Effects of omega-3 fatty acid supplementation on heart rate variability

Figure 1 Graphical abstract. HRV: Heart rate variability; RMSSD: Root mean square of successive differences; SDNN: Standard deviation of normal-to-normal intervals.

Figure 2  PRISMA flow diagram.

Figure 3 Meta-analysis. A: Meta-analysis of the root mean square of successive differences (RMSSD) (pre-post). Forest plot of the effect of omega-3 supplementation on RMSSD [time-domain heart-rate variability (HRV) index]. Each square represents the mean difference (MD) with 95%CI; the diamond represents the pooled estimate. The pooled mean difference (MD = -11.69 milliseconds, 95%CI: -18.50 to -4.87, P = 0.0008) indicated a significant improvement with low heterogeneity (I² = 0%, P = 0.35); B: Meta-analysis of the standard deviation of normal-to-normal intervals (SDNN) (pre-post). Forest plot of the effect of omega-3 supplementation on SDNN (time-domain HRV index). The pooled mean difference (MD = -26.13 milliseconds, 95%CI: -35.84 to -16.42, P < 0.00001) indicated a significant improvement with low heterogeneity (I² = 0%, P = 0.46); C: Meta-analysis of the percentage of successive normal-to-normal intervals differing by more than 50 milliseconds (pNN50%) (pre-post). Forest plot illustrating the effect of omega-3 supplementation on pNN50, a time-domain HRV index reflecting parasympathetic activity. The pooled mean difference (MD = -9.45; 95%CI: -14.27 to -4.64; P = 0.0001) indicated a significant improvement with no heterogeneity (I² = 0%, P = 0.65).

Figure 4 Meta-analysis. A: Meta-analysis for high-frequency (HF) heart-rate variability. Forest plot showing the effect of omega-3 supplementation on HF power, representing parasympathetic activity. The pooled mean difference [mean difference (MD) = -0.18, 95%CI: -0.61 to 0.25; P = 0.41] indicated no significant change compared with controls. Heterogeneity was minimal (I² = 0 %, τ² = 0.00, P = 0.85); B: Meta-analysis for low-frequency (LF) heart-rate variability. Forest plot comparing omega-3 supplementation and control groups for LF power, representing mixed sympathetic and parasympathetic modulation. The pooled mean difference (MD = -4.59, 95%CI: -23.26 to 14.08; P = 0.63) showed no significant difference. No heterogeneity was observed (I² = 64 %, τ² = 127.15, P = 0.10); C: Meta-analysis for low- to high-frequency (LF/HF) ratio heart-rate variability. Forest plot illustrating between-group comparison of the LF/HF ratio following omega-3 supplementation. The pooled mean difference (MD = 0.95, 95%CI: -27.13 to 29.03; P = 0.95) demonstrated no significant change. However, heterogeneity was substantial (I² = 93%, τ² = 381.96, χ² = 13.78, P = 0.0002), reflecting variability among included trials.

Figure 5 Heart-rate variability changes after omega-3 supplementation. Summary of heart rate variability metric changes following omega-3 supplementation. Significant improvements were observed in time-domain indices (standard deviation of normal-to-normal intervals, root mean square of successive differences), whereas frequency-domain indices (high frequency, low frequency) showed non-significant changes. Dark bars indicate statistically significant outcomes (P < 0.05). HF: High frequency; LF: Low frequency; RMSSD: Root mean square of successive differences; SDNN: Standard deviation of normal-to-normal intervals.

Figure 6 Proposed mechanisms of omega-3 on cardiac autonomic modulation. Membrane incorporation of eicosapentaenoic acid and docosahexaenoic acid stabilizes ion channels, reduces sympathetic drive, and contributes to improved heart rate variability metrics (standard deviation of normal-to-normal intervals, root mean square of successive differences). HRV: Heart rate variability.