Summary of findings 4. Zinc versus placebo.
| Zinc versus placebo | ||||||
| Patient or population: people with AMD Setting: community Intervention: zinc* Comparison: placebo | ||||||
| Outcomes | Anticipated absolute effects** (95% CI) | Relative effect (95% CI) | № of participants (studies) | certainty of the evidence (GRADE) | Comments | |
| Risk with placebo | Risk with Zinc | |||||
| Progression to late AMD (neovascular AMD, geographic atrophy or both) | Low | OR 0.83 (0.70 to 0.98) | 3790 (3 RCTs) | ⊕⊕⊝⊝ LOW 1, 2 | Average follow‐up in study contributing most of the events was 6 years | |
| 15 per 1000 | 12 per 1000 (11 to 15) | |||||
| High | ||||||
| 430 per 1000 | 385 per 1000 (346 to 425) | |||||
| Progression to neovascular AMD | Low | OR 0.76 (0.62 to 0.93) | 2442 (1 RCT) | ⊕⊕⊕⊝ MODERATE2 | Average follow‐up 6 years | |
| 10 per 1000 | 8 per 1000 (6 to 9) | |||||
| High | ||||||
| 300 per 1000 | 246 per 1000 (210 to 285) | |||||
| Progression to geographic atrophy | Low | OR 0.84 (0.64 to 1.10) | 2442 (1 RCT) | ⊕⊕⊕⊝ MODERATE2 | Average follow‐up 6 years | |
| 10 per 1000 | 8 per 1000 (6 to 11) | |||||
| High | ||||||
| 300 per 1000 | 265 per 1000 (215 to 320) | |||||
| Progression to visual loss (loss of 3 or more lines on logMAR chart) | Low | OR 0.87 (0.75 to 1.00) | 3791 (2 RCTs) | ⊕⊕⊕⊝ MODERATE2 | Average follow‐up in study contributing most of the events was 6 years | |
| 15 per 1000 | 13 per 1000 (11 to 15) | |||||
| High | ||||||
| 430 per 1000 | 396 per 1000 (361 to 430) | |||||
| Quality of life | Not reported | |||||
| Adverse effects | In some studies, gastrointestinal symptoms was reported as a reason for withdrawal. Of 286 people randomised into trials of zinc sulfate supplementation compared with placebo (not including AREDS), 5/146 zinc‐treated people withdrew due to gastrointestinal symptoms compared with 2/140 controls. No‐one developed copper‐deficiency anaemia (high zinc intakes can inhibit copper absorption). In AREDS participants in the zinc arms reported more anaemia (13.2% versus 10.2%, P = 0.004), however, serum haematocrit levels were the same. In AREDS zinc was associated with higher risk of genitourinary problems in men, but no difference seen between high‐ and low‐dose zinc groups in AREDS2 | ⊕⊝⊝⊝ VERY LOW 3 | ‐ | |||
| Resource use and costs | ‐ | ‐ | ‐ | ‐ | ‐ | Not reported |
| * Most of the evidence in this table is drawn from the AREDS study which studied a daily dose of zinc 80 mg as zinc oxide, copper 2 mg as cupric oxide. **The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). The assumed risk in the comparison group is estimated using data from AREDS: low risk = AREDS category 2; high risk = AREDS category 4. CI: Confidence interval; RR: Risk ratio; OR: Odds ratio; | ||||||
| GRADE Working Group grades of evidence High‐certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate‐certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low‐certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low‐certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect | ||||||
1 Downgraded one level for inconsistency because study effects ranged from 0.50 to 2.31, although I² = 14%
2 Downgraded one level for imprecision because confidence interval crossed line of minimum important difference.
3 Downgraded for one level for imprecision (as included studies were underpowered to look at adverse effects), one level for risk of bias (adverse effects were inconsistently reported) and one level for inconsistency (inconsistent results reported).