Vitamin K2 (180 μg daily) significantly reduced frequency, severity, and duration of nocturnal leg cramps in older adults over 8 weeks with good safety.

Background

Nocturnal leg cramps (NLCs) are common and distressing in older adults, yet few therapies are both safe and effective. Quinine is no longer recommended due to serious adverse effects, and evidence for alternatives (e.g., magnesium) is limited. Prior work suggested vitamin K2 may reduce dialysis-related cramps, prompting this randomized trial in community-dwelling older adults with NLCs.

Patients

• Population: 199 community-dwelling adults ≥65 years in China with ≥2 NLC episodes during a 2-week screening period
• Mean age: 72.3 years; Female: 54.3%
• Key exclusions: Cramps due to specific metabolic/neurologic conditions (e.g., hypothyroidism, Parkinson disease, radiculopathies), malignancy, use of diuretics, vitamin K antagonists, or vitamin K2 within prior 2 months; patients on hemodialysis
• Centers: Third People’s Hospital of Chengdu and Affiliated Hospital of North Sichuan Medical College

Intervention

• Vitamin K2 (menaquinone-7), 180 μg orally once daily at night for 8 weeks

Control

• Matching placebo orally once daily for 8 weeks

Outcome

• Primary: Mean number of NLC episodes per week
• Secondary:
  • Duration of cramps (minutes)
  • Severity of cramps (analog scale 1–10)
  • Safety (adverse events)

Study Design

• Multicenter, double-blind, randomized, placebo-controlled clinical trial
• Allocation 1:1; computer-generated randomization; identical-appearing capsules
• Weekly telephone follow-up and self-reported cramp diaries
• Intention-to-treat analysis; mean imputation for missing data
• Trial registration: NCT05547750

Level of Evidence

Level I (randomized, double-blind, placebo-controlled trial)

Follow up period

8 weeks

Results

• Participants: 103 vitamin K2; 96 placebo; baseline weekly cramp frequency similar (2.60 vs 2.71)
• Primary outcome:
  • Mean weekly NLCs during intervention: 0.96 (vitamin K2) vs 3.63 (placebo)
  • Between-group difference: −2.67 episodes/week (95% CI, −2.86 to −2.49)
• Secondary outcomes:
  • Severity (1–10): End-of-study mean 1.12 (vitamin K2) vs 2.08 (placebo); mean reduction from baseline −2.55 vs −1.24
  • Duration (minutes): End-of-study mean 0.25 (vitamin K2) vs 0.98 (placebo); mean reduction from baseline −0.90 vs −0.32
  • Safety: No adverse events attributed to vitamin K2
• NNT: Not applicable (no dichotomous outcomes reported)

Limitations

• Short duration (8 weeks); community-dwelling cohort with relatively mild baseline symptoms
• Self-reported outcomes; mean imputation for missing data
• No assessment of sleep quality or quality-of-life outcomes
• Generalizability to patients with more severe or secondary cramp etiologies is uncertain
• Vitamin K2 may interfere with warfarin anticoagulation (not studied here)

Funding

Third People’s Hospital of Chengdu Scientific Research Project (2023PI05) and China Health Promotion Foundation (Z093001). Study products supplied by Sungen Biotech. Funders had no role in study design, conduct, analysis, or publication decisions.

Citation

Tan J, Zhu R, Li Y, Wang L, Liao S, Cheng L, Mao LX, Jing D. Vitamin K2 in Managing Nocturnal Leg Cramps: A Randomized Clinical Trial. JAMA Internal Medicine. 2024;184(12):1443-1447. doi:10.1001/jamainternmed.2024.5726. ClinicalTrials.gov: NCT05547750.