Cockle 2000.

Methods	2‐arm, parallel group, double‐blind, placebo‐controlled RCT (Intended duration was 48 weeks, but due to very high dropout after 24 weeks, no data were reported beyond 24 weeks).
Participants	Location: One site in UK Recruitment: subjects recruited by newspaper advertisement Number randomised: 69 in intervention, 70 in comparison Participant baseline characteristics: Age: overall: median 70 years placebo: mean 70.2 (5.4) and median 70 (60‐81) intervention: mean 70.7 (5.6 and median 70 (60‐81) Gender: overall: 51 males and 88 females placebo (24 males and 46 females) intervention (27 males and 42 females) Main diagnosis: All subjects were in good physical and mental health and had no history of significant disease or mental illness, as determined by a medical examination and health questionnaire. MMSE: intervention: 28.9 (SD:1.4) placebo: 28.6 (SD:1.5) Inclusion criteria: not reported Exclusion criteria: not reported
Interventions	Intervention (n = 69): Multivitamin supplements: two gelatine capsules orally each day. Each capsule contained vitamin A palmitate 3334 IU, thiamine mononitrate 14 mg, riboflavin 16 mg, pyridoxine 22 mg, vitamin B12 0.03 mg, vitamin C 600 mg, dl‐alpha‐tocopherol acetate 100 mg, folic acid 4 mg, d‐biotin 2 mg and nicotinamide 180 mg. Quote: "The dosing was calculated to provide the equivalent of one US RDA (National Research Council, 1980) of vitamin A and ten US RDAs of the remaining vitamins." Capsules supply were provided at baseline and, in patients who were compliant, a second supply was given at week 12 for an intended treatment duration of 24 weeks. Comparator group (n = 70): matching placebo (rape seed oil) Use of additional interventions (common to both treatment arms): not reported
Outcomes	Primary Outcomes: Relationship between vitamin status and cognitive function. "At each visit, treatment compliance, blood vitamin levels and Critical Flicker Fusion, Choice ReactionTimeTask, Sternberg Memory ScanningTask, Word ScanTask, and the Profile Of Mood States questionnaire were carried out". "MMSE, Sundrom Kurtz Test, National Adult Reading Test, Alice Heim's 4, Alice Heim's 5 and the Geriatric Depression Scale were assessed at baseline and at week 48." Eligible cognitive outcomes: episodic memory measured with Sternberg Memory Scanning Task (msec), lower values indicated benefit episodic memory measured with Word scan task (msec), lower values indicated benefit* speed of processing measured with Total reaction time (msec), lower values indicated benefit* speed of processing measured with Recognition reaction time (msec), lower values indicated benefit speed of processing measured with Motor reaction time (msec), lower values indicated benefit * outcome data used in statistical analyses
Notes	Quote: "the objectives of the study were to examine the relationship between vitamin status and cognitive functioning and mood in healthy, elderly volunteers and to assess the subsequent impact of multivitamin supplementation on these measures". Funding sources: none stated Declarations of interest: none stated, but second author from Roche Pharmaceutical
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: “Subjects were allocated to each treatment group according to a predetermined randomization schedule." Comment: insufficient information about the sequence generation method
Allocation concealment (selection bias)	Unclear risk	Quote: “Subjects were allocated to each treatment group according to a predetermined randomization schedule." Comment: insufficient information about allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "The study was a double‐blind, placebo‐controlled, parallel group study with each subject receiving a multivitamin supplement or placebo daily for up to 24 weeks." Quote: "Treatments were given orally as two soft gelatine capsules containing either multivitamins or matching placebo (rape seed oil)". Comment: The study was reported as double‐blinded with the use of matching placebo.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote: "at each visit, treatment compliance, blood vitamin levels and Critical Flicker Fusion, Choice Reaction Time Task, ...were carried out". Comment: It was not reported whether outcome assessment was blinded.
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote: ‘Due to circumstances not related to the study treatment, there was a significant dropout of subjects after the first six months of this study, with no participants continuing through to visit 4. Data from 139 subjects was available at baseline, from 127 subjects at visit 1 and from 90 subjects at visit 2. Due to the high dropout of subjects between visit 2 and visit 3, data from the latter visit was not included." Comment: There were 12 dropouts (8.6%) at visit 1 (12 weeks) and 49 dropouts (35.8%) at visit 2 (24 weeks). Outcome data were completely missing from planned visits 3 and 4 (36 and 48 weeks).
Selective reporting (reporting bias)	High risk	Comment: A number of tests of cognition and functioning reported in the Methods to have been measured at baseline and 48 weeks were not reported (including MMSE).
Other bias	Low risk	No other risks identified