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wormwood

Artesunate and Artemesinin are wormwood extracts that have a large range of potential in multiple cancer types. These derivatives are thought to be synergistic with IV Vitamin C Therapy and Hyperbaric Oxygen Treatment. 


Artesunate and other wormwood can be administered alongside IV vitamin C as they have additive actions. High doses of Artesunate and Wormwood Derivatives can be used along with Vitamin C with an excellent tolerability profile in Breast and Colon Cancer and Melanoma; there is data its use in Lung Cancer. Because of the oxidative oxygen dependant mechanisms, they are thought to also synergize with Hyperbaric Therapy.



Disclaimer: This page is for informational purposes only


It has been included to provide a comprehensive look at common alternative treatments


At EICT we use Artemesinin the parent compound of Artesunate.

The results of Artesunate can be generalized to Artemesinin. 

Artesunate is a derivative of Artemesinin. 



Wormwood extracts are synergistic with IV Vitamin C and Hyperbaric Oxygen Therapy.



Questions about treatments?

Call Us 780-757-8378

wormwood: In-Depth

Artesunate is derivative from Wormwood (Artemesia): it is used as an anti-malarial treatment around the world. Because of its widespread use, the safety of it as an oral and IV agent is well known1. Artesunate has excellent tolerability and no obvious side effects with even high dose, rapid infusions.


Artesunate is available in oral forms. IV administration of Artesunate has synergy with an IV treatment we offer: Intravenous Vitamin C "IVC." The effects of IVC cannot be replicated with oral dosing. IV artesunate dosing avoids any die-off reactions that can occur from oral Artesunate consumption interacting with gastrointestinal flora and infections.


Many cell studies demonstrate Artesunate’s anti-cancer effects against Glioma2 (brain tumor), AML3 (acute myeloid leukemia), Ovarian Cancer4, Liver Cancer5, Breast cancer6,7,9, Kidney Cancer8, Pancreatic cancer1, Colon cancer10 and Lung Cancer12


It is thought that the primary mechanism of action of Artesunate is reactive oxygen species generation from reactions between the Artesunate and Iron that has accumulated in tumor cells1 Because of the Oxygen dependence it is thought that Hyperbaric Oxygen can enhance the action of Wormwood derivatives. 


In a 2010 study, the hypothesis was whether Hyperbaric Oxygen enhances anticancer activity of artemisinin. "Molt-4" human leukemia cells were cultured in artemisinin and exposed for 90 min to one of three different conditions: control, room air control, or Hyperbaric Oxygen Therapy.


After 48 h of incubation, growth of cells treated with artemisinin alone or Hyperbaric Oxygen alone was 85% of that of cells grown under artemisinin-free control conditions. Combined artemisinin and Hyperbaric treatment resulted in an additional 22% decrease in growth. The authors concluded "Combined HBO(2) and artemisinin exposure may be an effective anticancer chemotherapeutic strategy."30

Clinical trials

Although Artesunate has a broad range of cancers it has potential benefit in, our clinic uses the parent compound Artemesinin in Breast and Colon cancer and Melanoma. 


Two human studies have demonstrated Artesunate's efficacy in Breast cancer11,23 and another in Colon cancer10.  

Artesunate has also shown efficacy in a small human case report series in Uveal (eye) Melanoma14.


We are beginning to consider wormwood derivatives in Lung Cancer as evidence was demonstrated in a human trial in combination with chemotherapy in advanced lung cancer13. Artesunate can potentially be used in Prostate Cancer as there is evidence of its efficacy for this condition15.    


One double blind placebo controlled trial gave human colorectal cancer patients oral Artesunate prior to surgery. During a 42 month average follow up time, 1 patient in the Artesunate group had a recurrence of colon cancer compared to 6 patients in the placebo group10. 



Artesunate and Colon Cancer


Artesunate and survival probability in colon cancer


Preliminary data from Bastyr Integrative Oncology Research Center (BIORC) showed that IV Vitamin C with Artesunate made a substantial difference in patients with Stage 4 Breast cancer.  After 1 year the group that received IV Artesunate and Vitamin C has a 90% survival rate whereas the group receiving Naturopathic care without infusions had a 74% survival rate. By year 2 the results were even more profound as the group without IV treatment had a 68% survival rate compared to 90% in the treatment group.11


Artesunate was also studied in breast cancer patients in a 2016 study where it was given in high doses daily for 4 weeks. However the study was not designed to comment on efficacy against cancer, it merely commented on potential ototoxicity (ear) from daily oral Artesunate dosing21 A 2014 study also investigated oral dosing of Artesunate in 23 breast cancer patients over 4 weeks but was not designed to evaluate tumor response22. 


A 2017 trial looked at Artesunate dosing in metastatic breast cancer patients alongside standard therapies. Twenty-three women received either 100 or 150 or 200 mg oral artesunate for 4 weeks. Some minor hematologic effects (changes in the blood counts) were seen in 3 patients with minor changes in hearing in 3 patients and vertigo in 1. Most importantly, stable disease was found in ten patients23. Potential compatibility with: capecitabine, gemcitabine, pegylated liposomal doxorubicin, bisphosphonates, & trastuzumab was suggested by this study as well.


Artsenunate and Stage 4 Breast Cancer

Improved survival in Stage IV Breast Cancer patients using Artesunate and IV Vitamin C


A lung cancer clinical trial with 60 patients receiving Artesunate + Chemotherapy were compared to 60 patients only receiving chemotherapy.  The disease control rate of the trial group was 88.2% compared to 72.7% in the control group and the trial group had a longer time to first progression.12 This is fairly clear evidence of Artesunate efficacy in Lung cancer.


Artesunate and Lung Cancer Graph



In a 2011 trial, ten cervical cancer patients (stage III or IV) were treated with oral Dihydroartemesinin (DHA) also known as Artenimol for 28 days. DHA is the active metabolite that both Artesunate and Artemesinin convert into. DHA induced clinical remission with a median time for the disappearance of the symptoms (pain and vaginal discharge) being 7 days29.

Mild adverse effects (grade 1 or 2) were noted in 5 of the patients. Six patients experienced clinical relapse at an average of 6 months(four patients did not relapse). Four of six patients with relapse were challenged with a second 28-day treatment period, which again resulted in clinical remission29.

Case Reports

In Uveal melanoma, Artesunate was used in the treatment of two metastatic patients in combination with standard chemotherapy who were progressing on chemotherapy alone. The first patient had a temporary response after the addition of artesunate to his chemotherapy. The second patient first experienced a stabilization of the disease after the addition of Artesunate to his chemotherapy, followed by objective regressions of spleen and lung metastases.14


In prostate Cancer, as described in a 2015 case report, a patient with metastatic advanced prostate cancer presented with a  PSA level >800 µg/l. The combination of bacalitumide (anti-androgen for 14 days) and long-term oral treatment with Artemesia capsules the PSA level dropped down to 0.98. However, re-emergence of the PSA did occur 7 months later15. Furthermore there is cell study evidence of Artesunate for prostate cancer16,17,18,19,20.

A 47-year-old stage 4 breast cancer had tumor regression on CT scan upon Artesunate treatment; another breast cancer patient had a comparable experiences24. A 47-year-old patient with liver cancer and abdominal ascites was still alive 2.5 years after taking taking artesunate24. However exact details of these were not able to be found.  

Another case report described the artesunate therapy of a laryngeal squamous cell carcinoma patient. 15 days of artesunate (60mg by injection) was followed by 50mg orally for at least two months. After 2 months the tumor reduced in size by 70%25.


wormwood active in:

Breast Cancer11,24
Lung Cancer12
Prostate Cancer15
Melanoma14 

Colon Cancer10

Liver Cancer24

Laryngeal Cancer25
Cervical Cancer26


Clinical use

Wormwood derivatives are an option for Colon10, Breast11,23, Melanoma14 and Lung Cancer12. 
There is also potential for Laryngeal25 and Liver Cancer24.

Wormwood derivatives can be used in conjunction with IV Vitamin C as their effects are both considered oxidative in nature and therefore synergistic and the research from BIORC in Breast Cancer patients. Because of the oxygen dependent reactions involved, Wormwood derivatives are thought to be enhanced by Hyperbaric Oxygen Therapy. Our Edmonton office has two Hyperbaric Chambers.


Hepatoxicity developed in one patient taking temozolomide, artesunate and Chinese herbs; of which one of the herbs are associated with hepatotoxic effects as well as two medications the patient was taking27. Also death from hepatotoxicity occured in a patient taking DCA and artesunate26. DCA cause a rare rapid increase in hepatic enzymes but not to dangerous levels from a single administration. Although simultaneous administration of DCA and Artesunate is not a commonly suggested protocol and the patient was on 4 other medications and had finished temozolomide chemotherapy a few months prior26. Two of the medications, valproic acid and levetiracitam for seizures are associated with hepatotoxicity27. Also the patient passed after initial hepatotoxicity stabilized and systemic signs of infection, and a series of epileptic seizures started and the family denied further medical intervention26.

Although liver toxicity is not a typical concern with Artesunate23,27.

To be cautious we suggest occasionally monitoring liver enzymes in patients undergoing wormwood derivative treatment. 


We currently monitor patients that are using wormwood derivatives for possible blood and hearing abberations although the incidence is mild and infrequent23. It is also suggested that wormwood derivatives can alter blood iron studies but that it is rarely of clinical significance29. However, we have seen occasional drops in red blood cell counts and therefore run a CBC within the first few weeks of treatment.


Adminstration suggestions vary. Daily oral use of wormwood derivatives has been seen in some of the case reports14. Oral dosing of wormwood derivatives is also suggested in an "on-off" fashion: 3-4 days "on" and 4-3 days "off" to allow for cellular repletion of iron.


IV Artesunate administation is usually done twice weekly alongside IV Vitamin C1,29,13.


However, we use the oral parent compound Artemesinin. 


Questions about treatment?

Call Us 780-757-8378



References


1. Paul Anderson 2016. Artesunate Monograph – Artesunate for Parenteral Use.

Accessed August 20 2016.


2. Oncol Rep. 2016 Aug;36(2):984-90. doi: 10.3892/or.2016.4847. Epub 2016 Jun 2.

Artesunate attenuates glioma proliferation, migration and invasion by affecting cellular mechanical properties.

Lian S1, Shi R2, Huang X3, Hu X2, Song B2, Bai Y4, Yang B2, Dong J5, Du Z6, Zhang Y5, Jia J7, Ma N1, Guo G1, Wang M1


3. Cancer Chemother Pharmacol. 2016 Jun;77(6):1231-43. doi: 10.1007/s00280-016-3038-2.

Evaluation of artemisinins for the treatment of acute myeloid leukemia.

Drenberg CD1,2, Buaboonnam J3, Orwick SJ2, Hu S1,2, Li L3, Fan Y4, Shelat AA5, Guy RK5, Rubnitz J6


4. Mol Carcinog. 2016 Feb 15. doi: 10.1002/mc.22474. [Epub ahead of print].

Contribution of reactive oxygen species to ovarian cancer cell growth arrest and killing by the anti-malarial drug artesunate.

Greenshields AL1, Shepherd TG2,3,4, Hoskin DW1,5,6. PMID 26878598


5. Curr Top Med Chem. 2016;16(22):2453-63.

Artesunate as an Anti-Cancer Agent Targets Stat-3 and Favorably Suppresses Hepatocellular Carcinoma.

Ilamathi M, Santhosh S, Sivaramakrishnan V1. PMID: 26873192


6. Chin J Cancer Res. 2014 Apr;26(2):200-7. doi: 10.3978/j.issn.1000-9604.2014.04.07.

Antitumor effects of artesunate on human breast carcinoma MCF-7 cells and IGF-IR expression in nude mice xenografts.

Dong HY1, Wang ZF1. PMID: 24826061

 

7. Anticancer Drugs. 2014 Jul;25(6):652-62. doi: 10.1097/CAD.0000000000000089.

Artesunate induces G2/M cell cycle arrest through autophagy induction in breast cancer cells.

Chen K1, Shou LM, Lin F, Duan WM, Wu MY, Xie X, Xie YF, Li W, Tao M. PMID: 24518199


8. Oncotarget. 2015 Oct 20;6(32):33046-64. doi: 10.18632/oncotarget.5422.

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.

Jeong da E1, Song HJ2, Lim S3, Lee SJ4, Lim JE5, Nam DH1,4,6, Joo KM1,2, Jeong BC5, Jeon SS5, Choi HY5, Lee HW


9. J Biol Chem. 2011 Feb 25;286(8):6587-601. doi: 10.1074/jbc.M110.210047.

Artesunate activates mitochondrial apoptosis in breast cancer cells via iron-catalyzed lysosomal reactive oxygen species production.

Hamacher-Brady A1, Stein HA, Turschner S, Toegel I, Mora R, Jennewein N, Efferth T, Eils R, Brady NR.


10 .EBioMedicine. 2014 Nov 15;2(1):82-90. doi: 10.1016/j.ebiom.2014.11.010. eCollection 2015.

A Randomised, Double Blind, Placebo-Controlled Pilot Study of Oral Artesunate Therapy for Colorectal Cancer.

Krishna S1, Ganapathi S2, Ster IC1, Saeed ME3, Cowan M4, Finlayson C1, Kovacsevics H1, Jansen H5, Kremsner PG6, Efferth T3, Kumar D2. PMID: 26137537


11. Macleod, Adam. Dreamhealer.wordpress.com Accessed August 20th 2016.


12. Zhong Xi Yi Jie He Xue Bao. 2008 Feb;6(2):134-8.

Artesunate combined with vinorelbine plus cisplatin in treatment of advanced non-small cell lung cancer: a randomized controlled trial]

Zhang ZY1, Yu SQ, Miao LY, Huang XY, Zhang XP, Zhu YP, Xia XH, Li DQ.


13. Mckinney, Neil. Advanced Clinical Naturopathic Oncology Course Notes, March 2015. 


14. Oncol Rep. 2005 Dec;14(6):1599-603.

Artesunate in the treatment of metastatic uveal melanoma--first experiences. Berger TG1, Dieckmann D, Efferth T, Schultz ES, Funk JO, Baur A, Schuler G.


15. Phytomedicine. 2015 Dec 15;22(14):1223-31. doi: 10.1016/j.phymed.2015.11.001

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

Michaelsen FW1, Saeed ME2, Schwarzkopf J3, Efferth T4.


16. Zhong Xi Yi Jie He Xue Bao. 2008 Jun;6(6):591-4. doi: 10.3736/jcim20080609.

[Artesunate induces prostate cancer cell line PC-3 differentiation and cell cycle arrest].Huang XF1, Yuan D, Zhang CC, Zhang XP.


17. Int J Oncol. 2001 Apr;18(4):767-73. The anti-malarial artesunate is also active against cancer.  Efferth T1, Dunstan H, Sauerbrey A, Miyachi H, Chitambar CR.


18. Life Sci. 2016 Jul 15;157:1-11. doi: 10.1016/j.lfs.2016.05.033. Epub 2016 May 24. Mechanism of dihydroartemisinin-induced apoptosis in prostate cancer PC3 cells: An iTRAQ-based proteomic analysis. Xu G1, Zou WQ1, Du SJ1, Wu MJ1, Xiang TX2, Luo ZG3.


19. Cancer Biol Ther. 2010 May 15;9(10):819-24. Epub 2010 May 18.

Dihydroartemisinin upregulates death receptor 5 expression and cooperates with TRAIL to induce apoptosis in human prostate cancer cells.

He Q1, Shi J, Shen XL, An J, Sun H, Wang L, Hu YJ, Sun Q, Fu LC, Sheikh MS, Huang Y.


20.  Anticancer Drugs. 2010 Apr;21(4):423-32. doi: 10.1097/CAD.0b013e328336f57b.

Effect of artemisinin derivatives on apoptosis and cell cycle in prostate cancer cells.

Morrissey C1, Gallis B, Solazzi JW, Kim BJ, Gulati R, Vakar-Lopez F, Goodlett DR, Vessella RL, Sasaki T.


21. Investigation of ototoxicity of artesunate as add-on therapy in patients with metastatic or locally advanced breast cancer: new audiological results from a prospective, open, uncontrolled, monocentric phase I study. König M1, von Hagens C2, Hoth S1, Baumann I1, Walter-Sack I3, Edler L4, Sertel S5.


22. Eur J Clin Pharmacol. 2014 Dec;70(12):1453-63. doi: 10.1007/s00228-014-1754-2.

Population pharmacokinetics of artesunate and dihydroartemisinin during long-term oral administration of artesunate to patients with metastatic breast cancer.

Ericsson T1, Blank A, von Hagens C, Ashton M, Äbelö A.


23. Breast Cancer Res Treat. 2017 Jul;164(2):359-369. doi: 10.1007/s10549-017-4261-1. Epub 2017 Apr 24.
Prospective open uncontrolled phase I study to define a well-tolerated dose of oral artesunate as add-on therapy in patients with metastatic breast cancer (ARTIC M33/2).

von Hagens C1, Walter-Sack I2, Goeckenjan M3,4, Osburg J3,5, Storch-Hagenlocher B6, Sertel S7, Elsässer M8, Remppis BA9,10, Edler L11, Munzinger J12, Efferth T13, Schneeweiss A14, Strowitzki T3.


24. Semin Cancer Biol. 2017 Oct;46:65-83. doi: 10.1016/j.semcancer.2017.02.009. Epub 2017 Feb 28.
From ancient herb to modern drug: Artemisia annua and artemisinin for cancer therapy.

Efferth T


25. Archive of Oncology 2002;10(4):279-80

Case report of a laryngeal squamous cell carcinoma treated with artesunate

Narendra P. S. Krishna B. 


26. Front Oncol. 2016 Oct 7;6:204. eCollection 2016.
Fatal Liver and Bone Marrow Toxicity by Combination Treatment of Dichloroacetate and Artesunate in a Glioblastoma Multiforme Patient: Case Report and Review of the Literature.
Uhl M1, Schwab S1, Efferth T2


27. Arch Toxicol. 2017 Apr;91(4):1833-1846. doi: 10.1007/s00204-016-1810-z. Epub 2016 Aug 12.
Hepatotoxicity by combination treatment of temozolomide, artesunate and Chinese herbs in a glioblastoma multiforme patient: case report review of the literature.

Efferth T1, Schöttler U2, Krishna S3, Schmiedek P4, Wenz F4, Giordano FA4.


28. Paul Anderson 2016. IV Artesunate Considerations - https://www.consultdranderson.com/iv-artesunate-considerations/

Accessed August 20 2016.


29. Anticancer Res. 2011 Dec;31(12):4417-22.
First study of oral Artenimol-R in advanced cervical cancer: clinical benefit, tolerability and tumor markers. Jansen FH1, Adoubi I, J C KC, DE Cnodder T, Jansen N, Tschulakow A, Efferth T.


30. Anticancer Res. 2010 Nov;30(11):4467-70.
Effect of hyperbaric oxygen on the anticancer effect of artemisinin on molt-4 human leukemia cells
Yusuke Ohgami 1, Catherine A Elstad, Eunhee Chung, Donald Y Shirachi, Raymond M Quock, Henry C Lai





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