Canine Atopic Dermatitis: New Evidence on Sphingolipids, Glycosaminoglycans and Nucleotides

Canine atopic dermatitis (CAD) represents one of the most complex challenges in current veterinary practice.

It is a chronic, genetically predisposed and progressive disease that significantly affects patients' quality of life and generates frustration in both veterinarians and owners.

The pathophysiology of CAD: a multifactorial problem

CAD is not simply a skin allergy. Recent research demonstrates that it involves a complex interaction between three fundamental components: the skin barrier, the immune system and the dermal microbiome.

In dogs with CAD, the skin barrier presents significant structural and functional alterations. Ceramide levels in the lipid matrix are reduced, filaggrin expression (an essential protein for stratum corneum integrity) decreases, and keratinocytes show dysfunction. As a result, permeability to allergens and transepidermal water loss increase, while chronic inflammation and secondary infections perpetuate the pathological cycle.

Recent studies, including the work of Dr. Rosanna Marsella published in 2025, indicate that environmental factors are playing an increasingly relevant role in the rising number of atopic dermatitis cases.

Urban life, processed food, reduced outdoor exercise, exposure to environmental pollutants and excessively clean environments appear to contribute to the increase of this pathology.

Multimodal management of the skin barrier

The current veterinary consensus establishes that CAD treatment must be multimodal and tailored to each patient. This approach includes three therapeutic pillars:

1. Skin barrier repair: reduces permeability to allergens, transepidermal water loss, inflammation and secondary infections.
2. Pruritus and inflammation control: through antipruritic and anti-inflammatory agents that improve clinical signs and prevent secondary damage.
3. Cutaneous microbiome stabilization: which contributes to reducing inflammation and infections, improving skin barrier stability.

Crucially, scientific evidence indicates that skin barrier repair is necessary in all cases, regardless of severity. Topical therapy is key to this objective, and this is where functional ingredients based on scientific evidence gain special relevance.

Innovative solutions with scientific backing

Bioiberica has developed three functional ingredients for cutaneous health maintenance, each with specific mechanisms of action:

Hyaluronic acid-rich matrix: Dermial®

Some glycosaminoglycans, especially those extracts rich in hyaluronic acid, have demonstrated positive effects on multiple aspects of cutaneous health. In vitro studies show that these compounds:

• Improve cutaneous hydration (effect measured through hyaluronan production)
• Significantly increase cell proliferation
• Stimulate cell migration of fibroblasts and keratinocytes
• Increase elastin production

These properties translate into an improvement in the skin's regenerative capacity and in maintaining its elasticity and hydration.

Sphingolipids: Biosfeen®

The lipid extract rich in sphingomyelin represents a significant advance in skin barrier restoration. Studies conducted with in vitro models of canine skin have revealed notable effects:

• Increase in ceramide levels: essential components of the intercellular lipid matrix of the stratum corneum
• Increase in the number of lamellar bodies: structures that release lipids to form the lipid matrix of the skin barrier
  Improvement in filaggrin expression: crucial protein for the formation of the natural moisturizing factor
• Stimulation of antimicrobial peptide (AMP) production: natural defenses against pathogens
• Transmission electron microscopy images clearly showed the presence of well-formed lamellar bodies after treatment with the sphingolipid extract, validating its capacity to normalize the skin barrier structure.
   

Nucleotides: Nucleoforce®

Dietary nucleotides, traditionally recognized in human pediatric nutrition since the 1980s, act as immunonutrients. These low molecular weight bioactive compounds:

• Modulate the immune response
• Stimulate fibroblast migration and proliferation
• Improve tissue repair

Although normally obtained from the diet or by endogenous synthesis, their contribution can become conditionally essential in situations of stress, growth or disease.

Clinical evidence: synergistic combinations

Studies have evaluated not only individual ingredients, but also their combinations, with especially promising results.

Sphingolipids + Glycosaminoglycans

An in vitro study demonstrated that the combination of both ingredients produces synergistic effects on dermal fibroblasts, with significant increases in:

• Filaggrin expression (67% increase compared to baseline control)
• Antimicrobial peptide hBD-2 production (67% increase with the combination vs. 39% with GAGs alone or 39% with sphingolipids alone)

Clinical trials in dogs with CAD have shown statistically significant improvements after 8 weeks of topical treatment:

• Reduction of the Canine Atopic Dermatitis Extent and Severity Index (CADESI) (from 20 to 11 points)
• Decrease in the Pruritus Index in Canine Atopic Dermatitis (PICAD) (from 17 to 10 points)
• Improvement in the Pruritus Visual Analog Scale (PVAS) (pruritus score assessed by owners)
   

Nucleotides + Glycosaminoglycans + Omega-3

This oral combination has demonstrated:

• Improvement in cell migration in in vitro models (P=0.024)
• Significant reduction in pruritus (PVAS) in atopic dogs after 30 days of treatment (P=0.0011)

These results have been published in peer-reviewed scientific journals, including International Journal of Molecular Sciences and Veterinary Sciences, providing a solid scientific evidence base.

Format innovation: the Atopivet® collar

Responding to the challenges of therapeutic adherence/treatment compliance—a complex problem of global scope—Bioiberica has developed a collar with nutrients such as Biosfeen® that offers practical advantages for both veterinarians and owners:

• Sustained release: in vitro kinetic studies show a gradual release of approximately 20% of the lipid extract over 20 days
• Ease of use: significantly improves treatment adherence
• Versatility: available in two sizes (35 and 75 cm)
• Technical characteristics: made of TPU (thermoplastic polyurethane), water-resistant, with natural and patented plasticizer
   

Efficacy data

A multicenter pilot study evaluated the efficacy in maintaining skin health and the collar's safety in dogs with confirmed CAD diagnosis over 8 weeks. The results showed:

• Safety: no adverse effects reported
• Acceptance: excellent feedback from owners and veterinarians on product characteristics (color, odor, effects)
• Efficacy: statistically significant improvements in CADESI, PICAD and PVAS after 8 weeks
   

Compatibility studies

A crucial aspect for practical application is compatibility with other treatments. Stability studies have demonstrated that the collar maintains adequate levels (recovery 93-101%) of:

• Lipid extract (Biosfeen®)
• Imidacloprid (antiparasitic)
• Flumethrin (acaricide)
• Deltamethrin (insecticide)

This compatibility allows simultaneous use with common antiparasitic treatments, facilitating comprehensive patient management.
 

Practical implications for veterinary practice

The evidence presented supports several relevant conclusions for practice:

1. Maintaining skin barrier integrity should be a priority in CAD management and other dermatopathies, regardless of other treatments employed.
2. Functional ingredients with scientific evidence—sphingolipids, glycosaminoglycans and nucleotides—offer complementary mechanisms of action that act on different skin levels.
3. Evidence-based multimodal management improves clinical outcomes and patients' quality of life, while the availability of different formats (topical, oral, collars) facilitates therapeutic adherence.
4. Translational research—from in vitro models to clinical trials—provides a solid scientific foundation that allows veterinarians to make informed decisions.
5. Cutaneous conditions go beyond CAD: these functional ingredients have potential in various pathologies affecting skin barrier integrity, such as sebaceous adenitis, and conditions associated with skin aging.

New evidence

Optimal management of cutaneous health in companion animals requires a comprehensive approach that combines pathophysiological understanding, scientific evidence and practical solutions adapted to each patient and owner. Advances in the development of specific functional ingredients—backed by in vitro, in vivo studies and clinical trials published in scientific journals—are providing veterinarians with more effective and evidence-based tools.

The future of veterinary dermatology lies in this type of innovation that not only controls symptoms, but addresses the fundamental mechanisms of the disease, thus improving patients' quality of life and owner satisfaction.

For more information about these developments and to access the complete scientific publications, veterinary professionals can consult the journals 'International Journal of Molecular Sciences', 'Veterinary Sciences' and 'BMC Veterinary Research', where the mentioned studies have been published.