Omega-3 and oxidative stress: how they modify endogenous antioxidants

The properties of Omega 3 against oxidative stress are emerging ever more clearly. Among the mechanisms identified is the regulation of endogenous antioxidants. For now the effect of supplements does not appear to be single and universal: find out when and how they might regulate the enzymes that neutralize reactive oxygen species!

Oxidative stress is one of the main factors underlying the development of numerous chronic diseases. Yet the production of reactive oxygen species (ROS, Reactive Oxygen Species) is a natural consequence of cellular metabolism. It is no coincidence that all organisms living in the presence of oxygen (humans included) are equipped with equally natural defense weapons that allow them to cope with this production.

In fact, problems arise when the balance is lost between the amount of ROS and other oxidizing molecules (reactive nitrogen species, or RNS, Reactive Nitrogen Species) and the capacity to neutralize their dangerousness. And, unfortunately, there is no shortage of factors capable of upsetting this balance; it is enough to cite two to understand the precariousness of the situation: air pollution and tobacco smoke.

Diet too can be a source of oxidants. On the other hand, many factors of dietary origin are considered molecules with antioxidant effects. Among the latter are also the polyunsaturated fats Omega 3, associated by numerous studies with not only anti-inflammatory but also antioxidant effects.

Their actions would in fact also include the ability to modulate endogenous antioxidants, that is, the substances produced by the human body to defend itself against oxidative stress. Let's find out where research on the subject stands, starting by answering a fundamental question: why are ROS so dangerous?

The reasons why oxidative stress damages health

The reason why ROS (free radicals and non-radical forms) must be neutralized is their extremely reactive nature. Indeed, free radicals are molecules containing one or more unpaired electrons that seek to react with other molecules; when two of these molecules share their unpaired electrons, non-radical forms are created. But both these types of ROS can damage the cell, altering the functioning of its components.

In particular, ROS can:

• modify DNA in many different ways;
• damage carbohydrates;
• peroxidize lipids and compromise the structure of cell membranes, inactivating the receptors and enzymes associated with them and increasing tissue permeability;
• fragment proteins, alter their electrical charge, cause them to bind to one another and oxidize specific amino acids, increasing the susceptibility of the entire protein to degradation;
• induce the expression of genes involved in the inflammatory response, such as the one encoding the pro-inflammatory transcription factor NF-kB.

Given these effects, the regulation of the body's oxidation-reduction (“redox”) state is critical for cell survival, cell proliferation and organ function.

An overload of oxidizing species leads precisely to oxidative stress, a metabolic condition that involves cells, organs and the entire organism, playing an important role in the development of cardiovascular diseases, diabetes, cancer and several other conditions.

Endogenous antioxidants: internal defenders

Fortunately, there is no shortage of antioxidants able to neutralize reactive oxygen species and to promote the body's redox balance.

There are two known types:

• Non-enzymatic antioxidants: small compounds such as vitamin C, vitamin E, beta-carotene, uric acid and GSH (glutathione).
• Enzymatic antioxidants: enzymes that neutralize free radicals. These are endogenous antioxidants produced by the body, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), heme oxygenase 1 (HO-1), thioredoxins (TRX), peroxiredoxins (PRX) and glutaredoxins.

Since the main reactive oxygen species in cells is the superoxide ion, SOD is considered particularly important for the health of the cell.

Omega 3 and endogenous antioxidants

The possible role of Omega 3 as regulators of endogenous antioxidants has emerged from several studies.

In 2012, for example, a group of researchers from Hannover, Germany, published in Nutrition & Metabolism data indicating that the daily intake of a dose of fish oil containing 1.14 g of DHA (docosahexaenoic acid) and 1.56 g of EPA (eicosapentaenoic acid), the two biologically active Omega 3, increases the expression of antioxidant enzymes such as catalase.

In 2019 a research group sought to take stock of the situation in a systematic review with meta-analysis published in the journal Pharmacological Research.

The meta-analysis was conducted on data from 39 studies, for a total of 2,875 participants. It revealed a reduction in malondialdehyde (MDA), particularly significant in cases of diabetes or metabolic disorders.

Furthermore, Heshmati and colleagues detected the ability of Omega 3 to significantly increase total antioxidant capacity and GPx activity. The effects on GSH, SOD and catalase did not, however, appear significant.

Omega 3 can be considered factors capable of strengthening antioxidant defenses against ROS.

Regarding the effect on SOD, the authors emphasize that it is a statistically non-significant increase, but noteworthy from a clinical standpoint. In fact, fish oil significantly increased SOD activity in diabetic patients or those with metabolic problems.

As for GPx, the effect seems to be significant only in the absence of metabolic problems, perhaps due to different baseline levels. Moreover, the effect of Omega 3 supplementation would be greater at doses below 2,000 mg per day.

The most recent data

More recent data support the conclusions of this meta-analysis. Particularly interesting is a study on a mouse model conducted in Saudi Arabia and published in 2026 in the Italian Journal of Food Science.

The aim of the study was to evaluate in vivo the antioxidant properties of EPA and DHA and the possibility of taking them to reduce oxidative stress induced by exposure to cadmium.

For this purpose the mice were divided into four groups:

• control group;
• group treated with Omega 3 without exposure to cadmium;
• group exposed to cadmium;
• group exposed to cadmium and treated with Omega 3.

In this last group a significant increase was observed in total antioxidant capacity and in several antioxidants, including glutathione, SOD, GPx and catalase, together with a reduction in markers of oxidative stress such as MDA.

Specific effects for population subgroups

Other research seems to confirm also the possibility that the effects of Omega 3 on antioxidant enzymes depend on specific characteristics of those who take them.

A pilot study published in 2025 in Nutrients associated the intake of EPA and DHA supplements with a temporary reduction in GPx and a decline in SOD only in athletes and not in amateur sportspeople.

Physical activity is one of the possible factors triggering the production of reactive oxygen species. If kept at moderate levels, this production can mediate desirable physiological responses; conversely, excessive production of ROS during intense activity can damage muscles.

The study participants, all runners, took 9 grams of Omega 3 per day for 30 days. SOD, CAT and GPx levels were measured before and after a running session followed by sprints.

According to the authors, the effects observed on SOD and GPx in athletes could reflect an altered redox regulation and only further studies will be able to clarify their physiological and functional consequences.

Omega 3 against oxidative stress

The data available today therefore seem to point in one direction: Omega 3 supplementation can modulate the body's antioxidant defenses. Their effects, however, could depend on specific characteristics of those who take them, such as health status and training levels.

Keep reading the Omegor Blog to find out what new research on the subject will reveal.

Bibliographic references

• Al-Zharani M. et al. (2026). Italian Journal of Food Science, 38(1), 270-285. DOI: 10.15586/ijfs.v38i1.3243
• Birben E. et al. (2012). World Allergy Organization Journal, 5(1), 9-19. DOI: 10.1097/WOX.0b013e3182439613
• Heshmati J. et al. (2019). Pharmacological Research, 149:104462. DOI: 10.1016/j.phrs.2019.104462
• Martinšek B. et al. (2025). Nutrients, 17(18):2985. DOI: 10.3390/nu17182985