What is the recommended dosage of Aristolochic acid in herbal medication in India?
| Chandrakant Bhanushali |
In Ayurveda, Aristolochic acid (AA) is not used directly as a constituent; but in a few Ayurvedic drugs the herbal sources of AA, especially Aristolochia indica (Ishvari/Nakuli) root is used. Aristolochia indica is used in a very small quantity (around two per cent) in these products when prescribed for internal use.
Ayurveda is well versed with the toxic effects of Aristolochia indica (Sanskrit: Nakuli, Ishwarmool). It is clearly mentioned that this herb, if taken in very high doses, causes inflammation of stomach and kidney, leading to nausea, vomiting, colic and even coma or death due to respiratory failure, if not treated immediately.
In Ayurveda, Aristolochia indica is indicated in fevers, as a pain killer in arthritic and colic pains and to induce labour pains. It is also indicated in snake poisons. The dose is very low (0.625 to 1.875 gm of whole plant powder) compared to the dose of routine herbal powders (which varies from 3 to 15 gm) in most of the Ayurvedic formulations. Aristolochia indica is only recommended for short durations.
Joelle LN, et al (N Engl J Med 2000; 342:1686-92), in their publication, mention that Aristolochia with total doses of more than 200 gm taken for mean duration of 15 months was associated with a higher risk of urothelial carcinoma. This dose is almost more than 100 times the dose recommended in Ayurvedic texts and that too for quite a long duration.
What are some of the medications being sold in India?
Ayurvedic medicines that contain Aristolochia indica include:
Mahavishagarbha Taila (for external application): Percentage not worked out as decoction of many herbs is processed with oil.
Poogakhanda (for internal use in debility, gastric-peptic disorders patients): Used in approximately 0.5 per cent as processed with ghee, sugar, herbal juices and milk. Market sale (turnover) of this product is negligible.
Gorochanadi Vati (for internal use in fever): Used in quantity of two per cent of the whole formulation. Market sale (turnover) of this product is negligible.
Since when have these products been banned in the US and why?
Aristolochic acid nephropathy (AAN), also known as Balkan endemic nephropathy, was evident in 1992 in a Belgian cohort of more than 100 patients after the intake of slimming pills containing a Chinese herb, Aristolochia fangchi. In April 2001, the Food and Drug Administration in the US issued a consumer health alert warning against consuming botanical products, sold as ‘traditional medicines’ or as ingredients in dietary supplements, containing AA. The agency warned that consumption of AA-containing products was associated with “permanent kidney damage, sometimes resulting in kidney failure that has required dialysis or transplantation. In addition, some patients have developed certain types of cancers, most often occurring in the urinary tract.”
What percentage of people in India suffer from kidney failure and is there any clinical evidence of it being attributed to AA in herbal medicines?
There are more than 20,00,000 patients with renal failure in India as of 2010, and 100,000 new patients with end-stage renal failure (ESRD) every year who require treatment. Of these patients alone, 9,00,000 patients will require dialysis, apart from the already existing patients. We could not find kidney failure prevalence that can be attributed to AA in herbal medicines, as there are very few herbal drugs in the Indian market which contain AA or Aristolochia species.
What is the current export of Indian herbal medicines with its CAGR?
Indian herbal medicines worth Rs 1730.41 crores were exported with an annual growth rate of 31.22 per cent. The biggest markets by sale include CIS and the African countries. We expect the exports to touch Rs 2000-crores figure this year.
What are the current standards being followed in order to ensure safety of the drugs?
Currently in India, standards as laid down in Ayurvedic Pharmacopoeia of India are being followed. A majority of adverse events (AEs) reported in relation to the use of herbal products and herbal medicines can be attributed to poor quality of the product and uneducated administration of the herbal drugs. In order to promote the safety and effective use of herbal medicines, internationally recognised guidelines for assessing their quality are established.
The World Health Assembly — in resolutions WHA31.33 (1978), WHA40.33 (1987) and WHA42.43 (1989) — has emphasised the need to ensure the quality of medicinal plant products by using modern control techniques and applying suitable standards. Today, the herbal medicines are by and large manufactured in GMP set-ups, and quality of the raw material as well as the finished products is assessed using the best methods currently available.
The analysis of herbal medicines is done at various levels, be it in view of the standard raw material based on the contamination limits or the qualitative and quantitative analysis of the active principles. The endeavour doesn’t end here, rather many techniques similar to those used for the analysis of synthetic drugs are also frequently employed (e.g. volumetric analysis, gravimetric determinations, gas chromatography, column chromatography, high performance liquid chromatography and spectrophotometric methods).