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 • Bhutavidya Psychiatry • Agada Tantra Toxicology• Rasayana Tantra Nutrition, Detoxification and

Rejuvenation • Kaumarabhrtya Paediatrics/Obstetrics/

Gynaecology• Vajikarana Fertility and Virility• Shalakya Otorhinolaryngology

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: 282-283

Heavy metal content • England 1979: 30% (11/37) samples of “kushtay”

– Aslam M et al.Public Health. 1979;93:274-284

• India 1988: 64% contain lead and mercury,

41% arsenic and 9% cadmium. – McElvaine MD et al. JAMA. 1990;264:2212-2213

• Boston USA 2003: 20% (14/70) of preparations contain toxic concentrations of lead, mercury and arsenic.– Saper KB et al.JAMA 2004;292: 2868-2873.

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. 1991 ;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: 285-288.

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;124:229-336

Teratogenicity

• Asparagus racemosus roots– Teratogenic in rats– Goel RK et al.Indian J Exp Biol. 2006 ;44(7):570-3.

• 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):1868-74.

• 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 1493-1541

Charaka samhita

• Sutra sthana 1/124-127

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;19:117-125

Conclusion

• Ayurvedic medicines contain potent biologically active ingredients.

• Risk of heavy metal poisoning

• Regulation of these products desirable.