About twelve years ago, Dr. Leo Galland and Dr. Herman Bueno worked together in New York City and began using artemisinin as a broad spectrum antiparasitic agent.

[Guest guest]

This has been posted under Herbals at the website, as there is no category

for Chinese medicine.

 

About twelve years ago, Dr. Leo Galland and Dr. Herman Bueno worked

together in New York City and began using artemisinin as a broad spectrum

antiparasitic agent.

 

From the Townsend Letter for Doctors & Patients

December 2002

Artemisinin: From Malaria to Cancer Treatment

by Robert Jay Rowen, MD Editor-in-Chief, Second Opinion

 

 

 

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Artemisinin, the key ingredient obtained from Artemisia annua,

has a long history of use as an antimalarial remedy. Artemisia annua, or

“sweet wormwood,” is mentioned in the Recipes For 52 Kinds Of Diseases found

in the Mawangdui Han Dynasty tomb, dating from 168 B.C. In that work, the

herb is recommended for use for hemorrhoids. It is also mentioned in the

Zhou Hou Bei Ji Fang (Handbook of Prescriptions for Emergency Treatments)

written in 340 A. D. The major active principal was first isolated in l972,

and investigators at the Walter Reed Army Institute of Research located and

crystallized the active component in l984.1

 

Artemisinin and two synthetic derivatives, artemether and sodium artesunate,

were evaluated in the l970’s. A number of the tropical countries have

conducted trials. In China in 1979, wherein 2,099 patients infected with P.

viva and P. falciparum, Artemisinin had good therapeutic effects and

improved or cured all patients. Furthermore, the treatment with Artemisinin

was without any obvious side effects. Artemisinin is also effective in

cerebral malaria. Body temperature of patients normalized within 72 hours,

and asexual parasites were eliminated within 72 hours. However, there was a

relapse rate of 21%.2

 

In clinical trials in Vietnam, children ages 1 to 15 years were randomly

selected to receive artemisinin suppositories or oral quinine. The results

indicated that the suppositories rapidly cleared asexual P. Falciparium

parasitemia in children and confirmed the problem reoccurrence rates.3

 

Artemisinin has been extensively researched for malaria, and has been used

on over a million patients, mostly in China and Vietnam. It is very helpful

for drug resistant malaria. Extensive review articles are available

documenting the extensive testing that has been done.4-6

 

Various oral dosage regimens have been adopted in treating over one million

patients. Early studies suggested that an optimum total dosage of 3 grams

(about 50 mg/kg) was administered over a 3 to 5 day period. In most cases

parasite and fever clearance times were in less than two days. Recurrence

were much more common with tablets than with parenteral formulations.

Because of the very rapid clearance time of fever and parasites, the use of

artemisinin was favored, and recurrences, which were common, were treated

with artemisinin again or with another drug.7

 

About twelve years ago, Dr. Leo Galland and Dr. Herman Bueno worked together

in New York City and began using artemisinin as a broad spectrum

antiparasitic agent.

 

“Artemisinin is a powerful oxidant. I have used it orally to treat small

bowel bacterial overgrowth, Clostridial overgrowth and (along with other

herbal extracts, such as berberine, grapefruit seed extract and oregano oil)

as a treatment for intestinal parasites.” Leo Galland, MD.

 

Very recently, news reports have trumpeted Artemisinin as a leading

treatment for malaria. Affected nations are calling for it to be accepted as

the number one first line treatment, but the USA has blocked its acceptance

as the primary treatment, alleging yet more studies are needed.

 

For the past ten years, the Hoang medical family, with three generations of

sophisticated physicians, have used artemisinin in combination with several

other herbs to treat cancer, and eliminate necrosis material from the body;

for example, from wounds; from intestines of people who have ulcerative

colitis, and from Crohn’s disease. The efficacy of the artemisinin compound

is very impressive for the treatment of breast cancer and possibly to

prevent it. It is not only because of direct anticancer activity, but also

due to hormonal balancing properties of the artemisinin. Herein, doses of

300 mg twice per day were adequate with other herbs.8

 

“The herb itself, Artemisia annua, is one of the best things for PMS,

cramping, excessive bleeding and all symptoms of hyper-estrogenemia and

hyperprolactinemia.” Dr. Hoang, MD.

 

Artemisinin contains an internal peroxide group. Due to this group, reactive

oxygen is already present in the molecule. This belief is in agreement with

the observations that derivatives of artemisinin lacking the peroxide

moiety, are devoid of antimalaria activity.9

 

Additional support for oxygen-mediated toxicity of artemisinin is generated

from other studies. The antimalarial activity of artemisinin in vitro,

against P. falciparum, could be enhanced by increased oxygen tension. Drugs

such as miconazole and doxorubicin, which are known to work via oxygen

radical effects, enhance the activity of artesunate, a derivative of

artemisinin. The effectiveness of artemisinin is reduced by catalase,

dithiothreitol and alpha tocopherol.10

 

Furthermore, Levander, et al. found that manipulation of the host

antioxidant defense status could provide prophylactic or therapeutic

enhancement for the control of malaria. In this study, mice were fed with

diets deficient in vitamin E or a diet supplemented with cod liver oil,

which would deplete antioxidants. Vitamin E deficiency enhanced the

antimalarial action of artemisinin against P. yoelii, but selenium

deficiency did not. A diet containing 5% cod liver oil had a very strong

antimalarial action.11

 

Artemisinin has been shown to work through oxygen and carbon based free

radical mechanisms. Its structure includes an endoperoxide bridge. Peroxides

generate free radicals in a Fenton type reaction when exposed to unbound

ferrous iron. Malaria, which grows in the erythrocytes, has the opportunity

to accumulate much excess iron which can spill into the unbound form.

Electron microscopy has confirmed destruction of plasmodium membranes with

morphology typical of free radical mechanisms.

 

With the knowledge of a high accumulation of iron in cancer cells,

researchers Henry Lai and Narenda Singh of the University of Washington

became interested in possible Artemisinin activity against malignant cells.

In 1995, they published a paper in Cancer Letters concerning the use of

artemisinin against numerous cancer cell lines in vitro. This article has

mobilized interest in artemisinin as an addition to anticancer treatment.12

 

There are a number of properties shared by cancer cells, which favor the

selective toxicity of artemisinin against cancer cell lines, and against

cancer in vivo. In addition to higher rates of iron flux via transferren

receptors than normal cells, cancers are particularly sensitive to oxygen

radicals.13

 

A subsequent article appeared in Life Science in 2001 by Singh and Lai on

the selective toxicity of artemisinin and holotransferrin towards human

breast cancer cells.14 In this article, rapid and complete destruction of a

radiation-resistant breast cancer cell line was achieved when the in vitro

cell system was supported in iron uptake with holotransferrin. The cancer

cell line was completely nonviable within 8 hours of combined incubation

with minimal effect on the normal cells.

 

Artemisinin becomes cytotoxic in the presence of ferrous iron. Since iron

influx is naturally high in cancer cells, artemisinin and its analogs

selectively kill cancer cells under conditions in vivo. Further, it is

possible to increase or enhance iron flux in cancer cells using the

conditions that increase intracellular iron concentrations. However, intact

in vivo systems do not need holotransferrin, the living body provides all

the necessary iron transport proteins.

 

A third paper, by Efferth et al., published in Oncology in 2001 stated that

the antimalarial artesunate is also active against cancer.15 This article

described dramatic cytotoxic activity against a wide variety of cancers

including drug resistant cell lines. Artesunate (ART) is a semi-synthetic

derivative of artemisinin, and has been analyzed for its anticancer activity

against 55 cell lines by the Developmental Therapeutics program of the

National Cancer Institute, USA. ART was most active against leukemia and

colon cancer cell lines. Mean growth inhibition 50% (GI 50) 1.11microM and

2.13 microM respectively. Non-small cell lung cancer cell lines showed the

highest mean (GI50 26.62 microM) indicating the lowest sensitivity towards

ART. Intermediate GI 50 values were obtained for melanomas, breast, ovarian,

prostate, CNS, and renal cancer cell lines. Most important, a comparison of

ART’s cytotoxicity with those standard cytostatic drugs showed that ART was

active in molar ranges comparable to those of established antitumor drugs.

Leukemia lines resistant to either doxorubicin, vincristine, methotrexate,

or hydroxyurea were tested. Remarkably, none of these drug resistant lines

showed resistance to ART. The theorized reason for this is the absence of a

tertiary amine in ART, present in virtually all other chemotherapy agents,

which is required for cellular transport systems to usher the drug outside

the cell.

 

Cancer Cells Are Deficient in Antioxidant Enzymes

 

Cancer cells are notoriously deficient in antioxidant enzymes - both forms

of superoxide dismutase, the manganese form in mitochondria, and the copper

zinc form in the cell cytoplasm are generally low in cancer cells. Cancer

cells are grossly deficient in catalase and glutathione peroxidase, both of

which degrade hydrogen peroxide. It is these deficiencies in antioxidant

enzymes which lead to the use of many of the common chemotherapeutics which

are superoxide generators.16

 

The higher iron fluxes, especially associated with the reproductive phase of

tumor cells, should render these cells even more susceptible to oxidative

damage via hydrogen peroxide and superoxides. Normally, the profound

catalase deficiency in cancer cells is credited with creating vulnerability

to oxidants, in relationship to IV vitamin C or IV hydrogen peroxide.

However, since all of these protective antioxidant enzymes are most often

deficient in transformed cells, the oxidant vulnerability should be enhanced

dramatically, and further so, due to enhanced unbound iron during cell

division.

 

Dr. Hugh Riordan has suggested that very high doses of IV vitamin C can kill

cancer cells via conversion of vitamin C to hydrogen peroxide, and due to

deficiency of catalase. For this procedure to work, very high levels of IV

vitamin C are required to reach “kill concentrations.” IV vitamin C may be

one of the best-documented alternative cancer treatments.17

 

Artemisinin may be a most effective method, and certainly one of the

easiest, of delivering a knockout oxidative stress to cancer cells.

 

Artemisinin is appealing for oral use in that the pharmacodynamics, dosage

and toxicity have been well studied for use in relationship to the treatment

of malaria. Artemisinin is relatively safe with little side effects even at

high dosages (70 mg/kg per day) in short term malaria use.

 

Artemisinin has two semisynthetic derivatives. Artesunate is a water-soluble

derivative with no reported toxicity at usual levels. However, its serum

half-life is relatively short. Artemether is a lipid soluble derivative,

effective in cerebral malaria, and therefore may be more effective in brain

cancers by better penetration of the blood-brain barrier. Artemether,

however, has been reported to cause some neural toxicity in laboratory

models in rather high doses. Artemisinin has an intermediate half life and

can cross the blood-brain barrier. The two semisynthetic derivatives are

available overseas in both oral and injectable for artesuante and

artemether.

 

As mentioned, Lai used holotransferrin, which is iron-loaded transferrin, to

further sensitize tumor cell lines to the oxidizing properties of

dihydroartemisinin, which is derived from the parent compound metabolically

in vivo. A human leukemia cell culture, Molt-4-lymphblastoid cells, and

normal human lymphocytes were used in this experiment.

 

A significant decrease in cell count was noted with artemisinin alone, with

p<.035. Greater effects were noted when transferrin and dihydroartemeisin

were used together. In combined treatment, considerable tumor cell death was

observed at a concentration of dihydroartemisinin of 1 uM after 8 hours of

incubation. Furthermore, there is reason to believe that artemisinin can

work at lower concentrations in vivo than in vitro, due to destruction of

the artemisinin molecule in vitro.

 

Lai suggests that this procedure would be most effective for the treatment

of aggressive cancers, in which large numbers of transferrin receptors are

expressed on the cell surface. It may not be effective for T cell leukemias,

which have defective internalization of transferrin receptors, and therefore

may not be susceptible to this treatment.12

 

Case reports

 

1. Patient D.A. a 47 year-old mechanic who presented with a 4.5 cm.

Non-Hodgkin’s lymphoma on the right side of his head, with gaping incision

from a recent biopsy, and tremendous inflammatory erythema. Artesunate, 60mg

was administered IM 14 consecutive days and he switched diets to high

protein/vegetable (Kelley parasympathetic type diet). At the end of two

weeks, a depression appeared at the apex of the tumor. Four weeks later, the

mass was completely gone, skull surface smooth, incision totally healed and

erythema virtually cleared. Apparantly cancer-free as of this writing 6

months later.

 

2. Patient V.M. an 83 year old Toronto resident. Healthy most of her life,

she now had a non-small cell lung carcinoma in the right lower lobe,

considered non-resectable because of heart failure and circulatory problems.

She received Artemisinin 500mg BID from Allergy Research Group and Carnivora

oral, via nebulizer, 5cc BID. In 4 months the tumor shrunk to 1x2 cm and her

oncologist felt this represented scar tissue and declared her cancer free.

(Her heart condition improved considerably with CoQ10, 600mg daily).

 

3. Patient D.E., a 47 year-old Alaska resident with stage 4 breast cancer

and metastases to T1 with significant pain, vertebral collapse and local

neurological impairment. First seen May 2001, she received a series of IPT

(insulin potentiation therapy-low dose chemotherapy), high dose vitamin C

infusions, supplements, and dendritic cell vaccine, dietary management

(Kelly sympathetic type diet), and detoxification strategies. Most symptoms

had cleared within 4 months (October 2001). In January 2002, she received

artesunate IV (source: mainland China), plus oral artemisinin 300 mg BID

(ARG and Wellcare Pharma) which has been continued. Six months later she was

happy to report she has no symptoms whatsoever and is living a normal life.

Her local provider believes the regressed mass is now scar tissue.

 

4. Patient F.A., an 81 year-old Californian with multiple skin cancers

including one active recurrent quarter-sized lesion that had been burned 4

times previously. Topical artemisinin (one capsule ARG artemisinin in 50%

DMSO) applied twice daily caused the large lesion to fall off within 5 days

and other smaller skin cancers to regress. His wife reported the same with

her skin cancers.

 

5. L.L. is a West Coast woman in her 40’s with breast cancer and extremely

painful metasteses all over her spine. She had received limited radiation

therapy to reduce the pain in the thoracic spine prior to consulting me. She

began artemisinin, and a variety of complementary strategies, including

diet, detoxification and Kelly type proteolytic enzymes (from Allergy

Research Group). Immediately, her energy exploded. Her pain level took a

dive when she received treatment from an Edgar Cayce Foundation healer. Her

comment after two weeks on artemisinin was " Last week I thought I was dying,

and today for the first time in months, I believe I am going to live. " Four

months into therapy using oral supplements alone (no IV therapy), diet and

detoxification strategies, a PET scan, the most efficient and sensitive

study for spread of cancer, did not show any activity anywhere in her spine,

even in places that were present before and not radiated! Further, the scan

did not confirm definite cancer activity anywhere else!

 

All patients who took oral artemisinin did so in the morning and evening on

an empty stomach with either conjugated linoleic acid and/or omega 3

supplements and/or some full fat cultured organic dairy product to enhance

absorption. Simultaneous iron in the stomach might neutralize its

effectiveness.

 

Conclusion

 

Artemisinin has been used for about 30 years in Vietnam and China for cancer

treatment. And the experience with artemisinin for this purpose is

increasing. This history probably led to the recent cited cancer research

with artemisinin.

 

The fact that artemisinin’s direct antineoplastic effects closely resemble

that of high-dose intravenous vitamin C is intriguing. The potential benefit

of artemisinin in cancer treatment should be further explored because it is

simple, safe, well-understood, and capitalizes on the multifold weakness in

cancer cells to defend themselves against oxygen radicals. Enhancing the

oxidant activity with other oxidation agents (such as carnivora, ultraviolet

blood irradiation, H2O2, or higher oxygen tension itself) may add

significant synergism. Adding artemisinin to low dose chemotherapeutic

regimens inducing cytotoxicity via free radical mechanisms (such as

doxorubicin), may safely add to the effectiveness of such treatment.

 

Dr. Singh, in a personal communication to me, has shared that he has been

following a series of cancer patients with nearly universal improvement on

artemisinin or its derivatives. He believes artemisinin will prove to be the

most powerful, yet extremely inexpensive and safe, chemotherapeutic agent

yet found, and effective orally for home use. However, like myself, he and

the Hoang family of physicians, believes it should only be used in a

professional atmosphere together with complementary strategies employing

detoxification, diet, immune support, spiritual work, etc. This use of

complementary strategies and professional supervision cannot be emphasized

enough, especially since long term use of artemisinin and/or its derivatives

has had little study. The Hoang family has indicated to me a 50-60%

long-term remission in over 400 cancer patients utilizing artemisinin

together with a comprehensive cancer strategy, and with no observed

toxicity.

 

I gratefully acknowledge Drs. Lai and Singh in their pioneering work and

their personal assistance in providing me with the information needed to

work with artemisinin and its derivatives for the benefit of my patients.

 

 

 

Correspondence:

 

Robert Jay Rowen, MD

95 Montgomery Dr., Suite 220

Santa Rosa, California 95472 USA

 

Email: drrowen

Web site: www.doctorrowen.com

 

 

 

 

References

 

1. Klayman D. Qinghaosu (Artemisinin): Antimalarial Drug from China.

Science, 1985, Vol. 238, May 31, p.1049

 

2. China Cooperative Research Group on Qinghaosu and its Derivatives as

Antimalarials. J. Trad. Chin. Med 2, 17, 1982.

 

3. Keith Arnold, Tran Tinh Hien, Nguyen Tran Chin, et al. A randomized

comparative study of artemisinine suppositories and oral quinine in acute

falciparum Malaria.

 

4. Transactions of the Royal Society of Tropical Medicine and Hygiene (1990)

84:499-502.

 

5. Bharel S, Gulati M, Abdin P, Srivastava S. Structure biosynthesis and

functions of artemisinin. Fitoterapia Vol LXVII No 5, l996.

 

6. Gulati A, Bharel S, Srivastava M, Abdin MZ. Experimental Studies on

Artemisia, an herbal remedy for malaria. Fitoterapia Vol LXV11 No 5, 1996.

 

7. Hien T, White N. The Lancet 1993 Vol 341 March 6 p 603-651.

 

8. Personal communication from Dr. Hoang, M.D., 2002.

 

9. Ames JR, Ryan MD, Klayman DL. Charge transfer and oxy radicals in

antimalarial action. J. Free Rad Biol. Med 1985, 1:353-61.

 

10. Krungkrai SR, Yuthavong. The antimalarial action of Plasmodium

falciparum of qinghaosu and artesunate in combination with agents which

modulate oxidant stress. Trans. R Soc. Trop. Med Hyg 1987, 81:710-4.

 

11. Levander OA, Ager AL, Morris VC. Qinghaosu, dietary vitamin E, selenium

and cod liver oil: effect on susceptibility of mice to the malarial parasite

Plasmodium yoelii. Am. J. Clin. Nutr. 1989; 5:346-52.

 

12. Lai H., Narendra S. Cancer Letters, 91:41-46, 1995.

 

13. May WS. J Membr. Biol., 88:205-215, 1985.

 

14. Singh NP, Lai H. Life Sci Nov 21, 70(1):49-56, 2001.

 

15. Efferth T, Dunstan H, Sauerbrey A, Miyachi H, Chitambar CR. Antimalarial

artesunate is also active against cancer, Oncol. 2001, Apr;18(4):767-73.

 

16. Levine SA, Kidd PM. Antioxidant Adaptation: Its Role in Free Radical

Pathology. Allergy Research Group, San Leandro, California, 1985.

 

17. Journal of Orthomolecular Medicine, Special Edition, 1999.

 

 

 

 

 

 

 

 

 

 

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