Skin boosters, Profhilo to Skinvive.

VYC-12 is a low-concentration, lightly cross-linked HA from the Vycross family, injected as intradermal microdroplets across the cheeks; VYC-12L adds lidocaine. Its evidence is the strongest in the category and still amounts to one randomised trial: 131 treated versus 71 untreated, 86% women, median age 58, responder rates of 57.9% on the cheek-smoothness scale and 58.3% on the fine-lines scale at month 1 against 4.5% and 5.4%, "consistent throughout the 6-month follow-up", six treatment-related adverse events and no discontinuations (Alexiades 2023). The prospective single-arm study provides the curve — roughness responders 96.2% at month 1, 76.3% at month 4, 34.9% at month 6, 87.1% after repeat, hydration improved through month 9 (Niforos 2019) — and the patient-reported one the satisfaction: 90.8% at month 1, 76.4% at month 9, 94% back to normal activities the next day (Ogilvie 2020). Digital texture analysis found 25.9% improvement at 45 days and 30.7% at six months (Cavallini 2019); explant work found collagen density, fibrillin-1, aquaporin-3 and glycosaminoglycans up against a hydrating comparator (Nakab 2020). Two retrospective safety analyses cover 1,577 and 2,126 treatments (Zarbafian 2022; delayed events).

Moderate rather than strong: one manufacturer-run randomised trial against no treatment, not a sham, and a six-month effect. It is nonetheless the product to choose if you want the booster whose result was measured by people who could not see which arm you were in. The filler guide carries the same row.

NASHA — non-animal stabilised hyaluronic acid — in a small-particle, low-cross-linked form, placed in the mid-dermis by micropuncture. The Hamburg studies established the pattern: significant improvement in elasticity and surface roughness with "extremely positive" feedback (Kerscher 2008) and increased firmness and viscoelastic recovery on a cutometer (Reuther 2010). The randomised evidence: a split-face trial by stamp-type injector with corneometer hydration higher on the treated side at weeks 2 through 12 and elasticity improved, melanin and redness unchanged (Roh 2016); the evaluator-blind hand study against saline, sustained to month 12 (Gubanova 2015); the 100-subject randomised hand trial with 87–96% still improved at 15 months (Wu 2020); a multicentre randomised comparison of two versus three initial sessions in which 75–84% were judged improved at three months with measurably increased hydration (NCT02403986). Real-world use in Korea: 77% satisfied, 66% reporting an effect beyond four months, roughness and brightness the strongest changes (Lee 2015).

And the counterweight: the double-blinded, sham-controlled, split-face cheek trial of transparent HA microdroplets, 14 patients, one treatment, no significant improvement over saline in wrinkling or elastosis (Jones 2018). The consensus protocol is three sessions then maintenance every four to six months, with "progressive enhancement of skin texture" reported to twelve months (Belmontesi 2018). Moderate: the longest record, the best body data, and the one clean negative.

Belotero Revive is a low-viscosity cohesive polydensified matrix HA with glycerol, marketed for "early intervention". The pivotal open-label study found gross elasticity increased at weeks 9 and 12, firmness to week 24, skin tone, radiance and hydration to week 36, roughness reduced to week 28 and redness to week 36, with a good safety profile (Hertz-Kleptow 2019). A randomised study of biophysical properties found firmness significantly improved after one (p = 0.028) and three (p = 0.003) treatments, with skin fatigue and density improving in the multiple-treatment group (Kleine-Börger 2022). The Korean study documented improvements across glow, firmness, surface evenness, tone evenness and transepidermal water loss at weeks 12 and 24 with a 100% improvement rating at week 12 (Park 2025). The split-face randomised pore trial is in Part 01 (Rutnumnoi 2025).

The most useful study is the comparison: HCC (Profhilo) on one side and CPM-HA20G on the other in healthy women — both improved surface hydration, elasticity, water loss and melanin from baseline, with "no significant differences between the tested products in the observed skin characteristics over time" (de Wit 2022). Delivery by cannula, needle or stamp gave comparable results with less pain by cannula (Booysen 2026). Moderate, on consistent small studies with two randomised designs and no saline arm.

Un-cross-linked HA lasts days in the skin, so its effect has to be biological — water drawn in, fibroblasts nudged — rather than a resident gel. The evidence is small and unusually well designed. Fifty-five women received non-cross-linked HA with mannitol (14 mg/g) in one cheek and saline in the other, three monthly sessions, blinded: skin stiffness fell only on the HA side at one and three months, dermal thickness rose on both sides at one month and only on the HA side at three, and a blinded panel scored complexion radiance better on the HA side at three months (p = 0.012) (Baspeyras 2013). In the hands, HA against saline by ultrasound: dermal density +24% versus +6% at four weeks and +18% versus 0% at ten months in responders (Tedeschi 2015). An open-label post-marketing study of a non-cross-linked gel raised skin capacitance from 23.1 to 33.2 units with no adverse events (Chahine 2025); a two-product protocol combining a filler with a Viscoderm booster improved hydration and water loss over the filler alone (Iannitti 2016); a retrospective controlled ultrasound study of a cannula-delivered HA hydrogel reported a 92.7% rise in skin density against no change in controls (Majewska 2025).

Moderate: the saline-controlled designs are the best in the class, the studies are small, and the effect needs repeating every few months. If a clinic's "skin booster" is plain HA at a plain price, the evidence does not say you are getting less than the branded gel — it says the branded gel lasts a little longer.

The premise is that amino acids are collagen's raw material and HA fragments the signal; the products (Sunekos, Jalupro and several Asian composites) mix them for intradermal injection. The systematic review and meta-analysis found 11 studies: wrinkle severity reduced by 2.15 points, global aesthetic improvement up 3.13 at three months, dermal thickness up 0.42 mm, cell viability improved in vitro, and an adverse-event risk ratio of 5.20 with a confidence interval from 0.53 to 50.77 — that is, unknown (Mosteirin 2026). The single large trial is Chinese: 456 enrolled, 439 completed, randomised 2:1 to three monthly injections of a sodium hyaluronate solution with glycine, proline, leucine and lysine or no treatment; 97.56% versus 3.95% improved at one month, hydration and elasticity better to three months, adverse events in 1.67% (Yang 2026). A histological study of HA fragments with amino acids found more fibroblast activity, type III collagen and vessels on biopsy, and "no statistical difference in skin thickness" on ultrasound (Scarano 2024); an HA-amino-acid-vitamin complex raised hydration and viscoelasticity 11–12% and density 23% at 42 days "without causing changes in skin wrinkles" (Siquier-Dameto 2024).

Moderate on the meta-analysis and the one large untreated-control trial; the European brand names return no controlled trials under their own names in PubMed, so a clinic offering Sunekos or Jalupro is offering the class's evidence, not the product's. The systematic review of HA skin quality found HA alone outperformed cocktails (Ghatge 2023) — the amino acids may be doing less than the marketing says.

Profhilo's hybrid cooperative complexes are stable to hyaluronidase digestion and, in fibroblast and 3D skin models, raised expression of collagens I, III, IV and VII and elastin above either HA fraction alone (Stellavato 2016). The clinical literature is reviewed by its own scientists as showing "a reduction in wrinkle severity, improvement in skin roughness profile and reduction of skin laxity with pronounced improvement in superficial skin hydration lasting up to 6 months" (Tintor 2025; Sparavigna 2026). The independent comparison found it equal to Belotero Revive on every measured property (de Wit 2022). The trial that matters is the randomised, triple-blind, split-face study of twelve women aged 45–65: two sessions of 1 ml a side around the mouth against saline; at 60 days stereophotogrammetry showed visual improvement in wrinkles and pores, ultrasound showed dermal thickness increased with Profhilo (p = 0.016) and with placebo (p < 0.001), 36.4% expressed dissatisfaction with the decision and 54.5% with the outcome, and the authors concluded that "its impact on dermal thickness did not exceed the placebo effect" (Zanella 2026).

Emerging: the "bioremodelling" claim rests on the laboratory and the open-label studies, and the one blinded test of it was negative on its objective endpoint; the hydration effect is real and equal to a cheaper product. What is beyond argument is safety — 371 adverse events across a projected 1,091,956 patients, 0.034%, mostly swelling and redness (Salti 2025), twelve reports in the first three years (Cassuto 2020). The fat-compartment version, Profhilo Structura, has a pilot study and a review, and is a filler question (Sparavigna 2024; Forte 2024).

NCTF 135HA carries 5 mg/ml of non-cross-linked HA and a list of some fifty vitamins, amino acids, minerals, coenzymes and nucleic acids. Its randomised trial allocated 146 subjects 107:38 to three sessions of NCTF or a routine anti-aging cream: at days 75 and 120 NCTF "significantly reduced wrinkles in all three areas and improved facial radiance scores compared with the control", hydration rose within a week of the last injection, self-esteem scores improved, and adverse events were mild and injection-related — "funded by Laboratories FILLMED" (Fanian 2023). The 2026 split-face trial of premixed toxin and NCTF against toxin alone is in Part 01 (Alzayadneh 2026).

Emerging rather than moderate because a cream is not a sham: a hundred microinjections of anything would be expected to beat a moisturiser on a wrinkle scale at day 75, and the systematic review of the category found HA alone outperforming HA cocktails (Ghatge 2023). Pleasant, plausible, cheap per session, and unproven beyond "injecting hydrating things hydrates".

Polynucleotides sit on the booster menu and in the biostimulator literature at once. The systematic review found nine studies of low-to-moderate quality in 219 patients with promising wrinkle, texture and elasticity results and "limited consensus regarding their optimal use" (Lampridou 2025); the phase 3 trial that launched Rejuran found no statistically significant difference from an HA filler on crow's feet (Pak 2014); the periocular split-face trial found no difference from HA on the visual scales, with better instrument scores for elasticity, hydration, roughness and pores (Lee 2022); the Italian consensus sets out protocols by area (Cavallini 2021).

Emerging, for the reasons the biostimulator guide gives at length: equal to HA in the trials that compared them, never tested against saline, and sold on the device route. As a booster it is a reasonable choice for someone who reacts to HA products or wants an alternative; it is not an upgrade.

A search of PubMed titles for Neauvia's HA-and-calcium-hydroxyapatite booster returns no clinical trial under the product name; the studies that exist for that manufacturer concern its cross-linked fillers, including a reassuring one in patients with Hashimoto's disease (Kubik 2023). Clinic-mixed "vitamin cocktails" have no CE mark, no lot number and no trial. PRP applied as a facial booster borrows the evidence of the biostimulator guide, where it is moderate for skin thickness and weak for wrinkles; exosome serums are graded limited there for the reasons the FDA's safety notice gives. The newest entrant, an injectable particulated acellular dermal matrix, has one randomised split-face trial and no European track record (Lee 2026).

Limited on evidence, not necessarily on effect: an unstudied HA gel probably hydrates like the studied ones. But the price of a booster is paid for a product, and the products with trials cost the same. Insist on one.