Anemia and Insomnia: A Cross-Sectional Study and Meta-Analysis
Insomnia is a prevalent sleep disorder affecting approximately 10% to 30% of the global population, with half of these cases classified as chronic. It is characterized by difficulty falling asleep, staying asleep, or experiencing non-restorative sleep. Insomnia has been linked to various psychosocial, psychiatric, and medical disorders, impairing daytime functioning, memory performance, and overall quality of life. Identifying risk factors for insomnia is thus of significant clinical importance.
Recent genome-wide association studies (GWAS) have suggested that insomnia and anemia may share common genetic components. Specifically, the MEIS1 gene, associated with restless legs syndrome (RLS) and iron-deficiency anemia (IDA), has also been implicated in insomnia. This genetic overlap raises the possibility of a biological link between anemia and sleep disturbances. While studies in infants and children have shown associations between anemia, particularly IDA, and sleep alterations, only a few studies have explored this relationship in adult populations. These studies, however, have limitations, such as inadequate adjustment for confounders like inflammation status and other sleep parameters.
To address these gaps, this study aimed to examine the association between anemia and insomnia in a large-scale, community-based cohort of Chinese adults. Additionally, a meta-analysis was conducted to pool results from this study and previous research to provide a more comprehensive understanding of the relationship.
Methods
The study was conducted as part of the Kailuan Study, an ongoing cohort of 101,510 Chinese adults aged 18 to 98 years living in Tangshan City, China. The current cross-sectional analysis included 12,614 participants who had complete data on sleep parameters, hemoglobin levels, and other major covariates. Anemia was defined based on hemoglobin levels: below 12.0 g/dL for women and below 13.0 g/dL for men. Insomnia was assessed using the Chinese version of the Athens Insomnia Scale (AIS), with a total score of 6 or higher indicating insomnia.
The study adjusted for various potential confounders, including age, sex, education level, income, occupation, physical activity, smoking and alcohol status, body mass index, history of chronic diseases (e.g., myocardial infarction, stroke, cancer), hypertension, diabetes, and blood concentrations of triglycerides, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Sensitivity analyses were conducted by excluding participants with chronic inflammation (C-reactive protein [CRP] levels ≥1 mg/L) and those with severe chronic kidney disease (estimated glomerular filtration rate [eGFR] <30 mL/min per 1.73 m²).
A meta-analysis was performed to combine the results of this study with three previously published cross-sectional studies on the association between anemia and insomnia in adult populations. The meta-analysis included a total of 22,134 participants and used a fixed-effects model due to the absence of significant heterogeneity across studies.
Results
In the cross-sectional analysis, 4.3% of the participants were classified as having anemia, and 15.2% reported insomnia. Individuals with anemia had a higher prevalence of insomnia compared to those without anemia (15.2% vs. 10.6%). After adjusting for potential confounders, anemia was associated with a 32% increased odds of having insomnia (adjusted odds ratio [OR]: 1.32; 95% confidence interval [CI]: 1.03–1.70). This association persisted even after excluding participants with chronic inflammation (adjusted OR: 1.68; 95% CI: 1.22–2.32) or severe chronic kidney disease (adjusted OR: 1.30; 95% CI: 1.01–1.67).
A dose-dependent relationship was observed between the severity of anemia and the likelihood of insomnia. Participants with severe anemia had significantly higher odds of insomnia (adjusted OR: 1.95; 95% CI: 1.06–3.62), while those with mild or moderate anemia did not show a significant association. Anemia was particularly associated with difficulties in sleep induction (adjusted OR: 1.34; 95% CI: 1.08–1.67) and early morning awakening (adjusted OR: 1.31; 95% CI: 1.04–1.64), but not with night awakenings.
The association between anemia and insomnia was stronger in men (adjusted OR: 1.70; 95% CI: 1.22–2.36) than in women (adjusted OR: 1.03; 95% CI: 0.69–1.52), with a significant interaction observed (P-interaction = 0.04). No significant interaction was found between anemia and age in relation to insomnia.
The meta-analysis confirmed the positive association between anemia and insomnia, with a pooled OR of 1.39 (95% CI: 1.22–1.57). The included studies showed no significant heterogeneity (I² = 18.3%), and there was no strong evidence of publication bias.
Discussion
This study provides robust evidence that anemia is associated with a higher likelihood of insomnia in adults. The findings are consistent with previous research and are further supported by the meta-analysis, which included over 22,000 participants. The association remained significant even after adjusting for various confounders and conducting sensitivity analyses, suggesting that the relationship is independent of factors such as chronic inflammation and kidney function.
The observed association may be explained by several mechanisms. One possibility is the shared genetic component between anemia and insomnia, particularly the MEIS1 gene, which is involved in iron metabolism and has been linked to both conditions. Additionally, anemia may lead to sleep disturbances through its impact on brain function, such as altered cerebral blood flow or neurotransmitter activity. Fatigue, a common symptom of anemia, could also contribute to sleep problems.
The sex difference in the association between anemia and insomnia is an interesting finding. The stronger association in men may be related to differences in hormonal profiles, particularly the protective effect of estrogen in women. Further research is needed to explore the biological mechanisms underlying this sex difference.
This study has several limitations. First, insomnia was assessed using a self-reported questionnaire, which may be subject to recall bias. Second, the study did not measure iron biomarkers, so it was unable to distinguish between iron-deficiency and non-iron-deficiency anemia. Third, residual confounding is a concern, as the study did not account for psychological factors such as anxiety and depression, which could influence both anemia and insomnia. Finally, the cross-sectional design limits the ability to establish a temporal relationship between anemia and insomnia.
Despite these limitations, the study has important clinical implications. If anemia is indeed a risk factor for insomnia, treating anemia could potentially alleviate insomnia symptoms. Healthcare professionals should consider evaluating insomnia in patients with anemia and exploring interventions that address both conditions.
Conclusion
In conclusion, this large-scale, community-based study and meta-analysis provide strong evidence that anemia is associated with a higher likelihood of insomnia in adults. The findings highlight the importance of considering anemia as a potential risk factor for sleep disturbances and suggest that addressing anemia could have benefits beyond improving hemoglobin levels. Future prospective studies with objective sleep measures and direct assessment of iron status are needed to further elucidate the relationship between anemia and insomnia. If confirmed, clinical trials could explore whether treating anemia improves insomnia symptoms.
doi.org/10.1097/CM9.0000000000001306
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