Articles

Lyme Disease

Introduction

Lyme disease is a multi-system disease that develops from infection with Borrelia burgdorferi. The small, spiral shaped bacterium (spirochete) is transmitted by infected deer ticks (Ixodes scapularis) and black legged ticks (Ixodes pacificus). Ixode ticks are found predominantly on deer, but can also be carried by field mice, rabbits, sheep, and cattle. The disease is transmitted when an infected ixode tick bites a human, exposing him to the Borrelia bacteria. From 1992 to 1998, 92 percent of Lyme disease cases were reported from eight states in the Northeast and Mid Atlantic, as well as Wisconsin and Minnesota. (1) Lyme disease is named after the town in which it was first identified, Lyme, Connecticut. In the early 1970's, a cluster of unexplained arthritis cases appeared among young children in the area. After researching the cases, clinicians were able to determine the source of the illnesses and identify the bacterium responsible. (2)

Lyme disease has proven itself a challenging disease on a number of fronts. The difficulty begins with identification of the disease. Ixode ticks are extremely small, about the size of a pinhead, making them difficult to see. This is especially challenging on areas of the body with hair. Furthermore, tick bites are essentially painless and many people are bitten unknowingly. Initial infections are often asymptomatic, although in about half the cases, a characteristic rash (erythema migrans) appears at the site of the bite. The rash, known as a "bull’s eye", is the only hallmark sign of Lyme disease. Blood tests may not be reliable, since it takes as many as four weeks after infection before antibodies can be detected. After several weeks, the most sensitive test, the enzyme-linked immunoassay (ELISA), can be used to confirm a clinical diagnosis, followed up with a Western blot. A new genetic engineering technique, polymerase chain reaction (PCR), is under development, which can detect genetic material from the Lyme bacterium in human fluid and tissue. (3) Furthermore, the disseminated disease resembles many other illnesses, and is often misdiagnosed as chronic fatigue, fibromyalgia, depression, or multiple sclerosis.

Statistic

Centers for Disease Control, 1999.

    182,000 cases of Lyme disease have been identified since 1982. The number of early diagnosis doubled in 1992.

Signs and Symptoms

[span class=alert]The following list does not insure the presence of this health condition. Please see the text and your healthcare professional for more information.[/span]

Lyme disease is a progressive illness that can be identified in three stages of infection: early, early disseminated, and late. Early infection is characterized by the erythema migrans (EM) rash, known as the "bull’s eye" rash. It begins as a small, red lesion at the site of the tick bite. Over a period of days or weeks, the spot grows to a round or oval rash, which can vary in diameter. The lesion may be as small as a dime or as large as a watermelon. The bull’s eye appearance results from the appearance of a red ring around a clear middle, with a small red mark remaining in the center. The rash may appear in other places as the infection progresses. The erythema migrans is often accompanied by mild, flu-like symptoms (fever, headache, fatigue, and muscle tenderness) that persist for 6 to 8 weeks after initial infection.

Early disseminated infection manifests in more specific neurological symptoms. Temporary facial paralysis (Bell’s palsy), meningitis (headache, sore neck, back pain), and neuropathies have been identified during this phase. Intermittent joint inflammation and tenderness are also reported. Arthritis marks the onset of late infection. Several months after initial infection, more than half of those exposed to B. burgdorferi develop chronic, intermittent arthritis. (4) About 10 percent develop arrhythmias, dizziness, and shortness of breath. Other symptoms include mental confusion, conjunctivitis, skin disorders, and poor motor coordination.

Early Infection

  • Erythema migrans (EM) rash at the site of the bite that over a period of days or weeks grows to a round or oval rash, which can vary in diameter
  • The rash may appear in other places as the infection progresses
  • The erythema migrans is often accompanied by mild, flu-like symptoms persisting for 6 to 8 weeks after initial infection

Early Disseminated Infection

    Temporary facial paralysis Meningitis type symptoms Neuropathies Intermittent joint inflammation and tenderness

Late Infection

    Chronic, intermittent arthritis Arrhythmias Dizziness Shortness of breath Mental confusion Conjunctivitis Skin disorders Poor motor coordination

Treatment Options

Conventional

The main course of treatment for Lyme infection is antibiotic therapy. The key to successful treatment of the disease is early intervention. The longer the infection goes untreated, the longer the course of therapy will be. Some experts argue that Lyme disease is a multi-species infection, involving more than one parasite. (5) One of the species identified (Piroplasmosis [Babesiosis]) is a protozoa. Furthermore, new information exists that B. burgdorferi can take at least three forms: bacterial, spheroblast, or cystic, each responding to different classes of antibiotics. (6) There are four classes of antibiotics used to treat B. burgdorferi.

    Tetracyclines have a broad spectrum of antibiotic activity, and are especially effective at destroying spirochetes. This class is the first choice for treating Lyme disease. However, tetracyclines can cause a wide range of adverse effects, including gastric irritation, nausea, vomiting, diarrhea, kidney toxicity, liver toxicity, and alterations in blood coagulation. Permanent staining of the teeth may result if tetracyclines are given to young children, or in utero. Because of the broad spectrum of activity, those taking tetracyclines are subject to recurrent Candida overgrowth in the mouth, vagina, and bowel. Newer tetracyclines (doxycyline, minocycline) may also be used. Penicillins (amoxicillin, penicillin V) are also effective against gram negative bacteria such as B. burgdorferi, but high doses are needed. Because of the short half-life of these antibiotics, they are sometimes given with probenecid, which slows excretion by the kidneys. Blood levels should be monitored to ensure adequate dosage. Cephalosporins (ceftriaxone) are effective in cases where tetracyclines are contraindicated, or penicillins have failed. First and second generation cephalosporins are not any more effective than the other antibiotics, so third generation agents are used. These are not the first drugs of choice because they must be administered by intramuscular or intravenous routes, and they are expensive. Potential adverse effects include cholecystitis and intestinal overgrowth of Candida. Macrolides (erythromycin) bind to bacterial ribosomes and prevent protein synthesis. This class of antibiotics is marginally effective against B. burgdorferi at high doses; however, resistance to erythromycin develops rapidly among gram-negative bacteria. (7) Azithromycin and clarithromycin, newer forms of the macrolides, produce GI distress and yeast overgrowth, rendering them intolerable for extensive therapy. One reason for the failure of these antibiotics is the low pH of the vacuole that surrounds B. burgdorferi within a cell. (8) Therefore, the efficacy of macrolides is improved when administered concurrently with hydroxychloroquine or amantadine, which increase the pH of the intracellular medium.

Note: For many patients, multiple rounds of antibiotics can affect the normal flora of the intestinal tract. Co-administration of probiotics at least two hours apart from the antibiotic dose reduces the likelihood of the development of dysbiosis.

Vaccination Vaccination against Lyme disease has been used successfully in animals for many years. A human vaccine is currently under clinical trial. The vaccine works by stimulating anti-Borrelia antibody production. However, there is considerable controversy about the safety of this vaccine, and it has not obtained approval from the FDA.

Nutritional Supplementation


Multivitamin

Optimal nutrition is important any time the body is challenged. Taking a high potency multivitamin/mineral supplement will help to boost energy reserves and the immune system.


Antioxidant Nutrients

Lyme disease is capable of causing widespread inflammation in many tissues throughout the body. (9) , (10) Since free radical production is a normal part of inflammatory activity, taking extra amounts of antioxidant nutrients might help to minimize the damage that is produced by the ensuing inflammation. Antioxidants to consider include vitamins A, C, E, beta-carotene, selenium, coenzyme Q10, and lipoic acid. Functions ranging from immune activity, inflammation response, to energy production are dependent on these nutrients.

One group of researchers investigating Lyme disease in an animal model reported that vitamin A deficiency predisposes the host for a strong inflammatory response, suggesting that it may foster susceptibility to diseases, such as Lyme arthritis, in which activated macrophage and inflammatory cytokine production are pathogenic. Based on the results of their studies with mice infected with Lyme disease, they stated that vitamin A deficiency may exacerbate acute Lyme arthritis by enhancing an acute arthritogenic inflammatory response initiated by spirochete-driven IFN-gamma secretion. Conversely, vitamin A may lessen acute Lyme arthritis pathology by blocking IFN-gamma and IL-12 synthesis. (11)


Lactobacillus acidophilus

According to one study, patients with inactive Lyme disease have been treated with an average of 3.25 rounds of antibiotics. Since antibiotic therapy is a regular part of the medical treatment for this condition, patients who have taken or who are taking antibiotic should be educated about the importance of repletion of beneficial bacteria in the gastrointestinal tract. With approximately 50 percent of immunity located within the GI tract, and with beneficial flora playing an important role in gut function, this recommendation should strongly be considered. Probiotic dosing is generally 10-15 billion cfu twice daily with meals for a minimum of six months, and then maintaining at a 1-2 billion, 1-2 times a day dosing regimen.


Omega-3 Fatty Acids

In particular fish oil, omega-3 fatty acids, in doses of 2-6 grams a day may reduce pain associated with soft tissue inflammation, as evidenced in rheumatoid arthritis. (12) Regulation of inflammatory prostaglandins may influence both pain and articular discomfort that can occur with Lyme patients.

Herbal Supplementation


Reishi Mushroom

Reishi mushroom is called the "mushroom of immortality" in China where it has been used as a tonic and strengthening medicine for thousands of years. Uses in traditional healing include increasing intellectual capacity and memory, promoting agility, and lengthening lifespan. (13) Reishi is reported to have some of the most active polysaccharides in the plant kingdom. Polysaccharides are claimed to have immunomodulating activity. Reishi is also reported beneficial as an antioxidant, antihypertensive, hypoglycemic, antiviral, and hepatoprotective agent.

Reishi extracts have been reported to significantly increase the lifespan of fruit flies by significant amounts (16-17 percent) in several studies, and also enhancing endurance and cellular oxygenation. (14) Reishi has been reported to inhibit superoxide activity and hydroxyl radical activity in vitro, supporting its role as an antioxidant. (15) The constituents with antioxidant activity have been reported to include the triterpenes. (16)

Reishi extracts have been reported to inhibit tumor growth in laboratory animals. (17) , (18) In one study, an isolated polysaccharide from reishi (b-1, 3-glucan) was administered to laboratory mice and was reported to produce tumor-inhibiting rates of greater than 90 percent, with complete tumor regression of over 75 percent of the mice. (19) A study of 48 patients with advanced stage carcinomas (including renal, gastric, and breast cancers) were administered an extract of reishi mushroom (1:10w/v) before chemotherapy. (20) Immunocompromised patients showed increased levels of CD4/CD8 ratio and T-cell counts, and lowered levels of T-suppressor cell counts. Radio- and chemotherapy intolerance reportedly was reduced in the cancer patients on the reishi extract, and leukopenia from the treatments improved. The patients also reported improved vigor and appetite. Reishi also decreased the immunosuppression seen in whole body ¡-irradiated mice, showing a greater degree of recovery vs. the control group. (21)

Reishi extracts have also reported hypoglycemic activity both in laboratory animals and in human subjects. (22) A small two-month open label trial of eight diabetic patients reported that an extract of reishi produced hypoglycemic effects comparable to that of insulin and oral hypoglycemic agents. (23)

Polysaccharides in reishi have been reported in several clinical studies to have anti-herpetic properties. It has been used in treating herpes (24) and postherpetic neuralgia, decreased pain dramatically in two patients with post-herpetic neuralgia recalcitrant to standard therapy, and two other patients with severe pain due to herpes zoster infection. (25) The triterpenoid constituents in reishi have reported anti-HIV-1 and anti-HIV-1-protease activity in vitro. (26)


Boswellia

Boswellia, or Olibanum, is a close relative of the biblical incense frankincense, and has been used historically in the Ayurvedic medical system of India for arthritis, dysentery, liver diseases, obesity, neurological disorders, ringworm, boils, and other afflictions. (27) Boswellia is a proprietary gum-resin extract from the stem bark of the Boswellia serrata tree, and is emerging as a novel dietary supplement agent in the management of symptoms associated with arthritis. (28)

Animal studies performed in India reported ingesting an extract of boswellia decreased polymorphonuclear leukocyte infiltration and migration, decreased primary antibody synthesis, and caused almost total inhibition of the classical complement pathway. (29) An in vitro study of the isolated chemical constituent b-boswellic acid on the complement system reported a marked inhibitory effect on both the classical and alternate complement systems. (30)

Boswellia’s anti-inflammatory activity seems to be produced by blocking the synthesis of 5-lipoxygenase products, including 5-hydroxyeicosatetraenoic acid (5-HETE), and leukotriene B4 (LTB4). (31) , (32) Also, it is reported that NSAIDs can cause a breakdown of glycosaminoglycan synthesis which can speed up the articular damage in arthritic conditions. (33) Boswellia was reported to significantly reduce the degradation of glycosaminoglycans compared to controls, whereas the NSAID ketoprofen was reported to cause a reduction in total tissue glycosaminoglycan content. (34)


Turmeric

In Ayurvedic medicine, turmeric rhizome has been used for centuries internally as a tonic for the stomach and liver and as a blood purifier, and externally in the treatment and prevention of skin diseases and in arthritic complaints. (35) The laboratory and clinical research indicates that turmeric and its phenolics have unique antioxidant and anti-inflammatory properties. (36) The anti-inflammatory strength of turmeric is reportedly comparable to steroidal drugs such as indomethacin. (37) Turmeric has been reported to be anti-rheumatic, anti-inflammatory, and antioxidant. (38) Curcuminoids reportedly inhibit enzymes which participate in the synthesis of inflammatory substances (leukotrienes and prostaglandins) derived from arachidonic acid. It is claimed they are comparable in activity to the NSAID. (39) In a double-blind study of individuals with rheumatoid arthritis, curcumin produced significant improvement in all subjects. (40) Turmeric is also claimed to inhibit platelet aggregation. (41)

Curcumin reportedly has a similar action to that of aspirin and aspirin-like anti-inflammatory agents. (42) However, an advantage of curcumin over aspirin is claimed, since curcumin, unlike aspirin, is reported to selectively inhibit synthesis of inflammatory prostaglandins but does not affect the synthesis of prostacyclin. (43) Curcumin may be preferable for individuals who are prone to vascular thrombosis and require anti-inflammatory and/or anti-arthritic therapy.


Grapefruit Seed

Grapefruit seed extract has been reported to be a broad-spectrum antimicrobial both in vitro and in vivo. Studies indicate that the antimicrobial activity of grapefruit seed extract exists in the cytoplasmic membrane of the invading bacteria. Where the uptake of amino acids is prevented, there is disorganization of the cytoplasmic membrane and leakage of low molecular weight cellular contents, ultimately resulting in inhibition of cellular respiration and death. (44)

Grapefruit seed extract also inhibits the growth of H. pylori and C. jejuni, both causative agents in gastrointestinal ulcers. (45) In vivo, grapefruit seed extract is a useful agent in maintaining bowel integrity. (46) In this human study, an improvement in constipation, flatulence, abdominal distress, and night rest were noticed after four weeks of therapy. Most clinicians now agree on the importance of maintaining homeostasis of the microflora in health and disease. (47) , (48)


Olive Leaf

Olive trees, widely cultivated throughout Mediterranean countries as a source of olives and olive oil, have been traditionally used not only in foods, but in health conditions including malaria, infections, cardiovascular diseases, and general well-being. (49) The natural antioxidants including oleuropein from the olive tree may play a role in prevention of cardiovascular diseases through a decreased formation of atherosclerotic plaques by inhibiting of LDL oxidation. (50)

Olive leaf extract has been reported to be an effective antimicrobial agent against a wide variety of pathogens, including Salmonella typhi, Vibrio parahaemolyticus, and Staphylococcus aureus (including penicillin-resistant strains); and Klebsiella pneumonia and Escherichia coli, causal agents of intestinal or respiratory tract infections in man. (51) The component usually associated with olive leaf’s antimicrobial properties is oleuropein. (52) , (53) Oleuropein also has been reported to directly stimulates macrophage activation in laboratory studies. (54)

Olive leaf extract has reported antiviral activity, reportedly caused by the constituent calcium elenolate, a derivative of elenolic acid. (55) , (56) Recent laboratory studies in laboratory animals reported hypoglycemic and hypolipidemic activity. (57) , (58) The constituent with the activity was reported to be oleuropein, with a proposed mechanism of action being potentiation of glucose-induced insulin release, and an increase in peripheral blood glucose uptake.


Oregano

Oregano has been used as a cooking spice and also as a medicinal agent for centuries. Oregano volatile oil has been used traditionally for respiratory disorders such as coughs, bronchial catarrh, and as an expectorant, and also for dyspepsia, rheumatoid arthritis, and urinary tract disorders. (59) Oregano oil is now used as an antifungal and antibacterial agent in various conditions. (60)

A widely used application for oregano extract is its reported antibacterial and antifungal activity. (61) Oregano has also been reported as an effective agent in vitro again Aspergillus spp. (62) Oil of oregano was orally administered to 14 adult patients whose stools tested positive for enteric parasites, Blastocystis hominis, Entamoeba hartmanni, and Endolimax nana. After six weeks of supplementation with 600mg emulsified oil of oregano daily, there was reportedly complete disappearance of Entamoeba hartmanni (four cases), Endolimax nana (one case), and Blastocystis hominis in eight cases. Also, Blastocystis hominis scores declined in three additional cases. Gastrointestinal symptoms improved in seven of the 11 patients who had tested positive for Blastocystis hominis. (63) The constituents thymol and carvacrol have reported antibacterial properties. (64)

Binding to intracellular progesterone receptors has also been reported in vivo with the use of oregano extract. (65) Oregano also has reported antioxidant activity. (66) Constituents in oregano that have reported antioxidant activity include flavonoids (rosmarinic acid) and the nutritive tocopherols. (67)

Rosmarinic acid (also found in rosemary and basil) has been reported to have cyclooxygenase inhibiting ability in laboratory studies, comparable to ibuprofen, naproxen, and aspirin as an anti-inflammatory agent. (68) Rosmarinic acid also increases the production of prostaglandin E2, reduces the production of leukotriene B4 in human polymorphonuclear leukocytes, and inhibits the complement system. These properties make oregano and other supplements containing rosmarinic acid potential agents in inflammation, cancer, and immune therapies. (69) , (70)

Oregano does contain naringin and naringenin, chemical constituents contained in grapefruit juice, that have been reported to cause alterations in the metabolism of some drugs. (71) Use with caution in individuals on medications metabolized by the CYP3A4 pathway.

Diet & Lifestyle

Preventing Tick Bites

The only way to avoid Lyme disease is to prevent tick bites. Extra precautions should be taken in Lyme-infested areas, especially the coastal regions of the Northeast. However, ixode ticks have been reported in virtually every area of the country. The high-risk season for tick bites is early summer through early fall: especially May, June, and July.

    Avoid densely wooded areas, and regions with tall grass. Wear a hat, long pants and shirts with long sleeves when working in the yard or walking through areas where ticks may thrive. Check frequently for ticks on the body and head. Ixode ticks are very small; look for a mark that resembles a small freckle or a piece of dirt. Use insecticide on clothing for extra protection. If a tick is found, remove immediately with tweezers. Research indicates that it takes approximately 48 hours for an infected tick to transmit the Lyme bacterium. (72) Remove the tick from the head, do not squeeze or handle the body. Save the tick on a piece of tape sealed in a plastic bag to confirm the identification. Swab the bite with an antiseptic. After outdoor outings, remove and wash clothing immediately.

Clinical Lab Assessment

Some of the following laboratory testing can provide information necessary for diagnosis and treatment. In addition, the tests listed may also give insight to functional metabolism and functional nutrient status in the body.

Lyme Urine Antigen Test (LUAT)

LUAT has a higher reliability for identifying Lyme disease than does ELISA, but multiple sampling days are more effective in identifying pathological organisms than a single collection. (73) , (74)

Polymerase Chain Reaction (PCR)

The PCR assay for B burgdorferi identifies the presence of B burgdorferi DNA in blood, urine, or serum.

Western Blot for B burgdorferi

This is the most useful antibody test for Lyme disease when performed under high quality control standards by an experienced laboratory.

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