PDRN Serum Risks: What It Is and What Is Still Unknown

The Risks Where I Stand What It Is How It's Made Residues The Studies Questions to Ask FAQ

PDRN (polydeoxyribonucleotide) is fragmented DNA, most often purified from salmon or trout sperm, that is now sold in serums, microneedled into faces as the "salmon sperm facial," and injected as a "skin booster." It has no long-term safety data for cosmetic use. Its human trials are small and short, several were written with the companies that sell it, and the delivery methods that make it work carry it past the skin's own barrier. I treat a new skincare treatment as unproven until time says otherwise, so this article starts with the risks and the unknowns, then covers what PDRN is, how it is made, and what the manufacturing process can leave behind.

Key Takeaways

• No study has followed cosmetic PDRN users long term. The longest randomized trial ran six months, and a 2026 dermatology review states that no long-term data exist.
• "No serious adverse events" comes from fewer than 200 trial participants, a number too small to rule out a serious reaction rate as high as 1 in 61.
• The phase III trial of the best-known injectable was retracted over undisclosed manufacturer funding.
• Microneedling and injection carry the product past the skin barrier, and case reports link needled serums to granulomas (firm inflammatory bumps) that resisted treatment.
• The original drug-grade process included a step to strip the DNA of its genetic "informational capability." The cosmetic PDRN papers cited here do not mention that step.
• Extraction patents name phenol, chloroform, isopropanol, strong salts, and in one case the hormone hCG. No independent residue testing of retail PDRN serums has been published.
• No polynucleotide brand is on the FDA list of approved dermal fillers, and cosmetics reach the US market without premarket approval.

This article is for education only and does not diagnose, treat, or prevent any condition. I am a clinical herbalist, not a physician, dermatologist, or licensed esthetician. Do not start, stop, or change a medication or a prescribed treatment based on this article. Allergies, pregnancy, breastfeeding, autoimmune conditions, and recent procedures all change the picture, and people respond differently to the same product. Bring questions about your own skin and health history to a qualified clinician. Trouble breathing, swelling of the face or throat, or a fast-spreading rash after any product or procedure is an emergency: call 911 or your local emergency number.

PDRN Risks and Side Effects: What Is Known and What Is Not

Evidence: limited. Short trials, review papers, case reports, and one statistics paper. The largest gap is the absence of any long-term data.

No one has followed users long term

A 2026 dermatology review of PDRN states it plainly: "No data however is present on the long-term evaluation of the drug."¹ Among the randomized trials of PDRN and its close relative polynucleotide (PN), the longest follow-up is six months.² Nothing published can say what repeated use does to skin over ten or twenty years.

"No serious adverse events" means less than it sounds

Both systematic reviews of these products report no serious adverse events.³² The randomized trials enrolled 183 people in total.² A statistics paper published in JAMA in 1983 gives the math for this situation, known as the rule of three: when zero events are seen among a group of people, the true rate can still be as high as 3 divided by the size of the group, at 95% confidence.⁴ For 183 people that ceiling is 1 in 61, and it sits higher still because some of those participants were in comparison groups and never received PDRN.

The short-term reactions that the trials did record were pain, swelling, itching, bruising, and redness at the injection site.³ The dermatology review adds that both PN and PDRN "can cause temporary histamine reactions."¹ A trial of this size cannot detect a rare harm, and a trial of this length cannot detect a slow one.

Much of the research is tied to the sellers

The phase III trial of the injectable Rejuran was retracted in 2016 after the journal's publication board found a wrong conflict of interest disclosure, and Retraction Watch reported that a pharmaceutical company had paid the trial's expenses.⁵⁶ Several of the newer papers cited in this article list employees of PDRN manufacturers or skincare companies among their authors, and each of those ties is noted in the sources list.

Needles carry the product past the skin's own defenses

The outer layer of skin blocks large molecules and contains an enzyme, DNase 2, that breaks down DNA.⁷ PDRN fragments are 100 to 3,000 times larger than the 500-dalton size that dermatology researchers consider able to cross intact skin.⁸⁹ Clinics get around both defenses with microneedling, lasers, or injection.¹⁰¹¹ Those methods deliver foreign DNA, and everything else in the bottle, into living tissue the barrier would have kept it out of.

A 2014 report in JAMA Dermatology described three women who developed facial granulomas after microneedling with topical products. Two of them had the same vitamin C serum needled into the skin and later tested positive to it on patch testing. Biopsies showed foreign body-type granulomas, and steroid treatment did not clear them.¹⁰ A 2024 systematic review counted 15 patients in 13 reports and concluded that these reactions "may be treatment-resistant."¹²

None of those cases involved PDRN, but the authors' explanation applies to any serum: needling a product made for the skin surface carries its particles into the dermis, where the immune system can react to them.¹⁰ The federal regulation that covers microneedling devices for aesthetic use excludes devices intended for "transdermal delivery of topical products," such as cosmetics, drugs, or biologics.¹³

Fish allergy, pregnancy, and other cautions on record

The dermatology review says a patch test "is warranted in patients who give a history of hypersensitivity to fish."¹ No study testing PDRN in people with a diagnosed fish allergy turned up in a PubMed search. The same review states that use in pregnancy and lactation "is not recommended due to a lack of studies," and its contraindications table lists age under 18, autoimmune conditions, and active infection in the treatment area.¹

Open questions that no one has studied

PDRN is described as working by switching on the adenosine A2A receptor and raising VEGF, a signal that drives new blood vessel growth.⁹ A 2006 mouse study in PNAS found that the same receptor protects tumors from the immune cells that attack them, and its authors proposed blocking the receptor as a cancer therapy.¹⁴ That study did not involve PDRN, and no study located for this article has tested whether repeated cosmetic use of a product that activates this receptor changes cancer risk in either direction.

On genetic safety, the dermatology review states that "No mutagenic potential of the drug has been reported so far," but also that "some concerns about its theoretical mutagenic potential have been raised."¹ The manufacturing section below covers a step the drug makers added to address the genetic question.

No one reviews it before sale

In the US, injectable dermal fillers are Class III devices that require premarket approval. The FDA list of approved products in that category, retrieved on October 8, 2026, included no polynucleotide brand: Rejuran, Plinest, Newest, and Nucleofill were all absent.¹⁵ PDRN serums are sold as cosmetics, and US law does not require cosmetic products or ingredients, other than color additives, to have premarket approval,¹⁶ so no agency checks a serum's purity or residues before it goes on sale.

Why I Stay in the Control Group

This section is my opinion and my personal practice, not medical advice.

Every new ingredient has a stretch of years when its early users are the long-term safety study. My practice with new skincare and cosmetic treatments is to stay in the control group for that stretch and let time and independent research do their work. I do not inject anything into my skin, and I am slow to adopt any product that is younger than the questions about it.

PDRN has been prescribed as a wound drug since 1994,¹⁷ and decisions about medical wound care belong to a patient and their doctor. Using it on healthy faces for appearance is the recent part, and that is the use with no long-term record.

The skin care I write about on this site leans on things with generations of human use behind them, and my articles on nourishing the skin's microbiome and mineral sun protection start from that same place. If you decide to try PDRN anyway, the questions near the end of this article are the ones I would want answered first.

Handmade in Montana

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What Is PDRN?

Evidence: strong for what the ingredient is. The proposed way it works comes mostly from cell and animal studies.

PDRN is a mixture of DNA chains with molecular weights between 50 and 1,500 kilodaltons (kDa), taken from the sperm of salmon trout (Oncorhynchus mykiss) or chum salmon (Oncorhynchus keta).⁹ It does not occur in this form in nature. It is fish DNA that has been extracted, purified, heat-treated, and cut to size in a factory.¹⁷¹

The first drug with PDRN as its active ingredient, Placentex from the Italian company Mastelli, was approved in 1994 as an injectable.¹⁷ Its move into anti-aging serums, facials, and cosmetic injections is recent. Rejuran, the injectable most closely tied to the trend, is made by PharmaResearch in South Korea and uses longer DNA chains called polynucleotide (PN).¹¹ On a cosmetic ingredient list, PDRN usually appears as Sodium DNA or Hydrolyzed DNA.¹⁸

How PDRN is thought to work

Researchers propose two actions for PDRN: switching on the adenosine A2A receptor, a receptor on the cell surface tied to lower inflammatory signaling and new blood vessel growth, and supplying nucleotide building blocks that cells recycle into new DNA, a process called the salvage pathway.⁹¹⁸ The main support for the receptor theory comes from cell and animal experiments in which a receptor-blocking compound cancelled the effects of PDRN.⁹

How Is PDRN Made?

Evidence: limited. Process descriptions come from review papers and patents, and manufacturers keep their full specifications proprietary.

The 2026 dermatology review lists the steps in order: sperm is collected from mature male fish, the cells are broken open with buffers, debris is removed by filtration and centrifugation, bacterial endotoxins are removed with resins, the DNA is purified by high-performance liquid chromatography, and the product is sterilized and freeze-dried into a powder.¹ A 2025 review adds that the drug-grade process patented in the 1990s uses high-temperature treatment, a protein-digesting step, and three separation steps, with sterilization in an autoclave at 250°F (121°C).¹⁷

The step that strips the DNA's genetic information

That same drug-grade process includes "controlled partial depurination," a chemical treatment that removes some of the bases, the letters of the genetic code, from the DNA chain. The 2025 review explains the reason: because PDRN is DNA, it "fundamentally bears an informational function," and depurination was added to "add an extra layer of safety by eliminating the polymer's informational capability," which the authors describe as limiting "the transfer of genetic codes for viruses, oncogenes."¹⁷

The makers of the original drug, in other words, treated the genetic information in foreign DNA as something to remove for safety. The cosmetic PDRN papers cited in this article, the eye cream trial and the peony study, describe extraction and fragmentation but do not mention a depurination step.¹⁹²⁰ The salmon PDRN in the eye cream trial averaged about 1,200 base pairs per fragment.¹⁹

Purity figures leave a remainder

One pharmacology review states that the drug is more than 95% pure, with proteins and peptides inactivated.⁹ The 2025 review puts DNA purity at "up to 90%" and names what else is present: "low amounts of free amino acids, low-MW peptides, and glycosaminoglycans."¹⁷ The cosmetic raw material in the eye cream trial was listed at 96% or higher.¹⁹ None of these papers reports a measured level of residual protein or of processing chemicals.

The dermatology review lists "Inter-batch variability from the same source" among the limitations of PDRN and states: "Challenges arise due to inadequate operating protocols and structured guidelines for sourcing and manufacturing."¹

Plant and "vegan" PDRN

Brands now sell PDRN made from plants such as rose and peony²¹²⁰ and from Lactobacillus bacteria.²² A 2026 review of plant-derived PDRN, with a co-first author employed by a Korean company in the field, states that the evidence "remains predominantly preclinical and should not be construed as demonstrating clinical equivalence" to the fish-derived material.⁷ The one human test of a plant PDRN located for this article enrolled 10 people for four weeks with no comparison product, and all of its authors work at a company's skin science research center.²⁰

What Can the Manufacturing Process Leave Behind?

Evidence: limited. Patents and manufacturing reviews name the reagents. No independent residue testing of retail PDRN serums turned up in the search for this article.

Each step that separates DNA from fish tissue uses a reagent, and the question for the person using the product is how much of each one remains in the finished powder. Manufacturers do not publish that number, though patents show which chemicals are in play.

• Organic solvents. A 2023 US patent assigned to the Korean company Bio Medi Pharm states that "phenol and chloroform are used to isolate DNA from fish tissues" and that PDRN is conventionally "extracted with a mixture of ethanol or sodium acetate and isopropanol." The same patent notes that with organic solvent extraction, "various substances soluble in the organic solvent are inevitably extracted."²³ An earlier patent from another Korean company describes phenol as "harmful to humans."²⁴
• Strong salts and reactive chemicals. That earlier patent replaces phenol with its own recipe for pulling DNA from fish and squid milt: a 4-molar sodium nitrate solution made alkaline with sodium carbonate, the chelator EDTA, acetic anhydride, ammonium sulfate, and ethanol. Its background section lists cosmetics among the uses for DNA of this kind.²⁴
• A hormone. The Bio Medi Pharm patent treats salmon testes with human chorionic gonadotropin (hCG), at 25 to 200 IU per gram of tissue, "to induce artificial sexual maturation of the testicular cells to sperm" before extraction. It describes the PDRN as a material for "therapeutics and cosmetics" but the patent text reviewed for this article does not describe a step that removes the hCG or a test for it in the final product.²³
• Fish protein. In salmon sperm, DNA comes packaged with protamine, a protein that is isolated from the same source for use as a drug. Given into a vein, protamine is associated with hypersensitivity reactions that range up to life-threatening.²⁵ PDRN purification is designed to remove or inactivate protein,⁹ but the amount left in a finished serum goes unpublished.
• Bacterial endotoxin. Endotoxins are fragments of bacterial cell walls, and manufacturers describe removing them with resins.¹ No published test results for endotoxin in retail serums turned up.
• Breakdown products. A 2026 review notes that free nucleotides, nucleosides, and other degradation products may be present depending on extraction, sterilization, and storage, and lists them among the fractions a PDRN preparation should be tested for.⁷
• Plant leftovers. Plant-derived PDRN can carry polysaccharides, phenolics, pigments, RNA, and residual protein from the source plant.⁷ The peony study's authors chose a non-chemical method because of what they called a drawback of chemical extraction: "the presence of residual chemicals."²⁰
• Pollutants from the source fish. A PubMed search in October 2026 turned up no published testing of PDRN raw material or finished serums for heavy metals or persistent pollutants, so whether any carry over from the fish is an open question.
• The rest of the formula. PDRN is one line on a long ingredient list. In the microneedling case reports, two patients tested positive on patch testing to the serum that had been needled into their skin,¹⁰ which makes the full list part of the question, including preservatives, solvents, and fragrance and essential oils.

A patent describes what a company claimed as its method, but it does not show what any one serum on a shelf contains. The way to find out is a certificate of analysis for the batch that lists DNA purity, fragment size, residual protein, residual solvents, endotoxin, heavy metals, and microbial count.

What Do the Studies on PDRN Show?

Evidence: moderate for injected PDRN in wound healing, limited for cosmetic injections, preliminary for serums. None of the randomized trials reviewed runs longer than six months.

Wound healing by injection

The largest human trial enrolled 216 people with diabetes and hard-to-heal foot ulcers at two medical centers in Italy. Participants received PDRN or a placebo for eight weeks, injected into muscle and around the ulcer, and neither they nor the researchers knew who received which. Complete healing was recorded in 37.3% of the PDRN group and 18.9% of the placebo group.²⁶ The trial weighed a prescription drug against a serious medical problem, which is a different calculation from using the same material on healthy skin for appearance.

Cosmetic injections

A 2025 systematic review of polynucleotide injections in aesthetic medicine found nine studies covering 219 patients and rated them low to moderate in quality.³ A 2026 systematic review limited to randomized trials found seven, with 183 participants in total, and the largest analyzed 42 people. The reviewers rated three trials at low risk of bias, three with some concerns, and one at high risk.² Both reviews reported improvements in wrinkles, skin texture, scars, or healing, but both called for larger or more rigorous trials.³²

The phase III trial of the injectable Rejuran compared it with a hyaluronic acid filler for crow's feet in 72 patients. The Journal of Korean Medical Science retracted that paper in 2016 after a reader raised concerns, and its publication board concluded that the article was "an impaired publication of conflict of interest by wrong disclosure."⁵ Retraction Watch reported that the paper had declared no financial ties and listed only a government program as its funding, while one author worked in the manufacturer's research center and the corresponding author said a pharmaceutical company paid the trial's expenses.⁶

A later randomized, double-blind, split-face trial in 27 people compared a PN filler with a non-cross-linked hyaluronic acid filler around the eyes. Overall appearance scores did not differ between the two sides, while measured skin roughness and pore volume improved more on the PN side.²⁷

A 2026 expert paper states that no cases of granuloma or vascular occlusion from PN had been reported in the literature to date, but adds that "the possibility of rare events cannot be fully excluded." Two of its six authors work for Rejuran's manufacturer.¹¹ In a rabbit study from the same year, PN injected directly into an ear artery blocked blood flow temporarily, without the tissue death that a cross-linked hyaluronic acid filler caused.²⁸

Serums and creams

One randomized, double-blind, split-face study in 31 women compared an eye cream containing 0.1% salmon PDRN with the same cream base containing 0.1% retinol for 28 days. Crow's feet wrinkle area and count fell by 20% or more on the PDRN side and by 7% or less on the retinol side, and no adverse reactions were reported over those four weeks.¹⁹

That study had no plain-cream comparison, and two of its five authors list a skincare company's research institute as their workplace. The authors also wrote that longer studies are needed "to distinguish early hydration- or plumping-related changes from sustained dermal remodeling."¹⁹ A 2026 dermatology review states that topical PDRN products "may have limited penetration and, hence, are less efficacious than injections."¹

A 2026 journal supplement described eight selected patients who used a multi-ingredient serum after lasers, microneedling, or chemical peels. The serum combined bacteria-derived PDRN with a botanical complex, ectoin, a peptide, glycerin, and hyaluronic acid, so its results cannot be credited to PDRN alone, and one of the authors is employed by SkinCeuticals.²²

What to Ask Your Esthetician Before a PDRN Treatment

Evidence: a practical checklist drawn from the studies, patents, and regulations cited above.

My own answer to PDRN is to wait. For anyone who is offered it and is weighing the decision, these questions follow from the research above and from the principle of informed consent, which means being given enough information to weigh a service before agreeing to it.

1. How will the PDRN be delivered: on the surface, with microneedling, or by injection? Needles and injections carry the product past the skin barrier, and that is where the granuloma reports come from.¹⁰
2. What long-term safety data exist for this exact product? The longest randomized trial of any PDRN or PN product ran six months.²
3. What is the exact product, and can I read the full ingredient list? PDRN appears as Sodium DNA or Hydrolyzed DNA, and every other ingredient goes wherever the PDRN goes.
4. Where does the DNA come from: salmon, trout, a plant, or bacteria? The answer matters for fish allergy and for how much of the research applies to the product.
5. Which solvents and reagents were used to extract it, and has the DNA been depurinated? Patents name phenol, chloroform, and isopropanol,²³ and the drug-grade process added depurination as a safety step.¹⁷
6. Does the manufacturer provide a certificate of analysis for this batch? A full one lists DNA purity, fragment size, residual protein, residual solvents, endotoxin, heavy metals, and microbial count.
7. Is the product sterile, single-use, and labeled by its maker for use with needling? The granuloma case reports involved serums made for the skin surface that were needled into the dermis.¹⁰
8. Which device are you using, and what is it cleared to do? The federal device category for aesthetic microneedling excludes delivering topical products through the skin.¹³
9. Is this service within your license in this state, and is a medical provider involved? Rules on who may perform microneedling and injections differ from state to state.
10. How do you screen for fish allergy, autoimmune conditions, pregnancy, and active skin infection? A published review lists each of these as a caution or contraindication and calls for a patch test with a history of fish hypersensitivity.¹
11. Which studies support this product by this route, and who paid for them? Several of the papers cited here have authors employed by manufacturers, and one phase III trial was retracted over undisclosed funding.⁵
12. What reactions have you seen, and who do I contact if bumps or redness appear weeks later? The granulomas in the published cases did not clear consistently with treatment.¹²

If the answers are not available, that tells you how much is known about what is going into your skin.

PDRN Serum FAQ

Evidence: each answer draws on the sources cited in the sections above.

Is PDRN serum safe?

Its long-term safety is unknown, because no randomized trial has followed users beyond six months and a 2026 dermatology review states that no long-term data exist.¹² Short trials in fewer than 200 people recorded only local reactions,³ but trials of that size and length cannot detect rare or slow-developing harms.⁴

What are the side effects of PDRN?

The trials list pain, swelling, itching, bruising, and redness at the injection site, and a dermatology review adds temporary histamine reactions.³¹ Case reports tie serums that were microneedled into the skin to granulomas, although none of those reports involved PDRN.¹²

Is PDRN made from salmon sperm?

Most PDRN is purified from the sperm of salmon trout or chum salmon, and newer versions come from plants or Lactobacillus bacteria.⁹²² The label reads Sodium DNA or Hydrolyzed DNA either way, so the source usually has to come from the brand.¹⁸

Is PDRN natural?

The DNA comes from fish, plants, or bacteria, but the finished ingredient is a factory product: it is extracted with reagents, purified, heat-sterilized, and cut to a chosen size.¹¹⁷

Is PDRN FDA approved?

The FDA list of approved dermal fillers, retrieved on October 8, 2026, included no polynucleotide brand such as Rejuran, Plinest, Newest, or Nucleofill.¹⁵ PDRN serums are sold as cosmetics, and US law does not require cosmetic products or ingredients, other than color additives, to have premarket approval.¹⁶

Does PDRN serum work without microneedling?

One 28-day study of a 0.1% PDRN eye cream reported a larger drop in wrinkles than a retinol cream produced, with no plain-cream comparison and with skincare company researchers among its authors.¹⁹ A 2026 dermatology review states that topical PDRN has limited penetration and is less effective than injection.¹

Can you use PDRN if you have a fish allergy?

A 2026 dermatology review says people with hypersensitivity to fish "should be cautious" with these products and that a patch test is warranted first.¹ No published study has tested PDRN in people with a diagnosed fish allergy, which makes this a question for an allergist.

Can PDRN change your DNA?

A 2026 dermatology review states that no mutagenic potential has been reported so far but that theoretical concerns have been raised.¹ The original drug-grade process included a depurination step meant to remove the DNA's "informational capability," but the cosmetic PDRN papers cited here do not mention that step.¹⁷¹⁹

Is vegan PDRN safer than salmon PDRN?

No study has compared their safety in people. A 2026 review states that the evidence for plant-derived PDRN is mostly preclinical and should not be read as showing equivalence to fish-derived PDRN, and it lists plant residues and batch variation among the open issues.⁷

Sources

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2. Alhussain AM, 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. ↩
3. Lampridou S, Bassett S, Cavallini M, Christopoulos G. The Effectiveness of Polynucleotides in Esthetic Medicine: A Systematic Review. Journal of Cosmetic Dermatology. 2025;24(2):e16721. doi:10.1111/jocd.16721. Two authors practice at private aesthetic clinics. ↩
4. Hanley JA, Lippman-Hand A. If nothing goes wrong, is everything all right? Interpreting zero numerators. JAMA. 1983;249(13):1743-1745. PubMed 6827763. ↩
5. Notice of Retraction: Pak CS, et al. A Phase III, Randomized, Double-Blind, Matched-Pairs, Active-Controlled Clinical Trial and Preclinical Animal Study to Compare the Durability, Efficacy and Safety between Polynucleotide Filler and Hyaluronic Acid Filler in the Correction of Crow's Feet. Journal of Korean Medical Science. 2016;31(2):330. doi:10.3346/jkms.2016.31.2.330. ↩
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10. Soltani-Arabshahi R, Wong JW, Duffy KL, Powell DL. Facial allergic granulomatous reaction and systemic hypersensitivity associated with microneedle therapy for skin rejuvenation. JAMA Dermatology. 2014;150(1):68-72. doi:10.1001/jamadermatol.2013.6955. ↩
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22. Wu Y, Guénin S, Fung E, et al. Real-World Cases Using Phyto Polydeoxyribonucleotide (PDRN) Serum. Journal of Drugs in Dermatology. 2026;25(9):15491s2-15491s14. doi:10.36849/JDD.15491. Journal supplement; one author is an employee of SkinCeuticals. ↩
23. Kwon ON, Kim TH, Kim SH, inventors; Bio Medi Pharm Co., Ltd., assignee. Method for extracting high-purity polydeoxyribonucleotide from salmon testes. US patent 11,795,447 B2. Granted October 24, 2023. patents.google.com. ↩
24. Park HO, Lee IW, inventors; Bioneer Corp., assignee. Method for obtaining DNA from fish spermatogonium. US patent 6,759,532 B2. Granted July 6, 2004. patents.google.com. ↩
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