicals from multiple sources on a daily basis.

A common chemical BPA (Bisphenol A) is an endocrine disruptor. Exposure to BPA early in life contributes to breast displasias later in life due to its impact on mammary gland gene expression. BPA is found in plastics, linings of canned food containers and credit card receipts.

Limit exposure to plastics, polycarbonate food and water containers and canned foods to reduce BPA exposures. Breastfeeding women should be cautious as BPA is found in human breast milk.

Parabens, p-hydroxybenzoic acid esters, are widely used preservatives in personal care products and cosmetics. Parabens are endocrine disruptors. Parabens enable the Hallmarks of Cancer, characteristics of tumor cell survival and proliferation through multiple pathways. Parabens are also found in human breast milk. Parabens bind to estrogen receptors, inhibit apoptosis, promote proliferation, angiogenesis and metastasis. A lifelong commitment to avoiding all products that contain parabens will dramatically reduce exposures. Many European countries have banned the use of parabens. European made products are often paraben free as well as select brands made in the US.

Visit the Environmental Working Group Cosmetics Data base https://www.ewg.org/skindeep/ for a list of safe and not so safe products.

Single Nucleotide Polymorphisms in P450 enzymes, particularly CYP1BI metabolism. Mulitple methylation pathways also influence detoxificaton pathways and estrogen metabolism.

A healthy microbiome, particularly rich in Bifidobacteria and butyrate support normal estrogen conjugation and excretion. MANY breast cancer treatments contribute to dysbiosis, increased inflammation and alterations in estrogen metabolism and mood.

Pelvic and Abdominal radiotherapy, surgeries, chemotherapy agents, steroids, antibiotics administered to cancer patients and compromise gut health, immunity and inflammation control. Increasing butryate in the intestines improves the health of the microbiome.

Butyrate and the health of intestinal microbiome can be easily increased by ingesting 6-8 grams of soluble fibers daily. The Onion-Garlic family and the Brassica-Cabblage family vegetables are high in soluble fibers.

The use of oral contraceptives, fertility drugs and hormone replacement therapy all alter breast tissue. Thus, medical care itself leads to nosocomial trends in breast cancer. Patients BEWARE!!!

Many pesticides and herbicides cause endocrine disruption. Commercial production of many animal food sources including the additional of estrogens and growth hormones to feed.

Patients should be well versed and take a tour of their home room by room to identify toxic, endocrine disrupting chemical exposures.

Patients can be overwhelmed when we give them a long list of products and foods to avoid.

In our clinic we employ nutritional health coaches to assist patients in successfully implementing a lifestyle and diet that reduces exposures to estrogenic environmental chemicals.

Download your complimentary copy of the
OUTSMART CANCER CARE PLANNER History and Intake Form

OutSmart Cancer Care Planner

Let The Oncologist Be The Disease Expert. Become The Health Expert That Cancer Patients Are Looking For.

You may not treat cancer in your practice, but you do have patients who are at risk due to personal and family history, patients who may be undergoing or recovering from treatments, patients who are survivors worried about recurrence and patients living with cancer as a chronic illness.  And you may also have patients who are family members concerned about their loved ones. 

 

There is no HEALTH MODEL in conventional oncology care, yet health and wellbeing, peace of mind and sense of agency are in the center of the hearts and minds of cancer patients, cancer survivors and their families. 

 

There will be 19 million cancer survivors in the US alone by 2024.  Who is supporting their health?  Who is trained to help them recover and keep them well??  …not the oncologist.

 

How can you help these patients?

A  breast cancer survivor who successfully completed her treatments 8 years ago comes into your office as a new patient complaining of persistent peripheral neuropathy and ongoing cognitive changes since her treatment.  How can you resolve these long-term adverse effects?

 

An ovarian cancer patient currently undergoing aggressive treatment every 21 days comes into your office complaining of severe diarrhea, neuropathy and sleep disruption.  What can you do to help her get through her treatments with less adverse effects, maintain her weight and nutritional status?

 

A colorectal cancer survivor who completed his treatment 3 months ago is continuing to have 10-15 bowel movements daily and is profoundly fatigued.  What will you do to restore normal bowel function?


A prostate cancer patient on endocrine blockade therapy is suffering from
hot flashes. Should you also be concerned about loss of bone mass and sleep cycle disruption?

 

An endometrial cancer survivor is suffering from dermatitis and colitis, adverse effects of her dramatically successful immunotherapy treatment and now has chronic autoimmune inflammation. How will you manage this?

 

A head and neck cancer patient who has trouble swallowing is losing weight and muscle mass.


How can you provide a plan for repair from oral mucositis, restoration of the oral mircrobiome and repletion of calories and nutrients?

 

These patients are searching for clinicians that can guide and support them through every phase of their cancer journey.  Just as in helping your patients navigate other chronic illnesses, patients look to you for a plan, for monitoring and guidance so that they can maintain and regain their health during and after their treatments.

 

When a patient has a collaborative team providing integrative care everyone wins, the patients, families and care providers.  Patients who have a clear plan and support have the opportunity for better outcomes, better prognosis, greater peace of mind, a sense of control and agency and an improved quality of life. 

 

Let the oncologist be the cancer expert. You can be the health expert on their team.

 

Standard of care in oncology must  change such that care includes not only a team of disease experts (usually medical oncologist, surgeon, radiologist) but ALSO a team of health experts.

 

Towards this end  I founded the American Institute of Integrative Oncology Research and Education and  have created an online self-paced training program for front line clinicians who want to expand their skills and their practice and  fill the huge need in our communities and serve these patients.  If you did not specialize in oncology, you probably had one course on this topic but you need to fill the gap in your training to feel confident in doing so.

 

The Foundations of Integrative Oncology Training is not for clinicians who want to practice oncology.  It is front-line clinicians who want to feel confident, knowledgeable and well trained in supporting the health side of the cancer equation. This self- paced online training is for clinicians who want to increase their impact, expand and grow their practice and represents 35 years of clinical practice and experience.

 

The first step is learning how to take a comprehensive and complete history of patients whose lives have been touched by cancer.  

 

You can receive a complimentary copy of the

OUTSMART CANCER CARE PLANNER History and Intake Form

and learn more about the Foundations of Integrative Oncology training here

 

OutSmart Cancer Care Planner

What If Every Cancer Patient Had a Health Plan and not Just a Disease Plan

What If Every Cancer Patient Had A Plan For Health And Not Just Plan For Disease?

“An integrative health focused cancer support plan should begin at diagnosis and persist through long term healthy survivorship and promote a body where cancer cannot thrive.”

 

By the year 2024 there will be over twenty million cancer survivors in the US alone. This rapidly growing population of survivors obliges all frontline clinicians to learn how to support patients at every stage of the cancer journey.  Read more