Skip to main content
. 2018 Dec 17;2018(12):CD011906. doi: 10.1002/14651858.CD011906.pub2

Lewerin 2005.

Methods 2‐arm, double‐blinded, parallel group RCT, 4 months treatment and follow‐up
Participants Location: one centre, Goteborg, Sweden
Recruitment: outpatient clinic
Number randomised: 126 in intervention, 69 in comparison.
Participant (baseline) characteristics in Vitamin (n = 126) and placebo (n = 69)
Age:

  • vitamin 75.7 (± 4.7);

  • placebo 75.6 (± 4.0)

  • whole group (n = 209) mean age: 76 years and 5 months. Median 76 years (range 70‐93)


Gender (males %):

  • vitamin: 38% (48/126)

  • placebo: 44% (30/69)


Inclusion criteria: community‐dwelling subjects. Inclusion criteria not reported
Exclusion criteria: quote: "Those who had taken any vitamin supplements during the last 3 months or pharmacological doses of vitamin B12, folic acid and/or vitamin B6 during the last 3 years were not allowed to enter the study".
Interventions Intervention (n = 126):
Daily tablet containing 500 µg cyanocobalamin, 800 µg folic acid, and 3 mg vitamin B6 hydrochloride (manufactured and supplied by Recip AB, Årsta, Sweden)
Comparator group (n = 69): daily oral placebo
The duration of treatment was 4 months.
Use of additional interventions (common to both treatment arms):
Use of cardiovascular medication:

  • vitamin: 47%

  • placebo: 49%


Use of antiepileptics, neuroleptics, or antidepressants (%)

  • vitamin: 22%

  • placebo: 23%
Outcomes Outcomes evaluated: postural‐Locomotor‐Manual test and cognitive tests
Postural‐Locomotor‐Manual test:

  • Movement time

  • Postural phase

  • Locomotor phase

  • Manual phase

  • Simultaneity index


Cognitive tests:

  • Digit span forward

  • Digit span backward

  • Identical forms

  • Visual reproduction

  • Synonyms

  • Block design

  • Digit symbol

  • Thurstone’s picture memory test

  • Figure classification


No clear distinction between primary and secondary outcomes
In Lewerin 2003, cognitive and functional tests not reported in the Methods
Cognitive testing was conducted by the same psychologist at baseline and after 4 months.
Follow‐up: 4 months (measurements before and after treatment). Mean or median follow‐up not reported
Eligible cognitive outcomes:

  • executive functioning measured with synonyms at 4 months, on a scale from not reported to 30 with higher values indicating benefit*

  • episodic memory measured with Thurstone's picture memory test at 4 months, on a scale from not reported to 28 with higher values indicating benefit

  • episodic memory measured with identical forms (Dureman 1959) at 4 months, on a scale from not reported to 60 with higher values indicating benefit

  • episodic memory measured with Wechsler visual reproduction at 4 months, on a scale from not reported to 14 with higher values indicating benefit*

  • working memory measured with Wechsler digit span forward at 4 months, on a scale from not reported to 9 with higher values indicating benefit

  • working memory measured with Wechsler digit span backward at 4 months, on a scale from not reported to 8 with higher values indicating benefit*

  • speed of processing measured with Wechsler digit symbol at 4 months, on a scale from 0 to 90 with higher values indicating benefit*

  • speed of processing measured with Thurstone's figure classification at 4 months, on a scale from not reported to 30 with higher values indicating benefit


Function outcome extracted: none reported
Quality of life outcome extracted: none reported
Safety outcome extracted: none reported
* outcome data used in statistical analyses
Notes Funding sources, quote: "Supported by grants from the Hjalmar Svensson Foundation, the Göteborg Medical Society, the Medical Faculty at Göteborg University, the Wilhelm and Martina Lundgren Foundation, and the Magnus Strandqvist Foundation. Recip AB supported the study and provided the vitamin and placebo tablets".
Declarations of interest, quote: “None of the authors had a personal or financial conflict of interest with respect to this study".
Treatment adherence: quote "To ensure compliance, all subjects received a specified blinded number of tablets, and at the end of the study, the number of remaining tablets was compared with the initial number and planned intake during the study".
Data on treatment adherence were not clearly reported in the results.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk Quote: “Of these 195 subjects, 126 were randomly assigned to receive vitamin therapy and 69 to receive placebo."
Comment: method of random sequence generation not reported
Allocation concealment (selection bias) Unclear risk Quote: “Of these 195 subjects, 126 were randomly assigned to receive vitamin therapy and 69 to receive placebo."
Comment: method of allocation concealment not reported
Blinding of participants and personnel (performance bias) 
 All outcomes Low risk Quote: “and all subjects in the placebo group received an identical (other than the vitamin content) placebo tablet. " To ensure compliance, all subjects received a specified blinded number of tablets..."
"The tablet was identical in shape and composition to the placebo tablet apart from the vitamin content"; "double‐blind" study.
Comment: Both participants and physicians were apparently blinded.
Blinding of outcome assessment (detection bias) 
 All outcomes Unclear risk Quote: “Cognitive testing was conducted by the same psychologist (GS) at baseline and after 4 mo."
Comment: Blinding of outcome assessors was not reported.
Incomplete outcome data (attrition bias) 
 All outcomes Unclear risk Quote: "From flow diagram, 30/209 (14%) did not provide cognitive outcome data."
Comment: no information about group allocation of excluded participants
Selective reporting (reporting bias) Unclear risk Comment: protocol not available
Other bias Low risk Comment: no other risks identified