The human body is an immensely complex biological machine with millions of different biochemical functions happening simultaneously. Lab tests provide an ever so small glimpse at certain key functions. From those indicators, determinations can be made about how well the body is functioning and whether illness is present.
Laboratory assessment, however, is far from absolute. Because the human body is so complex, the ability of lab testing to predict a specific chronic illness is often limited. All labs are subject to variability and different interpretations.
For this reason, it’s important not to get too wrapped up in lab results alone. The problem of chronic Lyme disease cannot be solved exclusively by looking at lab results. If fact, getting too obsessed with lab results can hold back your recovery.
There are literally thousands of different lab tests that can be performed, but only a fraction of them are well understood. Many should be left for research purposes only. Problems arise when doctors order obscure tests that are still poorly understood.
Before you have labs drawn, ask your doctor to explain the purpose of each test.
The information provided by labs is only valuable if it is put to good use. Millions of dollars are wasted yearly on labs that were obtained, but the information was never used. Before you have labs drawn, ask yourself and your doctor: “Will the information provided by this lab (or any other diagnostic test) influence my approach to getting well?” If the answer is no, then you may want to reconsider having that test performed.
For chronic illnesses such as chronic Lyme disease and fibromyalgia, general lab evaluations are often unremarkable. The greatest value of labs is ruling out the possibility of a more threatening condition. Lab values that are mildly abnormal generally return to normal as wellness is restored.
The following is a guide to the labs that I find to be most valuable in evaluating chronic illnesses such as chronic Lyme disease and fibromyalgia. It is, by no means, an absolute or exclusive list.
Basic Testing That Everyone Needs
There are certain basic tests and a few specialized tests that have great value. These are the tests that everyone should consider getting. The following list of labs can be ordered by any healthcare provider. Typically, these tests are covered by health insurance.
Complete blood count (CBC with diff). Measures cellular components of blood.
Blood chemistries. Measure of common chemical components of the body.
Glucose metabolism. Excessive carbohydrate consumption is a major system disrupter that must be controlled before recovery is possible. Three primary tests: fasting blood glucose, hemoglobin A1c, and fasting insulin define insulin resistance and abnormal glucose metabolism.
Minerals. Magnesium and calcium are the primary minerals measured.
Thyroid function. Complete thyroid function should include Thyroid Stimulating Hormone (TSH), free T4, free T3, reverse T3, and thyroid antibodies. Illnesses associated with chronic immune dysfunction are commonly associated with abnormal thyroid function. Correcting abnormal thyroid function can accelerate recovery. Testing for thyroid antibodies (TPO and thyroglobulin) is important to identify Hashimoto’s disease, a form of autoimmune thyroid dysfunction.
Lipid panel. Basic evaluation for cardiovascular risk. Cholesterol commonly increases with age and decline in liver function. The nutrition guidelines in this book help maintain normal cholesterol levels. Significantly elevated cholesterol, however, should be addressed by your healthcare provider.
Autoimmune Testing. Chronic Immune Dysfunction and stealth microbes play a major role in autoimmunity. The type of autoimmune illness that occurs is related to the factors that disrupt immune function, the person’s genetics, and the spectrum of stealth microbes. Though diagnosis of specific autoimmune illnesses is complex and requires extensive testing, basic screening for autoimmunity can be done with two tests.
C-reactive protein (CRP). CRP is a measure of inflammation. It is probably more valuable for monitoring health habits than anything else. High levels (>10) correlate with poor health habits and increased risk of disease. Normal CRP levels, however, are often present in individuals who follow good dietary habits, despite suffering from a chronic illness. It is not a specific marker for Lyme disease, fibromyalgia, or chronic fatigue.
Vitamin D. Vitamin D is not only important for healthy bones, but also very important for normal immune function. There are several forms of vitamin D — calcidiol (25 OH vitamin D) is the most commonly measured form in blood tests. Normal ranges for blood levels of Vitamin D and indications for supplementation are both controversial. The official Institute of Medicine defines calcidiol levels >20 ng/ml as normal and >50 ng/ml as too high. Their recommendations for daily vitamin D include sun exposure or 600-1000 IU of vitamin D3 daily. The Vitamin D Council, however, recommends 40-100 as the normal range, generally requiring much higher doses of supplementation. Levels of >40 ng/ml have been associated with reduced risk of many cancers and chronic disease in general. Achieving consistent vitamin D levels >40 ng/ml is important for recovery. Ideally, have your levels checked every 6 months.
Vitamin B12. Low B12 levels (normal ranges vary between labs) can be a sign of low intake (vegetarians), but more commonly a sign of inadequate absorption and gastric dysfunction. Vitamin B12 generally increases spontaneously with improved health habits, but in the short term, B12 injections or sublingual (under the tongue) supplements can improve energy levels. Activated forms of B12 are better absorbed orally than the more common inactive forms used in most multivitamin products.
Ferritin. Ferritin measures iron stores. Low ferritin levels can indicate low stores of iron in the body, which can be associated with fatigue and restless legs syndrome. High ferritin levels indicate abnormal retention of iron in the body (called hemochromatosis), which can be associated with liver damage and nonspecific symptoms. High levels can also be associated with autoimmunity and chronic infection (Zandman-Goddard 2009).
Urinalysis. Test strips for urine testing can be obtained over the Internet without a prescription.
Mold and mycotoxins. Evaluation for mold is indicated anytime there is any suspicion of mold. Mycotoxins (mold toxins) are potent immune disruptors and cause a wide spectrum of nonspecific symptoms including neurological symptoms and persistent insomnia. Testing for mold in your environment can be important for your recovery (see Chapter 27, Mold and Mycotoxins for more information).
TB skin test. The skin test for tuberculosis should be performed if there is a history of recent exposure or chronic pulmonary symptoms.
Omega-3/omega-6 ratio. The ratio of omega-3 fatty acids to omega-6 fatty acids is a marker for balance of inflammatory factors in the body. Optimal omega-3/omega-6 ratio balances inflammation in the body. The vast majority of people do not get adequate intake of omega-3 fatty acids. Testing can guide optimal supplementation.
Advanced Testing
If you have all the symptoms of chronic Lyme disease (or fibromyalgia or chronic fatigue), then immune dysfunction, the presence of stealth microbes, adrenal dysfunction, hormone imbalances, and mitochondrial dysfunction can all be assumed — you don’t necessarily need labs to prove it. And, if you are going about recovery in the right way and all the symptoms are resolving, you don’t necessarily need specialized labs to prove that you are getting well.
If your illness is severe or you are not getting well, however, specialized lab testing can sometimes help direct your recovery efforts. Most Lyme specialists or integrative doctors will require you to get a large battery of tests as part of the evaluation. The following discussion is provided to help you understand what the different tests mean and the value they may offer.
Testing for Immune Dysfunction and Disrupted Homeostasis
Chronic immune dysfunction is a given in chronic Lyme disease, fibromyalgia, and chronic fatigue syndrome, but sometimes defining the level of dysfunction can help guide recovery.
Th1/Th2 Pathways
Immune function pathways can be defined by types of lymphocytes (white blood cells) and chemical messengers (cytokines) that are used to direct immune functions. T lymphocytes (because they originate from the thymus gland) are important for cell-mediated immunity (direct neutralization of threats by white blood cells). Neutrophils and natural killer cells (NK cells) are an important part of cell-mediated immunity. B lymphocytes (originate from bone marrow) produce antibodies against threats. Specialized lymphocytes, called T helper lymphocytes (Th), direct the immune response by secreting cytokines. Though there are a variety of different T helper subsets, for chronic illnesses associated with stealth microbes, Th1 and Th2 pathways are most important.
In the early stages of Lyme disease (or infection with any intracellular stealth microbe), the immune system mounts an aggressive Th1 response. Stealth pathogens upregulate IL-10 to suppress the Th1 response and shift it to Th2. Shifting to a Th2 response allows the pathogens to maintain a low grade chronic infection. This happens over months to years. Herbs that aggressively stimulate Th1 functions (astragalus, echinacea) are beneficial in acute Lyme disease, but should be avoided in chronic Lyme disease. Other herbs for modulating immune function are discussed in Chapter 14. Though measurement of key cytokines can sometimes be useful, the cytokine dynamics of chronic stealth microbe illness can be quite strange; cytokines are not always as expected.
Lymphocyte Activity
Testing can be done for specific types of WBC activity, including natural killer cell activity (NK cell: CD 16 and 56), T lymphocytes (CD 3), and T helper cells (CD 4).
CD 57 markers are a subset of mature natural killer cells that have more deadly killer-cell activity. CD 57 markers are sometimes low in Lyme disease, but are not always reliable or specific (see Borrelia testing in Chapter 10).
Coagulation Factors
Microbial infections commonly cause activation of coagulation as part of the body’s defense mechanisms. How much coagulation is activated depends on the degree of illness. In a severely ill patient, fibrin, one of the chief components of scar formation, can coat the inner lining of blood vessels. This can block absorption of nutrients and hormones such as thyroid (hypothyroid symptoms occur even with normal thyroid hormones). Labs for monitoring coagulation function include D-dimer, prothrombin fragment 1+2, thrombin-antithrombin complex, and SFM. Testing is only indicated with severe illness.
ATP profile
ATP is the energy molecule of metabolic functions. The ATP profile is an indirect measure of ATP activity in neutrophil mitochondria. It has value in analyzing mitochondrial activity in the body and also the presence of acute infection. Individuals with chronic fatigue often display low ATP function, suggesting decreased mitochondrial function and reduced neutrophil capacity (which is a fundamental problem associated with any fatigue-related disorders, so testing for it isn’t usually necessary).
IGF-1 (insulin-like growth factor-1)
IGF-1 affects tissue and bone growth by regulating growth hormone. IGF-1 secretion mirrors growth hormone secretion, but unlike growth hormone, which fluctuates, IGF-1 is stable throughout the day, making it useful for monitoring secretion of growth hormone. Low IGF-1 is associated with aging, chronic illness, and decreased immune function.
Summary of Indicators
Because chronic immune dysfunction is different for every person (different microbes, different genes, different system disruptors), defining immune dysfunction with labs is rarely straightforward. None of following markers are always abnormal.
Hormone testing
Management of stress and menopause will be addressed in Chapter 28.
Testing for Toxins
Gastrointestinal Function
Food sensitivities. Chronic gastrointestinal dysfunction is often associated with sensitivities to commonly consumed foods (not the same as food allergies, such as peanut allergy). Symptoms associated with food sensitivities are commonly delayed for 1-2 days after the food is consumed. Typical symptoms include fatigue, joint pain, muscle pain, and general achiness—in fact, food sensitivities alone can be the root of many symptoms. Food sensitivities will be discussed more thoroughly in Chapter 24, Digestive Dysfunction.
Breath testing. Testing the breath for hydrogen and methane after taking a dose of glucose or lactulose is used to define the presence of Small Intestine Bacterial Overgrowth (SIBO). SIBO is commonly associated with symptoms of gas, bloating, nausea, and diarrhea. It can also be associated with fatigue, joint pain, and depression. Generally, symptoms alone are satisfactory for diagnosing SIBO, but in severe cases, breath testing can be valuable. SIBO is discussed in Chapter 24.
Comprehensive stool analysis. Stool analysis is valuable for defining gastrointestinal dysfunction and diagnosing parasites and yeast overgrowth. This expensive test is generally reserved for extreme cases when dietary modifications and supplements are not enough to overcome gastrointestinal problems. It is rarely necessary.
Folate and methylation
MTHFR is a gene that codes for an enzyme called methylenetetrahydrofolate reductase. This enzyme is vital for creating 5-methyltetrahydrofolate, an essential substance for converting the amino acid homocysteine into the amino acid methionine. Methionine is essential for amino acid synthesis, formation of glutathione (important intracellular antioxidant), formation of DNA, and detoxification. Methionine is important for formation of SAMe, which plays a key role in metabolism of dopamine, serotonin, and melatonin.
There are about 40 different genetic mutations that can affect MTHFR. About 40% of the population has one affected gene. About 12% of the population has two affected genes. It is important to note that mutations cause variations in the enzymes, not defective enzymes. The enzymes are still functional, but to varying degrees. It is also important to note that because methylation is so important, the body has many redundant pathways for methylation; it is not solely dependent on MTHFR.
Problems that have been weakly associated to MTHFR mutations include elevated risk of stroke and heart attack; increased cancer risk; defects in embryo development (spinal tube defects); and neurological symptoms including insomnia, irritability, depression, brain fog, neuropathy (burning/tingling feet and hands), restless legs syndrome, fibromyalgia, and chronic Lyme disease. How much of a factor it is in these illnesses is still controversial.
For five years of my medical practice, I had the fortune of being associated with a lab that did MTHFR mutation testing for free. Therefore, virtually every one of my patients had MTHFR testing. This amounted to a couple thousand people. Surprisingly, I found it played less of a role in recovery than I expected. I had chronic Lyme sufferers who were severely symptomatic who had no mutations and perfectly healthy people who had double mutations. It may be a factor in chronic illness, but is probably minor compared to other things.
TESTING
MTHFR problems can be detected indirectly by checking for elevations of homocysteine and deficiencies of RBC folate in the blood. MTHFR mutations can also be detected directly by specialized labs. Avoid DIY home labs because testing may be inaccurate. Avoid practitioners who suggest that all your problems are related to MTHFR mutations.
SOLUTIONS
The best solution is getting plenty of natural 5-methyltetrahydrofolate (methylfolate for short). Leafy greens are a great source, but if know you have a mutation, supplementing is a good idea. Folic acid, found in most multivitamin products, will not work because it must be converted by the deficient enzyme.
You must supplement with 5-methyltetrahydrofolate. 5-methyltetrahydrofolate 400-800 micrograms daily is generally adequate for anyone with a single mutation (especially if you eat plenty of leafy greens). If you have a double mutation, it is a good idea to take an extra 400-800 micrograms daily. For additional benefit, you can add SAMe 400-800 mg daily. SAMe supports detoxification and can improve sleep (by taking it in the evening).
Chemical components called “methyl groups” that are essential for proper detoxification can also be supplied by vitamin B6 and vitamin B12. It is, however, important to get the activated forms of these important vitamins. The activated form of vitamin B6 is pyridoxal 5-phosphate, and the active form of vitamin B12 is methylcobalamin. You can also take SAMe (400-800 mg daily), especially if poor sleep and depression are an issue.
Healthful diet and adequate supplementation of substances that provide methyl groups is generally adequate for recovery. MTHFR testing is only necessary if recovery is not progressing.
Testing Beyond the Laboratory
Certain types of symptoms require evaluation by diagnostic procedures conducted by specialists in their respective field.
Neurological symptoms - Severe neurological symptoms are evaluated with a nerve conduction test and MRI of the brain. The purpose is ruling out multiple sclerosis.
Cardiac symptoms - Chest pain and irregular heartbeat are evaluated by EKG and Holter monitor. Findings may lead to cardiac catheterization.
GI symptoms - Stomach pain and symptoms are often evaluated by upper endoscopy. Lower intestinal and colon symptoms are evaluated by colonoscopy. Routine colon cancer screening with colonoscopy is recommended every 10 years for everyone over 50.