The term “salmon DNA” is growing in popularity in Asia with cosmetic dermatology and aesthetic medicine clinics advertising injections and treatments that promise benefits for the skin as well as skin care manufacturers including this ingredient in their formulations for a multitude of alleged benefits.
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What is exactly Salmon DNA or PDRN?
Salmon DNA is the marketable term that refers to Polydeoxyribonucleotide (PDRN), a range of bioactive molecules derived from the purified and sterilized DNA extracted from the sperm of two fish species: chum salmon and salmon trout. The way PDRN is processed makes it safe for use without risks of triggering immune reactions.
Why sperm DNA?
You may wonder why using sperm cells to extract PDRN and not any other cell of the body since all contain DNA. The reason is simple, somatic cells, which are the cells of the body other than sperm and egg cells, when processed have a higher risk of carrying impurities in the final preparation, like proteins or pieces of proteins (peptides), and lipids, while with sperm cells extracted and purified at high temperature there is no such risk, making it a perfect source for PDRN.
How does PDRN work?
Salmon DNA seems to exert its effects primarily in 2 ways:
- binding to the adenosine receptor A2A
- salvage pathway
PDRN unlike other molecules isn’t metabolized by the liver, but it is attacked by enzymes known as DNA nucleases which degrade the large DNA molecule into smaller pieces called nucleotides and nucleosides, the first being the building block of DNA and RNA and the second being precursors to the former while also being bioactive molecules themselves.
The main action is caused by the binding of some of these nucleosides to the adenosine receptor A2A. This is a unique property of salmon DNA as it seems that different sources of PDRN, different mixes of polynucleotides or different manufacturing processes can’t replicate it. The interaction with this receptor causes a long-lasting cascade of events as it is involved in modulating inflammation, oxygen consumption, ischemia, cell growth and angiogenesis among the many.
A second action is caused by the availability of the nucleotides generated by the breakdown of the PDRN, which allows for what is known as “salvage pathway”: instead of synthetizing DNA from scratch, these pieces can be used to repair existing DNA; this is important because damaged or hypoxic cells, unlike healthy cells, often can’t synthetize new DNA. This allows them to heal, grow and proliferate leading to a faster tissue regeneration and healing process when compared to having to build and synthetize everything back from zero.
What are the effects of salmon DNA on the skin?
Most studies on PDRN are in-vitro, on cell cultures, and in-vivo animal studies focusing on tissue regeneration and healing of wounds.
Studies on fibroblasts cultures, the cells in the dermal layer of the skin that produce collagen, hyaluronic acid and elastin among the many, show that PDRN increases their proliferation. Studies on osteocytes (bone cells) and chondrocytes (cartilage cells) show that salmon DNA increases their proliferation and metabolism while reducing tissue degradation, showing potential in tissue regeneration. Salmon DNA extract also exerts anti-melanogenesis properties by inhibiting tyrosinase activity.
Thanks to its involvement in the salvage pathway, salmon DNA seems to have a protective effect against UV-induced DNA damage being able to enhance the DNA repair processes.
Animal studies confirm the ability of PDRN to improve wound re-epithelialization decreasing healing time not just by increasing cell proliferation and activity, but also through angiogenesis, which is new blood vessel formation: new and more blood vessels means restored blood flow to wounds and damaged tissue as well as more oxygen and nutrients to support tissue regeneration.
In animal studies, PDRN effectively decreased inflammatory markers, reduced damage and overall protected tissues in models of several diseases such as arthritis, colitis and periodontitis. Finally, salmon DNA has been tested in ischemia scenarios where it protected tissues from damage, reduced inflammation and limited the reperfusion injury.
Human studies are still limited in number and in sample size, but overall from what is available to date PDRN seems to have confirmed its tissue regeneration potential, proven effective in improving healing and/or managing symptoms of diabetic foot ulcers, surgical skin grafts, pressure ulcers, osteoarthritis, plantar fasciitis, corneal epithelium regeneration, rotator cuff disease and lichen sclerosus.
PDRN Injection (Rejuran, Placentex, ) as skin booster in aesthetic medicine
Salmon DNA injections are getting very popular in aesthetic medicine clinics. They are used to improve skin texture and quality, treating loss of volume, improving the look of scars, managing pigmentation issues, reducing pores size, improving skin hydration and are overall used as anti-aging mesotherapy treatment.
PDRN injections work by:
- Promoting synthesis of dermal matrix components such as collagen and elastin
- Inhibiting elastin degradation
- Reducing hyperpigmentation by inhibiting melanogenesis (inhibiting tyrosinase activity).
- Exerting an anti-inflammatory action
- Protecting from reactive oxygen species (ie. “free radicals”) reducing damage to cells, dermal proteins, DNA, …
- Anti-aging, by helping repair the DNA of damaged or hypoxic tissues and restoring normal cell proliferation and growth.
PDRN may also be helpful to fight hair loss and promoting hair growth, although more studies are needed to evaluate this effect. Another proposed application of PDRN injection is for skin priming prior to other minimally-invasive cosmetic procedures like lasers or prior to surgical procedures to reduce healing time, scarring and overall for better results.
In order to produce visible results, you’ll have to undergo several treatment sessions due to the short half-life of PDRN with most clinics advising to perform at least 3-4 sessions at 2-4 weeks intervals, plus maintenance treatments once or twice a year.
PDRN in skin care formulations as antiaging ingredient
Most studies available show the effectiveness of Salmon DNA when given to cell cultures or when injected in the dermis or in muscle tissue. In other studies, the effects of PDRN were evaluated in open wounds, when the skin barrier was disrupted due to mechanical injury. With skin care products, one of the hurdles for a formulation to be effective is that it must be able to penetrate the stratum corneum, the outermost layer of the skin, to reach the cells where it can exert its action.
PDRN molecules are 100 times to 3,000 times larger than what is known to be the right size for skin penetration; moreover, it is a hydrophilic molecule making it even harder to pass through the stratum corneum.
I have been in contact with a biotech company that markets skincare formulations containing PDRN to better understand how they addressed this issue: while they have been responsive and happy to help at the beginning of our conversation, they turned quiet once I highlighted the lack of evidence when claiming that salmon DNA is effective when applied topically to undisrupted skin and that such a large molecule is not able to penetrate the stratum corneum. The lack of answers when I got more technical makes me think they never solved, or even evaluated, the penetration issue.
A simple solution to this could be to use a dermaroller or microneedling device prior to the application of the topical PDRN formulation allowing it to cross the epidermis through the disruptions and micro-channels created by the microneedles. This may help the smaller polynucleotides close to the 50 KDa size cross the skin barrier, but it still won’t be enough for the larger polynucleotides close to the 1,500 KDa molecular weight. Other techniques like iontophoresis, sonophoresis, and radiofrequency may help at improving the penetration of PDRN, although the molecule may still be too large to cross the skin barrier and all these techniques would have to be proven effective in clinical trials first before claiming they are effective when used in combination with PDRN.
Another solution would be to break down the PDRN molecule and make it into smaller pieces: while this may still be partly effective from the salvage pathway point of view, it may not exert other actions or be as effective. A paper comparing the efficacy of different molecular weight PDRN molecules already showed that the 50-1,500 KDa size is the most effective when compared to molecules smaller than 50 KDa or larger than 1,500 KDa, hence more clinical trials would be needed to prove the efficacy of the preparation made with tiny salmon DNA pieces.
Complications and side effects of PDRN treatment
According to the published studies, PDRN treatment seems to be very well tolerated, with no toxic effects on brain, muscle tissue, liver, heart or lungs and no immune reactions. The only side effects reported by most subject are discomfort, bruising and itching in the injection area, common symptoms following any injection therapy that do not require medical intervention and spontaneously resolve within 1 week.
Issues with PDRN treatment
PDRN is promising, but it still has many issues before we can state without doubts that it is effective and safe.
One issue is that there is no definitive treatment protocol (number of sessions, interval between sessions, optimal dose, etc). There aren’t many rigorous studies and only few are human studies on a limited number of subjects, especially for the proposed aesthetic medicine applications. Studies are often funded or sponsored by the PDRN producers which does not necessarily implicate they have been designed to show good results, but it certainly increases the risk of bias in the investigators.
PDRN has a short half-life, meaning it is likely to require continuous injections for good results. An experiment comparing a gel for continuous release vs single injection vs control showed that the single injection did only slightly better than the control, while the gel significantly improved wound healing and angiogenesis. This may suggest that treatment with daily injections for several days to be repeated every few months may be the key to optimal and considerable results.
As highlighted in the previous paragraph on PDRN as skincare ingredient, the penetration of this molecule in the human epidermis is unknown and is unlikely to happen hence skincare formulations containing PDRN have yet to be proven effective in undisrupted skin.
Conclusion on PDRN treatment
In-Vitro and In-Vivo animal studies show that salmon DNA is effective and highlight its mechanism of action. Results seem to be consistent, especially when used in wound healing. When it comes to PDRN injections in aesthetic medicine, although there are still issues to be solved, overall the results seem promising and we can expect to see more high quality evidence and broader application of this substance in the near future. For cosmeceutical preparations containing PDRN, unless they address the skin penetration issue, they are unlikely to produce any result at all.
Sources
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F Squadrito – Frontiers in Pharmacology, Apr 2017
DOI: https://doi.org/10.3389%2Ffphar.2017.00224 - Polydeoxyribonucleotide-delivering therapeutic hydrogel for diabetic wound healing.
DY Shin – Scientific Reports, Oct 2020
DOI: https://doi.org/10.1038/s41598-020-74004-0 - An effective range of polydeoxyribonucleotides is critical for wound healing quality.
KH Hwang – Molecular Medicine Reports, Dec 2018
DOI: https://doi.org/10.3892/mmr.2018.9539 - Polydeoxyribonucleotide: A promising skin anti-aging agent.
A Khan – Chinese Journal of Plastic and Reconstructive Surgery, Dec 2022
DOI: https://doi.org/10.1016/j.cjprs.2022.09.015 - A Mixture of Topical Forms of Polydeoxyribonucleotide, Vitamin C, and Niacinamide Attenuated Skin Pigmentation and Increased Skin Elasticity by Modulating Nuclear Factor Erythroid 2-like 2.
HM Kim – Molecules, Feb 2022
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KY Park – Dermatologic Therapy, Feb 2016
DOI: https://doi.org/10.1111/dth.12299 - Comparison of the effects of polynucleotide and hyaluronic acid fillers on periocular rejuvenation: a randomized, double-blind, split-face trial.
YJ Lee – Journal of Dermatological Treatment, Feb 2022
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DOI: https://doi.org/10.1111%2Fjocd.13679
