Not all Chinese medicinal herbs are safe. One group in particular causes serious kidney diseases and cancers due to a series of compounds found in a wide variety of related plants. These compounds are the aristolochic acids (AA). They are found mainly in the Birthworts, or Dutchman’s Pipes which are common names for about 500 species of plants called Aristolochia (family: Aristolochiacceae) and in another genus, the wild gingers (Asarum).
The Birthworts are so named because they were given during childbirth to prevent parasite infection and promote healing. The plant has widespread use even in Europe where the European Birthwort can be found.
Aristolochic Acids
The aristolochic acids have long been known as carcinogens and mutagens with the capability of causing serious damage to the kidneys. A number of plants in both geni have been used in Chinese herbal medicine for centuries for weight loss. There is however renewed interest in the plants and their drugs, and warnings have been issued about the safety of some of the medicines derived from these two groups of herbs.
Chinese-Herb Nephropathy
A condition called Chinese-herb nephropathy occurs where the kidneys are slowly destroyed by a progressive interstitial nephropathy and by cancer. It is a form of renal fibrosis which prevents them from effectively filtering our urine. The condition was first observed amongst women taking weight-loss pills that supposedly contained a herb called Stephania tetranda (han fangji) (Vanherweghem et al., 1993). Analysis of the plant revealed the presence of aristolochic acids (AAs) rather than the expected compound, tetrandrine (Vanahelen et al., 1994). A clear case of misguided swopping of one plant for another was suspected rather then deliberate adulteration. The plant in question supplying the carcinogens was Aristolochia fangchi (guang fangji). These were later confirmed as AA derivatives or adducts in the kidneys of affected patients (Schmeiser et al., 1996; Nortier et al., 2000).
It is now recognised that use of AA containing drugs is endemic because of the desire to use slimming pills which contain the herb, Aristolochia fangchi (Debelle et al., 2008). The degree of research into the issue is extensive because the condition has become so widespread. Kidney diseases have been identified in the infamous Balkan endemic nephropathy situation (Grollman et al., 2007; Jelaković et al., 2012) which we discuss briefly later on, and in Taiwan too. These slimming pills are now banned in Belgium, UK, Canada, Australia, and Germany (Hashimoto et al., 1999; Lee et al., 2002; Zhou et al., 2013).
The latest evidence regarding the safety of aristolochic acids indicates a link with liver or hepatic cancers as reported in the journal Science Translational Medicine (Ng et al., 2017). In this study, 98 liver tumours stored in Taiwanese hospitals were found to have 78 per cent of mutation patterns associated with carcinogen damage. Comparisons with liver cancer samples in mainland China and from other countries indicated such well-defined similarities that AAs were suspected. It is thought that the effects of the AA based derivatives might take longer to show their effects in the liver compared to the kidney.
Briefly, one of the toxicological mechanisms induced by aristolochic acids is to induce ‘oxidative stress’ of the internal organs. The kidneys are more sensitive in many ways than the liver to this type of damage.
Balkan Endemic Nephropathy
Kidney diseases caused by aristolochic acids are not just restricted to poor quality control in chinese herbal medicines. A recent study has found that aristolochic acids are contaminating various foodstuffs especially grains grown throughout the Balkan Peninsula (Li et al., 2018). The offending weed is Aristolochia clematitis which grows easily in fields of all sorts of crops from this area. The condition they cause is Balkan endemic nephropathy which has been an issue for many years.
However, this study also looked at ways of combating such contamination. Using a combination of food additives acting as antioxidants and different cooking methods, the concentration of these aristolochic acids was reduced. The antioxidants are ones which are regarded as ‘healthy’ in their own right such as cysteine, glutathione, ascorbic acid, citric acid and magnesium.
Antioxidants counter the nephrotoxicity of these acids. A mix of magnesium with ascorbic acid converts the acids to non-mutagenic aristolactams. Aminothiols and glutathione convert the acids to aristolic acids which are also non-mutagenic.
References
Chen, C. H., Dickman, K. G., Moriya, M., Zavadil, J., Sidorenko, V. S., Edwards, K. L., … & Pu, Y. S. (2012). Aristolochic acid-associated urothelial cancer in Taiwan. Proceedings of the National Academy of Sciences, 109(21), pp. 8241-8246.
Debelle, F. D., Vanherweghem, J. L., & Nortier, J. L. (2008). Aristolochic acid nephropathy: a worldwide problem. Kidney International, 74(2), pp. 158-169
Grollman, A.P., et al.(2007) Aristolochic acid and the etiology of endemic (Balkan) nephropathy. Proc Natl Acad Sci USA 104 pp. 12129–12134
Hashimoto, K., Higuchi, M., Makino, B., Sakakibara, I., Kubo, M., Komatsu, Y., et al. (1999). Quantitative analysis of aristolochic acids, toxic compounds, contained in some medicinal plants. J. Ethnopharmacol. 64, pp. 185–189. doi: 10.1016/S0378-8741(98)00123-8
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Jelaković ,B., et al. (2012) Aristolactam-DNA adducts are a biomarker of environmental exposure to aristolochic acid. Kidney Int. 81 pp. 559–567
Lee, T. Y., Wu, M. L., Deng, J. F., and Hwang, D. F. (2002). High-performance liquid chromatographic determination for aristolochic acid in medicinal plants and slimming products. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 766, pp. 169–174. doi: 10.1016/S0378-4347(01)00416-9
Li, W., Chan, C-K., Wong, Y-L., Chan, K.K.J., Chan, H.W., Chan, W. (2018) Cooking Methods Employing Natural Anti-oxidant Food Additives Effectively Reduced Concentration of Nephrotoxic and Carcinogenic Aristolochic Acids in Contaminated Food Grains. Food Chem., https://doi.org/10.1016/j.foodchem.2018.05.052
Ng, A.W., Poon, S.L., Huang, M.N., lim, J.Q., Boot, A., Yu, W., Suzuki, Y., et al., (2017) Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia. Science Translational Medicine. 9 (412), eaan6446 DOI: 10.1126/scitranslmed.aan6446 18th October 2017
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What a weird plant and keep writing about them. I see loads of these plants in my back garden in Ghana. They grow like weeds. I am not sure of they are meant to be there. May be we cut them all down so we do not get ill.