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  • Writer's pictureDr Emma Derbyshire

Omega-3 Polyunsaturated Lipophenols – Do They Show Promise from a Health Stance?

Polyphenols and n-3 polyunsaturated fatty acids (PUFAs) are natural compounds with proven health benefits. The two classes of compounds possess biological activity on oxidation, inflammation, cancer, cardiovascular and degenerative diseases, which have all been shown both in vitro and in vivo research studies.


Polyphenols are phytochemicals that are found abundantly throughout the plant kingdom and are characterised by the possession of one or more hydroxyl groups attached to an aromatic ring. They possess antioxidant properties aiding the protection of our cells from free radical damage, and thus the ageing process. If free radical damage is not counteracted, tissue degradation can occur leading to degenerative diseases eg, Alzheimer’s disease, Parkinson’s disease, age-related macular degeneration (AMD), heart disease and cancer. Research into the role of polyphenols in our diet and evidence for their role in the prevention of such diseases is starting to emerge. Thousands of polyphenol compounds have been identified in foods, such as black and green tea, cocoa, vegetables, fruits, spices and nuts.

n-3 Polyunsaturated Fatty Acids (PUFAs)

Omega-3 fatty acids are n-3 PUFAs, which are found abundantly in nature and are an important component of animal lipid metabolism. n-3 PUFAs are characterised by the possession of a double bond three atoms away from the terminal methyl group in their chemical structure and play an important role in human physiology. Much research has been conducted to show that omega-3 fatty acids are an important constituent of the human diet and offer significant health benefits by reducing the production of triglycerides in the body. A high level of triglycerides can lead to heart disease, coronary artery disease and stroke, thus the consumption of omega-3 polyunsaturated fatty acids can help reduce triglyceride levels in the blood. The three types of omega-3 fatty acids recommended as part of a healthy diet are α-linolenic acid (ALA), found in plant oils, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), found in marine oils.

Combining Polyphenols and n-3 PUFAs

Scientists at the Institute of Biomolecules Max Mousseron (IBMM) in France have been working towards combining polyphenols and n-3 PUFAs leading to n-3 lipophenol derivatives. They hypothesised that combining the therapeutic aspects of n-3 PUFAs and of polyphenols in a single lipophenolic molecule could result in conjugated derivatives with enhanced biological activities.

Research suggests that increasing the lipophilicity of natural polyphenols may be a valuable way to improve their formulation for use as drugs in humans. By increasing the polyphenols lipophilicity the resultant compound is proposed to have an enhanced protective effect on lipid matrices and also improved absorption. A study these Scientists have recently published in Antioxidants (Basel) reports the conjugation of polyphenols resveratrol, phloroglucinol, quercetin and catechin to various n-3 PUFAs using classical chemical strategies or enzymatic reactions. These new compounds were tested for the ability to treat the resultant oxidative damage caused by AMD.

Introducing PUFA into the structure resulted in a reduction in the polyphenol reactive oxygen species (ROS) scavenging activity and it was discovered that the positions of the PUFA on the polyphenol core appeared to influence the antioxidant effect of the lipophenolic compound. Furthermore, the polyphenol quercetin when conjugated to linoleic or α-linolenic acid was found to be a promising lipophilic antioxidant, which protected ARPE-19 cells from A2E-induced cell death more effectively. Many scientific studies have reported the use of ARPE-19 cell lines to investigate potential agents for the treatment of AMD and for the identification of novel compounds to protect RPE cells against A2E oxidation.

The mechanisms of lipophenol cellular protection need to be fully investigated to identify how these novel lipophilic antioxidant compounds exert their positive health benefits. It is imperative that their future potential be determined in retinal models both in vitro and in vivo towards the development of novel drug entities, using natural polyphenol and n-3 PUFA compounds.

Concluding Points

The evidence around omega-3 fatty acids is well established from a health stance. Now it appears that combining omega-3 fatty acid and polyphenols, thus forming lipophenols could confer other health benefits. Ongoing research is needed as most work to date has been driven forward by scientists at the Institute of Biomolecules Max Mousseron. In particular, in conditions where oxidative stress plays a central role in the development and exacerbation of the disease, such as in AMD, is where lipophenol drug development could have most promise. Continued work is warranted.


Moine E et al. (2018) New Lipophenol Antioxidants Reduce Oxidative Damage in Retina Pigment Epithelial Cells. Antioxidants (Basel). Dec 19;7(12)

Crauste C et al. (2016) Omega-3 polyunsaturated lipophenols, how and why? Biochimie. Jan;120:62-74



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