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

Abstract

BACKGROUND

Obesity and overweight are major public health challenges and are associated with autonomic imbalance and decreased heart rate variability (HRV), a non-invasive indicator of cardiovascular risk. Omega-3 polyunsaturated fatty acids have shown cardioprotective effects and may modulate autonomic function. Nevertheless, the effect of omega-3 supplementation on HRV in individuals who are overweight or obese remains unclear.

AIM

To study the effect of omega-3 supplementation on HRV in overweight and obese individuals and to explore the heterogeneity across different study designs.

METHODS

In accordance with PRISMA guidelines, a systematic review and meta-analysis were conducted. PubMed, Science Citation Index, and Scopus were searched for randomized controlled trials (RCTs) assessing the impact of oral omega-3 supplementation on HRV in overweight or obese participants. Primary outcomes were the impacts of omega-3 supplementation on time-domain HRV indices [root mean square of successive differences (RMSSD), standard deviation of normal-to-normal intervals (SDNN), and percentage of successive normal-to-normal intervals differing by more than 50 milliseconds (pNN50%)], and frequency-domain indices [high-frequency (HF) power, low-frequency (LF) power, and LF/HF ratio].

RESULTS

Four RCTs (n = 134 participants) met the inclusion criteria. Two trials compared pre- vs post- omega-3 supplementation, and two compared omega-3 with placebo on HRV in overweight and obese children and adults. In the within-subject analyses, omega-3 supplementation was associated with a significant increase in RMSSD [mean difference (MD) = -11.69 milliseconds, 95%CI: -18.50 to -4.87, P = 0.0008), SDNN (MD = -26.13 milliseconds, 95%CI: -35.84 to -16.42, P < 0.00001), and pNN50% (MD = -9.45, 95%CI: -14.27 to -4.64, P = 0.0001). Between-group comparisons showed that omega-3 supplementation had no significant effect on HF power, LF power, or the LF/HF ratio.

CONCLUSION

Omega-3 supplementation represents a promising and low-cost strategy for enhancing autonomic balance and potentially reducing cardiovascular risk in overweight and obese populations, as it improves time-domain HRV measures.

Key Words: Autonomic nervous system; Heart rate variability; Meta-analysis; Obesity; Omega-3 polyunsaturated fatty acids; Randomized controlled trials

Core Tip: Overweight and obesity have become serious global health concerns that frighteningly impact both adults and children. Obesity is intimately linked to decreased heart rate variability (HRV), which is considered a non-invasive indicator of cardiovascular risk. Omega-3 fatty acids supplementation acts as a promising adjuvant cardio-protective therapy that may improve time-domain HRV in the overweight and obese individuals.

INTRODUCTION

Obesity has become a serious global health concern, affecting both adults and children at alarming rates[1]. Beyond its association with metabolic diseases such as type 2 diabetes and dyslipidemia, obesity profoundly impacts the autonomic nervous system (ANS) function, often manifesting as altered cardiac autonomic regulation. One of the most widely accepted non-invasive markers of ANS balance is heart rate variability (HRV), which reflects the interaction between parasympathetic and sympathetic activity[2]. HRV is a readily available, non-invasive, and reliable independent indicator of ANS function. Since reduced HRV has been linked to ANS dysregulation, impaired stress reactivity, increased cardiometabolic risk, and premature death, regular HRV monitoring is becoming more common in adults as a means of assessing ANS activity[3]. Reduced HRV is strongly associated with increased cardiovascular morbidity and mortality, making it a valuable prognostic indicator in populations at cardiometabolic risk, including individuals with obesity[4].

Nutritional interventions have been increasingly studied as strategies to improve autonomic function and reduce cardiovascular risk. Among these, Omega-3 polyunsaturated fatty acids (PUFAs) have attracted particular interest due to their cardioprotective properties, including decreasing triglyceride levels, minimizing inflammation, and enhancing endothelial function[5]. Importantly, omega-3 PUFAs are hypothesized to beneficially modulate autonomic tone, potentially improving HRV and reducing the risk of arrhythmias[6]. Observational studies suggest that habitual fish consumption is associated with a reduced resting heart rate and improved HRV[7]; however, intervention trials in humans have produced inconsistent results, particularly in overweight or obese populations.

Rationale for the systematic review

To date, no systematic review has specifically synthesized the evidence on omega-3 supplementation and HRV outcomes in overweight and obese populations. Given the rising prevalence of obesity across all age groups and the prognostic importance of HRV in cardiovascular health, a critical appraisal of the literature is warranted. Accordingly, this systematic review aims to evaluate the effects of omega-3 supplementation on HRV and resting heart rate in overweight and obese individuals, as well as to explore heterogeneity across study designs and dosing regimens (Figure 1).

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

MATERIALS AND METHODS

Protocol registration

This review adhered to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2009 guidelines and was prospectively registered in PROSPERO (CRD420251149899). The protocol was finalized prior to data extraction and analysis.

Eligibility criteria

We used the population, intervention, comparator, outcomes (PICO) framework to define eligibility:

Population: Studies involving overweight or obese individuals (adults or children)[8-11]

Intervention: Oral omega-3 supplementation.

Control: Obese patients who did not receive omega-3 supplementation were studied to evaluate differences in the frequency-domain measures of HRV[8,9]. Regarding time-domain measures of HRV, only one study used obese participants as controls[11], which was insufficient for the meta-analysis. Therefore, baseline data were used as controls[10,11]. Contact with the corresponding author was made whenever essential data for this review was not reported.

Outcomes: Primary outcomes were time-domain HRV measures; root mean square of successive differences (RMSSD), standard deviation of normal-to-normal intervals (SDNN), and the percentage of successive normal-to-normal intervals differing by more than 50 milliseconds (pNN50%). Secondary outcomes included resting heart rate and frequency-domain measures: High-frequency (HF) power, low-frequency (LF) power, and low-to-high-frequency (LF/HF) ratio.

Study design: Randomized controlled trials (RCTs) (parallel or crossover) and pre-post intervention studies published in peer-reviewed journals.

Search strategy

Three major databases, PubMed, Scopus, and Clarivate Web of Science, were systematically searched to identify all relevant studies. The search strategy was designed to be broad and combined the terms omega-3 and HRV. For example, the PubMed search strategy included: ("Fatty Acids, Omega-3"[Mesh] OR "Fish Oils"[Mesh] OR omega-3 OR EPA OR DHA) AND ("Heart Rate"[Mesh] OR "Heart Rate Variability"[Mesh] OR HRV).

Study selection

EndNote X8 was used to import all received records, and duplicate studies were removed. Titles, abstracts, and the full texts of potential studies were filtered using the PICO framework. Study selection was carried out independently by two reviewers. After merging search results and removing duplicates, we screened abstracts and titles, followed by a thorough assessment of the complete texts of possibly eligible research. Any disputes that arose during this process were handled through discussion.

Data extraction

A standardized data-extraction format was used, including research identifiers, settings, sample sizes, event counts, outcomes, and notes. One reviewer extracted the data, and the other verified the accuracy.

Statistical analysis

Meta-analyses were carried out with Review Manager (RevMan, Version 5.4, The Cochrane Collaboration, 2020). For continuous outcomes, we calculated the mean difference and 95% confidence interval (CI) when all studies used the same scale. The standardized mean difference was used for outcomes reported in different units (e.g., normalized units vs absolute power for HF).

We employed a random-effects model for all analyses, as we anticipated clinical heterogeneity due to variations in study populations and intervention methods. The I² statistic was used to measure heterogeneity, with a value above 50% indicating significant heterogeneity. The χ² test (Cochran’s Q) was also used, with a significance level of P < 0.10 indicating significant heterogeneity. Because the number of papers (< 10) for each outcome, assessment of publication bias using funnel plots was not feasible.

Risk of bias assessment

Using the Cochrane Risk of Bias tool (ROB 2.0), two reviewers independently assessed the risk of bias in the included RCTs. This tool evaluates bias across five domains: (1) Randomization process; (2) Deviations from intended interventions; (3) Missing outcome data; (4) Measurement of the outcome; and (5) Selection of the reported result. Each study was judged to have a “low risk”, “some concerns”, or “high risk” of bias for each domain. The overall risk of bias judgment for each article was then calculated. A summary of the risk of bias across domains is illustrated in Table 1.

Table 1 Risk of bias assessment.

Ref.	Domain 1: Randomization process	Domain 2: Deviations from intended interventions	Domain 3: Missing outcome data	Domain 4: Measurement of the outcome	Domain 5: Selection of reported results	Overall risk of bias (auto)
Ninio et al[8], 2008	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Sjoberg et al[9], 2009	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Baumann et al[10], 2018	High risk	Some concerns	Low risk	Some concerns	Low risk	High risk
Ibrahim et al[11], 2025	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk

RESULTS

Study selection and screening

Our initial systematic search of PubMed, Scopus, and Clarivate yielded 228 records. After eliminating 33 duplicates, we reviewed the abstracts and titles of 195 distinct studies. The vast majority (n = 191) were excluded because they did not meet the eligibility criteria. This left four studies for full-text review[8-11]. All four were deemed suitable for inclusion and were subsequently used in qualitative synthesis and meta-analysis (Figure 2).

Figure 2  PRISMA flow diagram.

Quality assessment

We used the ROB 2.0 tool to evaluate the methodological quality of the included RCTs. The risk of bias was deemed low for three studies[8,9,11]. These trials demonstrated robust randomization protocols, minimal variations from the intended interventions, and thorough outcome data reporting.

Study characteristics

The four included RCTs, published between 2008 and 2025, enrolled a total of 134 participants. Of these, 90 were assigned to omega-3 supplementation groups and 94 to control groups (placebo or standard care). Table 2 presents the socio-demographic criteria of the enrolled studies.

Table 2 Summary of included studies.

Ref.	Country	Study design	Population/sample size	Intervention/exposure	Comparator	Outcome(s)	Duration	Main findings	Type and dose of omega-3 fatty acid, mg/day
Ninio et al[8], 2008	Australia	A randomized, double-blind, parallel trial	Fifty overweight, sedentary adults with risk factors for coronary disease	DHA-rich fish oil 6 g/day (providing 1.56 g DHA + 0.36 g EPA) (n = 23)	Sunflower seed oil (placebo) (n = 27)	Resting heart rate, heart rate during submaximal exercise, and HRV parameters (high-frequency and low-frequency power)	12 weeks	DHA-rich fish oil significantly increased high-frequency power (indicative of enhanced parasympathetic/vagal tone). Resting heart rate and heart rate during exercise were significantly reduced compared with placebo	DHA-rich fish oil: Approximately 1560 mg DHA/day and approximately 360 mg EPA/day (total 6 g fish oil)
Sjoberg et al[9], 2009	Australia	A randomized, double-blind, placebo-controlled, parallel dose-response supplementation trial	Thirty-four overweight or obese adults	DHA-rich fish oil (n = 17)	Placebo (6 g/day of sunola oil) (n = 17)	HRV, specifically the low frequency, high frequency, and (LF/HF) ratio	12 weeks	The LF/HF ratio of HRV decreased with increasing doses of fish oil. The changes in these biomarkers may reflect that fish oil-induced improvements in arterial function and cardiac autonomic regulation	The 2, 4, and 6 g/day doses of fish oil provided 0.52, 1.04, and 1.56 g DHA/day, respectively
Baumann et al[10], 2018	Germany	A parallel randomized interventional control trial	20 obese children/adolescents (BMI > 95th percentile)	Daily omega-3 fatty acid supplementation (fish oil capsules)	Same obese subjects before supplementation	Time-domain HRV parameters (SDNN, RMSSD, pNN50)	At least 3 months, average of approximately 214 days (≈ 7 months) between baseline and follow-up ECG in the obese group	Omega-3 fatty acid supplementation may be used for cardiovascular prophylaxis in obese children and adolescents	Fish oil capsules containing at least 400 mg EPA and 120 mg DHA per day
Ibrahim et al[11], 2025	Egypt	A parallel randomized interventional control trial	30 overweight and obese children	Omega-3 supplementation	Same obese children before supplementation	HRV differences in RMSSD, SDNN, pNN50%, and lipid profiles	3 months	Significant increases in HRV measures (RMSSD, SDNN, pNN50) in the omega-3 group compared to controls. Significant improvements in lipid profile: Decreased triglycerides and increased HDL in the omega-3 group	400 mg EPA and 200 mg DHA daily for 3 months was taken (the ratio of EPA to DHA to 2:1)

BMI: Body mass index; DHA: Docosahexaenoic acid; EPA: Eicosapentaenoic acid; HDL: High-density lipoprotein; HRV: Heart rate variability; LF/HF ratio: Low-to-high-frequency ratio; pNN50%: Percentage of successive normal-to-normal intervals differing by more than 50 milliseconds; RMSSD: Root mean square of successive differences; SDNN: Standard deviation of normal-to-normal intervals.

Meta-analysis

Heart rate variability parameters: This part of the meta-analysis included data from two studies[10,11], involving 50 participants in the omega-3 group and 50 in the control group.

RMSSD: A meta-analysis of RMSSD demonstrated a significant improvement in parasympathetic activity following omega-3 supplementation. The forest plot showed a statistically significant increase in RMSSD compared to the baseline with a mean difference (pre-post) of -11.69 (95%CI: -18.50 to -4.87; P = 0.0008). The random effects model (I² = 0%, τ² = 0.00, χ² = 0.88, P = 0.35), which denoted a low heterogeneity (Figure 3A).

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).

SDNN: A meta-analysis of SDNN revealed a significant increase in the omega-3 group compared to the baseline, with a pooled mean difference (pre-post) of -26.13 (95%CI: -35.84 to -16.42, P < 0.00001). Heterogeneity was low (I² = 0%, τ² = 0.00, χ² = 0.55, P = 0.46), Figure 3B.

pNN50%: A meta-analysis of pNN50% demonstrated a statistically significant improvement in parasympathetic activity following omega-3 supplementation. The pooled mean difference favored the omega-3 group with a mean difference (pre-post) of -9.45 (95%CI: -14.27 to -4.64, P = 0.0001). Heterogeneity across studies was negligible (I² = 0%, τ² = 0.00, χ² = 0.20, P = 0.65), indicating consistency of effect across trials (Figure 3C).

This finding complements the improvements observed in RMSSD, SDNN, and pNN50%, collectively reinforcing the beneficial effect of omega-3 supplementation on vagal-mediated cardiac modulation in overweight and obese individuals.

Frequency domain parameters

This part of the meta-analysis included two studies[8,9], with 40 individuals in the omega-3 group and 44 individuals in the control group. Analysis of HF Power, LF Power, and LF/HF ratio showed no significant difference between groups, with mean differences of -0.18 (95%CI: -0.61 to 0.25, P = 0.41), -4.59 (95%CI: -23.26 to 14.08, P = 0.63), and 0.95 (95%CI: -27.13 to 29.03, P = 0.95), respectively. HF and LF power analyses showed no heterogeneity (I² = 0%, τ² = 0.00, χ² = 0.04, P = 0.85) and (I² = 64%, τ² = 127.15, χ² = 2.77, P = 0.10), respectively (Figure 4). A summary of HRV metric changes is provided in Figure 5.

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.

Sensitivity/subgroup

Subgroup analyses by comparator type and sensitivity analyses excluding pilot trials were pre-specified but could not be conducted due to only three RCTs. Publication bias was not assessed because of the small number of articles.

DISCUSSION

Principal findings

This systematic review and meta-analysis demonstrate that omega-3 supplementation significantly improves time-domain HRV measures (SDNN, RMSSD, and pNN50%) and lowers resting heart rate in overweight and obese individuals. These changes suggest an enhanced parasympathetic (vagal) tone and improved autonomic balance. The effects of omega-3 supplementation on the frequency-domain measures were mixed, with little overall evidence of improvement. Omega-3 PUFAs, therefore, show promise as a safe, low-cost intervention to enhance cardiac autonomic regulation in obesity.

Mechanistic considerations

Omega-3 fatty acids can affect cardiac autonomic function through incorporation into cell membranes, altering ion channel function and membrane fluidity, thereby stabilizing cardiac electrophysiology. They may suppress sympathetic activity and enhance vagal tone by modulating sodium and calcium channel currents and reducing inflammation. The proposed mechanisms are illustrated in Figure 6. Clinically, fish-oil intake is linked to lower resting heart rate and improved HRV. In the dose-response trial, reductions in the LF/HF ratio were accompanied by increased arterial compliance and higher erythrocyte eicosapentaenoic acid (EPA) levels, suggesting vascular and anti-inflammatory effects as mediators. Improved lipid profiles observed in adolescents may further support autonomic regulation.

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.

Comparison with previous literature

Our results align with previous meta-analyses showing that omega-3 supplementation modestly reduces resting heart rate and may enhance parasympathetic modulation. However, earlier reviews often focused on post-myocardial infarction or dialysis patients. By concentrating on overweight and obese populations, this review extends the evidence base and quantifies improvements in time-domain HRV measures. The inconsistent frequency-domain findings mirror mixed results across the broader literature.

Supplementing with omega-3 fatty acids, specifically docosahexaenoic acid (DHA)-rich fish oil, showed positive benefits on cardiac autonomic function in the four trials. DHA supplementation in overweight and obese adults improved HRV indices and arterial compliance in a dose-dependent manner. It also improved heart rate responses and recovery after exercise. Similarly, omega-3 fatty acids supplementation significantly enhanced HRV measures in obese children and adolescents, normalizing them toward levels seen in healthy controls, indicating better autonomic balance and vagal tone. Collectively, these data support the possible benefit of omega-3 fatty acids in enhancing cardiovascular autonomic regulation and reducing cardiovascular risk in obese and overweight populations[8-11].

Strengths of the study

Strengths of this study include an extensive search across several databases, a prospectively registered protocol, rigorous risk of bias assessment, and inclusion of both pediatric and adult populations.

Study limitations

Limitations of this study include the small number of eligible studies, modest sample sizes, and heterogeneity in dosing, duration, and HRV measurement methods. One pre-post study lacked randomization, and the short intervention durations preclude assessment of long-term effects.

Clinical and research implications

Given its favorable safety profile, omega-3 supplementation could be considered an adjunct strategy to improve autonomic function in overweight and obese individuals. Doses ≥ 1 g/day of combined DHA + EPA and at least three months of treatment may be needed to observe meaningful changes. Future research should include larger, multicenter RCTs with longer follow-up, explore dose-response relationships and EPA: DHA ratios, standardize HRV assessment, and investigate mechanistic pathways. Combining omega-3 supplementation with lifestyle interventions, such as exercise, may yield synergistic benefits.

CONCLUSION

This systematic review and meta-analysis provide evidence regarding the positive effects of omega-3 fatty acid supplementation on HRV indices, specifically the time-domain measures, in obese and overweight populations.