Sex-Specific Heart Rate Variability Associations With Vitamin B12, Folate, and Iron Status

The sex-specific impact of micronutrient status on heart rate variability (HRV) in adults presenting with palpitations to cardiology outpatient clinics remains unclear. Thus, this study aimed to assess the demographic and biochemical determinants of HRV in a clinical cohort of patients presenting with complaints of palpitations.

This retrospective study included 213 adults aged 18-65 years who presented with palpitations and underwent 24-hour Holter monitoring at our institution between 2023 and 2024. Patients with cardiovascular disease, known arrhythmias, chronic inflammatory conditions, renal dysfunction, or use of medications that affected autonomic function were excluded from the study. Demographic variables, laboratory parameters, and HRV indices were statistically analyzed. The standard deviation of all normal-to-normal intervals (SDNN) was the primary HRV parameter used in both univariate and multivariate linear regression analyses.

The SDNN was significantly lower in women and older adults. In the univariate analyses, age (β = -0.203; p = 0.003), male sex (β = 0.529; p < 0.001), ferritin, serum iron, folate, and Vitamin B12 were all associated with the SDNN. However, in the multivariable model, only male sex (β = 0.467; p < 0.001), iron-binding capacity (IBC) (β = -0.377; p < 0.001), and folate (β = 0.117; p = 0.037) remained independent predictors. Elevated IBC, reflecting functional iron deficiency, was strongly associated with a reduced SDNN, whereas higher folate levels were associated with better autonomic modulation.

In patients presenting with palpitations, the SDNN is influenced by both demographic factors and biochemical markers of iron metabolism. Elevated IBC, reflecting alterations in iron metabolism and iron availability, was associated with impaired autonomic regulation, even in the absence of overt anemia. In contrast, adequate folate status appeared to support a more favorable autonomic function. These findings highlight the importance of integrating iron-vitamin assessment into the evaluation of autonomic function and underscore the need for prospective studies to determine whether correcting these abnormalities can improve HRV and clinical outcomes.