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No toxicity detected for Artemisia annua or afra

August 5, 2019 - 19:06 -- Pierre Lutgen

Artemisias are used since millenaries and never any toxic effect was noticed. If there was one it would have been highlighted by Bigparma because the plant competes with their pills.

The WHO guidelines state that, if the herbal product has been traditionally used without demonstrated harm, no specific restrictive action should be undertaken. In this case WHO maintains the position that there is no requirement for pre-clinical toxicity testing. Pre-clinical toxicity testing is only required for new medicinal herbal products which contain herbs of no traditional history of use.

The scientific literature however describes a wide array of toxic effects for ACTs: haemolytic, hepatotoxic, cytotoxic, neurotoxic, cardiotoxic, genotoxic, ototoxic, embryotoxic, spleenotoxic, hemolytic, atherosclerosis, spermatoxicity, immunodepressive effects of chemical artemisinine derivatives and artemisinin combined therapies (ACTs). Some recent research, mostly in relation with the resistance to ACT pills and/or artesunate injections, has highlighted serious secundary health effects at the doses prescribed by WHO.

The most convincing human trial on toxicity of the Artemisia plant  comes from Uganda. In Wagagai flower farm more than 2000 workers take artemisia tea every week they since 2006. No negative effect and malaria no longer a problem (Patrick Ogwang, personal communication).

         Radulović NSRandjelović PJStojanović NM, Toxic essential oils. Part II: chemical, toxicological, pharmacological and microbiological profiles of Artemisia annua L. volatiles. Food Chem Toxicol. 2013 Aug;58:37-49.

Taking into account its relatively low toxicity, the usage of A. annua volatilesdoes not represent a health risk.

         Nahrevanian HSheykhkanlooye Milan BKazemi M, Antimalarial Effects of Iranian Flora Artemisia sieberi on Plasmodium berghei In Vivo in Mice and Phytochemistry Analysis of Its Herbal Extracts. Malar Res Treat. 2012;2012:727032.

The results of this assessment showed no toxicity even by high concentration of herbal extract. A significant reduction in percentage of parasitaemia was observed; no alterations of hepatosplenomegaly and body weight were indicated in study group.

         Meshnick. Annual Wormwood (Artemisia annua L.)International Journal for Parasitology. 2002 Volume: 32, Issue: 13, Pages: 1655-1660

Artemisia has no reported toxicity if taken in recommended doses for short periods in the treatment of malaria

        I Muzemil, PhD Thesis Addis Ababa, 2009

The results showed that 70 % ethanol and hot water extracts of A. annua were safe in oral administration in mice. This could explain the safe use of the plant by the local people, in traditional treatment of malaria, in “Chencha” area of Gamogofa in Southern parts of Ethiopia

         Yang B, Zhou S, Li C, Wang Y Toxicity and side effects of artemisiae annuae  Zhongguo Zhong Yao Za Zhi. 2010 Jan;35(2):204-7.

Artemisia annua has low poisonous function, and has a promising prospect for potential application.

          Ribnicky DM, Poulev A, O'Neal J, Wnorowski G, Malek DE, Jäger R, Raskin Toxicological evaluation of the ethanolic extract of Artemisia dracunculus L. for use as a dietary supplement and in functional foods. Food Chem Toxicol. 2004 Apr;42(4):585-98.

No noteworthy signs of toxicity were noted in feeding or body weight, functional observational battery or motor activity. Gross necropsy and clinical chemistry did not reveal any effects on organ mass or blood chemistry and microscopic examinations found no lesions associated with treatment. No adverse effect level in rats is established at 1000 mg/kg/day.

             Mbeh Ubana Eteng . Biochemical and Haematological Evaluation of Repeated Dose Exposure of Male Wistar Rats to an Ethanolic Extract of Artemisia annua. Phytotherapy Research. 2013, 04 2

In this study, biochemical and haematological evaluations of ethanolic leaf extracts (EAA) derived from Artemisia annua were carried out in 20 male Wistar rats. The results showed that the liver function and haematological indices, and testosterone levels were not adversely affected. High density lipoprotein -cholesterol was reduced at 100 mg/kg of EAA, atherogenic index as well as low density lipoprotein -cholesterol was raised, and glucose concentration was reduced significantly at the 100 and 200 mg/kg of EAA.

             Mukinda JTSyce JA. Acute and chronic toxicity of the aqueous extract of Artemisia afra in rodents. J Ethnopharmacol. 2007 May 30;112(1):138-44. Epub 2007 Feb 14.

Artemisia afra "African Wormwood" is widely used traditionally in South Africa The aqueous extract  used in this assay mimicked the traditional decoction dosage No significant changes were observed in organ weights, and histopathological results showed normal profile suggesting no morphological alterations. Collectively, the results indicate that Artemisia afra extract is non-toxic when given acutely, has low chronic toxicity potential and, in high doses, may have a hepatoprotective effect.

Tomoko MUTO Thirteen-week repeated dose toxicity of wormwood (Artemisia absinthium) extract in rats. J Toxicol Sci. 2003 Dec;28(5):471-8.

A 13-week repeated dose toxicity study of wormwood extract was performed in both sexes of Wistar ats. All rats had survived at the end of the study, and no changes indicating obvious toxicities that are attributable to the treatment of wormwood extract were observed in the body weights, hematological and serum biochemical examinations, organ weights, and histopathological examinations.

             Thèse de Doctorat,  Sadia MANSOUR 2015, Université des Sciences et de la Technologie d’Oran

             Nikodimos Eshetu, Mekbeb Afework, Eyasu Makonnen. Evaluation of the Acute and Sub-chronic Toxic Effects of Aqueous Leaf Extracts of Artemisia afra on Liver, Kidney and Some Blood Parameters in Wistar Rats Advances in Bioscience and Bioengineering 2016; 1(1): 1-9

For acute toxicity study, aqueous extracts of the leaves were administered in a single dose of 200, 700, 1200, 2200, 3200, 4200 and 5000mg/kg body weight, while the low dose (600mg/kg) and triple of lower dose (1800mg/kg) were used for sub-chronic toxicity studies.  The current study showed that the median oral lethal dose (LD50) was greater than 5000mg/kg. Acute toxicity study revealed some changes in general behavior of the rats above 3200mg/kg. The levels of blood parameters did not change though AST level decreased significantly in female animals after 90 days of sub-chronic treatment with 1800mg/kg. Histopathological presentations were generally normal.  The aqueous extract of Artemisia afra at the test doses did not show significant toxicity: the minor inflammatory changes observed in this study were not accompanied by significant change in any of the hematological andbiochemical markers of liver injury.

           G.A. Chuipet. Etude préliminaire à l’utilisation d’une phytothérapie d’Artemisia annua à l’usage d’enfants < 5 ans.Thèse de doctorat en pharmacie, Université des Montagnes, 2011

Neither aqueous decoctions of Artemisia annua, nor a lemonade made thereof showed any toxic effect

           G Chu J Toxicol Sci. 2003 Dec;28(5):471-8.

           A Moufid and M Eddouks. Artemisia herba alba , a popular plant with potential medicinal properties, Pak J Biolog Sci. 2012, 15(24) 1152-1159

           Muto T, Watanabe T, Okamura M, Moto M, Kashida Y, Mitsumori K

           Idris Ahmed Issa and Mohammed Hussen Bule. Hypoglycemic Effect of Aqueous and Methanolic Extract of Artemisia afra on Alloxan Induced Diabetic Swiss Albino Mice . Evidence-Based Complementary and Alternative Medicine Volume 2015 (2015), Article ID 752486,

           Maria Kokkini.  Evaluation of toxicity in infusions of Artemisia absinthium of Greek flora and determination of α- and β-thujone in them. 2nd International Conference on Food Safety and Regulatory Measures,

           Nefeli-Sofia Maria K.Kokkini , Determination of ɑ-and β-thujone in Wormwood and Sage Infusions of Greek flora and Estimation of their Average Toxicity. Current Research in Nutrition and Food Science Vol. 4(SI. 2), 152-160 (2016)

          TC Mungho, G Tobela. Acute toxicity and hypertensive effects of Artemisia afra in spontaneously hypertensive rats. Research Journal of Biotechnology 2018 13, 1-5

These papers have confirmed that Artemisia infusions are innocuous up to 5000 mg/kg of dried plant extracts and although it administers doses of artemisinin 100 x lower than those of the ACT pills, it cures >95% of the malaria infections. The authors evluated the toxicity against Vibrio fischeri and found no correlation between thujone content and toxicity content, indicating that toxicity might be attributed to other constituents of the wormwood and sage infusions.

It has no toxicity against bone marrow

        Lofty AA, Ghanem LY, Shenawy AM Assessment of the toxicity of Artemisia inculta extract on the bone marrow of mice infected by schistosomiasis. Arzneimitelforschung 2006, 56(2), 104-7

Many studies have shown that Artemisia annua stimulates the immune system. This effect is probably due to other constituents than artemisinin: essential oils, flavonoids, coumarins, polysaccharides, saponins, tannins, pentacyclic triterpenes. The research work from the University des Montagnes in Cameroon even indicates that Artemisia annua tea lowers the alanine aminotransferase (ALAT) and could be hepatoprotective. The outcome suggests that artesunate toxicity may possibly cause damages to the hepatocytes and liver function; effect contrary to that of A. annua, who keeps cells alive and is hepatoprotective.

         N k u i t c h o u - C h o u g o u o K. Ro s i n e D . , Kouamouo Jonas, Titilayo O. Johnson, Djeungoue P. Marie-Ange, Chuisseu Pascal, Jaryum, Kouemeni Lysette,  Lutgen Pierre , Tane Pierre, Moudipa F. Paul.  Comparative study of Hepatoprotective and Antioxidant Activities of Artesunate and A r t e m i s i a  a n n u a Flavonoids on rats hepatocytes. Pharmacognosy conference Sao Paolo, Aug 29-30, 2016

Pamela Weathers in a personal communication : « In all our animal studies using mainly mice, but also rabbits and rats, we have never observed any toxicity of up to 100 mg of Artemisia annua-delivered artemisinin per kg animal body weight. Indeed, in several trials powdered Artemisia leaves were gavaged daily into mice for up to 9 and 14 days, respectively, with no adverse effects on any of the animals.