The dismal scenario of groundwater arsenic intoxication in third world countries –
Prolonged exposure to arsenic (As), a toxic metalloid, has caused various illnesses in millions of people globally distributed over some 20 countries. In Bangladesh and its adjoining part of West Bengal (India) alone, about 100 million people are at risk1 of As poisoning from drinking contaminated groundwater with concentration of As ranging from 60 to 560.23 µg/l (even exceeding 3000 µg/l at certain spots). This greatly exceeds the maximum permissible limits of 10-20 µg/l for some advanced countries and 50 µg/l for developing countries as laid down by both WHO2 and the US Environmental Protection Agency3. The problem of arsenic poisoning in third world countries is compounded by poor diet as well as prevailing health and hygiene conditions, especially in the rural areas. The attempts made so far by both Governmental and Non-Governmental organizations to provide As-free drinking water to the highly affected areas remain grossly inadequate. Various attempts are still being made to procure arsenic-free drinking water at an affordable cost. Serious effort should also be directed to remove As after it enters the body, because As also enters body through other sources. However, such efforts through orthodox medicines (e.g. chelating agents like DMSA, DTPA etc and some anti-oxidants) have not yet been reported to be successful by and large 1,4,5.Chronic exposure generally leads to various ailments and dysfunctions of several vital organs like liver, kidney, lung etc.6, more so when there is an accompanying nutritional/dietary deficiency7. Therefore, the overall situation is extremely gloomy in the arsenic contaminated areas, particularly in the developing third world countries. Unless something can be done, which is affordable by a large population of poor people, millions of them have to die a slow but sure death. In such a scenario, our efforts are directed to find a remedy that is cheap, easy to administer, effective in low doses and has no toxic effect of its own. Potentized homeopathic remedies in general fit the bill. The encouraging results of early attempts made8-9 to mobilize As in rats through micro doses of Arsenicum Album, and of our own studies in mice10-16 in this regard suggested that Arsenicum Album-30C and Arsenicum Album 200C have the potential to be used for alleviating As toxicity in humans as well. With financial support from the Boiron Laboratory, Lyon, France, a human trial was conducted to study some of the important aspects of arsenic toxicity and the efficacy of Arsenicum Album 30C and 200C in ameliorating symptoms of arsenic toxicity (arsenicosis) in humans exposed to groundwater arsenic 17-21 was tested.
Protocols of the study:
The following protocols of study were used:
(i) Assay of arsenic mobilization through urine from blood, and cytotoxicity in humans exposed to groundwater arsenic, as revealed from several toxicity biomarkers like acid and alkaline phosphatases, alanine aminotransferases (ALT) and aspartate amino transferases (AST), lipid peroxidation (LPO), reduced glutathione (GSH), gamma-glutamyl-transferase in (GGT), lactate dehydrogenase (LDH), glutathione-s-transferase (GST), and catalase (CAT) activities etc. in their sera;
(ii) Assay of erythrocyte sedimentation rate, Hb content, blood glucose, total and differential count (T.C./D.C), packed cell volume(PCV), cholesterol (HDL/LDL), urea/BUN, bilirubin, creatinine, albumin, triglyceride etc. of blood samples , lymphocyte viability tests (apoptosis) ;
(iii) Immunoassay through use of ANA, dsDNA, Scl-70 antibody titer tests deploying ELISA READER etc.
(iv) Assay of expression of Matrix Metalloproteinases (MMPs) in blood sera of humans living in risk prone zones (and also p53 and Bcl2 gene products) and DNA damage through Ladder/Comet assay.
What exactly was under focus?
In suitable placebo controlled animal experiments, the effects of sub-lethal doses of arsenic trioxide on an animal model were tested. Mice have been studied and the efficacy of the potentized homeopathic drug, Arsenicum Album-30 (and 200th potency) in ameliorating arsenic toxicity has been assessed by analysis of data collected from some of the protocols mentioned above. These are all scientifically accepted protocols for determining the patho-physiological status of animals and humans.
In the subsequent human trial, a periodic survey of arsenic content of urine and blood samples has been made, before (to get baseline data) and at different periods after administration of the homeopathic remedy, keeping suitable placebo controls. Similarly, several enzyme toxicity biomarkers have also been analyzed from blood samples periodically before and after drug administration, using initially a few placebo fed controls for a limited period, to be sure that the drug showed a positive response as compared to controls. The “verum fed” group of subjects showed considerable improvement in appetite, digestive ability, energy level (arsenic affected people are extremely morose, frustrated and devoid of motivation and energy to work) and in their general health condition.
Similarly, periodic monitoring of other blood parameters, including ANA tests, were made before and after administration of the homeopathic remedy. These tests supported the visibly noted improvement in general appearance of and statements made by the patients taking the homeopathic remedies. There was amelioration of their joint and muscle pains, and noticeable improvement in their liver functions and other sufferings.
What results were significant?
The results were encouraging. There was clear indication of the ability of the homeopathic remedy to ameliorate arsenic toxicity in terms of both urinary arsenic excretion and corresponding positive modulations as revealed from the several toxicity biomarkers analyzed in randomized populations. An alarmingly high frequency of ANA positive cases had been recorded in two arsenic infested villages, Ghetugachhi and Dakshin Panchpota (under Chakdaha Block, Nadia, West Bengal) among random populations. Even some 9-13 year old children tested ANA positive. Many of them were also showing higher levels of blood glucose. Results showed that the potentized homeopathic remedy could reverse ANA positive cases to ANA negative ones. Even symptoms of arsenicosis (particularly of skin lesions and liver ailments) showed signs of improvement. Blood glucose levels, which were generally found to be high in people inhabiting high-risk arsenic contaminated areas, showed signs of amelioration and in most, the glucose level could be brought down to normal or near-normal levels by the administration of these remedies. The efficacy of a millesimal potency (Arsenic album 0/3) has also been tested to yield positive results (unpublished).
More works are needed:
More such studies, preferably by other independent groups of researchers with an open mind are necessary to verify, confirm (or refute) the findings, because we think this could ameliorate the sufferings of millions of people to a considerable extent, particularly where provision for supply of arsenic-free drinking water has not yet been made. The remedies would also help to ameliorate symptoms of arsenic victims who had been drinking arsenic-contaminated water for varying periods of time before arsenic-free water was actually made available to them. It must be emphasized that efforts to provide arsenic-free drinking water to all the affected people must go on, but this remedy can give an interim relief to a considerable extent before such measures are taken.
On the mechanism of action of the potentized homeopathic remedy
Potentized Arsenicum Album 30C and 200C used in the study was diluted 1/1060 and 1/10120 times, respectively. These dilutions were much beyond Avagadro’s limit, and thus cannot be theoretically expected to contain even one molecule of Arsenic trioxide, the initial source material from which the remedy was derived (by the homeopathic method of succussions and serial dilutions). Further, 8 small sugar globules soaked with a tiny drop (0.01 ml approx) of this remedy served as a single dose for a human subject. Thus the question, how can this act as a medicine, is quite pertinent. Homeopathy is unacceptable to many for lack of an authentic scientific explanation.
The problem of explaining the mechanism of action of potentized homeopathic remedies is basically three-fold: one has to explain i) how the medicinal property can be transferred to and retained by the “vehicle” (more often ethyl alcohol 40-70%), ii) how the ultra-low dose of the drug can transmit “information” to the cell receptors, and thereafter iii) is able to bring about often visible and quantifiable changes in many parameters of study. A large number of hypotheses have been proposed to explain the mechanism of action of the potentized remedies, and quite a few of these are appealing 22.
To explain the first part of the problem, a hypothesis has to satisfy that the “vehicle” must have the ability to retain the “memory” of the original drug molecule (either as clathrate or other form of bubble)23 for a long time and also have the ability to produce smaller replicates of the “memory” molecules in larger numbers during dilution and succussion procedures. Thus, the receptor(s)24 of the cell (ion-gated channels/aquaporins?), which must be conformationally changed owing to action of the actual poison (Arsenic trioxide) must be able to recognize the “molecular signal/imprint/information” of Arsenic trioxide (imprinted in the remedy) that comes in contact with it (them). The cell surface receptors with different degrees of conformational changes (and of different sizes as well) will be able to get the signals in greater numbers if signals (even smaller in size) were available. For example, if one knows what an “alphabet B” looks like, one will identify without fail the alphabet B in any size, big or small. And if an “alphabet” carries a specific signal for the cell to perform, the more signals, the greater will be the activity by signal transduction in an amplified manner, triggering a cascade of downstream activity through a chain of activation/inactivation of genes, necessary for correcting the “mistake in functioning” of these genes in question. Hence, the dictum “like cures like”, and greater the dilution and higher the potency, the stronger and longer will be the action of the medicine, as claimed by the homeopathic doctrine.
It is well documented that life begins with the orderly expression of a large number of genes, many of them being regulatory in function. Right from the maturation of ova, several genes start acting in a definite manner so that the eggs ripen. After fertilization, the zygote starts a cascade of gene activities, controlled by some specific genes (regulatory), either dictated by orientation of some cells, or merely by relative position of some gene products. A perfect circuitry of gene action is in-built in each organism, and throughout the developing (embryonic) stages all genes act in perfect harmony of one another and in serial order, and in a specific manner, depending on this circuitry. Incidentally, the gene activity has a gradient nature and can eventually trigger a cascade of downstream activity in order to perform all the functions of different organs and systems unless there arises a “chaos” in such orderly activity, mostly brought about by either some disease force and/or any other physiological disorder by external insult/influence. Some apoptotic genes are responsible for sending death signals to cells when required, that is, when hope of recovery of the cells in question is absolutely lost.
For example, if there is a genetic arrangement existent in the same reading frame with a gradient and cascade of gene action, a series of actions can be seen. If we take an area of DNA that produces four gene products in the same reading frame and arbitrarily express them to be MADAM, then by orderly “repression” of first “M”, it will be “ADAM” which is expressed. By the repression of both “M” and “A”, DAM will be expressed, and with the repression of “M”, “A” and “D”, subsequently only AM will be expressed. But if the disease force or any external toxic agent alters the orderly functioning by repressing the last “A” instead of the first “M”, there will be no synthesis of MADAM (which will now read MADM owing to repression of “A”), no subsequent ADAM, and no DAM etc. Again the functioning can be rectified and the correct position restored if repression at the wrong site is removed, and this is possibly done by the regulatory action of the homeopathic remedy through a signal transduction mechanism in one of the many pathways. Admittedly, this is an oversimplified account of regulation of gene expression, and for achieving this goal some other intermediate mechanisms have to be involved and explained. Since repair of chromosome/DNA/protein damage has been well documented and involves specific corrective action of some known genes, and since all enzymatic changes are in fact firmly established to be under specific transcriptional activities of relevant parts of DNA, when a potentized homeopathic remedy without any physical existence of original drug molecule can be shown to bring about the spectacular changes in the action of such target enzymes, one has to think logically and on strong scientific ground that one possible explanation could be that potentized homeopathic drugs act through regulation of gene expression, as their nature of functioning suggests that it is “regulatory” in essence. Some other detailed scientific arguments in favour of this contention may be obtained from some published papers25-28. In the meantime, the possibility of using homeopathy under the supervision of qualified homeopathic practitioners, particularly in remote villages where medical facilities are generally unavailable, may be given serious consideration.
A.R. Khuda-Bukhsh, Ph.D. – Professor and former Head, Department of Zoology, University of Kalyani, Kalyani-741235, West Bengal, India.
Acknowledgements: The author is grateful to Boiron Laboratories for the financial support, and to Dr. Philippe Belon, Ex-Director and Dr. N. Boujedaini of Boiron Laboratories, Lyon, France for their kind encouragements.
1. Chowdhury UK, Rahman MM, Mondal BK, Paul K, Lodh D, Biswas BK, Basu GK, Chanda CR, Saha KC, Mukherjee SC, Roy S, Das R, Kaies I, Barua AK, Palit SK, Quamruzzaman, Chakraborti D. Groundwater arsenic contamination and human suffering in West Bengal, India and Bangladesh. Environ Sci 2001, 8: 393-415.
2. WHO, in WHO guidelines for drinking water quality, (WHO, Geneva,ed. 2); 1996, 2, 940-949.
3. U. S. EPA, .
4. Guha Mazumder DN, Das Gupta J, Santra A, Pal A, Ghosh A, Sarkar S, Chattopadhyaya N, Chakraborti D, Non-cancer effects of chronic arsenicosis with special reference to liver damage, in Arsenic: Exposure and Health Effects (Edited by: Abernathy CO, Calderon RL, Chappell WR) Chapman & Hall, London, 1997, pp. 112-123..
5. Ratnaike RN. Acute and chronic arsenic toxicity. Postgrad Med J. 2003, 79: 391-396.
6. Patrick L. Toxic metals and antioxidants: Part II. The role of antioxidants in arsenic and cadmium toxicity. Alt. Medorrhinum Rev, 2003, 8: 106-127.
7. Spallholz JE, Boylan LM, Rhaman MM. Environmental hypothesis: is poor dietary selenium intake an underlying factor for arsenicosis and cancer in Bangladesh and West Bengal, India? Science of the Total Env. ; 2004, 323: 21-32.
8. Boiron J, Abecassis J, Belon P. A pharmacological study of the retention and mobilization of arsenic, as caused by Hahnemanian potencies of Arsenicum Album. In: Aspects of research in homeopathy; 1983, vol.I: 19-37.
9. Cazin JC , Cazin M, Gaborit JL, Chaoui A, Boiron J, Belon P, Cherruault Y, Papapanayotou C. A study of the effect of decimal and centesimal dilutions of arsenic on the retention and mobilization of arsenic in the rat. Human Toxicol., 1987, 6: 315-320.
10. Mitra K, Kundu SN, Khuda-Bukhsh AR Efficacy of a potentized homoeopathic drug (Arsenicum Album-30) in reducing toxic effects produced by of arsenic trioxide in mice. I. On rate accumulation of arsenic in certain vital organs.Comp Ther Med, 1998,6: 178-184.
11. Mitra K, Kundu SN, Khuda-Bukhsh AR. Efficacy of a potentized homoeopathic drug (Arsenicum Album-30) in reducing toxic effects produced by of arsenic trioxide in mice. II. On alterations of body weight, tissue weight and total protein.Comp Ther Med, 1999, 7: 24-34.
12. Datta S, Mallick P, Khuda-Bukhsh AR.Efficacy of a potentized homoeopathic drug (Arsenicum Album-30) in reducing genotoxic effects produced by of arsenic trioxide in mice. I. Comparative studies of pre-, post- and combined pre- and post- oral administration of and comparative efficacy of two microdoses. Comp Ther Med, 1998, 7: 62-75.
13. Datta S, Mallick P, Khuda-Bukhsh AR. Efficacy of a potentized homoeopathic drug (Arsenicum Album-30) in reducing genotoxic effects produced by of arsenic trioxide in mice. II. Comparative efficacy of an antibiotic, Actinomycin D alone and in combination with either of two microdoses of the homeopathic drug, Arsenicum Album.Comp Ther Med, 1998,7: 156-163.
14. Kundu SN, Mitra K, Khuda-Bukhsh AR Efficacy of a potentized homoeopathic drug (Arsenicum Album-30) in reducing cytoxic effects produced by of arsenic trioxide in mice. III. Tissue damage recovery, and enzymatic changes in liver. Comp Ther Med, 2000,8: 76-81.
15. Kundu SN, Mitra K, Khuda-Bukhsh AR. Efficacy of a potentized homoeopathic drug (Arsenicum Album-30) in reducing cytotoxic effects produced by of arsenic trioxide in mice. IV. On certain pathological conditions, gel electrophoretic protein profiles, DNA and RNA. Comp Ther Med , 2000, 8: 157-165.
16. Mallick P, Chakrabarti Mallick, J, Guha B, Khuda-Bukhsh AR. Ameliorating effect of microdoses of a potentized homeopathic drug, Arsenicum Album, on arsenic induced toxicity in mice. BMC Complementary and Alternative Medicine, 2003, Vol. 3/7 p. 1-19.
17. Khuda-Bukhsh AR, Pathak S, Guha B, Roy Karmakar S, Das JK, Banerjee P, Biswas JK,Mukherjee P, Bhattacharjee N, Chaki Choudhury S, Baberjee A, Bhadra S., Mallick P, Chakrabarti J , Mandal B.. Can homeopathic arsenic remedy combat arsenic poisoning in human exposed to groundwater arsenic contamination? a preliminary report on first human trial. Evid Based Complement Alternat Med 2005;2(4):537-48.
18. Belon P, Banerjee P, Chaki ChoudhuryS, Banerjee A, Biswas SJ, Roy Karmakar S, Pathak S, Guha B, Chatterjee S, Bhattacharjee N, Das JK, Khuda-Bukh AR. . Can administration of potentized homeopathic remedy, Arsenicum Album, alter anti-nuclear antibody (ANA) titer in people living in high risk arsenic contaminated areas? :I.A correlation with certain hematological parameters. Evid Based Complement Alternat Med 2006;3(1):99-07.
19. Belon P, Banerjee A, Roy Karmakar S, Biswas SJ, Chaki Choudhury S, Banerjee P, et. al. Homeopathic remedy for arsenic toxicity? : Evidence-based findings from a randomized placebo controlled double blind human trial. Sci Total Environ 2007; 384: 141-150.
20. Belon P, Biswas SJ, Roy Karmakar S, Banerjee P, Banerjee A, Das JK, Pathak S, Chaki Choudhury S, Bhattacharjee N, Guha B, Khuda-Bukhsh AR. Is an elevated antinuclear antibody titer in subjects living in two groundwater arseic contaminated villages indicative of a time-dependent effect of arsenic exposure? 2007; Env Sci:An Indian Journal, 1(1). pp-1-8.
21. Khuda-Bukhsh AR, Roy-Karmakar S, Banerjee A, Banerjee P, Pathak S, Biswas SJ, Haque S, Das D., Boujedaini N, Belon P. A Follow-up Study on the Efficacy of the Homeopathic Remedy Arsenicum Album in Volunteers Living in High Risk Arsenic Contaminated Areas. eCAM 2009;Page 1 of 8 doi:10.1093/ecam/nep122
22. Khuda-Bukhsh AR. Mice as a model for laboratory research. Homeopathy (2009), doi:10.1016/
23. Anaganostasos, GS, Vithoulkas G, Garzonis P, Tavouxoglu C. A working hypothesis for homeopathic microdiluted remedies. Berlin J Res Hom, 1991, 1: 141-147.
24. Matsumoto, J.Molecular mechanism of biological responses to homeopathic medicines. Med Hypothesis, 1995, 45: 292-296.
25. Khuda-Bukhsh AR, Potentized homeopathic drugs act through regulation of gene expression: a hypothesis to explain their mechanism and pathways of action in vivo. Com Ther Med, 5 (1997) 43-46.
26. Khuda-Bukhsh AR, Towards understanding molecular mechanisms of action of homeopathic drugs: An overview. Mol Cell Biochem, 253 (2003) 339-345.
27. Khuda-Bukhsh AR. Laboratory Research in Homeopathy. Integr Cancer Ther 2006;5(4):1-13.
28. Khuda-Bukhsh AR, Pathak S. Homeopathic drug discovery: theory update and methodological aspect. Expert Opin. Drug Discov 2008;3(8):979-90.