Beneduce, A.

Ciocan, C.

Declementi, M.

Garzaro, G.

Godono, A.

Loia, R. C.

Mansour, I.

Milanesio, N.

Pira, E.

English

Institutional Research Information System University of Turin

Lead poisoning from Ayurvedic treatment: a further caseCatalina Ciocan1,2, Ihab Mansour1, Alessandro Beneduce1, Riccardo Corgiat Loia1, Nicolò Milanesio1, Michael Declementi1, Alessandro Godono1, Giacomo Garzaro1,2, Enrico Pira1,2 1 University of Torino, Department of Public Health and Pediatrics, Turin, Italy2 Città della Salute e della Scienza di Torino University Hospital, Occupational Health Service, Turin, ItalyMed Lav 2021; 112, 2: 162-167DOI: 10.23749/mdl.v112i2.10576Received 2.9.2020 - Accepted 14.10.2020Corresponding author: Dr. Michael Declementi, Via Zuretti 29, 10126 Turin, Italy - E-mail: michael.declementi@unito.itKey words: Ayurvedic; lead poisoning; anaemia; chelation; drug safetysummaryPurpose: We report a case of a 30 years old Indian sailor with microcytic anemia (Hb 9.9), persistent ab-dominal pain, emesis, dark stool, hyperchromic urine, latent jaundice and asthenia. Lead intoxication was conf irmed (blood lead value of 102 µg/dL). The patient assumed Ayurvedic medicines in the previous months. Ayurveda is an ancient form of Indian traditional popular medicine aiming to re-establish health and body function through herbal preparations, heavy metals are often added. Our purpose was to treat the patient and to establish the source of poisoning. Methods: After testing blood and urine lead concentration of oth-er 3 crew members and analyzing over than 150 products used on the ship professional exposure was ex-cluded. We analyzed the two   Ayurvedic drugs assumed by the patient with an Inductively Coupled Plasma Mass Spectrometry. The patient underwent three chelation cycles with Calcium Disodium Ethylenediami-netetraacetic acid (EDTA) while monitoring blood and urinary lead levels. Results: The f inal blood lead level at discharge, after three chelation cycles, was 36.27 µg/dL. One of the two drugs contained extremely high concentrations of lead and mercury. The three different mixtures of this preparation showed lead concen-trations of 12,638.54 mg/kg (Sample 2A), 23,043.02 mg/kg (Sample 2B), 21,352.97 mg/kg (Sample 2C); these levels are much higher than the highest values reported in literature for the indian soil (32 mg/kg). Conclusions: This case and similar cases raise the safety alert on complementary and alternative medicines; Ayurvedic medicine users should be carefully informed about potential risks and signs of poisoning. open access www.lamedicinadellavoro.itAyurveda is a form of traditional medicine native to India which has been practiced extensively in the subcontinent for more than 2000 years (1) and is used approximately by 80% of Indians (2). Recently, Ayurveda is gaining popularity as a complementary treatment. As a result, approximately 40% of adults in the United States report using complementary and alternative medicines (CAMs) (3). Increasing numbers could probably be observed in countries where Ayurveda is not yet so practiced, due to work migration (4). Ayurvedic formulations are based on herbal products but often include heavy metals, intentionally added to restore health and normal body function, as part of Rasa Shastra (5).Contrary to allopathic medicine, manufacturing and access to CAMs are poorly regulated. Ayur-vedic medicines in Western countries are not con-sidered as drugs. Rather, as food supplements, they lead poisoning from ayurvedic treatment 163are available without medical prescription through multiple sources including the Internet. Although even some physicians overlook possible risks asso-ciated with ayurvedic tratments, it is estimated that over 20% of ayurvedic medications distributed by U.S. and Indian companies contain toxic metals (5); some preparations have been found to contain lead and/or mercury exceeding by 100 to 10,000 times the limits set for food (6).From 2000 to 2003, the Centers for Disease Control reported 12 cases of lead poisoning in adults associated with Ayurvedic medication intake occurring in five different states (7). Less than 20 scientific reports on lead poisoning could be found through scientific literature analysis of the past 10 years (Mesh key words: “lead poisoning” AND “Ayurvedic medication”). The contamination of herbal formulations with metals presents potential health risks. The most common diagnosis is lead poisoning, which is frequently revealed by the in-vestigation of anaemia.Lead is considered as an inhibitor of haem synthe-sis and a haemolysis promotor. Lead related anaemia can be normocytic or microcytic mainly due to the inhibition of delta aminolevulinic acid dehydratase and ferrochelatase.  As a result, protoporphyrin ac-cumulates in erythrocytes forming zinc protopor-phyrin. Lead levels exceeding 30 μg/dL determine elevated blood levels of free erythrocyte protopor-phyrin and zinc protoporphyrin. Anaemia develops when blood lead levels exceed 50 to 60 μg/dL. Lead has a prevalent urinary excretion, the non-excreted portion being deposited in bones. Other characteris-tic manifestations of lead poisoning include gastro-intestinal and neurological symptoms (8).In Western countries, industrial lead exposure control played a key role in minimizing job exposure (9) and in the last decades cases of saturnism requir-ing hospitalization were mostly non-occupational, due to contaminated wine (10). We recently had the chance to admit to our Department a young Indian sailor with high levels of blood lead. During a resi-dential period in his country from 14/10/2019 to 31/01/2020 the patient presented lower back pain due to the recurrence of a pilonidal cyst, previously experienced in 2008 and 2013. In both cases, he was treated with Ayurvedic topic medications while, for this last recrudescence, his Ayurvedic practitioner (referred to as “shaman”) prescribed an oral formu-lation. In February, the patient returned to Italy and rejoined his crew in Genoa (Italy) with whom he carried out different maintenance activities on board. At the beginning of March, due to persistent abdominal pain, he underwent gastroenterological examination and a few days later he presented em-esis, dark stool, hyperchromic urine, latent jaundice and asthenia and was referred to Hospital Galliera in Genoa. The first blood test showed hemoglobin 9.9 mg/dL, total bilirubin 3.5 mg/dL (direct biliru-bin 1.1 mg/dL), SGOT 90 mg/dL, SGPT 160 mg/dL (Table 1). Esophagogastroduodenoscopy was negative. The only finding in the chest and abdomi-nal CT was hepatic steatosis. At the end of April, the patient underwent haematological counselling for microcytic anaemia associated with hyperfer-ritinemia and reticulocytosis. A screening for lead poisoning showed a blood lead value of 102 µg/dL. On 8/6/2020, after passing the COVID-19 hos-pital prevention protocol (1), the patient came to our observation: during the previous three months the ayurvedic treatment had been withdrawn, and symptoms gradually disappeared thereafter. In April and May 2020, the patient did not undergo any blood tests.During the first hospitalization in our depart-ment, we excluded occupational exposure. Blood and urine lead levels of other crew members were in a normal range and over 150 products used on board resulted lead free. At the admission in our department, the patient was asymptomatic, and the main haemato-chemical values were within the re-spective refence intervals (Table 1-2), whereas the basal lead values in blood (B-Pb) and urine samples were still high (74.61 µg/dL and 94.7 µg/L, respec-tively). In consideration of the B-Pb (12, 13), a chela-tion protocol was initiated with the administration of Calcium Disodium Ethylenediaminetetraacetic acid (EDTA) 2 g in 500 ml of physiological solu-tion (PS) in 12 hours for the first day, followed by four days of EDTA 1 g at the same dilution and infusion speed. Hematic and urinary lead variation during three chelation cycles is reported in Figure 1. B-Pb at discharge was 36.27 µg/dL. ciocan et al164The sailor referred that he used to assume an oral intake of 1 dose (about one spoon) of “product 1” mixed with 1 dose of each of the three parts of “product 2”, twice a day (products 1, 2A, 2B, 2C).Our Industrial Toxicology Laboratory analysed 0.5 g of each product sample: we added 2.5 ml of concentrated Nitric Acid to each sample and after 1h of treatment in a furnace at 80°C we made up to 25 ml, we diluted the solutions (1:1000) and used an inductively coupled plasma mass spectrometry (ICP-MS) searching for arsenic, mercury, copper, chromium, manganese, iron, nickel and lead.Finally, we compared our values with data in the literature regarding the highest values in different soil samples of Uttar Pradesh, our patient’s home region; results are summarized in Table 3 (14-16).ConClusionLaboratory findings confirmed the source of poi-soning. The absence of mercury-related symptoms despite a high content of mercury in the samples 2A, 2B and 2C could be explained by the species of the metal, as inorganic mercury is known to be poorly absorbed by the gastrointestinal tract. A pe-culiar aspect of this case is that haemoglobin (Hb) usually takes several months to return to normal values in the absence of chelation while our patient had a fast normalization of Hb values in less than three months, before arrival in our hospital (Ta-ble 2). This case and similar cases of lead poison-ing caused by Ayurveda practice raise the safety alert of complementary and alternative medicines. The increasing number of users of Ayurvedic drugs Table 1 - Blood values of biomarkers of lead intoxicationAt admission (08/06/2020)At discharge  (10/07/2020)Reference valuesALA Dehydratase, U.I./ml 11.5 20.8 20.0 – 40-0Blood Lead Level (ICP-MS), μg/dL   74.61 42.2 0.50 – 10.0Baseline Urinary Lead (ICP-MS), μg/dL 94.70 93.6    5.00 –  30.00Total Hemoglobin, g/dL 12.80 13.9 14.00 – 18.00Zinc protophorphyrin – ZP,  μg/dL Hb   0.66 0.52 < 2.00ALAU - Delta-aminolevulinic acid, mg/g creat 14.89 1.96 < 4.50CPU – Coproporphyrin, μg/dL creat 423 3 < 100.00Table 2 - Selected haemato-chemical valuesInitial values (11/04/2020)At admission (08/06/2020)At discharge (10/07/2020)Reference valuesCreatinine, mg/dL 0.9 0.93 1.04 0.60 – 1.30Sodium, mEq/L 139 143 142 135 – 145Potassium, mEq/L 4.6 4.4 3.8 3.5 – 5.0Leukocytes, No.x109/L 9.73 6.51 5.99 4.00 – 10.00Erythrocytes, No.x1012/L 3.23 4.58 5.12 4.50 – 5.80Haemoglobin, g/dL 8.40 13.0 14.1 13.5 – 18.00Hematocrit, % 25.5 41.0 42.4 40.0 – 52.0Mean corpuscular volume, fL 78.9 90 83 79 – 96Platelet Count, No.x109/L 300 270 223 140 – 450lead poisoning from ayurvedic treatment 165Figure 1 - Blood and urine lead levels during chelation therapyTable 3 - Concentration of analysed elements in the environment and in the ayurvedic drug taken by the patient Highest soil  concentration in literature (mg/kg)*Concentration in sample product  1 (mg/kg)Concentration in sample product  2A (mg/kg)Concentration in sample product  2B (mg/kg)Concentration in sample product  2C (mg/kg)Lead 520 2.31 12,638.54 23,043.02 21,352.97Mercury 0.49 2.54 89,076.70 126,640.27 145,710.64Arsenic 12 0.35 134.94 103.98 122.30Copper 323 3.96 1,511.04 2,168.79 2,356.80Chromium 0.9 1.14 8.86 7.68 12.04Manganese 45.1 26.34 146.74 172.53 149.75Iron 389 288.04 14,990.34 16,498.80 15,767.59Nickel 100 0.66 7.24 8.02 9.21* Values referred to different sites of Uttar Pradesh region, except for mercury that is referred to whole Indiaciocan et al166worldwide calls for establishing standardized label-ling and regulations of manufacturing and distri-bution of these treatments. Moreover, consumers should be properly informed about potential risks and clinical signs of poisoning. We believe it is im-portant to stress these concepts and to be extremely vigilant, as the number of case reports is dwindling in the last ten years, while this work proves that the problem persists.referenCes  1.  Datta-Mitra A, Ahmed O Jr.: Ayurvedic medicine use and lead poisoning in a child: a continued concern in the United States. Clin Pediatr (Phila) 2015; 54: 690-692. doi:10.1177/0009922814553397   2.  Saper RB, Kales SN, Paquin J, et al. Heavy metal content of ayurvedic herbal medicine products. JAMA. 2004; 292: 2868-2873. doi:10.1001/jama.292.23.2868  3.  Eisenberg DM, Davis RB, Ettner SL, et al. Trends in al-ternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA 1998; 280: 1569-1575. doi:10.1001/jama.280.18.1569  4.  Mucci N, Traversini V, Giorgi G, et al. Migrant Workers and Physical Health: An Umbrella Review. Sustainabil-ity 2019; 11: 232  5.  Mikulski MA, Wichman MD, Simmons DL, et al. Toxic metals in ayurvedic preparations from a public health lead poisoning cluster investigation. Int J Occup Environ Health 2017; 23: 187-192. doi:10.1080/10773525.2018.1447880  6.  Gunturu KS, Nagarajan P, McPhedran P, Goodman TR, Hodsdon ME, Strout MP. Ayurvedic herbal medi-cine and lead poisoning. J Hematol Oncol 2011: 51. doi: 10.1186/1756-8722-4-51. PMID: 22185092; PMCID: PMC3259062  7.  Centers for Disease Control and Prevention (CDC). Lead poisoning associated with ayurvedic medications--five states, 2000-2003. MMWR Morb Mortal Wkly Rep 2004; 53: 582-584  8.  Kales SN, Christophi CA, Saper RB. Hematopoietic toxicity from lead-containing Ayurvedic medications. Med Sci Monit 2007; 13(7):CR295-CR298  9.  Pira E, Garzaro G, De Cillis E, et al. Evolution of the concept OS&H from the second Post-war to today: From prescriptive system to assessment and manage-ment of risks in system quality -The extended model in collaboration with large Facilities. Evolution of multi-disciplinary culture of safety and OS&H. GEAM 2018; 55: 16-2010.  Perrelli G, Capellaro E, Pira E, et al. Further cases of lead poisoning from wine. Am J Ind Med 1984; 5: 377-381. doi:10.1002/ajim.470005050611.  Garzaro G, Clari M, Ciocan C, et al. COVID-19 infec-tion and diffusion among the healthcare workforce in a large university-hospital in northwest Italy. Med Lav 2020; 111: 184-194. doi:10.23749/mdl.v111i3.976712.  Flora SJ, Pachauri V. Chelation in metal intoxication. Int J Environ Res Public Health 2010; 7: 2745-2788. doi:10.3390/ijerph707274513.  Schroeder AP, Tilleman JA, DeSimone II EM. Lead Toxicity and Chelation Therapy, US Pharm 2015; 40: 40-4414.  Singh S, Raju NJ, Nazneen S. Environmental risk of heavy metal pollution and contamination sources us-ing multivariate analysis in the soils of Varanasi en-virons, India. Environ Monit Assess 2015; 187: 345. doi:10.1007/s10661-015-4577-415.  Raj D, Maiti SK. Sources, toxicity, and remediation of mercury: an essence review. Environ Monit Assess. 2019; 191:566. doi:10.1007/s10661-019-7743-216.  Adimalla N. Heavy metals pollution assessment and its associated human health risk evaluation of urban soils from Indian cities: a review. Environ Geochem Health 2020; 42:173-190. doi:10.1007/s10653-019-00324-4No potential conflict of interest relevant to this article was reported by the authorsla raCColta Completa della nostra rivista diventa digitaleProcede la digitalizzazione della raccolta completa della nostra rivista (“Il Lavoro” dal 1901 al 1924 e poi  “La Medicina del Lavoro” dal 1925 in poi). Oltre agli ultimi 20 anni, già accessibili nel sito della casa editrice  (www.lamedicinadellavoro.it), i volumi pubblicati nei primi 50 anni (1901-1950) sono ora disponibili sia in formato fotografico (.tiff o .jpg) che come documento ricercabile (.pdf ). Tutti i volumi disponibili saranno online e ad accesso libero subito dopo la firma di una convenzione tra la struttura (SIML - Società Italiana di Salute sul Lavoro) e l’Università degli Studi di Milano (proprietaria dell’archivio storico della rivista). Nel frattempo, chi intendesse realizzare progetti sulla storia della medicina del lavoro utilizzando i volumi pubblicati nella prima metà del XX secolo è pregato di contattarci (redazione[at]lamedicinadellavoro.it). the Complete ColleCtion of our journal goes digitalThe digitalization of the complete collection of our journal (“Il Lavoro” and then “La Medicina del Lavoro” from the 16th volume onwards) is advancing. In addition to the last 20 years already accessible from the journal’s site (www.lamedicinadellavoro.it), all the volumes published during the first 50 years (1901-1950) are now available both in photographic format (.tiff and .jpg) and as a searchable document (.pdf ). Open access will be provided soon once an agreement is signed between the property (SIML – Italian Society of Occupational Health) and the University of Milan (owner of the journal’s historical archive). Meanwhile, scholars willing to implement projects on the history of Occupational Medicine relying on the volumes published during the first half of the 20th   century are kindly requested to contact us (redazione[at]lamedicinadellavoro.it).

Lead poisoning from ayurvedic treatment: A further case

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Lead poisoning from ayurvedic treatment: A further case

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