Nocturnal leg cramps (NLCs) are spontaneous contractions of muscles. The gastrocnemius is
commonly involved, lasting from a few seconds to a few minutes. Patients might wake up
with pain during attacks, making it difficult to sleep for a short period. It commonly
occurs >60-year-old. The medical history and physical examination are usually sufficient
to differentiate nocturnal leg cramps from other conditions, such as restless legs
syndrome, claudication, myositis, and peripheral neuropathy. Factors that may lead to leg
cramps attacks include hemodialysis, electrolyte imbalance, metabolic disorders, and
congenital disorders. The cramps can be relieved by passive stretching of the
gastrocnemius and deep tissue massage, but such prevention is limited, especially in
patients with refractory muscle cramps. Quinine has been shown to be effective in
treating NLCs but is not recommended by the US Food and Drug Administration due to severe
side effects. Magnesium supplements are often used as a preventative treatment for NLCs;
however, their effectiveness is controversial. Magnesium supplements are widely marketed
for the prophylaxis of NLCs since a double-blind, placebo-controlled study proved their
effectiveness in pregnant women. However, magnesium administration did not show
significant benefits in NLCs in double-blind, placebo-controlled studies. Meta-analysis
of some randomized control trials (RCTs) showed that magnesium therapy did not appear to
be effective in the treatment of NLCs in the general population, but may have a
negligible effect in pregnant women. Therefore, seeking new approaches to manage NLCs is
imperative.
Vitamin K is a fat-soluble vitamin involved in carboxylation and activating several
dependent proteins. It is found in two isoforms (phylloquinone (vitamin K1) and
menaquinone (vitamin K2)) that differ in length and degree of saturation of the side
chain. In addition to their role in coagulation, vitamin K-dependent proteins are
involved in vascular calcification and osteoporosis physiology. Accumulating evidence has
shown the beneficial effects of vitamin K2 supplementation on cardiovascular and bone
health.
Another study revealed that vitamin K3 relieved muscle cramps by effectuating the
voltage-dependent calcium channels to release the calcium stored in the cells, thus
reducing the frequency of muscular contractions. To the best of our knowledge, no study
has yet investigated the efficacy of vitamin K in NLCs. In addition, vitamin K2 has a
good safety profile compared to other medications. Our pilot study demonstrated that
vitamin K2 supplementation decreases the frequency, duration, and severity of muscle
cramps in hemodialysis patients. To further investigate the efficacy and safety of
vitamin K2 in NLCs, we designed this prospective, multicenter, randomized, double-blind
trial.