Maylor 2006.

Methods	3‐arm, parallel group, randomised, placebo‐controlled trial with 6 months duration of treatment and follow‐up
Participants	Location: Two centres (Coleraine, UK and Clermont‐Ferrand, France) recruited younger participants (55‐70 years) and another two centres (Rome, Italy and Grenoble, France) recruited older participants (70‐87 years). Recruitment: Participants were recruited through posters, leaflets, local television and radio, and community groups and organizations serving older individuals living independently. Sample size: Number randomised: 201 younger participants (55‐70 years), 232 older participants (70–87 years) Number completed study with compliance > 80% and included in analysis: 188 younger, 199 older Participant baseline characteristics (baseline characteristics provided only for study completers): Age in years, mean (SD): 15 mg/d: younger 61.4 (4.55), older 74.3 (3.91) 30 mg/d: younger 61.7 (4.57), older 74.6 (3.89) placebo: younger 62.3 (4.09), older 74.2 (3.58) Gender, males/females: 15 mg/d: younger 30/30, older 34 /32 30 mg/d: younger 31/34, older 34 /32 placebo: younger 32/31, older 35 /32 Inclusion criteria: men and women aged between 55 and 87 years; BMI between 20 and 30 kg/m2 good health; MMSE score greater than 23; geriatric depression scale score less than 6. Exclusion criteria: “Participants were excluded from further involvement in the study according to the following criteria: (l) tobacco consumption of more than 10 g/day; (2) alcohol consumption of more than 30 (men) or 20 (women) g/day; {3) unconventional dietary habits (for example, vegetarians, vegans); (4) use of a mineral supplement during the preceding 3 months; (5) use of more than three (55‐70 years) or four (70‐87 years) prescription drugs per day; (6) use of antidepressants, laxatives, or hormone replacement therapy; (7) pathological diseases, including cancer and diabetes. For participants satisfying the inclusion criteria, a biochemistry profile was performed, which included a full blood profile and tests of kidney and liver function. On the basis of these data, participants were excluded if there was insufficient renal and hepatic performance, malabsorption or inflammatory chronic pathologies, and were included if there was negative serology for the HIV and hepatitis C viruses.” Quote: “49 % of the initial 842 volunteers being excluded from the study at screening on the basis of cognitive impairment, depression, pathological conditions, medications, and so on”.
Interventions	Intervention Intervention A: Zn supplementation as zinc gluconate 15 mg/day, two tablets at the same time each day (usually after breakfast) for 6 months Intervention B: Zn supplementation as zinc gluconate 30 mg/day, two tablets at the same time each day (usually after breakfast) for 6 months Comparator group: placebo/zinc gluconate 0 mg/day, two tablets at the same time each day (usually after breakfast) for 6 months Use of additional interventions (common to both treatment arms): not reported
Outcomes	Primary Outcomes: Cognitive measures (Cambridge Automated Neuropsychological Test Battery, CANTAB) Visual memory was tested by pattern recognition memory; working memory was tested by spatial span and spatial working memory (SWM); and attention was tested by reaction time and matching to sample visual search (MTS). Quote: “Cognitive Function was assessed in the laboratory at baseline (before supplementation) and after 3 and 6 months of supplementation, using different (parallel) versions of the CANTAB tests on each occasion." Secondary Outcomes: serum and urinary zinc Quote: “Participants fasted overnight for 12h before blood and urine samples were taken on each of these occasions to determine Zn levels.”
Notes	Funding sources, quote: “European Commission 'Quality of Life and Management of Living Resources' Fifth Framework Programme. contract no. QLKl‐CT‐2001‐00168.” Declarations of interest: not reported Treatment adherence “Compliance was less than 80% for three older participants and so they were also excluded.” Outcome data were not reported separately for the Zinc and placebo groups
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Participants were assigned to one of three levels of Zn supplementation (placebo or 0 mg/d, 15 mg/d and 30 mg/d) according to the same standardised random order in each centre." Comment: not described how sequence generation was done. The possibility that this was quasi‐randomised could not be ruled out.
Allocation concealment (selection bias)	Unclear risk	As above
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Quote: “…Zn supplementation (0, 15 or 30 mg/d) was administered as zinc gluconate, participants taking two tablets at the same time each day (usually after breakfast) for 6 months. (Tablets were identified by a code so that neither the experimenter nor the participants knew the dose. The code was not broken until the study had been completed and all the data had been entered into computer files ready for analysis)". Comment: Although a placebo was mentioned, there was no description of its appearance or whether it could be distinguished from the zinc supplements.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: as above. Unclear whether blinding was adequate
Incomplete outcome data (attrition bias) All outcomes	High risk	Comment: There was no description of the completeness of outcome data for each main outcome, including attrition and exclusions from the analysis.
Selective reporting (reporting bias)	High risk	Comment: CANTAB data for the different interventional groups was shown graphically only. Number of participants for each outcome was not reported.
Other bias	Unclear risk	Baseline characteristics were shown only for participants who completed the trial.