Omega-3 for an Irreducible Immune System

The secret to a robust immune system is kept in a capsule – a fish oil capsule. It was in 1932 that scientists discovered the potential of Omega-3s – in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) – as natural anti-inflammatories. Since then, research into the benefits of Omega-3s for the immune defences has never stopped, and today we know that these precious fats of marine origin are key allies for an immune response that, when kept under control, is truly useful to the body.

Why does inflammation need to be kept under control? Because, as in many other circumstances, "too much of a good thing" can backfire. And when inflammation becomes chronic, the whole body pays the price.

Indeed, inflammation is a true double-edged sword. If excessive, it can damage tissues and organs. You may remember hearing a lot about it during the Covid-19 pandemic: an abnormal immune response, characterised by strong inflammation, can lead to results opposite to those desired, hindering recovery.

Nutrients with immunomodulating properties, such as Omega-3s and vitamin D, help prevent the situation from getting out of hand. But let's take it step by step: what exactly are the immune response and inflammation?

Inflammation and the immune system

You can picture your body as a fortress with two main lines of defence: inflammation and specific immunity.

Inflammation is like a general alarm that goes off when there is an aggression, which can be:

• a trauma (such as a fall);
• a chemical aggression (such as an overly harsh detergent);
• a microbial invasion (such as an infection).

As far back as the 1st century AD, a Roman physician named Aulus Cornelius Celsus described the 4 classic signs of inflammation in the De Artibus. Today we recognise 5:

• redness (in Latin rubor): the area turns red;
• heat (in Latin calor): the area becomes warm;
• swelling (in Latin tumor): the area swells;
• pain (in Latin dolor): the area hurts;
• loss of function (in Latin functio laesa): the inflamed part "works" less well.

If inflammation is like a general alarm, specific immunity is instead a much more targeted response. There are two types:

• humoral (or antibody-mediated) immunity: produces antibodies to fight invaders;
• cellular immunity: uses special cells to attack enemies directly.

In the event of inflammation or an immune response, your body produces molecules called interleukins and eicosanoids, "messengers" that tell your body an inflammation is under way. This is exactly where Omega-3 fatty acids come into action, reducing the production of pro-inflammatory eicosanoids and carrying out an anti-inflammatory action.

The anti-inflammatory role of Omega-3s

Clinical studies have highlighted the ability of fish oil supplements, rich in Omega-3s, to keep inflammation under control.

In addition, a study published in 2005 in the Journal of Experimental Medicine shed light on a unique property of essential fatty acids: that of being converted by enzymes present in human cells into resolvins, molecules capable of reducing inflammatory processes. Not only that: DHA also gives rise to docosatrienes, which act as powerful anti-inflammatories and immune system regulators.

In light of all these discoveries, Omega-3s are today often used also in the management of autoimmune diseases, so called because at their root lies an abnormal response of the immune system that attacks the body itself. An example? Certain rheumatic diseases.

Omega-3s and rheumatic diseases

Autoimmune diseases are like fires constantly burning in the body. Rheumatoid arthritis, psoriatic arthritis, spondylitis, systemic lupus erythematosus, scleroderma: what do all these conditions have in common? A state of chronic inflammation involving the whole body.

With their anti-inflammatory power, Omega-3s emerge as perfect allies to help tame them.

The first signs of their benefits for the proper functioning of the immune system date back to the 1970s, when a low incidence of autoimmune and inflammatory diseases was observed in Inuit populations who consumed large amounts of fish rich in Omega-3s.

The benefits of fatty acids for the immune system were then summarised and formalised by Artemis Simopoulos, president of the Center for Genetics, Nutrition and Health in Washington, in an article published in 2002 in the Journal of the American College of Nutrition.

After carefully analysing several conditions (atherosclerosis, obesity, depression, rheumatoid arthritis, inflammatory bowel diseases, asthma), Artemis Simopoulos concluded that treatment with fish oil could lessen the severity of symptoms and also reduce the need for anti-inflammatory drugs.

Subsequently, two researchers, Trevor Mori and Lawrie Beilin, took stock of the beneficial effects of Omega-3s against inflammation. In a paper published in Current Atherosclerosis Reports they examined a wide range of clinical and laboratory studies.

The conclusion? Fish oil can reduce the production of molecules that cause inflammation. This means that fatty acids could be a valuable aid in treating inflammatory and autoimmune diseases.

But that's not all: the two researchers highlighted that EPA and DHA (the main biologically active Omega-3s) are also effective in improving the health of the blood vessel wall and can therefore help protect us from cardiovascular disease.

Omega-3s for your immune defences

In 2003, a study published in The American Journal of Clinical Nutrition provided further evidence of the benefits of Omega-3s: in healthy people who consumed fish oil for just one month, a reduction in inflammatory molecules was observed.

Over the years, scientists have continued to study Omega-3s, and all the research has confirmed that taking essential fatty acids is safe and is like having an ally that fights every day to support your immune system.

Among the most recent publications on the subject is a review of the scientific literature published in Molecular Nutrition & Food Research at the end of March 2025. Its authors, led by Mahmut Bodur (Ankara University, Turkey) and Birsen Yilmaz (Tata Institute of Fundamental Research, Hyderabad, India), reaffirm the role of EPA and DHA in promoting the transition from a pro-inflammatory to an anti-inflammatory state that favours the switching off of ongoing inflammatory processes.

In this way, Omega-3s help manage inflammation, restore tissue balance and support immune health.

"Their effects extend to several immune cells, including B lymphocytes, T lymphocytes, macrophages and neutrophils, contributing to the prevention of immune dysfunction and chronic inflammatory conditions."

Omega-3s and the immune system: what we know today

Bodur, Yilmaz and colleagues explain that Omega-3s – both those obtained from food and those taken as food supplements – are incorporated into the cell membranes of immune system cells. This incorporation:

• increases membrane fluidity;
• improves communication between immune cells;
• modulates the activity of molecules that regulate gene expression (transcription factors), such as the well-known NF-kB.

Increased membrane fluidity allows the reorganisation of the proteins within them and of specific areas of the membranes, resulting in an improved ability of cells to communicate and respond promptly to infections, and a moderation of the inflammatory response, with one important detail: this moderation is selective and does not involve general immune suppression.

Looking more closely at the effects of Omega-3s on the various immune cells, the authors of the review stress that they:

• enhance the ability of macrophages and neutrophils to engulf (phagocytose) pathogens and promote their migration, reducing the production of pro-inflammatory chemicals and promoting tissue clearance;
• modulate the activation of T lymphocytes, limiting their proliferation and guiding the development of regulatory T cells (Tregs), essential to avoid disproportionate immune responses or autoimmune reactions. They also promote a balance between responses involving different lymphocyte subsets (Th1 and Th2) and regulate the production of antibodies and of the cytokine IL-2.

Finally, at the molecular level, EPA and DHA reduce the production of pro-inflammatory cytokines (such as the cytokines TNF, IL-6 and IL-18) and of reactive oxygen species. They also act as precursors of fats that help bring inflammation to an end (Specialized Pro-resolving Mediators, or SPMs), which include the resolvins and protectins already mentioned.

These compounds play a key role in the active switching off of inflammation and in the restoration of tissue balance. In addition, through the activation of nuclear receptors such as PPAR-γ and the inhibition of signalling pathways such as NF-κB, Omega-3s indirectly influence gene expression, with protective effects at the cardiovascular level (with prevention of atherosclerosis), neurological level (with support for synaptic plasticity and neuroprotection) and oncological level (with modulation of key factors such as COX-2 and caspases).

Omega-3s: "fine" regulators for your immune defences

Current knowledge therefore allows us to regard Omega-3s as sophisticated, fine regulators capable of balancing the defences against infections and protection from the damage of chronic inflammation.

That is why you shouldn't go without them, not only if you need to manage conditions involving immune reactions, but also during those times of the year or in those circumstances when your defences are more likely to be triggered by external threats that set off an inflammatory response, such as viruses and bacteria.

References

Bodur M, Yilmaz B, Ağagündüz D, Ozogul Y. Immunomodulatory Effects of Omega-3 Fatty Acids: Mechanistic Insights and Health Implications. Mol Nutr Food Res. 2025 May;69(10):e202400752. doi: 10.1002/mnfr.202400752