Every time you look in the mirror, do you sigh at your thin lips or vertical wrinkles?
"I'd like to try it, but I'm scared"—if you've been caught in that loop, searching month after month or year after year.
Your anxiety is justified. Lip injections do carry real risks if approached without knowledge.Without proper knowledge, there are indeed risks.But at the same time, when properly understood, it's a treatment that doctors worldwide have trusted for over 20 years.
In this article, we clarify three things based on scientific data and the latest clinical trials.
- To the lipsHyaluronic acid injectionisWhy it achieves immediate effects and long-term rejuvenation simultaneously
- Combination therapy with botulinum toxin for wrinkles around the mouthHow specifically it can be approached
- 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 neither "avoid it out of fear" nor "just try it on a whim,"but will be able to make decisions based on sound reasoning.
Hyaluronic acid injection to the lips and face: Basic mechanism for achieving your ideal lip 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 binds powerfully with water molecules, replacing the volume at the injection site to deliverinstant volume enhancement.This is stage one—in other words, "physical gap-filling."
But the story does not end there.
As the second stage, hyaluronic acid physically expands the extracellular matrix (ECM), thereby applying mechanical tension to fibroblasts. This tension acts as a trigger, andstimulation of new collagen and elastin productionhas been confirmed as a biological effect——even after the formulation itself is absorbed.
When you look at its duration in numbers, it is remarkably long. In the case of Restylane, a single retreatment maintains18 monthsof wrinkle and volume improvement, and with Juvederm products,18–21 monthsof improvement is sustained according to the data.
If you choose injection treatment, you should make that choice 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 lips and perioral lines (Perioral lines)
"Does it really work?"——to that question, there is clinical data from specialists around the world.
For treatment of lips and perioral lines (Perioral lines), there is a standardized injection approach. Specifically,a technique is proposed in which symmetric injections are administered 2 times each in the lower and upper lips, for a total of 4 injections.
However, for severe wrinkles, hyaluronic acid alone may sometimes be insufficient. This is where botulinum toxin combination therapy comes in.
How rigorously has this been researched——in one randomized, double-blind trial,60 women aged 25 to 60(mean age 41.9 ± 8 years) underwent treatment over a 20-week period. 100% of participants were female, and the subjects were patients with perioral wrinkle scores rated as "moderate or severe (2 or 3)."
In this study, the dose of OnabotulinumtoxinA was compared between two groups.
- Group 1 (31 people, mean age 40.8 ± 7.1 years): A total of 7.5 units (5 units in the upper lip, 2.5 units in the lower lip)
- Group 2 (29 people, mean age 43.2 ± 8.7 years): A total of 12 units (8 units in the upper lip, 4 units in the lower lip)
The primary endpoint was "wrinkle improvement of 1 point or greater." So what were the actual safety numbers——in the next section, let's examine the comparison data with hyaluronic acid alone.
Scientific data proves: Hyaluronic acid alone vs. Botox combination comparison
"Won't combining them increase side effects too?"——many people think so. But the data defies that intuition.
In a multi-center randomized parallel-group trial by Carruthers et al.,30 people per groupwere compared for the safety of 3 types of treatments.
- Hyaluronic acid monotherapy group: Of 30 people, adverse events occurred in2 people
- Hyaluronic acid + OnabotulinumtoxinA 9 units combination 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 treatment, no extreme worsening in the incidence of adverse events was observed. Under appropriate technique,combination therapy functions as an effective option for rejuvenation around the mouth and lipshas been confirmed.
Now that safety is understood, let's learn about the differences in the formulations 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's a major misconception.
Hyaluronic acid fillers come in various types, and concentration, crosslinking degree, and particle size directly affect the gel's firmness, cohesiveness, and swelling rate. Broadly divided intomonophasic (single-phase)andbiphasic (two-phase)there are 2 types.
The monophasic typerepresentative 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 by splitting and spreading collagen fibersexcels at producing volume effect.
In contrast, thebiphasic typeCleviel Contour (C-C) is made with 4L crosslinking technology and contains 3 mg/mL lidocaine hydrochloride. What stands out is its concentration—50 mg/mL, which is2.5 timeshigher concentration hyaluronic acid than J-V. By creating large HA masses that compress surrounding collagen fibers to lift tissue,the risk of overcorrection (overfilling) is lowis a characteristic.
What matters is the result. Both of these fillersmaintain the facial profile for 48 weeks, the duration of effect has been confirmed. When designing delicate areas like the lips, understanding the physical properties (elasticity and cohesiveness) of the formulation is key to maintaining a beautiful finish.
Conversely, do you know that there are formulations that should absolutely never be used on the lips?
Filler formulations that should "absolutely be avoided" for lip injection?
This is information that, if you don't know, could result in irreversible consequences.
There are various types of injection agents used to restore facial volume loss, but there are formulations whose use is clearly not recommended for the lips—poly-L-lactic acid (PLLA: Poly-L-lactic acid)is one.
PLLA received FDA approval in August 2004 for use inHIV-related facial fat atrophy. Its mechanism works by triggering foreign body giant cell reactions in the subcutaneous tissue and promoting collagen production, therebygradually expanding volume over weeks to months.
Herein lies the problem.
Unlike hyaluronic acid fillers, PLLA cannot have its final appearance confirmed immediately after injection. In other words,the extent of swelling cannot be controlled. Therefore, lip enlargement (Lip enhancement) using PLLA results in outcomes that areunpredictableand PLLA injection into the lips or nose is strongly cautioned against by experts.
To safely achieve full, beautiful lips,Selecting a hyaluronic acid formulation that allows you to confirm the shape immediately after injection and has reversibilityis an absolute requirement.
So far, we have reviewed the current mainstream techniques. However, the future of injection therapy goes even further ahead.
Next-generation option: The potential of polynucleotide (HA-PN) composite fillers
Achieving both "regeneration" and "volume enhancement" simultaneously——research into such next-generation fillers is underway right now.
A "HA-PN composite filler" combining 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 showed the following:
- Juvederm VOLUMA:250mm³(maximum)
- Juvederm VOLBELLA:158mm³
- HA-PN 0.1%・0.5% composite filler:134mm³
- HA-PN 1% composite filler:127mm³
Subsequently, over 24 weeks the volume gradually decreased. However, even at week 24——
- VOLUMA at120mm³
- VOLBELLA and HA-PN 0.5% at98mm³
- HA-PN 1% at97mm³
- HA-PN 0.1% at92mm³
——all maintained their volume. Furthermore, what is particularly noteworthy is the pain index, whereHA-PN 1% composite filler suppresses the expression of the TRPV4 protein involved in pain sensation to a lower level than conventional HA fillers at 1.5% or 2.0% concentrationshas been confirmed. With the triple benefits of volume + regeneration + low pain, future developments are worth noting.
On the other hand, even with existing technologies, new approaches specialized in finer wrinkles and skin quality improvement are emerging.
Latest approach: Microneedle injection using mesoguns
"Lip volumization" is not the only injectable treatment. A method to fundamentally enhance fine wrinkles across the entire face and skin hydration——that isMesogun (automatic intradermal injector)hyaluronic acid injection using.
In a study of 60 Korean women (ages 19–60), a formulation containing 20.0mg/mL hyaluronic acid and 3.2mg/mL lidocaine was used. In a single treatment, across the entire face75 injection pointswith 0.02 mL at each point, for a total of 1.5 mL3 sessionsinjected over
Looking at the numerical data for improvement in moisture content, the difference is clear.
- 4 weeks after treatment (Week 8): HA group 43.32±16.14 vs Placebo 17.04±13.11
- 8 weeks after treatment (Week 12): HA group 45.21±14.24 vs Placebo 17.26±15.19
- 12 weeks after treatment (Week 16): HA group 44.68±14.37 vs Placebo 19.98±15.28
Over 16 weeks, more than twice the moisture improvement of placebo was maintained. For those concerned about fine wrinkles, it is worth knowing as an approach different from conventional point injection.
So far we have focused mainly on the discussion of "effects." But finally, we must address the most important matter——the truth about risks.
Side effects and risks: The truth about safety you need to know and recovery options
You have a duty to understand the risks as much as the possibility of becoming beautiful. Do not turn away from this.
While 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 injection into the face (primarily the nose and surrounding areas), transient vascular occlusion occurred in30 cases, and skin necrosis in7 casesand vision changes8 casesand infections6 caseswere reported according to data (DeVictor 2021).
This is precisely why technique is paramount. To minimize these vascular complications,precise injection into deep layers such as above the periosteum or perichondriumand,small-volume (aliquot) injection of less than 0.05ml to 0.1ml or less at low pressure and slowly with cautiontechnique is strongly recommended.
But this is the greatest strength of hyaluronic acid.
Hyaluronic acid has a "hyaluronidase" dissolving enzyme. In the event of a vascular occlusion or ischemia emergency, injecting hyaluronidase can break down the hyaluronic acid and restore blood flow. In animal model experiments, subcutaneous injection of hyaluronidase within 4 hours of vascular injury onset can reverse potential skin necrosishas been demonstrated (DeVictor 2021).
Other permanent or semi-permanent fillers such as calcium hydroxyapatite and PLLA do not have this option. "reversibility—the ability to reset when needed" is one of the main reasons why hyaluronic acid continues to be chosen worldwide as the safest option.
Summary of this article: 4 key facts you need to know to make your decision
- HA injection works in two stages.In addition to immediate volumization, it expands the extracellular matrix to stimulate fibroblasts and promotes collagen production for long-term rejuvenation effects. With Juvederm products, the effect persists for up to21 monthsafter one retreatment.
- For wrinkles around the mouth, there is a standard "4-point injection technique."Two injections in the upper lip and two in the lower lip respectively. Safety data demonstrates that combination therapy with hyaluronic acid and botulinum toxin 9 units can be administered safely 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.In the event of complications such as vascular occlusion,hyaluronidase injection within 4 hourscan prevent damage. This reversibility is the greatest reason why hyaluronic acid is easier to manage safety-wise than other agents (DeVictor 2021).
If you're wondering "What about my case?"
Book a free consultation
We do not engage in 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 Clinics
He has a track record of research presentations at domestic and international academic conferences and is involved in technical instruction and education across Zetith Beauty Clinic. He specializes in precision aesthetic medicine based on anatomical evidence and pursues natural results tailored to each individual's bone structure and tissues.