In his last self-portraits, Rembrandt van Rijn painted his own face without smoothing it. The lines are there in thick paint, including the creases that run from the nose toward the corners of the mouth. He was not flattering himself. He was recording what a life had done to a face.

Patients who ask me about nasolabial fold filler are often asking for the reverse. The nasolabial folds are the creases from the side of the nose to the mouth, which many people call laugh lines or smile lines, and the treatment is hyaluronic acid (HA) gel injected along them to soften the shadow. They want to know whether it works, whether it is safe in that spot, and whether the brand on the syringe matters.

My argument is that nasolabial fold filler is one of the better-supported filler treatments, and the fold is a comparatively forgiving place to inject for common side effects, but the evidence is much stronger on "does it work" than on "which product is right for you." Three papers carry the case: a 2025 randomized trial in the Journal of Cosmetic Dermatology, a 2024 network meta-analysis of randomized trials, and a 2023 systematic review and meta-analysis of adverse events.

What is nasolabial fold filler, and who is it for?

Nasolabial fold filler is a gel, most often hyaluronic acid, placed beneath the skin along the crease between nose and mouth to make the fold shallower. Researchers grade the crease with the Wrinkle Severity Rating Scale (WSRS), on which a lower score means a shallower fold (Cho et al., 2025).

The 2025 randomized trial enrolled adults with WSRS 3 or 4 who wanted temporary correction, so it speaks to moderate and severe folds rather than faint lines (Cho et al., 2025). That is worth remembering, because a patient with a mild fold may be asking a different question from the one these trials answered.

Does one hyaluronic acid filler beat another? A 2025 split-face trial

In a 2025 randomized, double-blind, split-face trial, a new HA filler was statistically noninferior to an established one at 24 weeks (Cho et al., 2025). Seventy-two healthy adults at two centers in South Korea received one filler in each nasolabial fold, assigned by a random-number table, and were followed for 48 weeks (Cho et al., 2025). A split-face design lets each person act as their own control. The test product was LASBEAU Strong and the comparator was Restylane Lyft (Cho et al., 2025).

The primary measure was the mean WSRS at week 24, scored by three independent investigators. It was 2.02 ± 0.71 for the new filler and 2.27 ± 0.68 for the existing one, a difference of −0.26 ± 0.69, with the upper limit of the one-sided 97.5% confidence interval at −0.01 against a noninferiority margin of 0.29 (Cho et al., 2025). In plain terms, the new product was not worse than the old one by more than the allowed amount.

The secondary scores moved the same way. Across visits at weeks 8, 16, 24 and 48, WSRS means were 2.38, 2.49, 2.71 and 2.88 for the new filler and 2.47, 2.57, 2.85 and 3.04 for the existing one, with no statistically significant difference at any visit (Cho et al., 2025). The scores drift upward over time in both arms, meaning the folds gradually deepened again, though the week 48 means still sit below the WSRS 3 to 4 required at entry (Cho et al., 2025).

Local side effects were common and similar between products. Pain was reported by 41.67% on the test side and 29.17% on the control side (p = 0.1168), swelling by 40.28% and 29.17% (p = 0.1614), and bruising by 23.61% on both sides (Cho et al., 2025). No systemic adverse events were judged related to the devices (Cho et al., 2025).

How does hyaluronic acid compare with other filler materials?

A 2024 network meta-analysis of 13 randomized trials reported that HA outperformed collagen fillers at six months and caused fewer nodules than bovine collagen, while poly-L-lactic acid (PLLA) looked promising (Li et al., 2024). I could read only the abstract of this paper, so what follows is limited to what the abstract reports.

At six months, WSRS scores were significantly lower with HA than with bovine collagen (mean difference −0.580; 95% CI, −0.777 to −0.383) and than with porcine collagen (−0.525; 95% CI, −0.790 to −0.260) (Li et al., 2024). Compared with PLLA, scores were higher with HA (0.630; 95% CI, 0.275 to 0.985), so PLLA scored better on that measure (Li et al., 2024). HA was less likely than bovine collagen to cause nodule formation (relative risk 0.593; 95% CI, 0.438 to 0.803) (Li et al., 2024). The authors concluded that HA is a safe filler for nasolabial folds and that PLLA showed potential (Li et al., 2024).

Is the nasolabial fold a safe place to inject? What pooled adverse event data show

In a 2023 meta-analysis of HA filler trials, the nasolabial fold had significantly less swelling and fewer lumps than other facial sites such as the midface, perioral lines and lips (Colon et al., 2023). The review pooled 19 randomized or clinical trials conducted in the United States and Canada between 2000 and 2022, covering 14 filler types, and rated all of them at low risk of bias with the Joanna Briggs Institute checklist (Colon et al., 2023).

Swelling was estimated at 17.1% (95% CI, 7.0 to 36.1) at the fold versus 73.4% (95% CI, 50.1 to 88.3) at other sites (p = 0.004). Lumps and bumps were 2.9% (95% CI, 0.01 to 13.8) versus 32.1% (95% CI, 7.3 to 73.9) (p = 0.027) (Colon et al., 2023). Pain (7.6% versus 12.3%, p = 0.627), bruising (7.9% versus 16.3%, p = 0.531) and erythema (9.9% versus 0.02%, p = 0.167) did not differ significantly (Colon et al., 2023).

Read those numbers with the confidence intervals beside them. They are wide, and heterogeneity (the degree to which studies disagree) was very high, with I² between 95.0% and 98.0% for these outcomes (Colon et al., 2023). The review also pooled only nine common injection-site events. It did not report pooled rates of rare emergencies such as vascular occlusion, so this section is reassurance about swelling and lumps, not about those events (Colon et al., 2023).

The strongest objection

Some will say that the 2025 trial shows a newer product works as well as an established one, so the brand does not matter and the choice is a matter of price. That is partly true. For the two products compared, at the endpoints measured, the difference was within the allowed margin (Cho et al., 2025).

But a noninferiority result answers a narrow question. The 0.29 margin was set from a historical comparison, the study was funded by the company that makes the test product, and the two syringes differed in HA concentration (24 versus 20 mg/mL) and needle gauge (26 versus 29) (Cho et al., 2025). The paper does not report participants' age or sex beyond adulthood, and its tables list week 24 means (2.71 and 2.85) that differ from the primary analysis values (2.02 and 2.27) without an explanation I could find (Cho et al., 2025). Across materials, the network meta-analysis suggests that the choice does matter, since collagen fillers performed worse and caused more nodules than HA (Li et al., 2024). Two HA gels being comparable does not make every filler comparable.

How should you choose a nasolabial fold filler?

The first question is what kind of fold you have. The trials enrolled moderate to severe folds (Cho et al., 2025), so a faint line may call for a different conversation than a deep one.

The second is the material and why it was chosen. The pooled trial data favor HA over collagen products for both correction and nodules (Li et al., 2024), and an alternative such as PLLA is worth asking about, with the caveat that the abstract I read gives only a short summary of it (Li et al., 2024). It is fair to ask what the plan is as the fold gradually returns, since scores rose between week 8 and week 48 in the best-controlled trial available (Cho et al., 2025).

The third is what to expect afterward. At this site, swelling and lumps were less frequent than elsewhere on the face, but local swelling, pain and bruising still occurred in a substantial share of treated sides (Colon et al., 2023; Cho et al., 2025).

The Clinical Bottom Line

Nasolabial fold filler with hyaluronic acid is a reasonable, well-studied option for moderate to severe folds. A 2025 randomized trial found two HA products comparable at 24 weeks (Cho et al., 2025), a 2024 network meta-analysis favored HA over collagen fillers (Li et al., 2024), and a 2023 meta-analysis found less swelling and fewer lumps at the fold than at other facial sites (Colon et al., 2023).

The caution is about what the evidence cannot yet say. Product comparisons are narrow and often manufacturer funded, safety data cover common events rather than rare ones, and I could not read the full network meta-analysis. We still lack long follow-up, independent head-to-head trials, and clear guidance on matching material to fold depth and to the patient.

Rembrandt kept the lines. A good consultation asks which of yours you want softened, and says plainly what the gel can and cannot do.

For clinical assessments and consultation in Seoul: itsdrbock.com

References

Cho, J. Y., Kim, S. H., Cho, H., Park, Y., Yang, H. J., An, J. S., Won, C. H., & Lee, J. H. (2025). Noninferiority study comparing the efficacy and safety of a new hyaluronic acid (HA) filler containing lidocaine with an existing HA filler for the treatment of nasolabial fold wrinkles: A randomized, double-blind, split-face trial. Journal of Cosmetic Dermatology, 24(7), Article e70309. https://doi.org/10.1111/jocd.70309

Colon, J., Mirkin, S., Hardigan, P., Elias, M. J., & Jacobs, R. J. (2023). Adverse events reported from hyaluronic acid dermal filler injections to the facial region: A systematic review and meta-analysis. Cureus, 15(4), Article e38286. https://doi.org/10.7759/cureus.38286

Li, M.-Y., Chien, W.-Y., Kang, Y.-N., & Chen, C. (2024). Efficacy and safety of fillers for the treatment of nasolabial folds: A network meta-analysis of randomized controlled trials. Aesthetic Plastic Surgery, 48(17), 3452–3462. https://doi.org/10.1007/s00266-024-03889-3