Serrapeptase

• Reduces inflammation and swelling
• Supports healthy inflammatory response
• May help break down non-living tissue and proteins
• Potential to reduce pain associated with inflammatory conditions

• May help break down biofilms in chronic infections
• Potential to enhance antibiotic penetration into tissues
• May support respiratory health by reducing mucus viscosity
• Potential to support cardiovascular health
• May help reduce post-surgical and post-traumatic swelling

Serrapeptase (serratiopeptidase) is a proteolytic enzyme originally isolated from the intestine of the silkworm Bombyx mori, where it helps the emerging moth dissolve its cocoon. It is now primarily produced by fermentation using the bacterium Serratia marcescens. As a metalloprotease, serrapeptase contains a zinc atom at its active site that is essential for its catalytic activity. The primary mechanism of action of serrapeptase centers on its ability to hydrolyze peptide bonds in proteins, particularly non-living proteins such as fibrin, inflammatory mediators, and damaged tissue.

This proteolytic activity contributes to several therapeutic effects. First, serrapeptase exhibits anti-inflammatory properties through multiple pathways. It can directly break down inflammatory mediators such as bradykinin, histamine, and serotonin, thereby reducing their concentration at inflammation sites. It also hydrolyzes inflammatory proteins and immune complexes that contribute to the inflammatory cascade.

Additionally, serrapeptase may reduce the production of pro-inflammatory cytokines, though the exact molecular mechanisms for this effect are not fully elucidated. Second, serrapeptase demonstrates anti-edemic (anti-swelling) effects by enhancing the drainage of fluid from inflamed tissues. By breaking down protein debris and inflammatory exudates, it helps reduce tissue fluid retention and improves microcirculation in affected areas. Third, the analgesic (pain-reducing) effects of serrapeptase are thought to result from its ability to block the release of pain-inducing amines from inflamed tissues and reduce inflammation-associated pressure on nerve endings.

By decreasing the concentration of inflammatory mediators that sensitize pain receptors, serrapeptase may help reduce pain perception. Fourth, serrapeptase has shown potential in breaking down biofilms, which are protective matrices formed by microorganisms that can shield them from antibiotics and the immune system. Research suggests that serrapeptase may degrade the protein components of biofilms, potentially making embedded microorganisms more susceptible to antimicrobial treatments and immune clearance. Fifth, studies indicate that serrapeptase may enhance the penetration of antibiotics into tissues.

By breaking down protein barriers and reducing inflammation, it may improve the delivery of antibiotics to infection sites, potentially enhancing their effectiveness. Sixth, in respiratory conditions, serrapeptase may help reduce the viscosity of mucus by breaking down mucoproteins, potentially improving expectoration and respiratory function. It’s important to note that while the proteolytic mechanisms of serrapeptase are well-established, some of its proposed therapeutic applications are based on limited clinical evidence. The enzyme appears to have selective activity, primarily targeting non-living proteins while generally sparing living tissue, which contributes to its safety profile when used appropriately.

Serrapeptase dosage is typically measured in enzyme activity units rather than simply by weight. The most common units are Serratiopeptidase Units (SPU) or Enzyme Units (EU). Dosages in clinical studies and commercial products range widely from 5,000 to 60,000 SPU per day. For general anti-inflammatory purposes, a common starting dosage is 10,000-30,000 SPU per day, often divided into 2-3 doses.

Higher therapeutic dosages of 30,000-60,000 SPU daily may be used for acute conditions under healthcare provider supervision. Serrapeptase should typically be taken on an empty stomach (at least 30 minutes before meals or 2 hours after) to maximize absorption and effectiveness, as food may interfere with its enzymatic activity. Enteric-coated or delayed-release formulations are essential to protect the enzyme from degradation by stomach acid.

Serrapeptase faces significant bioavailability challenges as a protein-based enzyme. When taken orally, it is vulnerable to degradation by stomach acid and digestive proteases in the gastrointestinal tract. Despite these challenges, research has demonstrated that serrapeptase can be absorbed from the intestinal tract in its active form, though the exact bioavailability rate has not been precisely determined in comprehensive human studies. A key study by Moriya et al.

(1994) using a rat model demonstrated that serrapeptase can be absorbed from the intestinal tract into the bloodstream, maintaining its enzymatic activity. Further research by the same group in 2003 showed that the absorbed enzyme could accumulate at sites of inflammation, suggesting targeted delivery to areas where it is most needed. This phenomenon may explain why relatively low systemic concentrations can still produce therapeutic effects. To overcome the bioavailability limitations, most commercial serrapeptase supplements are formulated with enteric coatings or delayed-release technologies that protect the enzyme from stomach acid, allowing it to reach the small intestine where absorption can occur.

The timing of administration (on an empty stomach) also significantly impacts bioavailability, as food can trigger increased production of digestive enzymes that may degrade serrapeptase before absorption.

Enteric coating or delayed-release capsule technology to protect the enzyme from stomach acid degradation, Taking on an empty stomach (30-60 minutes before meals or 2 hours after meals) to minimize exposure to food-stimulated digestive enzymes, Liposomal formulations that may protect the enzyme and enhance absorption, Nanoparticle delivery systems that have shown promise in research settings, Consistent timing of doses to maintain therapeutic levels, Some formulations include additional compounds that may help stabilize the enzyme during digestion, Avoiding simultaneous consumption of proteolytic enzyme inhibitors found in certain foods

For optimal absorption and effectiveness, serrapeptase should be taken on an empty stomach, typically 30-60 minutes before meals or at least 2 hours after meals. This timing minimizes the presence of food-stimulated digestive enzymes that could degrade the serrapeptase before absorption. When used for anti-inflammatory purposes, consistent daily dosing is important to maintain therapeutic effects. For those taking multiple daily doses, spacing them evenly throughout the day (e.g., morning, afternoon, and evening) helps maintain more consistent blood levels.

Some practitioners recommend taking the highest dose before bedtime when the digestive system is relatively inactive, potentially improving absorption. However, this approach is based more on clinical experience than on definitive research. When used specifically for biofilm disruption in chronic infections, some practitioners recommend taking serrapeptase 30-60 minutes before antimicrobial treatments to potentially enhance their effectiveness, though this approach is based more on theoretical mechanisms than on definitive clinical evidence. For post-surgical or dental procedure applications, starting serrapeptase 1-2 days before the procedure and continuing for several days afterward may provide optimal benefits for reducing swelling and pain.

• Gastrointestinal discomfort, including nausea, stomach upset, or diarrhea (uncommon)
• Skin reactions such as rash or itching (rare)
• Allergic reactions, including potential for anaphylaxis in sensitive individuals (very rare)
• Joint pain (rare)
• Muscle aches (rare)
• Cough (rare)
• Pneumonitis (very rare case reports)
• Coagulation abnormalities (theoretical risk, especially at high doses or in combination with anticoagulants)
• Potential for increased risk of bleeding (theoretical, particularly with high doses or when combined with other blood-thinning substances)

• Known allergy or hypersensitivity to serrapeptase or related enzymes
• Bleeding disorders or conditions with high bleeding risk
• Recent or planned surgery (within 2 weeks)
• Liver or kidney disease (use with caution)
• Pregnancy and breastfeeding (due to insufficient safety data)
• Concurrent use of anticoagulant medications without medical supervision
• Peptic ulcer disease (theoretical risk of exacerbation)
• History of Stevens-Johnson syndrome (rare case reports of serrapeptase involvement)
• Children under 18 (limited safety data)

• Anticoagulant medications (warfarin, heparin, direct oral anticoagulants): May increase bleeding risk
• Antiplatelet drugs (aspirin, clopidogrel): May have additive effects on platelet inhibition and increase bleeding risk
• NSAIDs (ibuprofen, naproxen): Potential for additive effects on bleeding risk, though often used together clinically
• Herbs with anticoagulant properties (ginkgo biloba, garlic supplements, fish oil): May have additive effects on blood thinning
• Antibiotics: May enhance antibiotic penetration into tissues, potentially beneficial but should be monitored
• Blood pressure medications: Theoretical interaction, monitor blood pressure when starting serrapeptase

The upper limit for safe serrapeptase dosage has not been definitively established through comprehensive safety studies. Most clinical studies have used dosages ranging from 10,000 to 60,000 SPU daily without reporting significant adverse effects. However, higher dosages increase the theoretical risk of side effects, especially in vulnerable individuals or those taking other medications that affect blood coagulation. As a general precaution, it is advisable not to exceed 60,000 SPU per day without medical supervision.

A systematic review by Bhagat et al. (2013) found that serrapeptase was generally well-tolerated across multiple studies, with adverse events being rare and mild. However, the review also noted the need for more rigorous safety evaluations. There have been rare case reports of serious adverse reactions, including Stevens-Johnson syndrome when serrapeptase was combined with other medications, and isolated reports of pneumonitis.

These rare events highlight the importance of monitoring for unusual symptoms when taking serrapeptase, particularly at higher doses or for extended periods.

In the United States, serrapeptase is regulated as a dietary supplement under the Dietary Supplement Health and Education Act (DSHEA) of 1994. It has not been approved by the FDA as a drug for treating, curing, or preventing any disease. As a dietary supplement, serrapeptase products cannot legally make specific disease claims on their labels or in marketing materials. Manufacturers are responsible for ensuring the safety of their products before marketing, but pre-market approval is not required by the FDA.

The FDA can take action against unsafe products or those making unsubstantiated health claims after they reach the market. Serrapeptase has not undergone the FDA’s New Drug Application (NDA) process, which would be required for it to be marketed as a pharmaceutical with specific therapeutic claims. The FDA has not issued any specific warnings or safety alerts regarding serrapeptase, though it maintains that there is insufficient evidence to support its use for specific medical conditions.

Japan: In Japan, serrapeptase has been approved as a pharmaceutical drug since the 1970s, marketed under brand names such as Danzen. It is prescribed for reducing inflammation and swelling after surgery, trauma, or infection. As a pharmaceutical, it undergoes rigorous quality control and is subject to stricter regulations than dietary supplements.

Eu: In the European Union, the regulatory status of serrapeptase varies by country. In some European countries, particularly Germany and Italy, it has been available as a prescription or over-the-counter medication. The European Medicines Agency (EMA) has not issued a centralized approval for serrapeptase, leaving regulation primarily to individual member states. In many EU countries, it is available as a food supplement.

Canada: Health Canada regulates serrapeptase as a Natural Health Product (NHP). Products containing serrapeptase must have a Natural Product Number (NPN) to be legally sold in Canada. Health Canada has approved certain claims for serrapeptase products, including ‘helps to relieve pain associated with osteoarthritis’ and ‘helps to reduce pain and swelling following trauma, surgery, or dental procedures’ under specific conditions.

Australia: The Therapeutic Goods Administration (TGA) regulates serrapeptase as a complementary medicine. Products containing serrapeptase must be listed on the Australian Register of Therapeutic Goods (ARTG) before they can be legally supplied in Australia. The TGA allows limited health claims for listed complementary medicines based on traditional use and available evidence.

India: In India, serrapeptase is widely available both as a standalone supplement and in combination with other ingredients, particularly NSAIDs. The Central Drugs Standard Control Organization (CDSCO) has approved several fixed-dose combinations containing serrapeptase for various inflammatory conditions.

Singapore: The Health Sciences Authority (HSA) of Singapore has approved serrapeptase as a pharmaceutical product for specific indications, including the reduction of swelling and pain after surgery or injury.

Moderate

Serrapeptase supplements typically cost between $0.30 and $1.50 per day for a standard dose of 10,000-30,000 SPU, depending on the brand, quality, and whether it’s purchased in bulk. This translates to approximately $9 to $45 per month. Higher-quality products with standardized potency, enteric coating, and third-party testing tend to be at the upper end of this price range. Products with higher enzyme activity (40,000-120,000 SPU) may cost between $0.80 and $2.50 per day, or $24 to $75 per month.

Japanese pharmaceutical-grade serrapeptase (when available) is typically more expensive than dietary supplement versions. The production process for serrapeptase involves fermentation, extraction, and purification steps, as well as specialized enteric coating technology, all of which contribute to its moderate cost compared to simpler supplements.

The value proposition of serrapeptase depends largely on the specific health concern being addressed and individual response. For post-surgical or post-traumatic swelling and pain, serrapeptase may offer good value compared to some alternatives. Clinical studies have shown effectiveness in reducing swelling, pain, and inflammation in these contexts, potentially reducing the need for higher doses of NSAIDs or other pain medications. When compared to NSAIDs for long-term use, serrapeptase may offer better value for some individuals, particularly those who experience gastrointestinal side effects from NSAIDs.

While the upfront cost is higher than generic NSAIDs, the potentially lower risk of adverse effects may translate to cost savings in terms of avoided complications and additional medications. For respiratory conditions, the value assessment is more nuanced. Some studies suggest benefits in reducing mucus viscosity and supporting respiratory function, but the evidence is not as robust as for post-surgical applications. For biofilm-related applications in chronic infections, the value assessment is challenging due to limited clinical evidence.

In these cases, serrapeptase is typically used as part of a comprehensive treatment protocol rather than as a standalone treatment, making its specific contribution to outcomes difficult to isolate. When comparing different serrapeptase products, higher-priced options from established manufacturers often provide better standardization of enzyme activity and more reliable enteric coating, potentially offering better value despite the higher upfront cost. Products with higher SPU counts are not necessarily more cost-effective on a per-unit basis, as the dose-response relationship is not linear for all applications. For preventive use in generally healthy individuals, the cost-benefit ratio may be less favorable, and other lifestyle interventions may offer better value for maintaining health.

The cost-effectiveness of serrapeptase may be enhanced when used as part of a targeted, time-limited protocol rather than as an indefinite daily supplement.

Serrapeptase, being a protein-based enzyme, has inherent stability challenges. In properly formulated and packaged supplements, serrapeptase typically has a shelf life of 2-3 years from the date of manufacture when stored according to recommendations. However, once the container is opened, the shelf life may be reduced due to potential exposure to moisture, air, and temperature fluctuations. The enzyme activity can gradually decrease over time, even in unopened packages, which is why most manufacturers include an expiration date.

Enteric-coated or delayed-release formulations generally have better stability than non-coated forms, as the coating provides additional protection against environmental factors. Some manufacturers use specialized processing techniques and stabilizing agents to extend shelf life. It’s important to note that the actual enzyme activity may decrease before visible signs of degradation appear, so adhering to expiration dates is particularly important for enzymatic supplements like serrapeptase.

Store serrapeptase supplements in a cool, dry place away from direct sunlight, ideally at temperatures between 59-77°F (15-25°C). Avoid storing in bathrooms or kitchens where humidity levels can fluctuate significantly. Keep the container tightly closed when not in use to protect from moisture, which can activate the enzyme prematurely and lead to self-degradation. If the product comes with a desiccant packet, leave it in the container to continue absorbing moisture.

Refrigeration is generally not necessary and may actually introduce moisture through condensation when the container is opened, unless specifically recommended by the manufacturer. Freezing is not recommended as freeze-thaw cycles can denature the enzymes. If traveling with serrapeptase, keep it in its original container and protect from extreme temperatures. For long-term storage, consider using airtight containers with desiccants if the original packaging is not resealable.

Exposure to moisture, which can activate the enzymes prematurely and lead to self-degradation, High temperatures (above 86°F/30°C), which can denature the protein structure of the enzymes, Acidic environments, such as stomach acid, which is why enteric coating is essential for oral supplements, Proteolytic enzymes in the digestive tract, which can break down serrapeptase if not protected, Oxidation from prolonged exposure to air, which can alter the enzyme structure and reduce activity, UV light and direct sunlight, which can degrade the protein components, Microbial contamination, which can occur if the product is exposed to moisture, Chemical interactions with certain minerals or compounds in multi-ingredient formulations, Freeze-thaw cycles, which can disrupt the protein structure, Extended storage beyond the expiration date, as enzyme activity naturally decreases over time

Synthesis Methods

Natural Sources

Quality Considerations

Serrapeptase has a relatively short history as a therapeutic agent compared to many traditional medicinal compounds. Its story begins with the silkworm Bombyx mori, which produces this enzyme to dissolve its cocoon and emerge as a moth. The observation of this natural process led to scientific interest in the enzyme’s proteolytic properties. The modern therapeutic use of serrapeptase began in Japan in the late 1960s, when researchers isolated the enzyme from the enterobacterium Serratia marcescens, which was found in the intestine of the silkworm.

The bacterium, rather than the silkworm itself, was identified as the actual producer of the enzyme. Japanese researchers, particularly those at the pharmaceutical company Takeda, were pioneers in developing serrapeptase as a pharmaceutical agent. By the early 1970s, serrapeptase was being used clinically in Japan under the brand name Danzen, primarily for reducing inflammation and edema associated with surgery or trauma. Throughout the 1970s and 1980s, clinical research on serrapeptase expanded in Japan and later in Europe, particularly in Germany and Italy.

The enzyme gained popularity for its anti-inflammatory, anti-edemic, and analgesic properties, with applications in various medical fields including surgery, otolaryngology, dentistry, and orthopedics. The first significant clinical studies on serrapeptase were published in the 1980s and early 1990s, establishing its efficacy for specific conditions such as post-operative swelling, sinusitis, and breast engorgement. A notable multicenter, double-blind study by Mazzone et al. in 1990 demonstrated its effectiveness in treating various ENT inflammatory conditions.

Serrapeptase remained relatively unknown in North America until the late 1990s and early 2000s, when it began to gain attention in the alternative and complementary medicine community. The enzyme’s introduction to Western markets coincided with growing interest in natural anti-inflammatory agents and alternatives to NSAIDs. In the 2000s, interest in serrapeptase expanded beyond its traditional anti-inflammatory applications to include potential uses in breaking down biofilms in chronic infections, enhancing antibiotic delivery, and supporting cardiovascular health. This broader application was driven partly by practitioners in integrative and functional medicine, though with varying levels of scientific support.

In recent years, research has continued to explore novel applications of serrapeptase, including its potential role in conditions such as Alzheimer’s disease, where it may help break down amyloid plaques, and in cancer therapy as an adjunct to improve drug delivery. However, these applications remain largely experimental. Today, serrapeptase is widely available as a dietary supplement globally, though its regulatory status varies by country. In Japan and some European countries, it has been used as a prescription medication, while in the United States and many other countries, it is regulated as a dietary supplement.

Despite its relatively short history compared to many traditional remedies, serrapeptase has established a significant presence in both conventional and complementary medicine, particularly for inflammatory conditions.

Clinical trials investigating serrapeptase’s effects on post-surgical outcomes in various surgical specialties, Studies examining the potential of serrapeptase as an adjunctive therapy for biofilm-associated infections, Research on serrapeptase’s effects on respiratory conditions and mucus viscosity, Investigations into the potential synergistic effects of serrapeptase with antibiotics for various infectious conditions