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Proton pump inhibitors (PPI) and histamine H2-receptor antagonists (H2A)

• Most commonly used drugs worldwide
• Causing iron deficiency and RLS (restless leg syndrome)

Observational study of blood donors

• In the United States (N = 13,403; REDS-III) and Denmark (N = 50,323; Danish Blood Donor Study, DBDS)
• After adjusting for age, sex, race, BMI, blood donation frequency, smoking, hormone use, and iron supplement use
• PPI/H2A use was associated with RLS (restless leg syndrome)
• Odds ratio [OR] = 1.41; 95% confidence interval [CI], 1.13–1.76; p = 0.002) in REDS-III for both
• PPI (OR = 1.43; CI, 1.03–1.95; p = 0.03)
• H2A (OR = 1.56; CI, 1.10–2.16; p = 0.01)
• DBDS
• PPIs/H2As (OR = 1.29; CI, 1.20–1.40; p < 0.001)
• PPIs alone (OR = 1.27; CI, 1.17–1.38; p < 0.001)
• H2As alone (OR = 1.18; CI, 0.92–1.53; p = 0.2)
• Found no evidence of blood iron stores mediating this association
• Association of PPI, and possibly H2A, consumption with RLS independent of blood iron status
• academic.oup.com/sleep/article/44/4/zsaa220/5942955