Omega-3 Fatty Acids and Cardiovascular Health

The trial was launched to explore the potential benefits of omega-3 fatty acids on cardiovascular health. After nearly three years of enrolling participants, the trial began in June 2017 and was stopped early in January 2020 due to futility, meaning that it did not yield positive results. These findings, published in the Journal of the American Medical Association, sparked widespread media coverage. For example, a Healthline article dated November 19, 2020, titled "Study Finds Fish Oil May Not Help Your Heart," presented the trial's conclusions out of context and without supporting evidence, leading to the erroneous belief that fish oils are ineffective for heart health.

While this article cannot delve deeply into the STRENGTH Clinical Trial or the science of omega-3 fatty acids, it can highlight some critical aspects that were overlooked.

The Healthline article stated, "The study found that a high dose of omega-3 fatty acids did not reduce people’s chances of experiencing a major cardiovascular event." However, the participants in the trial were not average individuals. They were statin-treated patients with high cardiovascular risk, hypertriglyceridemia, and low levels of high-density lipoprotein cholesterol (HDL-C). These criteria are crucial for understanding the therapeutic potential of omega-3 fatty acids and other natural substances that provide protection against chronic diseases.

To analyse the efficacy of any biological fuel, including omega-3 CA (carboxylic acid), we must consider five key parameters:

1. Chemical format and bioavailability, considering individual absorption, metabolism, and elimination rates
2. Presence or absence of necessary co-factors for optimal biochemistry
3. Availability of cellular energy for actions involving the substance (e.g., mitochondrial function)
4. Biological quality and functioning of the tissue on which the substance operates
5. Functioning of supportive organs or systems for acquiring, processing, transporting, delivering, and utilising the substance

The STRENGTH Clinical Trial was a double-blind, randomised, mmulticentre trial with 13 078 patients, comparing a daily supplementation of 4 g of omega-3 CA (Epanova by AstraZeneca) with corn oil in statin-treated participants with high cardiovascular risk, hypertriglyceridemia, and low HDL-C. The primary endpoint was a composite of major adverse cardiovascular events: cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary artery revascularisation, and hospitalisation for unstable angina. The trial was stopped early due to a low chance of clinical benefit and a statistically significant increase in atrial fibrillation in the omega-3 CA arm compared with the corn oil arm (2.2% vs. 1.3%).

Now, consider the five parameters above. These patients’ cardiovascular systems were severely compromised before the trial began. Using the analogy of a 5-litre bucket of water to extinguish a house fire, the omega-3 CA might have been too little, too late. Expecting it to put out the 'fire' in these high-risk patients is unrealistic.

The myocardium requires a steady supply of ATP, primarily derived from the mitochondrial catabolism of carbohydrates and fatty acids. PPARs (Peroxisome Proliferator-Activated Receptors) regulate metabolic pathways, with omega-3 fatty acids serving as relevant endogenous ligands. High-risk cardiovascular patients have various degrees of cardiomyopathy, where the PPAR/PGC-1α system is deactivated, leading to a decreased ability to utilise long-chain fatty acids like omega-3 despite increased supplementation. The increased EPA levels observed in the trial participants were not effectively utilised due to this dysfunction.

Dismissing the benefits of fish oils based on this trial is like claiming water cannot quench fire because a small bucket couldn't save a burning house. Omega-3 fatty acids have demonstrated beneficial effects on various cardiovascular risk factors. Concentrate on prevention, and health will take care of itself.