Wednesday, 16 May 2018

Geopharmaceuticals of Himalayan Sowa Rigpa medicine: Pharmacopoeial description, geochemical identification, their diversity and current utilization in Bhutan

Journal of Ethnopharmacology Available online 8 May 2018 In Press, Accepted ManuscriptWhat are Accepted Manuscript articles? Author links open overlay panelKarmaYeshiaPhurpaWangchukb a Wangbama Central School, Thimphu District, Bhutan b Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns Campus, QLD 4870, Australia Received 7 January 2018, Revised 7 May 2018, Accepted 7 May 2018, Available online 8 May 2018. Get rights and content Absract Ethnopharmacological relevance Geological materials/minerals have been used in the Himalayan Sowa Rigpa and Bhutanese traditional medicine (BTM) for treating various disorders for thousands of years. Aim of the study Our study reports the chemical identification of various geological materials and their ethno-medicinal uses for the first time. Materials and methods A five stage process was conducted including: (1) a survey of specialized ancient ethnomedical literatures (Pharmacopoeias and formularies); (2) freely listing the mineral ingredients reported in the ancient Sowa Rigpa medical texts and translating their ethnomedical uses in equivalent terms in English; (3) cross-checking the chemical names and chemical composition of identified minerals with various mineral databases and mineral handbooks; (4) Authentication and standardization of Sowa Rigpa names through open forum discussion with BTM practitioners; (5) further confirmation of the chemical names of identified minerals by consulting experts and pharmacognosist. Results Our current study chemically identified 119 geological materials/minerals described in Sowa Rigpa medical textbooks, out of which 29 are currently used in BTM herbo-mineral preparations. Out of 29 mineral ingredients included in the current formulations, 6 were precious metal and stones, 10 were earth, mud and stones, 8 salts and 5 essences and exudates. Conclusions Our study identified 119 mineral ingredients described in the Sowa Rigpa medical textbooks, out of which 29 are currently used in formulating 111 multi-ingredient prescription medicines in Bhutan to treat more than 135 ailments. Graphical abstract Download high-res image (263KB)Download full-size image Keywords Sowa Rigpa medicine Bhutanese traditional medicine Geological materials minerals geopharmaceuticals medical geology 1. Introduction The study of the impacts of geologic processes and materials of abiogenic origin including minerals, rocks, ores, gems, metalloids and soils on animal and human health is called medical geology or sometime referred to as geopharmaceutics/geopharmacology (Finkelman, 2006). Mineral or geological materials are applied in both traditional and modern medical systems for the treatment of various disorders. Ancient civilizations including Mesopotamian, Chinese, Indian, Egyptian, Greeks, Arabic, Roman and Tibetan used geological materials for their therapeutic values and as essential nutrients (Duffin, 2013, Limpitlaw, 2004, Abrahams, 2005; Carretero et al., 2007; Yu et al., 1995). Tibetan medicine is an amalgamated scholarly medical system, which incorporated principles and recipes including minerals from CTM, Indian Ayurvedic, Greco-Roman and Asia Minor medicines (modern Turkey). This medical system is popularly known as Sowa Rigpa (transliteration = gSo-ba Rig-pa) and is practiced in many parts of the world especially in Mongolia, Russia and the Himalayan region including Nepal, Ladakh and Dharamsala (India), proper Tibet (China) and Bhutan (Craig and Adams, 2008). In Bhutan, Sowa Rigpa has been adapted to the needs of the Bhutanese health care system by integrating it with the Bhutanese culture, traditions, ethnomedicines and conventional biomedical system (Wangchuk et al., 2007). For these reasons, Sowa Rigpa in Bhutan is often called the ‘Bhutanese traditional medicine’ (BTM). BTM recognises mainly four categories of medicinal raw materials: ngo-smen (high altitude medicinal plants), throg-smen (low altitude medicinal plants), sogcha-smen (animal parts) and sa-smen (minerals) (Wangchuk et al., 2007). Minerals (sa-smen) constitute second most bulk ingredients after medicinal plants in BTM. Today, Menjong Sorig Pharmaceuticals (MSP) in Bhutan produces more than 116 polyingredient formulations, which are distributed to 65 different traditional medicine hospitals and units in the country for delivering free health care and treatments to the patients. About 75 formulations are registered with the Drug Regulatory Authority of Bhutan (DRA), out of which 15 are categorised as over-the-counter (OTC) products. Most of these medicines are herbo-mineral preparations (known as Kushta in Unani and Ayurvedic medicines) and rest contain either herbo-animal(s) extracts preparations or all three ingredients combination (herbs:animal parts:minerals). The traditional concept and principle for herbo-mineral preparations is that effective drugs contain minerals as body and herbs as soul where non-living mineral is considered to have no therapeutic value but when it is combined with herb(s), the soul of the plant gets transferred to minerals resulting into an effective and acceptable therapy (Aziz et al., 2002). Thus, the therapeutic value of finished drug is attributed to herb(s) and minerals as simply body or vehicle. Minerals used in BTM are detoxified or pre-processed (locally referred to as conquering or taming hazardous minerals) using special traditional techniques prior to the herbo-mineral preparations. Aware of the health problems and benefits that are associated with geologic materials/minerals used in BTM, MSP have prioritized screening them for their quality, safety and control measures. The first step in quality control measures is to correctly identify the medicinal ingredients used in BTM formulations. We have previously reported on the botanical and zoological identification of medicinal plants and animals used in BTM (Wangchuk et al., 2011a, Wangchuk et al., 2016a, Yeshi et al., 2017a). However, minerals used in BTM received less attention and remain unexplored. This raises many research questions including: Does BTM use minerals? If it does use them, how many minerals are described in the Sowa Rigpa pharmacopoeias/traditional medical textbooks? What classes of minerals are used in the current formulations of BTM? How are these minerals sourced/collected and used in BTM formulations? What quantities of minerals are used? Are the minerals used in BTM chemically identified? What types of diseases do these minerals treat? Are there any health benefits and safety implications when using BTM medicines that contain minerals? What is the future of medical geology in Bhutan? To address these questions, we have conducted literature review of traditional medical textbooks, interviewed traditional physicians, translated ethnopharmacological uses of minerals, chemically identified the minerals, and assessed the data. The findings are presented here for the first time. The current findings will form a bridge between BTM and science to initiate extensive studies on the geopharmaceuticals/lithotherapeutic/medical geology. 2. Materials and Methods We followed the study design previously described for taxonomical description and identification of animal-derived products used in BTM (Yeshi et al., 2017a). It is a descriptive and an observational one. Firstly, the ancient Tibetan Sowa Rigpa textbooks which were available at Faculty of Traditional Medicine (FoTM), Department of Traditional Medicine Services (DTMS) and Menjong Sorig Pharmaceuticals (MSP) were reviewed and evaluated to generate a list of minerals and their uses. The main Sowa Rigpa textbooks/pharmacopoeias including Four Tantras (Gonpo, 2011a, Gonpo, 2011b, both reprint editions), ‘ (Dorje, 1995) and shel-gong-shel-phreng (Phuntshok, 1994) were accessed during the time of this study. The Dictionary of Tibetan Materia Medica (Arya, 1998) and Tibetan – English Dictionary of Tibetan Medicine and Astrology (Thakchoe and Dolma, 2005, revised and enlarged edition) were used for translating the traditional uses of minerals into English terminologies. Second, the BTM specific traditional medical documents including Rin-po-che dang g.ter-r.dzes-sman gi ‘ nor-bu’i dho-shal: ‘druk-sman gi ‘ (Dorji, 2011), Monograph on Traditional Medicine of Bhutan (2015), Formulary of Traditional Medicine of Bhutan (1983), and the Traditional Medicine Formularies of Bhutan (Tenzin, 2007) were assessed for generating a list of mineral ingredients that are used in the current formulations at MSP. Third, three Drungtshos at MSP, Mongar Regional Hospital under Ministry of Health, two Senior Procurement Officers, a Research In-Charge and a senior Pharmacognosist at MSP; one smenpa at DTMS under the Ministry of Health were consulted using open discussion forums to authenticate the information on the listed minerals. Informed oral consent were sought from the informants (Total number of participants = 7) prior to open forum discussion. We have translated the ethnopharmacological uses of each mineral ingredient into English medical terminologies with the help of Drungtshos, smenpas and other western educated research experts at MSP and presented them in Table 1. Table 1. Geological materials/minerals described in the Sowa Rigpa pharmacopoeias and the currently used ingredients in BTM formulations. Common name (Commonly Encountered Gemstones (CEGs), 2010, Korbel and Novak, 2001, Arya, 1998) Chemical name [Formula] (Dorji, 2011, Commonly Encountered Gemstones (CEGs), 2010; Agarwal, et al., 2007; Korbel and Novak, 2001; Arya, 1998) Chemical groups Sowa Rigpaname with synonyms Traditional therapeutic indications (Monograph on Traditional Medicine of Bhutan (MTMB), 2015, Dorji, 2011, Tenzin, 2007, Thakchoe and Dolma, 2005, Arya, 1998, Dorji, 1995, Phuntshok, 1994, Formulary of Traditional Medicine of Bhutan (FTMB), 1983) Status (FTMB, 2015) Actinolite Calcium magnesium iron silicate hydroxide [Ca2(Mg, Fe2+)5 Si8O22 (OH)2] Silicates rdo chu, rdo skyur, chu skyur rdo, rdo rul It cures cold disorders, phlegm, and stomach disorders. It joins bones and is beneficial for silver poisoning. NU Agate Silicon dioxide [SiO2] Oxides chu snying, chu chung n’i la ya Useful for overcoming epilepsy, fever, pain due to blood disorders. Beneficial for swellings and inflammation due to cold. It also protects from fire disasters. NU Agate Silicon dioxide [SiO2] Oxides gzi (Different types, such as nag khra, kham khra, zlum po stag log.) Old agate bearing different eyes with medicinal values; mainly used to heal brain and nerve disorders; protects from epilepsy and harmful negative energies and weapons. NU Agate Silicon dioxide [SiO2] Oxides khra man Used against epilepsy and disease causing evil spirits. NU Alloy (bronze) Copper-tin alloy [CuSn] Alloy ‘khar ba Overcomes poisons, useful for eye diseases; powder heals eczema and fungal infections. NU Amber Mixture of hydrocarbons [C10H16O] Organic Compounds sbur len Used for treating blurred vision, cataract, general visual impairment, fainting, dizziness and epilepsy; also used against harmful effects of evil spirits. NU Anhydrite Calcium sulfate [CaSO4] Sulfates dkar po chig thub, rdo chig thub, chig thub, dkar po mdung rtse Heals fractured bones and brain disorders and ophthalmic diseases. NU Aragonite Calcium carbonate [CaCO3] Carbonates mu tig Heals brain damage due to inflammation or injury, degeneration of nerves, stiffness and contraction of ligaments and tendons, paralysis, poisoning and prevents loss of cerebral fluid; also improves eyesight. U Argentite Silver sulphide [AgS] Sulfides dngul rdo Dries accumulation of serous fluid, pus and blood; heals fractured bones, cures septic wounds and malignant tumours. NU Asbestos rocks Hydrous magnesium silicate [Mg3Si2O5(OH)4] Silicates rdo rgyus, rdo rgyus pa, rdo rgyus bya bal ma It is a smooth white stone which heals disorders of tendons and ligaments. NU Ashes Contains potassium carbonate, calcium carbonate, phosphates and traces of other elements Salt thal tshva, sdong tshva, ldum tshva Heals abdominal cramps, swellings, belching or frequent eruption and improves digestion. NU Aurichalcite Zinc, copper carbonate [(Zn, Cu)5 (CO3)2 (OH)6] Carbonates ra gan Heals dermatological and ophthalmic disorders, and eliminates toxins from the body. NU Azurite Hydrous copper carbonate [Cu3(CO3)2(OH)2] Carbonates mthing sngon, mthing, ku shu’i khams, dus kyi me tog Cures kidney diseases and helps urinary incontinence; heals torn tendons and ligaments, and stiff contraction of the limbs and can be used as an emetic. NU A type of agate NS Oxides rdo yi snyin po, a smag bha, dra ma a smag ‘o Treats liver diseases caused by food poisoning. NU A type of clay A type of clay [NS] Mixture of natural soil materials including traces of quartz, metal oxides and organic matter. Medicinal soil sa smyag, sa zhag Anti-inflammatory; stops dysentery. NU A type of precious gem NA NA si ra ka It protects against poisonings and all kinds of Bhuta spirits (‘byuṅ po). NU Baking soda Sodium hydrogen carbonate [Na2HCO3] Carbonates byang-bul Useful against indigestion, tumour and ophthalmic diseases. U Beryl Beryllium aluminium silicate [Be3Al2(SiO3)6] Silicates mrgad Indicated as beneficial for all kinds of diseases. NU Bismuth Bismuth [Bi] Elements se rul, sa dreg bcas Suppresses poisonings and beneficial for those who are already poisoned. NU Blue asbestos rocks (Crocidolite) Hydrated sodium iron silicate [(Na2Fe32+Fe23+) Si8O22(OH)2] Silicates mthing rgyus, rdo rgyus It heals disorders of tendons and ligaments. NU Borax Sodium borate [Na2B4O5 (OH)4.8H2O] Borate tshva la Thins the blood & helps in blood circulation; dries up serous fluid and alleviates stomach disorders caused by indigestion. U Brass (alloy) Copper-zinc alloy [Cu3Zn2] Alloy li Heals dryness of eyes, gold needle therapy with this alloy cures malignant tumours and skin diseases, such as fungal infections. NU Brass (ore) Copper-zinc alloy [Cu3Zn2] Alloy ’khro,’khro ser,’khro nag It is used against parasitic infections and poisons. NU Calcite Calcium carbonate [CCaO3] Carbonates dngul zil It gives tone to the bone, remove discoloration of bones and cures poisoning. It is also useful for traumatic injuries. NU Calcite Calcium carbonate [CaCO3] Carbonates chu tshen rin bsrel Heals evil afflictions from spirits. NU Calcinated powder Calcium carbonate [CaCO3] Carbonates cong zhi rgod brtul Powder curing angina, abnormal growth of flesh, tumorous quinsy and lcags dreg (a type of chronic disease of stomach wall). U Carbon Carbon [C] Elements sol rdo Heals wounds and dries up serous fluid. NU Cassiterite (stannic oxide) Tin dioxide [SnO2] Oxides gsha’ dkar Heals wounds and inflamed tissues and promote growth of new flesh under a curing wound when combined with mercury. NU Chalcanthite Copper(II) sulfate pentahydrate [CuSO4.5H2O] Sulfates big pan, sag rtsi, sag ram rtsi, mtshur sngon Useful for treating cancer; removes tumours; also used in treating abscesses, ophthalmic disorders, ulcers, pimples and oral diseases. U Chalcopyrite Copper iron sulfide [CuFeS2] Sulfides gser rdo It heals fractured bones, poisoning, nervous disorders and excessive lymphatic fluid secretions. NU Chrysocolla Copper phyllosilicate hydrate [(CuAl)2H2Si2O5 (OH)4. nH2O] Silicates rma bya’i mgrin’dra Cures fever. NU Chrysotile Hydrous magnesium silicate [Mg3(Si2O5)(OH)4] Silicates shel, chu shel It treats fever, lethargy, drowsiness and promotes the clarity of mind. It cures illnesses caused by nagas and evil spirits. NU Cinnabar Mercury(II) sulfide [HgS] Sulfides da chu, ‘tshal dkar Heals fractured bones, cures septic wounds, and cures inflammation in the nerves, and the diseases of endocrine glands and malignant disorders. NU Cinnabar Mercury(II) sulfide [HgS] Sulfides cog la Useful for brain sickness and paralysis fractured bones, poisonings, injuries, lung disorders and hepatitis. NU Cinnabar Mercury(II) sulfide [HgS] Sulfides cog la ma It heals fractured bones, cuts and wounds, hepatitis, pneumonitis, neuritis, nervous disorder, arteriosclerosis and cranial nerve disorders. NU Cinnabar Mercury(II) sulfide [HgS] Sulfides mtshal, tam ka na dang, ka shar na zer, rgya mtshal Heals wounds, pulmonary infections, hepatic infections and nerve disorders. U Cinnabar Mercuric sulphide [HgS] Sulfides rdo mtshal Useful for contagious diseases and ophthalmic diseases. NU Coal Coal [NS] Non-specific mixture C + O, N, H, etc… Elemental mixture rdo sol Dissolves kidney and gallstones; has an antitoxic effect on precious metal and mineral poisoning; also stops bleeding and hels in the coagulation of blood. NU Copper ash Copper [Cu] Elements zangs thal Dries pus formed in the lungs; cures pneumonitis and hepatitis. U Copper metal Copper [Cu] Elements zans It dries away pus and cure fevers associated with lungs and liver disorders. NU Copper ore Copper iron sulfide [CuFeS2] Sulfides zangs rdo It dries pus and cures fever associated with lungs and liver disorders. NU Corundum Aluminium oxide [Al2O3] Oxides pad ma ra’ga, padma rak ta Used against provocative effects of evil spirits; brain tonic useful in the treatment of nerve disorders. NU Corundum (Lapis lazuli) Aluminium oxide [Al2O3] Oxides bee dur ya, nor bu bee dur ya Used for treating all three humors, protects from radiation and harmful spirits and cures all kinds of poisonings including poison from snake bite. NU Covellite Copper sulfide [CuS] Sulfides rag rdo/brag rdo Heals ophthalmic disorders. NU Diamond Carbon [C] Elements rdo rje pha lam Excellent remedy against naga spirit attacks; protects from other provocative evil spirits. NU Fibroferrite Ferric sulphate [Fe3+ (SO4) (OH). 5H2O] Sulfates nag tshur, ser tshur Prevents decay and heals tumour. NU Fibroferrite Iron sulfate [Fe3+(SO4)(OH).5H2O] Sulfates ser mtshur, sa mtshur, sho’na ka Recommended for septic wounds and tumours in the mouth; used for hair colouring. NU Glauber's salt Sodium sulfate decahydrate [Na2SO4 10H2O] Sulfates mze tshva It thins blood and dries out serous fluid from wounds. NU Glus /brick NA Mineral Stone phe’u, sa phag Hot compress useful for wind (rlung) related disorders; dries up pus in joints. NU Gold Gold [Au] Elements gser, gser thal It promotes longevity, cures glandular fever, abscess, (calcinated gold powder) exudes poisoning and used as rejuvenation. NU Granite (Quartz and feldspar mixed) Silicon dioxide [SiO2] Calcium sodium/potassium aluminium silicate [NS] Oxides Silicates Solid solution ‘dzeng Heals wounds and lesions. NU Halite Sodium chloride [NaCl] Salt lan tshva, yul tshva, mtsho tshva, gter tshva Useful in treating indigestion, poisoning and constipation; also helps to disintegrate tumours. U Halite derivative Sodium chloride [NaCl] Salt kha ru tshva, bi da, nima lo na Used against indigestion, distension of stomach, belching and rlung disorders; also heals fever due to intestinal disorders. U Hematite ‎Iron(II) oxide [Fe2O3] Oxides smug po sbal rgyab, smug po chig thub, smug po mdung rtse Heals fractured bones, wounds and prevents accumulation of serous fluids in the chest region. It is also useful for brain disorders. NU Humus NA NA lba tshva, sa zhag, yul skad le yang ba tshva. It differentiates fluids of hot and cold natures, and purges diseases; reduces swelling of thyroid gland and cures goitre. NU Iodized salt Sodium chloride [NaCl] Salt va tshva bsreg thal Anti-goitre salt or iodised salt. NU Iron Iron [Fe] Elements lcags, lo ha, a ya, sha tra’ kam, lcags phyi Cures liver diseases, eye infection, and fevers due to poisoning and oedema. U Iron Iron [Fe] Elements zi la It is used against contact poison and abscess. NU Iron ash Iron [Fe] Elements lcags thal It is mainly used to cure three stages of oedema, eye diseases and hepatic poisoning. NU Jasper Silicon dioxide with impurities [SiO2] Oxides khyung skyugs It is used against compound poisons and removes poisons made from precious substances. NU Kaolinite Aluminium silicate hydrate [( Al2Si2O5(OH)4. 2(H2O)] Elements yugs, yugs rdo, smug rdo, rdo’i khrag lnga rdo, rdo’i khrag lnga It is used for treating ophthalmic diseases and bone fever. Dries away serous fluid. NU Laberitum Iron oxide [Fe2O3] Oxides btsag, gee ri ka, tum ya, le rGan me tog Useful for ophthalmic diseases and inflammation of the bones; dries up excess lymphatic fluid. NU Lazurite (Lapis lazuli) Sodium calcium aluminium silicate sulfur sulfate [(Na, Ca)8 Al6Si6O24 (S, SO4)] or {Na6Ca2Al6Si6O24S2} Silicates mu men It is effective as an antidote for disorders caused by poisoning. It also heals dermatological diseases, leprosy, lymphatic disorders and dyes hair. U Lime powder Calcium carbonate [CaCO3] Carbonates dkar rtsi, mchod rten na bza’, sa dkar, rdo dkar, dkar rag Prevents old age diseases, heals bones and tissues, and improves vitality. NU Limestone Calcium carbonate [CaCO3] Carbonates cong zhi, she li da ka, mtsan mo’i ‘od chan, gchong nad gcig thub Anti-diarrhoeal. It is used for treating disability, chronic gastritis, brown phlegm, sour watery vomitus; and heals cracks and fractured bones. U Limestone Calcium carbonate [CaCO3] Carbonates rdo thal, rgya rdo, tshos rdo, zhun rdo, brag rdo, rdo dkar Reduces excess mucus accumulated in the abdomen. NU Limonite Hydrous basic iron oxide [FeO(OH). nH2O] Oxides rdo mkhris, rdo’i mkhris pa Stops bleeding and it is also useful for hepatic disorders. NU Limonite Hydrated iron(III) oxide-hydroxide [Fe2O3.nH2O] Oxides grdu bzhi, brgya rdo, zhang blon bla rdo It is indicated as beneficial for 18 types of paralytic diseases caused by lower realms and evil spirits. NU Limonite Iron(III) oxide-hydroxide [FeO(OH).nH2O] Oxides sin dhu ra, rgya mtsho’i breg pa, mkha’’gro’i mnyal khrag Heals wounds of the five vital and six hollow organs and blood disorders; also effective in the treatment of fevers and severe burns. U Limonite (Iron ore) Hydrous iron oxides [FeO(OH). nH2O] Oxides lcags rdo It increases lifespan and it is considered as an elixir. NU Litharge Lead(II) oxide [PbO] Oxides mtshal dkar Prevents wounds from rotting by drying away pus; heals parasitic infections; useful for poisons and bse dri. U Magnesite Magnesium carbonate [MgCO3] Carbonates rdo klad Brain tonic; stimulates growth of new flesh. U Magnetite Iron(II,III) oxide [Fe2+Fe3+2O4] Oxides khab len Cures bone fractures and cranial nerve disorders; helps to remove metals lodged inside the body (like nails, needles, bullets etc.). U Malachite Copper carbonate hydroxide [Cu2(CO3) (OH)2] Carbonates spang ma, spang snyon po, spang ma brtul ma Dries up serous fluid, cures cataract and male genital disorders; also promotes hair growth. NU Malachite Copper carbonate hydroxide [Cu2(CO3) (OH)2] Carbonates lig bu mig, nag po si sa mdung rtse Cures eye disorders, colitis and dries up serous fluids. NU Massicotite Lead monoxide [PbO] Oxides stang zil, rdo bung ba, po skra’dra, stong tse rog It is recommended for head injuries, haemorrhage and vomiting. NU Mercury (liquid) Mercury [Hg] Elements dngul chu, su ra, suda ra, rgyug byed, tsa pa la,’ded byed, su ra to ram, khu ba’i dbang po Elemental liquid mercury is known to be toxic in Sowa Rigpa, however specific practices are applied to tame the toxicity. Detoxified mercury has excellent potency to remove toxins; also dries up serous fluids, kills worms, prevents provocative effects of evil spirits and is considered as an elixir for both body and mind. NU Mineral pitch, Shilajita Organic compound mixture. Contains fulvic acid and other microelements and vitamins Plant humic matter (organic constituents) brag zhun, brag zhun khan dra, srid pa’i byang dmar po It is used in treating gastritis, hepatitis, nephritis, intestinal colitis, brown phlegm, gout, ophthalmic disease, oedema, debility and fever of all origins. U Mineral Stone NA Mineral Stone phag mgo Strengthens bones and dries pus. NU Minium Lead tetroxide [Pb2+Pb4+O4] Oxides li khri, sa’i dbangs ma, ngur smig mdog can, bye ma dmar, dri’dzin skyes Dries pus and unwanted secretions, and heals wounds and promote growth of new flesh under the healing wounds; also helpful to unblock veins and arteries. NU Mirabilite, glauber's salt Sodium sulfate decahydrate [Na2SO4. 10(H2O)] Sulfate salt ya bag ksar Improves digestive heat, cures tumours and constipation. NU Morganite Beryllium aluminium cyclosilicate [Be3Al2 (SiO3)6] Silicates nal It is used against compound poisoning and hepatomegaly. NU Mud brick NA Medicinal Soil so phag, rdza gyam, rdza gser, gyo mo Alleviates dryness of pharynx and thirst, and hepatic poisoning. NU Muscovite (mica) Potassium aluminium silicate [KAl2(AlSi3O10)(F,OH)2] Silicates lhang tsher, a bha ha ra, dngul za byed, rdo me long Heals wounds, stops bleeding; cures acne, brain disorder, insanity, epilepsy and diseases arising from ‘disturbance’ (‘khrugs pa); suppresses poisons. NU NA Calcium carbonate [CaCO3] Carbonates rwa ‘dra Cures fever and pain associated with bone disorders and ophthalmic disorders. NU Niter, Saltpeter Potassium nitrate [KNO3] Nitrates ze tshva,’ju rtsi, sa’i shel, tshva hrag can, me’bar tshva Dissolves kidney stones, gastric stones and stones formed inside the urinary bladder; eliminates tumours in the solid and hollow organs; removes urinary tract obstructions and toxins from the body. U Nodal silica (Bambusa textilis) Silicon dioxide [SiO2] Oxides cu gang It subside fever of the lungs, chronic fever, and inflammation due to wounds, yellow sclera and infectious diseases. U Orpiment Arsenic sulfide [As2S3] Sulfides ba bla, ha ri ta la, agan te, ser po dri ldan, lha’I na bza’, gar gyi rgyan, sna tsog mdog, ba lang so Protects harmful effects of evil spirits. NU Medicinal properties are similar to realgar; It controls malignant glandular growth, glandular fever, heals septic wounds, swelling of the throat and tongue and necrosis. It is also anti-dote for the toxins of scorpions, snakes and poisonous bees. Parmela NA Lichen-rock derivative rdo dreg, brag gi me tog, khrag gi ut pal, dbugs med pags pa, pha vang dreg pa, brtan po’i dreg pa Used against poisonings and fevers. Anti-diarrhoeal; It is useful in the treatment of the vomit reflex and chronic fever. Restores appetite, impaired vision, and heals lymphatic disorders and promotes healthy skin. NU Plagioclase feldspar stone Calcium sodium aluminium silicate [(Ca,Na)((Al,Si)2Si2O8)] Silicates me shel, su rya kan ti, su rza kan ti ‘m Cures cold and epilepsy. NU Plumbum Lead [Pb] Elements zha nye, zha ne, ro nye, tson ma teng, llu nag, lku’u dbang po It eliminates toxins from the body, heals infected wounds, neutralises the harmful side-effects of mercury and enhances hair colour. NU Pyrite Iron sulfide [FeS2] Sulfides pha vang long bu Cures nerve damage and heals diffused fever; fixes broken bones and heals ophthalmic diseases. NU Pyrite Iron sulfide [FeS2] Sulfides gser zil It heals disorders of bone and returns them to their natural tone and radiance. NU Quartz Silicon dioxide [SiO2] Oxides dkar gong, mkhar do’i gong, a dKar, thun rdo, rdo’ phyag rdor, gdug pa tshar gcod Kills worms and removes poisons. Useful for dental microbial infections and in detecting the poisons. It can also protect against provocative effects of evil spirits. NU Quartz Silicon dioxide [SiO2] Oxides bae-snabs Used against harmful earth spirits and leprosy; heals fractured bones, tonifies muscles and cures inflammation in the glands. NU Realgar Arsenic monosulfide [AsS] Sulfides ldong ros, man shel, ma ni tsha, dmar po dri ldan, gar mkhan ma, glu lche ba Controls malignant glandular growth, glandular fever; useful in the treatment of skin and lymphatic diseases, swelling of the throat and tongue, and necrosis. Kills worms; antidote for the toxins of scorpions, snakes and poisonous bees. NU Red coral Calcium carbonate [CaCO3] Carbonates byi ru Cures hepatitis, and other fevers due to colon infections, and poisoning; also useful for cranial nerve disorders, epilepsy and anxiety. U Rose quartz Silicon dioxide [SiO2] Oxides gni dha Prevents afflictions from evil spirits like nagas. It is also useful for leprosy. NU Sal Ammoniac Ammonium chloride [NH4Cl] Salt rgya tshva, lce’bigs, rdo’i dangs ma’i tshva, tshva rgyal, chu dbyid, reg’bigs Used for treating tumours, stagnated menstrual flow, oedema, abdominal cramps, capillary disorders and nerve disorders, diphtheria, poisoning and microbial infections. U Sallucidum Sodium chloride [NaCl] Salt rgyam tshva, sam bah ba It is used against indigestion and disorders of rlung. U Salt derivative NA A type of salt mtshal tshva, bdud rtsi da chu Cures nerve disorders, and disintegrates blood tumour. NU Salt derived from animals’ horn. NA A type of salt rwa tshva Cures gastritis, colitis and inflammation of the blood vessels. NU Sand Silicon dioxide [SiO2] Silicates bye ma, sred gyi bye ma, bskal pa’i bye ma, bye ma reg gcod Diuretic, useful for the treatment of kidney diseases, joint pains and nerve disorders. NU Sapphire Aluminium oxide [Al2O3] Oxides ain dra ni la Used against fevers and all diseases. NU Silver Silver [Ag] Elements d.ngul, rgya dngul It remedies disorders of gout, arthritis, and abscess and dries up serous fluid and impure blood. NU Silver ash Silver [Ag] Elements dngul, rgya dngul, dngul thal It dries accumulated serous fluid and controls circulation of impure blood, proliferation of abscess and also heals gout and arthritis. U Smithsonite Zinc carbonate [ZnCO3] Carbonates gangs thigs, lha zhi, gangs dkar chad pa’i dum bu Literally means ‘drops of snow’; heals fractured bones and cures hepatitis. U Smooth pebbles Calcium carbonate [CaCO3] Carbonates chu-rdo It removes pain due to blood disorders. NU Soil NA Medicinal Soil thabs kyi sa tshig, thab sa tshig rnying Cures microbial infections in intestine. U Soot Carbon [C] (depends on source) Elemental mixtures dud pa ral pa, khang dud Useful for skin diseases and gout. U Soot from sla nga (parch, roast, fry) NA Essences slang drek, snag tshva’i rgyu Antidiarrheal. It heals wounds. NU Stalactite Calcium hydrogen carbonate [Ca(HCO3)2] Carbonates dkar po sbal rgyab Useful for phlegm and wind related disorders. Heals fractured bones and brain injury, dries pus or serous fluids and cures inflammation of the bones. NU Stalactite Calcium carbonate [CaCO3] Carbonates ba nu Heals disorders in tendons and ligaments, and restores the red bone marrow. NU Sulphur Sulphur [S] Elements mu ljang Regulates or maintains body homeostasis. NU Sulphur nativum Sulphur [S] Elements mu zi, sol ti, ga si ta, gan taha k ate, dri can, durga te, dri ngan, patra la hi, tsha ba’i dbugs can, sa bcud gser ldan, sa’i khro chu, za byed, btsun mo, dmar cha Heals skin disorders, lymphatic disorders and promotes the rapid healing of wounds; Mu zi nag po (black variety) used for fatal diseases, such as cancer, ulcers and swellings in the throat; yellow variety known as Mu zi ser po used for skin diseases, and against provocative effects of evil spirits; also used as anti-pruritic treatment. U Talc Hydrated magnesium silicate [Mg3Si4O10 (OH)2] Silicates ha shig, kha tam gi ga, khu dkar, ka ko dri ka, thod le kor Stops diarrhoea and purges channel disorders and is recommended for neurological diseases and wounds. NU Trona Sodium hydrogen carbonate hydrate [Na3(CO3)(HCO3).2H2O] Carbonates bul tog Recommended against indigestion, flatulence, tumours, abdominal cramps, septic wounds; acts as an anthelmintic. Also used to treat necrosis, (undigested) tshampa (roasted barley) and poisoning. U Turquoise Hydrated copper aluminium phosphate [CuAl6 (PO4) 4 (OH)8 4H2O] Phosphates g.yu (8 types) bai ra dza Treats hepatic disorders, ophthalmic diseases and eliminates toxins from the body. NU Vermiculite Hydrated magnesium iron aluminium silicate [(Mg,Fe, Al)3 [(SiAl)4O10] 4H2O] Silicates gser gyi bye ma, gser bye It heals kidney disorders, urine retention, oedema and fractured bones. NU Zinc Zinc [Zn] Elements ti tshva Heals wounds, prevents accumulation of serous fluid, correct blurred vision and cures conjunctivitis. It also eliminates toxins from the body and neutralises mercury's harmful effects. NU Abbreviations: U – Used; NU – Not Used in present BTM formulations; NA – Not Available; NS – Not Specific Note: There are different types of minerals with same common English names, which may appear to be repetitive. However, the minerals have been ascribed different Sowa Rigpa names and for clarity, we have retained as separate entity. Finally, based on the list of Sowa Rigpa names of mineral ingredients (drawn from the literatures and confirmed by BTM experts), we conducted chemical identification of these mineral ingredients. Chemical names and chemical compositions of minerals cited were updated in accordance with the mineral handbooks including: The Complete Encyclopedia of Minerals: Description of over 600 minerals from around the world (Korbel and Novak, 2001), Commonly Encountered Gemstones (CEGs) (2010), Rock and Mineral Identification for Engineers (1991), and Precious Minerals in Everyday Life (2011-2012). Chemical names and compositions of identified minerals were further crosschecked with the online mineral databases such as (2017); (2014); and PubChem (2017). Availability status of minerals was obtained from the imported medicinal raw material database maintained by procurement section at MSP. The information collected from the literature and confirmed by the participants/experts was entered into MS excel sheet, analysed them and then the data were represented either in table forms or in bar graph/pie chart. 3. Results 3.1. Chemical identification and the diversity of mineral ingredients described in the Sowa Rigpa pharmacopoeia The content analyses revealed 119 different types of geological materials/minerals are being described or recorded in the literature, textbooks and pharmacopoeia of Sowa Rigpa (Table 1). We found that these minerals belonged to diverse chemical classes and maximum numbers of these minerals were oxides (22), followed by carbonates (21), elements (20) and silicates (15) (Fig. 1). According to Sowa Rigpa, these medicinal minerals can be grouped into five major classes as: a) ma-zhu-ba’i-khams-kyi-rinpoche sman (prized metal and stone that do not melt), b) zhu-ba’i-khams-kyi-rinpoche-sman (prized metal and stone that can melt), c) sa-rdo’i-sman (drugs from earth, mud and stone), d) tshva-sna’i-sman (medicinal salts), and e) rtsi-sman (essences and medicinal exudates). Fig. 1 Download high-res image (1MB)Download full-size image Fig. 1. Representative mineral ingredients in the Sowa Rigpa medicine (photo courtesy: PW). (A) dorji-phalam (diamond); (B) d.ngul (silver); (C) nal (morganite); (D) g.yu (turquoise); (E) byi-ru (red coral); (F) g.zi (Tibetan agate); (G) mu-men (lazurite); (H) spang-ma (malachite); (I) smug-po-sbal-rgyab (hematite); (J) ain-dra-ni-la (sapphire); (K) sin-dhu-ra (limonite); (L) ldong-ros (realgar). 3.2. Geological materials/minerals used in the current BTM formulations Out of 119 geological materials/minerals described in the Sowa Rigpa pharmacopoeia/ textbooks, only 29 of them (Table 1) are currently used by MSP for formulating 111 polyingredient BTM medicines. Out of 29 currently used minerals, nodal silica (cu-gang) obtained from Bambusa textilis was used in maximum number of herbo-mineral preparations (26 formulations), followed by mineral pitch (brag-zhun, 21 formulations), calcite (cong-zhi, 13 formulations) salt (rgyam-tshva, 10 formulations) and cinnabar (mtshal, 7 formulations) (Fig. 2). Fig. 2 Download high-res image (177KB)Download full-size image Fig. 2. Diversity and chemical classes of geopharmaceutical ingredients described as remedies in the Sowa Rigpa pharmacopoeias. 3.3. Sourcing geological materials/minerals used in the current BTM formulations Unlike medicinal herbs, which have specific collection time, sites or locations in Bhutan, mineral ingredients used in BTM are sourced from both within and outside the country. Since there is very scarce documentation on mineral deposits in Bhutan, majority of medicinal mineral ingredients are outsourced. Our study found that, out of 29 minerals used, only 7 of them (approximately 23%) are sourced from within the country, while rest 24 (approximately 77%) are imported from neighbouring countries like India, Nepal, Tibet (China) and Afghanistan. Imported minerals are not directly purchased by MSP but they are procured and supplied by the registered suppliers and dealers based in Bhutan. Market prices of these minerals are determined mainly by their rareness and the cultural significance attached to them. Precious metals, corals, pearl products and gemstones are very expensive in comparison to sea salts, rocks, and soils.(Fig. 3) Fig. 3 Download high-res image (380KB)Download full-size image Fig. 3. Mineral ingredients used or cited in current BTM formulations. 3.4. Mode of usage of minerals and herbo-mineral preparations Even though the therapeutic indication of an individual mineral (Table 1) is described in Tibetan and BTM pharmacopoeia, they are never used as a single component drug or without detoxification of toxic minerals. Minerals, which are considered traditionally dangerous/toxic) are first detoxified or pre-processed using traditional techniques. For example, mercury (Tsothel), which is not used in BTM, has to undergo detailed and very elaborate detoxification processes before using it in the herbo-mineral preparations (Gerke, 2014). In Bhutan, according to the study participants, MSP currently follows three major pre-processing or detoxification methods including: a) frying (b.rngo), b) boiling (b.tso) and c) burning (thal-ba-b.zo). For examples, while Tsha-la, ze-tshva, and mtshal are pre-processed using frying technique; bgyi-ru, mu-tig, mu-men, g.zi, g.ser, dngul, zangs, brag-zhun and cong-zhi are processed using boiling method. Completion of pre-processing/detoxification process is mainly determined by changes in colour and physical properties of the minerals. Minerals are mixed with medicinal plants/herbs/animal parts in standardised formulation ratios, and then finally prepared into six different dosage forms as capsules, tablets, pills, ointments, and powder. Addition of mineral ingredients in various formulations is exclusively guided by standardised ratios indicated in the ancient textbooks/pharmacopoeias and the recently developed BTM formulary book (Table 1). Except in few formulations such as brag-zhun-9-pa (main ingredient as mineral pitch) and lda-shel-dud-rtsi-ma (main ingredients as lcags-thal – powdered iron) where minerals constitute principal or major ingredients, rest of the herbo-anima-mineral formulations contain herbs or animal-derived products as main ingredients. These medicines are never meant for self-medication. It requires prescription from the trained traditional physicians (Drungtshos), who are extensively trained in this field for 5.6 years (Bachelor of medicine in Traditional Medicine) at the Faculty of Traditional Medicine, Khesar Gyalpo University of Medical Sciences of Bhutan. It is believed that these 111 herbo-anima-mineral preparations can treat more than 135 ailments and the medicines are usually administered through oral routes (eaten with lukewarm water). 4. Discussions The geological processes and geological materials impact humans and animals both positively and negatively. However, we found that many books, articles and symposia involving medical geology has been focused on health problems caused by exposure to ambient/environmental dust; geologic processes such as earthquakes and volcanic eruptions; geologic materials such as arsenic, mercury, lead, fluorine, selenium, and uranium, asbestos, quartz, and pyrite; and excess or deficiency of trace elements. There is limited attention or research focus or published information on the beneficial health effects of natural minerals, elements, inorganic and organometallic compounds, minerals, rocks, gemstones, precious metals, and rare earth metals used in traditional medicines. The ill-effects/geohazards of some of the toxic properties of these geological materials especially arsenic, mercury and lead have eclipsed the long, rich and varied record of health benefits of other minerals used in traditional medicines. Researching and reporting the good side of any geological materials or the traditional medicines that uses minerals especially those ores that may contain toxic elements have become very sensitive worldwide and consequently there is least concern on reporting geopharmaceutical information as compared to plants. Such sensitivity problem with the use of geological materials (not necessarily toxic elements) in Bhutan was evident in most of our study participants. Paracelsus, the father of pharmacology (1493–1541) stated that, ‘All substances are poisons and only the right balance/right dosage differentiates a poison and a remedy’ (Dissanayake, 2005) and possibly taking cue from his wisdom the World Health Organisation have set acceptable limits for heavy and toxic metals. Modern medical system have capitalised on his wisdom and made modern drug doctrines of dose and dosage forms. Nuclear medicine and radiation therapy, which is perceived as geohazards, uses radioactive iodine or radiation from elements in right doses for treating various types and forms of cancers. The question is ‘does traditional medicine has any doctrine of dose and dosage forms?’ Some scholarly traditional medical system including Chinese, Ayurvedic, Tibetan and Bhutanese medicines does have this doctrine of dose and dosage forms. These medical systems also have well documented traditional methods for detoxifying toxic minerals or geological materials including mercury. Whether these detoxification techniques have any scientific validity and if these detoxified minerals are really safe enough to include as ingredients for herbo-mineral preparations remains unknown. Thus, providing context of traditional uses and ethnomedical settings that is befitting to local culture, mode of usage, and treatment protocols would greatly reduce the sensitivities in reporting as well as risks to the study participants. This is more important while conducting the ethnopharmacological surveys on minerals used by the local healers, private practitioners, and private companies, which is not covered in this study. This study focused on the government operated Sowa Rigpa medical system in Bhutan, which is manufactured using in-house Good Manufacturing Practices and strictly regulated by the Drug Regulatory Authority of Bhutan. It is in this context that we derived our discussion of the results. 4.1. Geological materials description in Sowa Rigpa pharmacopoeia, current utilization in BTM and their quality control system In ancient Sowa Rigpa (mostly Tibetan) pharmacopoeia, more than 119 different types of geological materials/minerals were described. However, our study found that BTM uses only 29 minerals in the current herbo-mineral preparations. Most of the herbo-mineral preparations including precious pills that use toxic elements are omitted in the current formulary list of BTM. Many geological materials are omitted from the current BTM formulations for various reasons including: a) concern for geohazards, toxicity and safety of some toxic minerals used in few herbo-mineral preparations, b) few geological materials including gemstones, and precious metals are very expensive making BTM herbo-mineral preparations a high-priced commodity, and c) rare mineral substances/geological materials are hard to obtain making the production of herbo-mineral preparations unsustainable. BTM was the sole medical system before the advent of modern medicine in 1956. It was integrated with the modern health care system in 1967 and today, there are 65 traditional hospitals/units attached to modern hospitals/Basic Health Units in all 20 districts catering free medications to the people. For the last 50 years it has successfully coexisted with modern medicine and has gained trust of the Bhutanese patients (mostly old-aged) owing to its cultural alignment, spiritual connection and perceived minimal side effects. At the time of this study, MSP was producing 116 formulations using 13 medicinal animals (Yeshi et al., 2017a), 116 high altitude medicinal plants (HAMP) (Yeshi et al., 2017b), 113 low altitude plants (LAMP) (Wangchuk et al., 2017) and 29 minerals/geological materials. It is believe that the Sowa Rigpa was originally propounded by Medicine Buddha (Sangay-smen-lha) more than 2500 years ago and therefore efficacy of BTM is hardly questioned both by the Drungtshos or by the patients. However, the Essential Drug List Committee (EDLC) of Bhutan review the current BTM formulations every 2 – 3 years and decides whether to retain all previous years’ formularies/formulations or be replaced by other new formulations based on standard criteria including: a) emerging disease pattern, b) availability of medicinal ingredients, and c) safety, efficacy and popularity of the current formulations. Once revised formulations are approved by the EDLC, products are registered with Drug Regulatory Authority (DRA) and finally Product Master File (PMF) is developed and maintained by MSP. Recognising the growing popularity of BTM and the urgency to improve their quality, safety and efficacy. MSP have recently developed stringent quality control parameters and quality assurance system especially for plants and animal-derived products, which is described elsewhere in details (Wangchuk and Tashi, 2016b). Under numerous international funding bodies including World Health Organization (WHO, 1980s), Italian DISVI project (1990s), and two successive European Union (EU) projects (Phase I in 1994–1998; Phase II in 2006–2009); various technical experts/assistants including Chemists, Doctors, Pharmacognosists, Herbalist, Pharmacologists and Pharmacists from Europe, India and Thailand have been recruited at MSP to: a) develop quality parameters and quality control system, b) conduct research and documentation activities, d) introduce Good Manufacturing Practices (GMP) and Good Laboratory Practices (GLP). While various scientific studies on BTM medicinal plants (Wangchuk et al., 2010, Wangchuk et al., 2011b, Wangchuk et al., 2012, Wangchuk et al., 2013, Wangchuk et al., 2014, Wangchuk et al., 2015, Wangchuk et al., 2016a, Wangchuk et al., 2016c, Wangchuk et al., 2016d, Wangchuk et al., 2016e, Wangchuk et al., 2017, Shepherd et al., 2018, Wangchuk and Tashi, 2016b) validated their traditional uses and improvements in the quality of botanicals/phytotherapy were observed, medical geology/ geopharmaceuticals remains less explored. There is urgent need to study the quality, safety and potency of geological materials/minerals and their herbo-animal-mineral preparations. It may be easy to omit/discard the geological materials containing toxic elements from the formulations. However, it would be worthwhile to first understand their traditional therapeutic indications, process of detoxification (taming bad effects) and herbo-mineral preparation, biochemistry or chemical profile of the individual mineral ingredients (whether toxic or known to be non-toxic), acceptable limits set by WHO, and biological interactions. There is common conception that any substance containing mercury is toxic. It must be understood that mercury exist in different forms as organic mercury (e.g. methylmercury, ethylmercury), vapor mercury, soluble inorganic mercury (e.g., mercuric chloride, mercurous chloride), and insoluble mercury (e.g. mercuric sulphide); and that their toxicities vary greatly (Li et al., 2018). While vapour mercury possess strong toxicity on the central nervous system, soluble inorganic mercury are characterized by severely renal toxicity and gastrointestinal toxicity, the insoluble mercuric sulphide (HgS) does not appear to be toxic in itself (Clarkson and Magos, 2006, Liu et al., 2008). Li et al. (2018) on Tibetan herbo-mineral preparation containing mercury (Zuotai) showed chemical speciation, spatial distribution and toxicity of mercury on mouse treated with Zuotai, HgS and HgCl2, which indicated that deposition level and toxicity of mercury from Zuotai and HgS were far less than that of HgCl2. Other studies on Tshothel (detoxified mercury), Cinnabar (HgS) and Zuotai (herbo-mineral preparation) indicated that they can, not only can allay excitement, promote sleep, produce an antipyretic effect, have anti-inflammatory effects, extend the life of fruit flies; but may exert a possible beneficial effect on neurocognitive function (Zhou et al., 2011, Sallon et al., 2017, Jiang et al., 2009, Chen et al., 2011). Unlike, Tibetan medicines, BTM uses only cinnabar in the current herbo-mineral preparations. Despite promising health benefits shown by HgS and its herbo-mineral preparations, we should be aware of its high dose exposure and long-term treatment health implications, and therefore must be judicious in their utilization. The main sources of pollutants and adulterants including heavy metals, toxic trace minerals and plasticides are from environments, agriculture, industries, volcanic eruptions, and soils. Therefore, it would be pragmatic to screen all BTM formulations for these pollutants, which would ensure the safety of patients. 4.2. Challenges and future of medical geology/geopharmaceuticals in Bhutan Currently, 29 minerals are procured annually by MSP through their registered suppliers in Bhutan. Only 7 (22.58%) minerals/geological materials are sourced within the country, while rest 24 (77.42%) are imported from neighbouring countries like India, Nepal, Tibet (China) and Afganistan. One of the major challenges is sourcing authentic and high quality geological materials. Geology and mineral deposit exploration is rare in Bhutan. As a result, MSP and her registered suppliers are lacking in information on geological materials that can be found in Bhutan. There is lack of documentation, mineral herbarium and database on minerals. As a result of this information gap, the suppliers are left without option to buy/import the geological materials from neighbouring countries, whose supplies may be prone to adulteration and low quality materials. There are limited quality parameters for minerals and MSP exclusively relies on physical observations and verification/authentication of geological materials including colour, taste, density, hardness/rigidness, pH, melting point, and solubility. Titration method is applied to few minerals in order to analyse their chemical content. Thus, there is urgent need to conduct research and establish more comprehensive quality parameters for minerals/geological materials used in BTM. The existing quality control laboratory requires both expertise and the advanced quality testing technologies including Atomic Mass Spectrometry, Electron Microscopy, laboratory apparatus for determining heavy metals and other toxic/geohazardous materials, and chemical technologies for inorganic substances/materials/goods. Given the above challenges, the future of medical geology/geopharmaceuticals in Bhutan looks unsustainable. However, BTM garners huge respect for its alignment with cultural and traditional belief of the people and therefore, their use (omitting toxic elements) in BTM will continue. In addition, the geological materials/minerals used in Sowa Rigpa (in general) and BTM (in particular) contain rich geopharmaceutical information that could guide modern inorganic and metal-based drug discovery. The medicinal inorganic chemistry and metal-based complexes/metallodrugs are re-emerging and the researches related to herbo-mineral, and herbo-animal-mineral preparations provide new avenues for medicinal exploration. Other than lone mineral/ geological material/elements studies, no scientific investigations were performed for the herbo-mineral preparations. Such studies could lead to the discovery of novel mechanism of drug action and shed light on the synergism of herb-mineral interactions. 5. Conclusions and future direction The geopharmaceuticals or medicinal use of geological materials/minerals is most probably as old as mankind itself and it is being used in both traditional and modern medicines. The content analyses revealed that 119 minerals are described in Sowa Rigpa medical textbooks/pharmacopoeia (both Tibetan and Bhutanese) and 29 of them are currently used in BTM for preparing 111 herbo-mineral formulations. Out of 29 minerals currently in BTM, only 7 of them (23%) are sourced from within the country, while rest 24 (77%) are imported from neighbouring countries. Most of the currently used mineral ingredients belong to chemical classes of oxides, carbonates, elements and silicates. Nodal silica obtained from bamboos (Bambusa textilis) (cu-gang), mineral pitch (brag-zhun) and calcite (cong-zhi) were used in maximum number of herbo-mineral preparations. Considering these mineral classes and types used in major polyingredient formulations, it appears to us that these medicines are generally safe to consume under the prescription of a trained Drungtshos but not safe to self-medicate with the products. In future, there is urgent need to conduct research on medical geology in Bhutan and establish more comprehensive quality parameters for screening minerals/geological materials used in BTM. The existing quality control laboratory requires both expertise and the advanced quality testing technologies including Atomic Mass Spectrometry, Electron Microscopy, laboratory apparatus for determining heavy metals and other toxic/geohazardous materials, and chemical technologies for inorganic substances/materials/goods. Training MSP personnel in using such technologies and also on collecting, screening, pre-processing and detoxification of minerals would improve the quality and safety of BTM. Future work must also focus on research, documentation and database development of minerals/geological materials used in BTM. Research on detoxification methods to understand if they are effective in altering or reducing or enhancing the potency of medicines is essential for not only from the perspective of patient safety but also to see if it meets the WHO acceptable limits for human consumption. The mineral database must include several quality control parameters including the accurate chemical identity of a mineral, composition, traditional uses and contraindications, geohazards, handling and storage, physical and chemical properties, stability and reactivity, material safety data and toxicological information. Efforts must be put in to standardize existing herbo-mineral preparations to ensure reproducibility and scientific validity. So far, no studies on the availability of medicinal mineral ingredients in Bhutan was carried out and therefore merits immediate attention. Sourcing mineral ingredients from within Bhutan would, not only help curtail importing low quality or contaminated minerals from neighbouring countries, but could also generate income to the farmers and miners in Bhutan. Uncited references (Carretero, 2002, Gerke, 2013, Gomes and Silva, 2007, PubChem, Open Chemistry Database, 2017, Soetan et al., 2010) Acknowledgements We acknowledge Menjong Sorig Pharmaceuticals (MSP) for their administrative support. We are particularly grateful to Mr. Samten (Senior Pharmacognosist), Mr. Singye Wangchuk and Mr. Garab Dorji (Senior Procurement Officers), Mr. Sherab Tenzin (Research In-charge), Drung-tsho Dorji Nidup, Drung-tsho Wangdi Phuntshok, sMenpa Jigme Dorji for their invaluable participation in the interview and discussions of this study. PW is supported by NHMRC ECR Fellowship. Conflict of interest The authors declare that we have no conflicts of interest in this study. Author contributions KY collected the data, chemically identified the minerals, translated the traditional uses of individual minerals used in BTMS, analysed data and wrote the manuscript. PW designed, supervised the study and wrote the manuscript. References Abrahams, 2005 Abrahams, Peter W.: The involuntary and deliberate (geophagy) ingestion of soil by humans and other members of the animal kingdom. In, Essentials of Medical Geology, Selinus, et al., eds. Elsevier, N.Y.2005, p. 435-458. Arya, 1998 P.Y. Arya Dictionary of Tibetan Materia Medica Motilal Banarsidass Publishers Private Limited, Delhi, India (1998) Aziz et al., 2002 N. Aziz, A.H. Gilani, M.A. Rindh Kushta(s): unique herbo-mineral preparations used in South Asian traditional medicine Medical Hypotheses., 59 (4) (2002), pp. 468-472 ArticleDownload PDFView Record in Scopus Carretero, 2002 M.I. Carretero Clay minerals and their beneficial effects upon human health. A review Applied Clay Sci., 21 (2002), pp. 155-163 ArticleDownload PDFView Record in Scopus Chen et al., 2011 Z. Chen, P. Xianglan, W. Li, K. Wu, G. Lan, J. Cui The influence on Drosophila life of Tibetan medicine Zuota Lishizhen Med. Mater. Med. Res., 22 (2011), pp. 422-423 View Record in Scopus Clarkson and Magos, 2006 T.W. Clarkson, L. Magos The toxicology of mercury and its chemical compounds Crit. Rev. Toxicol., 36 (2006), pp. 609-662 CrossRefView Record in Scopus Commonly Encountered Gemstones (CEGs), 2010 Commonly Encountered Gemstones (CEGs), 2010. Gem Testing Laboratory. Department of Mining and Geology, Government of Kerala, India. Craig and Adams, 2008 S. Craig, V. Adams Global pharma in the land of snows: Tibetan medicines, SARS, and identity politics across nations Asian Medicine, 4 (2008), pp. 1-28 CrossRef Dissanayake, 2005 C. Dissanayake Of stones and health: Medical geology in Sri Lanka Science, 309 (5736) (2005), pp. 883-885 CrossRefView Record in Scopus Dorji, 1995 Dorji, G., 1995. (Immaculate Crystal Mirror of Materia Medica Illustrations). Mirigs dpe skrun khang, Beijing. Dorji, 2011 Dorji, Y., 2011. Rin-po-che dang g.ter-r.dzes-sman gi ‘ nor-bu’i dho-shal: ‘druk-sman gi ‘ Mejong Sorig b.zo-b.skrun-khang.’i-lhan-khag. Thimphu, Bhutan. Duffin, 2013 Duffin, C.J., 2013. Lithotherapeutical research sources from antiquity to the mid-eighteenth century. In A History of Geology and Medicine. Duffin, C.J., Moody, R.T.J., Gardner-Thorpe, C (Eds). Geological Society Special Publication, 375, 7-43. Finkelman, 2006 R.B. Finkelman Health benefits of geologic materials and geologic processes Int. J. Environ. Res. Public Health., 3 (4) (2006), pp. 338-342 CrossRefView Record in Scopus Formulary of Traditional Medicine of Bhutan (FTMB), 1983 Formulary of Traditional Medicine of Bhutan (FTMB), 1983. Ministry of Social Service. Thimphu, Bhutan. Gerke, 2013 B. Gerke (2014). The social life of Tsotel: Processing mercury in contemporary Tibetan medicine Asian Med: Trad. Moder., 8 (1) (2013), pp. 120-152 CrossRefView Record in Scopus Gomes and Silva, 2007 C.S.F. Gomes, J.B.P. Silva Minerals and clay minerals in medical geology Applied Clay Sci., 36 (2007), pp. 4-21 ArticleDownload PDFView Record in Scopus Gonpo, 2011a Gonpo, Y.Y., 2011a. The Subsequent Tantra from the Secret Quintessential Instructions on the Eight Branches of the Ambrosia Essence Tantra Reprinted ed.. Men-Tsee-Khang Publications, Dharamsala. Gonpo, 2011b Gonpo, Y.Y., 2011b. The Root Tantra and The Explanatory from the Secret Quintessential Instructions on the Eight Branches of the Ambrosia Essence Tantra Reprinted 2nd ed.. Men-Tsee-Khang Publications, Daramsala. Jiang et al., 2009 E.N. Jiang, C.G. Zhang, J.H. Wang, Z.G. Li, F. Cheng, X. Xue, Z.P. Liu Study on the pharmacodynamics of Tibetan medicine zuotai Lishizhen Med. Mater. Medic. Res., 20 (2009), pp. 3-4 View Record in Scopus Korbel and Novak, 2001 Korbel, P., Novak, M., 2001. The Complete Encyclopedia of Minerals: Description of over 600 minerals from around the world. Grange Books PLC, United Kingdom. Li et al., 2018 C. Li, W. Xu, S. Chu, Z. Zheng, Y. Xiao, L. Li, H. Bi, L. Wei The chemical speciation, spatial distribution and toxicity of mercury from Tibetan medicine Zuotai,β-HgS and HgCl2 in mouse kidney J Trace Elem Med Biol., 45 (2018), pp. 104-113 ArticleDownload PDFView Record in Scopus Limpitlaw, 2004 Limpitlaw U. G.: The medical uses of minerals, rocks, and fossils. Geological Society of America 2004 Annual Meeting, Abstracts with Programs, Abstract 48-5, 2004, Vol. 36, No. 5, p.130. Liu et al., 2008 J. Liu, J.Z. Shi, L.M. Yu, R.A. Goyer, M.P. Waalkes Mercury in traditional medicines: is cinnabar toxicologically similar to common mercurials? Exp. Biol. Med., 233 (2008), pp. 810-817 CrossRefView Record in Scopus, 2017, 2017. The Minerals and Gemstone Kingdom: Complete Information Guide to Rocks, Minerals, and Gemstones. Accessed at: 〈〉. (Accessed on 2 August 2017). Monograph on Traditional Medicine of Bhutan (MTMB), 2015 Monograph on Traditional Medicine of Bhutan (MTMB), 2015. Ministry of Health, Thimphu, Bhutan. Phuntshok, 1994 D.T. Phuntshok Shel-gong-Shel-phreng T.M.A.I Publishers, India (1994) Precious minerals in everyday life, 2011-2012 Precious minerals in everyday life (2011-2012). The wealth of India Division. CSIR National Institute of Science Communication and Information Resources. New Delhi, India. PubChem, Open Chemistry Database, 2017 PubChem, Open Chemistry Database, 2017. National Centre for Biotechnology Information (NCBI). Accessed at: 〈〉. (Accessed 11 July 2017). Rock and Mineral Identification for Engineers, 1991 Rock and Mineral Identification for Engineers (1991). U.S Department of Trasnportation. Federal Highway Administration. U.S.A. Sallon et al., 2017 S. Sallon, Y. Dory, Y. Barghouthy, T. Tamdin, R. Sangmo, J. Tashi, S. Yangdon, T. Yeshi, T. Sadutshang, M. Rotenberg, E. Cohen, Y. Harlavan, G. Sharabi, T. Bdolah-Abram Is mercury in Tibetan Medicine toxic? Clinical, neurocognitive and biochemical results of an initial cross-sectional study Exp. Biol. Med., 242 (3) (2017), pp. 316-332 CrossRefView Record in Scopus Soetan et al., 2010 K.O. Soetan, C.O. Olaiya, O.E. Oyewole The importance of mineral elements for humans, domestic animals and plants: A review African J. Food Sci., 4 (5) (2010), pp. 200-222 View Record in Scopus Tenzin, 2007 S. Tenzin Traditional Medicine Formularies of Bhutan Menjong Sorig Pharmaceuticals, Thimphu, Bhutan (2007) Thakchoe and Dolma, 2005 Thakchoe, T., Dolma, T., 2005. 2nd ED. Tibetan-English Dictionary of Tibetan Medicine and Astrology. Drungtsho Publications. Dharamsala, India. Wangchuk et al., 2007 P. Wangchuk, D. Wangchuk, J. Aagaard-Hansen Traditional Bhutanese medicine (gSo-BA Rig-PA): an integrated part of the formal health care services Southeast Asian J Trop Med Public Health., 38 (1) (2007), pp. 161-167 View Record in Scopus Wangchuk et al., 2010 P. Wangchuk, J.B. Bremner, Samten., B.W. Skelton, A.H. White, R. Rattanajak, S. Kamchonwongpaisan Antiplasmodial activity of atisinium chloride from the Bhutanese medicinal plant, Aconitum orochryseum J Ethnopharmacol., 130 (2010), pp. 559-562 ArticleDownload PDFView Record in Scopus Wangchuk et al., 2011a P. Wangchuk, S.G. Pyne, P.A. Keller Ethnobotanical authentication and identification of khrog-sman (Lower Elevation Medicinal Plants) of Bhutan J. Ethnopharmacol., 134 (2011), pp. 813-823 ArticleDownload PDFView Record in Scopus Wangchuk et al., 2011b P. Wangchuk, P.A. Keller, S.G. Pyne, M. Taweechotipatr, A. Tonsomboon, R. Rattanajak, S. Kamchonwongpaisan Evaluation of an ethnopharmacologically selected Bhutanese medicinal plants for their major classes of Phytochemicals and biological activities J. Ethnopharmacol, 137 (1) (2011), pp. 730-742 ArticleDownload PDFView Record in Scopus Wangchuk et al., 2012 P. Wangchuk, P.A. Keller, S.G. Pyne, A.C. Willis, S. Kamchonwongpaisan Antimalarial alkaloids from a Bhutanese traditional medicinal plant Corydalis dubia J Ethnopharmacol., 143 (2012), pp. 310-313 ArticleDownload PDFView Record in Scopus Wangchuk et al., 2013 P. Wangchuk, P.A. Keller, S.G. Pyne, J. Korth, Samten, M. Taweechotipatr, R. Rattanajak, S. Kamchonwongpaisan Antimicrobial, antimalarial and cytotoxicity activities of constituents of a Bhutanese variety of Ajania nubigena Nat Prod Commun., 8 (2013), pp. 733-736 View Record in Scopus Wangchuk et al., 2014 P. Wangchuk, S.G. Pyne, P.A. Keller, M. Taweechotipatr, S. Kamchonwongpaisan Phenylpropanoids and furanocoumarins as antibacterial and antimalarial constituents of the Bhutanese medicinal plant, Pleurospermum amabile Nat Prod Commun., 9 (2014), pp. 957-960 View Record in Scopus Wangchuk et al., 2015 P. Wangchuk, S. Navarro, C. Shepherd, P.A. Keller, S.G. Pyne, A. Loukas Diterpenoid alkaloids of Aconitum laciniatum and mitigation of inflammation by 14-O-acetylneoline in a murine model of ulcerative colitis Sci Rep., 5 (2015), p. 12845 Wangchuk et al., 2016a P. Wangchuk, K. Namgay, Y. Dorji Medicinal plants of Dagala region in Bhutan: their diversity, distribution, uses and economic potential J. Ethnobiol. Ethnomed., 12 (2016), p. 28 Wangchuk and Tashi, 2016b P. Wangchuk, Tashi Quality assurance of the university medical education, hospital services and traditional pharmaceutical products of the Bhutanese So-wa-rig-pa health care system BMC Complement. Altern. Med., 16 (2016), p. 283 Wangchuk et al., 2016c P. Wangchuk, P.R. Giacomin, M.S. Pearson, M.J. Smout, A. Loukas Identification of lead chemotherapeutic agents from medicinal plants against blood flukes and whipworms Sci.Rep., 6 (2016), p. 32101 Wangchuk et al., 2016d P. Wangchuk, M.S. Pearson, P.R. Giacomin, L. Becker, J. Sotillo, D. Pickering, M.J. Smout, A. Loukas Compounds derived from the Bhutanese daisy, Ajania nubigena, demonstrate dual anthelmintic activity against Schistosoma mansoni and Trichuris muris PLoS Negl. Trop. Dis., 10 (2016), p. e0004908 CrossRef Wangchuk et al., 2016e P. Wangchuk, T. Sastraruji, M. Taweechotipatr, P. Keller, S. Pyne Anti-inflammatory, anti-bacterial and anti-acetylcholinesterase activities of two isoquinoline alkaloids–scoulerine and cheilanthifoline Nat. Prod. Commun., 11 (12) (2016), pp. 1801-1804 View Record in Scopus Wangchuk et al., 2017 P. Wangchuk, K. Yeshi, K. Jamphel Pharmacological, ethnopharmacological, and botanical evaluation of subtropical medicinal plants of Lower Kheng region in Bhutan Integr Med Res., 6 (4) (2017), pp. 372-387 ArticleDownload PDFView Record in Scopus Shepherd et al., 2018 C. Shepherd, P. Giacomin, S. Navarro, C. Miller, A. Loukas, P. Wangchuk A medicinal plant compound, capnoidine, prevents the onset of inflammation in a mouse model of colitis J Ethnopharmacol., 211 (2018), pp. 17-28 ArticleDownload PDFView Record in Scopus, 2014, 2014. Mineralogy Database. Accessed at: 〈〉. (Accessed on 2 August 2017). Yeshi et al., 2017a K. Yeshi, P. Morisco, P. Wangchuk Animal-derived natural products of Sowa Rigpa medicine: Their pharmacopoeial description, current utilization and zoological identification J. Ethnopharmacol., 207 (2017), pp. 192-202 ArticleDownload PDFView Record in Scopus Yeshi et al., 2017b K. Yeshi, P. Yangdon, S. Kashyap, P. Wangchuk Antioxidant activity and the polyphenolic and flavonoid contents of five altitude medicinal plants used in Bhutanese sowa rigpa medicine J. Biologically Active Products from Nature., 7 (1) (2017), pp. 18-26 CrossRef Yu et al., 1995 W. Yu, H.D. Foster, T. Zhang Discovering Chinese Mineral Drugs J. Orthomolecular Med., 10 (1) (1995), p. 1995 View Record in Scopus Zhou et al., 2011 X. Zhou, L. Wang, X. Sun, X. Yang, C. Chen, Q. Wang, X. Yang Cinnabar is ot converted into methylmercury by human intestinal bacteria J Ethnopharmacol., 135 (1) (2011), pp. 110-115 ArticleDownload PDFView Record in Scopus © 2018 Elsevier B.V. All rights reserved.