Intervention Review

You have free access to this content

Zinc supplements for treating thalassaemia and sickle cell disease

  1. Kye Mon Min Swe1,*,
  2. Adinegara BL Abas1,
  3. Amit Bhardwaj2,
  4. Ankur Barua3,
  5. N S Nair4

Editorial Group: Cochrane Cystic Fibrosis and Genetic Disorders Group

Published Online: 28 JUN 2013

Assessed as up-to-date: 20 JUN 2013

DOI: 10.1002/14651858.CD009415.pub2


How to Cite

Swe KMM, Abas ABL, Bhardwaj A, Barua A, Nair NS. Zinc supplements for treating thalassaemia and sickle cell disease. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD009415. DOI: 10.1002/14651858.CD009415.pub2.

Author Information

  1. 1

    Melaka-Manipal Medical College (MMMC), Department of Community Medicine, Melaka, Malaysia

  2. 2

    Melaka-Manipal Medical College (MMMC), Department of Orthopaedics, Melaka, Melaka, Malaysia

  3. 3

    International Medical University (IMU), Department of Community Medicine, Kuala Lumpur, Malaysia

  4. 4

    Manipal University, Department of Statistics, Manipal, Karnataka, India

*Kye Mon Min Swe, Department of Community Medicine, Melaka-Manipal Medical College (MMMC), Jalan Batu Hampar, Bukit Baru, Melaka, 75150, Malaysia. khmoneminswe@gmail.com.

Publication History

  1. Publication Status: New
  2. Published Online: 28 JUN 2013

SEARCH

 
Characteristics of included studies [ordered by study ID]
Acrasoy 1987

MethodsRCT. Parallel design.


Participants32 thalassaemia patients (19 female and 13 male).

Age (1 - 18 years).


InterventionsZinc acetate supplementation (n = 21 patients with blood transfusion): elemental zinc age-dependent doses: 22.5 mg - 45 mg for ages 1 - 4 years; 67.5 mg for ages 4 - 10 years; and 90 mg for aged over 10 years.

Control group (n = 11 patients): no zinc supplementation.


OutcomesLinear growth of the patient.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "Randomly selected the patients......".

Did not describe the method of randomisation.

Allocation concealment (selection bias)Unclear riskNot mentioned.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll 32 participants completed study.

Selective reporting (reporting bias)Low riskAll the outcomes were reported.

Other biasUnclear riskNot mentioned.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot mentioned.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot mentioned.

Bao 2008

MethodsRCT. Parallel design.


Participants36 ambulatory SCD adult patients (homozygous) (11 male and 7 female in each group).

Age (18 - 47 years).

Exclusion criteria were as follows:
1. nonambulatory;
2. receiving more than 6 transfusions per year or taking hydroxyurea;

3. history of substance abuse;
4. neurological or psychiatric deficits that could affect compliance;
5. use of immunosuppressive drugs;

6. patients who were positive for HIV; and

7. patients who were positive for hepatitis B.


InterventionsZinc acetate supplementation (n = 18): 25 mg zinc acetate orally 3 times a day for 3 months.

Control group (n = 18): placebo.


OutcomesInfection, vaso-occlusive pain crisis.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskAll patients were randomly divided into 2 groups.

Did not describe the method of randomization.

Allocation concealment (selection bias)Unclear riskAllocation concealment was not described.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll participants completed study.

Selective reporting (reporting bias)Low riskAll outcomes stated in methods section reported in results.

Other biasUnclear riskNot discussed.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskZinc-supplemented or placebo groups in pairs by the technician’s blinded choice of 1 of 2 identical bottles labelled as study drug, not labelled as zinc or as placebo (one contained zinc pills, and the other contained placebo pills).

Blinding of outcome assessment (detection bias)
All outcomes
Low riskTechinicians were blinded.

Gupta 1995

MethodsRCT. Parallel design.


Participants145 participants randomised, but 15 lost to follow-up, so data for 130 participants presented (intervention group 46 males and 19 females; control group 50 males and 15 females).

Age (intervention group 12 - 27 years (mean 16.4 years); control group 14 - 19 years (mean 18 years)).

Inclusion criteria: Age more than 5 years with SS disease confirmed by Hb electrophoresis.

Exclusion criteria: Patients with chronic persistent infection.


InterventionsZinc sulphate supplementation group: 220 mg zinc sulphate 3 times per day.

Control group: placebo.

Participants were seen weekly, at follow up until 1.5 years.


OutcomesSickle cell crisis: vaso-constrictive mix; haemolytic sequestration; aplastic anaemia; days in hospital and working day loss.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskPatients were randomly allocated to receive zinc or placebo (using New Castle software for randomisation).

Allocation concealment (selection bias)Unclear riskNot explained.

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk145 participants recruited,15 patients lost to follow-up and these were not accounted for in the study publication.

Selective reporting (reporting bias)Low riskAll outcomes stated in the methods section were reported in the results.

Other biasUnclear riskLittle information on baseline characteristics, disease severity, medical history of participants making it difficult to ensure that the groups were similar at the start of the trial.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskBoth patients and treating physician were blinded regarding the drug being administered during the trial. The control group received placebo capsules of identical appearance 3-times-a-day. Care was otherwise the same in the both groups.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskDouble-blinded, treating physicians were blinded. The control group received placebo capsules of identical appearance 3-times-a-day. Care was otherwise the same in the both groups.

Prasad 1981 (1)

MethodsCCT. Cross-over design.


Participants4 participants (all male).

Age (16 - 28 years)

Inclusion criteria: ambulatory, stable participants with homozygous SCD.


InterventionsZinc acetate supplementation group: 15 mg oral zinc 3-times-a-day as acetate.

Control group: oral placebo.


OutcomesPlasma zinc level, alkaline phosphatase in neutrophils, basal testosterone and testosterone following intravenous gonadotrophin releasing hormone (GnRH).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot discussed.

Allocation concealment (selection bias)Unclear riskNot discussed.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll participants completed the study.

Selective reporting (reporting bias)Low riskAll outcomes stated in the methods section were reported in the results.

Other biasUnclear riskNot discussed.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskPatients were blinded as to the type of supplementation.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskEndocrinologist (AA) was blinded as to the type of supplementation.

Prasad 1981 (2)

MethodsCCT. Parallel design.


Participants14 participants (all male, 7 in each group).

Age (16 - 28 years).

Inclusion criteria: ambulatory, stable participants with homozygous sickle cell disease between ages of .


InterventionsZinc supplementation group: 15 mg oral zinc 3 times a day as acetate.

Control group: oral placebo.


OutcomesPlasma zinc level, alkaline phosphatase in neutrophils, basal testosterone and testosterone following intravenous gonadotrophin releasing hormone (GnRH).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot discussed.

Allocation concealment (selection bias)Unclear riskNot discussed.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll participants completed the study.

Selective reporting (reporting bias)Low riskAll outcomes stated in methods section reported in results.

Other biasUnclear riskNot discussed.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskThe study was conducted in a double-blind fashion. Patients were blinded as to the type of supplementation.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskThe study was conducted in a double-blind fashion. Endocrinologist (AA) was blinded as to the type of supplementation.

Prasad 1999

MethodsRCT. Parallel design.


Participants32 SCD participants who were divided in three groups (16 males and 16 females): Group A (n = 11) and B (n = 10) were zinc deficient based on cellular zinc criteria and Group C (n = 11) were zinc sufficient.

Age (19 - 49 years).


InterventionsZinc supplementation group A: Group A participants were observed for 1 year (baseline), following which they received zinc acetate (50 to 75 mg of elemental zinc orally daily) for 3 years.

Zinc supplementation group B: Group B participants were observed for 1 year (baseline), following which they received placebo for 1 year and then switched to zinc supplementation (50 to 75 mg of elemental zinc orally daily) for 2 years.

Control group: Group C participants did not receive any intervention in as much as they were zinc sufficient.


OutcomesLymphocyte and granulocyte zinc, change in interleukin-2 production, incidence of infections, number of hospitalizations and number of vaso-occlusive pain crises.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot mentioned.

Allocation concealment (selection bias)Unclear riskNot mentioned.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll 32 participants completed the study.

Selective reporting (reporting bias)Unclear riskOutcomes are not clearly mentioned.

Other biasUnclear riskNot mentioned.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot mentioned.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot mentioned.

Rashidi 2011

MethodsRCT. Parallel design.


Participants120 beta thalassaemia patients (57 males and 63 females).

Age (older than 18 years, mean (SD) 21.1 (9.7) years; males mean (SD) 21.6 (3.8) years and females mean (SD) 22.2 (4.6) years).


InterventionsZinc supplement group (n = 40): 220 mg zinc sulphate containing 50 mg zinc daily for 3 months.

Vitamin E supplement group (n = 40): 400 mg vitamin E daily for 3 months.

Zinc supplement with vitamin E supplement (n = 40): similar doses and duration to previous supplement groups.

Control group: no supplements.


OutcomesThe effect of supplementations on serum zinc and vitamin E, SOD, GPX, TAC and BMI.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe patients were randomly assigned into 4 groups with 30 participants in each group using a random allocation method. (Random allocation method was a random permuted block or block balanced randomisation using 8 characters blocks containing A, B, C and D).

Allocation concealment (selection bias)Unclear riskNot discussed.

Incomplete outcome data (attrition bias)
All outcomes
Low risk120 participants completed study.

Selective reporting (reporting bias)Low riskAll outcomes stated in methods section reported in results.

Other biasUnclear riskNot discussed.

Blinding of participants and personnel (performance bias)
All outcomes
Low risk"Double-blinded RCT."

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot discussed.

Serjeant 1970

MethodsRCT. Parallel design.


Participants34 SCD patients (16 male and 18 female).

Age (not stated)


InterventionsZinc supplementation group (n = 17): 200 mg zinc sulphate.

Control group (n = 17): placebo (200 mg lactose).


OutcomesUlcer healing rate and serum zinc level.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskPatients were alternatively allocated for treatment.

Allocation concealment (selection bias)Unclear riskIdentical tablets were given to conceal their allocation in control or intervention group.

Incomplete outcome data (attrition bias)
All outcomes
Low risk34 patients were included in the trial and 4 patients defaulted from the clinic during the trial (3 from zinc group; 1 from placebo group) and another one from the treatment group was excluded because a large scab overlying the ulcer area made reliable assessment of the ulcer size impossible.

Selective reporting (reporting bias)Low riskAll outcomes stated in methods section reported in results.

Other biasUnclear riskNot discussed.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskNeither person assessing the ulcer size knew which tablet contained zinc.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskNeither person assessing the ulcer size knew which tablet contained zinc.

Zemel 2002

MethodsRCT. Parallel design.


Participants42 children with SCD-SS (22 males and 22 females).

Age (4 - 10 years).


InterventionsZinc supplementation group (n = 20): 10 mg elemental zinc acetate in 5 ml cherry syrup.

Control group (n = 22): 5 ml cherry syrup alone.


OutcomesImprove linear growth and body composition.


NotesIntervention and control prepared by the research pharmacy at CHOP.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomization was stratified according to age group.

Allocation concealment (selection bias)Unclear riskNot discussed.

Incomplete outcome data (attrition bias)
All outcomes
Low risk42 children participated in the trial and 38 completed the study. 4 dropouts in total: 2 children moved away from the region, while 2 families refused to complete the study. All available information on all children were used in the analyses that was conducted.

Selective reporting (reporting bias)Low riskAll outcomes stated in methods section reported in result.

Other biasUnclear riskNot discussed.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot discussed.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot discussed.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Mehdizadeh 2008It was a matched case-control study and not a randomised controlled trial.

Prasad 1975Not a controlled trial.

Prasad 1983aNot a controlled trial.

Tschumi 1981Participants did not have a diagnosis of either sickle cell disease or thalassaemia.

 
Characteristics of ongoing studies [ordered by study ID]
NCT00459732

Trial name or titleZinc & Bone Health in Thalassemia: The Think Zinc Study (ThinkZn).

MethodsRCT. Parallel design. Double-blind. Intention to treat analysis between the zinc and placebo groups.

ParticipantsEnrollment: 45 thalassaemia patients.

InterventionsDietary Supplement: Zinc
Dietary Supplement: Placebo

OutcomesPrimary Outcome Measures:
Change in lumbar spine BMD by DXA (Baseline to 18 Months)
Change in pa spine BMD by DXA between baseline and 18 months
Change in whole body BMC by DXA (Baseline to 18 Months)

Secondary Outcome Measures:

Osteocalcin (a marker of bone formation)

Absolute change in serum osteocalcin between 0 and 18 months

Starting dateApril 2006.

Contact informationEllen B. Fung, PhD, RD (efung@mail.cho.org).

NotesCompleted: February 2011.

 
Comparison 1. Zinc versus placebo (thalassaemia)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Serum zinc level1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    1.1 At 3 months
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Body mass index1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    2.1 At 3 months
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Height velocity1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    3.1 At
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 2. Zinc versus placebo (sickle cell disease)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Haemoglobin2Mean Difference (IV, Fixed, 95% CI)Totals not selected

    1.1 At 3 months
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 At 1 year
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Serum zinc level3Mean Difference (IV, Fixed, 95% CI)Subtotals only

    2.1 At 3 months
136Mean Difference (IV, Fixed, 95% CI)14.90 [6.94, 22.86]

    2.2 At 1 year
235Mean Difference (IV, Fixed, 95% CI)20.25 [11.73, 28.77]

 3 Serum zinc level1Mean Difference (Fixed, 95% CI)Totals not selected

    3.1 At 1 year
1Mean Difference (Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Body mass index1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    4.1 At 1 year
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Weight1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    5.1 At 1 year
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Sickle cell crisis2Mean Difference (IV, Fixed, 95% CI)Totals not selected

    6.1 Zinc sulphate (at 1 year)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.2 Zinc acetate (at 1 year)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 7 Total number of infection1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

    7.1 At 3 months
1Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 8 Total number of infection1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    8.1 At 1 year
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 9 Improvement in leg ulcer1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

    9.1 At 6 months
1Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Table 1. Gupta 1995 - Types of crises

Types of crisisControl (n = 65)Intervention (n = 65)

Vaso-occlusive220 (63.95%)91 (58.87%)

Mixed68 (19.76%)38 (23.75%)

Haemolytic40 (11.62%)17 (9.37%)

Sequestration12 (1.48%)12 (1.25%)

Alastic4 (1.16%)2 (1.25%)

Total344160

 Data represent number of events.