Aristolochic acid

Aristolochic acids are various derivatives of aristolochic acid (molecular formula C17H11NO7). Aristolochic acid is a plant acid, a yellow, bitter-tasting crystal powder that is easily soluble in alcohol, ether and chloroform.

The versch. Aristolochic acids are secondary plant compounds, toxic aromatic nitro compounds found in species of the genera Aristolochia(pipe flowers), Asarum (hazel root), Saruma and Thottea, from the family Aristolochiaceae (Easter lily family). The occurrence of aristolochic acids outside the family Aristolochiaceae is not documented in plants.

Various aristolochic acids were formerly contained in some common slimming preparations, mainly from Chinese medicine, as well as in tonics (e.g., women's gold). Various preparations contained the sodium salt of aristolochic acid and were used as immunostimulants in infections.

Aristolochic acid has been shown to be nephrotoxic and carcinogenic. Thus, the so-called "Balkan nephropathy" (see acute tubulointerstitial nephritis), a chronic toxic interstitial kidney disease endemic in some regions of Romania, Bulgaria and Serbia, is caused by aristolochic acid (Turesky RJ et al. 2015). It was common there to mix bread flour with seeds of the common Easter lucis (Aristolochia clematitis). This caused the toxic kidney damage. Furthermore Aristolochic acid is mutagenic. The mutagenicity is based on a transversion of A-T nucleotide pairs to T-A at different locations in the genome.

In Germany, all "human and veterinary medicinal products containing aristolochic acid, including phytotherapeutic and homeopathic medicinal products produced using plants containing aristolochic acid" are considered to be of concern. According to § 5 AMG, placing on the market is therefore prohibited (www.bfarm.de/cln).

Excluded are homeopathic medicinal products containing preparations of plants of Aristolochia Asarum from potency level D11 onwards (www.bfarm.de/cln). An acceptable risk is assumed for this potency level. It corresponds to a maximum daily exposure of 3.6 pg Aristolochic acid.

Aristolochic acid is found in contaminated alternative Chinese remedies and was the trigger of the so-called "Chinese herb nephropathy" that occurred in Belgium and Japan, a chronic interstitial nephritis that led to a slowly progressive renal insufficiency (Luciano RL et al. 2015) with a partly fatal course, respectively increased cancer risk.

1. Debelle FD et al (2008) Aristolochic acid nephropathy: a worldwide problem. Kidney Int 74:158-169.
2. Luciano RL et al (2015) Aristolochic acid nephropathy: epidemiology, clinical presentation, and treatment. Drug Saf 38:55-64.
3. Turesky RJ et al. (2015) Aristolochic acid exposure in Romania and implications for renal cell carcinoma. Br J Cancer 114:76-80.
4. Yi JH et al. (2018) Effects of aristolochic acid I and/or hypokalemia on tubular damage in C57BL/6 rat with aristolochic acid nephropathy. Korean J Intern Med 33:763-773.
5. https://www.bfarm.de/SharedDocs/Downloads/DE/Arzneimittel/Pharmakovigilanz/Risikoinformationen/RisikoBewVerf/a-f/aristolochia_bescheid.pdf?__blob=publicationFile
6. https://www.aerzteblatt.de/archiv/20236/Phytotherapeutika-Wie-harmlos-sind-sie-wirklich

7. Tanaka A et al (1997) Chinese herbs nephropathy. Jap J Nephrol 39(8): 794-797