Clinical toxicology of Ayurvedic medicines Ruben Thanacoody NPIS (Edinburgh)

Ayurvedic medicine Comprehensive holistic medical system 4500BC “Knowledge or science of life” Kayachikitsa Internal Medicine Shalya Tantra General Surgery BhutavidyaPsychiatry Agada TantraToxicology Rasayana Tantra Nutrition, Detoxification and Rejuvenation KaumarabhrtyaPaediatrics/Obstetrics/ Gynaecology VajikaranaFertility and Virility ShalakyaOtorhinolaryngology

Ayurvedic medicines Individually prepared Based on herbs and minerals Classification in Caraka Samhita (150BC-100AD) –Elemental constituents –Taste –Potency –Postdigestive effect –Therapeutic action (50 groups) Commercialisation Increasing use Wider availability –Health food stores –Ethnic shops –Internet retailers Lack of Regulation

THE MAKING OF MADONNA Traditional medicine takes on the world India drug gives Alzheimer's hope EXCLUSIVE: MADONNA BABY BID MADONNA is using old Indian fertility remedies to try for a third child at the age of 46. She hopes a stash of Ayurvedic medicines will help her conceive. Source: BBC website

Clinical Toxicology Contamination/Incomplete processing/ Adulteration –Heavy metal poisoning Herb-drug interactions Genotoxicity Teratogenicity

Case history 37 year old man admitted with weakness, dizziness and muscle pain. He visited India and had bought several Ayurvedic medicines. Hb 7.8 g/dl Blood lead 58 μg/dl Urinary arsenic 24.1 μg/dl/L (normal<20) Lead content of Ayurvedic medicine 238 μg/gm. Spriewald et al. Occup Environ Med 1999; 56:

Heavy metal content England 1979: 30% (11/37) samples of “kushtay” –Aslam M et al.Public Health. 1979;93: India 1988: 64% contain lead and mercury, 41% arsenic and 9% cadmium. –McElvaine MD et al. JAMA. 1990;264: Boston USA 2003: 20% (14/70) of preparations contain toxic concentrations of lead, mercury and arsenic. –Saper KB et al.JAMA 2004;292:

Saper et al 2004

Lead poisoning and anaemia Kales SN et al. Med Sci Monit. 2007;13: 295-8

Contaminant or incomplete processing? Medicinal properties Toxicity well-known Detoxification process –Complex oxidation processes –Bhasmas (Ash) Vatsanabha (Aconitum sp.) Detoxification of aconite (samskaras) Crude aconite –100% mortality at a dose of 2.6 mg/mouse Fully processed aconite –no mortality at 8x dose crude aconite). Thorat S, Dahanukar S. J Postgrad Med ;37(3):157-9.

Adulteration/Contamination Fake preparations containing steroids Organochlorine pesticide residues –Rai V et al. Environ Monit Assess. 2007(in press)

Herb-drug interactions Brahma Rasayana is beneficial for promoting mental clarity, improved memory and cognition whilst improving resilience to mentally demanding lifestyles. Amla (Emblica officinalis), Haritaki (Terminalia chebula), Mandukaparni (Centella asiatica), Pippali (Piper longum), Shankapushpi (Convovulus pluricalis ), Plava (Cyperus scariosus), Musta (Cyperus rotundus), Chandana (Santalum album), Agaru (Aquallaria agolcha), Yastimadhu (Glycirrhiza glabra), Haridra (Curcuma longa), Vacha (Acorus calamus), Nagakeshar (Messua ferrea), Ela (Eletaria cardamomum), Twak (Cinnamomum zeylanicum), Bilva (Aegle marmelos), Agnimantha (Clerodendrum phlomides), Syonaka (Orroxylum indicum), Patala (Stereospermum suaveolens), Gambhari (Gmelina arborea), Shalaparni (Desmodium gangenticum), Brihat (Solanum indicum), Prishniparni (Uraria picta), Kantakari (Solanum xanthophylum), Gokshura (Tribulus terrestris), Punarnava (Boerhaavia diffusa), Mudga parni (Phaseolus trilobus), Mashaparni (Teramnus labialis), Bala (Sida cordifolia), Eranda (Ricinus communis), Jeevanti (Leptatenia reticulate), Shatavari (Asparagus racemosus), Shara (Saccharum munja), Ikshu (Saccharum officinarum), Kasha (Saccharum spontaneum), Darbha (Desmostachya bipinnata), Kapikacchu (Mucuna pruriens), Sesame oil, Rock sugar, Honey

Pharmacodynamic interactions Sarpaghandha (Rauwolfia serpentina) Datura (Datura metal) Yavani (Hyoscyamus niger) Kapikachchha (Mucuna pruriens)

Phenytoin/Shankhapuspi Interaction Single dose of phenytoin and this herb did not alter phenytoin serum levels in rats but decreased antiepileptic activity. Multiple dose co-administration reduced both antiepileptic activity and serum phenytoin levels. Dandekar et al. J Ethnopharmacol 1992;35:

Ashwagandha and Digoxin Assay Ashwagandha (Withania somnifera) contains withanolides structurally similar to digoxin Interferes with both –FPIA digoxin assay(falsely elevated) –MEIA digoxin assays (falsely low). Dasgupta et al.Am J Clin Path 2005;124:

Teratogenicity Asparagus racemosus roots –Teratogenic in rats –Goel RK et al.Indian J Exp Biol ;44(7): Lead-containing preparations –Congenital paralysis and sensorineural deafness

Genotoxicity Birthwort (Isharmul, sunanda) –Contraceptive –Aristolochia indica –Carcinogen banned in Europe and US Salacia oblonga roots –Weak genotoxicity in vitro –Flammang AM et al.Food Chem Toxicol. 2006; 44(11): Arsenic-containing preparations –Skin and haematological cancers Gold LS. NEJM 2003; 349: 1576 (letter)

All substances are poisons; there is none which is not a poison. The right dose differentiates a poison from a remedy.” Paracelcus

Charaka samhita Sutra sthana 1/ Type and dose of the drug as per the specification of every individual, if done by a physician before the use of the medicine, he should be called a quality physician If processed and used properly, a deadly poison can become a life saving medicine. A lifesaving medicine medicine can become poison if not used properly Rastogi et al. Int J Risk & Saf Med.2007;19:

Conclusion Ayurvedic medicines contain potent biologically active ingredients. Risk of heavy metal poisoning Regulation of these products desirable.