Walk into any supplement store or search online for systemic enzyme supplements, and you'll quickly notice three names appearing again and again:

• Nattokinase

• Serrapeptase

• Lumbrokinase

These enzymes have become increasingly popular among people interested in healthy aging, cardiovascular wellness, and proactive nutrition. Yet despite their growing popularity, they're also among the most misunderstood ingredients in the supplement industry. 

Many articles either make exaggerated claims that aren't supported by evidence or oversimplify the science to the point where readers are left with more questions than answers.

Questions like:

• What exactly is a systemic enzyme?

• How is it different from a digestive enzyme?

• Why do some supplements combine nattokinase, serrapeptase, and lumbrokinase?

• What do FU and SPU actually mean?

• Does more milligrams always mean a better supplement?

• What does current scientific research actually say?

• How do you choose a high-quality enzyme supplement?

This guide was created to answer those questions using a balanced, evidence-informed approach.

Rather than promoting miracle claims or sensational headlines, we'll explore what researchers currently know, where the evidence is strongest, where uncertainty remains, and how to evaluate enzyme supplements with confidence.

Whether you're completely new to systemic enzymes or comparing different formulations before making a purchase, this guide is designed to help you make an informed decision.

Nattokinase vs Serrapeptase vs Lumbrokinase: What's the Difference?

Why Are These Enzymes Often Combined?

Can You Take Nattokinase, Serrapeptase & Lumbrokinase Together?

Yes.

Many comprehensive enzyme supplements combine nattokinase, serrapeptase and lumbrokinase into a single formula.

Because each enzyme has different characteristics, manufacturers sometimes formulate them together alongside complementary ingredients such as bromelain, papain and CoQ10.

Always follow the serving directions provided on the product label and consult a healthcare professional if you have questions about your personal circumstances.

What Are Systemic Enzymes?

Systemic enzymes are enzymes intended to be used as part of a wellness routine beyond their traditional role in digestion.

Unlike digestive enzymes, which primarily help break down proteins, fats, and carbohydrates from food inside the digestive tract, systemic enzymes are commonly formulated for use away from meals and are studied for functions beyond digestion. The concept behind systemic enzyme supplementation is that enzyme activity may support various physiological processes when the enzymes are absorbed rather than being used solely to digest food. While research continues to evolve, systemic enzyme supplements have become an established category within nutritional wellness.

This distinction is important because it explains why two enzyme products can appear similar on a label yet be designed for very different purposes.

Digestive Enzymes vs. Systemic Enzymes

Although both categories contain enzymes, their intended roles differ significantly.

Why Are Systemic Enzymes Becoming More Popular?

Consumer interest in preventive wellness has grown dramatically over the last decade.

Instead of waiting until health challenges arise, many people are building long-term wellness routines that include:

• Regular physical activity

• Balanced nutrition

• Quality sleep

• Stress management

• Evidence-informed dietary supplements

Systemic enzyme supplements have become part of this broader conversation because researchers continue to investigate their biological activity and potential applications. While many laboratory and animal studies have produced interesting findings, it's important to recognize that human clinical evidence is still developing for many proposed uses. This distinction is essential when evaluating supplement claims.

A trustworthy supplement brand should acknowledge both the promise and the limitations of current research.

Why Are Nattokinase, Serrapeptase, and Lumbrokinase Often Mentioned Together?

If you've researched systemic enzymes, you've probably noticed that these three ingredients frequently appear in the same conversation.

That's not a coincidence.

Each enzyme has a different origin, different characteristics, and a different history of scientific investigation.

Rather than relying on one enzyme alone, many premium formulations combine multiple systemic enzymes to create a more comprehensive ingredient profile.

This approach reflects a broader philosophy in nutritional formulation: instead of expecting one ingredient to do everything, combine complementary ingredients that contribute to an overall wellness-focused formulation.

Importantly, this doesn't mean the enzymes perform identical functions or that combining them guarantees greater effectiveness. Instead, formulators often include multiple enzymes because each has been studied independently and contributes a different aspect to the formulation's overall design.

Understanding why requires looking at each enzyme individually.

Nattokinase: Understanding One of the Most Studied Systemic Enzymes

What Is Nattokinase?

Nattokinase is an enzyme produced during the fermentation of soybeans into natto, a traditional Japanese food that has been consumed for centuries.

Natto is made by fermenting cooked soybeans with the bacterium Bacillus subtilis var. natto. During fermentation, the bacteria produce nattokinase, which has attracted scientific interest because of its unique enzymatic activity.

Today, purified nattokinase is commonly used as an ingredient in dietary supplements rather than requiring consumers to eat natto itself.

Why Has Nattokinase Attracted Scientific Interest?

Researchers have investigated nattokinase for several decades.

Much of the early interest came from laboratory research exploring its enzymatic properties. Since then, animal studies, observational research, and a limited number of human clinical studies have examined various aspects of nattokinase.

However, it's important to distinguish between laboratory findings and conclusions that can be confidently applied to people.

Laboratory studies help scientists understand mechanisms.

Animal studies provide additional biological insight.

Human randomized controlled trials provide stronger evidence.

Systematic reviews and meta-analyses generally provide the highest level of evidence because they evaluate multiple studies together.

Understanding this evidence hierarchy is essential for interpreting supplement research responsibly.

Why Is Nattokinase Measured in FU Instead of Milligrams?

One of the most confusing aspects of enzyme supplements is the label.

Many people expect supplements to list only milligrams.

Enzymes work differently.

Unlike vitamins or minerals, enzymes are valued for their biological activity rather than simply their weight.

For nattokinase, activity is commonly expressed as:

FU = Fibrinolytic Units

These units reflect standardized enzyme activity rather than the amount of powder present.

Two products could contain similar milligram weights yet differ significantly in measured enzyme activity.

This is why reputable enzyme manufacturers emphasize activity units instead of relying only on milligrams.

Understanding activity units allows consumers to compare enzyme products more meaningfully than comparing weight alone.

What Does Current Research Say About Nattokinase?

Research into nattokinase continues to evolve.

Scientists have explored its biological activity through laboratory experiments, animal models, and a limited number of human studies.

Some findings have generated considerable scientific interest, but authoritative reviews consistently note that larger, well-designed clinical trials are still needed before firm conclusions can be drawn for many proposed applications.

This balanced interpretation is important because it reflects the current state of evidence rather than overstating what research has demonstrated.

For consumers, the practical takeaway is simple:

Nattokinase remains one of the most widely recognized systemic enzymes, but supplement decisions should be based on transparent labeling, overall formulation quality, and realistic expectations—not sensational marketing claims.

How Is Nattokinase Used in Modern Supplement Formulas?

Rather than appearing only as a standalone ingredient, nattokinase is increasingly incorporated into multi-ingredient systemic enzyme formulations.

These products often pair nattokinase with other proteolytic enzymes, botanical antioxidants, and nutrients such as Coenzyme Q10.

The goal is not to suggest that these ingredients replace one another, but to create a broader wellness-focused formulation that combines complementary components within a single daily supplement.

One example is the inclusion of nattokinase alongside serrapeptase and lumbrokinase, which we'll explore in the next section.

Serrapeptase: Understanding the Science Behind This Proteolytic Enzyme

What Is Serrapeptase?

Serrapeptase (also called serratiopeptidase) is a proteolytic enzyme, meaning it belongs to a group of enzymes that break down proteins into smaller peptides and amino acids.

Originally isolated from Serratia marcescens bacteria found in the digestive tract of silkworms, serrapeptase has been used in parts of Europe and Asia for decades and has become one of the most recognizable enzymes in systemic enzyme supplements.[4][5]

Today, serrapeptase is commonly included in dietary supplements either as a standalone ingredient or as part of multi-enzyme formulations alongside nattokinase and lumbrokinase.

Why Is Serrapeptase Measured in SPU?

Unlike vitamins or minerals, enzymes are measured by biological activity rather than weight.

For serrapeptase, activity is typically expressed as:

SPU = Serratiopeptidase Units

These units indicate enzyme activity under standardized laboratory conditions.

This means that comparing two products based only on milligrams can be misleading.

A product with a higher milligram weight does not necessarily have greater enzyme activity.

Whenever possible, consumers should evaluate enzyme supplements using standardized activity units instead of relying solely on ingredient weight.

Why Has Serrapeptase Become Popular?

Interest in serrapeptase comes largely from its enzyme activity.

Over the past several decades, researchers have investigated serrapeptase in laboratory studies, animal models, and human clinical research.

It has also been widely discussed in review articles examining its biochemical properties and potential applications.

However, it's important to separate scientific investigation from established clinical conclusions.

The current body of evidence remains mixed.

Some studies report encouraging findings in specific settings, while systematic reviews consistently conclude that additional high-quality human trials are needed before stronger conclusions can be made.[4][5]

That balanced interpretation is far more useful than either dismissing the ingredient entirely or presenting it as a miracle compound.

What Does Current Research Say?

One of the largest systematic reviews evaluating serrapeptase examined available clinical studies across multiple medical specialties.

The review concluded that while serrapeptase has been widely studied, many clinical trials suffered from limitations such as:

• Small sample sizes

• Inconsistent study design

• Variable dosing protocols

• Limited long-term safety data

Because of these limitations, the authors concluded that stronger evidence is still needed to fully establish many proposed health applications.[4]

More recent reviews have echoed a similar message.

Although laboratory findings and early clinical studies continue to generate scientific interest, additional well-designed randomized controlled trials remain necessary before broad clinical recommendations can be made.[5]

This illustrates an important principle when evaluating supplements:

Scientific interest does not automatically equal scientific certainty.

The strongest supplement brands acknowledge both the promising research and its current limitations.

Why Is Serrapeptase Often Combined with Other Enzymes?

Rather than using serrapeptase in isolation, many premium formulations combine it with additional systemic enzymes.

This approach recognizes that enzymes differ in their origins, characteristics, and mechanisms of action.

Instead of relying on one ingredient, formulators often create broader enzyme profiles that include complementary proteolytic enzymes.

This is one reason serrapeptase is frequently paired with nattokinase and lumbrokinase.

Each contributes a different enzymatic profile while allowing the formulation to offer a more comprehensive enzyme blend.

Lumbrokinase: The Third Component of a Comprehensive Systemic Enzyme Formula

What Is Lumbrokinase?

Lumbrokinase is a group of naturally occurring enzymes isolated from certain species of earthworms.

Unlike nattokinase, which originates from soybean fermentation, or serrapeptase, which originates from bacterial fermentation, lumbrokinase has a completely different biological source.

This unique origin is one reason it has attracted attention among researchers studying enzyme diversity.

Today, purified lumbrokinase is used in dietary supplements designed around systemic enzyme formulations.

Why Is Lumbrokinase Measured in FU?

Like nattokinase, lumbrokinase activity is commonly expressed in:

FU (Fibrinolytic Units)

Again, this reflects biological activity rather than ingredient weight.

Consumers comparing enzyme supplements should understand that standardized activity measurements provide more useful information than milligram values alone.

Why Has Lumbrokinase Attracted Research Interest?

Compared with nattokinase and serrapeptase, lumbrokinase has a smaller—but steadily growing—body of scientific literature.

Researchers have investigated its enzyme activity in laboratory settings, animal models, and selected clinical contexts.

Recent systematic reviews and meta-analyses have evaluated lumbrokinase in specific medical settings, while also emphasizing the need for additional high-quality clinical research before broad conclusions can be drawn.[6]

As with any dietary supplement ingredient, laboratory findings should not be interpreted as proof of clinical benefit in healthy individuals.

Why Is Lumbrokinase Included in Premium Formulas?

Every enzyme has unique biochemical characteristics.

Rather than attempting to replace nattokinase or serrapeptase, lumbrokinase expands the overall enzyme profile.

Think of it this way:

A well-designed enzyme formula isn't about finding one "best" enzyme.

It's about combining complementary ingredients that contribute to a broader formulation.

This philosophy explains why premium systemic enzyme supplements increasingly feature all three enzymes together.

Why Premium Formulas Combine Nattokinase, Serrapeptase, and Lumbrokinase

One of the most common questions consumers ask is:

"Why not just take nattokinase by itself?"

The answer lies in formulation philosophy rather than marketing.

Each of these enzymes differs in:

• Biological origin

• Enzyme classification

• Activity measurements

• Research history

• Biochemical characteristics

Because they are distinct enzymes, formulators often combine them to create a more comprehensive enzyme profile.

Importantly, combining ingredients does not automatically make a supplement more effective.

Instead, the goal is to create a balanced formulation where complementary ingredients contribute to the overall design.

This same principle explains why many high-quality multivitamins contain dozens of nutrients rather than relying on a single vitamin.

Evidence Hierarchy: Understanding What Research Can—and Cannot—Tell Us

One of the biggest challenges in supplement research is misunderstanding different types of evidence.

Not every scientific study carries the same weight.

Understanding the hierarchy of evidence helps consumers interpret research more accurately.

Laboratory Studies (In Vitro)

Laboratory studies examine cells, tissues, or biochemical processes under controlled conditions.

These studies help scientists understand mechanisms, but they cannot predict how the human body will respond.

Animal Studies

Animal research provides valuable biological insights and often serves as a bridge between laboratory experiments and human clinical trials.

However, results observed in animals do not always translate directly to humans.

Human Clinical Trials

Randomized controlled trials provide stronger evidence because they evaluate outcomes in people under carefully designed conditions.

Even so, individual clinical trials may have limitations related to sample size, duration, or methodology.

Systematic Reviews and Meta-Analyses

These represent some of the strongest forms of scientific evidence because they analyze findings from multiple clinical studies.

Instead of relying on one experiment, systematic reviews evaluate the overall body of available research.

This approach helps reduce the influence of isolated findings and provides a more balanced understanding of current evidence.

When reading about dietary supplements, prioritizing systematic reviews over individual laboratory studies can lead to a more accurate interpretation of the science.

Key Takeaway

The research surrounding nattokinase, serrapeptase, and lumbrokinase continues to evolve.

Collectively, these enzymes have generated substantial scientific interest and have been the subject of laboratory research, clinical investigations, and systematic reviews.

At the same time, many researchers emphasize the need for additional high-quality human studies before stronger conclusions can be made regarding many proposed applications.

For consumers, this reinforces the importance of choosing products based on transparent labeling, thoughtful formulation, realistic expectations, and evidence-informed education rather than exaggerated marketing claims.

Looking for a Comprehensive Systemic Enzyme Formula?

If you're researching supplements that combine Nattokinase, Serrapeptase, and Lumbrokinase, it's worth looking beyond ingredient names alone.

A well-designed formula should also provide:

• Clearly disclosed enzyme activity units (FU & SPU)
• Transparent Supplement Facts
• Complementary ingredients with a defined purpose
• Practical daily serving sizes
• Thoughtful formulation rather than unnecessary ingredient loading

Matevara Premium Nattokinase, Serrapeptase & Lumbrokinase with CoQ10 brings these principles together in a single daily formula by combining three systemic enzymes with Coenzyme Q10, botanical antioxidants, complementary enzymes, vitamins, and minerals all made in USA.

👉 Explore the complete ingredient profile and Supplement Facts on the product page.

References Used in This Section

[4] Bhagat S, et al. Serratiopeptidase: A Systematic Review of the Existing Evidence. International Journal of Surgery (2013). PubMed / ScienceDirect Abstract

[5] Mazzone A, et al. Serratiopeptidase: Insights into the Therapeutic Applications. PMC Review. PubMed Central (PMC) Review

[6] Therapeutic Potential of Lumbrokinase in Acute Ischemic Stroke: A Meta-analysis of Efficacy and Safety. PubMed Central (2025). PubMed Central Article