Omega-3 fatty acids from microalgae

Natural omega-3 oil from Schizochytrium sp. algae containing 150 mg EPA and 100 mg DHA in a single capsule with a vegan composition

A formulation with a higher ratio of EPA to DHA from microalgae was chosen on the basis of its demonstrated health effects. EPA helps reduce inflammatory reactions, supports heart function and may contribute to a better mood, while DHA supports brain and eye health. Together, EPA and DHA thus contribute to maintaining the normal function of the heart, brain and vision and to the body’s overall resilience.

Introduction

Omega-3 fatty acids are long-chain polyunsaturated lipids belonging to the group of essential fatty acids, which the human body cannot synthesise de novo and which must be obtained from food or food supplements (1). The most important biologically active forms are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (2). These lipids are an integral part of cell membranes, where they influence membrane fluidity, the function of membrane proteins and cell signalling (3).

EPA and DHA also have significant regulatory effects on inflammatory processes through the modulation of the synthesis of eicosanoids, resolvins and protectins, and also influence mitochondrial functions and cellular energy metabolism (4,5).

The beneficial effects of EPA and DHA on human health have been the subject of extensive clinical and epidemiological research for more than four decades (6).

Whereas fish oil was the traditional source of EPA and DHA, modern knowledge clearly confirms that microalgae are the primary producers of these fatty acids. Fish accumulate them through the food chain, mainly by eating algae or organisms that feed on them (7,8).

Microalgal oils naturally have a higher content of docosahexaenoic acid (DHA) than eicosapentaenoic acid (EPA); however, modern fermentation and selective processing technologies make it possible to adjust their ratio in a targeted way so that it approaches the natural omega-3 fatty acid profile of fish oil, while the triglyceride structure and the bioavailability of the lipids are preserved.

Microalgal oil as a natural source of omega-3 fatty acids

Oil obtained from microalgae is a biologically primary and technologically advanced source of long-chain omega-3 fatty acids. Unlike fish oil, which is a secondary source of these lipids, microalgae produce EPA and DHA directly as part of their metabolism (9).

A significant advantage of microalgal oil is its high purity and safety profile. It is produced in closed fermentation systems with precisely controlled conditions, which minimises the risk of contamination with heavy metals, dioxins and polychlorinated biphenyls, which can accumulate in sea fish as a result of ocean pollution (10,11). The European Food Safety Authority (EFSA) has confirmed the safety of microalgal oils as a source of DHA and EPA and their suitability for use in foods and food supplements (12). From a technological point of view, producing oil from algae makes it possible to preserve the natural triglyceride form of omega-3 fatty acids without the need for chemical or enzymatic modification. This form is natural to the body and is readily processed by digestive enzymes, which allows better absorption of omega-3 fatty acids. Compared with the ethyl ester (EE) form, which arises from technological processing and requires an additional step in digestion, the triglyceride form is a more natural way for the body to use them.

Such interventions can therefore affect the absorbability and metabolism of omega-3 fatty acids in the body (13,14). Algal oil obtained by gentle extraction retains its natural molecular structure, which is regarded as an advantage in terms of physiological use.

Another aspect is oxidative stability. With correct production and stabilisation, microalgal oils show low peroxide and anisidine values as well as a low TOTOX index, which are regarded as key indicators of the freshness and quality of omega-3 oils (15).

Compared with fish oil, algal oils are often more stable, less prone to oxidation and more appealing to the senses, mainly thanks to the absence of the typical fishy taste and smell (16).

From an environmental and ethical point of view, microalgal oil is a more sustainable alternative. Producing algae does not require fishing, does not increase pressure on marine ecosystems and allows a high yield of omega-3 fatty acids per unit of input resources. This approach is therefore in line with current recommendations aimed at the sustainable production of nutritionally important substances (17).

In the context of growing demand for omega-3 fatty acids, microalgal oil is thus a scientifically supported, safe and long-term sustainable solution.

Clinical studies

• The effects of omega-3 fatty acids on human health are among the most extensively researched areas of nutrition research.
• The clinical evidence comes from randomised controlled trials, cohort studies and meta-analyses, and their results formed the basis for the authorisation of health claims.

Cardiovascular health

Cardiovascular diseases are among the most common causes of death worldwide, which underlines the need for effective preventive and therapeutic approaches. Omega-3 long-chain polyunsaturated fatty acids, above all eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are also the subject of extensive research for their potential cardioprotective effects (18).

Omega-3 fatty acids influence cardiovascular health through several complementary mechanisms. One of the most important effects is a reduction in blood triglyceride levels, which are an important risk factor for the development of atherosclerosis (damage to blood vessels) and subsequent cardiovascular events. Besides their favourable effect on the lipid profile, omega-3 fatty acids also show a marked anti-inflammatory effect, thereby helping to suppress chronic inflammation in the vessel wall, which plays a key role in the development of atherosclerosis.

Another important mechanism is a reduction in platelet aggregation, which leads to a lower risk of thrombus (clot) formation and thrombotic complications. At the same time, omega-3 fatty acids favourably influence the electrical stability of the heart muscle, thereby reducing susceptibility to serious cardiac arrhythmias and sudden cardiac death. Taken together, these mechanisms explain the potential protective effect of omega-3 fatty acids on the cardiovascular system that has been observed in clinical and interventional studies (18,19).

An important milestone in the clinical evaluation of the effect of omega-3 fatty acids was the GISSI-Prevenzione study, which, as one of the first large randomised clinical trials, showed a reduction in total and cardiovascular mortality in patients after myocardial infarction with EPA and DHA supplementation (18).

The study enrolled 11,324 patients, who were randomised to groups taking 1 g/day of n-3 PUFA (EPA + DHA), vitamin E, a combination of both, or no supplementation, with follow-up lasting up to 42 months. Omega-3 fatty acid supplementation significantly reduced total and cardiovascular mortality, especially sudden cardiac deaths, and the relative risk of combined endpoints (death, non-fatal myocardial infarction, stroke) was reduced by 15%.

These results confirm the favourable effect of EPA and DHA on cardiovascular health and support their inclusion in the secondary prevention of patients after myocardial infarction, with the aim of reducing the risk of its recurrence, in combination with modern pharmacological treatment and a recommended diet.

Subsequent studies focused on lipid metabolism and the importance of lowering triglycerides, pointing to differences between the individual components of omega-3 fatty acids. A higher intake of omega-3 fatty acids, especially EPA and DHA, is associated with lower mortality from coronary disease, particularly in individuals with raised cardiovascular risk. Raised triglycerides are a significant risk factor for atherosclerosis and are common in the population with a low omega-3 intake.

The study by Ryan et al. evaluated the effect of a supplement with a high ratio of EPA to DHA (4 g/day, ratio 2.3 : 1) in 20 adults with mild hypertriglyceridaemia over 228 days. The results showed a significant reduction in triglycerides of 48% (19).

Similarly, the JELIS study showed that high-dose EPA (1.8 g/day) significantly reduces the risk of coronary events in patients treated with statins. These findings support the efficacy of products with a high ratio of EPA to DHA in lowering triglycerides and cardiovascular risk (20).

This development culminated in modern, methodologically robust clinical trials such as REDUCE-IT, which provided compelling evidence of the efficacy of pure EPA in reducing major cardiovascular events in patients treated with statins (21).

Methods

The REDUCE-IT clinical trial included approximately 7,990 patients with cardiovascular disease or diabetes and raised triglycerides, who were taking statins. The intervention group received an EPA supplement of 2 g twice a day (4 g/day), the control group a placebo containing mineral oil. Randomisation was stratified by cardiovascular risk, ezetimibe use and region. Patients were followed at 473 sites in 11 countries from November 2011 to August 2016. The primary endpoint was the occurrence of major cardiovascular events, the secondary endpoint the combined incidence of cardiovascular death, non-fatal heart attack and non-fatal stroke. The efficacy analysis was carried out on an intention-to-treat basis using the Cox model and Kaplan–Meier analysis (21).

Results

The study demonstrated that EPA significantly reduces the risk of major cardiovascular events in patients with raised triglycerides. Among patients taking EPA there was a lower incidence of the primary composite endpoint – cardiovascular death, myocardial infarction and non-fatal stroke, coronary revascularisation or unstable angina pectoris – compared with placebo.

The secondary endpoint, comprising cardiovascular death, myocardial infarction and non-fatal stroke, also showed a favourable effect of the EPA supplement compared with placebo (Fig. 1).

Conclusion

The results of the study demonstrated that EPA significantly reduces the risk of major cardiovascular events in patients with raised triglycerides who are treated with statins.

Inflammation, immunity and mental wellbeing

Chronic inflammation, disorders of immune regulation and mental disorders represent a significant burden on health and are closely linked to the development of several diseases of civilisation. While acute inflammation is an essential part of the body’s defence mechanisms, its inadequate regulation or persistence can lead to tissue damage and the development of pathological conditions (5).

Omega-3 fatty acids, especially EPA and DHA, help regulate inflammation and immune responses by influencing the production of inflammatory substances and cytokines, thereby supporting balance in the body.

Besides anti-inflammatory effects, omega-3 fatty acids are also associated with a favourable influence on mental wellbeing, with clinical data suggesting a significant role of EPA in particular in supporting mental health (22).

Methods

The anti-inflammatory effects of omega-3 fatty acids were evaluated on the basis of experimental, ex vivo and interventional studies in animals and humans that examined the effect of oral intake of EPA and DHA on the fatty acid composition of cell membranes and on the function of cells involved in inflammation.

The parameters evaluated included changes in the proportion of arachidonic acid (AA), EPA and DHA in leukocyte phospholipids, the production of eicosanoids and specialised lipid mediators, neutrophil and monocyte chemotaxis, and the expression and secretion of inflammatory cytokines.

The analysis of fatty acid composition was carried out by gas chromatography, while functional cell responses were evaluated under in vivo, ex vivo and in vitro conditions, taking into account the dose, the duration of supplementation and the form of the fatty acids.

Results

An increased intake of omega-3 fatty acids led to a dose- and time-dependent increase in the content of EPA and DHA in the membrane phospholipids of cells involved in inflammation, with a simultaneous decrease in the content of arachidonic acid (the precursor of several pro-inflammatory mediators). A stable fatty acid composition was usually reached within several weeks.

The change in the membrane profile reduced the production of pro-inflammatory eicosanoids derived from arachidonic acid (e.g. PGE₂, LTB₄) and increased the formation of EPA-derived eicosanoids with lower biological activity. EPA and DHA also served as substrates for the formation of anti-inflammatory mediators (resolvins, protectins), which reduced neutrophil migration and cytokine production (TNF-α, IL-1β). There was also a reduction in the motility of neutrophils and monocytes and an influence on the activity of NF-κB and PPAR-γ, which altered the regulation of genes involved in inflammation.

Conclusion

Targeted supplementation with omega-3 fatty acids increases the proportion of EPA and DHA in cell membranes at the expense of arachidonic acid, which reduces the availability of the substances needed to form inflammatory mediators and promotes a milder inflammatory profile.

Brain and vision

Long-chain omega-3 polyunsaturated fatty acids, above all DHA and EPA, are key to the proper function of the brain and vision. DHA makes up a significant part of the fatty acids in the grey matter of the brain and influences learning, memory and cognitive abilities. A higher intake of DHA and EPA is associated with a lower risk of cognitive decline and supplementation may support memory and visuospatial learning in older adults and in individuals with mild cognitive deficit (23).

Epidemiological and observational studies have shown that a higher intake of DHA and EPA is associated with a lower risk of progression of wet age-related macular degeneration (wAMD), the main cause of vision loss in older people. Meta-analyses show that dietary intake of these fatty acids may reduce the incidence of wAMD by 30–50%, with effects observed across different populations and dietary habits (24). Omega-3 fatty acids are thus a significant nutritional factor supporting eye health and slowing the progression of degenerative retinal diseases.

Methods

The study was carried out on a sample of 485 participants aged ≥55 years with age-related cognitive decline (ARCD). Participants were randomly divided into two groups: a group taking 900 mg/day of DHA (n=242) and a group taking placebo (n=243), with supplementation taking place daily for 24 weeks.

The primary aim was an improvement in performance in the CANTAB PAL 6 pattern test; other tests of cognition, memory and daily function, including plasma DHA levels, were evaluated as secondary outcomes.

Results

After 24 weeks of DHA supplementation, participants showed a significant reduction in the number of errors in the CANTAB PAL 6 pattern test compared with placebo (ITT difference −1.63 ± 0.76, P = 0.032), which corresponded to an improvement equivalent to a 7-year shift in cognitive age versus 3.6 years in the placebo group. Supplementation also significantly improved immediate and delayed verbal memory (VRM test, r = −0.52, P < 0.001).

Plasma DHA levels increased significantly, adherence was high (>82%) and supplementation was well tolerated. These results support the efficacy of DHA in improving cognitive function in older adults with ageing-related mild memory decline.

Conclusion

DHA supplementation significantly improved episodic memory and visuospatial learning in older adults with mild subjective cognitive decline. These results suggest that DHA may serve as an effective nutritional means of supporting cognitive function.

References

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