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Omega-3s & Heart Rate Variability

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A recent meta-analysis published in the World Journal of Clinical Pediatrics examined the link between omega-3 fatty acid supplementation and heart rate variability (HRV) among children and adults with overweight or obesity. HRV has gained acceptance as a non-invasive marker for autonomic nervous system (ANS) balance, or the interaction between parasympathetic and sympathetic activity, which is known to be dysregulated with obesity, suspected to be caused by hypothalamic inflammation, at least in part. Omega-3 fatty acids may favorably modulate ANS activity, but there are few clinical trials that have evaluated the effects of supplementation.

Four randomized, controlled trials (parallel or crossover) with a total of 134 participants were included in this meta-analysis; two compared pre- vs. post-omega-3 supplementation, and the remaining two compared omega-3 supplementation with placebo. The primary outcomes of the trials were time-domain HRV measures (RMSSD, SDNN, and pNN50%), with multiple secondary outcomes including resting heart rate and frequency-domain measures.

Omega-3 supplementation significantly improved all three time-domain HRV measures and reduced resting heart rate. SDNN, for example, increased by a mean of 26.13 ms, not only a significant finding but a clinically meaningful one. SDNN is generally decreased among people with obesity or overweight, and in one of the studies included in the meta-analysis, there was nearly a doubling in HRV compared to baseline. For context, in a study of 433 participants with heart failure, a decrease of 41.2 ms in SDNN was associated with a 62% higher all-cause mortality risk. In that study, the annual mortality for participants with an SDNN of >100 was 5.5%, compared to a mortality rate of 12.7% for an SDNN between 50-100 ms, and 51.4% at < 50ms. Additionally, in a meta-analysis of observational studies published in the Journal of Electrocardiology, multiple markers of HRV were associated with cardiovascular mortality post-myocardial infarction, with SDNN having the best predictive power (SDNN has also been found to be the best predictor of the HRV measures for mortality among people with heart failure). Thus, an increase of 26.13 ms could potentially meaningfully shift the risk due to ANS imbalance, at least among people with overweight/obesity, and at the very least, it points to a shift in the right direction.

It’s not clear if the improvement in HRV observed among people with overweight or obesity with omega-3 supplementation would also be found in other populations. A meta-analysis of 51 randomized and controlled trials published in the European Journal of Clinical Nutrition found a significant reduction in heart rate with fish oil supplementation, particularly DHA, again pointing to improved autonomic function. At least some of the purported mechanisms driving an ANS imbalance involve inflammatory pathways, including TNF-α and activation of the NF-κB/IKK-β pathway, providing a plausible mechanism of action for EPA/DHA, at least among people with conditions linked to impairment of the inflammatory pathway.

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