The flip side of Ayurveda.UM Thatte, NN Rege, SD Phatak, SA Dahanukar
Dept. of Pharmacology, Seth GS Medical College & KEM Hospital, Parel, Bombay, Maharashtra.,
Keywords: Adverse Drug Reaction Reporting Systems, Aged, Anemia, chemically induced,Case Report, Coma, chemically induced,Consumer Product Safety, Drug Industry, Drug Labeling, Fatal Outcome, Human, Hypoglycemia, chemically induced,Male, Medicine, Ayurvedic, Middle Age, Patient Education, Physician′s Role, Plants, Medicinal, classification,
"A 62 year old male patient was brought to the casualty in an unconscious state. A detailed history from relatives revealed that he was a known diabetic whose hyperglycemia was well controlled with insulin and glibenclamide. Five days earlier he had started an ayurvedic drug for psoriasis. He developed giddiness following ingestion of the drug, but ignored it. Subsequently, he became unconscious. He was diagnosed to be in hypoglycemic coma to which he ultimately succumbed."
While investigating the causes for such sudden hypoglycemia, the attending physician would naturally question, "Could the ayurvedic drug be responsible for the hypoglycemia?". This case was referred to the Adverse Reactions (Ayurvedic drugs) Monitoring Cell of the Ayurveda Research Centre of King Edward Memorial Hospital. On scanning available ayurvedic literature, no reference could be found describing metabolic actions of any of the constituents of this medication. Subsequent animal studies revealed, however, that in occasional mice a significant hypoglycemia occurred, reiterating the fact that the adverse interaction in the patient could have been due to the inadvertent co-administration of the ayurvedic agent and powerful hypoglycemic agents.
This case dramatically illustrates the sequel of self-administering 'ayurvedie' drugs and emphasises the fact that there is indeed a flip side to Ayurveda. We present in this brief article, the other side of Ayurveda.
A question that will arise at the outset is why read about adverse effects of ayurvedic drugs (let alone their uses or benefits) if we do not practice Ayurveda? The answer to this question is simple: over 80% of our population takes ayurvedic medicines - either self-prescribed or through a ‘Vaidya’. These same patients expect to be treated by our medicines while simultaneously taking ayurvedic medicines often leading to interactions of the type described above.
Another point to note is that a large number of herbal preparations are in the market under the label 1 ayurvedic Drugs'. Due to aggressive salesmanship and over-the-counter (OTC) availability, these drugs are prescribed by doctors and consumed by patients widely.
Hence, it is obvious, that at least in our country, we have to be aware of salient beneficial and adverse effects of commonly used ayurvedic drugs as much as of allopathic agents.
Ayurvedic drugs that one is likely to encounter in practice can be discussed under two broad categories: a) the traditional formulations including for example kadhas (decoctions), arishthas (decoctions containing alcohol) or gutis (pills) and b) the so called ayurvedic formulations which are a combination of different herbal extracts (sometimes aqueous, sometimes alcoholic). These plants are prescribed individually or together for a particular condition in ayurvedic texts. However, their fixed dose combination, as marketed, may not be mentioned therein. These herbal medicines are prescribed for a wide variety of non-specific conditions like improving vitality, anti-stress effects, boosting immunity and increasing appetite or memory!
Since, in this article we are discussing adverse reactions, we shall for the moment assume efficacy of these herbal preparations. It is an old adage of pharmacology that teaches us that if a drug is effective it is most likely to produce a side effect .
In fact, standard text-books of Ayurveda mention that ayurvedic drugs, if improperly used can be toxic. Charaka states in the Sutrasthana of the Charaka Sarnhita - "A potent poison also becomes the best drug on proper administration. On the contrary, even the best drug becomes a potent poison if used badly".
Ayurvedic texts classify toxic plants (See [Table - 1]) into different categories depending on the part of the plant that is toxic. Subsequent research has revealed the exact chemical nature of the toxic alkaloid validating the knowledge laid down in ayurvedic texts.
In fact, in Ayurveda, there is a separate science which deals with toxicological aspects and is known as Vishagarvajrodhika tantra' (toxicology).
There are enough grounds to conjecture that some knowledge regarding toxicity of plants was obtained through observation of behaviour of insects and animals towards these plants. Plants, which were never infested with insects, were considered dangerous: these were later shown to contain repellants like anthraquinone, naphthalene or nimbidine. Plants like vinca or nerium from which animals steer clear have later been shown to contain toxic materials. Aconitum does not allow any other plant in its vicinity! An interesting feature about ancient ayurvedic physicians worth noting, and perhaps emulating, is their ability to improvise on information they had, using whatever facilities were at hand. Thus, for example, when the physicians discovered that a particular plant was visciously toxic and perhaps fatal, they evolved ways by which the toxic components could be destroyed and converted them not only to safe but further therapeutically useful entities! The story of Aconitum heterophyllum is illustrative in this respect. The roots of this plant are considered toxic (they contain an alkaloid aconitine) and following ingestion of roots, the toxicity manifests in the form of tingling numbness of mouth and throat, abdominal pain, loss of muscle power, visual and auditory disturbances and finally clonic convulsions . However, aconite forms an important constituent of ayurvedic formulations. The aconite used in the formulations is not a crude agent but one, which is processed. This processing involves boiling of roots with 2 parts of cow's urine (7 hours per day) for 2 consecutive days. The roots are then thoroughly washed with water and boiled with 2 parts of cow's milk for the same duration. These are washed again with lukewarm water, cut into pieces, dried and ground. It has been shown that aconite becomes safe only after this elaborate process and all the steps are 6 essential for complete detoxification,.
Besides toxicology, ayurvedic pharmacology describes in some detail the side effects that can occur with different therapeutically useful drugs. Further, it also describes ways (which also include manufacturing techniques) to minimise these side effects. Just like we, for example, would advise that NSAIDs should not be taken on an empty stomach, Ayurveda gives instructions regarding time of drug administration, the relationship with food, type of food which should be avoided/permitted with the drug etc. The do's and don'ts are clearly enunciated. For example, amalki (amla, Emblica officinalis) should be avoided at bedtime to prevent harmful effects on teeth . Chyavanprash contains large quantities of Amla - one wonders whether the package insert with any Chyavanprash mentions this precaution! Similarly, pippali (Piper longum) used in asthma should be avoided in patients with peptic ulcer disease and should be consumed with milk .
Tribhuvankirti is a combination of several plants which is very commonly used to treat a "cold in the head" and fever. There are clear instructions in Ayurveda that because it contains aconite [Table - 1] it should be used cautiously. When used, it should be taken with tulsi (holy basil) juice, ginger juice or honey.
Guggul is derived from the resin of Commiphora mukul  and is used in a variety of diseases including hypercholestrolemia (in fact gugglulip has been introduced into the market for this condition) and arthritis. Ayurveda specifies that guggul should be used cautiously in patients with peptic ulcer disease. While on guggul therapy the patient is advised to avoid sour food, alcohol and heavy exercise,.
The subject of teratogenecity also figures in Ayurveda. Thus, certain plants like Terminalia hebula (harda) are to be avoided in pregnancy. This is a constituent of a large number of OTC preparations. It is a powerful purgative and is supposed to stimulate GI motility and would therefore be contraindicated in pregnancy! This fact is not sufficiently publicised.
Apart from plants, Ayurveda also includes metals in its formulary. Thus, several preparations containing metals like mercury, lead and copper are available readily in the market on OTC basis. These metals have to be deligently processed before they are suitable for human consumption and there is again a long list of do's and don'ts regarding their use. Unfortunately, there are no quality control methods to standardise such metal containing drugs and to find out whether processing of metal is done appropriately so as to render it nontoxic. This thus increases the probability of toxic effects.
The case history of a 70-year-old male patient referred to the ADR monitoring cell illustrates the relevance of being aware of these. This patient was taking a 'herbo-mineral' preparation 'Mahayograj Guggul' in the dose of 4 tablets three times a day, for the complaints of joint pains for well over two years. He got relief from the arthritis but developed symptoms of lead poisioning including severe anaemia with classic basophilic stippling of the RBCs. The case was referred to the ADR cell with the query whether Mahayograj Guggul could lead to this problem. As this preparation contains lead, our centre adviced immediate withdrawal of the preparation.
This particular preparation is prescribed for rheumatoid arthritis in ayurvedic texts and contains several plants and metals as shown in [Table - 2]. Ayurvedic textbooks recommend a special pharmaceutical process to detoxify the metals. The lead in this preparation has to be processed by first heating over a fire till it glows. It should then be cooled by dipping into a mixture of sesame oil, buttermilk, cow's urine and a decoction of three plants, viz. amia (E.officinalis), beheda (T. bellerica) and harda (T. chebula). After repeating this procedure thrice, the lead is heated the fourth time following which it is dipped into a churna (powder) made of the rind of tamarind and Piper longum. This lead is then mixed with arsenic sulphide and wrapped in a betel leaf and warmed in a crucible to a fixed temperature. This process is repeated thirty times before nagabhasma or processed lead is ready for use. In addition, in the doses that this patient was taking the drug he would have consumed a phenomenal 414 mg lead per day for more than 2 years leading to lead toxicity. There are two points to note in this case. Firstly, Ayurveda definitely reconimends Mahayogiraj Guggul for rheumatoid arthritis but has cautioned about duration of therapy, which was overlooked. Secondly, as there are no quality control procedures in existence, there is rio way to know whether the lead in this formulation had been processed in the complex way it should have been.
This brings us to the second group of the 'herbal' formulations marketed under the label 'Ayurvedic'. All doctors are aware that such preparations are available, many may be prescribing them and some will come across patients self-medicating themselves with these drugs. What exactly are these drugs and what do we know about them? Most doctors prescribe these agents, in spite of lack of sufficient clinical studies (using the randomised controlled clinical trial model) proving their efficacy in comparison to allopathic drugs, in the utopian misconception that "never mind if they are ineffective, they will be safe!"
What adverse effects can occur with such formulations? The most glaring are possible drug interactions with the usually co-administered allopathic drugs. Several plants have been shown to alter bio-availability of allopathic drugs.
Similarly when used in combination with allopathic drugs they may alter their pharmacodynamics. The example in the diabetic patient described earlier is illustrative. Further, such herbal preparations may produce toxicity, often unexpectedly, per se.
A very herbal remedy is the need to conduct safety studies on them. Protagonists for this believe that with the changing ecological environment, use of pesticides, new manufacturing techniques, modern formulations and combinations of herbs not prescribed in ayurvedic texts, the need for looking at ayurvedic herbal drugs as new drug entities cannot be ignored. This is being seriously considered by the office of the Drugs Controller of India and an amendment to the laws governing manufacture and sale of ayurvedic drugs is on the anvil.
Opponents feel however that herbal remedies are natural remedies and are beyond conventional toxicity studies. Further developmental costs would be formidable.
Is there a via media? Perhaps incorporation of any or all of the methods summarised in [Table:3] would optimise use of ayurvedic drugs.
The Adverse Drug Reaction monitoring cell for Ayurvedic Drugs has been set up at the Ayurveda Research Centre of King Edward Memorial Hospital, Mumbai with several aims. Alongwith documenting anecdotal case reports suggestive of adverse effects to ayurvedic drugs, (please see ADR reporting card) we also, where necessary conduct studies in animals to confirm or rule out the cause and effect relation between the drugs and side effects reported. Further we give information related to ayurvedic drugs.
In conclusion we can reiterate that in view of the fact that we are
a) not using ayurvedic drugs only in the form as described in standard texts,
b) making over-the-counter formulations without much heed to the need for individualisation,
c) giving ayurvedic drugs in combination with allopathic agents which have a narrow therapeutic margin,
d) using raw plant material that is possibly polluted by environmental and ecological devastation,
e) not having good quality control methodologies,
We must beware. We must not wait for a thalidomide- like tragedy in Ayurveda to shake us out of our complacence that ayurvedic drugs are safe!
[Table - 1], [Table - 2]