NLR score

[beach sunrise]

How Can You Tell If Your Immune System Is Deficient?
One simple way to tell if your immune system is deficient is to learn how to interpret your complete blood count (CBC). If any of the numbers are too high or too low (indicated by the letter “H” or “L” next to the score) this is a clear indication of a problem.

But there is a quick and efficient way that (although well known to physicians) patients are rarely told about. Doctors either ignore this or don’t feel their patients need to know it. This is a calculation of your physiological stress level. It is called the NLR, which stands for the “neutrophil-to-lymphocyte ratio.”

The NLR is of particular importance to cancer patients. The importance of this ratio was first described in 1967 as a way to measure exposure to toxic ozone gas. Its relevance to cancer was initiated in 2014 by a study in the Journal of the National Cancer Institute (JNCI), which surveyed 100 journal articles that included a total of 40,559 cancer patients. The authors concluded that an NLR greater than four was associated with an 81% increase in death. This was observed in all types of cancer, all sites, and all stages. The hazard ratio for disease-free survival was a whopping 227%.

These dozen authorities from five countries concluded:
“A high NLR [of over 4.0] is associated with an adverse overall survival in many solid tumors. The NLR is a readily available and inexpensive biomarker.”
Since few patients know about it, you might think this discovery is obscure. Not at all. It has had over 10,000 views, and 5,000+ downloads, and has been cited by 800+ other publications!

In other words, the NLR is an open secret. Tthere are about 100 new papers on the topic every month. It is, in short, “an easily accessible prognostic marker.” Yet, we have to meet a patient aware of this fact. To emphasize this point, here is how the NLR correlates with a worse prognosis in some cancer situations:

Lung cancer (NSCLC):
“Elevated pretreatment NLR is associated with shorter overall survival and progression-free survival and with lower response rates in patients with metastatic lung cancer (NSCLC) treated with nivolumab immunotherapy, independently of other prognostic factors.”
(Diem S, Schmid S, Krapf M, et al. Neutrophil-to-Lymphocyte ratio (NLR) and Platelet-to-Lymphocyte ratio (PLR) as prognostic markers in patients with non-small cell lung cancer (NSCLC) treated with nivolumab. Lung Cancer. 2017 Sep;111:176-181. doi: 10.1016/j.lungcan.2017.07.024. Epub 2017 Jul 24. PMID: 28838390, edited)
Breast Cancer (triple-negative breast cancer):
High NLR is associated with poor overall survival and disease-free survival in patients with breast cancer, especially in those patients with estrogen receptor (ER-) and HER2-negative disease.” There is no mention of the PR status, but this finding might be relevant to those with triple-negative disease.

Stomach Cancer (gastric adenocarcinoma):
In the high-NLR patients, there was a four times greater chance of postoperative complications. The median survival time was 216 days shorter in the high-NLR patient group and disease-free survival was approximately half.

(Miyamoto R, Inagawa S, Sano N, et al. The neutrophil-to-lymphocyte ratio (NLR) predicts short-term and long-term outcomes in gastric cancer patients. Eur J Surg Oncol. 2018 May;44(5):607-612. doi: 10.1016/j.ejso.2018.02.003. Epub 2018 Feb 13. PMID: 29478743)
Melanoma:
“NLR is a simple, inexpensive, and readily available biomarker that could be used to help predict response to immunotherapy in patients with advanced melanoma.”
There are similar findings on almost every major kind of cancer, including esophagus, liver, cervix, ovarian, colorectal, and head-and-neck cancer.

Since the NLR measures both inflammation and immunity, it serves as an early warning system for death of all kinds. Another study found that this simple and inexpensive test was remarkably accurate in predicting an impending catastrophe:

“The NLR is a predictor of all-cause mortality and cardiovascular events” (edited).
Simply put, people who score high on the NLR also have about double the risk of dying of heart attacks, strokes, or any cause compared to people with low-normal NLR scores.

How to Calculate Your NLR
You can calculate your NLR by dividing the number of neutrophils by the number of lymphocytes from a typical CBC blood test. (You can also divide the percentage of neutrophils by the percentage of lymphocytes, and the results will be the same. But you cannot compare one absolute number to one percentage number.)

What Is A Normal NLR Score?
There is general agreement that a high NLR score is associated with an increased risk of disease and death. But there is no universal agreement on what constitutes a normal score. We have seen estimates ranging from 2.5 to 4.0, or even higher. But the most convincing study came from Patrice Forget, MD, clinical professor of anesthesiology at the University of Aberdeen. In a study, routine blood samples were obtained from 413 healthy individuals, who had a median age of 38. This study established that the normal NLR values in an adult, non-geriatric, population in good health were between 0.78 and 3.53. The average (mean) number was 1.65.

This tells us that the normal NLR number is likely to be between 1 and 3, with 1.65 as probably ideal. The normal NLR value in an adult, non-geriatric population in good health is between 0.78 and 3.53. So an NLR higher than 3.53 suggests stress, inflammation, or infection in your body.

Why is this number so critical? The NLR measures the relationship between two key blood components. As you shall see, it is beneficial to have a high normal number of lymphocytes, 1,800 or 1.8K, or higher, because lymphocytes include the most active cancer-killing cells. In other words, from the point of view of cancer, lymphocytes are critically important. On the other hand, neutrophils are associated with chronic inflammation, which can be the seedbed of tumors:

“Neutrophils reflect a state of host inflammation, which is a hallmark of cancer. They can participate in different stages of the cancer process including tumor initiation, growth, proliferation, or metastatic spread. In general, neutrophils play a central role in inflammation within the tumor.”
(Ocana A, Nieto-Jiménez C, Pandiella A, Templeton AJ. Neutrophils in cancer: prognostic role and therapeutic strategies. Mol Cancer. 2017;16(1):137. Published 2017 Aug 15. doi:10.1186/s12943-017-0707-7, edited)
Here is how to calculate the NLR based on a standard Complete Blood Count (CBC):

Locate the absolute neutrophil number. (This may be abbreviated as ABS. NEUTS or some such designation.) Let’s say, by way of example, that this number is 3.0.
Next, find the absolute lymphocyte number. (This may be abbreviated as ABS. LYMPHS.) Let’s say this number is 1.5.
Divide the number of neutrophils (3.0) by the number of lymphocytes (1.5). This will yield an NLR of 1.5. Since anything below the cut-off point of 3.53 is average for healthy young adults, 1.5 represents a normal score.

In the above example, the two black arrows represent the absolute neutrophils (2597) and the absolute lymphocytes (1519). The ratio is 1.7, which is normal.

You can also use an online NLR calculator to find a rough NLR.

The Neutrophil-Lymphocyte Ratio (NLR) Calculator
This app allows you to enter either the absolute numbers or the percentage of these two WBCs to perform the calculation. [But please don’t mix and match absolute numbers and percentages.] Again, if we enter an absolute number of 3.0 for the neutrophils and 1.5 for the lymphocytes, the actual number is 1.5. But the calculator will simply return rounded off to the number TWO. This indicates normal physiological stress, but it isn’t very exact.

If you can’t find the absolute numbers, you can usually find the percentages. Thus, if the percent of neutrophils is 53.6%, while of lymphocytes is 33.2%, it will again return a score of TWO, which is NORMAL.

What To Do About a High NLR?
Some cancer patients have abnormally high NLRs (which, as a reminder, Prof. Forget defines as over 3.53). This could represent either one problem, or two problems converging in the same individual. In other words, these patients may have a low number of lymphocytes (often due to the effects of toxic treatments) or it can be due to an unusually high number of neutrophils. This is usually due to some inflammatory condition. Or both, simultaneously.

But what can you do about either, or both, of these problems?

Treatments that reduce systemic inflammation and/or enhance anticancer immunity can usually raise the too-low numbers of lymphocytes, or reduce too-high numbers of neutrophils, thereby rebalancing the neutrophil to lymphocyte ratio.

Much of our effort is directed at optimizing these two underlying situations (decreasing undesirable chronic inflammation and increasing immune potency).

There is good evidence that medicinal mushrooms and traditional Asian medicine (TCM, Ayurveda, Kampo, etc.) will lower the neutrophil-to-lymphocyte ratio. Japanese scientists have looked at changes in the NLR in patients who had previously undergone surgery for colorectal cancer. Patients were classified into those with a higher NLR versus a lower NLR. (Their cut-off point was 2.5, which was more rigorous than the 3.53 cited above.)

Each patient was given chemotherapy plus a registered anticancer medicine called PSK (polysaccharide K)) derived from shiitake mushrooms. In patients who began the trial with a relatively high NLR, “the use of postoperative PSK-chemotherapy controlled the NLR at low levels.” But patients who began the trial with a low NLR “tended to remain low.” The authors concluded:

“In patients who underwent colorectal cancer surgery, postoperative adjuvant therapy with a combination of chemotherapy and PSK [medicinal mushrooms] succeeded in controlling the NLR at low levels.”
(Yoshioka S, Kubo M, Yanagisawa K, et al. [Clinical significance of neutrophil to lymphocyte ratio in colorectal cancer patients receiving adjuvant chemotherapy combined with polysaccharide-K]. Gan To Kagaku Ryoho. 2013 Nov;40(12):2086-8. Japanese. PMID: 24394021)
This is a very important statement. It confirms our belief that good mushroom extracts should be efficacious in this situation.

As to lowering chronic inflammation, one can take non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen. You can read about these at the always helpful website, drugs.com. NSAIDs come with risks of their own, especially from long-term use. There is evidence, however, that some of the nutraceuticals (dietary supplements that are believed to provide health benefits) are quite effective at reducing inflammation. These include the following:

Curcumin
Resveratrol
EGCG (green tea)
Fish oil
Sesame lignans
Olive extract