Everything Wormwood/Artemisinin/Artemisia

Tarmander

Tarmander

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I have been using a wormwood tincture for the last week and had some pretty cool effects. I have seen info sprinkled around the forum, but not a dedicated thread. Here is a list of studies, feel free to add to it:

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Artesunate alleviates hepatic fibrosis induced by multiple pathogenic factors and inflammation through the inhibition of LPS/TLR4/NF-κB signaling p... - PubMed - NCBI
•Fights Endotoxin and that toll like receptor crap

Artemisinin Blocks Prostate Cancer Growth and Cell Cycle Progression by Disrupting Sp1 Interactions with the Cyclin-dependent Kinase-4 (CDK4) Promoter and Inhibiting CDK4 Gene Expression

Activity of Artemisia annua and artemisinin derivatives, in prostate carcinoma. - PubMed - NCBI
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•Ray from email exchange: "I think the first safer thing would be flowers of sulfur for about 3 days, then the herbs [wormwood, black walnut hull and cloves] if you don't see results with the sulfur."

•I have noticed quite the psychological effect come over me after about 30 minutes of ingestion. I get super focused, lazer like, and become very very relaxed. Almost verges on feeling a bit high. Also reminds me of the feeling I used to have as a kid looking at something new...no worries, no extraneous thought, and this added element to whatever I am perceiving as being bigger then it seems in front of me. Dopamine? Maybe

Would love to hear experiences and other research that people have found.
 
L

lollipop

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Maybe @charlie could merge the other recent thread about the loading dose with this one? Lots of great info on that thread. This thread you have created seems to have a bigger theme and might be the good overarching thread. What do you think @Tarmander? Are you okay with adding that thread info in here?
 
OP
Tarmander

Tarmander

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@lisaferraro You know when I made this thread I did not see that other one as it did not show up with Wormwood in the title. I would be down to merge the threads but I like a more general one then just about loading doses. It seems multiple people are on the same wavelength!
 
L

lollipop

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Tarmander said:
@lisaferraro You know when I made this thread I did not see that other one as it did not show up with Wormwood in the title. I would be down to merge the threads but I like a more general one then just about loading doses. It seems multiple people are on the same wavelength!
Click to expand...
Yeah I agree! That is why I suggested merging that thread into yours as yours is a broader topic :):

Edit: saw an opportunity but didn’t want to be presumptuous and thus asked you.
 
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DaveFoster

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It's the foulest thing I've ever tasted, and there's the lowest circle of hell reserved for constant filtering of wormwood into the sinner's orifice.
 
Constatine

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DaveFoster said:
It's the foulest thing I've ever tasted, and there's the lowest circle of hell reserved for constant filtering of wormwood into the sinner's orifice.
Click to expand...
Lol. I love wormwood but it might make me tired with continued dosing.
 
burtlancast

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Amazoniac

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burtlancast said:
Yes, it's very simple: absinthium is the species used for digestive problems ( as well as one of the main ingredients in the fabrication of absinthe) but has no activity against malaria or cancer, contrary to annua.
Click to expand...
I was confused because there are a few experiments using absinthium for cancer as well. Thank you! ♥

- https://www.cancertreatmentsresearch.com/artemisia-annua-its-extract-artemisinin/
Artemisia Annua, Artemisinin & 2015 Nobel Prize in Medicine
Background:

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

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

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

Furthermore, artemisinin and artemisinin-derived compounds have been shown to exhibit antiviral, anti-inflammatory, anti-parasitic, anti-allergic, anti-fibrotic, anti-arrhythmic, immunoregulatory and contraceptive actions, and the agents were found to be active for autoimmune diseases (Ref1., Ref.2, Ref3).
During the past years, Artemisinin has also also been identified as a substance with a strong anti cancer potential in various cancer cells such as

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

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

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

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

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

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

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

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

Case reports in animals:

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

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

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

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

Case reports or clinical trials in human:

  • A Randomised, Double Blind, Placebo-Controlled Pilot Study of Oral Artesunate Therapy for Colorectal 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.
Note that the studies above used one component only, i.e. Artesunate, and not the whole plant.

Anecdotal stories in humans:

Mechanism:

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

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

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

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

Other mechanisms behind Artemisinin compounds: reduction or inhibition of

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

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

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

Formulation:

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

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

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

Administration & Dose:

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

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

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

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

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

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

  • Artemether + Lumefantrine (Ref.)
  • Dihydroartemisinin + Piperaquine (Ref.)
Summary from literature:

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

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

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

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

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

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

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

Synergy:

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

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

Source and Price:

Artemisia annua – whole plant extract – oral capsules:

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

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

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

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

Storage:

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

References:

Artemisinin: Discovery from the Chinese Herbal Garden

Pharmacogenomics of Scopoletin in Tumor Cells

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

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

Artemisia annua – Pharmacology and Biotechnology

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

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

Dried whole plant Artemisia annua as an antimalarial therapy.

The Surprising Efficiency of Artemisia annua Powder Capsules

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

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

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

Anticancer Effect of AntiMalarial Artemisinin Compounds

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

Artesunate induces necrotic cell death in schwannoma cells

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

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

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

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

- http://www.tandfonline.com/doi/full/10.3109/13880209.2010.497815
 
Amazoniac

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Dried-leaf Artemisia annua: A practical malaria therapeutic for developing countries? (robbed from the first link of the previous post)

"We and others proposed direct consumption of A. annua either as a tea infusion[16–19] or by oral consumption of the leaves[20–24]. In contrast to the oral consumption of pure artemisinin, we showed that the presence of plant material significantly enhanced appearance of artemisinin in the serum of healthy and Plasmodium chabaudi-infected mice[22]. Because of the plethora of mild antimalarial compounds naturally present in the dried leaves of the plant, we have termed this orally consumed dried leaf therapeutic plant-based artemisinin combination therapy, or pACT. These whole plant approaches are similar to the more than 2000 year traditional use of the plant by the Chinese[25]."

"Recently, Elfawal et al[23] measured parasitemia in mice infected with P. chabaudi that were fed two different doses (0.6 or 3.0 mg artemisinin; 24 and 120 mg/kg) of either pure artemisinin in mouse chow or as pACT. Artemisinin delivered via pACT was at least five times more effective, and with a longer lasting response, than pure artemisinin in reducing parasitemia. Excluding artemisinin there are > 600 phytochemicals that have been identified in Artemisia annua[35], but there is currently a lack of information on the chemistry, effect of the preparation method (harvesting, drying, storage, etc.), and overall bioavailability of these chemicals[36]."

"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."

"[..]Compared to the usual large pure 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[39], patients treated with pACT had generally better therapeutic outcomes (Table 2). The measured pACT cure rate also was comparable to or exceeded other results using pure artemisinin[40,41], and similar levels of artemisinin (artesunate, artemether, etc.[42]). Furthermore, the positive therapeutic response using pACT appeared somewhat independent of dose beyond the second level of dose tested (Table 2[20]). Although oral doses used in the ICIPE[20] trials were far less than any tea studies, levels of recrudescence were much lower than tea and often better than in studies using pure artemisinin[39] (Table 2). Indeed, about 100 total mg of total artemisinin delivered via pACT for a full malaria treatment yielded a better recrudescence rate than the 4000 mg of pure artemisinin used by Giao et al[39] (Table 2). This 40-fold difference correlates well with the early pharmacokinetic studies by Weathers et al[21] that showed 45-fold enhanced bioavailability of the drug when delivered as pACT.

These results suggest that the natural phytochemical blend in pACT is important especially when orally administered as tablets. The results are also consistent with a study in China on mice infected with P. berghei, which compared the effects of pure artemisinin with crude A. annua extracts[43], and the studies by Elfawal et al[23] and Weathers et al[22]. In all three studies the administered products had comparable levels of artemisinin, but crude preparations and pACT were at least 3.5 times more effective in reducing parasitemia than pure artemisinin, suggesting a synergistic role for non-artemisinin constituents in the extracts and orally consumed dried leaves."

"There are as yet no pharmacokinetic studies of pACT in humans. In a small PK study of healthy mice fed artemisinin there was about 45-fold more artemisinin delivered via pACT than when delivered as the pure drug[21]."

"The presence of plant material affected artemisinin pharmacokinetics. At 60 min no artemisinin was detected in serum of mice fed pure artemisinin at 100 mg/kg body weight. When plant material was present, however, as mouse chow or A. annua pACT, artemisinin level in the serum rose to 2.44 and 4.32 µg/mL, respectively, demonstrating that the presence of plant material, even mouse chow, had a major positive impact on the appearance of artemisinin in the blood[22]."

"Using the dosing information obtained from the Kenyan human malaria trial[20], each adult needs about 100 mg artemisinin total over 6 d for a malaria treatment, so for A. annua leaves with 0.7% artemisinin, 15 g of dried leaves would be needed for a 6 d treatment course." "For leaves containing 1.4% artemisinin, only 7.5 g of dried leaves are required, so from a hectare of land producing 2 tons of leaves twice as many patients could be treated (Table 3)."

"Considering that A. annua is nontoxic and safe to consume orally, dose may not have to be adjusted for children. On the other hand, the leaves taste bitter, so masking the taste, perhaps with sugar, should help with pediatric treatment. Our recent simulated digestion study showed that adding table sugar (sucrose) to pACT did not significantly alter the amount of artemisinin released after digestion, with the added benefit of doubling the amount of flavonoids released[115]."​

Weathers PJ[Author] dried - PubMed - NCBI

http://www.who.int/medicines/publications/traditional/ArtemisiaStatement.pdf

"Due to the instability of artemisinin in raw materials of Artemisia annua L, the leaves need to be stored in cool conditions — preferably below 20°C. Most malaria endemic countries have warm climates and people generally lack access to refrigeration, so it is difficult for patients to keep artemisinin-containing tea bags under 20°C in their homes.

Artemisinin contained in raw materials of Artemisia annua L is unstable when heated. Boiling water to make tea may cause it to lose any anti-malarial properties it may have."​

@soontobecomeaherbalist
 
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Mossy

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Amazoniac said:
I was confused because there are a few experiments using absinthium for cancer as well. Thank you! ♥

- Artemisia Annua, Artemisinin & 2015 Nobel Prize in Medicine – Mihaela Catalina Stanciu Foundation for Life
Artemisia Annua, Artemisinin & 2015 Nobel Prize in Medicine
Background:

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

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

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

Furthermore, artemisinin and artemisinin-derived compounds have been shown to exhibit antiviral, anti-inflammatory, anti-parasitic, anti-allergic, anti-fibrotic, anti-arrhythmic, immunoregulatory and contraceptive actions, and the agents were found to be active for autoimmune diseases (Ref1., Ref.2, Ref3).
During the past years, Artemisinin has also also been identified as a substance with a strong anti cancer potential in various cancer cells such as

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

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

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

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

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

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

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

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

Case reports in animals:

Treatment of Iron-Loaded Veterinary Sarcoma by Artemisia annua. Treatment of Iron-Loaded Veterinary Sarcoma by Artemisia annua. - PubMed - NCBI

“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. A Randomised, Double Blind, Placebo-Controlled Pilot Study of Oral Artesunate Therapy for Colorectal Cancer. - PubMed - NCBI
    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. Artesunate in the treatment of metastatic uveal melanoma--first experiences. - PubMed - NCBI
    We report on the first long-term treatment of two cancer patients with ART in combination with standard chemotherapy. These patients with metastatic uveal melanoma were treated on a compassionate-use basis, after standard chemotherapy alone was ineffective in stopping tumor growth. The therapy-regimen was well tolerated with no additional side effects other than those caused by standard chemotherapy alone. One patient experienced a temporary response after the addition of ART to Fotemustine while the disease was progressing under therapy with Fotemustine alone. The second patient first experienced a stabilization of the disease after the addition of ART to Dacarbazine, followed by objective regressions of splenic and lung metastases. This patient is still alive 47 months after first diagnosis of stage IV uveal melanoma, a situation with a median survival of 2-5 months.
Note that the studies above used one component only, i.e. Artesunate, and not the whole plant.

Anecdotal stories in humans:

Mechanism:

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

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

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

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

Other mechanisms behind Artemisinin compounds: reduction or inhibition of

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

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

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

Formulation:

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

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

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

Administration & Dose:

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

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

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

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

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

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

  • Artemether + Lumefantrine (Ref.)
  • Dihydroartemisinin + Piperaquine (Ref.)
Summary from literature:

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

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

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

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

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

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

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

Synergy:

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

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

Source and Price:

Artemisia annua – whole plant extract – oral capsules:

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

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

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

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

Storage:

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

References:

Artemisinin: Discovery from the Chinese Herbal Garden

Pharmacogenomics of Scopoletin in Tumor Cells

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

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

Artemisia annua – Pharmacology and Biotechnology

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

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

Dried whole plant Artemisia annua as an antimalarial therapy.

The Surprising Efficiency of Artemisia annua Powder Capsules

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

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

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

Anticancer Effect of AntiMalarial Artemisinin Compounds

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

Artesunate induces necrotic cell death in schwannoma cells

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

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

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

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

- http://www.tandfonline.com/doi/full/10.3109/13880209.2010.497815
Click to expand...
Thank you, Amazoniac, for the detailed info.

I’m surprised there has been no more discussion about the “iron-dependent” aspect mentioned throughout—considering the anti-iron position within Peating. Does anyone have any thoughts or insight, whether this could be the rare scenario where iron may be wanted?

I did search the site for any discussion on it, and though I did see @bzmazu and @Sheila chatted about it breifly, I didn’t see anything definitive on it. Maybe because there isn’t, as far as this forum goes.

Also, I stumbled upon an interesting comment within an A. annua user review on amazon, which I will research further as I get a chance:

“...it prevents your body from breaking down nicotine, caffeine and alcohol, so just exercise caution.”
​
Any thoughts on this would be great, as well.

I’ve just started taking A. annua. I know others are taking it as well, and thought these questions may be of interest.
 
B

Braveheart

Guest
Mossy said:
Thank you, Amazoniac, for the detailed info.

I’m surprised there has been no more discussion about the “iron-dependent” aspect mentioned throughout—considering the anti-iron position within Peating. Does anyone have any thoughts or insight, whether this could be the rare scenario where iron may be wanted?

I did search the site for any discussion on it, and though I did see @bzmazu and @Sheila chatted about it breifly, I didn’t see anything definitive on it. Maybe because there isn’t, as far as this forum goes.

Also, I stumbled upon an interesting comment within an A. annua user review on amazon, which I will research further as I get a chance:

“...it prevents your body from breaking down nicotine, caffeine and alcohol, so just exercise caution.”
​
Any thoughts on this would be great, as well.

I’ve just started taking A. annua. I know others are taking it as well, and thought these questions may be of interest.[/QUOTE

To answer some questions on iron....
Scientists develop new cancer-killing compound from salad plant

According to Dr Henry Lai, it is not necessary to supplement additional iron.
Click to expand...
 
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burtlancast

burtlancast

Member
Joined
Jan 1, 2013
Messages
3,263
Amazoniac said:
I was confused because there are a few experiments using absinthium for cancer as well. Thank you! ♥

- Artemisia Annua, Artemisinin & 2015 Nobel Prize in Medicine – Mihaela Catalina Stanciu Foundation for Life
Artemisia Annua, Artemisinin & 2015 Nobel Prize in Medicine
Background:

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

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

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

Furthermore, artemisinin and artemisinin-derived compounds have been shown to exhibit antiviral, anti-inflammatory, anti-parasitic, anti-allergic, anti-fibrotic, anti-arrhythmic, immunoregulatory and contraceptive actions, and the agents were found to be active for autoimmune diseases (Ref1., Ref.2, Ref3).
During the past years, Artemisinin has also also been identified as a substance with a strong anti cancer potential in various cancer cells such as

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

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

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

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

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

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

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

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

Case reports in animals:

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

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

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

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

Case reports or clinical trials in human:

  • A Randomised, Double Blind, Placebo-Controlled Pilot Study of Oral Artesunate Therapy for Colorectal 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.
Note that the studies above used one component only, i.e. Artesunate, and not the whole plant.

Anecdotal stories in humans:

Mechanism:

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

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

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

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

Other mechanisms behind Artemisinin compounds: reduction or inhibition of

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

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

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

Formulation:

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

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

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

Administration & Dose:

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

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

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

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

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

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

  • Artemether + Lumefantrine (Ref.)
  • Dihydroartemisinin + Piperaquine (Ref.)
Summary from literature:

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

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

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

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

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

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

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

Synergy:

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

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

Source and Price:

Artemisia annua – whole plant extract – oral capsules:

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

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

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

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

Storage:

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

References:

Artemisinin: Discovery from the Chinese Herbal Garden

Pharmacogenomics of Scopoletin in Tumor Cells

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

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

Artemisia annua – Pharmacology and Biotechnology

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

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

Dried whole plant Artemisia annua as an antimalarial therapy.

The Surprising Efficiency of Artemisia annua Powder Capsules

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

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

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

Anticancer Effect of AntiMalarial Artemisinin Compounds

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

Artesunate induces necrotic cell death in schwannoma cells

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

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

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

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

- http://www.tandfonline.com/doi/full/10.3109/13880209.2010.497815
Click to expand...


The only person hinting at a cancer usage is Daniel, but he gives no source whatsoever for it.

Read carefully the links you provided, you'll realize Absinthum has only been used as an antispasmodic, febrifuge, stomachic, cardiac stimulant, anthelmintic, for the restoration of declining mental function and inflammation of the liver, to improve memory and various infectious diseases, Crohn's disease, and IgA nephropathy.
 
Amazoniac

Amazoniac

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burtlancast said:
The only person hinting at a cancer usage is Daniel, but he gives no source whatsoever for it.

Read carefully the links you provided, you'll realize Absinthum has only been used as an antispasmodic, febrifuge, stomachic, cardiac stimulant, anthelmintic, for the restoration of declining mental function and inflammation of the liver, to improve memory and various infectious diseases, Crohn's disease, and IgA nephropathy.
Click to expand...
There are exceptions: Artemisia absinthium (AA): a novel potential complementary and alternative medicine for breast cancer
 
Last edited:
burtlancast

burtlancast

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Amazoniac

Amazoniac

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burtlancast said:
That's an IN VITRO study; i don't believe they tried it IN VIVO.
Click to expand...
There must be compounds in common since they are related. I wouldn't doubt if absinthium worked to some degree.
By your description it should be helpful, especially because you already commented about the infectious component of cancer. The problem is the toxicity, which seems easier to achieve from its chronic use.
 
Sheila

Sheila

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Dear Mossy
It is my findings that Artemisinin is a 'kind' chemotherapy more than a cure and it will probably produce a degree of anaemia given time. This, I think, but am not entirely sure, is a function more of the ability to mobilise iron from storage in the cancer state (I suspect iron stores are available). To do so is likely against the body's best interests. Rest is important to healing and the lack of rest makes the symptoms of anaemia more taxing. Ignoring the new plug for supplements, this site had some interesting information on the anaemia of chronic disease. http://www.irondisorders.org/anemia-of-chronic-disease I have found Artemisinin of greater benefit with older people as usually their cancer system is slower to develop and Art. is better able to keep things in check. In my experience it's part of a plan, not the whole plan. And no, I wouldn't consider iron supplementation per se, seen too many issues from this down stream - often seemingly unconnected until one looks back carefully.
I would be interested if you found the mechanism re Art and slower breakdown of nicotine et al., that might be most useful to understand.
Best regards
Sheila
 
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