Retinol Meets Hyaluronic Acid: A Potent Duo for Anti-Aging Skincare

Retinol and hyaluronic acid—two skincare giants—are often praised individually, but when combined, their impact on aging skin is transformative. A groundbreaking international clinical study published in the Journal of Cosmetic Dermatology has examined the synergistic effects of retinaldehyde (a form of retinol) and intermediate-size hyaluronic acid fragments (HAFi) in combating skin photoaging. With a large-scale subject group of 1,462 participants across 12 countries, this study offers robust, statistically significant evidence supporting the use of this potent anti-aging combination.

Let’s break down the research findings to understand how this powerful duo can rejuvenate aging skin and redefine your skincare routine.

Skin aging is a multifaceted process influenced by internal (chronological aging) and external factors (especially UV radiation, termed photoaging). Factors like stress, pollution, smoking, and rapid weight loss can further accelerate visible signs of aging such as wrinkles, pigmentation, and sagging.

Retinoids, including retinol and its derivatives, are compounds derived from vitamin A. While retinoic acid is known for its effectiveness, it can be irritating to the skin. That’s where retinaldehyde (RAL) comes in—a gentler, precursor molecule to retinoic acid that offers similar anti-aging benefits with better tolerance. Studies have shown that RAL increases epidermal thickness, stimulates collagen synthesis, and improves skin texture and wrinkles.

Hyaluronic acid (HA) is a natural sugar molecule present in the skin’s extracellular matrix. It's renowned for retaining water and keeping skin plump. When skin ages or is damaged, HA breaks down into fragments. Interestingly, these fragments, particularly the intermediate-sized ones (HAFi, 50–400 kDa), have been found to promote keratinocyte proliferation and skin regeneration.

Combining RAL and HAFi was hypothesized to offer enhanced effects on aging skin—and the results did not disappoint.

The study aimed to evaluate the effectiveness of topical applications containing a combination of retinaldehyde and intermediate-size hyaluronic acid fragments (HAFi) in improving signs of facial photoaging.

Specifically, it sought to determine:

• The degree of wrinkle reduction on targeted facial areas
• Improvement in clinical signs of aging (e.g., pigmentation, ptosis, dryness, and elasticity)
• Skin evenness and texture through digital profilometry
• Product tolerability and patient satisfaction

Three product regimens were tested:

1. Group 1: RAL 0.05% + HAFi 0.5% cream (Eluage® Cream)
2. Group 2: RAL 0.05% + HAFi 1% anti-wrinkle concentrate
3. Group 3: Combination of both products

Study Design & Participants

• Type: Open, multicentric, international clinical study
• Duration: 90 days
• Participants: 1,462 subjects (96% women), ages 45–89 (mean: 54)
• Countries Involved: France, Germany, Italy, Poland, China, Argentina, Canada, Mexico, etc.
• Skin Type: Mostly dry or combination skin; Phototype II (35%) and III (44%)

Application Routine

• Eluage® Cream (RAL 0.05% + HAFi 0.5%) applied to the full face and neck.
• Antiwrinkle concentrate (RAL 0.05% + HAFi 1%) applied to deeper wrinkles.
• Group Allocation:
  • Group 1: Cream only (17% of subjects)
  • Group 2: Concentrate only (13%)
  • Group 3: Both products (70%)

Participants were evaluated at Day 0 (D0), Day 30 (D30), and Day 90 (D90).

Evaluation Metrics

• Photoaging Severity: Larnier’s 6-point photographic scale
• Wrinkles: 4-point visibility scale (0 = none, 3 = highly visible)
• Skin Texture: Measured by optical profilometry
• Complexion Evenness: Visual Analog Scale (0 to 10)
• Clinical Signs: Dryness, pigmentation, elasticity, ptosis
• Satisfaction & Tolerance: Evaluated by dermatologists and users

1. Significant Reduction in Overall Photoaging

Across all three groups, participants showed significant improvement:

• Group 1 (Cream): Larnier’s score dropped from 3.01 to 2.51 (↓15%)
• Group 2 (Concentrate): Dropped from 3.53 to 2.85 (↓19%)
• Group 3 (Both): Dropped from 3.73 to 3.03 (↓18%)

Larnier's Scale ranges from 1 (mild) to 6 (very severe photoaging)

2. Noticeable Wrinkle Reduction in Targeted Areas

Using a 4-point wrinkle visibility scale, Group 2 and 3 (those using the concentrate) saw:

• Crow’s Feet: ↓27% in both groups
• Forehead Wrinkles: ↓19% (Group 2), ↓10% (Group 3)
• Nasolabial Folds: ↓20% (Group 2), ↓16% (Group 3)
• Perioral Wrinkles: ↓34% (Group 2), ↓23% (Group 3)
• Glabellar Frown Lines: ↓14% (Group 2), ↓15% (Group 3)

All changes statistically significant at P < 0.001

3. Clinical Signs of Aging Greatly Improved

Dermatologists observed remarkable reductions in aging symptoms for Groups 1 and 3:

• Dryness: ↓65% (Group 1), ↓62% (Group 3)
• Hyperpigmentation: ↓34% (Group 1), ↓31% (Group 3)
• Ptosis (Sagging): ↓18% (Group 1), ↓22% (Group 3)
• Loss of Elasticity: ↓32% (Group 1), ↓33% (Group 3)

4. Complexion Evenness and Glow Enhanced

Skin evenness improved steadily:

• Group 1: ↑33%
• Group 2: ↑38%
• Group 3: ↑53%

Improvement evaluated on a visual scale from 0 (uneven) to 10 (very even)

To objectively quantify changes, optical profilometry (a skin surface analysis technique) was used in a subgroup of 18 subjects from Group 3:

• Wrinkle Roughness (Spa): ↓10.9%
• Wrinkle Depth (Sptm): ↓9.2%
• Skin Surface Density (Sdev 100): ↓13.3%

Skin replicas clearly showed smoother, less wrinkled skin after 90 days.

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Excellent Tolerability and High Satisfaction Among Users

• Tolerance Ratings:
  • Group 1: 98% rated as good/very good
  • Group 2: 97%
  • Group 3: 96%
• User & Dermatologist Satisfaction:
  • Group 1: 97% satisfied or very satisfied
  • Group 2: 94%
  • Group 3: 94%
• Usage:
  • Most users applied about 1 full tube/month of each product.

Participants appreciated the texture, scent, and absorption rate of the products.

This large-scale international study—possibly the first of its kind involving over 1,400 participants—proves that combining retinol (retinaldehyde) and hyaluronic acid fragments results in significant anti-aging benefits, including wrinkle reduction, improved elasticity, reduced pigmentation, and enhanced skin texture.

What makes this study stand out:

• Large, diverse international population
• Quantifiable improvements with statistical significance
• Real-world usage conditions
• Dual approach addressing both dermal and epidermal layers

Whether you're battling fine lines or looking to restore your skin’s glow, incorporating a formulation with retinaldehyde and HAFi may offer a scientifically proven pathway to youthful skin.