Download 8/17 ******** Herbal medicine and lead intoxication

8/17 中西醫聯合討論會 Nephro Fellow 1 潘恆之
 Sources of toxic chemicals in herbal products :
A. Contamination –
1. Environmental conditions
2. The conditions under which they are air-dried
3. The storage and transport conditions
4. The manufacturing processes
~ Some aspects of toxic contaminants in herbal medicines – chemosphere 52 (2003)
1361-1371
 B. Deliberate inclusion as an ingredient –
1. For therapeutic purpose.
2. to increase the weight of the product prior to sale.
~ Lead Encephalopathy Due to Traditional Medicines – Current Drug Safty 2008
January; 3(1):54-59
~ Toxicology 181-182 (2002) 571-576
 California offiical study analysed 251 Chinese medicine:
24/251 products contained lead. 36/251 products
contained arsenic. 35/251 products contained mercury;
at least 83/251 (32 %) contained heavy metals, and 23
had more than one adulterant.
~ Adulterants in Asian Patent Medcines – NEJM Vol 339, No.12, Sep 17, 1998
 Koh and Woo analysed 2080 traditional Chinese
medicine in Singapore: 42/2080 medicines contained
metals – 28/2080 products contained mercury, 8/2080
products contained lead, 6/2080 products contained
arsenic. 1/2080 product contained both mercury and
lead and another contained both mercury and arsenic.
~ Toxic heavy metals and undeclared drugs in Asian herbal medicines – TRENDS in
Pharmacological Sciences Vol.23 No.3 March 2002
 Melchart et al. analysed all 317 Chinese herbs in
German . Heavy metal content was detected in 3.5%.
~ Toxic heavy metals and undeclared drugs in Asian herbal medicines – TRENDS in
Pharmacological Sciences Vol.23 No.3 March 2002
~ Heavy metals in traditional Chinese medicines: A systematic review –
Clinical Pharmacology and Therapeutics, Vol 70, No. 6, Dec 2001
~ Heavy metals in traditional Chinese medicines: A systematic review –
Clinical Pharmacology and Therapeutics, Vol 70, No. 6, Dec 2001
~ Heavy metals in traditional Chinese medicines: A systematic review –
Clinical Pharmacology and Therapeutics, Vol 70, No. 6, Dec 2001
~ Heavy metals in traditional Chinese medicines: A systematic review –
Clinical Pharmacology and Therapeutics, Vol 70, No. 6, Dec 2001
~ Heavy metals in traditional Chinese medicines: A systematic review –
Clinical Pharmacology and Therapeutics, Vol 70, No. 6, Dec 2001
~ Heavy metals in traditional Chinese medicines: A systematic review –
Clinical Pharmacology and Therapeutics, Vol 70, No. 6, Dec 2001
 Up to 10-15% of Asian patent medicines contained lead,
mercury or arsenic. Such as Lithargyrum (密陀僧 –
lead), Cinnabaris (硃砂—mercury sulfide), for sedative
purposes. Sulphur (硫磺), Realgar (雄黃—arsenic) ,
Calomela(輕粉—mercury chloride), ‘hydrargyri
oxydum rubrum’ (mercury oxide) and Chalcanthitum
(膽礬) for systemic infection, ulcer and insomnia.
~ Hong Kong Med J Vol 8 No 4 August 2002
~ Toxic heavy metals and undeclared drugs in Asian herbal medicines – TRENDS in
Pharmacological Sciences Vol.23 No.3 March 2002
 Ba Bow Sen (八寶散) – contain more than 1000 ppm lead
=> lead encephalopathy
~ Lead Encephalopathy Due to Traditional Medicines – Current Drug Safty
2008 January; 3(1):54-59
~ Medical Hypotheses 72 (2009) 285-287
~ Current Drug Safety 2008 January;3(1):54-59
 Po Ying Tan (保嬰丹) – mean lead content of 7.5 mg/pc
~ Three patient with lead posioning following use of a Chinese herbal pill -HKMJ Vol 8 No 1 February 2002
 Bao ning dan (保寧丹), Cordyceps (冬蟲夏草), Hai ge fen
(海蜇粉), Ji jue di huang wan (杞菊地黃丸)
~ The Science of the Total Environment 182 (1996) 193-195
~ Childhood lead poisoning in China– The Science of the Total
Environment 181 (1996)101-109
 Lonicera japonica Thunberg’s dry flos (金銀花) and
Radix Morinda officinalis How’s (巴戟天).
~ Some aspects of toxic contaminants in herbal medicines – chemosphere 52 (2003) 13611371
~ Heavy metals in traditional Chinese medicines: A systematic review –
Clinical Pharmacology and Therapeutics, Vol 70, No. 6, Dec 2001
~ Heavy metals in traditional Chinese medicines: A systematic review –
Clinical Pharmacology and Therapeutics, Vol 70, No. 6, Dec 2001
~ Heavy metals in traditional Chinese medicines: A systematic review –
Clinical Pharmacology and Therapeutics, Vol 70, No. 6, Dec 2001
 Lead exposure produces chronic interstitial nephritis,
progressive tubular atrophy, overexpression of
angiotensin II, oxidative stress, salt retention,
hypervolemia and hypertension
 more rapid progression of renal failure in CKD patient
 Arsenic affects the renal capillaries, tubules, and
glomeruli, causing tubular necrosis
~Blood Lead Levels in the US go Down, but Higher Levels Are Still
Associated with a Higher Burden of CKD – JASN 17:317-322,2006
 Mercury causes damage to the renal proximal tubule and
hemebiosynthetic pathways .
 Cadmium causes proximal tubular injury
~ A Review of Dietary Supplement-Induced Renal Dysfunction – CJASN
2:757-765 2007
 Lead is a xenobiotic metal, normal blood lead levels do
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not exist. Ideally, blood lead levels < 10 μg/dL.
Adult lead poisoning – blood lead level ≥40 μg/dL.
Symptoms usually begins with levels > 50-60 μg/dL
Gastrointestinal absorption 15 % of ingested lead. In
blood, 99 % lead is bound to the erythrocyte, 1% lead
is distributed in blood, bone, and soft tissues. Lead
also can crosses the blood-brain barrier, the placenta
and into breast milk.
Half-life : in blood -- several weeks
in soft tissues -- several months
in bone -- 5–15 years.
Excretion : primarily by kidney
~ Lead Encephalopathy Due to Traditional Medicines – Current Drug Safety
2008 January; 3(1):54-59
 Acute exposure: abdominal pain, constipation, joint
pains, muscle aches, headache, anorexia, decreased
libido, difficulty concentrating and deficits in shortterm memory, anemia, Fanconi-type syndrome
 Chronic exposure: myalgias, fatigue, irritability,
insomnia, anorexia, impaired short-term memory,
difficulty concentrating, hypertension,
neuropsychiatric defects, reproductive defects,
nephropathy, cataract, carcinogenic effect, mortality.
~ Lead Encephalopathy Due to Traditional Medicines – Current Drug Safty
2008 January; 3(1):54-59
Lead line
Basophilic
stippling
~ Herbal Medicine-Associated Lead Intoxication – Internal Medicine
Vol 36, No.1 ( Jan 1997)
~ Neural tube defects and herbal medicines contaiing lead: A possible
relationship – Medical Hypotheses 72 (2009) 285-287
~ Neural tube defects and herbal medicines contaiing lead: A possible
relationship – Medical Hypotheses 72 (2009) 285-287
 History –Ooccupational/environmental/medication
 Laboratory testing :
a. Blood lead level
b. Free erythocyte protoporphyrin (FEP) or zinc
protoporphyrin (ZPP) both measure the effect of
lead on hemoglobin synthesis
c. Others –CBC, blood smear morphology, BUN,
serum creatinine and urinalysis
 Other tests:
a. X-ray fluorescence
b. Neurobehavioral testing
c. Nerve conduction velocity testing
 Reducing lead exposure
 Chelation therapy:
a. DMSA
b. Ca-EDTA
c. Asorbic acid (?)
 The potential role of oxidative stress injury associated with
lead poisoning suggests to mitigate lead-induced toxicity
 The aim of the study was to evaluate the protective effect of
Smilax glabra against lead toxicity in rats.
 Calcium lactate, zinc sulfate, ferrous sulfate, ascorbic
acid and calcium-rich milk and natural antioxidants
(extract of Chinese wolfberry, extract of Hangzhou
white chrysanthemum and antioxidant extract of
bamboo leaves) have promising capacity of reducing
BLL in lead-exposed mice.
 Randomized controlled trials have found that calcium
supplementation reduced lead levels in pregnant and
lactating women.
Reduction of blood lead levels in lead-exposed mice by dietary supplements
and natural antioxidants -- J Sci Food Agric.2011 Feb;91(3):485-91. doi:
10.1002/jsfa.4210. Epub 2010 Oct 28.
 Heavy metals can indeed have therapeutic effects:
1. Salvarsan, an arsenical, was the most effective
treatment against syphilis until penicillin was
introduced in the 1940s
2. Potassium arsenite, an arsenic compound, was the
first chemotherapy introduced to treat leukemia in
1865 and used until the 1950s.
3. Arsenic trioxide was found to treat treat acute
promyelocytic leukemia (APL)in the 1970s
4. Arsenic compounds are now being tested against
various cancers
 Some traditional Chinese drugs are especially rich in
Zn, Fe, Se, Cu, Cr, and Mn. Appropriate use of these
CM materials might be valuable in the prevention and
treatment of heavy metal poisoning and maintenance
of healthy conditions.
 Garlic and Cilantro (Coriandrum sativum) also
reduced lead deposition in rats, mice, and sheep
 herbs should be tested in humans to see whether
an oral chelating effect is demonstrated.
~ Lead Encephalopathy Due to Traditional Medicines – Current Drug Safty
2008 January; 3(1):54-59
 In many cases, TCM intake had been prolonged until a
diagnosis of intoxication was made.
 It Would be important that health care professionals
be aware of the possibility of heavy metal
contamination, recognize clinical symptoms, and
inform their patients accordingly to prevent the
occurrence of heavy metal poisoning.
 When handling a suspicous herbal posioning:
1. What is the herb involved?
2. What condition was the herb used for?
3. What is the active ingredient?
4. What is its mechanism of action?
5. Are the symptoms and signs consistent with the
description in the literature ?
6. What are the toxicokinetics of the active ingredient ?
7. What is the associated pathology?
8. What is the most effective treatment of the victim ?