Artemisia Annua, Artemisinin & 2015 Nobel Prize in Medicine

Background: 

Artemisinin is a natural extract, coming out of a plant called Artemisia annua (sweet wormwood) used as a drug to treat malaria. It saved million of lives so far and as a results, its discoverer Mrs. Tu Youyou received the 2015 Nobel Prize in Physiology or Medicine (Ref.).

ArtemisiaannuaIts discovery goes back to 1969. While the whole world was searching a cure for a form of malaria resistant to chloroquine (another element with serious anti cancer potential), Tu, had an idea of screening Chinese herbs. She first investigated the Chinese medical classics in history, visiting practitioners of traditional Chinese medicine all over the country on her own. After screening 2,000 traditional Chinese recipes and made 380 herbal extracts, one compound was effective, i.e. sweet wormwood (Artemisia annua), which was used for “intermittent fevers,” a hallmark of malaria. Here is a complete story of Artemisinin: http://www.cell.com/cell/fulltext/S0092-8674(11)00950-0

Note that, there are various artemisinin derivatives that are also used against malaria, e.g. artesunate and artemether. All are absorbed well after oral intake and cross the blood brain barrier. Artelinic acid, artemether, artemotil (arteether, β-arteether) artenimol (dihydroartemisinin, β-dihydroartemisinin) and artesunate, are considered to be about five times more potent than artemisinin against malaria. (Ref.)

Furthermore, artemisinin and artemisinin-derived compounds have been shown to exhibit antiviral, anti-inflammatory, anti-parasitic, anti-allergic, anti-fibrotic, anti-arrhythmic, immunoregulatory and contraceptive actions, and the agents were found to be active for autoimmune diseases (Ref1., Ref.2, Ref3).

During the past years, Artemisinin has also also been identified as a substance with a strong anti cancer potential in various cancer cells such as

Artemisinin can be very effective because it selectively affects tumor cells without harming normal cells. This is because Artemisinin affects only cells that contain excessive amounts of iron which is the case for cancer cells. Indeed, via specific receptors cancer cells are demanding and depositing large amounts of Iron as they need it for cellular division. When coming in contact with Iron, Artemisinin triggers the release of intracellular free radicals that destroy cells.

Indeed, Artemisinin was shown to cause the arrest of cell growth and apoptosis in several tumor cell lines. As we will discuss below, besides the ample science behind there is a very large number of anecdotal reports coming from all over the world and supporting Artemisinin and the whole plant Artemisia annua as a cancer solution. For example, Artemisia annua is widely used in countries such as Romania (where they call it “pelin”) or Italy and there are constant positive reports coming out of those countries.

Artemisia annua is a plant that is very cheap and available almost everywhere. This is why people will tend to use the whole plant more than the extract Artemisinin. And this is probably better since the whole plant contains more anticancer substances such as Scopoletin. Recently, it has been reported that Scopoletin can be found in high amounts in Artemisia annua, it it better absorbed in the human body and is known for its cytotoxicity towards cancer cells. (Ref.) Next to Scopoletin there are other substances with anti cancer action as well. (Ref.) As a side note, I was just reading now an article coming to my e-mail box by chance, and indicating that Noni fruit is rich in Scopoletin.

The presence of a complex matrix of chemicals within the leaves of Artemisia annua seems to enhance both the bioavailability and efficacy of artemisinin. In healthy mice, artemisinin serum levels were > 40-fold greater in dried leaf fed mice than those fed with pure artemisinin. On the same line, human trial data showed that when delivered as dried leaves, 40-fold less artemisinin was required to obtain a therapeutic response compared to pure artemisinin. (Ref.)

This is a good reason to also add a whole plant extract or dried leaves powder next to Artemisinin when considering an anti cancer treatment strategy. And yes, it seems that most of the positive anecdotal reports are coming from the use of the whole plant and not Artemisinin only.

However, when using the whole plant we may get different results. One reason for that can be related to the fact that there are various species that are used depending on the region such as Artemisia absinthium (wormwood), A. annua (sweet wormwood), A. afra (African wormwood), A. capillaries (Korean wormwood), A. vulgaris (common wormwood) and A. asiatica (Asian wormwood). All belong to the same species and enjoy widespread and similar uses in traditional medicine in Africa (A. afra), in Asia (A. asiatica), in China (A. annua), far east (A. capillaries) and Europe (A. absinthium). While the various species above are all expected to have anti cancer effect, I would try to make sure we use A. annua since this is the specie mostly studied in terms of anti cancer effects.

Another point that may lead to various results in various patients is the preparation method of the whole plant extract. This is due to the poor water-solubility of artemisinin which is known since the detection of artemisinin. Youyou Tu, obtained inconsistent antimalarial effects at the beginning as she was extracting the artemisinin in warm water. Only as she went back to the original historical records on the traditional use in Chinese medicine (Handbook of Prescriptions for Emergency Treatment, Hou Bei Ji Fang, by Hong Ge, 281–340 B.C.), she recognized that the press juice rather than hot water extraction was recommended.

Therefore, Artemisinin specifically and Artemisia Annua in general seems to have great anti cancer potential as it acts via a mechanism that is relevant to nearly ALL cancer types. That is by converting cancer cells’s Iron storage in to “bombs”. But the source and administration method of Artemisinin and Artemisia Annua extract matters and it may make the difference in terms of success rate.

Case reports in animals:

Treatment of Iron-Loaded Veterinary Sarcoma by Artemisia annua. http://www.ncbi.nlm.nih.gov/pubmed/24859473

“Artemisinin, a constituent of Artemisia annua L., is a well-known antimalarial drug. Artemisinin-type drugs also inhibit cancer growth in vitro and in vivo. Herbal extracts of A. annua inhibit the growth of cancer cell lines. Here, we report on the use of capsules containing powder of Herba Artemisiae annuae to treat pet sarcoma. The surgical tumor removal as standard treatment was supplemented by adjuvant therapy with A. annua. One cat and one dog with fibrosarcoma survived 40 and 37 months, respectively, without tumor relapse. Two other dogs suffering from fibrosarcoma and hemangioendothelial sarcoma also showed complete remission and are still alive after 39 and 26 months, respectively. A. annua was well tolerated without noticeable side effects. These four cases indicate that A. annua may be a promising herbal drug for cancer therapy. ”

“After the decision was made to use Luparte®, the serum iron (normal range between 140 and 170 µg/dL) was measured. Between blood taking and getting back the serum iron results from the clinical diagnosis laboratory, iron was given p.o. b.i.d or intramuscularly every 3 days to mark the iron affine malignant cells. The initial “blind” dose of orally given iron (e.g. Ferrosanol® capsules 100 mg) was about 100 mg/30 kg b.i.d. or about 100 mg/10 kg weight Ursoferran i.m. two times a week. The iron application was continued for the entire treatment time, and was attuned to maintain the iron level at 250 ± 30 µg/dL. From the fourth day onward, the animals were treated p.o. two to three times daily with one capsule (150 mg in the cat, 450 mg in the dogs) of Herba A. annuae simultaneously.”

Note that the study above used the whole plant Artemisia annua.

Case reports or clinical trials in human:

  • A Randomised, Double Blind, Placebo-Controlled Pilot Study of Oral Artesunate Therapy for Colorectal Cancerhttp://www.ncbi.nlm.nih.gov/pubmed/26137537
    INTERPRETATION: Artesunate has anti-proliferative properties in CRC and is generally well tolerated.

    • The dose of artesunate for the study was 200 mg orally, daily for fourteen days, with medication stopped 48–72 h prior to surgery.
  • Case Report of a Pituitary Macroadenoma Treated With Artemether http://ict.sagepub.com/content/5/4/391.refs
    Artemether was administered orally to the patient over a period of 12 months. Although the tumor remained consistent in size, CT scan shows a reduction in its density, and clinically, the related symptoms and signs resolved significantly as therapy progressed.
  • Case report of a laryngeal squamous cell carcinoma treated with artesunate
    Artesunate was successfully used in the treatment of laryngeal squamous cell carcinoma and substantially reduced the size of the tumor (by 70%) after two months of treatment.

    • On day one of treatment, a capsule containing ferrous sulfate (150 mg) and folic acid (0.5 mg) was given orally at 2:00 PM after a meal. Injections of artesunate (60 mg I.M. per day; Cadila Healthcare Ltd., Ahmedabad, India) were given from day one (01/22/2001) to day 15 (02/05/2001) at 10:00 PM of each day. One tablet of artesunate (50 mg; Cadila Healthcare Ltd., Ahmedabad, India) was taken orally at 10:00 PM after the evening meal every day from day 16 (02/06/2001) onward.
  • Artesunate in the treatment of metastatic uveal melanoma–first experiences. http://www.ncbi.nlm.nih.gov/pubmed/16273263
    We report on the first long-term treatment of two cancer patients with ART in combination with standard chemotherapy. These patients with metastatic uveal melanoma were treated on a compassionate-use basis, after standard chemotherapy alone was ineffective in stopping tumor growth. The therapy-regimen was well tolerated with no additional side effects other than those caused by standard chemotherapy alone. One patient experienced a temporary response after the addition of ART to Fotemustine while the disease was progressing under therapy with Fotemustine alone. The second patient first experienced a stabilization of the disease after the addition of ART to Dacarbazine, followed by objective regressions of splenic and lung metastases. This patient is still alive 47 months after first diagnosis of stage IV uveal melanoma, a situation with a median survival of 2-5 months.

Note that the studies above used one component only, i.e. Artesunate, and not the whole plant.

Anecdotal stories in humans:

Mechanism:

Artemisinin combats malaria because the malaria parasite collects high iron concentrations as it metabolizes hemoglobin in the blood. Artemisinin contains two oxygen atoms connected together that break down in the presence of iron, by creating very reactive free radicals that kill malaria parasites and cancer cells. Therefore, Iron plays a crucial role in the cytotoxic activities of artemisinin-related endoperoxides through the generation of both ROS and carbon-centred radicals.

Both cancer cells and malaria parasites sequester iron, accumulating as much as 1000 times what normal cells store. In tumors, this is because cancer cells express a high concentration of transferrin receptors on cell surface and have higher iron ion influx than normal cells via transferrin mechanism. Iron is latter required by the cell for DNA replication during cell division. Giving artemisinin to people with malaria or cancer results in destruction of these abnormal cells and leaves normal cells unaffected. This iron-dependent cell death is called ferroptosis. The more cancer cells accumulate Iron the higher the chance for Artemisin therapy to work. Thus, the addition of iron several hours prior to artemisinin administration has been shown to enhance both the cytotoxicity and selectivity of the treatment.

It has been recently suggested that determination of iron-related genes may indicate tumor sensitivity to artemisinins. (Ref.)

Artemisinins usually promote apoptosis rather than necrosis in most of the systems, however in some cases both apoptosis and necrosis have been reported. Induction of apoptosis is a major benefit of artemisinins’ antitumor action as it prevents the collateral effects of inflammation and cell damage caused by necrosis. (Ref.)

Other mechanisms behind Artemisinin compounds: reduction or inhibition of

  • phosphoinositide 3-kinase (Ref.)
  • Akt (Ref.)
  • NF-κB activation (Ref.)
  • TNF-alpha (Ref.)
  • IL-6 (Ref.)
  • HIF1 and VEGF (Ref.)
  • and others

Pharmacokinetics:

Artemisinin has a half-life of about 3-4 hours, Artesunate 40 minutes and Artemether 12 hours. Peak plasma levels occur in 1-2 hours.

Artemisinin compounds inhibit their own absorption. It is possible this occurs more rapidly at higher doses. As a results, discontinuing the use of Artemisinin compounds rapidly (a few days to a couple weeks) returns absorption to normal. Absorption can be reduced by as much as 70 percent with 5-7 days of use (reference needed).

Formulation:

Formulation Source 1: From Wikipedia: its preparation was described in a 1,600-year-old text, in a recipe titled, “Emergency Prescriptions Kept Up One’s Sleeve”. At first, it didn’t work, because they extracted it with traditional boiling water. Tu Youyou discovered that a low-temperature extraction process could be used to isolate an effective antimalarial substance from the plant; Tu says she was influenced by a traditional Chinese herbal medicine source, The Handbook of Prescriptions for Emergency Treatments, written in 340 by Ge Hong, which states that this herb should be steeped in cold water. This book contained the useful reference to the herb: After reading the ancient Chinese medical description, “take one bunch of Qinghao, soak in two sheng (∼0.4 liters) of water, wring it out to obtain the juice and ingest it in its entirety”. (Ref.) After rereading the recipe, Tu realized the hot water had already damaged the active ingredient in the plant; therefore she proposed a method using low-temperature ether to extract the effective compound instead. The animal tests showed it was completely effective in mice and monkeys.

Formulation Source 2: Li’s group also developed suppositories containing artemisinin to treat cerebral malaria that are now being used in field clinics in Africa. Shortening the time to treatment by the use of suppositories improves survival. (Ref.)

Formulation Source 3: Artemisinin is soluble in ethanol (Ref.). Therefore we can use ethanol to extract artemisinin and the other main substances: Add 5g of dried powder into 10ml ethanol and let it stay for 3 days before usage

Administration & Dose:

Reference 1: In Democratic Republic of Congo, 54 malaria-infected volunteers were treated for 10 d with capsules containing powdered leaves of A. annua. Each patient was given 15 g dried leaves containing 15 mg of artemisinin (artemisinin content in leaves = 0.1%[38]). After 2 d all were free of fever and 51 (or 94%) were parasite free after 10 d. (Ref.)

Reference 2: In a study aimed at preventing severe post-operative malaria at Bangui, Central Africa, powdered leaves of A. annua were administered in capsules to 25 patients, 22 of them children aged 1–16 years[24]. Treatment duration ranged from 3–4 d with a dose of 0.4–0.5 g/d of A. annua dried leaves (0.1% artemisinin leaf content) delivering 0.4–0.5 mg/d artemisinin. In spite of the very low administered daily dose of artemisinin, average parasitemia dropped by 62% in the patients with an added benefit of a strong antinociceptive response, especially beneficial to post-operative patients. (Ref.)

Reference 3: artemisinin doses of 1000 mg on day 1 followed by 500 mg on each of days 2–7 that were administered to 227 malaria patients (Ref.)

Diet is an important consideration for any orally delivered drug, and when Dien et al[48] compared artemisinin oral doses given with and without food, Cmax values were similar between subjects who fasted and those who did not. Food consumption along with artemisinin did not seem to affect artemisinin absorption. In contrast, a later rodent study by Weathers et al[21] observed that when artemisinin was consumed as part of a complex plant material, pACT, approximately 45-fold more drug entered the serum of mice than orally administered pure drug. Similarly, when pure artemisinin was fed to mice, it was not detectable in the serum after 60 min. However, artemisinin was detected in the serum when consumed in conjunction with mouse chow, which consists of a variety of plant materials including soy, oats, wheat, alfalfa, beet pulp, corn, etc (Ref.)

Reference 4: The artemisinin content varies from 0.02% to 1.1% of the dry weight.6 Artemisinin and its semisynthetic derivatives are used in antimalarial treatment in artemisinin-based combination therapies, with daily doses between 100 and 200mg (Ref.)

Cotreatment: because of its short half-life, artemisinin requires another drug in combination to obtain a sustained cure against malaria. Indeed, combination therapy has been developed, which is now the standard treatment worldwide. Products that are used in combination with artemisinin, include mefloquine, lumefantrine, piperaquine, and pyronaridine. So combination therapies used today are:

  • Artemether + Lumefantrine (Ref.)
  • Dihydroartemisinin + Piperaquine (Ref.)

Summary from literature:

  1. Artemisinin is administrated at 500 to 1000mg/day
  2. Whole plant is better then artemisinin capsules in terms of reaching a specific level in blood even if the whole plant contains much much lower amount of artemisinin
  3. Whole plant tea infusion leads to shorter half life and needs to be administrated 4x/day (Ref.)
  4. Whole plant dried leaves better then tea infusion, but tea infusion better then pure artemisinin (Ref.)
  5. Dried leaves of the plant may be better and up to 15g/day of dried lives were administrated to patients for at least 10 days. In another study 0.5g/day was administrated to patients and was still effective. In yet another study 2–5 tablets of 500mg dried leves, twice on day 1, followed by 1–4 tablets twice daily for the next 5 d was administrated and effective anti malaria (Ref.)
  6. The whole plant seems to work best when administrated with or after meal (Ref.)

Main conclusions on administration and dose:

  • Oral consumption of A. annua dried leaves capsules is more effective than the pure drug. (Ref.1, Ref.2, Ref.3, Ref.4)
    • it can be found as whole plant or capsules online (or grown at home)
    • used dose of dried leaves powder is from 0.5g/day up to 15g/day; I would start with o.5g/day and increase the dosage to about 5g/day (Ref.)
    • administrated during or after meal
    • divide the daily dose in two or more administrations
    • Artemisnin compounds inhibit their own absorption. Discontinuing the use of Artemisnin compounds rapidly returns absorption to normal. As a result it is better to stop administration of Artemisinin compounds during the weekend.
      .
  • Oral consumption of A. annua dried leaves in hot water
    • dried lives can be boiled in hot water
    • 5g/day of dried leaves (or 25g of fresh leaves) (Ref.)
    • drank throughout the day
    • the disadvantage is that its taste is bitter
    • also the disadvantage is that is may be less effective compared to the dried leaves administrated as capsules
      .
  • Oral consumption of A. annua dried leaves in cold water or ethanol
    • I need to clarify more this formulation as it may be very relevant
      .
  • Oral consumption of Artemisinin or others derivatives is less effective compared to dried leaves but still used by many
    • can be found as capsules online
    • used doses from 2 mg/kg/day and higher; usually is taken at 100mg/day up to 1000mg/day
    • usually administrated 30 min before food – the common belief is that it needs to be taken on an empty stomach as the iron in food will react with the Artemisinin compounds – however most clinical trials and the anecdotal reports suggesting response were administrating with or after the meal
    • best to combine Artemisinin, Artesunate and Artemether
    • divide the daily dose in two administrations
    • Artemisnin compounds inhibit their own absorption. Discontinuing the use of Artemisnin compounds rapidly returns absorption to normal. As a result it is better to stop administration of Artemisinin compounds during the weekend.
      .
  • IV administration
    • Typically administrated as Artesunate, a few times/week
    • usually daily dose is 300mg or 5mg/kg/day
    • administrated in 250ml NaCl solution during about one hour
      (IV administration is based on best practices at German clinics)
      .
  • Others:
    • Avoid using glutathione supplements or other strong anti oxidants such as NAC as they may cancel out the pro-oxidant anti cancer effect of Artemisinin compounds

The belief is that

  • administrating Iron supplements a few days prior and during artemisinin treatment will enhance the effectiveness of the therapy (for safety reasons I would make sure there are some hours in between Iron administration and Artemisinin)
  • combining with Sodium Butyrate at about 3g/day dose may enhance the effectiveness of Artemisinin compounds. Sodium Butyrate is a substance with its own anti cancer effects and can be found as a supplement online.
  • vitamin C taken after breakfast and after lunch, enhances the iron absorption from the stomach so that Iron will reach the tumor prior to artemisinin administration
  • it is not recommended to use concurrent with radiation therapy due to damage to healthy cells from iron leakage from dying cancer cells

Toxicity:

In more than 4000 case studies, no significant toxicity from artemisinin has been found, which makes it far different than conventional chemotherapy.

It is not recommended to use concurrent with radiation therapy due to damage to healthy cells from iron leakage from dying cancer cells

In short term studies of single agent artesunate 8 mg/kg/day in normals, altered taste and slight decrease in reticulocyte count were the only side effects noted. (Ref.)

It may lead to slight decrease of Hemoglobin during teh treatment. Therefore monitoring hemoglobin is advised (Ref.)

Synergy:

Experimental studies showed additive or synergistic activities with antineoplastics, antibiotics, antifungals, sodium butyrate, and chloroquine, where it could become more effective in fever subsidence and disappearance of malarial symptoms. (Ref.)

Other interactions and synergies: http://www.hindawi.com/journals/bmri/2012/247597/tab3/

Source and Price:

Artemisia annua – whole plant extract – oral capsules:

  • e.g. Artecin (500mg/capsule), Italian product (600mg/capsule), Arthrem
    However, I think the best is to buy the powder and make our own capsules so that we know exactly what is inside (see below source for the whole plant powder)

Artemisinin oral capsules:

  • one of the best source based on chemosensitivity test I saw is Super Artemisinin which is sold by e.g. Nutricology and Allergy Research. This also contains oil extract from teh leaves.
  • one of the only source I know combining Artesunate & Artemisinin & Artemether is Artemix http://www.hepalin.com/artemix.htm

Artesunat IV

  • it costs about 50 euro a vial of 250 to 300mg. One source is Burg Apotheke

Seeds to grow Artemisia

  • a lady from Germany expert in growing Artemisia (Ref.)

Dried whole plant

Storage:

Artemisinin should be kept in a well-closed container, protected from light and stored in a cool place.

References:

Artemisinin: Discovery from the Chinese Herbal Garden

Pharmacogenomics of Scopoletin in Tumor Cells

Activity of Artemisia annua and artemisinin derivatives, in prostate carcinoma.

BACKGROUND: Artemisia annua L, artemisinin and artesunate reveal profound activity not only against malaria, but also against cancer in vivo and clinical trials. Longitudinal observations on the efficacy of A. annua in patients are, however missing as of yet.
METHODS: Clinical diagnosis was performed by imaging techniques (MRT, scintigraphy, SPECT/CT) and blood examinations of standard parameters from clinical chemistry. Immunohistochemistry of formalin-fixed, paraffin-embedded tumor material was performed to determine the expression of several biomarkers (cycloxygenase-2 (COX2), epidermal growth factor receptor (EGFR), glutathione S-transferase P1 (GSTP1), Ki-67, MYC, oxidized low density lipoprotein (lectin-like) receptor 1 (LOX1), p53, P-glycoprotein, transferrin receptor (TFR, CD71), vascular endothelial growth factor (VEGF), von Willebrand factor (CD31)). The immunohistochemical expression has been compared with the microarray-based mRNA expression of these markers in two prostate carcinoma cell lines (PC-3, DU-145).
RESULTS: A patient with prostate carcinoma (pT3bN1M1, Gleason score 8 (4+4)) presented with a prostate specific antigen (PSA) level >800 µg/l. After short-term treatment with bacalitumide (50 mg/d for 14 days) and long-term oral treatment with A. annua capsules (continuously 5 × 50 mg/d), the PSA level dropped down to 0.98 µg/l. MRT, scintigraphy and SPECT/CT verified tumor remission. Seven months later, PSA and ostase levels increased, indicating tumor recurrence and skeletal metastases. Substituting A. annua capsules by artesunate injections (2 × 150 mg twice weekly i.v.) did not prohibit tumor recurrence. PSA and ostase levels rose to 1245 µg/l and 434 U/l, respectively, and MRT revealed progressive skeletal metastases, indicating that the tumor acquired resistance. The high expression of MYC, TFR, and VEGFC in the patient biopsy corresponded with high expression of these markers in the artemisinin-sensitive PC-3 cells compared to artemisinin-resistant DU-145 cells.
CONCLUSION: Long-term treatment with A. annua capsules combined with short-term bicalitumide treatment resulted in considerable regression of advanced metastasized prostate carcinoma. Controlled clinical trials are required to evaluate the clinical benefit of A. annua in prostate cancer.

Artemisia annua – Pharmacology and Biotechnology

Dried-leaf Artemisia annua: A practical malaria therapeutic for developing countries?

Dried whole-plant Artemisia annua slows evolution of malaria drug resistance and overcomes resistance to artemisinin.

Dried whole plant Artemisia annua as an antimalarial therapy.

The Surprising Efficiency of Artemisia annua Powder Capsules

Repurposing the anti-malarial drug artesunate as a novel therapeutic agent for metastatic renal cell carcinoma due to its attenuation of tumor growth, metastasis, and angiogenesis

Willmar Schwabe Award 2006: antiplasmodial and antitumor activity of artemisinin–from bench to bedside.

Inhibition of human cytomegalovirus replication by artemisinins: effects mediated through cell cycle modulation.

Anticancer Effect of AntiMalarial Artemisinin Compounds

The wisdom of crowds and the repurposing of artesunate as an anticancer drug

Artesunate induces necrotic cell death in schwannoma cells

From ancient herb to modern drug: Artemisia annua and artemisinin for cancer therapy. https://www.ncbi.nlm.nih.gov/pubmed/28254675

Artemisia annua L. is used throughout Asia and Africa as tea and press juice to treat malaria and related symptomes (fever, chills). Its active ingredient, artemisinin (ARS), has been developed as antimalarial drug and is used worldwide. Interestingly, the bioactivity is not restricted to malaria treatment. We and others found that ARS-type drugs also reveal anticancer in vitro and in vivo. In this review, we give a systematic overview of the literature published over the past two decades until the end of 2016. Like other natural products, ARS acts in a multi-specific manner against tumors. The cellular response of ARS and its derivatives (dihydroartemisinin, artesunate, artemether, arteether) towards cancer cells include oxidative stress response by reactive oxygen species and nitric oxide, DNA damage and repair (base excision repair, homologous recombination, non-homologous end-joining), various cell death modes (apoptosis, autophagy, ferroptosis, necrosis, necroptosis, oncosis), inhibition of angiogenesis and tumor-related signal transduction pathways (e.g. Wnt/β-catenin pathway, AMPK pathway, metastatic pathways, and others) and signal transducers (NF-κB, MYC/MAX, AP-1, CREBP, mTOR etc). ARS-type drugs are at the stairways to the clinics. Several published case reports and pilot phase I/II trials indicate clinical anticancer activity of these compounds. Because of unexpected cases of hepatotoxicity, combinations of ARS-type drugs with complementary and alternative medicines are not recommended, until controlled clinical trials will prove the safety of non-approved combination treatments.

Cancer combination therapies with artemisinin-type drugs http://www.sciencedirect.com/science/article/pii/S0006295217301818

Artemisia annua L. is a Chinese medicinal plant, which is used throughout Asia and Africa as tea or press juice to treat malaria. The bioactivity of its chemical constituent, artemisinin is, however, much broader. We and others found that artemisinin and its derivatives also exert profound activity against tumor cells in vitro and in vivo. Should artemisinin-type drugs be applied routinely in clinical oncology in the future, then probably as part of combination therapy regimens rather than as monotherapy. In the present review, I give a comprehensive overview on synergistic and additive effects of artemisinin-type drugs in combination with different types of cytotoxic agents and treatment modalities: (a) standard chemotherapeutic drugs, (b) radiotherapy and photodynamic therapy, (c) established drugs for other indications than cancer, (d) novel synthetic compounds, (e) natural products and natural product derivatives, (f) therapeutic antibodies and recombinant proteins, and (g) RNA interference. I also summarize the activity of artemisinin-type drugs towards multidrug-resistant cells and tumor cells with other drug resistance phenomena. As synergistic interactions may not only occur in tumor cells, toxic reactions in normal cells (hepatotoxicity, drug interactions) were also considered. This review summarizes the scientific literature of more than 20 years until the end of 2016.

Disclaimer:

This site is not designed to and does not provide medical advice, professional diagnosis, opinion, treatment or services to you or to any other individual. Through this site and linkages to other sites, I provide general information for educational purposes only. The information provided in this site, or through linkages to other sites, is not a substitute for medical or professional care, and you should not use the information in place of a visit, call consultation or the advice of your physician or other healthcare provider. I am not liable or responsible for any advice, course of treatment, diagnosis or any other information, services or product you obtain through this site. This is just my own personal opinion regarding what we have learned on this road.

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Katja
Member
Katja

Dear struggeling friends, as I developed a strong pancreatitis after a 14-day i.v. Treatement without a pause, I will give away for free my remaining artesunate-vials. Each 60mg. There are 54 left and 45 ampules with the needed sodium bicarbonate. The missing 9 can be bought easily in any pharmazie. Additionally there are 300 cpsules of Hepalin, 300 caps. Of Hepamether, 60 cps of Artemix and 120 caps. Of Hepamether bought from the above mentioned US-company http://www.hepalin.com all for free or giving a donation to the foundation here, would be grate. Hope, anyone can use it. Best whishes Katja

Emad
Member
Emad

about the best sources you mentioned for capsules , the doses are not clear …

example : http://www.iherb.com/Nutricology-Super-Artemisinin-60-Veggie-Caps/3484

this one : is it 200mg/capsule ? or 180mg ?

for low doses capsules , to get better results (5g/day) we need to consume about 25 capsules daily !

this will make it hard and expensive , but may be the best !?

———————–

the powder here looks cheap even if you take high doses
http://www.teemana.de/de/preisliste.html

but I really don’t know which one is better against cancer ?

Emad
Member
Emad

I want to take sodium butyrate with it , is it better to administrate it before or with or after the artemisinin ?

do you know a good source for sodium butyrate ? there is a lot in amazon.com and I don’t know which one is the best

PS
Guest
PS

Hi Daniel,

U have been doing a very good job and it gives hope to everyone who’s fighting this kind of disease.
Can you also pls explain which supplements/ food should not be taken or what time gap should be maintained along with artemisinin.

Regards

jarisenthil
Guest
jarisenthil

Hi Daniel,
You have given a very brief literature on Artimesia Annua on MALARIA & CANCER .
1.Leaf powder of art.annua what is the dosage for cancer treatment ?
2. What is the period of dosage ?
3. Along with cannibis oil Artmisia annua can be taken ?
Kindly clarify.

Rob
Guest
Rob

Daniel,
I found the case report about fatal connection Artesuante + NaDCA:

https://www.ncbi.nlm.nih.gov/pubmed/27774434
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053977/
http://journal.frontiersin.org/article/10.3389/fonc.2016.00204/full

1. What do you think? Is it safe to use both medicaments together? How about connection of Artemisinin and NaDCA, both orally administrated?

2. And how about using anti oxidants? I know it is not recommended, but shoud it be stopped at all or it is enough to take Artemisinin a few hours after anti oxidants?

3. Is Artesuante better than Artemisinin in cancer treatment?

Thank you for your help 🙂

Best regards,
Rob

Meech
Member

Hi Rob, I’ve been using NaDCA and artemisinin tea for a while now and have not experienced any worsening in liver enzymes, etc. I haven’t been taking a large dose of artemisinin though, just one cup daily generally.

Shigella Philip Mateja
Guest

I have many clients whom are using artemisia for malaria,pile and skin diseases, I will also give it to cancer patients. Thanks for your transparent knowledge.

Wondering
Guest
Wondering

Hi,

it is also used against Lyme disease.

Thinus Coetzee
Guest
Thinus Coetzee

Hi Daniel
I am using the malaria tablet Coartem now since February 2016. I was diagnosed with tubular prostate cancer, Gleeson Score 8, PSA 901, black spot on the pelvis. Also received the terrible Lucrin injections until December 2016. My PSA is down to 0.23. A third bone scan last year August showed the black spot cleared up.
Kind Regards
Thinus Coetzee

Ergin
Guest
Ergin

Dear Thinus,
This is amazing.Could you please tell us more about your protocol.
Only coartem and Lucrin?Did you take chemo,surgery?
Kind Regards
Ergin

Wondering
Guest
Wondering

Thinus, would it be a normal / expectable reaction to Lucrin only?
cheers
W

Ben
Guest
Ben

from my reading around the chemistry and pharmacokinetics of Artemisia Annua it’s clear it is an unusual herb in several respects.
1, the active components are mainly found in tiny structures on the surface of the leaves and flowers/pre-flower buds in the top 1/3 of the plant – this is important when sourcing the herb as many sources out there are mainly stalks and stems ground up.
2, the active components in it ( notably artimisin – but also others) are heat, light and air sensitive – so drying and processing conditions are critical – to maintain the finished product potency
3, the herb is grown commercially in many countries for malaria medicine – and often high yield varieties are used that have 2-5x higher levels of active components – especially where it is grown for sudo-pharmacological drug production – but currently, herb suppliers do not typically have validated information about their sources – or the raw herb or finished herb product potency.
4, the chemicals in it have unusual absorption/excretion profile in humans/mammals – artemisinin blood concentrations in the blood are highest on the first day of dosing and fall rapidly to 25% of those by day 8. for this reason effective treatments are likely to be those that dose sufficiently from day 1 and continue for a relatively short course ( approx 30-40 days max ) – rather than slowly ramping up – or long-term use.

I highlight the above as I think it’s important for more of us to question our herb sources and ask for information on, growing processing and storage conditions, and concentration of active components in the herbs we buy. in the way, the industry will respond over time by providing more of this essential information to its customers. I also believe natural medicine should make the best use of the science we have available to us at this time, as well as the traditional and anecdotal resources.

I do not have references to hand but much of the above information is available online if you look for it – my knowledge of this herb stemmed from my initial reading of work by Stephen Buhner – a world renowned herbalist – and the references he cited in his books

if anyone locates a source of whole Artemesia Annua herb that can validate the above potency questions I would be very interested. As, other than growing your own, it seems very hard to find.

Karolina
Guest
Karolina

Daniel,

Thank you for the great article and all the information. My mother has neuroendocrine tumour with large liver metastasis and I hope artemisia annua can help. I have a few questions:

1. How much iron is recommended / safe to take daily as part of the artemisinin treatment? E.g. is 50 mg safe? Does it work without iron supplements as well?

2. Do you think it’s safe to take 2 x 5g artemisia annua powder + 2 x super artemisinin (180 mg artemisinin + 20 mg artemisia annua leaf oil)? (Taking the powder at the same time with a capsule, twice a day.)
I know that the whole plant powder is supposed to be more effective, but a lot of articles reference artemisinin at quite high dosages (up to 1000 mg per day) and I’m not sure how much whole plant is needed to reach the same levels in blood as by taking 1000 mg pure artemisinin.

Thank you, Karolina

Wim Goeteyn
Guest
Wim Goeteyn

Hi,

Artemisinin / Curcumin / Mangostin. This would be the most powerful Mix to win the battle against cancer.

With endless peer reviewed based documentation on pubmed. Please Share !

Wim.

Ergin
Guest
Ergin

Hi Wim,
For me hyperthermia and a heat shock protein inhibitor like quercetin + a SGLT inhibitor like phlorizin+ an OXPHOS inhibitor like ? is a top strategy. We must talk more.

Ergin
Guest
Ergin

Now i am working on ROS and the correlation between HSP

Katja
Member
Katja

Even, if the gardening season will take a few months, I found two sources for artemisia annua seeds (around 2 EUR for a seedbag ).
1.I know this company, they do a lot of healing plants from China and India… http://www.kraeuter-und-duftpflanzen.de and
2. http://www.templiner-kraeutergarten.de

Katja
Member
Katja

Hello, on my surch for a Artesunate-i.v. Therapy, which ist affordable, I am checking a direct-import from china (on the advice of friend, who works at the tropical institute in Bale).
The big companies only sell in big amounts, but there are smaller, with would deliver to Europe smaller packages (Germany is not popular because of it`s custom, France seems to work).
Has anyone done this before?
It would lower the costs for a “chemo-cycle” from 11000 to 800 EUR !!
The recommendation is: at least 15 infusions inbetween 3 to 4 weeks, every time 5mg/kg bodyweight. As most of the vials contain 60mg and cost in china 12$.
On this site:
http://www.anamed.edition.comit seems, they offer high quality
In the downloads are recxepies for tee-preparation with good serum-concentrations…
I let you all know, how it works, to get the good stuff and am interested, if one did it before?
Does anyone know, if there is a possibility, to check, what is in the chinese vials?
Additional to your collected trials, here is a new one about Livercancer treated with artemisia capillaris:

Oncol Rep. 2017 Jan;37(1):526-532. doi: 10.3892/or.2016.5283. Epub 2016 Nov 29.
Evaluation of antitumor activity of Artemisia capillaris extract against hepatocellular carcinoma through the inhibition of IL-6/STAT3 signaling axis.
Jang E1, Kim SY2, Lee NR2, Yi CM2, Hong DR2, Lee WS3, Kim JH2, Lee KT3, Kim BJ4, Lee JH1, Inn KS2
Interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signaling pathway plays critical roles in the development and progression of hepatocellular carcinoma (HCC). Artemisia capillaris (AC) has been widely used to treat various liver diseases including HCC as a herbal medicine. The effects of AC on IL-6/STAT3 signaling axis in HCC cells and subsequent anticancer activity of AC against HCC were analyzed using HCC cell lines and HBV W4P-LHB-expressing NIH3T3 cell line, which has been shown to gain tumorigenicity by activating IL-6/STAT3 signaling in our previous study. AC extract significantly suppressed the growth and colony formation of HCC cells. In addition, it inhibited the activation of STAT3 by IL-6 and subsequent synthesis of downstream molecules in HCC and W4P-NIH3T3 cells. Consequently, migration of cells was significantly suppressed by the AC extract. Collectively, the findings suggest that AC extract is capable of conferring various antitumor effects against HCC through the modulation of the IL-6/STAT3 pathway. The results provide a basis for the therapeutic use of AC in the treatment of HCC. Identification of the compound responsible for the effect may lead to the development of a novel anticancer agent against HCC.

Even if I read a lot about artemisia, I am not sure, what it means, that the trial was made with artemisia capillaris.?
Thank you for looking together for our lifes…Katja

a.a
Member
a.a

Hi Daniel
Thank you for the very interesting Information
my mother was diagnosed with breast cancer 5 years ago. the treatment was surgery and chemo. she has taken Femara for 5 years. Now metastasis in the spine (two places). got 10 Cycklen Radiotherapie and now we want to try Artemisia annua. I ordered in the Annamed and If I could possibly ask you:

1. Am I ok with the dosis:
Morning: 2.5 Artemisia (powder A-3) Lunch: 2,5g Moringa
Evening: 2.5g Artemisia or do I better 2x5g Arte?

2. Can you please say me if we need to take some other suplement?
Thank you very much
Regards Arb

Alex
Member

if the metastasis involves bone tissue, please look for zometa or other bisfosonates, talk to doctor.

a.a
Member
a.a

Thank you Alex,
Yes we‘ve started Ibandronat

Alex
Member

any information on genetic expression of tumor cells?

a.a
Member
a.a

In the biopsi bevor 5 years ER+ und HER2- . For 5 years treated with Letrozol

immanuelbader@gmail.com
Member

Hi Daniel,

you mentioned in your post that you ordered the powder from http://www.teemana.com.

Have you received the powder and do you think its good quality?

Thanks,
Immanuel

immanuelbader@gmail.com
Member

Hi Daniel,

another question about nutricology super artemisinin. Do you know if this really contains pure artemisinin or is it also an extract from the plant like other manufacturers have?

If its pure artemisinin, do you know anything about the bio availability when taking it oral? Is it in any way comparable with IV or IM? Or would you recommend IV or IM instead of oral intake?

Thank you so much for all your effort, i really appreciate it!

-Immanuel

immanuelbader@gmail.com
Member

I have another questions where i would really appreciate your thoughts on. What do you think of taking Sulforaphane, Curcumin and Artemisinin at the same time? Would this be a good combination?

Thanks a lot,
Immanuel

[email protected]
Member

Dear Daniel,
what is the difference between artemisinin and super artemisinin?
My sister (breast cancer stage 4) used 60 capsules of super artemisinin 2x/day (Nutricology), then I wronged to order Super artemisinin and ordered Artemisinin.
I want to know, It’s not a problem to use Artemisinin instead of Super artemisinin?
thanks

Shanti
Member
Shanti

Hi Daniel- Excellent article! We used Artemisinin 500mg bid 1 week on and 1 week off for about 6 months and then stopped for 6 months. We are about to start it up again but will now change strategies to lower the Artemisinin dose and add in some of the whole plant. Thanks Again!