1. Clinical toxicology of Ayurvedic medicines
Ruben Thanacoody
NPIS (Edinburgh)

2. 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
Ayurveda (meaning science of life in Sanskrit) is a comprehensive holistic medical system which evolved in India more than 5000 years ago. This medical system subsequently evolved into 2 schools of learning: the School of Physicians and the School of Surgeons, similar to allopathic medicine.

3. Ayurvedic medicines Commercialisation Increasing use
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
Ayurvedic physicians are encouraged to prepare their own Ayurvedic medicines which are remedies based on natural sources such as herbs, metals and minerals and prepared using traditional methods. They are classified in the Ayurvedic pharmacopoeia according to the constituents, taste, potency, postdigestive effect and any special action. Apart from being used by 80% of India’s population as a traditional system of healthcare, ayurvedic medicine has gained widespread acceptance in the Western world over the last few decades. As Ayurvedic medicines are marketed as dietary supplements, they are not subject to the same stringent regulations as pharmaceutical drugs with regards to efficacy and safety. The large increase in immigrant populations from the Indian subcontinent has led to increased availability and utilisation of traditional Ayurvedic medicines which may be purchased from retail stores and over the internet without medical consultation. This has been associated with a concomitant rise in reports of toxicity associated with these traditional remedies.

4. She hopes a stash of Ayurvedic medicines will help her conceive.
THE MAKING OF MADONNA
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.
Traditional medicine takes on the world
Source: BBC website

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

6. 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:
Patient was treated with a chelating agent D-penicillamine. His excretion of δ-aminolevulinic acid dropped to normal after four weeks.

7. 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:
Interview of 360 Indian patients living in the UK, 82 used “kushtay” used as tonic. 11 of samples from 37 patientds contained Hg, Pb and As.
22 samples in Bombay, Madras and Delhi collected by US researchers in 1988
Stores 20 miles or less from Boston City Hall that sold Ayurvedic HMPs from South Asia. Ayurvedic HMPs between April 25 and October 24, 2003 bought. A total of 14 (20%) of 70 HMPs (95% confidence interval, 11%-31%) contained heavy metals: lead (n = 13; median concentration, 40 µg/g; range, 5-37 000), mercury (n = 6; median concentration, 20 225 µg/g; range,  000), and/or arsenic (n = 6; median concentration, 430 µg/g; range, ). If taken as recommended by the manufacturers, each of these 14 could result in heavy metal intakes above published regulatory standards.

8. Saper et al 2004

9. Lead poisoning and anaemia
Kales SN et al. Med Sci Monit. 2007;13: 295-8
47 from Ayurvedic medicines
19 from lead paint
Higher blood lead concentrations
Lower haemoglobin

10. Contaminant or incomplete processing?
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.
Medicinal properties
Toxicity well-known
Detoxification process
Complex oxidation processes
Bhasmas (Ash)
Ayurvedic practitioners believe in the healing properties of heavy metals which form part of an estimated 40% of these preparations. Bhasmas, Ayurvedic metallic preparations with herbal juices or fruits are used for treating a variety of chronic ailments and contain metals such as mercury chelated with organic ligands derived from medicinal herbs Inherently toxic plant extracts e.g from Aconitum and Ricinus communis are included in some Ayurvedic formulations, although the traditional preparation process includes an elaborate detoxification technique (known as samskaras) specific to the ingredient. The usefulness of this process is unclear but has been shown to be effective in completely eliminating the toxicity of aconite in mice(1). Commercially available Ayurvedic preparations may not adhere rigidly to this complex procedure, therefore exposing patients to toxic unprocessed herbal ingredients.
4 successive rounds of boiling the crude root in cow's urine (twice) for 3-4 days and cow's milk (twice) for 6 hours.

11. Adulteration/Contamination
Fake preparations containing steroids
Organochlorine pesticide residues
Rai V et al. Environ Monit Assess. 2007(in press)
In view of the herbal nature of these medicines, contamination with pesticides is also a matter of concern. Organochlorine pesticide residues have been found in the stems and roots of herbs used in Dashmoola, a widely used Ayurvedic formulation. α-HCH and γ-HCH (hexachlorocyclohexane) were present in almost all the samples, but other pesticides were not detected in these samples. DDT and DDE were found only in two samples.
The widening market for ayurvedic medicines has resulted in the manufacture of fake preparations adulterated with synthetic drugs such as steroids

12. 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
Polypharmacy is the norm in Ayurvedic medicine. Preparations contain multiple active ingredients

13. Pharmacodynamic interactions
Sarpaghandha (Rauwolfia serpentina)
Datura (Datura metal)
Yavani (Hyoscyamus niger)
Kapikachchha (Mucuna pruriens)
Sarpagandha is the source of reserpine, an anti-hypertensive drug used briefly during the 1970's.
Traditional Ayurvedic Uses: nervous excitement, hysteria, insomnia, anxiety, intestinal colic, bronchial asthma, motion sickness.
Must be used in small amounts as it contains hyoscyamine, an atropine-like alkaloid which is sedative in large doses. Use 100 mg. of the powdered root twice per day with food.
Mucuna pruriens Kapikachchha
Traditional Ayurvedic Uses: general weakness, Parkinson's disease, hypercholesterolemia, nervous disorders
Seeds contain L-DOPA (L-3,4-dihydroxyphenylalanine) which is a neurotransmitter deficient in parkinsonism. Sushruta mentions these seeds as a virilifier.
Datura metal
Traditional Ayurvedic Uses: asthma, whooping cough, muscle spasm, sciatica (due to muscle spasm), painful menstruation
Contains tropane alkaloids, scopelamine, hyoscyamine and someatrapine

14. 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:
During routine phenytoin monitoring unexpected low levels of phenytoin were observed in two patients taking shankhapuspi and phenytoin.
Single dose SRC and phenytoin (oral/i.p.) coadministration did not have any effect on plasma phenytoin levels but decreased the antiepileptic activity of phenytoin significantly. On multiple-dose coadministration, SRC reduced not only the antiepileptic activity of phenytoin but also lowered plasma phenytoin levels.

15. Ashwagandha and Digoxin Assay
(Withania somnifera) contains withanolides structurally similar to digoxin
Interferes with both
FPIA digoxin assay(falsely elevated)
MEIA digoxin assays (falsely low) .
Latin Name: Withania somnifera
Traditional Ayurvedic Uses: general fatigue, rejuvenator, muscular weakness, stress- induced debility, anxiety, sexual debility in men and women, nervous exhaustion, rheumatoid arthritis pain, wound healing, asthma.
Withania somnifera Dunal, commonly known as ashwagandha, has been used for centuries in Ayurvedic medicine to increase longevity and vitality. Western research supports its polypharmaceutical use, confirming antioxidant, anti-inflammatory, immune-modulating, and antistress properties in the whole plant extract and several separate constituents.
Some preparations such as Ashwagandha contain withanolides which are structurally similar to digoxin and interfere with some digoxin assays, giving a falsely lowered digoxin concentration, potentially leading to unwarranted increase in the digoxin dose.
Dasgupta et al.Am J Clin Path 2005;124:

16. Teratogenicity Asparagus racemosus roots Teratogenic in rats
Goel RK et al.Indian J Exp Biol ;44(7):570-3.
Lead-containing preparations
Congenital paralysis and sensorineural deafness
Asparagus racemosus (AR) is a herb used as a rasayana in Ayurveda and is considered both general and female reproductive tonic. Methanolic extract of A. racemosus roots (ARM; 100 mg/kg/day for 60 days) showed teratological disorders in terms of increased resorption of fetuses, gross malformations e.g. swelling in legs and intrauterine growth retardation with a small placental size in Charles Foster rats. Pups born to mother exposed to ARM for full duration of gestation showed evidence of higher rate of resorption and therefore smaller litter size. The live pup showed significant decrease in body weight and length and delay of various developmental parameters when compared to respective control groups. AR therefore, should be used in pregnancy cautiously as its exposure during that period may cause damage to the offspring.

17. 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)
In addition to its carcinogenicity –urothelial carcinomas, aristolochic acid is also highly nephrotoxic and may be a causative agent in Balkan nephropathy.
Salacia oblonga has been used for thousands of years in Ayurvedic medicine for the oral treatment of diabetes. The root extract has been shown to inhibit the activity of intestinal alpha-glucosidases, therefore S. oblonga holds potential as a natural method to mitigate the blood glucose response for people with diabetes. A reproducible, although weak, positive chromosomal aberrations response in human lymphocytes is of concern and further toxicity research is recommended.

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

19. 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:

20. Conclusion
Ayurvedic medicines contain potent biologically active ingredients.
Risk of heavy metal poisoning
Regulation of these products desirable.
It is not possible to make accurate estimates of the risk of heavy metal poisoning associated with ayurvedic medicines but they have now surpassed environmental factors as the major cause of lead poisoning in Western countries. A history of ayurvedic medicine use should be actively sought in patients presenting with symptoms and signs of lead poisoning. Education of users about the potential risks and more effective regulation of these traditional remedies are required.