Every time you look in the mirror, do you sigh at the thinness of your lips or the vertical lines?
"I'd like to try it, but I'm scared"—if you've been stuck repeating searches for months or even years with that thought.
Your anxiety is valid. That's because lip injectionsdo carry real risks if you proceed without knowledgeBut at the same time, with proper understanding, it's a treatment that physicians worldwide have trusted for over 20 years.
In this article, we clarify three points based on scientific data and the latest clinical trials.
- to the lipsHyaluronic acid injectionisWhy it achieves both immediate results and long-term rejuvenation simultaneously
- Combination therapy with botulinum toxin for wrinkles around the mouthHow specifically it can address problem areas
- To avoid failureThe truth about risks you absolutely must know, and recovery methods in case of complications
If you read to the end, you will be able to avoid both "fear-based avoidance" and "doing it somewhat randomly,"and make decisions based on evidence.
Hyaluronic acid injection to lips and face: Basic mechanisms to achieve your ideal mouth shape
Over 20 years.That is how long hyaluronic acid (HA)-based fillers have been used as the "gold standard" in aesthetic medicine.
So why has it been supported for so long? The answer lies in "two-stage effects."
First, immediately after injection. Hyaluronic acid bonds strongly with water molecules, replacing the volume at the injection site, bringing aboutimmediate volume enhancement.This is the first stage—in effect, "physical gap-filling."
But the story does not end here.
As the second phase, hyaluronic acid physically expands the extracellular matrix (ECM), applying mechanical tension to fibroblasts. This tension triggersthe generation of new collagen and elastin—a biological effect confirmed even after the preparation itself has been absorbed.
Looking at its duration in numbers, it is remarkably long. In the case of Restylane, with a single retreatment18 months, and with Juvederm products18–21 monthsof sustained improvement in wrinkles and volume have been documented.
If you choose injection therapy, you should make that decision with knowledge of these numbers. Now let's look at the specific techniques used to address the lips and perioral area.
Practical injection techniques for lip and perioral wrinkles (Perioral lines)
"Does it really work?"—to that question, clinical data from experts around the world provides an answer.
For treatment of lip and perioral wrinkles (Perioral lines), there is a standardized injection approach. Specifically,a technique involving 4 symmetric injections total—2 in the lower lip and 2 in the upper lip eachhas been proposed.
However, for severe wrinkles, hyaluronic acid alone may be insufficient. This is where combination therapy with botulinum toxin comes in.
How rigorously it has been researched—in one randomized double-blind trial,60 women aged 25 to 60 years(mean age 41.9±8 years) underwent treatment over 20 weeks. 100% of participants were female, and the subjects had perioral wrinkle scores rated as "moderate or severe (2 or 3)."
In this study, OnabotulinumtoxinA dosages were compared between 2 groups.
- Group 1 (31 patients, mean age 40.8±7.1 years): a total of 7.5 units (5 units to the upper lip, 2.5 units to the lower lip)
- Group 2 (29 patients, mean age 43.2±8.7 years): a total of 12 units (8 units to the upper lip, 4 units to the lower lip)
The primary endpoint was "improvement of 1 or more points on the wrinkle scale." So what were the actual safety numbers?—in the next section, let's look at the comparative data with hyaluronic acid alone.
Scientific data proves: comparison of hyaluronic acid alone vs. Botox combination
"Wouldn't combining them increase side effects as well?"—many people think so. But the data contradicts that intuition.
In a multicenter randomized parallel-group trial by Carruthers et al.,30 people per groupwere the subjects for safety comparison of 3 types of treatment.
- Hyaluronic acid monotherapy group: Of 30 people, adverse events occurred in2 people
- Hyaluronic acid + OnabotulinumtoxinA 9 units combination therapy group: Of 30 people, adverse events occurred in3 people
- OnabotulinumtoxinA 9 units monotherapy group: Of 30 people, adverse events occurred in4 people
In other words, between hyaluronic acid monotherapy and combination therapy, no extreme worsening was observed in the incidence of adverse events. Under appropriate technique,combination therapy also functions as an effective option for perioral and lip rejuvenationhas been confirmed.
Now that safety is clear, let's understand the differences in the products themselves. In fact, the "type" of filler you choose greatly influences the final result.
Filler types and characteristics: Differences between monophasic and biphasic
"All fillers are the same"—that is a major misconception.
Hyaluronic acid fillers come in various types, and concentration, degree of crosslinking, and particle size directly affect the gel's firmness, cohesiveness, and hydration rate. Broadly speaking,monophasicandbiphasicthere are 2 types.
Monophasic typeThe representative Juvederm VOLUMA (J-V) contains 20 mg/mL hyaluronic acid and 0.3% lidocaine. A smooth gel created by crosslinking 10% high-molecular-weight HA and 90% low-molecular-weight HA, which spreads by dividing collagen fibers, excels atvolume-building effects.
In contrast,biphasic typeCleviel Contour (C-C) is made with 4L crosslinking technology and contains 3 mg/mL lidocaine hydrochloride. Notable is its concentration—50mg/mL, which is2.5 timesthe high-concentration hyaluronic acid contained. By creating large HA masses that compress surrounding collagen fibers to lift tissue, it has the characteristic oflow risk of overcorrection (overfilling).
What matters is the result. Both of these fillers are confirmed tomaintain the facial profile over 48 weeksin their sustained effects. When designing delicate areas like the lips, understanding the physical properties (elasticity and cohesivity) of the formulation is key to maintaining a beautiful finish.
So conversely, did you know there are filler formulations that should absolutely never be used on lips?
What filler formulation should be "absolutely avoided" for lip injection?
This is a matter that could have irreversible consequences if you don't know about it.
There are various types of injectable agents for recovering facial volume loss, but there are formulations that are clearly not recommended for use on lips——Poly-L-lactic acid (PLLA).
PLLA received FDA approval in August 2004for use against HIV-related facial fat atrophy. Its mechanism works by triggering a foreign body giant cell reaction in subcutaneous tissue to promote collagen production, therebygradually expanding volume over weeks to months.
This is the problem.
Unlike hyaluronic acid fillers, PLLA cannot confirm the result immediately after injection. In other words,the extent of swelling cannot be controlled. Therefore, lip enhancement using PLLA results inunpredictableoutcomes, and PLLA injection into the lips and nose is strongly warned against by experts.
To safely achieve full and beautiful lips,Choose a hyaluronic acid formulation that allows shape confirmation immediately after injection and has reversibility——this is an absolute requirement.to do so——this is a non-negotiable condition.
Now, we've examined the current mainstream technologies so far. But the future of injection therapy goes even further ahead.
Next-generation options: The potential of polynucleotide (HA-PN) composite fillers
Achieving both "regeneration" and "volume enhancement" simultaneously——research into such next-generation fillers is now underway.
A "HA-PN composite filler" that combines polynucleotides (PN) extracted from the reproductive cells of fish such as salmon with hyaluronic acid.
In a comparative experiment where 100μL of various fillers were injected into the dorsal region of mice, the volume at 4 weeks was shown as follows:
- Juvederm VOLUMA:250mm³(maximum)
- Juvederm VOLBELLA:158mm³
- HA-PN 0.1%・0.5% composite filler:134mm³
- HA-PN 1% composite filler:127mm³
Subsequently, the volume gradually decreased over 24 weeks. However, even at week 24——
- VOLUMA120mm³
- VOLBELLA and HA-PN 0.5%98mm³
- HA-PN 1%97mm³
- HA-PN 0.1%92mm³
——all maintained their volume. Furthermore, what deserves attention is the pain index, whereHA-PN 1% composite filler suppresses the expression of TRPV4 protein, which is involved in pain perception, to a lower level than conventional HA fillers at 1.5% or 2.0% concentrationhas been confirmed. Volume + regeneration + low pain—a triple advantage, with future developments attracting attention.
Meanwhile, even with existing technologies, new approaches specialized in finer wrinkles and skin texture improvement are emerging.
Latest approach: Microneedle injection using Mesogun
"Lip volume enhancement" is not the only injectable treatment. A method that fundamentally elevates fine wrinkles across the entire face and skin moisture levels from the base——that isMesogun (automatic intradermal injector)hyaluronic acid injection using.
In a study of 60 Korean women (ages 19–60), a formulation containing 20.0 mg/mL hyaluronic acid and 3.2 mg/mL lidocaine was used. In a single treatment, the entire face received75 injection points, with 0.02 mL at each point, totaling 1.5 mL injected over3 sessions.
When viewing skin moisture improvement data by the numbers, the difference is striking.
- 4 weeks after treatment (Week 8): HA group43.32±16.14vs. placebo17.04±13.11
- 8 weeks after treatment (Week 12): HA group45.21±14.24vs. placebo17.26±15.19
- 12 weeks after treatment (Week 16): HA group44.68±14.37vs. placebo19.98±15.28
Over 16 weeks, more than twice the skin moisture improvement of placebo was maintained. For those concerned about fine wrinkles, this represents an approach worth knowing about as distinct from traditional point injection.
So far, we have focused primarily on "results." But finally, there is something far more important we must discuss——the truth about risks.
Side effects and risks: The true safety facts you should know and recovery options
You have a duty to understand risks equally as much as the possibility of becoming more beautiful. Do not turn away from this.
Although hyaluronic acid has a safe profile among synthetic fillers, the risk is not zero. Small fragments of hyaluronic acid can cause inflammation and trigger side effects such as erythema, mild edema, hematoma, itching, and pain.
And as more serious complications——Vascular occlusion, skin necrosis, vision loss (blindness)these risks, though extremely rare, do exist. In surveys of filler injections to the face (primarily the nose and surrounding areas), transient vascular occlusion occurred in30 cases, and skin necrosis in7 casesvision changes,8 casesinfection,6 caseshave been reported according to data (DeVictor 2021).
That is precisely why technique makes all the difference. To minimize these vascular complications,precise injection into deep layers such as supraperiosteal or suprachondral planesand,injecting small volumes (aliquots) of less than 0.05ml to 0.1ml or less at low pressure slowly and carefullyis strongly recommended.
However, this is hyaluronic acid's greatest strength.
Hyaluronic acid has a "hyaluronidase" enzyme that dissolves it. Even in an emergency where blood vessel occlusion or ischemia is suspected, injecting hyaluronidase can break down the hyaluronic acid and restore blood flow. In animal model experiments, injecting hyaluronidase subcutaneously within 4 hours of the onset of vascular complications can reverse potential skin necrosishas been demonstrated (DeVictor 2021).
Other permanent and semi-permanent fillers such as calcium hydroxyapatite and PLLA do not have this option. "the reversibility of being able to reset in case of emergency" is one of the greatest reasons why hyaluronic acid continues to be chosen as the safest option worldwide.
Summary of this article: 4 key facts you need to know to make a decision
- HA injection works in two stages.Beyond immediate volume enhancement, it expands the extracellular matrix to stimulate fibroblasts and promote collagen production, providing long-term rejuvenation effects. With Juvederm products, after one retreatment session, effects can last up to21 monthssustained.
- For perioral wrinkles, there is a standard "4-point injection technique."2 injections each on the upper and lower lips. Data demonstrates that combination therapy using hyaluronic acid and 9 units of botulinum toxin can be safely administered without significant worsening of adverse event rates compared to monotherapy.
- PLLA must not be used on the lips.Results are unpredictable and explicitly contraindicated by experts.
- There are risks, but 4 hours is the lifeline.If complications such as vascular occlusion occur,hyaluronidase injection within 4 hourscan prevent damage. This reversibility is the main reason hyaluronic acid is safer and easier to manage than other agents (DeVictor 2021).
If you're wondering "What about my case?"
Book a free consultation
There is no high-pressure sales. Please feel free to contact us.
References
- Liew S, Scamp T, de Maio M, et al. Efficacy and Safety of a Hyaluronic Acid Filler to Correct Aesthetically Detracting or Deficient Features of the Asian Nose: A Prospective, Open-Label, Long-Term Study. Aesthetic Surgery Journal. 2016 DOI
- Rho N, Youn C, Youn S, et al. A comparison of the safety, efficacy, and longevity of two different hyaluronic acid fillers in filler rhinoplasty: A multicenter study. Dermatologic Therapy. 2021 DOI
- Trevidic P, Kim H, Harb A, et al. Consensus Recommendations on the Use of Hyaluronic Acid–Based Fillers for Nonsurgical Nasal Augmentation in Asian Patients. Plastic & Reconstructive Surgery. 2022 DOI
- Trevidic P, Kim H, Harb A, et al. Consensus Recommendations on the Use of Hyaluronic Acid–Based Fillers for Nonsurgical Nasal Augmentation in Asian Patients. Plastic & Reconstructive Surgery. 2022 DOI
- Chen B, Ma L, Ji K, et al. Rhinoplasty With Hyaluronic Acid. Annals of Plastic Surgery. 2020 DOI
About the author of this article
Hiromitsu NakamuraPhysician, Ginza Clinic
Zetith Beauty Clinic Ginza, Shinsaibashi Osaka, and Fukuoka locations
Has research presentation experience at domestic and international academic conferences, and is involved in technical guidance and education across Zetith Beauty Clinic. Specializes in precision aesthetic medicine based on anatomical evidence, pursuing natural results tailored to each individual's skeletal structure and tissues.