Zinc toxicity: demyelination? anemia neutropenia PEM; healthy gut is crucial

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The first citation had no abstract. But PubMed offers " related references " ,

which often include informative citations. Perusing those citations is often a

good " next step " . The citations linked to Prodan and Holland's article " CNS

demyelination from zinc toxicity? " included several possibly informative about

excessive and/or prolonged zinc ingestion. Questions include:

A. What are safe levels of temporarily increased Zn-ingestion in an

autism-spectrum child?

B. What is the duration after which those " safely " increased levels ought be

discontinued?

C. What lab signs can indicate that an increased level ought be discontinued?

Binstock

Researcher in Developmental & Behavioral Neuroanatomy

Zinc toxicity: cites from article 1 (which generated 192 cites).

1: Neurology 2000 Apr 25;54(8):1705-6

CNS demyelination from zinc toxicity?

Prodan CI, Holland NR.

Department of Neurology, University of Oklahoma Health Sciences Center, Oklahoma

City, USA.

PMID: 10762525 [PubMed - indexed for MEDLINE]

2: JAMA 1990 Sep 19;264(11):1441-3

Comment in:

JAMA. 1991 Feb 20;265(7):869.

Excessive zinc ingestion. A reversible cause of sideroblastic anemia and bone

marrow depression.

Broun ER, Greist A, Tricot G, Hoffman R.

Department of Medicine, Indiana University School of Medicine, Indianapolis

46202.

Two patients with sideroblastic anemia secondary to zinc-induced copper

deficiency absorbed excess zinc secondary to oral ingestion. The source of

excess zinc was a zinc supplement in one case; in the other, ingested coins. In

each case, the sideroblastic anemia was corrected promptly after removal of the

source of excess zinc. These two cases emphasize the importance of recognizing

this clinical entity, since the myelodysplastic features are completely

reversible.

PMID: 2094240 [PubMed - indexed for MEDLINE]

3: Neurology 1999 Nov 10;53(8):1893

Comment on:

Neurology. 1999 Feb;52(3):599-606.

Quantitative MRI in patients with clinically isolated syndromes suggestive of

demyelination.

Tenser RB.

Publication Types:

Comment

Letter

PMID: 10563658 [PubMed - indexed for MEDLINE]

4: Rev Neurol (Paris) 1998 Sep;154(8-9):573-5

Pathogenesis and treatment of central nervous system demyelinating disease.

Zamvil SS, Soos JM, Weiner HL.

Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Institutes

of Medicine, Boston, MA 02115, USA.

Publication Types:

Review

Review, Tutorial

PMID: 9809371 [PubMed - indexed for MEDLINE]

5: Curr Opin Neurol 2001 Jun;14(3):253-8

Classification of demyelinating diseases at the interface between etiology and

pathogenesis.

Lassmann H.

The classical demyelinating diseases include the 'autoimmune' inflammatory

demyelinating diseases, the inflammatory demyelinating diseases of infectious

aetiology, and the demyelinating or dysmyelinating diseases of

genetic/hereditary background. In addition, primary demyelination is present in

other conditions, such as brain ischaemia and intoxication. Irrespective of the

primary aetiology, selective demyelination can be mediated through various

pathogenetic pathways: the immune-mediated inflammatory pathway; the metabolic

pathway; and the ischaemic/excitotoxic pathway. These pathways are only partly

segregated with distinct aetiologies of demyelinating diseases, but they also

reflect the way in which the patient copes with the disease-inciting event in

relation to their particular genetic background. For future therapeutic

strategies it will be important to interfere with the specific pathogenetic

pathways of demyelination, which may be common to various demyelinating

diseases, but may differ in subgroups of patients who suffer from a particular

clinical demyelinating disease entity.

Publication Types:

Editorial

Review

Review, Tutorial

PMID: 11371746 [PubMed - indexed for MEDLINE]

6: Lancet 1998 Oct 3;352(9134):1146-7

Comment on:

Lancet. 1998 Jul 18;352(9123):220-8.

Disorders of sodium balance.

J.

Publication Types:

Comment

Letter

PMID: 9798615 [PubMed - indexed for MEDLINE]

7: Biol Trace Elem Res 2001 Jun;80(3):281-4

Low-dose zinc administration as an effective 's disease treatment.

Najda J, Stella-Holowiecka B, Machalski M.

Clinical Department of Internal Diseases and Oncological Chemotherapy, Silesian

Medical Academy, Katowice, Poland.

A case of a 11-yr-long 's disease treatment in a 16-yr-old boy with

neurologic presentation was analyzed and monitored. In the face of severe

symptoms of chelator intolerance, a comparatively low dose of 100 mg of zinc has

been administered for the entire 11-yr-long treatment. Considerable improvement

of clinical status was achieved, with accompanying regression of central nervous

system lesion. The parameters of copper metabolism were normalized with

effective urine elimination. The low-dose oral zinc intake proved to be

therapeutically effective, eliminating further copper tissue toxicity.

PMID: 11508632 [PubMed - indexed for MEDLINE]

8: Am J Hematol 1994 Jun;46(2):147-50

Zinc-induced sideroblastic anemia: report of a case, review of the literature,

and description of the hematologic syndrome.

Fiske DN, McCoy HE 3rd, Kitchens CS.

Department of Medicine, University of Florida College of Medicine, Gainesville.

Zinc ingestion has become increasingly popular in the lay and food faddist

population. Herein described by way of a case report and review of the 13 cases

in the literature is the syndrome of severe anemia associated with excessive and

prolonged intake of oral zinc. The syndrome is characterized by anemia,

granulocytopenia, and bone marrow findings of vacuolated precursors and ringed

sideroblasts. Serum analysis reveals increased zinc levels, decreased copper

levels, and a decrease in ceruloplasmin. The mechanism appears to be

zinc-induced copper deficiency, which is instrumental in producing the profound

bone marrow abnormalities, as zinc itself is of low toxicity. Importantly, the

syndrome is totally reversible with cessation of zinc intake. Hematologists

should be aware of this form of reversible sideroblastic anemia.

Publication Types:

Review

Review of Reported Cases

PMID: 8172183 [PubMed - indexed for MEDLINE]

9: Immunopharmacology 1997 Dec;38(1-2):43-50

The role of complement in disorders of the nervous system.

BP, Gasque P, Singhrao S, Piddlesden SJ.

University of Wales College of Medicine, Cardiff, UK.

The complement © system plays important roles in host defense but activation

at inappropriate sites or to an excessive degree can cause host tissue damage. C

has been implicated as a factor in the causation or propagation of tissue injury

in numerous diseases. The brain is an immunologically isolated site, sheltered

from circulating cells and proteins of the immune system; nevertheless, there is

a growing body of evidence implicating C in numerous brain diseases. In this

brief article we review the evidence suggesting a role for C in diseases of the

central and peripheral nervous system and discuss the possible sources of C at

these sites. Some brain cells synthesize C and also express specific receptors;

some are exquisitely sensitive to the lytic effects of C. The evidence suggests

that C synthesis and activation in the brain are important in immune defense at

this site, but may also play a role in brain disease.

Publication Types:

Review

Review, Tutorial

PMID: 9476113 [PubMed - indexed for MEDLINE]

10: Am J Hematol 1993 Feb;42(2):227-8

Comment in:

Am J Hematol. 1994 May;46(1):57.

Zinc abuse and sideroblastic anemia.

Ramadurai J, Shapiro C, Kozloff M, Telfer M.

Department of Medicine, Humana Hospital- Reese, Chicago.

We report the case of a young woman who presented with anemia and leukopenia. A

bone marrow aspirate revealed a marked excess of ringed sideroblasts. A detailed

dietary history disclosed excessive zinc intake. High serum zinc and low serum

copper concentrations were confirmed. After discontinuation of the zinc

supplements, she made a complete hematologic recovery. This report emphasises

the importance of trace metals and their role in the development of hematologic

abnormalities.

PMID: 8438885 [PubMed - indexed for MEDLINE]

11: Haematologica 1998 Jan;83(1):90

A case of microcytic anemia.

Invernizzi R, Locatelli F.

Dipartimento di Medicina Interna, Universita di Pavia, IRCCS Policlinico S.

Matteo, Italy.

PMID: 9542327 [PubMed - indexed for MEDLINE]

13: J Nutr Elder 1995;14(4):31-8

Appropriate protocol for zinc therapy in long term care facilities.

Eleazer GP, Bird L, Egbert J, C, Wei M, Guest K.

PMID: 8708978 [PubMed - indexed for MEDLINE]

14: Indian J Pediatr 1995 Mar-Apr;62(2):169-80

Assessment of zinc status in man.

Hambidge M, Krebs N.

Department of Pediatrics, University of Colorado School of Medicine, Denver

80262, USA.

Publication Types:

Review

Review, Tutorial

PMID: 10829865 [PubMed - indexed for MEDLINE]

15: Neuroimaging Clin N Am 2001 Feb;11(1):vii, 15-35

Demyelinating diseases, leukodystrophies, and other myelin disorders.

Suzuki K, Armao D, Stone JA, Mukherji SK.

Division of Neuropathology, Department of Radiology, University of North

Carolina School of Medicine, Chapel Hill, North Carolina 27599-7525, USA.

Magnetic resonance (MR) imaging recently has become the most sensitive clinical

test in the detection of white matter disorders, yet neuropathologic evaluation

remains the most specific. This article describes the gross and microscopic

pathology of various diseases primarily or selectively affecting white matter.

The discussion should provide deeper insight into the nature of white matter

disease and assist in the interpretation of CT and MR images. The subject of

white matter damage caused secondarily by such entities as neoplasia, trauma,

infarction, or neuronal degeneration is not included.

Publication Types:

Review

Review, Tutorial

PMID: 11331226 [PubMed - indexed for MEDLINE]

16: Am J Forensic Med Pathol 1997 Jun;18(2):148-53

Zinc toxicity following massive coin ingestion.

DR, Baird CJ, Chan KM, Crookes PF, Bremner CG, Gottlieb MM, Naritoku WY.

Department of Pathology, Los Angeles County-University of Southern California

Medical Center 90033, USA.

This is the first reported case of human fatality associated with zinc

intoxication following a massive ingestion of coins. Four hundred and sixty-one

coins were removed form the gastrointestinal tract of a schizophrenic patient

during the course of hospitalization. Many of the post-1981 pennies, which

consist primarily of zinc, showed severe corrosion due to their prolonged

contact with acidic gastric juice. The patient presented with clinical

manifestations consistent with the local corrosive as well as systemic effects

of zinc intoxication and died 40 days after admission with multi-system organ

failure. Tissue samples of the kidneys, pancreas, and liver obtained at autopsy

revealed acute tubular necrosis, mild fibrosis, and acute massive necrosis,

respectively, and contained high levels of zinc. The overall effects of zinc

intoxication on the various organ systems, possible hematological derangement,

and the impairment of copper absorption as well as the outcome with treatment

are discussed.

PMID: 9185931 [PubMed - indexed for MEDLINE]

17: Indian J Pediatr 1996 Mar-Apr;63(2):199-203

Serum, zinc and copper levels in children with protein energy malnutrition.

Singla PN, Chand P, Kumar A, Kachhawaha JS.

Department of Pediatrics, Banaras Hindu University, Varanasi.

Serum zinc and copper were measured by atomic absorption spectrophotometry in 58

children (3 months-5 years); of these, 46 children had protein energy

malnutrition (PEM), and 12 children served as controls. The levels of serum zinc

and copper were found to be significantly low in children with severe

malnutrition (grades III and IV PEM). There was a significant positive

correlation between serum zinc and height-for-age (r = 0.8809, p < 0.001). Serum

copper was found low only in children exhibiting marked linear growth

retardation (height-for-age < 85% of the normal). Hypoalbuminemia (serum albumin

< 2.5 g/dl), and anemia (hemoglobin < or = 8.0 g/dl) in malnourished children

were associated with significant decline in serum zinc and copper levels,

respectively.

Publication Types:

Clinical Trial

Randomized Controlled Trial

PMID: 10829989 [PubMed - indexed for MEDLINE]

18: Curr Gastroenterol Rep 1999 Oct;1(5):398-403

Zinc and intestinal function.

Semrad CE.

Columbia University College of Physicians and Surgeons, Physicians and Surgeons

Building, 10-508, 630 West 168th Street, New York, NY 10032, USA.

Zinc is an abundant trace element in the human body that is essential for growth

and development and immune function. It is important for the formation of

biomembranes and zinc finger motifs found in DNA transcription factors and has

catalytic function in metalloenzymes. The intestine is the site of zinc

absorption and the major route of zinc excretion. Dietary inadequacy or

conditions that decrease zinc absorption or increase its losses from the

gastrointestinal tract, urine, or skin may quickly cause zinc deficiency due to

the limited availability of rapidly exchangeable zinc pools in the body.

Diarrhea is both a sign and a cause of zinc deficiency. The mechanism by which

zinc deficiency causes diarrhea is not known. At this time, there is no readily

available sensitive test for the detection of zinc deficiency, and therefore

clinical suspicion remains the main mode of detection. In some individuals with

diarrheal disease, zinc supplementation lessens diarrhea. Those receiving

prolonged supplemental zinc therapy need to be monitored for copper deficiency.

Publication Types:

Review

Review, Tutorial

PMID: 10980978 [PubMed - indexed for MEDLINE]

19: J Pediatr 2000 May;136(5):688-90

Zinc-induced anemia and neutropenia in an adolescent.

Porea TJ, Belmont JW, Mahoney DH Jr.

Division of Pediatric Hematology-Oncology, Texas Children's Hospital, Houston,

TX 77030, USA.

We report an adolescent who developed anemia, leukopenia, and neutropenia after

prolonged use of over-the-counter zinc for treatment of acne. Hypocupremia and

sideroblastic anemia may result from long-term or excessive exposure to zinc.

PMID: 10802505 [PubMed - indexed for MEDLINE]

20: Postgrad Med J 1995 Sep;71(839):557-8

Pure white cell aplasia and health food products.

Forsyth PD, Davies JM.

Department of Haematology, University Hospital, Nottingham, UK.

The safety of 'health' foods and complementary medicine products is increasingly

questioned. We report a case of pure white cell aplasia developing in a patient

who took a variety of such products leading to an excessive intake of zinc.

Recovery was complete following the withdrawal of her 'medications'. The

aetiology of the pure white cell aplasia is discussed with respect to the

ingredients of the products ingested.

PMID: 7479471 [PubMed - indexed for MEDLINE]

ps: This post may be forwarded hither & yon.

[Guest guest]

Hi-- so what are you saying-- that our kids should not be taking zinc?

W

> The first citation had no abstract. But PubMed offers " related

references " ,

> which often include informative citations. Perusing those citations

is often a

> good " next step " . The citations linked to Prodan and Holland's

article " CNS

> demyelination from zinc toxicity? "