Polynucleotides: what they do for skin and under the eyes
Polynucleotides are purified DNA fragments injected to improve skin quality. How they work, what the early evidence shows, sessions and risks.
6 min readEducational content by RejuvelookUpdated in October 2026
In short
Polynucleotides are purified DNA fragments, usually from salmon or trout, injected into the skin to improve its quality rather than add volume. Small studies report better texture, elasticity and fine lines with mild side effects. The evidence is still early: one systematic review found nine studies with 219 patients, all of low or moderate quality.
Key points
- Polynucleotides aim to improve skin quality: they do not fill hollows or lift loose skin.
- A 2025 systematic review found nine studies with 219 patients, of low or moderate quality.
- A 2026 review of randomised trials found seven, with 183 participants; only four looked at skin rejuvenation.
- Under the eyes, a trial of 27 people found no overall difference against non-crosslinked hyaluronic acid.
- There are no long-term studies, so nobody can say reliably how long the effect lasts.
Polynucleotides have become a widely discussed injectable treatment in a few short years, especially in the UK. Many people who have moved to the Costa del Sol, or who spend the winter here, ask about them for the thin skin under the eyes, the neck or the face. They are promoted as a regenerative treatment, different from a filler. Before deciding, it helps to know what they are, how they are thought to work and how much the evidence can really tell you.
What polynucleotides are
Polynucleotides are chains of nucleotides, the building blocks of DNA, purified for injection. Most are extracted from the sperm cells of salmon or trout [1]. In aesthetic medicine they are sold as medical devices and placed into the skin with small, superficial injections.
You may see slightly different names for them, because they come in different chain lengths and the scientific literature has not always used the terms consistently [2]. For you as a patient, the practical point is the same: these are not fillers, and they are not muscle relaxants.
Their use in aesthetics grew out of earlier work on wound healing [4]. The aim is to improve the quality of the skin, its hydration, elasticity and texture, rather than to change its shape.
How they are thought to work
The proposed mechanism is that the DNA fragments act on a receptor on skin cells, the adenosine A2A receptor. In studies, this has been linked to cell growth, more production of the proteins that support the skin, and less inflammation [3]. Reviews also describe effects on collagen and on the formation of small blood vessels [1].
It is worth being clear about where this comes from. Much of it is based on laboratory and animal studies, and on wound healing rather than ageing skin [3]. A plausible mechanism is a good start, but it is not the same as proof that a treatment gives a visible, lasting change in your face.
What the evidence actually shows
The research is recent and still thin.
- A 2025 systematic review found nine studies with 219 patients treated in total. All were of low or moderate quality, and the products, areas and techniques varied a lot. The studies reported less wrinkling, better texture and better elasticity, with mild, short-lived side effects. The authors concluded that there is little agreement on how best to use them and that rigorous studies are needed [4].
- A 2026 review limited to randomised trials found seven, with 183 participants. Only four looked at skin rejuvenation. Results were favourable, with no serious adverse events, but the samples were small and the protocols very different from each other [5].
Under the eyes, a randomised, double-blind trial treated 27 people. Each had polynucleotides on one side and non-crosslinked hyaluronic acid on the other, three times at two-week intervals. Overall improvement scores were not significantly different between the two sides. Roughness and pore volume improved more on the polynucleotide side [6].
A 2026 review comparing the two for the under-eye area reached a similar balance. Hyaluronic acid is still the better option for structural correction, while polynucleotides improve skin quality measures such as elasticity, hydration and fine lines. Differences between studies and products mean firm conclusions are not yet possible [7].
In short: there are encouraging signals and a reassuring short-term safety record, but a small evidence base and very little long-term follow-up. Anyone promising a dramatic change is going further than the data.
How the doctor decides whether they make sense
The first step is understanding what you see in the mirror. Under-eye concerns can come from thin skin, pigment, hollowing, visible vessels or fat bags, and they often overlap. A 2026 systematic review of 50 studies sums it up: fillers remain the basis for volume loss, lasers address pigment and vessels, microneedling and polynucleotides target texture and fine lines, and surgery is preferred for fat bags and a weak lower eyelid [8]. We explain these types in our guide to dark circles and tear trough filler.
The same applies to the neck and face. Crêpey, thin skin is a different problem from deep folds, loose skin or prominent neck bands.
At the consultation, the doctor asks about allergies, especially to fish, medicines that make you bruise, autoimmune conditions and previous treatments in the area. Standardised photographs are taken, so that any change can be judged fairly later on.
Sessions, downtime and what to expect, realistically
- A course, not a single session. Protocols usually involve several sessions a few weeks apart. In the under-eye trial, there were three, two weeks apart [6]. There is no agreed standard [4].
- Small bumps afterwards. The injections leave small raised points that usually settle within hours or a day or two. Redness and the odd bruise are common, particularly under the eyes.
- A gradual, subtle change. If it works for you, the skin looks smoother, more even and a little less crêpey. Your features do not change.
- Uncertain duration. No study has followed patients long enough to give a reliable figure. Maintenance sessions are usually discussed, but on the basis of experience rather than data.
On the Costa del Sol, plan around the sun. Bruises and redness fade more evenly if you avoid strong sun for a few days, and daily sunscreen protects whatever improvement you gain.
Risks, and who they are not for
Side effects reported in studies are generally mild and short-lived [4], and the randomised trials reported no serious treatment-related adverse events [5]. The usual effects are those of any series of small injections: tenderness, small bumps, redness, swelling and bruising.
As with any injection, there is a low risk of infection or an inflammatory reaction. That is why it should be done in a licensed healthcare centre, with a traceable product, by a doctor who knows the anatomy of the area.
Because most products come from fish DNA, a known allergy to fish or to any component is a reason not to have them. They are also not suitable during pregnancy or breastfeeding, with an active infection or cold sore in the area, or with an uncontrolled autoimmune condition before the doctor has looked at your case.
They are not the right tool for hollows, heavy bags or loose skin. Used for those, they will disappoint.
How they compare with skin boosters and fillers
- Fillers use crosslinked hyaluronic acid to restore volume and support. They act on shape, and the result is visible straight away.
- Skin boosters use softer hyaluronic acid to hydrate the skin from within. The under-eye trial above used one as its comparison [6]. We cover them in our article on skin boosters.
- Polynucleotides aim at the quality of the skin through a biological effect, not through volume or hydration from a gel.
They are often combined, because they solve different problems. What matters is matching the tool to the cause.
How we approach it at Rejuvelook
At our clinic in Fuengirola, a doctor sees you for a medical consultation and looks at the area that concerns you, in the context of your face as a whole. For the under-eye area, that means working out which type of problem you have before thinking about treatment. We then recommend the option with the best support for your case, explain what change is realistic and over what time, and tell you when something will not help. We see patients in English or Spanish.
If you would like to understand the options for volume loss, read our patient guide to hyaluronic acid dermal fillers.
What the evidence says
Each statement shows its level of evidence and the sources behind it.
With caveats
Not enough support
- Under the eyes, they improve skin quality measures, but they do not correct volume loss, and overall results were similar to non-crosslinked hyaluronic acid in one trial.[6][7]Low-quality evidence
- The proposed mechanism, through the adenosine A2A receptor, comes mostly from laboratory, animal and wound-healing studies.[1][3]Experimental
- There is no reliable data on how long the effect lasts or on the ideal number of sessions.[4][5][7]Low-quality evidence
When to see a doctor
Book a medical consultation, or go to A&E if it is severe or sudden, if you notice:
- Hives, swelling of the lips, tongue or throat, or difficulty breathing after an injection: call 112.
- Any change in your vision after a treatment around the eyes: go to A&E (urgencias) or call 112.
- Redness, heat, pain or swelling that gets worse rather than better after two or three days, or a fever: contact the clinic.
- Lumps that are still there, or hard and tender, weeks after a session.
- Under-eye puffiness that is worse in the mornings or comes and goes: it needs a diagnosis before any injection.
Frequently asked
Does it hurt?
You feel each small injection, and the under-eye area is sensitive. A numbing cream or cold is usually applied first. Most people describe it as uncomfortable rather than painful, and it passes within minutes.
Can I go back to work the next day?
Usually, yes. The small bumps from the injections often settle within hours or a day or two. A bruise, if there is one, can take a week to fade and can be covered with make-up once the skin has closed.
Can I sunbathe, swim or fly afterwards?
Avoid strong sun, saunas, hot yoga and hard exercise for a day or two, and use a high-factor sunscreen every day. Flying is fine, but leave a few days between a session and a long trip in case of bruising.
When will I notice a difference?
The change is gradual. It is usually judged a few weeks after the last session of the course, by comparing standardised photographs taken with the same light and angle.
Can they be combined with other treatments?
Yes, they are often combined because they do different things. Filler can restore volume and anti-wrinkle injections relax muscle lines, while polynucleotides target the skin itself. The doctor decides the order and spacing.
I had them in the UK. Can I continue on the Costa del Sol?
Bring whatever details you have: the product, the dates and the number of sessions. The doctor will look at your skin as it is now and tell you whether continuing makes sense or whether another option has better support for your case.
Are polynucleotides the same as exosomes or PRP?
No. They are different products, with different mechanisms and different evidence. What they share is the aim of improving skin quality, and that their scientific support is still limited.
References
Sources checked against PubMed or Crossref. Cited as plain text, without links.
- 1.Kim TH, Heo SY, Oh GW, Heo SJ, Jung WK. Applications of Marine Organism-Derived Polydeoxyribonucleotide: Its Potential in Biomedical Engineering. Mar Drugs. 2021;19(6). doi: 10.3390/md19060296. PMID: 34067499.Verified on 19 October 2026
- 2.Marques C, Porcello A, Cerrano M, Hadjab F, Chemali M, Lourenço K, et al. From Polydeoxyribonucleotides (PDRNs) to Polynucleotides (PNs): Bridging the Gap Between Scientific Definitions, Molecular Insights, and Clinical Applications of Multifunctional Biomolecules. Biomolecules. 2025;15(1). doi: 10.3390/biom15010148. PMID: 39858543.Verified on 19 October 2026
- 3.Veronesi F, Dallari D, Sabbioni G, Carubbi C, Martini L, Fini M. Polydeoxyribonucleotides (PDRNs) From Skin to Musculoskeletal Tissue Regeneration via Adenosine A(2A) Receptor Involvement. J Cell Physiol. 2017;232(9):2299-2307. doi: 10.1002/jcp.25663. PMID: 27791262.Verified on 19 October 2026
- 4.Lampridou S, Bassett S, Cavallini M, Christopoulos G. The Effectiveness of Polynucleotides in Esthetic Medicine: A Systematic Review. J Cosmet Dermatol. 2025;24(2):e16721. doi: 10.1111/jocd.16721. PMID: 39645667.Verified on 19 October 2026
- 5.Alhussain AM, Turki M Albusayys S, Alfhadi MA, Bu Mozah SA, AlShammari SSS, Alanazi HAM, et al. Polynucleotides and Polydeoxyribonucleotides for Skin Rejuvenation, Postoperative Scar Prevention, and Wound Healing: A Systematic Review of Randomized Clinical Trials. Cureus. 2026;18(7):e112403. doi: 10.7759/cureus.112403. PMID: 42572627.Verified on 19 October 2026
- 6.Lee YJ, Kim HT, Lee YJ, Paik SH, Moon YS, Lee WJ, et al. Comparison of the effects of polynucleotide and hyaluronic acid fillers on periocular rejuvenation: a randomized, double-blind, split-face trial. J Dermatolog Treat. 2022;33(1):254-260. doi: 10.1080/09546634.2020.1748857. PMID: 32248707.Verified on 19 October 2026
- 7.Khan RS, Hafeez K. Hyaluronic Acid Fillers Versus Polynucleotides for Under-Eye Rejuvenation. J Clin Med. 2026;15(13). doi: 10.3390/jcm15134971. PMID: 42452433.Verified on 19 October 2026
- 8.Beer J, Boghosian T, Sherif R, Montes J, Tosti A, Rohrich R, et al. What's New With Under Eye Treatment: A Multispecialty Systematic Review of Recent Under Eye Treatments. Dermatol Surg. 2026;52(2):155-163. doi: 10.1097/DSS.0000000000004964. PMID: 41615388.Verified on 19 October 2026
Educational content. It does not replace a medical consultation or provide a diagnosis. Tests and treatments are indicated only after medical consultation and in line with regulation.