In this post and others to come, I am going to tell you about some very important lab tests that you should know about. These tests can help you monitor how well you are doing and if your body is healing from disease and/or responding well to treatments. These tests may also help you know where to focus your efforts with supplements, diet, exercise and more. Ideally, you will be working with a naturopathic doctor to guide you however, it is good for you to understand the basics of these tests and what they mean so you can track your own progress.
In this first post, I will be discussing the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and lactate dehydrogenase (LDH) tests. In a nutshell, these tests are inflammatory markers telling you if your body is inflamed, the degree and type of inflammation that may be occurring and possible causes. These three tests together, sometimes called the trifecta, provide a more comprehensive picture of a person’s inflammatory status and level of oxidative stress.
Oxidative stress is a state of imbalance between the production of harmful free radicals and the body’s ability to neutralize them with antioxidants. This leads to cell damage and is a common problem in cancer patients.
Without further ado, let’s get into what these tests are and how they can help you.
ERYTHROCYTE SEDIMENTATION RATE
Erythrocyte is another name for a red blood cell. The ESR test measures how quickly red blood cells (RBCs) settle to the bottom of a test tube over a one hour period. The faster the RBCs settle, the higher the ESR. It is used as an indirect marker of inflammation in the body and is a quick, simple and inexpensive test.
ESR is primarily driven by changes in plasma proteins, especially fibrinogen and immunoglobulins, both of which increase during inflammation. These proteins cause the red blood cells to clump together and form stacks known as “rouleaux” (roo-low). When the red blood cells stack up like this, it reduces their negative charge and makes them heavier, causing them to settle more rapidly.
NORMAL RANGES
Women have higher levels than men and being older increases ESR.
| Age < 50 years | ||
| Women | 0 to 20 mm/hr | |
| Age > 50 years | ||
| Women | 0 to 30 mm/hr | |
Every lab has their own ranges so make sure to check what the normal ranges are for your particular lab, but this gives you a general guideline. The ideal number you want is < or = 10 mm/hr.
CONDITIONS ASSOCIATED WITH ELEVATED ESR
The ESR is a non-specific test and mainly indicates chronic inflammation. However, the degree of elevation can give clues as to what may be going on. The ESR can also be used to monitor response to treatment. Here are some things that increase ESR.
- Autoimmune diseases (lupus, inflammatory bowel disease, rheumatoid arthritis)
- Cancer
- Diabetes
- Anemia or reduced hematocrit (decreased red blood cells – RBCs)
- Red blood cell abnormalities such as macrocytosis (larger than normal RBCs)
- Infections
- Kidney disease
- Trauma and tissue damage
- Fever
- Elevated fibrinogen in the blood
Elevated ESR can sometimes be caused by technical lab errors. These include dilution problems, tilting the test tube, increased temperature of the specimen or not enough anti-coagulant in the test tube. For this reason, if you have a mild elevation in ESR, it would be a good idea to repeat the test to see if it is a true reading.
A very elevated ESR 100mm/hr or higher is strongly associated with serious active disease. The most common of these are infections, kidney disease, collagen vascular diseases (lupus, rheumatoid arthritis, temporal arteritis) and metastatic, progressive cancer.
ESR >30, but <100 can be harder to interpret. It is most important to have this test monitored over time to see the trend. It may indicate a flaring autoimmune condition. If it is steadily increasing or jumps to a high level, this is cause for concern and further diagnostics are necessary to find the underlying cause. If it is at a steady state or decreasing then continued monitoring and working to reduce inflammation may be all that is necessary.
Elevated ESR can also be a sign of toxic, sludgy blood flow due to elevated fibrinogen. Fibrinogen is the main clotting protein in our blood. Cancer patients have higher risks of forming blood clots so this is something you want to monitor and be aware of.
It will also be important to interpret the results of the ESR in conjunction with the other inflammatory marker tests I will be discussing below to get a better picture of what might be going on.
C-REACTIVE PROTEIN
C-reactive protein (CRP) is part of the body’s innate immune system. It is a protein produced by the liver and increases in direct response to things like trauma, inflammation and infections. CRP is considered an acute phase reactant. This means the levels rise and fall rapidly with the onset and removal of an inflammatory stimulus. It is mainly produced in response to inflammatory cytokines being released such as IL-6, IL-1 and TNF-⍺.
Newer studies are now saying CRP elevation may actually reflect distressed or injured cells rather than an inflammatory response. Even mild elevations in CRP over time have been associated with poorer prognoses for a variety of diseases, including cancer. This is why it’s such an important test.
One possible explanation is that CRP is serving as an indicator of a wide variety of conditions that themselves represent risk factors. For example, many risk factors for cardiovascular disease are associated with raised serum concentrations of CRP including obesity, insulin resistance, diabetes, hypertension, poor physical conditioning and hypertriglyceridemia.
The test you want is the high-sensitivity CRP (hsCRP). Doctors do not routinely order this test, so you will need to request it on a regular basis to see if it is elevated. It will be important to try to figure out what may be causing the elevation so you can address it.
NORMAL RANGE
Ideally your hsCRP should be <1.0 mg/dL (0.1 for some labs)
FACTORS THAT CAN ELEVATE CRP
- Obesity
- Metabolic syndrome and insulin resistance
- Arthritis
- Diabetes
- Infections like the common cold, gingivitis and periodontal disease
- Smoking
- Insomnia
- Depression
- Genetics
- Autoimmune conditions
- Cancer
- Heart disease
- Pancreatitis
- Bronchitis
- Severe elevations > 10 mg/dL are most commonly associated with acute bacterial infections (90%), systemic inflammation of blood vessels (vasculitis) or major trauma
THINGS THAT CAN FALSELY LOWER CRP LEVELS
- Aspirin and other non-steroidal anti-inflammatories
- Statin drugs
- Magnesium supplementation
LACTATE DEHYDROGENASE
Lactate dehydrogenase (LDH) is an enzyme present in almost every cell throughout the body. Its main role is to produce energy in the cell by converting pyruvate to lactate in anaerobic (low oxygen) conditions. When there are fluctuating oxygen levels (i.e. in muscles during intense exercise), LDH allows cells to switch between aerobic and anaerobic metabolism, providing flexibility in energy production.
Normally, there are low levels in the blood, but when cells or tissues are damaged, LDH is released causing blood levels to rise. For this reason, LDH is used as a general marker of injury to cells and tissues. LDH levels will increase in response to injury, remain elevated for a period of time and then gradually decrease again.
Elevated LDH can be an early indicator of mitochondrial dysfunction. Mitochondria are tiny structures within cells that produce the energy needed to power cellular functions. When mitochondria are damaged, normal cells may shift to inefficient means of energy production including fermentation and aerobic glycolosis, which is also how cancer cells get energy.
Aerobic glycolosis is the process by which cancer cells convert glucose to lactate even in the presence of oxygen, called the “Warburg effect”. LDH is a critical enzyme in this process. For this reason, LDH is often upregulated in cancer cells.
Elevations in LDH are commonly found in cancer patients and can indicate a poorer prognosis and resistance to therapy. In fact, LDH is sometimes used as a supportive tool in diagnosing cancer and in monitoring the effects of cancer treatments.
NORMAL RANGE FOR LDH
140-175 U/L (may be 300-450 for different labs)
CONDITIONS ASSOCIATED WITH ELEVATED LDH
- Heart attack
- Cancer
- Liver disease (hepatitis, cirrhosis, fatty liver disease)
- Muscle damage
- Lung disease
- Anemias, including hemolytic anemia
- Kidney disease
- Trauma (i.e. fractures)
- Pancreatitis
NON-DISEASE CAUSES OF ELEVATED LDH
- Strenuous exercise
- Aspirin, narcotics and anesthesia
LOW LEVELS OF LDH
- Low levels of LDH may indicate malnourishment or certain genetic disorders
- High vitamin C supplementation can falsely lower LDH
DIFFERENT ISOENZYMES OF LDH
There are 5 different forms of LDH, called isoenzymes. Testing all the isoenzymes may help narrow down where the tissue damage is occurring.
- LDH 1 – heart, red blood cells and kidneys
- LDH 2 – also in the heart, red blood cells and kidneys, but at lower levels than LDH1
- LDH 3 – mainly in the lungs
- LDH 4 – lymph nodes, white blood cells, pancreas, liver and muscles (lower than LDH5)
- LDH 5 – liver and muscles, has been found to be elevated in endometrial cancer tissues
In several studies, they found that LDH-5 is up-regulated in many malignant tumors. It is responsible for maintaining aerobic glycolysis, which feeds cancer cells. By inhibiting LDH-5, it has an anti-proliferative effect on cancer cells.
One important thing to note is that cancer treatments, like chemotherapy and radiation therapy, can also increase these inflammatory markers. They can remain elevated even after treatment is done. This is why it is important to get baseline results before treatment begins if possible. It will also help to monitor the trends of these markers as a way to see if the treatments are working or if there is disease brewing. I highly recommend you talk to your doctors about these tests.
MORE DETAILS ON THE TRIFECTA
- It is important that these labs be interpreted in relation to your clinical history, physical exam findings and symptoms.
- In general, ESR is more useful for monitoring chronic inflammatory conditions.
- CRP and LDH are more useful in the diagnosis and monitoring of acute inflammatory conditions.
- Elevations in CRP and LDH typically indicate more rapid cell turnover and tissue damage.
- An elevated CRP and LDH, but normal ESR most likely indicates an acute disease process. Examples would be an infection, tissue trauma, blood clot formation, heart attack and some cancers (due to tumor activity and high cell turnover).
- Elevated ESR with normal CRP and LDH may indicate a subacute or more chronic disease process, such as a flaring autoimmune condition or malignancy.
- Mild elevations are a cause for concern, so make sure to discuss the findings with your doctor to see if anything should be done. If there are significant elevations, further testing is absolutely necessary to figure out what is going on.
- Elevated levels in all three tests suggest that cancer may be more aggressive and progressing, while normal levels indicate better control over the disease process. As with anything, there are exceptions to this and it is not full-proof. Some women with active cancer or other inflammatory diseases may have a normal trifecta.
I cannot stress enough the importance of working with a naturopathic doctor to interpret your results and help guide treatments.
SCIENTIFIC REFERENCES
- A practical prognostic peripheral blood-based risk model for the evaluation of the likelihood of a response and survival of metastatic cancer patients treated with immune-checkpoint inhibitors Read More
- C-Reactive Protein as a Prognostic Biomarker for Gynecologic Cancers: A Meta-Analysis Read More
- Lactate dehydrogenase 5 (LDH-5) expression in endometrial cancer relates to the activated VEGF/VEGFR2(KDR) pathway and prognosis Read More
- Pre-treatment inflammatory parameters predict survival from endometrial cancer: A prospective database analysis Read More
- Relation of inflammatory markers, disease stage and control and chemotherapy in patients with breast cancer Read More
ONE THING YOU CAN DO TODAY ON YOUR HEALING JOURNEY
Today I want to encourage you to think about your make-up. I don’t know about you, but I used to wear make-up every day for most of my adult life. Little did I know, regular make-up products have a lot of toxins in them! After my diagnosis, I decided to stop wearing make-up and now I only use it for special occasions. I also switched to non-toxic products.
Make sure to read labels! I used to think Ayurveda had safe products until I read the labels. Some common toxins you want to avoid include, parabens, phthalates, heavy metals, talc, titanium dioxide, sodium benzoate and synthetic colors, dyes and fragrances.
Here are some brands for safer, non-toxic make-up and skin care products you may want to research:
- Ilia
- RMS Beauty
- Merit Beauty
- Jones Road
- Kosas
- Alima Pure
- Well People
Another great resource is the Environmental Working Group site. You want to look for EWG verified make-up products. See link here.
Your word is a lamp to my feet and a light for my path. ~Psalm 119:105