Hello!
I didn't see a topic about artemisin yet, so I am opening one.
On the following link is a journal regarding antitumor acitivty or artemisin:
http://www.hindawi.com/journals/bmri/2012/247597/
It is fairly long, I will just copy paste some parts:
"Artemisinin and its analogs are naturally occurring antimalarials which have shown potent anticancer activity. In primary cancer cultures and cell lines, their antitumor actions were by inhibiting cancer proliferation, metastasis, and angiogenesis. In xenograft models, exposure to artemisinins substantially reduces tumor volume and progression.
One major obstacle for a successful anticancer therapy is the development of resistance over time. Many aggressive tumors become refractory to anticancer therapy with hardly any chemotherapeutic alternatives. A leading cause of drug resistance is the drug efflux generated by overexpression of membrane protein pumps, which results in ineffective low drug concentrations [108]. Anticancer activity of artemisinins has shown to be unaffected in otherwise resistant and multiresistant cancer cells"
I came across artemisin when friend's grandfather got me a tea from artemisia annua ( https://en.wikipedia.org/wiki/Artemisia_annua ), he also said I should take iron supplement when I drink it - folk's medicine like Stephen calls it :)
"In most of the systems, preloading of cancer cells with iron or iron-saturated holotransferrin (diferric transferrin) triggers artemisinin cytotoxicity [32–35] with an increase in artemisinin activity up to 100-fold in some cell lines [36].
Continued proliferation and growth of malignant cells require higher iron metabolism to achieve processes of cell survival [35]. Therefore, cancer cells exhibit an increase in transferrin receptors (TfR) which are responsible for the iron uptake and regulation of intracellular concentrations. Levels of expression of TfR in cancer cells may vary depending on the cell line. However, they differ substantially from normal cells leading to a high selectivity index of artemisinin and its derivatives. Efferth et al. reported that leukemia (CCRF-CEM) and astrocytoma (U373) cells express TfR in 95% and 43% of the cell population, whereas normal monocytes only account for approximately 1% [42, 43]. "
Does anyone have any experience or knowledge on artemisin?
Hi Matjaz,
ReplyDeleteArtesunate and artemether are semi-synthetic derivatives of artemisinin, and also used as anti-malarials. CUSP9 used to included artesunate, but it was dropped recently from that protocol, I believe due to myelosuppression, and replaced with minocycline.
There has been a single rodent study with artemether for brain tumors. I've added this study to the Library (folder 2 - Therapies - preclinical). Artemether is fat soluble, while artesunate is water soluble. So artemether is expected to have better brain penetration. I'm still not completely clear on potential for side-effects including neurotoxicity with artemether treatment.
A footnote to your post, the U373 cell line is most likely derived from a GBM (in spite of the "astrocytoma" designation, and certainly is not an IDH1-mutant lower grade astrocytoma. In fact, due to contamination, many studies done with "U373" were actually done with the GBM cell line U251. In short, U373 should not be presumed to resemble your low grade astrocytoma.
Some people here have tried artemisinin and derivatives so I'll turn it over to them now.
ReplyDeleteHi Matjaz
My son has been on Artesunate and Artemether both in the past when he was originally diagnosed with a lower grade astrocytoma in 2007 and since his more recent GBM diagnosis in October 2014. We have used high doses (900 mg daily) and moderate dose levels. My current thinking is moderate dosing, especially given the absorption issues mentioned below, is best. I am basing this on the very scientific method called taking a guess. I believe the CUSP9* ver2 protocol under dosed Artesunate. If using these compounds, be aware that adverse reactions have been reported. As far as I know, cause and effect have not been established. Maybe Steven has more information on Adverse effects.
There are several issues to be aware of when using these compounds.
• Artemisinin and its analogs rapidly inhibit their own absorption so a rotation schedule is needed. Various schedules have been recommended and which on is best is unknown. Jeremy is using a one week on, one week off rotation. We have adjusted the schedule as necessary so he was on these compounds while on TMZ. Higher doses will more rapidly inhibit absorption and it is possible long term use at low doses may not require as aggressive a rotation schedule.
• Taking with curcumin may have a synergistic effect. Taking with metformin may improve effectiveness
• As Steven points out, Artemether is fat soluble and artesunate and artemisinin are water soluble. They have differing half-life’s and differing potential for toxicity. Artemether is likely best for CNS tumors, but the water soluble compounds apparently also cross the BBB and are less toxic. Jeremy is currently using both Artesunate and Artemether. He will be switching to just Artemether soon.
• All 3 compounds need to be taken on an empty stomach. 40 minutes at least before a meal or 3-4 hours after a meal. These compounds will interact with iron in food rendering them essentially useless. Some recommend taking with a fish oil capsule, CLA or whole milk as they are better absorbed. My understanding is this is true for both the water soluble and fat soluble compounds.
• There is some concern for toxicity, especially with Artemether. I have seen recommendations for a maximum daily dose of 1-2 mg/kg. Artesuate and artemisinin are believed to have a much more tolerable dose range.
That’s about all I can think of right now. If something else comes to mind I will pass it along.
Thank you for your answer! I am in contact with dr. Singh from University of Washington, she said she will give me some guidelines...will paste them here when I get them
ReplyDeleteHello!
ReplyDeleteBelow are some guidelines from dr. Singh (she is author/coauthor of some journals regarding arthemeter):
"You may try Artemether from IPCA Pharmaceutical Company, India. Please try to find capsule form 40 or 80 mg per capsule. They usually come in oily liquid base either gel capsule or in glass ampule. If you cannot find the capsule form please buy injection of Artemether, commercially known as Larither. Open the ampule and fill up in a syringe using a needle, remove the needle from the syringe, and eject the contents of syringe in mouth, or it can be administered intramuscularly.
Artemether in capsule / injectable form may be taken 3 to 4 hours after dinner with a cup of milk or spoonful of ice cream (without flavors or additives, e.g. Breyers Natural Vanilla) and once a week with few spoons of yogurt (having fat, but no flavors or fruits) having live lactobacillus. The purpose of giving 3-4 hour interval after evening meal is to make sure stomach is almost empty, as the drug interacts with the iron contents of food. This 3 to 4 hour time interval should be used for pleasant physical and mental activities. Physically inactive individuals do not respond well to this treatment. Also, 250 mg of Vitamin C and 200 units of Vitamin E may be taken around breakfast and lunch if possible with plenty and variety of fruits and vegetables. The patient should not have a recent history of smoking (in last 6 months), radiations (in last 2 months), or chemotherapy (in last 2 weeks)
2 capsules/injection of Artemether of 40 mg each or 1 capsule/ injection of 80 mg per day should be enough for a person weighing 70kg. You may continue treatment every day for 8 weeks. Continue to monitor progress (symptoms, MRI, CAT scans, size of tumor, etc.) and if t there is some benefit you may continue to take Artemether on alternate days for 3 to 4 months but with Vitamin C and E daily. If there is no response in 8 weeks, switch to other therapies. Please calculate dosage based on ARTEMETHER contents (1mg/kg/day for eight weeks).
Additionally, you may take 4 capsules of butyrate with plenty of water (15863 N. Greenway-Hayden Loop, Ste 120 Scottsdale, AZ 85260, Phone: 1-866-601-5800, http://www.jigsawhealth.com/supplements/butyrex) at the same time along with Artemether. I would like to suggest that butyrate is very safe and effective in the treatment of cancer. Additionally, the patient may take 4 capsules of calcium magnesium butyrate (15863 N. Greenway-Hayden Loop, Ste 120 Scottsdale, AZ 85260, Phone: 1-866-601-5800, (http://www.jigsawhealth.com/supplements/butyrex) at the same time along with artemether. Minimize iron rich food, such as meat, as much as possible. Iron supplement is NOT necessary, if you are taking enough fruits and green leafy vegetables. Ideally, take antioxidants for breakfast and any food with high iron at lunch.
If vitamin D3 levels are low (D3 levels are usually low in cancer patients), they should be in normal range by supplementation D3 it has been shown to have anticancer properties. They should be taken at the same time as artemether and butyrate.
I want to let you know that this is not an FDA approved drug for cancers.There are no known side effects taken in suggested dosage for a use of up to 2 years.
All information given and communications sent are done in good faith only on a volunteer basis and I am not compensated for this service by anyone.
Please do not hesitate to call me if you have questions."
Also there was a case report in the email (unfortunately not for glioma), I will just copy paste the text:
Delete"December 23, 2011
New Application of Artemether for Treating Brain Cancer: A Case Report
ETDZS INDUSTRY LTD. has been exporting the anti-malarial drug, artemether, an artemisinin derivative (ARTEMOS) for many years. Recently, scientists from around the world have found the drug can kill cancer cells and the use of Artemos as an anti-cancer drug is a new application. Summarized here is the case of a patient suffering from brain cancer. Approximately five months after taking ARTEMOS, the patient experienced a miraculous recovery! In order for patients with associated
diseases and their family and friends to share this information, here is a short report on the treatment of the following:
Patient Zhou Heping, a Chinese female, 52 years old, weighing 62 kg, height 155 cm, previously in good health, experienced a drop in right limb muscle strength (muscle strength score of 3) in February 2011 and complained of mild headache but no nausea, no vomiting and no visual
changes. She went to the Navy General Hospital in Beijing for treatment and stereotactic surgery was performed. The intracranial biopsy pathology report showed a "diffuse large B-cell non-Hodgkin's lymphoma." One week post-operation, she returned home to Qinhuangdao City.
On April 10, 2011, the patient began treatment with ARTEMOS (artemether, an artemisinin derivative) at a dose of 80 mg (2 soft capsules of 40 mg each), every night with boiled water. Professor Singh of the Department of Bioengineering, University of Washington, Seattle, USA,
recommended the following treatment: vitamin C 250 mg and vitamin E 200 IU, every day after breakfast; artemether 80 mg at night, 3-4 hours after dinner, before going to bed; and daily walking for aerobic exercise. On April 11, at the First Hospital of Qinhuangdao magnetic resonance imaging (MRI) examination revealed left parietal lobe nodular masses in the thalamus area (Figure 1). Irregular groups of tumor-like shadows had maximum anteroposterior diameter of 47mm, maximum diameter from top to bottom 24mm, maximum diameter of about 28mm.
Tests of liver and kidney function revealed no abnormal indicators. In only one and a half months after treatment, symptoms were improved, muscle strength recovered to 4 + level and a review of MRI examination from May 26, 2011 (Figure 2) showed tumor shrinkage of 77%, the maximum anteroposterior diameter of 27mm, maximum diameter from top to bottom 14mm, maximum diameter of about 19mm. Patient was without any discomfort. Another MRI done three months after treatment began on July 7, 2011 (Figure 3) and there was further shrinkage (trace measurement). The MRI of September 13, 2011 (Figure 4) showed no discernible masses. Currently, the patient has returned back home to Wulumuqi city in Xinjiang and on December 19, 2011 switched to taking 80 mg of artemether every other day (continued to take vitamin C and E daily at the same dose as above) and now exercises daily by walking 4-5 km.
Figure 5 A, B and C MRI done June 28, 2012 show complete cure."
Unfortunately I can't paste pictures of MRI showing complete remission. Anyway, I am not promoting this as magical cure...just pasted all the information I got.
Matjaz
DeleteI was attempting to look up the contact email for Professor Singh in the bioengineering department. I can only find a Nerendra Singh, who is a male. You referred to Professor Singh as a female. Do I have the correct person? If not, what is their first name? Thank you.
This comment has been removed by a blog administrator.
DeleteBe happy to talk with you. My email is pacm@mtaonline.net
DeleteMatjaz, Could you possibly keep the conversation with Mike re artemether on the cocktail blog. I have been following your conversation and wouldn't like to miss out on any useful information. I have artemether and artemisinin ( I've had it for about 6 months) and want to add it to my huysband's cocktail so all information is valuable. Thanks
ReplyDeleteSure Linda! I wanted to ask Michael about experiences etc., since his son went through the same as I am going (low grade). I post everything I learn and others can benefit from it here, no worries :)
ReplyDeleteSo one question on this topic: if I understand correctly artemether is prescription only or can I get it some other way? I didn't find it on kiwidrug.
Thanks!
Check on the Drug and Supplement sources page at the top of this blog. You can purchase artemisinin/artesunate/artemether through the website hepalin.com
DeleteThanks Matjaz,really appreciate all the info you provide
DeleteOf course Linda, as old saying goes: strength is in numbers :)
ReplyDeleteHey Guys, I tried Singh's protocol in 2011 (after corresponding off and on with him). It did not shrink my tumor, and arguably grew slightly during the period. I was religious about timing/diet/etc. I add this not to deter anyone, but to share my experience. Background: Diagnosed 4/10 low grade diffuse astrocytoma complete resection, recurrent within 6 months - second total resection 10/12. Stable for the past three years (although under review for recurrence - no nodular enhancement, but possible increased flair signal). I love it that you guys are mentioning you're adding the protocol to existing cocktails. My concern is that it isn't strong enough for most glioma.
ReplyDeleteI just came to understand that artesunate was dropped from CUSP9 due to neurotoxicity issues. This was not apparent in the dose escalation phase, but came on later.
ReplyDeleteI am wondering what were symptoms of that neurotoxicity. My brother is taking all 3 art compounds for a while already I'm not sure if we should continue or not.
ReplyDeleteThis is interesting. Professor Singh says there is no evidence of toxicity with up to two years of use. Jeremy has been on artesunate and artemether for over a year without issues. Do you know what signs and or symptoms were associated with artesunate? Also, it was my understanding that artemisinin and artesunate were water soluable compounds and artemether was fat soluble. Dr. Singh told me to use artemether and if I wanted a higher dose to add artemisinin because both artemisinin and artemether were fat soluble and artesunate was water soluble. Just a FYI.
ReplyDeleteI suspect what Jessica said about these compounds not being strong enough is true. The questions, which is the same question we ask about all components of the cocktail, is whether there is synergy with other components. I am hoping the other drugs that increase ROS will be synergistic and that undermining metabolism with DCA and metformin will produce the results we are after.
Sorry, I don't know what the specific symptoms were. But perhaps it was due to some combination of the drugs in the cocktail, whereas you would have not seen toxicity with artesunate/artemisinins alone?
DeleteI can't tell you how happy I was to read that Dr. Singh recommends taking antioxidants at breakfast. Quick history: Husband dx GBM-IV in April. Resection got out 92%. He completed a 6-wk course of temozolomide + radiation about a week ago. He is taking 180mg artemisisin twice daily, curcumin in peanut butter 3xday, and a cocktail called Leukozepin twice per day under the direction of Dr. Wendy Zhang in Houston, under the watchful eye of husband's oncologist at MD Anderson. So far, all blood results have been normal and he is doing swimmingly. We wanted him to begin our favorite antioxidant, pycnogenol, after the radiation ended but were afraid it would scavenge the free radicals the artemisisin caused to form in the tumor. If he can take the artemisisin first thing in the morning and last thing at night, and take the pycnogenol with lunch, that would be super. Anyone see any problem with that?
ReplyDelete*artemisinin
ReplyDeleteHusband got his first, post-radiatin/chemo MRI. The tumor looks floppy, beat up, and permeable. The oncologist is happy enough to let us continue to try temo and artemisinin for another go-round. We'll get another MRI in a month.
ReplyDeleteHas this discussion closed down? I don't see anyone writing anymore. How are you MatJaz?
Hi can someone explain to me what is the actual difference between artemisinin/artesunate/artemether?
ReplyDeleteArtemisinin is a natural product, isolated from the Artemisia annua plant (sweet wormwood).
DeleteArtesunate is a semi-synthetic derivative of artemisinin. It's made from dihydroartemisinin (the main metabolite of artemisinin) in a chemical reaction with succinic acid anhydride.
Artemether is also a dihydroartemisinin derivative, also known as dihydroartemisinin methyl ether.
If you look at the molecular structure of all 3 molecules (for example on wikipedia) they are all very similar. All 3 are metabolized to dihydroartemisinin in the body.
One of the practical differences is that artemether is more lipophilic (fat soluble), while artesunate is water soluble. It's proposed that artemether probably has an advantage in penetrating brain tissue due to its relative lipophilicity.