Neuropathy, characterized by peripheral nerve damage causing pain, numbness, or dysfunction, remains a challenging condition to treat. Dietary supplements such as alpha-lipoic acid, acetyl-L-carnitine, benfotiamine, and others have demonstrated variable efficacy in mitigating neuropathic symptoms, primarily through antioxidant and neuroprotective mechanisms. Lysozyme—a naturally occurring antimicrobial enzyme found in secretions and egg whites—has shown promising immunomodulatory, antioxidant, and microbiota-modulating roles in preclinical studies. However, there is currently no direct clinical evidence supporting lysozyme supplementation for neuropathy. Given its biological activities—such as modulation of gut integrity, reduction of inflammation, and antioxidant potential—exploring lysozyme supplementation as a novel therapy for neuropathic conditions merits serious consideration.

As a leading enzyme supplier, Creative Enzymes offers premium raw lysozymes that are perfect for lysozyme supplementation. In this article, we explore the pathophysiology of neuropathy, the biology of lysozyme, relevant mechanistic research, potential therapeutic approaches, safety concerns, and research pathways for further investigation.

Overview of Neuropathy and Existing Supplement-based Therapies

Introduction, Causes, and Symptoms

Neuropathy, more precisely referred to as peripheral neuropathy, is a medical condition resulting from damage to the peripheral nerves, which are responsible for transmitting signals between the central nervous system (the brain and spinal cord) and the rest of the body. This disruption in nerve function can lead to a range of symptoms, including tingling sensations, burning pain, numbness, muscle weakness, and in some cases, impaired coordination or balance.

The causes of neuropathy are diverse and can include chronic conditions such as diabetes mellitus, autoimmune diseases, infections, traumatic injuries, nutritional deficiencies, exposure to toxins, and certain medications. The nature and severity of symptoms typically depend on the type and extent of nerve damage. Diagnosis often involves a combination of clinical evaluation, nerve conduction studies, and laboratory tests. Treatment focuses on addressing the underlying cause, managing symptoms, and preventing further nerve damage.

Current Supplement Approaches

Clinical and preclinical data support certain supplements:

• Alpha-Lipoic Acid (ALA): Antioxidant that reduces pain and improves numbness in diabetic neuropathy; typical clinical dosing is ~600–800 mg daily.
• Acetyl-L-Carnitine (ALC): Neuroprotective and analgesic properties, with measurable improvements in nerve function and pain scores in diabetic patients.
• Other Compounds: Glutamine, omega-3 fatty acids, vitamin B complexes, benfotiamine, and selenium exhibit varying degrees of efficacy, largely through oxidative stress reduction and metabolic support.

Despite these, substantive evidence for preventing or reversing neuropathy is limited, and no lysozyme-based supplement currently appears in peer-reviewed studies for neuropathy.

Lysozyme: Biological Functions and Supplement Modalities

Lysozyme Sources and Supplement Types

Lysozyme is naturally present in tears, saliva, mucus, breast milk, neutrophils, macrophages, and egg whites. Supplemental forms include hen egg white lysozyme (HEWL) and recombinant human lysozyme (rhLYZ), used in food preservation, immune modulation, and wound healing.

Figure 1. Structure of lysozyme. (Ferraboschi et al., 2021)

Known Biological Activities

• Antimicrobial: Cleaves bacterial peptidoglycan, primarily targeting Gram-positive species.
• Immunomodulatory: Stimulates cytokine responses, macrophage activity, peptidoglycan fragments acting via NOD receptors.
• Antioxidant: Scavenges reactive oxygen species (ROS), notably superoxide and hydroxyl radicals.
• Gut Barrier Support: Promotes Paneth cell function, maintains gut integrity, and modulates microbiota.

Linking Lysozyme Biology with Neuropathy Pathophysiology

Gut-Nerve Axis and Inflammation

Emerging literature reveals that intestinal dysbiosis and increased gut permeability contribute to systemic inflammation, neuroinflammation, and neuronal injury—an axis being explored in diabetic and chemotherapy-induced neuropathy (Houser and Tansey, 2017). Lysozyme supplementation in mice following traumatic brain injury helped normalize gut microbiota, reduce inflammation, and preserve barrier integrity . Extrapolating from this, lysozyme may restore homeostasis in neuropathy contexts linked to gut–systemic inflammation.

Figure 2. The microbiota-gut-brain axis uses several pathways that include interactions between the microbiota and the autonomic nervous system (ANS), enteric nervous system (ENS), and spinal nerves. Enteroendocrine cells (EEC) and cells of the immune system (IS), mixed with epithelial cells (EC) of the intestinal mucosa, mediate this interaction. The hypothalamic–pituitary–adrenal (HPA) axis is one of the major non-neuronal pathways used by the gut microbiota to communicate with the brain. (Longo et al., 2023)

Anti-inflammatory and Oxidative Stress Reduction

Neuropathy is tightly associated with chronic oxidative stress and elevated inflammatory cytokines (e.g., TNF-α, NF-κB activation). While lysozyme does not function as a traditional antioxidant supplement, its ROS-scavenging and mucosal anti-inflammatory roles may attenuate underlying oxidative injury. It may hence complement other supplements (ALA, ALC) by offering additional redox modulation.

Immune-Modulatory Effects

Lysozyme amplifies innate immune coordination via macrophage chemotaxis and peptidoglycan signaling through NOD receptors. Macrophage-mediated neuroinflammation is implicated in neuropathy; finely tuned immune activation by lysozyme might reduce neuroinflammatory damage while enhancing tissue repair.

Potential Therapeutic Applications of Lysozyme in Neuropathy

• Intestinal Neuropathy and Small-Fiber Neuropathy: Small-fiber neuropathy may correlate with gut barrier dysfunction and metabolic dysregulation. Lysozyme administered orally could restore gut homeostasis, decrease microbial translocation, and mitigate systemic factors contributing to nerve damage.
• Chemotherapy-Induced Peripheral Neuropathy (CIPN): CIPN arises from oxidative neuronal injury and inflammatory cascades. Nutritional supplements like L-carnosine and α-lipoic acid have shown partial mitigation of symptoms by reducing oxidative stress and apoptosis markers. Lysozyme may serve as adjuvant, augmenting mucosal resistance and systemic immune balance without interfering with anticancer therapies.
• Diabetic Peripheral Neuropathy (DPN): DPN involves hyperglycemia-induced oxidative stress, mitochondrial dysfunction, inflammation, and nerve ischemia. Given its multifaceted biological roles, lysozyme may modulate gut-derived endotoxemia, reduce systemic inflammatory burden, and support antioxidant capacity.
• Nerve Injury: Lysozyme activates neuronal TLR4 signaling during nerve injury, promoting hyperexcitability and pain. This discovery highlights lysozyme's role in neuroinflammation and neuropathic pain, offering a promising therapeutic target for treating nervous system pathologies without glial involvement. (Yadav and Surolia, 2019)

Proposed Mechanisms of Action in Neuropathy

While indirect, these mechanisms align with major pathogenic factors in neuropathic conditions and could form rationale for future intervention strategies.

Safety Profile and Regulatory Considerations

Lysozyme is GRAS-approved and widely used in food and pharmaceutical contexts. However, considerations include:

• Egg Allergy Risk: Individuals allergic to eggs must avoid HEWL-based supplements.
• Immunogenicity: rhLYZ is less allergenic but not yet evaluated for long-term systemic supplementation.
• Drug Interactions: Limited evidence; unlikely to interfere with conventional neuropathy medications.

Standard toxicology and immunogenicity studies would be required before any clinical trials in neuropathy populations.

Gaps in Current Knowledge and Research Recommendations

No Clinical Trials Exist

To date, no human clinical studies have assessed lysozyme supplementation for neuropathy treatment. Reports of lysozyme as a "drug" for neuropathy circulating online appear anecdotal and not scientifically validated.

Preclinical Research Needed

• Animal Models: Diabetic neuropathy, CIPN, or small-fiber neuropathy models with lysozyme supplementation to assess nerve conduction, histology, inflammatory markers, microbiome changes.
• Dose-Finding and Delivery: Identifying bioavailable oral doses, gastric-resistant formulations, or combination with probiotics/prebiotics.

Clinical Trial Design

Early-phase human studies should explore:

• Safety and Tolerability in healthy volunteers and neuropathy patients.
• Biomarker Endpoints inflammatory cytokines, oxidative stress indicators, gut permeability assays.
• Symptom Scales including pain, sensory thresholds, nerve conduction studies.

In summary, lysozyme possesses immunomodulatory, gut-restorative, and antioxidant properties that intersect with key mechanisms underlying various neuropathic conditions. While no direct human evidence supports its use for neuropathy at present, the theoretical rationale is compelling. Carefully designed preclinical and early-phase clinical studies are needed to determine whether lysozyme supplementation could serve as a novel adjunct in managing neuropathy—possibly in conjunction with established antioxidant or metabolic therapies.

Until such data materialize, lysozyme remains an intriguing "promising hypothesis" rather than a proven therapy. Patients and clinicians should exercise caution and rely on validated interventions. Nonetheless, the intersection of gut health, immune regulation, and neural integrity offers fertile ground for research—and lysozyme may yet find a role in a holistic neuropathy strategy.

At Creative Enzymes, we provide high-quality lysozyme products trusted for research and formulation development. As interest grows in lysozyme's broader biological roles, our reliable supply supports innovation at the intersection of gut, immune, and neurological health. Contact us with any questions!