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Lyme, Neurotoxins, and Hormonal Factors: an interview with Nancy Faass, MSW, MPH.

Wayne: It is my privilege to be here with Robert Gitlin, DO, an experienced Lyme-disease practitioner, trained in Osteopathic Manipulative Medicine, with expertise in the endocrine system and hormones. We would like to offer our perspectives on how guiding hormone therapy in the Lyme patient differs from treating other patients, given that intracellular infections have their own unique effects on the endocrine system.

I think that currently one of the problems in medicine is an excessive focus specifically on Lyme disease. What sometimes gets missed is the fact that this is a constellation of toxic influences that all have the same mechanism of action. Our patients may be struggling with infectious processes caused by borrelia or co-infections like babesia, bartonella, ehrlichia, or mycoplasma, as well as toxins such as mold species, petro-based chemicals, and heavy metals. All of those infections and toxins affect the regulatory systems of our body: the brain and nervous system, and the immune and endocrine systems.

Patient Symptoms

Unresponsive to Hormone Therapy

Potential Infection. Wayne: Most Townsend readers are familiar with all the essentials of hormone management. However, Lyme confuses hormonal responses in our patients, causing disorganization and dysregulation. As a result, lab testing and patient outcomes are different than those a provider would expect to see in both men and women with Lyme. When a Lyme infection is present, classic symptoms of hormonal transition can be exaggerated and hormone replacement may not improve symptoms or may improve them only temporarily.

If you are guiding bio-identical hormone replacement therapy (BHRT) and the patient is not responding, they may have an intracellular infection or neurotoxic build-up. I have come to realize that in some cases, the therapy is not working because this is not primarily a hormone patient, this is a Lyme patient. These patients may have a borrelia infection, masquerading as a hormone-related problem.

Toxins. Rob: In my patient population, hormone disruption can be due to environmental estrogen disrupters (EEDs). When I see a man who has low testosterone or a non-menopausal woman with low hormone levels or premature ovarian failure, often it is not Lyme but neurotoxins functioning as estrogen disrupters: for example, xenoestrogens, petrochemicals, or heavy metals. When I evaluate patients with these exposures, I find that many of them also have underlying Lyme. Although 90% of my case load is women, it is possible that males are equally sick in ways that we do not always associate with Lyme, like prostate cancer and cardiovascular disease--but we are not diagnosing their co-morbidities as well.

Adrenal Exhaustion. Rob: Clinically, I found that in a certain percentage of female patients, no matter what I did with hormone replacement or modification, there were failures. (Clinically, this is less often true of men, but it is still the case.) That led me to discover that in the vast majority of these cases, there was a problem with compromised adrenal function. If these issues are not adequately addressed, adrenal depletion will always prevent the patient from fully correcting other hormone issues involving thyroid, DHEA, estrogen, progesterone, and/or testosterone.

Difficult Hormonal Transitions

Wayne: When there is the overlay of intracellular infection and hormone depletion, these individuals really suffer. This is especially true of midlife women with Lyme, who may experience menopause as the worst thing that ever happened to them. Estrogen, progesterone, testosterone, DHEA, and thyroid are all steroidal hormones that have a major effect on how we experience inflammation. Cortisol also neutralizes inflammation and stimulates immune function. Decreases in these hormone levels are the opening that borrelia uses to gain a foothold.

We also see this with perimenopause. We've come to realize that perimenopause is not a gradual reduction of estrogen, but rather a phase in which estrogen levels are rapidly fluctuating, excessively elevated and then plummeting in a roller coaster pattern. Frequently high achievers who contract Lyme and are burning the candle at both ends hit perimenopause and crash. These vulnerabilities create incredible hormonal instability and a fertile environment for borrelia infection.

Rob: Women get half of their testosterone from conversion of DHEA and androstenedione in fat and skin tissues and the other 50% in equal parts from the ovaries and the adrenals. So there is major dependence upon the adrenal axis and greater vulnerability due to increased stress and decreased hormones. In men 90% of their testosterone comes from the testes and the other 10% from DHEA conversion (among others), which could explain why our menopausal Lyme patients are often sicker.

High Levels of Inflammation

Wayne: In Phases 1 and 2, neurotoxic infections and neurotoxins do not damage cells as regular bacteria do, but they trigger chronic inflammation. That inflammatory process impairs the function of cells, resulting in their symptomatic presentation. However, when hormone levels are adequate, they are protective against such inflammation. The men who show up in my practice with a Lyme infection tend to those experiencing drops in testosterone, driven down by an aggressive borrelia infection. Others are men in andropause whose testosterone is already dropping, reducing the protective anti-inflammatory effects of their hormones.

Rob: In terms of inflammation, men have an advantage over women given that testosterone appears clinically to have much more of an anti-inflammatory effect than estrogen and progesterone. Women tend to experience more inflammation clinically and those with Lyme are likely to be more symptomatic, and at a much earlier stage. Proactively balancing testosterone levels in these female patients seems to have a highly anti-inflammatory effect. DHEA and estrogen also have anti-inflammatory effects.

Moreover, in the research bio-identical transdermal estrogen has been shown to reduce hs-CRP and MMP9 as well. DHEA, the most abundant steroidal hormone in the body, has been shown to lower TNF-alpha and IL-6 levels in the Prasterone (GL701) studies with lupus using a pharmaceutical form of DHEA. DHEA also stimulates the immune system and enhances immune activation by increasing levels of NK cells and IL-2. Its synergistic effects with other therapies are exemplified by four-fold increases in HAI titers upon co-administration. Pregnenolone, known subjectively for reducing pain and spasms, also has anti-inflammatory effects, and in the past was used as a treatment for rheumatoid arthritis and other inflammatory conditions.

Complex Chronic Illness

Wayne: I encourage practitioners to suspect an underlying infection when you have provided a therapy that should have a predictable response

in the average patient, and you get a radically different response, one that is enigmatic or paradoxical. That type of response should be a trigger for the practitioner to suspect an underlying infection. My premise is not that everyone has these infections. However, integrative and functional medicine practitioners--as practitioners sought out by patients who have not responded to conventional therapies--see a disproportionately greater number of these patients. It is those who do not respond to hormone therapy that are most likely to have this complex presentation. For patients who have underlying infections, none of our tried-and-true therapies are going to be the solution. They will mitigate the symptoms, but in the long run, they are not going to resolve the symptoms. The symptoms will gradually creep back in, as the infection adapts to the new baseline.

Rob: These intracellular infections have the ability to hijack our immune system, just as cancer does. For instance, the organism can form blebs that bind free, circulating borrelia antibodies and have potent mitogenic activity that increases immune activation. Borrelia also has cloaking mechanisms in which the pathogen surrounds itself with the body's lymphocytic proteins, thus decreasing immune recognition. Moreover, these pathogens can congregate in biofilms that serve to protect the organisms from effective attack by the host immune system.

Testing and Diagnosis

Physical Exam. Rob: Wayne and I both share a love of the challenge of investigation, the process of clinical evaluation that comes with each new patient. In terms of our approach, as an osteopath I practice a little differently. I place a strong emphasis on the physical exam. I palpate the area around their gallbladder, liver, and spleen. I perform a neurological exam and check to see whether they have cerebellar ataxia and past-pointing, as well as heel to toe walking instability. Celiac patients also present approximately 40% of the time with cerebellar ataxia, a babesia physical exam finding (there are some crossover symptoms between celiac and babesia).

Testing and Challenge Trials. Wayne: The credibility of the Lyme diagnosis has been questioned for the last 30 years due to the inability to culture these bacteria. Laboratory evaluation has not yet caught up with the rapid worldwide proliferation of these microbes. The public health agencies that screen the blood supply are scrambling to nail down screening tests after patients who received blood transfusions developed babesia infections. We currently have antibody tests for two of over one hundred species of babesia. We have used the Advanced Laboratory Services culture for Lyme and are hopeful that it will successfully move forward in the clinical trials that are currently on going. At this point, IGeneX IgG and IgM Western blots are the most reliable testing we have available, reported to be correct 70% to 97% of the time. [A substantive article on testing for Lyme by Dr. Anderson appeared in Townsend Letter in June 2012 and is available online at no charge at TownsendLetter.com.]

Genetic testing. The LabCorp test DRB-HLA is an evaluation of 10 allele strands on the 6th chromosome associated with genetic vulnerability to neurotoxins. When the DRB-1 is 01 and the DQ is 05, this represents what Ritchie Shoemaker terms hypothalamic dysregulation. Clinically, what it often suggests is the need to be more aggressive in supporting hormones. Patients with this pattern tend to have more hormonal dysregulation, which probably reflects lack of communication from the hypothalamus to downstream hormones. Rob also has patients checked for MTHFR genetic mutations, which can be performed by any local lab. This is one of many bases we cover in seeking to detoxify our patients. It is also helpful to check and correlate B vitamins and homocysteine levels.

Generally speaking, patients with these genetic vulnerabilities are the sickest of our Lyme patients. For these people, it is particularly important to stop metal and chemical exposure and to chelate them with great care, because they are those most likely to be disrupted by chelation and metal detox. [For more information, see Ritchie Shoemaker's Mold Warriors and the website www.survivingmold.com.]

Challenge testing. Frequently we are left with only the patient's symptomatic presentation and response to therapeutic interventions for cues on the presence of intracellular organisms, which include pathogens like the rickettsial species, the smallest life forms on earth identified to date.

Challenge test protocol may be performed with a Byron White Formula, but it could even be done using an antibiotic. I learned about babesia from giving Mepron with Zithromax. The symptoms that got better in response to a trial of Mepron were often symptoms associated with babesia and the antibiotic served as a provoking agent in the absence of definitive testing. [Dr. Anderson's approach to challenge testing using the Byron White Formulas was published in an article in June 2012 that is available online at TownsendLetter.com]

Neurotoxic Build-up. Rob: Research on a representative population for exposure to approximately 200 known toxins such as petrochemicals, xenoestrogens, and fungicides found that 100% of the toxins were present in 100% of the people tested. These are all endocrine disrupters. We do not have to test for these things. By definition, all of us have disruption in our endocrine system, so diagnosis means looking deeper at what else is causing disruption. It is an interesting coincidence that for the average person, all hormones decrease by 14% per decade after the age of 30.

High Mercury, Low Magnesium, and Low Testosterone

Rob: Optimizing treatment involves normalizing levels of mercury, magnesium, and testosterone. I use the following guidelines:

If mercury levels are high, that must be addressed to achieve effective treatment. There is a documented synergistic relationship between borrelia and mercury. To test for mercury, I usually do a six-hour urinary DMSA pre-and post-provocation challenge test. To treat for high levels, I will generally use a gentle oral chelation protocol at the appropriate time in the treatment sequence. IV chelation is appropriate as well, and I typically send people to another clinic for that. [For further information on challenge testing for mercury, see the article by Joseph Hickey, MD in the November 2013 issue of Townsend Letter.]

Magnesium is rapidly depleted by Lyme, so we need to constantly replace magnesium when treating Lyme. Otherwise the Jarisch-Herxheimer reactions can be more severe. This is a vital aspect of the treatment protocol, since magnesium is an important co-factor in many of the hormonal production pathways, and in normal physiological functioning on a cellular level. To test for magnesium, it is best measured by using a serum RBC Mg+ level. However, I do not typically test for magnesium. In many cases, patients' history will reveal leg cramping at night, insomnia, or signs of occasional to frequent blepharospasms (eyelid spasms/twitches); these symptoms are surprisingly common. For treatment, I simply have patients titrate magnesium to bowel tolerance, with one to five capsules at bedtime, using an approach similar to the titration of vitamin C. The ideal amount indicates how much the body can absorb. Magnesium glycinate or malate are preferable.

A low-testosterone state provides an opening for opportunistic infections such as borrelia and the co-infections. Testosterone levels are best measured using the serum free and total levels at local labs. Some practitioners use spot blood, 24-hour urine levels, or salivary testing. I use measurements in serum, as that is the local standard of care.

Treatment Options

Clinical Design (Design is Everything)

Rob: When someone has acute Lyme of long-standing duration, there is a temptation to go right into Lyme treatment mode using antibiotics. However, the patients we are primarily discussing here are not the typical acute presenters; they are those who are chronically ill, have seen several practitioners, received short blasts of inadequate treatment, and are often very depleted.

I find clinical design to be everything in these cases. There is no rush to treat, since often the patient has been sick for years. We need to take the time to set the stage for a reasoned approach.

Any practitioner can start Lyme treatment, but once you start, you are soon in "the middle game." That is a place where you need to keep your bearings, or it is easy to get lost. This translates to frequent visits in which we are constantly tracking our patient's multitude of clinical symptoms, along with a thorough physical exam, and correlating those symptoms with the patterns currently triggered by the pathogen that is predominating at the time.

Sequencing Treatment

Infectious Agents. Wayne: In sequencing treatment, I go after the most pathogenic process, the pathogen that is most threatening to the immune system. Almost always, reproductive species (infectious agents) will have a more pathogenic effects than inert substances (metal and chemical), because by definition life forms proliferate and grow at logarithmic rates. Borrelia, bartonella, et al. are reproducing cyclically, whereas metals and chemicals are like sludge in our bodies. Each individual patient needs to be assessed for their unique situation. There are cases in which it is important to go after the metals first, when the accumulation of these toxins is so excessive that it compromises the patient's immune system and their ability to fight the Lyme effectively.

Heavy Metals. Rob: I start evaluating for heavy metals with a DMSA challenge and track the results and the patient's response during testing. Do they feel light headed, woozy, or develop a headache? And what are the actual numbers? Then we stop the upstream exposure, depending upon the biological terrain of the individual patient, which could mean having dental amalgams systematically removed while you are treating their Lyme. An additional option is to use an oral chelator such as Metalloclear from Metagenics, typically three tabs twice a day for at least two months, to slowly reduce the level of metal toxicity while not needing to replace minerals. Another useful remedy recommended by Richard Horowitz, MD, is low doses of chlorella, which effectively bind metals. Nutritionally you can also use a quarter cup of cilantro daily. You would be surprised how much of a herx patients can develop from this detox. Detoxification baths are also very helpful and well tolerated. Many of these approaches can take up to a year, but have the benefit of being slow and methodical, and minimizing herx reactions. [For more information on Dr. Horowitz' perspective, see Why Can't I Get Well: Solving the Mystery of Lyme and Chronic Disease, from St. Martin's Press, 2013.]

I tend to take a moderate approach to the issue of metals. I do not consider IV chelation an initial step in someone who has Lyme or co-infections, viruses, metals, and hormone dysregulation. If I am going to chelate Lyme patients, my goal is to initially reduce their Lyme load a little. In our experience, if chelation is performed too early in the sequencing of Lyme treatment, patients may experience increased disorganization neurologically or health-wise. Their symptoms tend to get worse, rather than better, an indication that treatment needs to be approached in a different order. In short, we stay away from metals until the end of treatment unless a compelling reason presents: for example, someone with a cadmium level of 6000.

Wayne: Churning up those neurotoxic metals has an additive effect and can cause a disproportionally negative response. All neurotoxins are additive, increasing inflammation, so if the patient has lead or mercury deposits stored in their fat tissue and you chelate that out, it can be like pouring gasoline on a fire, causing a flare of symptoms.

Tracking Clinical Responses to Lyme Treatment

Wayne: Let's talk about the pros and cons of replacing hormones. In functional medicine we thrive on replacing hormones. Here I'd like to look at reasons for delaying hormone replacement. First, you and I are in total agreement that each individual patient requires a different approach. That is absolutely the most important underlying principle. Second, as providers we need not be wedded to any one rigid philosophical approach to treatment. Third, as we have discussed, there is a difference in treating values outside the reference range as opposed to those inside the range or optimal. There is wisdom in reading the symptoms that reflect immune system activity in the moment. Fundamentally, in the absence of comprehensive and reliable testing, these symptoms are the most important evidence we have of elusive intracellular infections, and they guide treatment. So here is my controversial view: I do not always do hormone replacement first.

Treating new patients. If I'm seeing a new patient I don't want to interfere with my patient's symptomatic presentation by making hormonal changes. I want to be guided by the wisdom of the immune system and my understanding of how this patient is wired. I want to understand the underlining reason(s) for this patient's chronic illness. If I change the picture too soon, that could interfere with my ability to read this patient's symptoms and could delay my efforts to determine the type of infection for which the patient needs to be treated.

Hormones out of the reference range. If any of their hormones are out of range, then obviously I am going to treat those hormones, but if they are within range then often I'm going to take a wait-and-see approach. Rob reports that for those within the reference range, rather than using bio-identical hormones, he may work with adaptogenic herbs and supplements.

Tracking a single variable. If the patient has fatigue, I want to know that I have affected that fatigue with my antimicrobial approach. I don't want to wonder whether it was the tincture or the hormones that improved their fatigue. I want to know that I'm correct in my diagnosis. Does this patient have babesia or bartonella as the current dominant infection? The only way that I can be sure about that is by noting the patient's symptomatic response to just one treatment variable.

Optimizing Hormone Levels

Rob: What I learned with you and other Lyme-literate physicians around the country is that our primary goals are to support the immune, endocrine, and nervous systems. A good example is a patient that I just saw yesterday. He is 67 years old. His IGeneX Lyme test lit up like a Christmas tree with all the bands, an unequivocal positive test result. He also has a free testosterone of 35 and a total testosterone of 230. He meets the laboratory definition of androgen deficiency, and he marked nine out of ten positive responses on the ten-point questionnaire that I use from the St. Louis School of Medicine--a protocol that I use for objectifying andropause. In addition, he had adrenal insufficiency.

I found this gentleman to have severe babesia symptoms, which included heart palpitations, night sweats, chills, fevers, numbness, and tingling in his hands, as well as panic attacks, anxiety, brain fog, insomnia, air hunger, and migraine-like headaches with auras. I put him on the appropriate adrenal protocols (as many of these symptoms also overlap with those of adrenal insufficiency) and started him on a supplement of organic maca, a Peruvian herb that we use to help balance testosterone. He came back to see me this week, and he is 70% better with all of these symptoms. His headaches are nearly gone. Many of the babesia symptoms are nearly gone, but he still has anxiety, a little trouble sleeping, and brain fog, although his brain is much better. In my clinical experience with babesia, in particular, the anxiety response that men experience is much more pronounced than that of women, especially when testosterone is low. I put him on bio-identical testosterone this week, and on this protocol, he tapered down to a more normal anxiety level, comparable to that you would expect when testosterone is just starting to be replaced. I'll see him back in a month, and after that I'm going to start treating him for Lyme and babesia.

If you have been tracking the patient over time, I believe that you are not going to lose the clinical presenting features. I consider the addition of a hormone just one more factor whose effects I observe. This can be compared with how you would treat someone for babesiosis. I would put them on artemisinin and then see what changes with the babesia symptom pattern. In this case, we have put this patient on a testosterone adaptogenic herb and some adrenal support; the babesia symptoms are better, but the babesia is not gone. However, the patient is much more comfortable and as a result will be much more compliant in going through the treatment process. My experience is that the people for whom you can initially optimize hormones have fewer and less intense herx reactions when you treat them. I think that goes back to your poignant observation earlier, that inflammation is reduced when patients are on hormone replacement.

Clinically I worry less about confounding symptom patterns because I never see the neurologic exam appreciably improved by BHRT (and I do rely heavily on neurological evaluation with these patients). The neurological exam improves only with reducing the level of infectious pathogens and, in a subset of celiac patients, improvement with gluten-free diets. Also, I am inclined to agree with you about holding off on treating with BHRT in one regard and that is the gut. I will not treat with BHRT if the gallbladder or liver is tender on physical exam. Since most hormones are metabolized through the liver, compromised liver function is just a setup for failure. Generally speaking, these patients are the ones who will not tolerate BHRT.

Providing BHRT During Hormonal Transitions

Wayne: There are a few hormonal situations in which I am much more liberal with hormonal replacement or support. In particular, I want to track and support hormones when significant hormonal changes are occurring in the body: in puberty, during pregnancy or lactation, and in perimenopause, menopause, and andropause. We know that these neurotoxins compromise cellular function and make all cells less efficient. This can have an enormous impact on endocrine glands, in particular at times when they have to function at ultimate, peak performance.

Often people. with Lyme are only mildly symptomatic due to their underlining inflammatory disorders, but when they go through one of these hormonal transitions, will have a significant aggravation of their symptoms. In patients who are unaware that they have Lyme, these symptoms are simply regarded as typical of menopause or puberty, assuming that there will be more mood disorder or more behavioral dysfunction or more problems during those times without any awareness of the presence of an underlying infection.

Non-responders. I will treat hormones more aggressively in my non-responding patient. If I'm not getting much traction from my antimicrobials, I will then fall back and treat hormones more aggressively.

Chronic pain patients. This is another group that I will treat with hormones more aggressively. I think they need the advantage of the anti-inflammatory effects of those hormones. And yes, if their hormones are out of range, then obviously I'm going to treat those hormones, but if they are within range then I'm going to take a wait-and-see approach.

Patterns of genetic vulnerability. As mentioned, we often run LabCorp HLA-DRB genetic test and when we see any of these patterns of potential vulnerability, we treat that patient more aggressively hormonally, and earlier in treatment.

Supporting the Adrenals and the Depleted System

Rob: When we see someone who is not having the expected response to BHRT it is usually due to one of three reasons: They may have an underlying infection due to Lyme, a coinfection, or a build-up of neurotoxins. Another potential pattern is that they did not recover because their adrenals were not addressed. That can be significant. Lastly, their detoxification systems may not be open, in particular the hepatic, renal/lymphatic, or integumentary system.

Minimizing suffering. My approach is to support the patient's depleted system as much as possible with the primary goal of alleviating suffering, the suffering that is present before me and in the future reducing herx reactions (die-off). The majority of my patients are people who get up and go to work even though they do not feel that they can. They do not have the desire to get out of bed, but they have to work, and most, frankly, cannot afford to stop, so I try to alleviate their suffering as quickly as possible.

The pre-treatment phase. My experience has been that if I put someone on antibiotics right away, or if I put them on any of the herbs right away, they're going to have very severe herx reactions. Clinically, they will suffer less if I support their immune and endocrine systems in advance. So when necessary, I spend a great deal of time initially doing basic ground-level support for the adrenals and the thyroid, at a minimum, while at the same time working on detoxification.

Restoring the adrenals as a priority. I might not necessarily put someone on a thyroid supplement until I am sure that the adrenals are corrected, because the thyroid cannot become fully functional unless the adrenals are supported adequately. I would agree that often it is premature to put someone on a thyroid supplement unless the adrenals have had a chance to recover. It can be a temptation to think, "Okay, we gave them herbs for the adrenals, and we gave them hormone replacement. Let's go right to the thyroid."

But it can take six months or a year for the adrenals to come back into order. All of this is predicated on what the clinical and symptomatic picture looks like in the individual patient, as you so eloquently state. For instance, I will often use a botanical such as ashwaganda or a pure source adrenal supplement like neonatal bovine adrenal cortex, at the same time using an adaptogenic thyroid supplement. Then I reassess thyroid levels at regular intervals to see if the body has adequately recovered; people often do beautifully with concurrent Lyme treatment.

Endocrine Systems

The Hypothalamus and Pituitary

Wayne: The hypothalamus sits just above the pituitary in the brain, the master gland that initiates much of the hormone activity in the body. The hypothalamus communicates with the pituitary and the pituitary then communicates with the thyroid, adrenals, pancreas, and sex hormones, striving for homeostasis. Given that neurotoxins disproportionally affect the brain, the hypothalamus is also disproportionally affected, and hypothalamic dysregulation affects all of the hormones downstream.

Hypothalamic regulation also affects a number of basic physiological functions, including sleep, temperature tolerance, weight gain or loss along with appetite, thirst, hydration, fluid balance, and pain. just as the inflammatory processes of babesia, bartonella, and Lyme affect the brain, they also affect the regulatory systems of the hypothalamus. In some cases I intervene to try to regulate these effects on the hypothalamus, earlier rather than later if I think that patient needs support in that system. I focus on the downstream effects of hypothalamic dysregulation and thus support the thyroid, adrenals, and sex hormones when appropriate.

The Adrenals

Rob: It's a well-known fact that the adrenals are associated with increased vulnerability in acute and especially chronic infectious states. Every cell in the body has a receptor for cortisol and without it we cannot live. Cortisol is also indirectly involved with sex steroid synthesis. High cortisol levels often relate to frequent colds, infections, and difficulty losing weight, particularly adipose tissue. In general, we see our patients come in with phase I, II, or III adrenal insufficiency; most of them are in phase ll or phase III.

DHEA and cortisol. When patients have lower DHEA levels, they have problems with phase II detoxification in the liver, which affects proper flow from the gallbladder. If left unchecked long enough, this can severely hamper the immune system by causing the liver to develop congestion and the body to retain toxins. For instance there is a four- to five-fold decrease in breast cancer recurrence when DHEA levels are in the upper third of normal, with the correlary that low DHEA is associated with higher rates of breast cancer and its recurrence. We work on DHEA and cortisol levels, using various adaptogens and direct bio-identical hormone replacement. The supplements most often used in my practice are selenium, zinc, omega 3 (pure source) fish oil, B complex, vitamin C and D3, and DHEA with or without cortisol supplementation with Cortef or an extract from a pure animal source. Supplementation depends on how much reserve or depletion is present.

Pregnenolone and progesterone. It is also important to address pregnenolone and progesterone as they are also made in the adrenals through a complex and energy-consuming process. Supplementing these hormones exogenously saves the body from the taxing metabolism of cholesterol, and the adrenals do not have to work so hard to maintain adequate levels. This is important clinically in cases of bartonelosis, frequently associated with severe PMS in female patients. In these cases, one can try some pregnenolone, or bio-identical low-dose progesterone, at the same time addressing any magnesium deficiency. All sex hormones can be made from pregnenolone. In addition, pregnenolone makes cortisol, and in a chronic stress state (as we see with Lyme) nearly all the pregnenolone is going to cortisol instead of DHEA and the sex hormones. It makes sense to replace pregnenolone and DHEA in these chronic stress states.

Psychoneuroimmunology. When Lyme patients present, often they are in an altered psychological state, usually full of fear. Imagine the state of medicine today if cancer or hepatitis patients were tested with lab work that had up to a 92% false negative test result. How would people respond psychologically? Fear can become a chronic state that either drives cortisol upward or depletes it. Many of these patients are in phase II or phase III by the time they present. One of the most important things we can do from the very start is to give our patients hope, which will support the hypothalamic/pituitary axis, establishing better hormone levels and increasing endorphin production. It is well established that opioid compounds play a major role in immune modulation by enhancing the cell-mediated pathways, in contrast to the dysregulating effects of the fear response. As Wayne points out, the adrenals provide our primary anti-inflammatory, and they take a big hit in these illnesses both physically and psychologically.

The Thyroid

Rob: In the Lyme patient, thyroid is such an important issue to address because inflammatory cytokines often suppress thyroid function. We usually see this pattern begin with the adrenals. As you may recall, adrenal function must be intact in order to support a well-functioning thyroid, among other hormones. This balance is further disrupted if an autoimmune process such as Hashimoto's is present. However, Lyme is not the only culprit in terms of autoimmunity. Given that 70% of the immune system is in the digestive system, gastroenteritis, gut dysbiosis, or heavy metal toxicity can drive the autoimmune process as well. There are many effective thyroid protocols including Wilson's, the Wiley protocol, thyroid hormone optimization (with or without total T3/reverse T3 ratio), using any or all of the combinations of animal thyroid (Armour), Synthroid, Cytomel, and/or lodorol in conjunction with various nutrients, such as those used in the adrenal support protocol described earlier.

Thyroid optimization is a key ingredient in BHRT. For instance, T3 increases NK cell and immune modulation activity. Moreover, T3 and T4 repair DNA which acts as a free radical balancer. In clinical practice, I have observed Hashimoto's in approximately 25%-30% of my Lyme patients. When a low WBC (white blood cell count) is observed and no other apparent cause is found, the patient usually has Lyme. This is found in approximately 20% of my patients. Gilbert's syndrome, associated with elevated levels of bilirubin, correlates with the presence of Lyme in my patients approximately 92% of the time. When all three of these conditions are present in tandem (a low WBC count, Hashimoto's, and Gilbert's) in my patient population, that has been 100% predictive of the presence of Lyme disease. I am currently completing a retrospective study tracking this phenomenon (the Gitlin Triad). In my patient population, this triad is present in 5%-10% of cases. It provides a highly useful set of markers because it has a high predictive correlation and it saves patients health care dollars.

Wayne: This is fascinating! I know that my Lyme patients consistently have low WBCs, and many have Hashimoto's, but I had not associated those with Gilbert's syndrome. You are onto something here. What I like about your observation is putting together seemingly unrelated pieces of clinical information and creating a fascinating hypothesis. This is what we all need to be doing--tracking the patterns in the complex presentation of chronic inflammatory illness within the Lyme disease spectrum and seeing the connections. Great job.

Wayne Anderson, ND

Dr. Anderson holds a degree in naturopathic medicine from National College of Naturopathic Medicine in Portland, Oregon, and additional broad-based training in health and medicine. For the first two decades of his practice, Dr. Anderson worked in a busy community-based family medical center in a region in which Lyme was endemic. As he became aware of the prevalence of chronic Lyme disease and related conditions, he realized the important part they can play in chronic illness. In 2002, Dr. Anderson left family practice to work with Eric Gordon, MD, and focus on the treatment of Lyme disorders using leading-edge therapies from both conventional and integrative medicine.

Gordon Medical Associates

3471 Regional Parkway, Santa Rosa, California 95403

Office: 707-575-5180; Fax: 707-575-5509

info@gordonmedical.com

Robert Gitlin, DO

Dr. Gitlin graduated from the Kirksville College of Osteopathic Medicine in 1992 after completing an undergraduate teaching fellowship in Osteopathic Manipulative Medicine. He then became board certified with the AOBFP and the AAFP on completing family medicine studies with the osteopathic and allopathic (AOA and AMA) certifying program at the Shasta-Cascade Family Medicine Program at Mercy Medical Center in Redding, CA. He is a Lyme-literate physician in Northern California practicing integrative family medicine and osteopathic manipulative medicine with his wife, Karla, who is also an osteopathic physician in rural Redwood Valley, California.

Redwood Valley Medical Clinic

8501 West Road, Redwood Valley, California 95470

707-485-6900

Resources

Video on Genetic Testing (HLA-DRB)

A workshop video is available on genotype evaluation, presented by Wayne Anderson, ND, from the ILADS International Conference held in Boston, October 2012. To purchase a copy, go to ILADS.org, click on "Shop" then "Conference Videos. Click on the Boston Conference; Dr. Anderson's entry is the first on that page. The video is available for $15 and recommended to both physicians and patients.

Genetic Testing

If your patients have the desire to get additional testing beyond what is covered by their insurance, you can assess their metabolism with send-out test kits through Health Diagnostics Research, an institute that provides a Methylation Panel (info@hdri-usa.com). Further information on genetic testing can be found in Genetic Bypass, a book by Amy Yasko and on her website, www.DrAmyYasko.com, which contains a wealth of information at no cost.

Editorial

Nancy Faass, MSW, MPH, is a writer and editor in San Francisco who has worked on more than 45 books for publishers that include Elsevier, Harper, McGraw-Hill, Mosby, and others. Director of the Writers' Group, she also provides articles, white papers, and writing for the Web. For more information, contact info@HealthWritersGroup.com.

Gitlin "Lyme Triad"

Hashimoto's thyroiditis

Low WBC

Gilbert's syndrome

Wayne Anderson, ND, and Robert Gitlin, DO
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Title Annotation:Robert Gitlin and Wayne Anderson
Author:Anderson, Wayne; Gitlin, Robert
Publication:Townsend Letter
Article Type:Interview
Geographic Code:1USA
Date:Jul 1, 2014
Words:6281
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