Dolor de cabeza (sinusal)

5-HTP, the direct serotonin precursor, has been studied in the context of RLS and periodic leg movements, given evidence that serotonergic dysfunction contributes to RLS pathophysiology. A 1987 sleep study investigated 5-HTP and L-DOPA for periodic leg movements associated with RLS, and a PubMed review (1992) identified abnormal serotonin function as relevant to RLS pathophysiology.

D-ribose, a naturally occurring pentose sugar essential for ATP synthesis, has been reported to reduce RLS symptoms when taken daily. Life Extension's RLS protocol cites a 2008 report (Shecterle) suggesting D-ribose may decrease RLS symptom severity.

Diosmin, a natural flavone glycoside used to support venous function, has been shown in meta-analyses to reduce RLS symptoms as part of its effects on chronic venous disease. Since venous insufficiency is linked to secondary RLS, diosmin (as MPFF) addresses a recognized underlying mechanism.

GABAergic dysfunction is mechanistically implicated in RLS, and GABA is listed among supplements promoted for RLS by ConsumerLab. Pharmaceutical GABA analogs (gabapentin, pregabalin) are FDA-approved for RLS, providing strong indirect evidence that GABAergic supplementation is mechanistically relevant.

Iron deficiency is one of the most established secondary causes of RLS. Low serum ferritin is strongly associated with increased RLS prevalence and severity, and oral iron supplementation significantly improves symptoms in deficient patients. International guidelines (IRLSSG) recommend oral iron therapy when serum ferritin is below 75 µg/L.

Low serum magnesium levels are associated with greater RLS severity, particularly in pregnant women. A randomized controlled trial found magnesium oxide (250 mg/day) significantly improved both RLS symptom scores and sleep quality compared to placebo and was superior to vitamin B6. A 2024 systematic review of 10 RCTs confirmed magnesium as showing the strongest supplemental benefit.

In a prospective randomized placebo-controlled trial (n=37), 800 mg/day of valerian for 8 weeks significantly improved RLS symptoms and reduced daytime sleepiness in patients with Epworth Sleepiness Scale scores ≥10. A 2023 crossover RCT in hemodialysis patients also showed valerian significantly reduced RLS scores, though less effectively than gabapentin.

Oral vitamin B6 (pyridoxine) significantly improved primary RLS symptoms in a randomized controlled trial (p<0.0001 vs. placebo). A 2025 meta-analysis and a 2024 systematic review of 10 RCTs both confirmed that vitamin B6 significantly alleviates RLS symptom severity and improves sleep quality, though its effect was smaller than magnesium.

Low serum folate is associated with RLS risk specifically in pregnant women, and folic acid administration has been shown to alleviate RLS symptoms, potentially playing a role in primary familial RLS treatment. Pregnant women with lower folate levels were significantly more likely to develop RLS than those supplementing with vitamins during pregnancy.

Vitamin C significantly improved RLS symptoms in hemodialysis patients in a randomized, double-blind, placebo-controlled trial. A 2025 meta-analysis confirmed that oral vitamin C significantly reduces hemodialysis-associated RLS severity, likely through antioxidant mechanisms reducing oxidative stress in the striatum.

Vitamin E significantly improved RLS symptoms in hemodialysis patients in a randomized double-blind placebo-controlled trial. A 2025 meta-analysis confirmed oral vitamin E significantly reduces hemodialysis-associated RLS severity, equal in efficacy to vitamin C alone, likely via antioxidant reduction of oxidative stress.

Lower serum zinc levels have been significantly correlated with RLS severity, particularly in pregnant women. A study found zinc and magnesium levels in pregnant RLS patients were significantly lower than in controls, with an inverse correlation between serum zinc and symptom severity.

Restless leg syndrome (RLS) is listed as a use of inositol nicotinate in RxList, WebMD, and Wikipedia. However, Wikipedia explicitly states RLS is among IHN's uses with 'insufficient supporting evidence.' No RCTs specifically testing IHN for RLS were identified, making this a traditional/documented use without clinical trial support.