Summary of findings for the main comparison. B vitamins compared to placebo for MCI.

B vitamins compared to placebo for MCI
Patient or population: MCI Setting: community Intervention: B vitamins (B6, B12, folic acid) Comparison: placebo
Outcomes	Anticipated absolute effects* (95% CI)		№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with placebo	Risk with B vitamins
Incidence of dementia ‐ not measured	‐	‐	‐	‐
Overall cognitive function assessed with: MMSE Scale from: 0 to 30 follow‐up: range 6 months to 24 months	MD with B vitamins was 0.44 MMSE points higher (0.23 lower to 1.12 higher) than with placebo *		488 (3 RCTs)	⊕⊝⊝⊝ VERY LOW 1 2 3	Due to the very low‐quality of the evidence, we cannot be sure of any effect of B vitamins on overall cognitive function. * 2 studies reported final score; 1 study reported change from baseline. From the 2 studies (n=150) which reported final scores, the mean MMSE with placebo was 26.97 points.
Episodic memory assessed with: various word list recall instrumentsa follow‐up: range 6 months to 24 months	SMD with B vitamins was 0.09 higher (0.1 lower to 0.29 higher) than with placebo		397 (3 RCTs)	⊕⊕⊕⊝ MODERATE 3	B vitamins probably resulted in little to no difference in episodic memory.
Executive function assessed with: various instrumentsb follow‐up: range 6 months to 24 months	SMD with B vitamins was 0.03 higher (0.23 lower to 0.29 higher) than with placebo		392 (3 RCTs)	⊕⊕⊕⊝ MODERATE 4	B vitamins probably resulted in little to no difference in executive function.
Speed of processing assessed with: various instrumentsc follow‐up: range 6 months to 24 months	SMD with B vitamins was 0.04 higher (0.26 lower to 0.34 higher) than with placebo		173 (2 RCTs)	⊕⊕⊕⊝ MODERATE 4	B vitamins probably resulted in little to no difference in speed of processing.
Quality of life assessed with: D‐QOL Scale from: 1 to 5 follow‐up: 12 months	The mean quality of life was 3.5 points	MD 0 points (0.1 lower to 0.1 higher)	138 (1 RCT)	⊕⊕⊕⊝ MODERATE 5	B vitamins probably resulted in little to no difference in quality of life.
Mortality ‐ not reported	Reported by only one study (2/133 died in vitamin B group, 0/133 died in placebo group).		‐	‐
*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). MD: Mean difference; SMD: Standardised mean difference; 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 due to risk of bias. One study was at high risk of performance bias and at unclear risk of selection and detection bias.

² Downgraded due to inconsistency. I² = 87%.

³ Downgraded due to imprecision. 95% CI included little or no effect and small benefit of B vitamins.

⁴ Downgraded due to imprecision. 95% CI included small effects in either direction.

⁵ Downgraded due to imprecision. Result derived from one small study.

^aEpisodic memory assessed with Hopkins Verbal Learning Test, word learning and the Auditory Verbal Learning Test.

^bExecutive function assessed with CLOX, the Stroop test, and the Frontal Assessment Battery.

^cSpeed of processing assessed with Trail‐making Test A, digit cancellation, and the Digit‐Symbol Substitution Test.

^{CLOX: Clock drawing executive test
 D‐QOL: Dementia quality of life questionnaire
 MCI: Mild cognitive impairment
 MMSE: Mini‐mental state examination}