@Lyme Disease

This article is written especially for Mary D. Martinez, my twitter friend




Lyme disease is also known as Lyme borreliosis, defined as an infectious disease as the result of the bite of the infected black legged tick, fed on mice, squirrels, birds and other small animals carrying the bacterium. In US, the disease is mostly caused by bacteria Borrelia, a genus of bacteria of the spirochete phylum. The bacteria can spread throughout the body as it has been found in the skin, heart, joint, peripheral nervous system, and central nervous system, according to "The emergence of Lyme disease" by Allen C. Steere, Jenifer Coburn, and Lisa Glickstein. (a)

Ten Facts You Should Know About Lyme Disease, quoted from the IDSA(b)

1. Lyme disease is caused by bacteria called Borrelia burgdorferi that is only transmitted to humans when they are bitten by an infected tick.
   
2. To infect its host, a tick typically must be attached to the skin for at least 36 hours.
   
3. Most cases of Lyme disease occur in late spring and early summer.
   
4. The most common symptoms of Lyme disease include a red, circular “bulls-eye” rash often accompanied by muscle and joint aches. About 70 to 80 percent of people infected develop the rash, which shows up several days to weeks after the tick bite.
   
5. Lyme disease is diagnosed by medical history, physical exam, and sometimes a blood test. It may take four to six weeks for the human immune system to make antibodies against Borrelia burgdorferi and therefore show up in a positive blood test. That is why patients with the Lyme rash usually have a negative blood test and diagnosis is based on the characteristic appearance of the rash. Patients with other clinical manifestations such as Lyme arthritis will usually have a blood test. Anyone who has symptoms for longer than six weeks and who has never been treated with antibiotics is unlikely to have Lyme disease if the blood test is negative.
   
6. Most cases of Lyme disease are successfully treated with a few weeks of antibiotics. Using antibiotics for a very long time (months or years) does not offer superior results and in fact can be dangerous, because it can cause potentially fatal complications.
   
7. Approximately 95 percent of all cases of Lyme disease occur in the Northeast and the Upper Midwest.
   
8. Researchers didn’t identify the cause of Lyme disease and connect it with ticks until 1981. The bacterium that causes the disease is named in honor of Willy Burgdorfer, the scientist who made the connection.
   
9. There were nearly 30,000 confirmed cases of Lyme disease in 2009 and more than 8,500 probable cases. The number has risen steadily since 1995, when there were only 11,700 confirmed cases.
   
10. The best treatment for Lyme disease is prevention: Be cautious when walking in the woods, avoiding bushy and grassy areas. Wear long pants and long-sleeved shirts and wear insect repellent containing DEET on exposed skin. After walking in wooded areas, thoroughly check the skin for the poppy-seed sized ticks, paying particular attention to the scalp, armpits and groin. If you find a tick, carefully remove it with tweezers.
    

I. Symptoms
Symptoms of Lyme disease can be classified in 3 stages
A. Stage I
Erythema chronicum migrans or skin rash is one of most common symptom of the early stage of Lyme disease, often happened few days to a month after the tick bite as a result of skin infection , according to "Erythema migrans and early Lyme disease" by Nadelman RB, Wormser GP.(1)
Other symptoms include
1. Fatigue
It is either the result of the immune system engage in the fighting off the infected bacteria or the use of antibotic in treating the disease. It sometime can be mistaken as chronic fatigue syndrome or vice versa, according to "Post-treatment Lyme disease syndrome symptomatology and the impact on life functioning: is there something here?" by Aucott JN, Rebman AW, Crowder LA, Kortte KB.(2)

2. Chills or fever
As the result of high fever or fever due to immune system response to the infectious bacteria.

3. Persistent headache
As the disease has cause the affects on the cognitive function as the result of increased intracranial pressure, according to "Lyme disease presenting with persistent headache" by Moses JM, Riseberg RS, Mansbach JM.(3) and researchers indicated that increased intracranial pressure in association with neuroborreliosis can lead to blindness.

4. Muscle and joint pain
It is most common symptom of the patient with Lyme diseases in the early stage, if it is left untreated it can become more serious form of Lyme arthritis. Sometime it is mistaken as Parsonage-Turner syndrome, with with acute shoulder pain followed rapidly by weakness and wasting of the shoulder girdle muscles, according to "Parsonage-Turner syndrome revealing Lyme borreliosis" by Wendling D, Sevrin P, Bouchaud-Chabot A, Chabroux A, Toussirot E, Bardin T, Michel F.(4)

5. Swollen lymph nodes
Swollen lymph nodes is a result of acute infection with Borrelia burgdorferi, due to hybridomas generated from regional lymph nodes during acute infection showed reactivity against a small number of recombinant Borrelia-antigens, according to "Lymphoadenopathy during lyme borreliosis is caused by spirochete migration-induced specific B cell activation" by Tunev SS, Hastey CJ, Hodzic E, Feng S, Barthold SW, Baumgarth N.(5)

6. Etc.

B. Stage II: The second stage of Lyme disease, if it is left untreated
1. Lyme arthritis
"Lyme arthritis occurs when the spirochete, the bacteria that causes the disease, invades the joints and causes inflammation to the tissue that lines the joints," he said. "If left untreated, this inflammatory response can cause the cartilage within the joints to become damaged." according to "Effective Treatment of Lyme Disease-Related Arthritis Depends on Proper Diagnosis" posted in AAOS: American Academy of Orthopaedic Surgeons® / American Association of Orthopaedic Surgeons®(6)

2. Neurological disorders
Patient in the second stage of Lyme disease may be experience certain neurological symptoms many months or years after the initial infection, such as encephalomyelitis, epileptic crises, cognitive impairment, peripheral neuropathy and psychiatric disturbances such as depression, anxiety, panic attacks, catatonia, psychosis etc. Some patient continue to experience symptoms of fatigue, insomnia or psychiatric disorder in the post borrelia syndrome, according to " Tremor, seizures and psychosis as presenting symptoms in a patient with chronic lyme neuroborreliosis (LNB)" by Markeljević J, Sarac H, Rados M.(7)

3. Multiple erythema migrans
Patient with initial skin rash after bitten by tick and left untreated erythema migrans, up to 39 days after the onset of skin rash may experience with solitary and multiple erythema migrans, according to "Borrelia burgdorferi sensu lato bacteremia in Slovenian children with solitary and multiple erythema migrans" by Arnež M, Ružić-Sabljić E.(8)

4. Dizziness, palpitations and shortness of breath
Untreated of bitten by tick may result in atrioventricular (AV) block. In the report of Verbunt RJ, Visser RF, the scientist reported that a 40-year-old man was referred to the cardiology outpatient clinic with dizziness, palpitations and shortness of breath. He remembered being bitten by a tick two to three years previously, but had not noticed a characteristic skin rash. The ECG showed a prominent first degree atrioventricular (AV) block and ambulatory electrocardiographic monitoring showed an intermittent complete AV block. A definitive pacemaker was implanted. Antibodies to Borrelia were found, according to "[Total atrioventricular block following a tick bite].[Article in Dutch]" posted in PubMed (9)

5. Extreme fatigue and general weakness
As a result of prolonged period of infection as the bacteria has spread throughout the body.

6. Etc.

C. Stage 3If the disease left untreated or with out noticing by the patient after bitten by a tick may last months to years. It can lead to recurring arthritis and neurological problems.
1. Chronic and recurring arthritis
As a result of a hierarchy of shared somatic mutations between members of a given clone. Intraclonal diversity among plasma cells of close physical proximity points toward an ongoing process of diversification and affinity maturation, possibly driven by the chronic presence of an autoantigen, according to "In situ diversification of the antibody repertoire in chronic Lyme arthritis synovium" by Ghosh S, Steere AC, Stollar BD, Huber BT.(9)

2. Neurological problems
May be due to Cerebral metabolic changes with the frequent presence of present of various neurological symptoms. In the study of 23 patients with lyme disease, researchers found that hypometabolism was precented in the temporal lobes in 17/23 (74%) patients. Of these, 12 had bilateral temporal lobe hypometabolism, two had left temporal lobe, and three had right temporal lobe hypometabolism. Seven of the patients with temporal lobe hypometabolism had diffuse cortical hypometabolism that included the frontal and parietal lobes. Lyme disease appears to have two primary patterns of brain involvement on FDG PET scans, specific temporal lobe hypometabolism or a diffuse cortical hypometabolism, according to "Cerebral metabolic changes associated with Lyme disease" by Newberg A, Hassan A, Alavi A.(10)

3. Etc.

II. Complications
Beside the most of common arthritic and neurological complications, here are some uncommon complications.
1. Non-Hodgkin lymphoma
Scientists found that persons who did not recall Borrelia infection yet tested positive for anti-Borrelia antibodies (OR = 4.2 [2.0-8.9]) are association between B. burgdorferi infection and risk of mantle cell lymphoma, according to "Borrelia infection and risk of non-Hodgkin lymphoma" by Schöllkopf C, Melbye M, Munksgaard L, Smedby KE, Rostgaard K, Glimelius B, Chang ET, Roos G, Hansen M, Adami HO, Hjalgrim H.(11)

2. Retrobulbar optic neuritis
Retrobulbar optic neuritis is a condition of vision disorder as a result of inflammation of the optic nerve, causing nerve damage that occurs in the section of the optic nerve located behind the eyeball. Although, relationship between RON and Lyme disease remains controversial, but there is a report that Lyme disease can cause vision disorder complication, according to "Retrobulbar optic neuritis: a complication of Lyme disease?" by E Krim, D Guehl, P Burbaud, A Lagueny(12)

3. Diaphragmatic paralysis and respiratory failure
There are some recorded cases of diaphragmatic paralysis as a complication of Neuroborreliosi, which is a disorder of the central nervous system caused by infection with a spirochete of the genus Borrelia and in one special case, scientists also reported that a 59 year old female presented with a recent history of abdominal pain and falls because of a weakness in her right leg. She had been complaining of flu-like symptoms with twitches in her back and pain in her right side for a month.Oon day 3 of admission she became increasingly short of breath and on examination had decreased bibasal air entry. On day 4 her respiratory rate was 25/min and arterial blood gases (ABG) demonstrated hypoxaemia but adequate ventilation with pH 7.51, Po₂ 6.7 kPa, and Pco₂ 4.7 kPa. Her chest radiograph showed left basal changes. On day 5 her Pco₂ had risen to 6.8; she was admitted to the intensive care unit and non-invasive ventilatory support was commenced. She had a decreased inspiratory pressure and a decreased vital capacity, according to "Diaphragmatic paralysis and respiratory failure as a complication of Lyme disease" by R A Abbott,, S Hammans,, M Margarson,, B M Aji(13)

4. Neurobrucellosis
Neurobrucellosis is a rare neurological complication associated with brucellosis, leading to symptoms of Headache, fever, fatigue, drowsiness and neck stiffness were the common clinical features. Cerebrospinal fluid (CSF) showed pleocytosis in 100%, elevated protein levels in 89% and low glucose level in 47% of the patients, according to "Short-course treatment in neurobrucellosis: a study in Iran" by Asadipooya K, Dehghanian A, Omrani GH, Abbasi F.(14)

5. Acute brachial diplegia
Acute brachial diplegia is generally defined as condition caused by bilateral supratentorial brain lesions of the prerolandic cortical and subcortical area. In some rear cases, acute brachial diplegia is a rare manifestation of acute Lyme infection and responds promptly to antibiotic therapy, according to "Acute brachial diplegia due to Lyme disease" by Gorson KC, Kolb DA, Marks DS, Hayes MT, Baquis GD.(5)

6. Endometriosis
Scientists at University of Crete, Heraklion report there are evidences which links endometriosis as a complication of Lyme disease by investigatiing he medical files of 405 women with endometriosis and 200 without endometriosis were studied retrospectively. We report 3 cases with endometriosis and Lyme disease. Of 405 patients with endometriosis treated in our study over a 6-year period, 3(0.8%) had Lyme disease, according to "Endometriosis-associated Lyme disease" by Matalliotakis IM, Cakmak H, Ziogos MD, Kalogeraki A, Kappou D, Arici A.(16)

7. Haematological complications
It is defined as a condition of blood related diseases, such as agranulocytosis/ granulocytopaenia, thrombotic trombocytopenic purpura and rarely aplastic anaemia. In the report in the study of a 55-year-old male with aplastic anaemia which developed after 45 days of the therapy with 200 mg ticlopidine to prevent coronary thrombosis. The treatment with ticlopidine was withdrawn and broad spectrum antibiotics as well as transfusion of packed red cells, platelets and G-CSF were administered. Two weeks after the onset of the disease, the number of white blood cells dropped to 0.5 x 10(9)/l, along with drop of both haemoglobin concentration and the number of platelets. At that time, weakness of facial muscles due to bilateral facial nerve paralysis with Bell's phenomenon and after that weakness of muscles of both legs and signs of polyradiculoneuritis were developed. Western blot analysis of blood and liquor showed a high concentration of IgG and IgM antibodies against Borrelia burgdorferi, according to "[Neuroborreliosis in patient with aplastic anaemia secondary to therapy with ticlopidine].[Article in Serbian]" by Colović N, Bumbasirević L, Palibrk V, Vidović A, Colović M.(17)

8. Recurrent laryngeal nerve paralysis
Although, recurrent laryngeal nerve paralysis is an extremely rare complication of neuroborreliosis associated with Lyme disease, but there is a report that 15-year-old girl referred with hoarseness and soft voice as a result of recurrent laryngeal nerve paralysis due to subclinical Lyme borreliosis, according to "Recurrent laryngeal nerve paralysis due to subclinical Lyme borreliosis" by Karosi T, Rácz T, Szekanecz E, Tóth A, Sziklai I.(18)

9. Pregnancy loss
During the investigation of Lyme disease: association with tissue invasion and spirochete persistence.at University of Utah School of Medicine, researchers said "Invasion of maternal uterine tissue, but not direct invasion of fetal tissue, is associated with low levels of pregnancy loss in mice infected during gestation, consistent with the detrimental effect of inflammatory cytokines on pregnancy"(22)

IV. Causes
Please read the definition above

V. Diagnosis
Diagnosis of Lyme disease is based on symptoms as indicated in the symptoms section and the geographic location. If you have any or combination of symptoms or complications above, after being bitten by a tick.
1. Serology testing
It is a study of blood serum and other bodily fluids to determine the immunity against different infecting organisms via the dosage of IgG. and may provide valuable information in patients with Western blot(c) and Enzyme-linked immunosorbent assay ELISA(d). Although, the test may not be accurate in the early stage of the disease, it can be helpful in the last 2 stages of Lyme disease. But in two-tiered antibody testing in Enzyme-linked immunosorbent assay ELISA,
The 2-EIA algorithm in early LD had similar sensitivity as C6 testing alone, and both strategies had better sensitivity than did standard 2-tiered testing (61% and 64%, respectively, vs 48%; P = .03 and P = .008). For late disease, all 3 strategies had 100% sensitivity. The specificity of the 2-EIA algorithm was equal to that of standard 2-tiered testing, and both 2-tiered strategies were more specific than C6 testing alone (for both, 99.5% vs 98.4%; P = .01). The positive predictive value of the 2-EIA algorithm was 70%, compared with 66% for standard 2-tiered testing and 43% for the C6 EIA alone. The 2-EIA strategy matched the individual strengths of the C6 EIA and Western blotting, without the drawbacks. The 2 EIAs provided sensitivity comparable to that of the C6 EIA but maintained the specificity of standard 2-tiered testing, according to "Two-tiered antibody testing for Lyme disease with use of 2 enzyme immunoassays, a whole-cell sonicate enzyme immunoassay followed by a VlsE C6 peptide enzyme immunoassay" by Branda JA, Linskey K, Kim YA, Steere AC, Ferraro MJ.(f)

2. Urine antigen tests
The test of antigens in the urine of the patient with suspect of Lyme disease may have some draw back because of the low concentration below the detection limit of clinical immunoassays. But with Hydrogel microparticles functionalized with high affinity baits can dramatically increase the sensitivity of urinary antigen tests for infectious diseases, according to "The use of hydrogel microparticles to sequester and concentrate bacterial antigens in a urine test for Lyme disease" by Douglas TA, Tamburro D, Fredolini C, Espina BH, Lepene BS, Ilag L, Espina V, Petricoin EF 3rd, Liotta LA, Luchini A.(g)

3. PCR tests on urine
The Polymerase Chain Reaction (PCR) technique test on Urine, has some application limits therefore suggesting the evaluation of the sensibility (SE), specificity (SP), predictive positive value (PPV) and predictive negative value (NPV) of a PCR test detecting a target sequence of OspA gene of Borrelia burgdorferi sensu lato, according to "[Reliability of a polymerase chain reaction (PCR) technique in the diagnosis of Lyme borreliosis].[Article in Italian]" by Grignolo MC, Buffrini L, Monteforte P, Rovetta G.(h)

4. Etc.

VI. How to prevent
A. Externally, What precautions should you take to avoid Lyme disease?
In areas where ticks are found, people should know about the risk of Lyme disease and protect themselves.
1. Find out from the local public health office if there are ticks, especially blacklegged ticks, in the area.
2. When walking in tick-infested areas, wear clothing that will keep ticks from getting to bare skin. Wear closed shoes, long-sleeved shirts that fit tightly around the wrist and tuck them into pants. Protect your legs by tucking pants into socks or boots. Ticks show up better on light-colored clothing.
3. Insect repellents containing DEET are safe and can effectively repel ticks. Repellents can be applied to clothing as well as exposed skin but should not be applied to skin underneath clothing (note: DEET may damage some materials). Always read and follow label directions.
4. Check for ticks on clothing and skin after being in tick-infested areas. A daily total-body inspection and prompt removal of attached ticks (within 18 to 24 hours) can reduce the risk of infection. Blacklegged ticks are very small, particularly the younger stages, so look carefully. Do not forget to check children and pets as well.
5. Carefully remove attached ticks using tweezers. Grasp the tick's head and mouth parts as close to the skin as possible and pull slowly until the tick is removed. Do not twist or rotate the tick and try not to squash or crush the tick during removal.
6. After removing ticks, wash the bite site with soap and water or disinfect it with alcohol or household antiseptic. Note the day of the tick bite and try to save the tick in an empty pill vial or doubled zip-lock bag.
7. Contact a doctor immediately if you develop symptoms of Lyme disease, especially when you have been in an area where blacklegged ticks are found. If you have saved the tick, take it with you to the doctor's office. Source from the "Lyme Disease Fact Sheet " from the Public health Agency of Canada(19)

B. Internally
Although there is no specific Lyme disease diet, health diet with different types of antioxidant and healthy living style should be helpful in preventing Lyme disease as antioxidants have proven to be effective in fighting against foreign invasion, including bacteria and virus Source from all about antioxidants (20). Researchers at the The University of Texas at San Antonio indicated that superoxide dismutase A(SodA) plays an important role in combating oxidative stress and is essential for the colonization and dissemination of B. burgdorferi in the murine model of Lyme disease.(21)

VII. Treatments
A. In conventional medicine perspective
Lyme disease is defined as an infectious disease and primary is treated by antibiotics and doses are depending to the stages of the infection. Researchers at the Boston University School of Medicine, Boston Medical Center, indicated that some patients have persistence of profound fatigue, myalgias, arthralgias without arthritis, dysesthesia/paresthesia, and mood and memory disturbances after standard courses of antibiotic treatment for Lyme disease. This constellation of symptoms has been variously referred to as "chronic Lyme disease," "post-Lyme disease syndrome," and "post-treatment chronic Lyme disease." Persistent symptoms have been reported in patients who are seropositive for IgG antibodies against Borrelia burgdorferi as well as in patients who are seronegative.
According to the Infectious Diseases Society of America (IDSA) guidelines, the antibiotics of choice are
1. Doxycycline (in adults)
a. Doxycycline is a member of the tetracycline antibiotics, used commonly to treat a variety of infections. In the study conducted by Tulane National Primate Research Center, Tulane University for the antimicrobial function of Doxycycline, could exert control over the inflammation elicited by Borrelia burgdorferi, found that antibiotics significantly reduced the production of tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8 in a dose-dependent manner in all cell types. Microarray analyses of the effect of doxycycline on gene transcription in spirochete-stimulated monocytes revealed that the NFKB and CHUK (alias, IKKA) genes were down-regulated.(37)
Also number of studies showed that ceftriaxone and doxycycline are the 2 most efficient antibiotics, particularly in Lyme arthritis and in neuroborreliosis. In late Lyme borreliosis, these antibiotics are less efficient, and different treatment schemes with variations in dosage or duration did not produce convincing results(38)
b. Side Effects
Most common side effects includes
b.1. Digestive disorders such as nausea, diarrhea, vomiting, indigestion and heartburn
b.2. Reaction to sunlight (photosensitivity)
b.3. Loss of appetite
b.4. Etc.

2. Amoxicillin (in children)
a. Amoxicillin is a β-lactam antibiotic used to treat bacterial infections in children, but for For children who are unable to tolerate amoxicillin, there is currently no proven alternative oral therapy for LD. In a randomized, unblinded study compared 2 dosage regimens of cefuroxime axetil (20 mg/kg/d and 30 mg/kg/d) with amoxicillin (50 mg/kg/d), each given for 20 days, indicated that Children were enrolled if they were 6 months to 12 years of age, had erythema migrans, and met other eligibility requirements. Serologic testing occurred at entry and after 6 months. Follow-up evaluations for safety, tolerability, and efficacy occurred at 10 and 20 days, 6 months, and 1 year. Forty-three children were randomized (13 in the amoxicillin group, 15 in each cefuroxime axetil group); 39 completed 12 months of follow-up. At the completion of treatment, there was total resolution of erythema migrans in 67% of the amoxicillin group, 92% of the low-dose cefuroxime group, and 87% of the high-dose cefuroxime group, and resolution of constitutional symptoms occurred in 100%, 69%, and 87%, respectively. All patients had a good outcome, with no long-term problems associated with LD. One patient, who was well at the first 2 follow-up visits, was treated with doxycycline because of new constitutional symptoms(39)

b. Side effects of Amoxicillin is not limited to
b.1. Nausea, diarrhea, vomiting, rashes
b.2. Antibiotic-associated colitis
b.3. Etc.

3. Erythromycin (for pregnant women)
a. Erythromycin is an antimicrobial medicine similar to those of penicillin, and is often used for people who have an allergy to penicillins. The aims of the medicine is to provide an aggressive antibiotic treatment of the mother during pregnancy in preventing infection of the newborn.(40)
b. Side Effects
Side effects of the medicine is not limited to
b.1. Mild diarrhea, nausea, stomach discomfort, vomiting
b.2. Loss of appetite
b.3. Erythromycin can interact with other medicine, including simvastatin (Zocor), lovastatin (Mevacor), or atorvastatin
b.4. Etc.

4. Ceftriaxone
a. Ceftriaxone is a third-generation cephalosporin antibiotic used commonly against Gram-positive and Gram-negative bacteria. In a prospective, open label, randomized, multi-center study, a 14 day course of ceftriaxone was compared to 28 days of therapy conducted by New York Medical College, indicated that Ceftriaxone for 14 days eradicated the signs and symptoms of late Lyme disease in the majority of evaluable patients. Although there were more failures in the 14-day group than in the 28-day group, this study did not have the power to determine if a clinical subset of patients may benefit from 28 days of therapy.(41)
b. Side Efects is not limited to
b.1. Hypoprothrombinaemia and bleeding
b.2. Diarrhea, moderate pain, swelling, or redness at the injection site, nausea, vomiting.
b.3. Etc.

Despite numeral efforts and treatment with antibiotics, there is increasing evidence that some patients with the bacterial infection Lyme borreliosis (LB) have symptoms that persist for years afterwards such as symptoms of fatigue, musculoskeletal pain, and neurocognitive difficulties1 are attributed to a post-LB syndrome, also known as posttreatment chronic Lyme disease(42)

B. In Nutrition and Supplements perspective
Nutrition and supplements are always important during treatment of Lyme disease
1. Probiotics
It is very important for a patient with Lyme disease with antibiotics treatment as the medicine kills not only the infectious Borrelia, but also the good bacteria as well.

2. Antioxidants
All vitamins, supplements, phytochemicals of which can enhance the immune system in fighting against the forming of free radicals and raise the antioxidants will do

3. Co Q10
Co Q10 has played an important role in oxidative phosphorylation and has membrane stabilizing activity as it in oral form to treat various cardiovascular disorders including angina pectoris, hypertension, and congestive heart failure.(23)

4. Magnesium
Magnesium is essentail to keep muscle and nerve functioning normal and heart beat rhythmic. It also helps to support a healthy immune system, raises energy and enhances cognitive function.

5. Omega-3 polyunsaturated fatty acids (n-3 PUFAs)
Recent study showed that n-3 PUFAs display neuroprotective properties and exert beneficial effects on the cognitive function with aging. The brain's need of n-3 PUFAs is predominantly met by the blood delivery due to their limited synthesis in the brain. The present review focuses on the metabolism of n-3 PUFAs in the brain, including their accumulation and turnover(24)

6. NT factor
NT-Factor is a nutrient compound composed of phosphoglycolipids with with pre- and pro-biotics. The nutrient beside balances the health micro flora but also address the mitochondrial damage, reduce fatigue and cognitive dysfunction.

7. Etc.

C. In herbal medicine perspective
Since it is an emerging infectious disease, there is not much information about the use of herbal medicine in treating the disease, but herbalists view Lyme disease as a condition of overwhelming accumulation of toxins in the body as the result of the aggressive bacteria. Therefore detoxification of the organs and system toxins will bring the body back to harmonization.
1. The lymphatic system
The lymphatic system beside helps to regulate the body fluid but also perform essential functions including the removal of waste products from cellular metabolism. The proper function of the lymphatic system is vital for enhancing the immune system performance.
1. Cleavers
In the investigation of the phytochemical compounds in Galium aparine with various column chromatographic techniques in 95% ethanol extract of the plant, identified 1-(4-hydroxyphenyl)-ethanone (1), vanillic acid (2), 3,4-dihydroxybenzoic acid (3), p-hydroxycinnamic acid (4), gallic acid (5), 4-hydroxytruxillic acid (6). according to the study of "[Phenolic compounds from Galium aparine var. tenerum].

[Article in Chinese]" by Yang J, Cai X, Mu S, Yang X.(25)

2. Echinacea
a. Immune modulator
In the observation of ethanolic extract of fresh Echinacea purpurea and the changes in cytokine production in blood samples from 30 volunteers before and during 8-day oral administration found that Echinaforce regulates the production of chemokines and cytokines according to current immune status, such as responsiveness to exogenous stimuli, susceptibility to viral infection and exposure to stress, according to the study of "Effects of Echinaforce® treatment on ex vivo-stimulated blood cells" by Ritchie MR, Gertsch J, Klein P, Schoop R.(26)

b. Anxiety
In the evaluation of five different extract from Echinacea preparationsand it effects on anxiety found that three of these decreased anxiety but two of them had a very narrow effective dose range. Only one extract decreased anxiety within a wide dose-range (3-8 mg/kg). Anxiolytic effects were consistently seen in three different tests of anxiety, the elevated plus-maze, social interaction and shock-induced social avoidance tests. No locomotor suppressant effects were seen at any dose, according to "The effect of Echinacea preparations in three laboratory tests of anxiety: comparison with chlordiazepoxide" by Haller J, Hohmann J, Freund TF.(27)

c. Anti-viral properties
In the analyzing the extract from Enchinanea and its anti viral effect found that the extract interferes with the viral entry into cells. In sequential passage studies under treatment in cell culture with the H5N1 virus no EF-resistant variants emerged,according to "Anti-viral properties and mode of action of standardized Echinacea purpurea extract against highly pathogenic avian influenza virus (H5N1, H7N7) and swine-origin H1N1 (S-OIV)" by Pleschka S, Stein M, Schoop R, Hudson JB.(28)

3. Cat's claw
a. Anti-inflammatory and antioxidant activities
Oral extract of Cat's claw has demonstrated the activity of protection against indomethacin-induced gastritis, and prevention of TNFalpha mRNA expression and apoptosis, according to the study of `Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content`by Sandoval M, Okuhama NN, Zhang XJ, Condezo LA, Lao J, Angeles' FM, Musah RA, Bobrowski P, Miller MJ.(29)

b. Antimicrobial activity
Cat`s claw has exerted antimicrobial activity against microorganisms frequently found in infected root-filled teeth, including Enterococcus faecalis, Staphylococcus aureus, and Candida albicans, according to the study of `In vitro antimicrobial activity of phytotherapic Uncaria tomentosa against endodontic pathogens`by Herrera DR, Tay LY, Rezende EC, Kozlowski VA Jr, Santos EB(30)

4. Etc.

2. Liver detoxification (31)
a. Milk thistle
Milk thistle, a flower plant of the daisy family have been traditionally claimed in treating chronic liver disease. It contains silymarin that helps to protect liver function and the liver in expelling toxins.

b. Licorice
Licorice is a legume plant and and native to southern Europe and parts of Asia. It contains glycyrrhizin that not only has both estrogenic and anti-estrogenic activity but also is an important liver herb with strong hepatoprotectant properties in treating the suppression of hepatic stellate cell activation and subsequent liver fibrosis.

c. Tabebuia heptaphylla
Tabebuia heptaphylla is also known as pink trumpet tree. It contains alkaloids, flavonoids, sulfur and essential oils helping to support the immune system, and it also has antifungal, antibacterial and antibiotic properties. It is a powerful antioxidant that helps to cleanse toxins accumulated in the liver as well as protecting the forming of cancerous cells in the prostate.

d. Stilingia root
Stilinga root not only helps to strengthen the immune cells but also prevent and treating food allergies and eczema by stimulating the removal of toxins accumulation in the liver caused by long term eating of preservatives, canned foods, fast foods and excessive alcohol drinking.

e. Pricky ash
Pricky ash is also known as toothache tree. It has been used traditionally as a digestive aid, to strengthen the nervous system. It also is a tonic and stimulant herb for the liver and gallbladder.

f. St. John wort
St. John wort is also known as tipton weed or klamath weed. It has been used traditionally in treating depression. It contains different flavonoids and 3-O-coumaroylquinic acid that has anti-inflammation and antioxidant effects by stimulating the immune system in fighting allergies and liver protection from toxins.

g. Fennel
Fennel contains anethole, polymers and essential oil that helps the liver and pancreas in the metabolism of fats and sugars. It also helps to dissolve fat deposits of the body and restore damaged liver cells that cause jaundice, hepatitis and other liver disorders.

2. Kidney detoxification(32)
a. Dandelion leaf
Dandelion is a rich source of vitamins A, B complex, C, and D, as well as minerals such as iron, potassium, and zinc. Dandelion root has been used for centuries in traditional Chinese medicine in treating liver disease by stimulating the removal of liver toxins. Dandelion leaf on the other hand are used as a diuretic to stimulate the excretion of urine in removing the toxin accumulated in the kidney.

b. Echinacea
Commonly called purple coneflower. It contains a wide variety of chemicals that not only helps to strengthen the immune system but also stimulates the removal of toxins that causes kidney inflammation and infection.

c. Corn silk
Corn silks are the silky fibers that are found under the leaves and on top of an ear of corn. It contains flavonoids, essential oil and minerals that helps effectively in treating acute and chronic inflammation of the urinary system caused by toxins accumulated in the kidney.

d. Artichoke
Artichoke is a perennial thistle originating from southern Europe containing thiamin, riboflavin, niacin. These are antioxidants that besides helping strengthen our immune system, it also is used to treat kidney diseases and protein in the urine caused by toxins through poor diet for a prolonged period of time.

e. Golden rod
Golden rod is a yellow flowering plant in the family of Asteraceae. Golden rod has been used in traditional medicines as a kidney tonic, and treating urinary infections and stones. Golden rod juice also helps to cleanse of kidney and bladder caused by toxins and inflammation.
3. Skin detoxification(33)
a. Strawberry leaf
Strawberries come in endless varieties but all leaves of all strawberries contain healing tannins. It has also been used to aid in the treatment of anemia, eczema, jaundice and other skin problems caused by weakening of the liver.

b. Burdock root
Burdock has traditionally been used in treating chronic skin ailments such as eczema psoriasis, and dermatitis. It also helps to purify the bloodstream of toxins causing skin diseases.

c. Oats
Oats contain antioxidants such as IP-6, vitamin E, and zinc that is not only needed for a healthy heart and prostate gland but also help in rejuvenating our skin by fighting against inflammation in the skin caused by toxin accumulation or bacteria infection.

4. Colon detoxification(34)
a. Flax seed
Flax seed contains high amounts of omega 3 fatty acid, fiber and lignan that not only helps in controlling cholesterol in the blood stream and provides essential nutrition to our body, its fiber also helps to soften the stool and promote bowel movements for relief of constipation by removing all toxins accumulated in the colon.

b. Psyllium Psyllium contains about 70% soluble fiber and 30% insoluble fiber. Besides having proven record in Chinese medicine in treating high levels of cholesterol, its fiber portion has been used to treat constipation by softening stools and easing bowel movements .

c. Bentonite Bentonite is a natural clay that comes from volcanic ash. Taken internally, the adsorbent action of bentonite helps to eliminate and remove toxic material from the intestine.

d. Liquid clay
Liquid clay moves through our body and attaches to any bacteria, virus as well as toxins in our intestine and removes them out of our body as wastes resulting in improved intestinal regularity, easing chronic constipation and easing indigestion.

e. Buckthorn bark
Buckthorn bark is native to Europe and parts of western Asia. It contains anthraquinones that stimulate intestinal movement and also attracts more water to the intestines resulting in a softened stool and removing toxins accumulated in the intestine out as wastes.

f. Rhubarb root
Rhubarb root has been used in Chinese medicine in treating both constipation and diarrhea. Intake of rhubarb root helps to improve intestine tone, as well as remove toxins from the intestine.

g. Cascara sagrada
Cascara sagrada is known to tone the relaxed intestinal muscles in the digestive system. Intake of cascare sagrada helps promote the digestive process in people affected by disorders in the digestion as well as chronic constipation.

5. Lung detoxification(34)
a. Lotus Root Tea
Made from the root of the esteemed Asian water lily. It helps dissolve and eliminate mucus and lung congestion over time. Lotus root traditionally has been used to neutralize toxins accumulated in the lung as well as in treating other respiratory diseases such as asthma, tuberculosis, and coughing.

b. Platycodon Root
Platycodon has been used in Chinese medicine for over a century in treating abscesses,
respiratory disorders, and intestinal disorders.Study shows that platycodon roots not only help
to treat coughs due to purulent sputum and inflammation in the chest area but also removes toxins in the lung.
c. Wild Cherry Bark
Wild cherry bark traditionally has been used to treat irritable andpersistent cough of bronchitis,
and pertussis due to increased irritability of respiratory mucosa. Since it has antispasmodic
qualities, it has been used with other herbs to treat asthma andenhance relaxation as well as
removing toxins from the lung.
d. Mullein
Mullein contains coumarin and rotenone. It has a long history of being used as a medicine and
is an effective treatment for asthma and respiratory disorders. Mullein also helps in soothing
the mucous membranes, reducing inflammation and encouraging healthy fluid production in
the lungs.
e. Ephedra
Epphedra has been used  in Chinese medicine traditionally  for 5,000 years in treating asthma,
hay fever and the common cold. It also helps to support healthy sinus nasal lung and respiratory
function by removing toxins in the lung.
f. Elecampane
Elecampane is also called horse-heal. It has been used for treatment of shortness of breath and
helps to promote a strong lung. Elecampane is a wonderful lung tonic. Useful for asthma, and
soothing to the lining of the lungs

6. Blood detoxificationa. Raw sauerkraut
Sauerkraut is finely shredded cabbage and has been fermented by various lactic acid bacteria
with distinct sour flavor. It contains high amounts of  vitamin C, lactobacilli  and other nutrients
that helps to improve blood circulation and increase level of oxygen in the blood stream. It also
is said to have done a super job in purifying your blood as well as anti aging effects.
b. Garlic
Garlic is nature's super food. Besides having been used in strengthening the immune system,
fighting inflammation and infection caused by bacteria, virus, and chronic illness. It also is a
blood thinner, blood purifier as well as increasing the level of oxygen in the blood  and improving   blood  circulation.
c. Angelica root
Angelica root has been used in traditional Chinese medicine for thousand of years in improving
blood quality and purity, and help strengthen the immune system as it supports the body's
removal of toxins in the blood.

d. Red Clover Tops
Red clover tops traditionally has been used with other herbs  to support the quality of the
blood by increasing the level of oxygen circulation of blood to transport  nutrients to the cells
needs. It also is a liver tonic as well as maintaining healthy bowel function and supports
digestion. 

f. Burdock
Burdock, besides helping to cleanse our liver, it also contains substances that help to strengthen
our immune system as well as reducing inflammation caused by bacteria and virus.
Traditionally, burdock is very effective in providing the strength to clean and normalize the
blood stream.

g. Oregon Grape Root
Oregon Grape is a native plant on the North American west coast from British Columbia to
northern California. It's root contains  substances helping to decrease bacterial resistance to
antibiotics and antibacterial agents, as well as anti-inflammation. Oregon grape root is
described as one of  the best western herbs for supporting liver function. The  potent root  is also
recognized as a whole body cleanser and blood purifier. 

7. Etc.

D. In Traditional Chinese medicine perspective
Traditional Chinese medicine defined Lyme disease as a result of toxic fire caused by aggressive bacteria infection. Patient with toxic fire can be identified by examining the symptoms and physical appearance, such as early stage sores or carbuncles, red, painful, swollen,hot skin lesions, fever, mild chills, headache with Tongue thin coating, Pulse rapid forceful.
Traditional Chinese medicine herbal formulas Xian Fang Huo Ming Yin (Sublime Formula for Sustaining Life) main functions are to clear heat and relieve toxic fire while reducing swellings, promoting discharge of pus, invigorating the blood and alleviating pain.
1. Jin Yin Hua - 9g
Jin Yin Hua is also known as honey sucker flower. The sweet and cool herb has been used in TCM to treat respiratory tract infection, influenza, acute infection of the tonsils and the mammary glands, bacterial type of dysentery, etc. as it clears Heat, expels toxins, etc., by enhancing the functions of lung, heart, large intestine, and stomach channels.

2. Gan Cao (Licorice Root) - 3g
Gan Cao is also known as Licorice root. The sweet and neutral herb has been used in TCM as anti allergy, anti inflammation, anti ulcer, anti convulsion and to treat stomach weakness, tired and lack of strength, palpitation and short of breath, cough with abundance of phlegm, stomach and solar plexus pain, etc., as it tonifies the Spleen, benefits the Qi, moistens the Lungs, calms cough, deaf or acute pain, by enhancing all 12 channels.

3. Zhe Bei Mu - 3g
Zhe Bei Mu is also known as Fritillary Bulb, the slightly cold, sweet and bitter herb has been used in traditional Chinese medicine as antibiotic agent and to treat cough and get rid of phlegm, hot cough, etc, as it transforms Phlegm, relieve cough, clears Heat, dissolves nodules, etc., by enhancing the function of lung and heart channels.

4. Gua Lou 3g
Gua Lou or Gua Lou Gen or Tian Hua Fen, , is also known as trichosanthes root. The sweet, slightly bitter and cold herb has been used in TCM as anti HIV, anti tumor, anti bacteria, etc. agent and to enhance the immune system, promote abortion, lower blood sugar, etc., as it clears lung heat, dissolves phlegm, gets rid of toxicity, expels pus, etc., by enhancing the functions of lung and stomach channels.

5. Dang Gui - 6-12g
Dang Qui is also known as Angelica Root. The sweet, bitter, acrid and warm herb has been used in TCM to regulate the menses, lower lipids, reduce platelet coagulation and swelling, expel pus, relieve pain, etc/, as it tonifies and moves Blood, calms pain, moistens the Intestines, etc., by enhancing the function of heart, liver and spleen channels.

6. Chi Shao Yao - 3g
Chi Shao or Chi Shao Yao is also known as Red Peony Root, the bitter, sour and cool herb has been used in TCM to anti-spastic, antipyretic, anti-inflammatory, antibiotic, anticonvulsant, analgesic, sedative agnet and to lower blood pressure, dilate peripheral blood vessels, coronary arteries, treat viral hepatitis, chronic constipation, asthma, whooping coughs, diabetes, etc., as it clears Heat, cools Blood, eliminates Blood accumulation, calms paindilates, etc., by enhancing the functions of liver and spleen channels.

7. Ru Xiang 3g
Ru Xiang is also known as Frankincense Carterii, mastic. The bitter acrid and warm herb has been used in TCM to relieve pain due to blood clots, treat spastic muscle, carbuncles, gum bleeding, gingivitis, rheumatoid arthritis, cirrhosis of liver , etc., as it clears blood stasis, alleviates pain, resolves edema, promotes tissue regeneration, etc., by enhancing the functions of
heart, liver and spleen channels.

8. MoYao - 3g
Mo Yao is also known as Myrrha, It is exuded from the bark of a shrub of Abyssinia and Arabia, species Commiphora Myrrha, belonging the family Burseraceae. The bitter and neutral herb has been used in TCM as an antibiotic and to inhibits pain, reduces swelling and heal wound due to injuries, bruises, rheumatoid arthritis, tumors in the uterus, hemorrhoid by moving blood, relieving pain and promoting tissue regeneration as it enhances the function of liver, spleen, heart channels.

9. Fang Feng - 3g
Feng Fang is also known as Saposhniovia divaricate root. The sweet, warn and acrid herb has been used in TCM as antipyretic, antibiotoc, antiviral agent and to treat joint and muscle pain, blurry vision and headache, etanus, relieve pain, etc., as it expels Wind, releases the Exterior, disperses Dampness, calms pain, etc., by enhancing the functions of bladder, liver and spleen channels.

10. Bai Zhi - 3g
Bai Zhi is also known as angelica root. The acrid and warm herb has been used in TCM as Antipyretic agent and to relieves pain, stimulate CNS, respiratory system, increase blood pressure, slows heart rate, deepens breathing, etc., as it releases the exterior, expels Wind, dries Dampness, clear superficial swellings, etc., by enhancing the function of lung and stomach channels.

11. Chuan Shan Jia- 3g
Chuan Shan Jia is also known as Pangolin Scales. The salty, cool and tastless herb has been used in TCM to promote lactation, stop pain, pain in the joints of lower limbs, chronic malaria, rid of parasites, etc. as it moves Blood, resolves delayed menstruation and edema, promotes lactation, expels pus, etc, by enhancing the functions of liver and stomach channels.

12. Zao Jiao Ci - 3g
Zao Jaoi Zi is also known as Chinese Honeylocust Spine. The warm, acrid and slioghtly toxic herb has been used in TCM as antibiotic, anti-inflammation, anti virus, anti-allergy, anticoagulation, anti tumor agent and to regulate immune system, etc. as it expels toxins, promote circulation in channels, expel pus, invigorates Blood, etc., by enhancing the function of
liver and stomach channels.

13. Chen Pi 9g
Chen Pi is also known as Tangerine Peel, the bitter, acrid and warm herb has been used in Traditional Chinese medicine to improve digestion, stop vomiting, hiccups and bleeding increase blood pressure, stimulate blood vessels, regulate movement of uterus, as it regulate the movement of Qi, Middle burner, dries Dampness, transforms Phlegm, etc., by enhancing the functions of lung and spleen channels.
(35,36)

Author note: The article is for information and education purpose only, please consult with your doctor and the related field specialist before applying

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