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Artemisia Annua, Artemisinin & 2015 Nobel Prize in Medicine – A Cancer Fighting Plant

Author: Daniel S, PhD; Last update: January 31st, 2021

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). Artemisia annua also kills Schistosomiasis parasite in humans (Ref.1, Ref. 2).

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 Italy and there are constant positive anecdotal 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 Cancer. http://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.
  • Preliminary Case Series of Artemisinin for Prostate Cancer in a
    Naturopathic Practice
    Of those patients who have previously undergone RP, 2/5 (40%) had
    improved PSA kinetics after artemisinin therapy. Of those with no prior RP, 5/10 (50%) had improved PSA kinetics. No patient developed signs of metastasis and no patients died. There were no reported adverse effects.
  • Artesunate combined with vinorelbine plus cisplatin in treatment of advanced non-small cell lung cancer: a randomized controlled trial
    The negligible side effects and improvement of short-term and one-year survival rates were detected in the group with the artesunate-treated patients, compared with control group. Artesunat was used at 120 mg, once-a-day intravenous injection, from the 1st day to 8th day, for 8 days. At least two 21-day-cycles of treatment were performed.
  • reported to reduce the incidence and risk of metastasis in breast cancer and osteosarcoma patients (, )

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

Update April 2021: More studies are listed in this recent review https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564301/

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 suggested to enhance both the cytotoxicity and selectivity of the treatment (I would however not supplement Iron).

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.)
  • artemisinins improved glucose homeostasis (increase GABA signaling and prevent glucagon secretion by α cells so that α cells acquire β cell characteristics(Ref.)

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).

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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 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 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.)

Reference 5: 800 patients infested with Schistosomiasis (bilharzia) treated with Artemisia Annua tea. Conclusion of the study: “Both A. annua and A. afra provided faster effective treatment of schistosomiasis and should be considered for implementation on a global scale”.

Here is how they prepared and gave Artemisia tea in this study: “In the Artemisia treatment arms, patients drank 0.33L of A. annua or A. afra infusion 3 times daily for 7 days. Infusion was prepared as follows: 5g dried leaves and twigs of A. annua or A. afra were added to 1L of boiling water, infused for 10min, and filtered through a sterilized 1mm mesh.” (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 lower amount of artemisinin
  3. The whole plant tea infusion leads to shorter half life and needs to be administrated 4x/day (Ref.)
  4. And the 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 7 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 if the patient decided to take – but personally, I would not use Iron)
  • 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:

  • Food supplement compamies online

Artemisinin oral capsules:

  • Food supplement companies online

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.

Effect of Artemisia annua and Artemisia afra tea infusions on schistosomiasis in a large clinical trial https://www.ncbi.nlm.nih.gov/pubmed/30466622

RESULTS: Of 800 enrolled patients having an average of >700 Schistosoma mansoni eggs per fecal sample, 780 completed the trial. Within 14 days of treatment, all Artemisia-treated patients had no detectable eggs in fecal smears, a result sustained 28 days post treatment. Eggs in fecal smears of PZQ-treated patients were undetectable after D21. More males than females who entered the trial had melena, but both genders responded equally well to treatment; by D28 melena disappeared in all patients.

In all arms, eosinophil levels declined by about 27% from D0 to D28. From D0 to D28 hemoglobin increases were greater in PZQ and A. afra-treated patients than in A. annua-treated patients. Hematocrit increases were greater from D0 to D28 for patients treated with either PZQ or A. annua compared to those treated with A. afra. Gender comparison showed that A. afra-treated males had significantly greater hemoglobin and hematocrit increases by D28 than either PZQ or A. annua-treated males. In contrast, PZQ and A. afra-treated females had greater hemoglobin and hematocrit increases than A. annua-treated females. Both adults and pediatric patients treated with A. annua responded better compared to PZQ treatment.

CONCLUSION: Both A. annua and A. afra provided faster effective treatment of schistosomiasis and should be considered for implementation on a global scale.

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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117 thoughts on “Artemisia Annua, Artemisinin & 2015 Nobel Prize in Medicine – A Cancer Fighting Plant”

  1. 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 ?

  2. Hi Emad, the point of the article above is that the whole plant (Artemisia Annua) may be more effective than the pure Artemisinin.

    The dose of 5g/day and up to even 15g/day was connected to the whole plant such as that from teemana from Germany.

    On the other hand, the pure extract such as the Super Artemisinin cited above is usually taken at a daily dose of 100mg up to 1000mg.

    I hope this clarifies things.

  3. 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

      1. Hi Nicole,

        It is well known in the scientific literature that cancer cells usually increase the input of iron and inhibit its output, leading to intracellular iron accumulation. Given this fact, it is natural to expect that cancer cells have accumulated enough Iron.

        If cancer cells don’t have enough Iron, it means they can not develop, and I woudl be happy to keep that status, while I would find it risky to give them fuel for division when they don’t have enough iron. If on the other hand, cancer cells have enough Iron (as we woudl expect based on science), there is no point to further supplement.

        Furthermore, it has been shown that the availability of extracellular Iron reduces the effectiveness of Vitamin C https://www.nature.com/articles/srep05955 and I woudl expect the same applies to Artemisinin.
        (I discussed this paper some years back here https://www.cancertreatmentsresearch.com/high-dose-vitamin-c-cancer/ )

        In this context, the authors in the paper above even suggested it may be best to use Iron chelators prior to the use of Vitamin C in cancer therapy in order to remove some of the extracellular iron, and as a result enhance the effect of Vitamin C. This concept woudl apply to Artemisinin treatment strategy as well, and we therefore could argue it is even the opposite to the concept of using Iron prior to Artemisinin that is often promoted online (which is logical at first, without going into the details mentioned above).

        Iron chelator typically used at integrative clinics is EDTA.

        Kind regards,
        Daniel

  5. 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

    1. Hi PS, Thanks for the feedback. Regarding your question, I think Arte is similar to Vitamin C, i,e, one of the main anticancer mechanism is based on its interaction with Fe. So you want to have Arte reaching the cancer cell in order to interact with intracellular Fe and kill cancer cells. Due to this, I would avoid taking Arte with or after high Fe containing foods as it may end up reacting with Fe before reaching its target. Taking Fe chelators prior to Arte may help too. Kind regards.

      1. Thanks for replying.

        Also, would like to know if there may be interference of antioxidants with Arte. Should one continue curcumin, carrot juice (oxylates), vitamin C, asparagus, baking soda, wheatgrass, other vitamin and mineral supplements with Arte. If so, what time gap in your opinion will be reasonable to avoid any interference.

  6. 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.

    1. Hi, thanks for your questions:
      1. the answer is in the post
      2. i would probably check after one month if there is still progression or not and continue or stop accordingly
      3. I am not aware of any interaction between the two so I would use them at the same time

  7. 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

    1. 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.

    2. Hi Rob,

      Thank you Meech for helping out with teh response.

      1. I would not worry about combining the two as long as they are used in the oral version both. But if that is given IV, I would indeed follow the treatments with blood tests every week or so.

      2. In general, I would not worry about combination with anti oxidants unless you use very strong anti oxidants such as NAC. If that is the case, I would indeed give them some hours latter or even better stop them while using pro oxidant treatments. When the treatments are performed IV, I would clearly not combine anti oxidants with pro oxidants, not even days latter, as the antioxidants will cancel out the effects of the pro oxidant treatments. That is based on facts. To be clear, I am speaking about the use of strong antioxidants such as NAC and ALA.

      3. It doesn’t really matter because of the following: if given orally I prefer the whole plant from an effectiveness point of view; if given IV only Artesunate is available (so far and to my knowledge).

      Note: Based on personal experience Artesunate combined with Vitamin C, both given IV, may lead to decline of hemoglobin so I would avoid this combination – however, this change is reversible and hemoglobin will come back once the treatment is ended.

      I hope this helps.

      Kind regards,
      Daniel

      1. Daniel,
        Thank you for the answer and detailed explanation. I’m fighting with rectal cancer in a member of my family. It
        was diagnosed about 3 months ago and it is stage 3 (T3N1). The patient has also advanced cardiovascular disease
        CVD. Beacuse of coronary artery disease the chemotherapy was banned. Currently radiotherapy is in progress (5 x
        5Gy). After about 8 weeks the operation is planned. It is not simple case as we have two serious diseases, patient
        has 62 years and he its life style was fatal until now, so any changes are difficult to implement… Nevertheless
        what I did until now in nutrition and suplementing area:

        1. I completely changed the diet: it is now low fat, unprocessed plant only based diet based on rules described by
        Caldwell Esselstyn (http://www.dresselstyn.com/site/), Colin Campbell (http://nutritionstudies.org/), Dean Ornish
        (http://deanornish.com/) and finally David Servan-Schreiber (http://www.anticancerbook.com/) to use most anti
        cancer nutrition products.

        2. I applied a lot of suplements, extracts and cancer treatmens. I had a few goals:
        – elimination of nutritional deficiencies,
        – stimulation of the immune system,
        – direct fighting with cancer (increasing apoptosis, inhibition of proliferation and angiogenesis),
        – stopping CVD and reversal of atherosclerosis,
        – necessary supplementation in the vegan diet.

        I’ve used until now:
        – vitamins: D3, K2-MK4, K2-MK7, C (as acerola extract), B12,
        – minerals: zinc and copper (for a change), selenium, iodine, magnesium malate,
        – short and long chain Omega3 (ALA from flax/chia/hemp protein and EPA/DHA from microalgal oils),
        – others: Q10, CLA (Conjugated Linoleic Acid), ALA (Alpha Lipoic Acid), beta-alanine + histidine (for increasing
        carnosine synthesis), NAC+glycine+glutamine (for increasing glutathion synthesis; I stopped glutamine as I found
        CRC likes it), astaxanthin,
        – lot of plant extracts: piperinum, garlic extract, tumeric (row and as a Theracurmin), black and cayenne pepper (for increasing curcumin bioavailability), milk thistle (row and as a strong silymarin extract – synergistic with curcumin), grape seed (a lot of OPC), cat’s claw, resveratrol, ginkgo biloba, graviola leaves, gotu kola, hylandia dockrillii, ashwagandha, houttuynia, boswellia, olive leafs, green tea, fisetin, broccoli (as row seeds and as BroccoMax), shatavari, echinacea, noni, black cumin, moringa oleifera leaves, quercetin+bromelain, acai, cranberries,
        – mushrooms: oyster, cordyceps, chaga, reishi, shitake,
        – BioBran (Bibran): http://www.daiwa-pharm.com/english/product/biobran.html, http://www.biobran.org/.

        All used extracts has scientifically proven anticancer properties, sometimes in vitro or in mouse/rats, but it
        has. Daniel a few more questions to you:

        1. As it is not possible to use all of the above extracts and we have 4 weeks to reduce main tumor size, then
        please let me know what to use and what not. Maybe you also know some bad interactions between the above
        extracts, then let me know (in example I found that chaga can may magnify the effects of anticoagulant medications
        such as aspirin which we use; patient also uses beta blockers for hypertension).

        2. Regarding curcumin – I found that the best bioavailability has Theracurmin, so I choosed it. Theracurmin is
        better than BCM-95, BCM-95 is better than row curcumin and row curcumin is better than turmeric. Example research:
        https://www.ncbi.nlm.nih.gov/pubmed/25994138. Let me know what do you think.

        3. I plan to start NaDCA. What doses you suggest and what additions should be used. I found information about
        thiamine, ALA (alpha lipoic acid) and caffeine (preventing NaDCA-induced neuropathy) and omeoprasole (synergistic
        effect: https://www.ncbi.nlm.nih.gov/pubmed/22580646, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362455/).
        Please advice.

        4. Currently we use Artemisinin 2 x 200g orally administrated. According to your and Meech information it should be safe with NaDCA. Also, do you know good sources of row Artemisia annua extract?

        5. What other treatments you suggest? According to your website (in my opinion the best – congratulations!) I
        thought about mebendazole, methylglyoxal. Any suggestions will be appreciated.

        6. What do you think about BioBran? Treatment is in progress (3 x 1g MGN-3) and is not cheap, so if there is
        something definitely better then let me know.

        7. I found the information about retinoic acid in CRC (https://www.cancertreatmentsresearch.com/?p=137,
        https://www.sciencedaily.com/releases/2016/08/160830130817.htm). Retinoic acid it is not easy available and I
        don’t know what doses should be used in human, but maybe a lot of carrot juice and retinol suplementation would make
        the same effect?

        Thank you very much for your help!

        Best regards,
        Rob

        1. Dear Rob,

          Thank you for the overview and for the nice words regarding the website.

          Because your comment was so long it went directly to “Thresh” – I had to restore and approve that – that is why it took a bit more to see it published. If you will make a user account on this page I will not have to approve every of your future comment. It will be immediately visible, unless is detected as a spam due to e.g. too many links or too long, in which case it may go again to “Thresh”.

          There are many questions 🙂 I will try to shortly address all and if you have questions following the response just let me know.

          1. I recognize most of those supplements but there is no major interaction that comes to my mind, based on my (limited) knowledge about most of them. I would however avoid the use of Zinc and Cooper since they are debatable and specifically Copper since it helps angio genesis.

          2. There are many statements about various sources of Curcumin that are better than others. And there is marketing behind that. Curcumin is an extract from Turmeric. Curcumin is the most researched one but Turmeric has other powerful anti cancer components inside. For oral administration I would just pick a 1000mg capsule with piperine and use several of those each day. I would also administer a whole plant capsule with that (Turmeric) in order to get the benefits that may come from the other components. I would take this with some oil, e.g. Omega 3 capsules to help the absorption. With that, I would stop researching for the best source and move to a next treatment. Otherwise we may even write a PhD thesis on it and still not find the best version.

          3. With DCA, I would start with 10mg/kg and if no issue increase to 20mg/kg. 5 days on and 2 days off to reduce chance for side effects. If there is serious benefit to the patient that should become visible at this dose. Omeprazole and even more Metformin will both help DCA but also themselves having anti cancer properties. ALA and caffeine indeed help against potential side effects as well as B1. I will once write a post on DCA.

          4. I had a good source from Germany – I will search and if I find it I will let you know

          5. For CRC Mebendazole is great indeed – up to 1000mg/day but always starting with lower dose with anything new. Quercetin is also very good. For some 3BP works great to debulk fast.

          6. No specific opinion. Is a nice to have not necessarily a must have from my point of view. Coriolus can also help a lot the immune system and is cheaper.

          7. Retinoic acid is easy available to my knowledge – I do not have the source at hand but if you remind me in the coming days I will give you a link to their website

          I hope this answers your questions and helps.

          Kind regards,
          Daniel

          1. Daniel,
            1. I know about Cooper, but it was necessary as I use high doses os Zinc in order to fix its deficiency caused fatal diet before diagnosis. I planned to suplement Zinc for 2-3 months which has just elapse.

            2. Whole plant extract of Turmeric is simply Turmeric spice (I already use them), right?

            3. What doses of ALA/B1/Omeoprazole/Metformin you suggest in combination withDCA?

            5. Mebendazole and Cimetidine just purchased. Quercetin + Bromelain is already used. What about methyloglyohal? There is a lot of good info on your website (https://www.cancertreatmentsresearch.com/?p=1471) and it looks it should works also in CRC (https://www.ncbi.nlm.nih.gov/pubmed/27455418). Fast research shows Methyloglyoxal, 2-oxopropanal and Pyruvic Aldehyde are the same substances, right? I found it here: https://www.molport.com/shop/moleculelink/2-oxopropanal/1769006. Is that right choice?

            6. Coriolus just purchsed.

            4,7. Please let me know about good source of Artemisia annua row extract and retinoic acid. I found it here: https://www.molport.com/shop/search-results?searchkey=7FID7IHM2MR5G1B3PNL2SH, but there are a lot of versions: 9-cis-Retinoic Acid, Retinoic Acid, 11-cis Retinoic Acid, 13-cis-Retinoic acid, 13-cis Retinoic Acid Methyl Ester, 4-Oxo-9-cis-Retinoic Acid, 4-Keto 3-cis-Retinoic acid, 4-Keto all-trans-Retinoic Acid, 4-Keto all-trans-Retinoic Acid-d3, 9-cis Retinoic Acid Methyl Ester, 4-Keto all-trans-Retinoic Acid Methyl Ester. I don’t know the differences and don’t know the dosage in humans. To use it I need to be absolutely sure what I’m doing… Any advice?

            Thank you very much again for your help!

            Best regards,
            Robert

            1. For Metformin, I think Daniel has suggested 1000mg/day.

              In my experience, I take 1500mg, spread out as 500mg in the morning, evening, and before bed. I take it in conjunction with DCA.

              The only negative side effect I’ve had has been upset stomach and diarrhea. This has completely subsided though, as my body has adapted. It could have also resulted from not taking it with sufficient food.

            2. Forgot to mention that doctors frequently titrate Metformin when given as a standard drug for Type 2 Diabetes. They may start with a lower dose and build up gradually to the optimal dose to avoid side effects. I did not do this.

            4. Hi Robert,

              2. Whole plant Turmeric is the Turmeric spice.
              3. ALA 600mg should be not too low and not too high for this specific purpose. Omeprazole 40-80mg should be safe. Metformin 1000 to 2000 should be good but depends on weight, should be increased slowly as Meech suggested, and note that the plasma level may be increased by the Cimetidine so take care when combining the two – in this case 1000mg should be enough I think.
              5. Please check the CAS# on my MG post and you will find the answer to the question
              4.7. Retinoic acid http://uk-rxcart.com/44-buy-accutane.html

              Note: please chack the drugs you are adding new with your doctor – always add a new one after a few days not all at the same time – increase the dose step by step to the target dose, specificaly for those you expect side effects

              Kind regards,
              Daniel

  9. 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

    1. 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

  10. 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.

    1. Thanks a lot Ben for this great info! I totally agree, i.e. we need to have good sources of active supplements. In my view you touched an essential point, and i am considering now a way to verify that for other supplements as well. To my knowledge, here is one of the best sources on the whole plant Arte. Annua https://anamed.org/en/artemisia-annua-anamed.html However, I can not say if they validate all the points you mentioned. You can off course contact them and ask. Once, on of their members wrote a short note here but they never advertised which I also appreciated. In conclusion, you added very valuable points. Thank you.

      Kind regards,
      Daniel

  11. 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

    1. Dear Karolina,

      Thank you for your comment. Answering your questions:

      1. I think cancer cells have enough Iron compared to normal cells. Alos, too much Iron in the blood may reach to inefficency of Arte. in the same way as it doese for Vitamin C as explained here https://www.cancertreatmentsresearch.com/high-dose-vitamin-c-cancer/ So what I would do is to try the following:
      – first I would not use any Iron supplementation for several weeks, and if possible even use Iron chelators prior to Arte such as EDTA IV or e.g. Baicalein (found in Scute supplement from iHerb)
      – if after several weeks there is no impact on markers, you could try to use Iron supplementation. The safe dose should be easy to fin on the web. If you can not find please let me know and I will check that for you
      I would expect the first approach is the right one.

      2. The doses you are intending to use may be high and reaction may be different from person to person. What I would to in this case is to increase step by step the doses towards the target dose you mentioned. If there is any side effect at a specific dose, you can step back to the previous dose where there was no side effect. I would use this approach not only for these supplements but for any other drugs or supplements that are used by the patient for the first time.

      I hope this helps. Please let us know how things are going and if you have questions just post them here and myself or other friend here will try to help.

      Btw, for the large liver mets have you considered TACE at Prof Vogl in Germany (Frankfurt University Hospital)? He seems to be the best in the world doing this (TACE to the liver) and he is also one of my favorites docs in this world.

      Kind regards,
      Daniel

      1. Dear Daniel,

        Thank you for the quick reply, it has been really helpful. I will take your advice and start without Iron and in a smaller dose.

        I haven’t actually heard about TACE; we live in Hungary and I don’t think we can afford medical treatment abroad. I can ask the oncologist the next time we see her whether TACE would be an option. (I’m not sure since my mother has several tumours in the liver, smaller and larger as well.)

        Thanks again,
        Karolina

        1. Dear Karolina,

          TACE in Germany is about 4000 euro/ intervention. But it should also be available in Budapest – just that prof Vogl has the most experience in the world. TACE can be done such so that more tumors can be addressed. And if the spread is to large, not local but regional TACE can be done. I know TACE is also performed in Bucharest (my origin is Romanian).

          Beyond this, please read some of my posts on this website and you should be able to get more ideas in terms of treatment options.

          If you are considering chemo, there are posts discussing approaches to increase chemo effectiveness as well.

          If you have questions on them please let me know – if needed you can also send me an e-mail. All the best to your dear mom.

          Kind regards,
          Daniel

  12. 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.

  13. 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.

  16. 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

    1. Hi Katja,

      I would expect the Chinese version would be OK. However, 60mg for 12$ would be = with 30$ for 150mg. Adding the transport costs to that may go in the 35$ range. German Clinics are using 150mg to 300mg as I remember and the material cost for 150mg in Germany will not be far from 35$/vial. Adding the risks at the customs and everything around, I am not sure there is much gain ordering from China. Otherwise, I could order from China many things and receive them in good state and exactly what I ordered. But for Artesunate I would go for the German version since you can trust the quality and there is not a major price difference based on what I know. If you have a friend that is medical doctor you should be able to order it from various compounding pharma incl. I think dr. Miller http://www.dr-miller-gmbh.de/production2.htm
      I hope this helps.

      Kind regards,
      Daniel

      1. Hi Daniel!

        Do you know the names of some of the German compounding pharmacies doing Artesunate? My U.S. doctor is trying to find a European source for me since I live in Europe and I’m having a hard time finding any German pharmacies that make it. Google is only showing up Indian sources.

        Thanks 🙂

  17. 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

      1. Hi Daniel I am putting artesunate IV to my wife because he left 78 percent in test sensitivity,Do you know if there is any contraindication to mix it with DMSO,i can’t find anything about it. Thanks

  19. 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

      1. Hi Immanuel,

        What I would specifically avoid is to take Arte at the same time with food or supplements containing Iron. As long as that is not the case, I do not see a reason for not combining. I would also avoid taking at the same time of the day strong antioxidants such as ALA or NAC.

        Kind regards,
        Daniel

        1. @Daniel did you say not to take the iron with ARt you mean specifically together right? I believe we are to Never take artemisinin with iron or shortly after the iron.

          The iron first needs to be circulated and distributed into the blood in small amounts and act as both an activator and as a trojan horse meaning that cancer cells will absorb some of it (which is what we want).

          The artemisinin will then be activated by the small amounts of iron in the blood and should target any cells that have absorbed high concentrations of iron (cancer cells).

          If you take the artemisinin right after the iron then the artemisinin will react in the stomach with the large supply of iron and be spent and not reach the cancer. Is this your thought as well?

          1. HI Nicole,

            Indeed, I woudl clearly not take them together for the reasons you mentioned.

            The other question is if it makes sense to take Iron supplements or not, since the cancer cells have already high amounts of iron. Some like the idea to use Iron in the Arte protocol, others not. I think that if we decided to take it, we better take it from foods instead of supplements.

            Kind regards,
            Daniel

    2. Hi Immanuel,

      It contains Sweet Wormwood (Leaves) oil in addition to Arte which I find it helpful. In order to understand more about Sweet Wormwood (Leaves) oil you may want to read this review article: Essential Oil of Artemisia annua L.: An Extraordinary Component with Numerous Antimicrobial Properties https://www.hindawi.com/journals/ecam/2014/159819/

      There is a lot of research published on the bio-availability of Arte, e.g. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4020007/
      No it is not comparable with the IV form since that goes directly into the blood and will lead to higher plasma levels. I would use IV maybe 2-3 times/week for a few weeks cycle from time to time and during this time also the oral version. Or at least the days between the IV.

      Kind regards,
      Daniel

  20. 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

    1. Hi, I do not think this is a problem. Just that Super Arte is expected to be more effective because of the extra components it has inside. In any case, next to the Artemisinin capsule I would also add a capsule containing the whole plant of Arte Annua (as discussed in the post above). Kind regards, Daniel

  21. 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!

  22. 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

    1. Thank you so much for your kind offer to donate the Artesunate vials and the Hepalin capsules! If anyone is interested I will help them connect with you via e-mail. Kind regards, Daniel

    2. Hello Katja ,

      My son has recently diagnosed with Pancreatic Cancer I’m unfortunately I can’t afford purshasing Artesunate for him.

      Can you please donate the I.V. and the the Artesunate tablets for me ?

  24. Hi Daniel,

    As always this was an excellent article filled with lots of relevant info detailing all aspects of Artemisinia Annua. You mentioned that taking an Fe chelator prior to Artemisinin might be better to enhance efficacy of Artemisinin. WOuldn’t an Fe chelator be contra-indicated rather. May be I am missing something.

    Also, are there any interactions with Tetrathiomolybdate (which is a well known Copper Chelator but as one of its side effects can also lower Haemoglobin which is linked to potential drop in Fe).

  25. Hi Kapil,
    I know that I am not Daniel, but I also know he is traveling with limited availability, so I thought I would attempt to answer your question. You may find some of your answer here in Daniel’s earlier post: https://www.cancertreatmentsresearch.com/artemisia-annua-its-extract-artemisinin/#comment-5396 and also in the “Mechanism” section of the blog post itself. Basically, you want to keep the artemisinin out of contact with iron in the circulation. If the artemisinin comes into contact with iron in the circulation, there will be a free radical burst, but the artemisinin will be destroyed in the process. You want this to happen inside of the cancer cell, not before. In Daniel’s earlier post, he states that he believes cancer cells likely have enough concentrated iron without the need to take iron, so taking an iron chelator would clear iron from circulation, allowing the artemisinin to reach the tumor.

    Regarding TM, we almost used Tetrathiomolybdate(TM), and went as far as getting a prescription for it, but we opted not to use it at this time based on several factors related to my husband’s situation. TM depletes copper which is needed to produce RBCs and hemoglobin: https://en.wikipedia.org/wiki/Copper_deficiency. It may have some impact on iron absorption but it is not reported to cause iron deficiency. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3417757/. The anemia induced by TM is purely copper induced. That being said, those who have iron deficiency to the extent that it has lowered their RBC/hemoglobin count should correct it before starting TM. Those who have very low RBC/hemoglobin and/or WBCs as a result of cancer treatments may not be able to use TM since TM can drop WBC and RBC count even further. When people are using TM, ceruloplasmin and a complete blood count are used to monitor, if WBCs drop too low, the treatment is temporarily halted until they increase again.
    I hope that helps!

  27. Hi D and All-
    We would like to add some IV Artesunate to our weekly IVC. In a couple weeks my husband wants to do a week of daily IVC and I’d also like to use the IV Artesunate 3 times during that week. The suggested IV dose as documented by D is 300mg/day. I have access to 120mg Artesunate vials.

    My question is this: I noticed that for malaria treatment the Artesunate is either given as an IM injection or as an IV push ( but for the IV it is not typically given at a dose of 300mg in a single push for someone of my husband’s weight). We prefer to do a push rather than add more time and fluid on to the already lengthy IVC. I’m thinking of pushing in half of it before the IVC and the other half after the IVC. Does anyone see any potential issues with this?

    D, you have mentioned a drop in hemoglobin with artesunate/IVC combo, do you recall how much of a drop? My husbands tends to be just under or just over the normal range.

    Thank you!

    2. Hi Shanti,

      The drop in hemoglobin was gradual, from around 11 (normal range 11,9-14,6 g/dl) to around 7, during about one month (February to March 2014). After that we switched to DCA, Na Bic and Vitamin B17 (all intravenous) for 3 months and haemoglobin recovered so that in June 2014 was in a normal range, i.e. 13. I can not connect 100% the drop of hemoglobin with combo of Vit C and Arte, as there is one more point that I have to make: just after 2 months from surgery, in Jan 2014, there was a recurrence of about 4cm at the adrenal gland location. In June 2014, that became half (and latter was gone). Adrenal tumors are growing very fast, so another possibility is that the combo Vit C and Arte was not effective for us (and the drop of hemoglobin was due to fast growth of the tumor) and the next combo of DCA+B17+Na Bic was effective. However, because of the relative fast recovery of hemoglobin after switching to DCA+B17+Na Bic, I suspect it was Vit C +Arte too strong. Latter, we did Vit C and Arte but never combined and we never had this issue again.
      I hope these are not too many details, and it helps.

      I do not know anyone who did Arte bolus as you intend to do. If going for bolus, I would do it step by step, first with a smaller dose.

      Kind regards,
      Daniel

      1. Hi D,
        I appreciate you sharing your experience, the details are important, so definitely not too much detail. 11 to 7 is a pretty big drop in hemoglobin so we will monitor it closely if we do this therapy. We won’t go above 110mg artesunate in a push, which is the dose suggested for IV push malarial treatment, if we go higher in dose I will use a drip. I’ll also re-read the IVC post with info on iron chelation. My husband’s serum iron and ferritin tend to be at the low end of normal already.
        Warmly,
        Shanti
        PS This artemisia post is so comprehensive and useful, it is amazing to have this information pulled together in one place!

  29. Hi Johan,
    Thank you for the link and this very important consideration. In the study cited, the “high dose” vitamin C of 8.5 mg/kg/ day given to the mice along with the Artemether calculates to an HED of 54mg/day for a 170lb person. I am hoping that the high-dose vit C we are using in IV (75g) will have a different combination dynamic than low dose, as the action of the vitamin C is now pro-oxidant rather than antioxidant. This is the theory with some potential preliminary evidence outlined here: http://yaletownnaturopathic.com/how-does-artesunate-kill-cancer/, but truth be told, I’m not sure we know. I suppose I could leave the port in my husband and do a push or second drip in the second half of the day after the C has cleared from his system.

  30. Hi Shanti, thanks for the link to that article. Very interesting! Do you have more information on that study? Were any other treatments given alongside the ones mentioned? I’m asking because of this:

    Bastyr Breast Cancer Study Supplements
    No one “Bastyr protocol” exists, as researchers continue to investigate and refine approaches.
    Supplements used in one Bastyr protocol for breast cancer:
    IV artesunate
    IV ascorbic acid (vitamin C)
    Trametes versicolor (turkey tail mushroom)
    Tetrathiomolybdate for copper chelation
    Curcumin
    Bromelain
    Quercetin
    Low-dose naltrexone

    Best,
    Johan

    1. Hi Johan,

      The “preliminary Bastyr data” probably came from statements made by Dr. Standish in her work with Artesunate and IVC at Bastyr: https://bastyr.edu/news/general-news-home-page/2013/12/integrative-oncology-study-draws-attention-promising-results, but I have not seen any formal data from them on the combo, except that it is incorporated into some of their protocols: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5736066/.

      Dr. Paul Anderson discusses the synergy of IVC and artesunate and its mechanism here: https://www.naturalmedicinejournal.com/journal/2017-11/intravenous-therapies-oncology-practice-conversation-paul-anderson-nmd he discusses a study he allegedly took part in where both were used together, but I can’t actually find the study. The same study is discussed here, with a graph, but I still haven’t actually located said study: http://www.alternativecancertreatment.ca/artesunate-edmonton.

      This paper discusses co-administration of vitamin C and artesunate for malarial treatment: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4989825/. I think this quote gets to the crux of the issue, which is that vitamin C will likely protect against artesunate damage in its capacity as an antioxidant, but may potentiate it in its capacity as a pro-oxidant. This difference may also depend on the antioxidant reserves of the cancer cell.
      “Ascorbic acid has antioxidant properties and is reported to mop up free radicals. Since malaria infection imposes tremendous oxidative stress on the host, the antimalarials are often prescribed with vitamin C or similar antioxidant supplements. The antioxidant effect in erythrocytes has been reported to depend upon the presence or absence of glutathione. In the presence of glutathione, ascorbic acid has synergistic antioxidant activity against haem-mediated cell toxicity. In glutathione deficient red cells, as often happens in parasitized RBCs due to oxidative stress, ascorbic acid can react with iron or iron-containing compounds to generate hydrogen peroxide or hydroxyl radical and accentuate the hemolytic mechanisms in malaria.”

      After reading through Paul Anderson’s interview, it seems best to give the full Artesunate dose first and follow it up with the IVC. This is also consistent with the German clinic administration described by D. I can’t find any info on giving doses above approx 110mg as an IV injection so I’ll have to sell my husband on the pre-vitamin C artesunate drip.

        1. Hi D,
          We use green tea and pectasol which have some iron-chelating properties, but may not be enough. My husband also fasts the day before the IVC and until after the therapy. Ozone is used about half-hour beforehand.

          Have you used or spoken with anyone using Deferasirox or Desferal just prior to IVC and/or Artesunate? Tricky because we want the iron in the cancer cells, but not in the serum. As you know, some information indicates that iron administration timed correctly with artemisinin potentiates treatment.
          Thanks again,
          Shanti

          1. Hi Shanti,

            I have to check – I recommended this to a clinic and they were planning to implement EDTA chelation prior to high dose Vit C.
            Indeed, there are pros and cons regarding the use of iron prior to high dose Vit C or Arte like treatments. If we are not totally convince about one or the other way, we can also consider alternating the opposite approaches, e.g. one month take one approach and the other month switch to the other one.
            Iron is a key subject in cancer. As soon as I find more time I would like to focus on Iron in cancer and it’s manipulation – I did that in the past but I feel I should consolidate the info on this subject.

            Kind regards,
            Daniel

  32. Shanti, regarding iron admin prior to ART treatment:
    “I have been unable to give up thinking about the man with prostate cancer in Belgium who tried a unique approach to treatment with ART compounds. One day a week he took a supplemental iron pill with one meal and then took 700 mg of ART compounds that evening. He reported a substantial reduction in his PSA with this unique treatment approach. Unfortunately, there is no contact information to follow up on his long term results with this innovative approach. ”
    http://www.medicinacomplementar.com.br/biblioteca/pdfs/Cancer/ca-1735.pdf

    1. Hi Johan,
      It seems there are cases of ART compound efficacy both used with and without iron, but there is no doubt that maximizing the iron in the cancer cell increases efficacy. This is countered with the concern that too much iron in the serum and RBCs could reduce efficacy and cause RBC lysis. I have been giving my husband a 25mg iron injection once a month to help keep his ferritin and serum iron in the normal range, it also gives his hemoglobin a boost. I’m sure the cancer cells are also grabbing on to that same iron and storing it up. I read through the paper you linked to and info from D and, after some deliberation, I think we are going to try the artesunate initially without an iron supplement since the iron injection may be loading the cells, and see if we get a response. We will change our strategy if needed. My husband has done oral artemisinin combined with whole plant in the past, but more than 2 days in a row cause stomach upset. We probably won’t start this for a few more weeks as we wait for the medication to arrive. As always, thank you for taking the time to help and provide useful information, tips and important aspects I hadn’t considered.
      Warmly,
      Shanti

  37. Hi All-
    Here are 3 great resources on Artesunate IV administration from Paul Anderson, who has a significant amount of clinical experience:

    Artesunate Monograph- Covers initial administration building up to full dose, drip vs push, monitoring, complication and synergism with vitamin C. Also discusses iron (Anderson is of the opinion that it doesn’t need to be given unless clinically indicated due to anemia)
    https://www.academia.edu/20316500/Artesunate_Monograph

    Answers some additional questions on Artesunate
    https://www.consultdranderson.com/iv-artesunate-considerations-cont/
    https://www.consultdranderson.com/b17-artesunate-iv-vitamin-c-cont/

  38. Dear Daniel and all,
    I hope you all enjoy the new year holiday!

    I was looking further at Artemisia annua, which seems very promising and was also recommended in the 2nd opinion report we got, as another option for chloroquine (together with using Metformin).

    I happen to see some warning here, about possible cause of seizures due to use of Artemisia annua:
    https://www.mskcc.org/cancer-care/integrative-medicine/herbs/artemisia-annua
    “Do not take if: You are taking antiseizure medications: Artemisia can induce seizures making such medications less effective.”
    and…
    https://www.webmd.com/vitamins/ai/ingredientmono-729/wormwood
    “Seizure disorders, including epilepsy: Wormwood contains thujone, which can cause seizures. There is concern that wormwood might make seizures more likely in people who are prone to them”

    looking at this “thujone”, perhaps it is more relevant to another type of Artemisia?
    https://en.wikipedia.org/wiki/Thujone
    “Thujone is found in a number of plants… and wormwood, most notably grand wormwood (Artemisia absinthium)”.

    https://en.wikipedia.org/wiki/Artemisia_absinthium
    Remark – this becomes more confusing to me, since in this page it is mentioned that “Medicinal extracts of wormwood have not been shown to cause seizure or other adverse effects at usual doses”.

    So I’m not sure, is this warning less related/ not related to Artemisia annua?
    Have you heard of any case of seizures due to use of Artemisia annua?

    Many thanks!
    Best wishes,
    Nissim

    1. Dear Nissim,

      Nice to hear from you! I hope you had a good holiday too!
      Thank you for sharing your concerns regarding Artemisia Annua and it’s possible impact on the effectiveness of seizure medication.
      I am not aware of any such effects and I haven’t heard anyone reporting anything on this line.

      Kind regards,
      Daniel

  39. Dear Daniel,

    Thank you for the information.
    As there’s a lot “traffic” of information, sharing of ideas and experience in this blog, it is good to get such an opinion!

    Best wishes and a successful year,
    Nissim

  40. Hi Daniel,

    As there are missing references re autoinduction of Artemisinin and I had a related discussion somewhere else:
    “…Artemisinin oral clearance increased 5.3-fold (P <.001) by the tenth day of administration…."

    https://www.researchgate.net/publication/10675994_Artemisinin_autoinduction_is_caused_by_involvement_of_cytochrome_P4502B6_but_not_2C9?fbclid=IwAR0wAOuDrbPHKsNSAaU4PV7nntF_qvWeI7SwCynbsTWc0qTbrxEorM6IEfM

    I hope that one helps.

    Cheers,
    R.

  41. Hi Daniel and all!
    How are you?

    We were quite intense this week, as my brother had another (4th) brain MRI on Sunday and analysis with his oncologist yesterday.
    The MRI demonstrated stability after additional 2 chemo cycles (3 long months).
    This month it will 1 year with the GBM cancer and for now NO NEWS IS GOOD NEWS!

    This week we also got 200 gr of dried Artemisia annua whole plant and I have some questions about adding Artemisia into our chemo and alternative protocol:

    Q1 – we plan to use it along the day (3-4 times x 250ml) as “tea” extracted with warm (not hot) water and I was thinking of using it 1 week on & 1 off. any other suggestions?

    Also, as I understand Artemisia is a (strong?) prooxidant and as such I am not sure how to optimise its use in combination with chemo and our protocol:
    Q2 – is it ok or even recommended to use Artemisia on the week of chemo? (1 week of TMZ + CCNU every 6 weeks)
    Q3 – what about using Artemisia while taking other daily antioxidants (which we stop during the chemo)? We prefer not to stop using these while taking Artemisia, so how best to combine?
    Q4 – Just to be sure, I understand that all the following, which we use regularly or alternately are antioxidants? (in some level) –
    Boswellia, Curcumin, Berberine, Melatonin, Vit E, Vit D3, Omega 3, Astragalus, Milk thistle, EGCG, Bacopa monnieri, Honokiol and Ashwagandha.

    Many thanks!
    Wishing everyone stability and improvement of health!!!

    Best regards,
    Nissim

    1. Hi Nissim,

      Very nice to hear about the “no news”!

      I would use Artemisia regardless of chemo or not. Cycles are a great idea indeed, specifically because it may be a little heavy on the liver when taken continuously for long time. I would use Artemisia also during the days with Curcumin, etc. but just try to take them the tea at least half an hour apart from the others if possible and on empty stomach.

      All the best to you and your brother dear Nissim!

      Kind regards,
      Daniel

      1. Dear Daniel,

        Thank you very much for the tremendous support and encouragement along the way!
        This “project” is too hard and too complicated to deal with alone and I don’t have enough words to thank you especially and everyone who support us and advise in this amazing blog!

        All the best!
        Nissim

  42. Hi Daniel

    I don’t know whether paper below is relevant to this article. But just in case below it is:
    The Synergistic Anticancer Effect of Artesunate Combined with Allicin in Osteosarcoma Cell Line in Vitro and in Vivo
    https://www.ncbi.nlm.nih.gov/pubmed/24083713

    unfortunately both artemisia and garlic were administered IP, so this greatly impacts applicability for humans due to Garlic absorption.

      1. Hi Daniel

        Thank you.

        Yes, i went through this topic in the past. We have a chance to apply garlic intratumoral injections as tumor is easily accessible , but i am not capable of nether decision nor application. May be such option could be postponed.

        Kind Regards

        Asaf

  43. Hi @Daniel,

    I have received the liposomal quercetin today, has any sense to take high dosage of quercetin the four days that I do dried leaves plus 500 x 2 artemisinin extract?

    For the next rounds I have ordered Artemix Artemisinin Complex 140mg, how many caps daily would be a good therapeutic dosage?

    Thank you!

    Kind regards Inaki

  44. Hey Daniel,

    My mom has stage IV cervical cancer, she has 6 small baby tumors in her lungs. They are so small they have not been able to take biopsies, but my sister and I are hypothesizing it’s her cervical cancer that metastasized to her lungs after her hysterectomy.

    I’m very confused about Chloroquine and Artemisin, you said that they are synergistic? We have her on Hydroxychloroquine for autopaghy inhibition. We want to start her on Artemisin but you said in the chloroquine/hydroxychloroquine post that they may interfere with iron. They way Artemisin works is by coming into the cell via iron and wrecks havoc. How is it synergistic if the iron cannot come into the cell anymore due to Hydrocychloroquine? Wouldn’t the two drugs cancel each other out? We really want something for autophagy for when the cells are dying and the debris won’t be recycled by new cancer cells. What do you suggest?

    Sorry I spent all day trying to figure this out and got nowhere,

    Mihaela

    1. Dear Mihaela,

      First, with this I would like to thank you for the donation that helps a lot with maintaining this website which due to high traffic requires a good amount of resources to keep it up and running.

      Your question is of-course a very good one. Here is how I see the mechanisms that can explain both a synergy potentials and an antagonistic activity:

      HCQ inhibits autophagy leading to the interruption of degradation of damage mitochondria which in turn leads to increase ROS generation by the damage mitochondria. HCQ on the other hand also inhibits ferritin degradation in lysosomes, lowering the labile iron pool in the cytosol. https://dm5migu4zj3pb.cloudfront.net/manuscripts/115000/115301/cache/115301.1-20140626150537-covered-253bed37ca4c1ab43d105aefdf7b5536.pdf But Arte can induce lysosomal degradation of ferritin https://www.nature.com/articles/s41418-019-0352-3 that leads to increase ROS
      This can lead to two different mechanisms of ROS generation that can work in synergy https://pubmed.ncbi.nlm.nih.gov/25308836/

      It’s true that this can work only for a certain amount of time as long as Arte has on what to act to generate ROS. At some point there will be no ferritin left to degrade since HCQ inhibits further accumulation of iron (that can be stored in ferritin form) since iron from iron-saturated transferrin needs a low pH to be released, within the endosome, while HCQ interferes and alkalizes with endosomal.

      Latter, as there is no ferritin left for Arte to do it’s job, from an anti-cancer potential we are only left with HCQ to act as an anti cancer agent.

      Therefore, it’s a time dependent activity of this combo, first working in synergy towards increasing the ROS level, latter working in antagonism. Actually maybe I should not say antagonism since they do not cancel each other out, but just one of them will continue working only, i.e. HCQ.

      We could also argue that this is the theoretical picture, and that in real life HCQ does not totally inhibit the iron deployment into cells and the ferritin degradation, but only slows them down.

      If we stop HCQ to start Arte we may need to wait a few weeks for that to be totally out of the body, since the half-time of HCQ is some weeks.

      Another strong autophagy inhibitor could be this one but it’s an antibiotic https://www.cancertreatmentsresearch.com/community/autophagy-inhibitors/clarithromycin-is-an-autophagy-inhibitor/#post-2885

      A strategy along the line of ROS generation that may be relevant is discussed here https://www.cancertreatmentsresearch.com/modulating-the-yin-and-yang-energy-of-cells-to-fight-cancer-pro-oxidant-strategy/

      I hope this answers your question.

      Kind regards,
      Daniel

      1. Hi Daniel,

        No problem, you deserve it, your work is impressive to say the least. Since you have high traffic you should definitely be making money from it not the other way around. But you probably don’t want any bad advertising and for people to buy products that are not vetted.

        I interpreted how the ART got into the cytosol from the interstitial space, I don’t know why. I thought that the free iron bound to ART which in turn bound to the transferrin-receptor and together they entered the cell by endocytosis. Which makes no sense because there should not be any free iron, it’s transferrin. Then I thought well how is ART going to get out and cause ROS since the HCQ increase the pH in the vacuole not releasing ferritin, therefore not releasing ART in the cytosol either. The second mechanism of action for HCQ that you mentioned is what I was worried about. This was all in my head which is all wrong.

        I found this awesome paper that explains everything.
        http://microbialcell.com/researcharticles/the-molecular-and-cellular-action-properties-of-artemisinins-what-has-yeast-told-us/

        First of all ART is permeable to the cell membrane, so it enters through lipid layer no problem. ART doesn’t like being in the cytosol and goes to any lipid membrane since it’s hydrophobic. I now understand why ART induces lysosomal degradation of ferritin, therefore releasing free iron in the cytosol which is toxic for the cell.

        ART is reduced or activated by Fe2+, heme and Copper. Activated ART causes ROS, the apoptosis. If HQC reduces ferritin then there’s less heme to activate it, supply chain issue. But we just said that there would be more free iron in the cell from the degradation of ferritin, therefore it ART could be activated that way too for a period of time like you said.

        The paper suggests there’s another mechanism of action but only for yeast and malarial mitochondria. Again attacking the lipid membrane of the mitochondria. No energy factory, cell goes bye bye. Maybe just maybe if there’s less heme and at some point less free iron to activate ART, then it can focus on the anti-mitochondrial pathway even thought the paper said mammalian cells mitochondria didn’t respond to it.

        I do worry about iron deficiency anemia from the HCQ, do you suggest iron supplementation? Maybe we’ll just monitor her RBC count. Increasing iron will negate the anti-mitochondrial pathway.

        I definitely don’t want to stop HCQ. Definitely synergy in the beginning both causing ROS, then later maybe ART attacks the lipid membranes including the mitochondria since there’s less activation from heme or Fe2+, where else would it go, to the lipid layer of course. This is my hope.

        I thought about vitamin C for better iron absorption, but I don’t want Vitamin C rescuing the cell from ROS. Then I thought about high dose IV vitamin C but I don’t want her going out all that much with the coronavirus and it’s quite expensive treatment. I haven’t looked into liposomal vitamin C to see if bioavailability is equivalent to IV. There’s a lot of YouTube videos to make your own liposomal vitamin C as well. I wonder if we can get it high enough to generate hydrogen peroxide, that way we’d have even more ROS AND it will help the absorption of iron. How do you feel about liposomal drugs? There’s liposomal Artemisin and Curcumin, is it worth it?

        I’ll look into Clarithromycin as well.

        We started her on a lot of medications and supplements and ketogenic diet based off of Jane Mcclelland book – how to starve cancer. Same idea, cancer is a metabolic disease not genetic. Her last scan her biggest tumor went from 9mm to 7mm and all the other ones stayed the same so it’s working. Before that grew 1mm every 3 months. I worry about resistance and the cancer getting smart so that’s why I want to be as aggressive as possible.

        Thanks for all you knowledge!

        Mihaela

        1. HI Mihaela,

          Thank you so much. The high traffic indeed generates costs and not profits. Donations like yours help keep this running. I am now trying to convert this in a sustainable way for this kind of knowledge and be able to do much for for people without expecting donations. That is by (very soon) starting up a supplement company, which is my last and probably successful try to continue this in a sustainable way.

          Thanks a lot for sharing your knowledge on Art. That is very helpful.

          Regarding Vitamin C liposomal, I do not see that as an alternative to intravenous. But here is an idea how you could try to achieve that with oral Vitamin C, by combining DHA +Vitamin C + Liposomal Vit C https://www.cancertreatmentsresearch.com/community/postid/2747/

          During the past years I looked a lot into Liposomal options. Also now when starting up the supplement company I had to look into that to select partners to work with. I even had a deep discussion about this a few hours ago with a friend who is an expert in this. The conclusion is that Liposomal oral formulations are these days coming from so many different type of suppliers and most of them are not having the right quality and profile to induce 1. a high blood level of the drug 2. maintain a level that reaches tumors. First depends on the quality and second specifically on the formulation of liposomes since most of them will be eaten up by macrophages before getting to the tumor. PEG formulations are less affected by macrophages.
          So when it comes to oral formualstions my rule is like this ~75% of target dose use non-liposomal products and if budget allows ~25% use liposomal or other formulations that promise much higher absorption (the second will be a lottery ticket in case the product will rely deliver what is promised).
          So, I like liposomal but what is commercially available is questionable. And since here we deal with a matter of life, we do not want to fully depend on the promise of various food supplement companies. Intravenous formulations on the other hand can be often very relevant.

          Yes, Mihaela, Jane’s book is a good start into the world of repurposed drugs and metabolic cocktails. And it’s great to hear that the results are showing improving effectiveness. After all these years, to me is clear that 1. metabolism is one of the most important perspective to address cancer in a more controllable way 2. cocktails of drugs and supplements (oral and IV) help extend and improve life.

          Thank you!

          Kind regards,
          Daniel

        2. Synergic Effects of Artemisinin and Resveratrol in Cancer Cells:
          https://pubmed.ncbi.nlm.nih.gov/25048878/?dopt=Abstract

          “The combination of the two drugs also markedly reduced the ability of cell migration. Apoptosis analysis showed that combination of ART and Res significantly increased the apoptosis and necrosis rather than use singly.

          Additionally, ROS levels were elevated by combining ART with Res.”

  45. Hi Daniel,

    Well I hope your supplement company is off to a good start. I can’t imagine the amount of capital it would take to start something like that, hopefully you have some good investors.

    That’s a shame, I really wished liposomal drugs had better bioavailability than what they claim. Marketing <– for your supplement company. We will hold off on Vit C for now.

    Thank you responding and all that you do!

    Mihaela

    1. HI Mihaela,

      Thank you. I did found people willing to help even if the goal is to have most profits allocated to research projects and accelerate their translation to clinical space.
      More than the capital, is so much time that it takes to find good suppliers that are willing to make the products as I think its best.

      Regarding liposomal formulations, they can be good solution to increase bio-availability of supplements – and I would add some of those as discussed above as long as they are taken from a good supplier – but I would clearly not replace intravenous treatment with those.

      Kind regards,
      Daniel

  46. Hello,

    I’ve been administering Artemisia annua (Luparte) to my dog who has disseminated histiocytic sarcoma and I was hoping to ask you for some clarification on your statement that “Artemisinin compounds inhibit their own absorption”. I’ve been researching this but I haven’t found anything useful and since the supplement manufacturers doesn’t recommend suspending the treatment to increase absorption, I was wondering if you have any references for this? The treatment doesn’t seem to be very effective until now, so I’m trying to figure out if we’re doing everything correctly…

    Thank you!
    Claudia

    1. Dear M,

      The delivery of drugs and supplements via suppository is a good idea indeed. Making a suppository is very easy:
      – buy suppository molds – available online
      – buy organic coconut oil
      – warm up a little the coconut oil so that it becomes fluid, and after that mix the active ingredient at the concentration you like. Here you will need to check how much oil goes into one mold. If it goes 1ml oil, and you want to have a dose of 1000mg Curcumin in one suppository, you will need to make sure you mix this concentration in the oil. So if you want to prepare 100 suppositories at 1000mg each, you will need to mix 100g Curcumin in 100 ml coconut Oil (in this example)
      – the mixture is injected into the suppository mold using a syringe
      – the suppository molds containing the oil, need to be stored in the refrigerator overnight, before starting to use them – the coconut oil will become solid overnight and the next day, the suppository will be ready to be used.

      Kind regards,
      Daniel

  48. Hello,

    I have been searching for intravenous Artemisinin therapy for breast cancer, now found this site finally. I discovered the cancer back in 2019, full remission due to chemotherapy, then radiotherapy, operation, now hormone therapy (ER+, PR+, HER2-), currently symptom free but the residual tumor cells are still in my body..! When I found out that I had breast cancer I started to take Artemisinin orally and I literally felt better, it even stopped the cancer to spread to nearby organs…! So my cancer cells are basically sensitive to Artemisinin (=they are being destroyed by intake artemisinin annua) and it would be really important to kill the remaining cancer cells in my body with it. I am taking the supplement (orally) but not effective enough – would be better to have it intravenously. I don’t know where this treatment can be obtained for a Hungarian – I would be willing to travel abroad, even pay for it as it is not available in Hungary. Can you advise please?
    Thank you very much.

    1. Dear Budai,

      Thank you for sharing your experience with Arteisinin.

      Here is a compounding pharmacy in Germany (probably the largest) from where most of the cancer clinics are sourcing their intravenous substances, including Artemisinin:

      Burg-Apotheke
      e.Kfm. Apotheker Uwe-Bernd Rose
      Frankfurter Straße 7
      61462 Königstein im Taunus
      Tel.: +49 (0 )6174-95565-0
      Fax: +49 (0) 6174-95565-65
      [email protected]

      They sell Artesunat 100mg, 250mg, and 500mg vials. It is not sold on prescription, I think.
      You can ask a clinic in Hungary to buy it and administer it to you, but it woudl be best to go to a clinic that already has experience with it. One such a clinic you can find in Romania https://www.imuno-medica.ro/ They have many treatment options and are probably the largest integrative clinic that I know in Europe. Probably the cheapest since they are running based on donations from a billionaire that wants to help people.
      The other option is to search for German clinics such as those listed here https://www.cancertreatmentsresearch.com/clinics/

      I hope this helps.

      Kind regards,
      Daniel

      1. Thank you very much Daniel! My worry is that in Hungary it is not allowed to provide with this method – as this is not a standard procedure here yet. Not fitting the protocol.

        Erzsébet

  49. One more question Daniel… I contacted this German Pharmacy and they send me the pricelist with the available quantities… as you said I can order just by sending an email order. The biggest quantity is 500 mg of Artemisinin… my concern is that isn’t that too little amount in the bloodstream.. ( I mean capsules contain bigger doses…)? More importantly, do you have any knowledge for how long the Artemisinin circulates in the body after being injected intravenously (would be good to know the timelapse between multiple rounds..) ? Thanks for your reply. Have a nice day.
    Erzsébet

  50. Do you think Artemisia Annua could work for a vestibular schwannoma (benign brain tumor)? It appears to have activity specifically against schwann cells, inducing necroptosis by inhibiting apoptosis. It makes me concerned about also using supplements like curcumin and sulforaphane which work via apoptosis. Also, where the heck are people sourcing powdered Artemisia in the USA?

    https://www.nature.com/articles/cddis2014434
    Established as a potent anti-malaria medicine, artemisinin-based drugs have been suggested to have anti-tumour activity in some cancers. Although the mechanism is poorly understood, it has been suggested that artemisinin induces apoptotic cell death. Here, we show that the artemisinin analogue artesunate (ART) effectively induces cell death in RT4 schwannoma cells and human primary schwannoma cells. Interestingly, our data indicate for first time that the cell death induced by ART is largely dependent on necroptosis. ART appears to inhibit autophagy, which may also contribute to the cell death. Our data in human schwannoma cells show that ART can be combined with the autophagy inhibitor chloroquine (CQ) to potentiate the cell death. Thus, this study suggests that artemisinin-based drugs may be used in certain tumours where cells are necroptosis competent, and the drugs may act in synergy with apoptosis inducers or autophagy inhibitors to enhance their anti-tumour activity.

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