The History Behind Omega-3 vs. Statins

Omega-3 polyunsaturated fatty acids (PUFA) are considered essential because our body cannot synthesize them. The two most common long-chain omega-3 acids are called eicosapentaenoic acid (EPA, 20:5, ω 3) and docosahexaenoic acid (DHA, 22:6, ω 3). In fact, numerous studies involving the function of omega-3 PUFA on conditions such as neurological diseases, inflammatory derangements, and cardiometabolic issues have been published. However, despite EPA and DHA being commonly associated with anti-inflammatory properties and beneficial effects, they are now showing controversial commentaries.

Omega-3 History

Indeed, the beneficial effect of omega-3 PUFAs arose in the 1970s, when an association of increased fish consumption of Inuits in Greenland contributed to lower myocardial infarction rates compared with Western countries. Nowadays, they are about 250 clinical trials involving the ingestion or supplementation of omega-3 PUFAs and diseases such as metabolic syndrome, dyslipidemia, inflammation, hypertension, parenteral nutrition in the critically ill patient, and cardiovascular disease.

As mentioned before, the research history is not currently recommending the supplementation of omega-3 PUFAs as part of the treatment to reduce the risk of secondary events of CHD. In a previous report published by de Longeri et al., a punctual glimpse of the history of randomized controlled trials (RCTs) involving omega-3 and CVD revealed important information.

This publication mentioned that current RCTs are not recommending Omega-3 supplementation because patients are being treated with statins. Indeed, the cornerstone of CVD’s treatment is statin use to reduce the risk and prevent CVD, CHD, and secondary events. However, these authors ensure that current (2005) RCTs comparing the effectiveness of omega-3 v. statins are not long enough. They did not consider the baseline omega-3 status and that most of these patients are already taking statins.

Consequently, the authors recommend that all of the clinical trials that do not support the use of omega-3 polyunsaturated fatty acids as a protective agent against CVD should be considered individually with precaution. As well as looking for limitations in each trial, such as a short follow-up, small sample size, and heterogeneity of the considered population.

Also, we have to consider the publicity that large trials get and the American Heart Association guidelines and the time period these RCTs were published. For example, the DART and GISSI studies were published between 1980 and 19990, during the pre-statin period. Furthermore, these two studies supported the use of omega-3 fatty acids. The Lyon Diet Heart Study recommended the supplementation of omega-3 Alpha-linoleic acid, as a precursor of EPA and DHA, and linked it to reducing CHD complications and mortality.

Shortly after the publication of these studies, in 2002, the AHA stated that the consumption of fish twice a week and 1g of EPA+DHA are preventive recommendations to reduce CVD risk. Therefore, in recent studies (2005), patients have higher baseline omega-3 dietary and blood measurements, and they are taking statins in contrast to the first RCTs made with an omega-3 deficient population.

Other applications of Omega-3 Fatty Acids

Several review studies still suggest that, despite the aforementioned information, omega-3 supplementation and higher fish consumption are associated with reduced triglyceride levels and lessen heart susceptibility to arrhythmias.

Inflammation and Omega-3

Also, the supplementation of omega-3 fatty acids has effectively reduced muscular rigidity and neurological symptoms of patients diagnosed with Parkinson’s disease. In fact, the underlying function of omega-3 relies on its ability to increase peroxisome proliferation activator receptor gamma (PPAR-y) gene activity. Consequently, this activation may cause an improvement in lipid and insulin metabolism. This adds to the fact that omega-3 is a potent neural protective agent.

Besides this, DHA is the precursor of Neuroprotectin D1 (NPD1), a signaling molecule that protects neurons by modulating genes’ actions in the retina and brain. In Alzheimer’s disease, neuroinflammatory damage causes deleterious effects on the dendritic spines, affecting electrical signaling. NPD1 can downregulate the inflammatory response and promote cell survival. Also, NPD1 can reduce the size of stroke damage.

In the fetus, omega-3 fatty acids are needed for the baby’s nervous system development. Besides this, in maternal milk omega-3, fatty acids depend on the amount of the mother’s dietary intake of these compounds. An appropriate amount of omega-3 PUFA is associated with good visual development, higher birth weight, and a reduction in postpartum depression.

After reviewing this information, something is clear, omega-3 fatty acids are linked with better health outcomes. It has been said before, the underlying action of why omega-3 can promote these effects has to be studied more deeply. However, the theory lies in the fact that omega-3 is an inflammation promoter. It contains proinflammatory leukotrienes that are used as a substrate by COX enzymes. Luckily, EPA and DHA have shallow proinflammatory action, and instead of promoting an exacerbated inflammatory response, they cause a weak response or “anti-inflammatory” effect. – Ana Paola Rodríguez Arciniega, MS

References

Tiwari, Archana et al. “Therapeutic attributes and applied aspects of biological macromolecules (polypeptides, fucoxanthin, sterols, fatty acids, polysaccharides, and polyphenols) from diatoms – A review.” International journal of biological macromolecules vol. 171 (2021): 398-413. doi:10.1016/j.ijbiomac.2020.12.219

de Lorgeril, M., Salen, P., Defaye, P. et al. Recent findings on the health effects of omega-3 fatty acids and statins, and their interactions: do statins inhibit omega-3?. BMC Med 11, 5 (2013). doi.org/10.1186/1741-7015-11-5

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