Omega-3s: Beyond Fish Oil

written by Austin Perlmutter, MD Chief Science Officer | February 16, 2026
Fish oil capsules with omega 3 and vitamin D in a glass bottle on wooden texture, healthy diet concept, close up shot.

Think you know all there is to know about fish oil? That all Omega-3 supplements are mostly alike? The following article from my friends at Big Bold Health is guaranteed to provide you with new insights. And remember, you can try my preferred fish oil—Big Bold Health’s Omega-3 Rejuvenate—for 20% off when you use code HOFFMAN20.

—Dr. Ronald Hoffman

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Omega-3 fats have emerged as central dietary molecules capable of impacting health and especially the immune system. Within this family, there are three that research demonstrates are highly significant to human health: alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).

While our bodies can technically convert ALA into EPA and then DHA, the conversion is quite inefficient. Since ALA is the primary omega-3 fat in plant-based sources, consuming a plant-based diet alone means a low chance of achieving higher levels of EPA and DHA, which are the best-studied forms associated with positive health outcomes.

What Major Organizations Recommend

A host of large organizations, on review of the available data, have recommended optimizing diet for higher intake of omega-3 fats. For example, the American Heart Association recommends eating a variety of fish — preferably oily fish rich in omega-3s — at least twice weekly. Two servings of oily fish (think salmon, anchovies, sardines etc) provide roughly 500 mg of EPA + DHA, about 2 grams per week. This is also a target supported by reviews published in journals like JAMA and by guidance from Harvard researchers.

Why this level? Because consistent intake of EPA and DHA has been associated with measurable biological effects:

  1. In one study, 1 gram per day of omega-3s for one year slowed biological aging markers.
  2. A low-fat diet combined with 1.23 grams of EPA + DHA daily for 24 weeks showed multiple beneficial effects on markers of immune function.

Findings like the above reinforce a key theme in omega-3 research: consistent intake appears to support healthier immune signaling and cellular resilience.

Omega-3s and Immune Resolution

One of the most exciting areas of research around omega-3 fats takes the already compelling data one step further to explore compounds called pro-resolving mediators (PRMs), also referred to as specialized pro-resolving mediators (SPMs).

Just as ALA converts (inefficiently) into EPA and DHA, EPA and DHA themselves can be converted into resolving mediators, and rather than simply “boosting” immunity, resolving mediators are involved in helping the body resolve an immune response once it has been activated.

Emerging research suggests resolving mediators may:

  1. Help quell an overactive immune response
  2. Support return to immune balance
  3. Positively influence multiple biological systems tethered to immune health

Resolving mediators are naturally present in minimally processed fish oils but are also produced within our cells from omega-3 fatty acids.

Research shows that supplementation with fish oil rich in resolving mediators can elevate levels in humans. However, these compounds are sensitive — and that brings us to an often-overlooked issue around fish oil: processing.

The Problem with Industrial Fish Oil Production

Industrial fish oil production typically involves:

  1. Chemical solvents
  2. Acid treatment
  3. Bleaching steps
  4. High-temperature gas processing

Temperatures during refining can reach 270°C (518°F). At these levels, significant oxidative reactions and chemical transformations occur. Refining may remove certain contaminants, but in the process it alters natural molecular structures and can potentially reduce delicate compounds like resolving mediators while stripping out vitamins like A and D.

This highlights an important point: not all omega-3 products are equivalent.

Natural Forms, Bioavailability, and Fat-Soluble Nutrients

Omega-3 fatty acids found in sources like fish are naturally present in triglyceride form. Some research suggests triglyceride forms may have higher bioavailability compared to certain processed ester forms. But concentrated fish oils that claim high concentrations of DHA and EPA? They’re almost all in ester form.

Minimally processed fish oils may also contain:

  1. Natural vitamins A and D, both of which play important roles in immune regulation
  2. Unique fatty acids such as eicosenoic acid, which may support immune resolution
  3. Naturally occurring resolving mediators

These compounds work together as part of a biological matrix that is altered by excessive processing.

Why Source and Processing Matter

If choosing supplementation, consider the source and the processing.

For example, fish oils sourced from wild-caught Alaskan salmon and cod liver, processed rapidly after harvest and handled using lower-temperature pharmaceutical-grade methods may help preserve natural nutrient integrity.

Line-caught fishing methods reduce bycatch, while certifications such as: Marine Stewardship Council (MSC) and Alaskan Responsible Fish Management (RFM) help ensure sustainability and ecosystem responsibility. Additionally, local processing infrastructure and careful handling without excessive chemical treatment can make a meaningful difference in final product composition.