Understanding Neutrophil to Lymphocyte Ratio (Part 2): Research Demonstrating its Role as a Valuable Prognostic Marker in Cancer

A large body of research (as well as my clinical observations) point to chronic inflammation as a powerful force in the initiation, growth, and spread of cancer. As a result, an essential component of my protocol for health includes addressing inflammation.

As I discussed in part 1 of this series, there are three points to consider when evaluating the role of inflammation in cancer. First, a chronic inflammatory state can initiate cancer development. Second, it’s important to discover and address the root cause of the inflammation—for example, pathogenic (chronic infection), life-style, stress, and/or poor dietary habits. And third, recognize that the cancer itself creates inflammation—as the cancer energy mutates and gains intelligence, it manipulates the immune system, creating a pro-inflammatory micro-environment favorable to cancer growth.

Research indicates that the systemic manifestations of inflammation can provide a valuable biomarker for prognosis and treatment stratification. In particular, numerous studies indicate that a simple indicator of systemic inflammation—based on neutrophilia and/or lymphocytopenia—can provide prognostic information in a wide range of cancer types. In particular, the value of one index (the dNLR) derived from total white cell and neutrophil counts, is enabling large retrospective studies to be carried out.

Neutrophil to Lymphocyte Ratio May Be a Predictor of Mortality in All Conditions

White blood cell (WBC) count is one of the useful inflammatory biomarkers in clinical practice. For example, even if WBC is within normal range, subtypes of WBC including N/L ratio may predict cardiovascular mortality.

N/L ratio is a readily measurable laboratory marker used to evaluate systemic inflammation. There are many different conditions that can affect N/L ratio, including hypertension, diabetes mellitus, metabolic syndrome (1), left ventricular dysfunction, acute coronary syndromes, valvular heart disease, abnormal thyroid function tests, renal or hepatic dysfunction, known malignancy (2,3,4), local or systemic infection, previous history of infection (<3 months), inflammatory diseases, and any medication related to inflammatory conditions.

Here’s one example of how the N/L ratio can be useful as part of the evaluation of a specific cancer and the treatment protocol: not only N/L ratio but also mean platelet volume, red cell distribution width (5), platelet distribution width, CRP, uric acid and gamma-glutamyl transferase (6) are easy markers to evaluate the prognosis of colon cancer patients (7). However, one should keep in mind that N/L ratio itself alone without other inflammatory markers may not give exact information to clinicians about the prognosis of colon cancer patients. (8,9).

Inflammation is an essential part of our body’s immune defense. When we encounter pathogens such as bacteria, viruses, or parasites, our body responds with inflammation to fight the invaders and increase immune response. In these instances, inflammation is beneficial. But inflammation has a dark side—left unchecked, it can wreak havoc on cells, tissues, and organs. For example, it’s well established that chronic inflammation is a powerful force in the initiation, growth, and spread of cancer.

There are three essential points to consider: First, a chronic inflammatory state can, over time, initiate cancer development. Second, we still need to find the cause of the chronic state of inflammation—for example, pathogenic (chronic infection), life-style, stress, years of poor eating, or a combination of the above. And third, it is important to keep in mind that the cancer energy, as it gains in intelligence, manipulates our immune system, creating a cancer-favorable, pro-inflammatory micro-environment.

Research indicates that the systemic manifestations of inflammation can provide a valuable biomarker for prognosis and treatment stratification. Numerous studies indicate that a simple indicator of systemic inflammation—based on neutrophilia and/or lymphocytopenia—can provide prognostic information in a wide range of cancer types. In particular, the value of one index (the dNLR) derived from total white cell and neutrophil counts, is enabling large retrospective studies to be carried out.

Although not informative from a biological standpoint in distinguishing cause from effect, the results of these studies are likely to be of significance in how we approach cancer. In my practice, I always consider the role of inflammation in cancer and tailor protocols for patients accordingly. The following markers are among those I consider most important:

• Tumor-associated neutrophils (TANs)
  Bio-Markers: CD11b+, CD66b+, CD63+

Tumor-associated neutrophils (TAN) play a major role in cancer biology. Neutrophils are the most abundant circulating leukocyte in humans, and are phenotypically plastic. Neutrophils, as a key component in inflammation, often play a crucial role in inflammation driven tumorigenesis. TAN can take an anti-tumorigenic (what we are calling an “N1-phenotype”) versus a pro-tumorigenic (“N2”) phenotype. The anti-tumor activities of N1 TANs include expression of more immuno-activating cytokines and chemokines, lower levels of arginase, and more capability of killing tumor cells. N2 neutrophils are pro-tumorigenic, and secrete T2 cytokines.

I recently read a paper entitled “Integrative Oncology” ¹ published in a peer-reviewed medical journal. To say I was shocked at the misrepresentation presented as “fact” is an understatement.

I am strongly compelled to offer a rebuttal to this article. I can only hope that those who most need the perspective of someone who has worked in clinical practice with cancer patients on a daily basis for almost three decades will benefit from my experience.

Personally, I prefer to use the term “Unified Medicine” over “Integrative Oncology” to more appropriately describe the wholistic ETMS (Eclectic Triphasic Medical System) model I developed and practice, known as ‘Mederi Medicine’ or ‘Mederi Care’.

Mederi Medicine is an approach where all aspects of an individual are addressed for optimal health and well being. This includes the fundamental building blocks of nutrition, herbs, lifestyle, and spiritual and emotional health, with the tools of modern conventional medicine employed when necessary. As a musician, I think of Mederi Medicine as similar to the way that the various parts of an orchestra each play an essential role in creating beautiful music. The ETMS is not a fragmented approach, but is synergistic, meaning that the whole is greater than the sum of its parts. This harmonious approach is something that is sorely lacking in modern conventional medicine”.

“I think of Mederi Medicine as similar to the way that the various parts of an orchestra each play an essential role in creating beautiful music”

What’s Wrong with the “Integrative Oncology” Paper?

Honestly, when I first saw the title “Integrative Oncology” I felt hopeful. I thought perhaps this paper would offer helpful information to those suffering from cancer, or to those who dedicate their lives to working with people with cancer. Instead, I found bias, misrepresentation, and outright twisting of the facts and outcomes of studies. This paper clearly states that it has been peer-reviewed, but given the many errors, I find that difficult to believe.

I find it strange that the subtext delineates “integrative approaches (e.g., lifestyle, meditation, yoga, acupuncture, massage)” but overlooks botanical and nutritional medicines, which are widely used as adjunct therapies in cancer protocols. I have no idea what the underlying agenda is in this paper. Why would scientifically and clinically proven modalities be dismissed or overlooked when they offer the potential for help without harm?

I’ve spent the past four decades researching and refining the diet that I’ve found best supports health and healing. The Eclectic Triphasic Medical System (ETMS) approach to diet is based on traditional wisdom and supported by scientific research. It is sensible, balanced, diverse, nutrient-rich, and delicious.

In my last post, I addressed the currently popular ketogenic diet, which many people have adopted for weight loss. Other people pursue the carbohydrate-restrictive, fat-laden keto diet with the hope of curing cancer. Neither of these outcomes is supported by research.

Guidelines for the ETMS Diet: An Optimal Nutrition Plan

The primary guidelines of the ETMS diet are based on a pesca-flexa-vegetarian diet, which I describe in detail here: https://www.donnieyance.com/pesca-flexa-vegetarianism. 

Enhancing Cellular Defense Mechanisms with Adaptogens

Aging is associated with a decrease in adaptive abilities along with increased vulnerability to stress. At the same time, aging is a complex process involving a persistent activation of some stress response systems, often involving transcriptional reprogramming, and the activation of vitagenes, which can be consider a ‘geroprotective’ adaptation.¹³   Environmental stressors induce specific and predictable epigenetic changes that can eventually result in an adaptive response to the stimulus. It seems likely that mild stress-induced hormetic response involves mechanisms similar to those that underlie developmental epigenetic adaptations.

The illustration below shows the involvement of hormesis in the epigenetic processes that determine age-related disorders and longevity.¹⁴

Dose–response curve depicting the quantitative features of hormesis

Hormesis is a biological phenomenon whereby a beneficial effect (improved health, stress tolerance, growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses.

I’m often asked what I consider to be the healthiest diet. Through decades of nutritional research and experimentation, I’m convinced that a diet of primarily organic, plant-based Mediterranean foods—including whole grains, fruits, vegetables, nuts, legumes, eggs, dairy products (cow, goat and sheep milk derived) and healthy fats (mostly olive oil), with fish and seafood playing a key role as a main protein source—is by far the best diet for long term health. The term “pesca-flexa-vegetarian” comes closest to describing the diet that my family and I eat.