Tuesday, March 15, 2011

LYME DISEASE: Treatment with Chinese Herbs

by Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon

Lyme disease is the result of a spirochetal infection (Boerrelia burgdorferi) transmitted to humans by deer ticks (mainly Ixodes scapularis, though a relative, I. pacificus is the carrier in the Western U.S.). The infection sometimes results in a serious disease pattern, most often characterized by progressively worsening arthralgia, though a central nervous system disorder or even a heart disorder may arise (1, 2, 3, 10). The disease is named for the town (Old Lyme, Connecticut) where, in 1975, a number of children presenting symptoms similar to juvenile rheumatoid arthritis were eventually found to have acquired this Boerrelia infection.

The occurrence of Lyme disease is regional, being dependent on:

the distribution of the ticks that carry the bacteria (prevalent in forested areas in temperate climates, such as northern U.S. and northern Europe);
the presence of this particular bacteria in the ticks. The bacteria is carried by animals, particularly mice and deer, that are bitten by the tick; in the endemic area, only about 15-30% of ticks are infected; and
exposure of the human population to the ticks, which generally requires living in or venturing into areas where the ticks can be directly encountered.
Contact with a tick does not necessarily mean the disease will be experienced. In fact, it is estimated that only 1-3% of tick bites result in Lyme disease. While the region where infection is a somewhat likely possibility is expanding, the primary distribution still remains limited. As of 1995, it was reported that Boerrelia infections in the U.S. occurred mainly in 8 states of the northeastern U.S. and one Midwest state (Wisconsin). Retrospective studies indicate that there were probably a few cases of this disease many decades earlier, with cases appearing in Massachusetts and Wisconsin in the 1960s, and in northern Europe as early as the 1920s. There is some evidence to suggest cases of this or a very similar disease in Germany-a country that was heavily forested and full of deer-in the 1880s. The reason for the sudden epidemic of the disease during the past 25 years has been the change in land use and lifestyle that occurred, such as new growth of forests in abandoned farm land and movement of city dwellers into the forested countryside, either for recreation or for a new place to live. For those who are at risk for acquiring the infection, a vaccine against Boerrelia burgdorferi has been approved by the FDA and is now readily available.

There is no reference to Lyme disease in the Chinese literature and there may be none for some time, as most of China's forests have been eliminated. There are other spirochetal infections that have been addressed by Chinese physicians and by Chinese researchers conducting clinical trials or laboratory tests of infection-inhibiting properties. The relevant organism most often studied in China is Leptospira, which causes the disease called leptospirosis. This organism is carried by a wide range of animals, and is not uncommon in animals raised for food. In China, it has long been common practice for each family to keep animals, such as pigs and chickens, in and around their homes, so exposure has been possible for a large portion of the population. The bacterium can enter the body through the skin, usually from contact with animal urine. A small outbreak occurred at Fort Bragg in the U.S. in 1942, and the disease was nicknamed Fort Bragg Fever. Its cause was traced to swimming in ponds and streams that had been contaminated by livestock urine. Fewer than 200 cases occur in the U.S. each year, mostly in the warm southeastern states.

TRADITIONAL AND MODERN VIEWS OF LEPTOSPIROSIS AND ITS TREATMENT
The Leptospira infection causes fever and chills, headache, and muscle ache (especially in the shoulders). These symptoms match the Shang Han disease described in the ancient text Shang Han Lun. In fact, the initial course of leptospirosis follows a pattern, over a period of several days, that is somewhat like that described in the ancient text. In the advanced stage, leptospirosis can cause liver disease (with jaundice) or a severe form of meningitis; the symptoms of some cases of advanced Shang Han disease are similar. According to proponents of the general application of the Shang Han Lun as a guide to treatment of disease, the formulas recommended in that text could be used for modern diseases with similar symptom presentation. Accordingly, early stage of spirochetal infection, such as Lyme disease and Fort Bragg fever, might be treated by the same formulas used in the Shang Han Lun (see: A modern view of the Shang Han Lun).

Modern understanding of these infectious diseases may help reflect on the development of Chinese concepts of disease causation and treatment. Shang Han disease occurred most frequently in winter, the time of year when animals were brought into the house, thereby increasing opportunity for exposure to pathogens; thus, exposure of people to cold may not have been the reason that some diseases were observed to occur during the cold season. Similarly, the summer heat syndrome, which often produces digestive system disturbances, may not be the direct result of exposures of humans to the damp, hot climate, but exposure to pathogens that grow in that climate and infect the food and water supplies (see the articles: The six qi and six yin and Pill Curing and Huoxiang Zhengqi Pian).

The book Modern Study and Application of Materia Medica (4) provides information about herbs reputed to inhibit Leptospira based on laboratory testing (herb extract applied to cultured bacteria causing them to die) and, in some cases, clinical evaluation (herbs administered to infected patients resulting in clearance of symptoms). The following list of leptospira-inhibiting herbs was culled from the Chinese medical literature:

Isatis leaf Smilax
Isatis root Gardenia
Andrographis Hu-chang
Coptis Chien-li-kuang
Scute Verbena
Phellodendron Sanguisorba
Forsythia Ching-hao
Most of these herbs treat a condition described as damp-heat; many of the herbs have broad-spectrum antibiotic and antiviral properties. The book Thousand Formulas and Thousand Herbs of Traditional Chinese Medicine (5), no doubt relying on the same source material, listed the first nine ingredients of the above list as inhibitors of Leptospira; this text also presents five traditional formulas suggested for treating leptospirosis, divided by syndrome:

Exogenous pathogen invading the qi phase (this corresponds to the initial disease symptoms, which may include a flu-like pattern): Yin Qiao San (Lonicera and Forsythia Formula).
Summer heat and damp heat misting the three burners (for treatment of skin manifestations of the disease, such as rashes): Sanshi San (Three Stone Powder, made with calamine, gypsum, and red kaolin; this is applied topically).
Acute jaundice (this is the manifestation of leptospirosis as liver disease): Ermiao San (Red Atractylodes and Phellodendron Powder; this is a general formula for damp-heat).
Summer heat injuring the lung: Xin Jia Xiangru Yin (Modification of Elsholtzia Combination; the base formula contains elscholtzia, dolichos, and magnolia bark; a common addition is coptis).
Heat invading the pericardium with liver wind moving internally (this is the manifestation of leptospirosis as meningitis): Zhengan Xifeng Tang plus Angong Niuhuang Wan (Decoction to Subdue Internal Wind plus Pill of Ox Gallstone to Pacify the Palace).
All of the recommended formulas treat a heat syndrome, and include herbs that alleviate damp-heat, though they include few herbs from the list of those that have thus far been shown to inhibit the subject organism in laboratory and clinical tests. The herbal therapies may alleviate symptoms without curing the spirochetal infection, while it is the cure of the disease, defined by freedom from the bacteria, that is the goal of most Western patients and their physicians.

CLINICAL EVALUATIONS
There was considerable clinical research into treatment of leptospirosis in China during the early 1970s (9). It was reported that tablets prepared from equal amounts of the extracts of scute, lonicera, and forsythia, administered three times daily in large amounts were useful for treating mild and moderate cases of the disease. Andrographis extract, in the form of an injection or tablets of the crude extract or of the isolated lactones, was reported to effectively treat leptospirosis. In one evaluation, 31 of 35 cases were said to be cured by the andrographis lactones (mainly diterpene lactones, which are also found in the anticancer herb rabdosia).

More recently, Deng Shifa reported on efforts at prevention and treatment of leptospirosis (6, 7). He administered a decoction prepared from fresh, rather than dried, herbs, using ching-hao, houttuynia, eclipta, imperata, mentha, lonicera stem, humulus (lucao), and rhubarb. This formula only includes one herb, ching-hao, from the list of individual herbs above. The drink was consumed 4-6 times per day (that is, at intervals of 2-4 hours), and it was reported that recovery from symptoms occurred, on average, in about 11 days. The results obtained with the Chinese herbs were similar to those obtained with penicillin, based on cure rate, which was 97%. The same herb formula, with rhubarb deleted, was said to help prevent leptospirosis.

Another spirochete, Treponema, gives rise to two diseases, syphilis (from T. pallidum) and yaws (from T. pertenue). Since these diseases are easily controlled by modern antibiotic therapy, there is little mention of herbal remedies in the literature. Smilax (tufuling), an herb for damp-heat that is included in the list of anti-leptospira herbs, is still prominently mentioned for this application (4, 8). In Western herbal practice, a species of Smilax, known popularly as sarsaparilla, was used for treatment of syphilis. This repeated reference to the herb in clinical use supports the idea that smilax may have a reliable inhibitory effect for spirochetal infections. Treponemes have been isolated from the blood of patients with Lyme disease, suggesting that the ticks may harbor both types of spirochetes.

TCM ANALYSIS OF LYME DISEASE
The traditional Chinese medicine (TCM) analysis of a new disease, such as Lyme disease, depends on the disease manifestations and the analysis of other diseases that have some characteristics in common with it. The salient features are these:

the tick introduces the pathogen into the blood stream directly;
the infection typically yields a blotchy red rash, often in a "bull's eye" pattern of red skin coloration and swelling, about 3-20 days after the tick bite;
there may be flu-like symptoms, including fever, headache, sore throat, nausea, fatigue, swollen glands, stiff neck, aching muscles; and
if unresolved there may be recurrences of fever and, usually after several months, arthralgia, usually in the knees, with swelling and hot feeling.
It is estimated that 25-50% of those infected do not get the rash or flu-like symptoms, and that about half of those who experience the rash go on to experience arthralgia. The disease may be interpreted in TCM terms most simply as a heat pathogen entering the blood, which can reside as a "hidden toxin" in some individuals, manifesting disease symptoms later, after some factor activates it.

As an example of traditional prescribing that might be appropriate to Lyme disease, a formula recommended for a heat toxin entering the blood and producing eruption of macules (11) is Lonicera and Gypsum Combination (Liangxue Baidu Tang; Cool Blood and Defeat Toxin Decoction). It contains forsythia, gardenia, scute, and coptis, which are included in the list of anti-leptispirosa herbs, along with gypsum, talc, lonicera, anemarrhena, carthamus, moutan, raw rehmannia, scrophularia, and imperata (the original formula also included horns of antelope and rhino).

TREATMENT OPTIONS IN THE WEST
Medical studies suggest that if the Boerrelia infection can be treated soon after it occurs with antibiotics, there is strong likelihood of it being eliminated quickly and completely. The current medical treatment for Lyme disease is a course of therapy using doxycycline, amoxicillin, penicillin, or erythromycin. These are taken orally except in severe cases in which they may be administered intravenously instead. Many of those who become infected spontaneously recover within days or months even without antibiotics (no doubt, the bacteria eventually succumbs to the immune system). For those who have the infection for months prior to treatment without improvement, antibiotics may need to be administered for several months before the infection finally resolves, and some cases may entirely escape cure with this therapy due to the characteristics of the bacteria (ability to avoid the immune system by antigenic changes on its surface and ability to avoid antibiotic inhibition by infiltrating areas of the body, such as the joints, that have lower levels of exposure to the drug).

The absence of direct clinical evaluation of Chinese herbs in relation to Lyme disease means that there is some difficulty recommending that this method be used in lieu of the currently accepted course of antibiotics. Some individuals may wish to attempt to increase the chances of success with antibiotics or even shorten the duration of treatment with antibiotics by combining a Chinese herbal treatment, and a few individuals may wish to try using Chinese herbs alone, saving the antibiotic therapy as a back-up. One would apply herbs that are reputed to inhibit other spirochetes (since these should have an excellent chance of inhibiting this one), as well as any herbs that might treat the specific symptoms or the patient's constitution.

The Seven Forests herb formula tablet Isatis 6 provides isatis leaf, hu-chang, and andrographis from the list of herbs given above, and the Seven Forests formula Forsythia 18 provides forsythia, gardenia, scute, phellodendron, and coptis, which are also on that list. Together, these formulas may provide the bacterial inhibition that is sought from Chinese herbs in a convenient form of administration (suggested dosage would be 3-5 tablets of each formula, three times daily). As with treatment of any infection, the intended application is a high dosage for a few days or weeks. Since the formulas fall into the category of clearing heat, persons with symptoms and signs indicating a constitutional cold syndrome would probably do better to have a personalized formula made (e.g., extract granules), combining the desired anti-bacterial ingredients (which have a cold nature) with herbs for addressing the constitutional imbalance.

The single herb ching-hao may be of interest in treating this disease. This is an herb for damp-heat that is one of the most effective herbal agents for treating malaria, another parasitic disease (though a very different pathogen) introduced directly into the blood stream by an insect (mosquito). It was included in the formula recommended by Deng Shifa for treatment and prevention of leptospirosis. Aside from being listed as an anti-spirochete based on laboratory evaluation, this herb also helps regulate the immune system in cases of autoimmune disorders. For example, it is found useful in treating the autoimmune attack against connective tissue (mainly skin and joints) in patients with lupus (9). The arthralgia experienced by persons with advanced Lyme disease may involve some autoimmune component (at this time, it is unclear whether persistence of the bacteria is solely responsible for persisting symptoms or if there is an induced autoimmune process that contributes to the symptoms).

Further, if the symptoms of arthralgia have already developed, then herbs traditionally used for that purpose would also be administered (selection of ingredients would depend on symptom presentation and constitutional factors). Lonicera stem, included in the treatment for leptospirosis described by Deng Shifen, may be of interest, as it is used like lonicera flower as an anti-toxin agent, but is considered a specific treatment for arthralgia.

Based on the analysis that has been presented here, for patients willing to take a decoction or dried decoction, the following is proposed as a base formula that may be modified, if deemed necessary, for individual needs:

Anti-Spirochete Mixture
(equal parts)
Smilax
Ching-hao
Forsythia
Hu-chang
Andrographis
Lonicera stem

When using a decoction, the dosage of individual herbs should be 12-15 grams for a one day dose. Using dried decoctions, a daily dosage of 15-18 grams of the mixture would be appropriate. Three times per day dosing is a usual recommendation for the treatment of infections.

REFERENCES
Biddle W, A Field Guide to the Germs, 1995 Henry Holt and Co., Inc., New York.
Karlen A, Man and Microbes, 1995 G.P. Putnam's Sons, New York.
Lane K (executive editor), Merck Manual of Medical Information, Merck & Co., Inc., West Point, PA.
Dong Zhi Lin and Yu Shu Fang, Modern Study and Application of Materia Medica, 1990 China Ocean Press, Beijing.
Huang Bingshan and Wang Yuxia, Thousand Formulas and Thousand Herbs of Traditional Chinese Medicine, vol. 1, 1993 Heilongjiang Education Press, Harbin.
Deng Shifa, Preliminary study on the prevention and treatment of leptospirosis with traditional Chinese medicine, Lianing Journal of Traditional Chinese Medicine 1985; 9(5): 15-17.
Deng Shifa and Sheng Rixin, Treatment of leptospirosis with Qixian Drink, Zhejiang Journal of Traditional Chinese Medicine 1991; 26(7): 293-294.
Hong-Yen Hsu, et al., Oriental Materia Medica: A Concise Guide, 1986 Oriental Healing Arts Institute, Long Beach, CA.
Hson-Mou Chang and Paul Pui-Hay But (eds.), Pharmacology and Applications of Chinese Materia Medica, (2 vols.), 1986 World Scientific, Singapore.
Robbins SL, Cotran RS, and Kumar V, Pathologic Basis of Disease, Third Edition, 1984 W.B. Saunders Company, Philadelphia, PA.
Hsu HY and Wang SY, The Theory of Feverish Diseases and Its Clinical Applications, 1985 Oriental Healing Arts Institute, Long Beach, CA.
June 1999

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