1. Objectives
To compare the effectiveness of iodized salt with other forms of iodine supplementation or placebo on the prevention of iodine deficiency disorders. Additional objectives were to identify the optimal level of salt iodization under given conditions, and to assess any adverse effects associated with salt iodization
2. How studies were identified
The following electronic databases were searched to August 2004:
- CENTRAL (The Cochrane Library, Issue 3, 2004)
- MEDLINE
- The Register of Chinese trials developed by the Chinese Cochrane Centre
- The Chinese Med Database
- LILACS
- PAHO
- metaRegister of Controlled Trials (mRCT)
The Internet and websites of the International Council for the Control of Iodine Deficiency Disorders, the Thyroid Disease Manager and the WHO were also examined, and handsearching of relevant journals and reference lists was performed
3. Criteria for including studies in the review
3.1 Study type
Randomized and quasi-randomized controlled trials, and prospective non-randomized controlled trials
3.2 Study participants
Adults and children living in areas with low iodine intake
(Controlled trials of iodine supplementation before or during pregnancy with outcomes referring only to the neonate were excluded as these are reviewed elsewhere)
3.3 Interventions
Iodized salt, using iodide or iodate, compared with placebo or with other forms of iodine supplementation
3.4 Primary outcomes
- Mortality related to iodine deficiency disorders
- Goitre (thyroid size)
- Physical and mental development in children
- Symptoms of hypothyroidism (reproductive failure/infertility, myxoedema, tiredness, lethargy, slowing of mental function, cold intolerance and/or cardiac complications)
Secondary outcomes included urinary iodine concentration, thyroid-stimulating hormone concentration in blood and neonatal cord blood, serum thyroglobulin concentration, adverse effects (iodine-induced hyperthyroidism), health-related quality of life, cost, adherence, and socioeconomic and related effects (e.g., school performance, per capita income)
4. Main results
4.1 Included studies
Six trials, involving more than 20,666 individuals, were included in this review:
- Four studies were randomized controlled trials; two studies were prospective controlled trials with no or unclear methods of randomization
- Units of randomization/allocation were individuals or groups, including schools, villages or other geographical regions
- Sample sizes varied, with the smallest trial being in 35 pregnant women and the largest trial including more than 20,000, villagers. Trial duration ranged from four months to five years
- Four of the six trials included a control group where no iodine treatment was used; one trial compared iodized salt with iodized water; one trial compared iodized salt with iodized oil; two trials compared different types of iodized salt (specially prepared versus commercially available, and potassium iodide versus potassium iodate). All interventions were consumed orally
- Specific amounts of salt consumption were not prescribed; instead salt was provided/sold for normal household consumption. Levels of salt iodization were 12 to 53 parts per million
4.2 Study settings
- China, Germany, India, Italy, Malaysia, and South Africa
- All trials were conducted in areas of known iodine deficiency with rates of goitre ranging from 10% to 83%
4.3 Study settings
How the data were analysed
Due to a lack of consistency in the reporting of outcomes and an overall paucity of high-quality data from randomized controlled trials, pooled analyses were not attempted. Data were instead summarized in a narrative format, without the presentation of estimates of treatment effect or confidence intervals. Data were also presented in tabular form in appendices without analyses of treatment effect (i.e., data from each intervention group were listed separately and no statistical comparisons were made by the reviewers).
Results
Goitre
Statistically significant reductions in goitre rates or thyroid volumes among groups using iodized salt in comparison to controls were reported in three studies. Allocation to iodized salt was found to statistically significantly lessen the increase in thyroid volume in pregnancy in one trial of 35 women, with an increase of 4% among women using iodized salt in comparison 16.25% among those using plain salt. While the remaining two trials reported a trend towards a reduction in goitre rates with iodized salt use, these results were not statistically significant.
Urinary iodine excretion
Urinary iodine excretion was not significantly increased with salt use among children less than six years of age in the Malaysian study, with an increase of 5.3 µg/L in comparison to 87.0 µg/L among those allocated iodized water. In the four remaining studies reporting on this outcome, urinary iodine excretion was statistically significantly increased with the use of iodized salt, and in three of the studies, the WHO target of 100 µg iodine/L of urine was reached. No clear relation was observed between the concentration of salt iodization and urinary iodine excretion, nor between form of iodization (potassium iodide or potassium iodate) and urinary iodine excretion.
Different forms of iodine supplementation
Goitre rates decreased similarly following salt fortification with either potassium iodide or potassium iodate. In comparison to iodized salt, iodized water was more effective in decreasing goitre rates among children less than six years of age, although in women aged 15 to 40 years, there was no difference between treatment groups. In the Chinese study, specially prepared iodized salt and commercially available iodized salt with a supplementation of iodized oil were both more effective than commercially available iodized salt alone in reducing goitre rates, likely due to the variable iodine content of commercially available salt.
Children versus adults
In two of the studies, children below six years of age benefited less than adults from salt iodization, and the authors of both these trials suggested salt consumption in children had been lower than that of adults.
Adverse effects
Adverse effects of iodine supplementation were not reported.
5. Additional author observations*
Five of the six included trials were judged to be of poor methodological quality, and two were not randomized or did not specify methods of randomization, thus limiting the confidence that can be placed in the results of this review. Nevertheless, the included trials represented populations from both low-/middle- and high-income countries, and although focusing on children and women of childbearing age, also included men and pregnant women.
Overall, goitre volume was reduced with iodised salt treatment, although this was not statistically significant in all studies. Iodine status, as measured in the included trials by urinary iodine excretion, was also improved in most studies, although this did not always reach the levels recommended by the WHO, and children less than six years of age did not receive the same benefit. Urinary iodine excretion does not reflect long-term iodine status, as would thyroglobulin levels or iodine excretion profiles, which were not reported in the reviewed trials. In addition, the incidence of adverse effects, including the potentially fatal iodine-induced hyperthyroidism, was also not reported.
Further controlled trials of high methodological quality are needed. These studies should determine the most effective level of salt iodization to be used under given conditions, should have adequate sample sizes, should be of at least two years duration, and should include participants of all ages, with the effects assessed separately for children and adults.
