Polynucleotides or Profhilo: How the Two Skin Injectables Differ and What the Evidence Shows

Short answer: Profhilo and polynucleotides are different products. Profhilo is a hyaluronic acid injectable. Polynucleotides are purified DNA fragments, normally from fish. Both are used to improve skin quality rather than to add volume. As of 5 November 2026 we found no published trial that compares the two directly, so no source can say that one works better than the other. The choice is made at a consultation, based on your skin, your concerns, your history and your own goals.

What each treatment is

	Profhilo	Polynucleotides
Main ingredient	Hyaluronic acid (HA). It is a blend of high- and low-molecular-weight HA, described in the literature as "hybrid cooperative complexes".	Purified DNA fragments. Progen's polynucleotides page says they come from salmon or trout.
Described purpose	Skin hydration, firmness and laxity.	Skin quality, texture and repair.
Proposed way it works	HA attracts and holds water. Manufacturer-linked research proposes that this blend also prompts collagen and elastin activity.	Proposed to act on fibroblasts, reduce inflammation and oxidative stress. Most of this is laboratory-based reasoning rather than proven in people.
Contains HA?	Yes.	Plain polynucleotide products do not. Some combined products do, so ask which product is being used.

The old Progen article on Cellular Matrix and Profhilo describes the Profhilo formula as 32 mg of high-molecular-weight and 32 mg of low-molecular-weight HA in 2 mL. We could not check that against the manufacturer's current product information, so confirm it with your practitioner if the detail matters to you.

What the evidence shows for each

Profhilo. A 2026 systematic review (Sparavigna et al., Plastic and Aesthetic Nursing) pooled 9 studies with 278 participants. It reported improvements in skin laxity, hydration, elasticity, density and wrinkles, with mild side effects that usually settled within three days. Three of its authors are listed as employees of IBSA, the manufacturer. Other recent Profhilo studies we found were single-arm, open-label or very small, and several were also written by IBSA employees. That does not make the findings wrong, but it is not independent evidence.

Polynucleotides. A 2025 systematic review (Lampridou et al., Journal of Cosmetic Dermatology) covered 9 studies with 219 patients. It reported promising results for wrinkles, texture and elasticity, but rated the studies low to moderate quality and found limited agreement on how best to use polynucleotides. A 2026 review of randomised trials (Alhussain et al., Cureus) included 7 trials with 183 participants. It found benefits for wrinkles, scar quality and satisfaction, and the authors point to small samples and very different protocols.

In plain terms: both treatments have early, mostly short-term evidence from small studies. Neither has been shown to give a specific result to a specific person.

Has anyone compared them directly?

We did not find a trial of polynucleotides against Profhilo. The closest evidence compares polynucleotides with a different hyaluronic acid product:

• A randomised split-face trial of 27 people (Lee et al., Journal of Dermatological Treatment, 2022) injected one side of the under-eye area with a polynucleotide filler and the other with non-crosslinked HA. Overall improvement scores did not differ significantly between the sides. The polynucleotide side showed higher improvement in roughness and pore volume. No serious adverse events were reported.
• A 2026 review of HA fillers and polynucleotides for under-eye rejuvenation (Khan and Hafeez, Journal of Clinical Medicine) concluded that HA is stronger for structural volume correction, while polynucleotides show consistent improvements in skin quality. The authors say study designs are too varied for firm conclusions and call for direct comparison trials.

That HA was not Profhilo, and the under-eye area is not where Profhilo is typically discussed, so these findings should not be carried over to the two products as a whole.

Why clinic comparison pages disagree

Clinic pages on this topic often say that Profhilo shows results faster and polynucleotides work more deeply, or the reverse. Some say a course of one is two sessions and of the other three or more. Timings quoted for first visible results range from about two weeks to about six weeks. None of the pages we read gave a study for these timings. Session numbers and spacing in published studies also differ by product and by trial. Your practitioner will confirm what is planned for you.

Side effects and who should ask first

Both are injections, so the usual effects are redness, swelling, bruising and small bumps at injection sites. For Profhilo, a manufacturer-authored review of reports from 2018 to 2023 estimated more than one million patient exposures and an adverse event rate of roughly 0.03 to 0.04%, with swelling, redness and discomfort most common (Salti et al., Journal of Cosmetic Dermatology, 2025). Those figures come from spontaneous reports, so minor and unreported events will be missed. For polynucleotides, the systematic reviews above describe side effects as mild and transient, based on small numbers.

Things to raise with your practitioner before either treatment:

• Fish or shellfish allergy. The American Academy of Ophthalmology's EyeWiki page on periorbital polynucleotide injections advises against polynucleotides for people with these allergies, noting that purification lowers but may not remove the risk. Progen's polynucleotides page also asks you to mention fish allergy.
• Allergy to hyaluronic acid products, past reactions to injectables, or a history of delayed swelling after previous fillers. EyeWiki notes delayed reactions weeks to months after injection, which it links in some cases to the HA in combined products.
• Pregnancy or breastfeeding. EyeWiki reports no evidence of harm from polynucleotides but advises avoiding them.
• Active skin infection, cold sores, bleeding disorders or blood-thinning medicines, and autoimmune conditions.

Do not stop or change any prescribed medicine because of this page. Your practitioner will confirm whether either treatment is suitable and how it would be planned.

Questions worth asking at a consultation

1. Which product exactly would be used, and does it contain hyaluronic acid?
2. What am I hoping to change: hydration and glow, texture, fine lines, scars, or looseness? Is an injectable the right route at all, compared with PRP facial or laser? Our comparison of polynucleotides and PRP facial covers that side.
3. How many sessions are planned, how far apart, and when would we judge the result?
4. What are the risks for me, given my allergies, medicines and health history?
5. Is there anything about my skin that should be assessed first?

Next step

If you are weighing the two, start with the polynucleotides treatment page to see the options Progen lists, then arrange a consultation. Ask there which treatments the clinic currently offers and which suit your concern. For pricing, see prices, or use the contact page to ask a question first.

Evidence accessed on 5 November 2026. This article is general information and not a diagnosis or treatment advice. Results vary and cannot be guaranteed.

Frequently asked questions

Is Profhilo the same as polynucleotides?

No. Profhilo is a hyaluronic acid product. Polynucleotides are purified DNA fragments, usually from fish. Some combined products contain both, so ask which product is being used.

Which is better, polynucleotides or Profhilo?

We found no published trial comparing the two directly, so no source can say that one is better. Both have small, mostly short-term studies. A practitioner can discuss which is more suitable for your skin concern at a consultation.

Can you have polynucleotides if you have a fish allergy?

The American Academy of Ophthalmology's EyeWiki page advises against polynucleotide injections in people with fish or shellfish allergy, as purification may not remove the risk completely. Tell your practitioner about any allergy, and they will confirm suitability.

Can polynucleotides and Profhilo be used together?

Several clinic pages say they can be combined, but none cited a study. Whether it is appropriate, and how the timing would be planned, is a decision for your practitioner after assessing you.

Is the Profhilo research independent?

Not entirely. Several of the recent Profhilo studies we found include authors who are employees of the manufacturer, IBSA, including the 2026 systematic review and the 2025 post-marketing safety update.

Read about polynucleotide treatment and arrange a consultation

Sources and further information

• Lee et al., J Dermatol Treat 2022;33(1):254-260 (DOI 10.1080/09546634.2020.1748857): randomised, double-blind split-face trial, 27 subjects, polynucleotide filler vs non-crosslinked HA, three injections two weeks apart; overall scores not significantly different; PN side higher improvement in roughness and pore volume; no serious adverse events. Accessed 5 Nov 2026.
• Sparavigna et al., Plastic and Aesthetic Nursing 2026;46(2):80-92: systematic review of 9 studies, 278 participants, improvements in laxity, elasticity, hydration, density, wrinkles; mild side effects usually resolved within three days. Salti et al., J Cosmet Dermatol 2025;24(7):e70197: post-marketing, over one million exposures, adverse event rates about 0.03-0.04%. Accessed 5 Nov 2026.
• Cassuto et al., BioMed Res Int 2020 (DOI 10.1155/2020/8159047): 12 spontaneous adverse event reports to the IBSA safety database Feb 2015 to Feb 2018, none serious. Accessed 5 Nov 2026. Not quoted in the article text beyond context.
• Lampridou et al., J Cosmet Dermatol 2025;24(2):e16721: 9 studies, 219 patients, low to moderate quality, limited consensus, mild transient side effects. Alhussain et al., Cureus 2026;18(7):e112403: 7 randomised trials, 183 participants, small samples, heterogeneous protocols, no serious treatment-related adverse events. Accessed 5 Nov 2026.
• Khan and Hafeez, J Clin Med 2026 (DOI 10.3390/jcm15134971): review concluding HA is stronger for structural volume correction, PN improves skin quality, designs too varied for definitive conclusions, head-to-head trials needed. Accessed 5 Nov 2026.
• Polynucleotide products are purified fish-derived DNA polymers. Proposed fibroblast, antioxidant and anti-inflammatory mechanism. Common effects settle in hours to days. Advises against use in fish or shellfish allergy, since purification reduces but may not eliminate the risk. Avoidance in pregnancy and breastfeeding advised although no harm is evidenced. Delayed reactions linked in some cases to HA in combined products. Accessed 5 Nov 2026; page status as noted in the previous poly-03 run was 'Up to Date' 13 May 2026.
• Used only to show what ranking clinic pages say about timings and session counts, and that they disagree and cite no studies. Accessed 5 Nov 2026.