Importance: Currently, there are no treatments for nocturnal leg cramps (NLCs) that have been proven to be both safe and effective. Seeking safe and effective approaches for managing NLCs is of crucial importance.
Objective: To determine whether vitamin K2 is better than placebo in managing NLCs.
Design, setting, and participants: This multicenter, double-blind, placebo-controlled randomized clinical trial was conducted in China between September 2022 and December 2023. This study used a volunteer sample comprising community-dwelling individuals 65 years and older with 2 or more documented episodes of NLCs during 2 weeks of screening. Researchers performed a history and physical screening of candidates recruited from the community through advertisements, and eligible participants were randomized in a 1:1 ratio to receive vitamin K2 or a placebo for 8 weeks.
Interventions: Patients orally took capsules containing either vitamin K2 (menaquinone 7), 180 μg, or a similar-looking placebo every day for 8 weeks. The study products were custom manufactured to have identical packaging and for the capsules to have matching appearance and identical excipients that shared similar taste and weight.
Main outcomes and measures: The primary outcome was the mean number of NLCs per week between the vitamin K2 and the placebo group. Secondary outcomes included the duration of muscle cramps measured in minutes and the severity of muscle cramps assessed using an analog scale ranging from 1 to 10.
Results: Among the 310 participants, 111 participants were excluded. Of the 199 enrolled individuals, 108 (54.3%) were female, and the mean (SD) age was 72.3 (5.5) years. A total of 103 patients (51.8%) were randomly assigned to receive vitamin K2 and 96 (48.2%) were assigned to placebo. The mean (SD) baseline weekly frequency of cramps was comparable in both the vitamin K2 group (2.60 [0.81]) and the placebo group (2.71 [0.80]). During the 8-week intervention, the vitamin K2 group experienced a reduction in the mean (SD) weekly frequency of cramps to 0.96 (1.41). Meanwhile, the placebo group maintained mean (SD) weekly frequency of cramps at 3.63 (2.20). The between-group difference was statistically significant (difference, -2.67; 95% CI, -2.86 to -2.49; P < .001). The vitamin K2 group had a more significant mean (SD) reduction in NLC severity (-2.55 [2.12] points) compared with the placebo group (-1.24 [1.16] points). The vitamin K2 group exhibited a more pronounced mean (SD) decrease in the duration of NLCs (-0.90 [0.88] minutes) than the placebo group (-0.32 [0.78] minutes). No adverse events related to vitamin K2 use were identified.
Conclusions and relevance: This randomized clinical trial showed that vitamin K2 supplementation significantly reduced the frequency, intensity, and duration of NLCs in an older population with good safety.
Trial registration: ClinicalTrials.gov Identifier: NCT05547750.