Summary of findings 1. Vitamin K compared to control for people with cystic fibrosis.

Vitamin K compared to control for people with cystic fibrosis
Patient or population: people with cystic fibrosis Setting: community or health care facilities Intervention: vitamin K Comparison: placebo or no intervention
Outcomes	Anticipated absolute effects* (95% CI)		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with Placebo	Risk with Vitamin K
Time to cessation of bleeding Follow‐up: 12 months	Outcome not reported.
Bone mineral density: lumbar spine z score Follow‐up: 12 months	The mean (SD) change in the placebo group in z score at the lumbar spine was 0.041 (0.15) g/cm³ and in the treatment group it was ‐0.073 (0.30) g/cm³.			38 (1)	Very low ⊕⊝⊝⊝a,b	The trial authors also reported mean change in z score in those participants 25 or under and those that were over 25 years. They concluded that vitamin K had no significant effect except in participants that were over 25 years. where vitamin K may have a protective effect against decline in BMD (Kuitert 2010). The mean (SD) change in the placebo group at the femoral hip z score was 0.053 (0.19) g/cm³ and in the treatment group was ‐0.20 (0.31) g/cm³. The mean change in femoral hip z score ≤ 25, but there is not enough information to comment on the statistical significance of this. The authors report no significant effect of vitamin K on bone mineral density.
QoL: CFQ‐R Follow‐up:12 months	Outcome not reported.
QoL: CFQoL Follow‐up: 12 months	Outcome not reported.
Adverse events Follow‐up: 12 months	Outcome not reported.
PIVKA II levels: change in PIVKA II (ng/mL) Follow‐up: 12 months	Mean (SD) PIVKA‐II concentrations increased significantly when participants were not supplemented (5.1 (3.2) ng/mL in the supplemented group and 21.8 (3.2) ng/mL in the unsupplemented group) and almost one third (5 out of 18) of the participants had PIVKA‐II levels within the normal range (≤ 2 ng/mL) following supplementation.			18 (1 study)	Very low ⊕⊝⊝⊝b,c
Uncarboxylated osteocalcin: change in carboxylation of osteocalcin (% Glu‐OC) Follow‐up: 1 month	See comments.					Two studies (total n = 56) narratively reported that vitamin K improved carboxylation of osteocalcin (Beker 1997; Kuitert 2010).
*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; CFQoL: Cystic Fibrosis Quality of Life; CFQ‐R: Cystic Fibrosis Questionnaire ‐ Revised; PIVKA‐II: proteins induced by vitamin K absence; SD: standard deviation.
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

^a Downgraded twice due to an unclear risk of bias in one RCT, particularly for the domains of randomisation, allocation concealment and blinding.

^b Downgraded once due to imprecision as numbers were too low to meet the optimal information size.

^c Downgraded twice due to risk of bias within one RCT. The randomisation and allocation concealment processes were unclear and it wasn't possible to blind either participants or healthcare providers. It was unclear whether the outcome assessors were blinded.