Aspergillus

Aspergillus: A Comprehensive Reference on the Dietary Supplement and Natural Ingredient

1. Identity, Taxonomy, and Natural Source

Aspergillus is a genus of filamentous, saprophytic fungi belonging to the division Ascomycota, family Aspergillaceae. As a genus of filamentous fungi, Aspergillus has a rich and longstanding history in traditional medicine and nutritional practices. Within this large genus — encompassing several hundred species — a small number of species are of primary relevance as dietary supplements and food-processing agents. These are principally:

• Aspergillus oryzae (Ahlburg) Cohn — also known by its Japanese common name, koji mold (kōji-kin).
• Aspergillus niger van Tieghem — the black mold widely used for industrial enzyme and organic-acid production.
• Aspergillus awamori — a close relative of A. niger, prominent in Okinawan fermentation traditions.

Aspergillus oryzae is a filamentous micro-fungus used for centuries in fermentation of different foods in many countries across the world, and is also a rich source of many bioactive secondary metabolites. A. oryzae produces many extracellular enzymes that degrade carbohydrates, polypeptides, and nucleic acids; it has been used widely as the starter culture for the preparation of koji in the production of traditional Oriental fermented foods and alcohol.

Aspergillus niger is a filamentous fungus with a longstanding history of use in the food and biotechnology industries; traditionally, it has played a critical role in the large-scale production of citric acid, a common food additive and preservative, since the early 20th century.

Common Forms and Preparations

In the supplement and food industries, Aspergillus-derived ingredients appear in several distinct forms:

• Koji: The primary solid-state fermentation preparation, consisting of steamed grain (most commonly rice, wheat, or barley) or legumes colonized by A. oryzae mycelia and spores.
• Enzyme preparations: Purified or semi-purified extracts of specific enzymes (amylases, proteases, lipases, and prolyl endoproteases) derived from A. oryzae or A. niger fermentation, sold as digestive supplement tablets or capsules.
• Dried fermentation biomass: Spray-dried or lyophilized whole-fermentation products containing the intact organism or its heat-inactivated residue.
• Postbiotic preparations: Heat-inactivated (non-viable) fermentation products retaining metabolites, cell-wall constituents, and enzymes.
• Organic acid products: Citric acid (E330) and gluconic acid (E574) derived from A. niger fermentation, used as food additives.

One of the distinctive features of the use of A. oryzae in traditional Japanese fermentation is the use of solid-state cultivation (SSC) on rice grain, soybean, and wheat bran. Manufacturers can use A. oryzae to produce enzymes in both solid-state fermentation (SSF) and submerged fermentation (SmF); since A. oryzae has GRAS status, a variety of substrates inoculated with koji can be used to produce amylases, proteases, glutaminase, and metallopeptidase for food and pharmaceutical applications without complicated purification procedures.

2. Traditional and Historical Use

East Asian Origins and Koji Tradition

It is said that the solid-state culture of filamentous fungi originated approximately 2,000 years ago in China. The technology of the solid-state cultivation was imported to Japan during that period (the Yayoi period) and applied to food fermentation. Inocula from filamentous fungi for fermentation have been commercially available as koji seeds since A.D. 1400 (Muromachi period in Japan).

Aspergillus oryzae, commonly known as "koji mold," plays a crucial role in the fermentation of various food products in East Asian cuisine. The A. oryzae-based preparation of koji, which has a long tradition of more than 1,000 years, is used in the production of sake (rice wine), shoyu (soy sauce), amazake (rice koji beverage), osu (rice vinegar), kurosu (black rice vinegar), shochu (distilled alcoholic beverage fermented with koji), and miso (soybean paste).

The Japanese dynasty and nation have domesticated and utilized koji fermented with non-pathogenic fungus Aspergillus oryzae for more than 1,300 years. Recent research has elucidated that koji contains medicinal substances such as Taka-diastase, acid protease, koji glycosylceramide, kojic acid, oligosaccharides, ethyl-α-d-glucoside, ferulic acid, ergothioneine, pyroglutamyl leucine, pyranonigrin A, resistant proteins, deferriferrichrysin, polyamines, Bifidobacterium-stimulating peptides, angiotensin I-converting enzyme inhibitor peptides, 14-dehydroergosterol, beta-glucan, biotin, and citric acid. This review introduces potential medical applications of such medicinal substances to hyperlipidemia, diabetes, hypertension, cardiovascular and cognitive diseases, chronic inflammation, epidermal permeability barrier disruption, and anti-cancer therapy.

Eiji Ichishima of Tohoku University called the kōji fungus a "national fungus" (kokkin) in the journal of the Brewing Society of Japan, because of its importance not only for making the kōji for sake brewing but also for making the kōji for miso, soy sauce, and a range of other traditional Japanese foods. His proposal was approved at the society's annual meeting in 2006.

Traditional Medicinal Applications

The health benefits of red rice koji have been recognized in China for approximately 700 years. Its medical use was first described in the Compendium of Materia Medica, written in 1498 A.D., indicating that it clears the blood and supports digestion of foods in the intestine. In traditional East Asian practice, koji-fermented foods were valued broadly for digestive support, vitality, and preservation. The enzyme Taka-diastase — an amylase first isolated from A. oryzae in 1894 by the Japanese-American chemist Dr. Jokichi Takamine — became one of the first commercially sold enzyme preparations in the world, and was used as a digestive remedy.

Pfizer started to produce citric acid from Aspergillus niger in 1919, and this method is still used today across the world, particularly in China. The industrial fermentation of A. niger for citric acid production thus represents one of the earliest major applications of fungal biotechnology.

3. Key Constituents and Active Compounds

The bioactive profile of Aspergillus-derived preparations is exceptionally broad. Compounds can be divided into primary metabolites (principally enzymes and structural components) and secondary metabolites (small-molecule bioactives produced during fermentation).

Primary Metabolites: Enzymes

The capacity of A. niger to secrete a wide array of enzymes, such as amylases, proteases, and lipases, has made it invaluable for producing industrial enzymes used in food processing, beverage clarification, and nutritional supplements. For A. oryzae, A. oryzae produces many extracellular enzymes that degrade carbohydrates, polypeptides, and nucleic acids.

Key enzyme classes identified in Aspergillus fermentation products include:

• α-Amylase and glucoamylase: Hydrolyze starch into maltose and glucose. The history of safe use for A. niger comes primarily from its use in the food industry for the production of many enzymes such as α-amylase, amyloglucosidase, cellulases, lactase, invertase, pectinases, and acid proteases.
• Proteases (acid protease, neutral protease, alkaline protease): Cleave dietary proteins into amino acids and peptides. Aspergillus oryzae culture contains high-activity enzyme series, including neutral protease activity (1020 IU/g), alkaline protease activity (770 IU/g), and cellulase activity (482 IU/g).
• Prolyl endoprotease (AN-PEP): A serine endoprotease derived from A. niger with a specific ability to cleave peptide bonds adjacent to proline residues. The Aspergillus niger-derived prolyl endoprotease (AN-PEP) successfully cleaves immunogenic epitopes into smaller, non-immunogenic peptides of eight amino acids or smaller. AN-PEP is active between a pH of 2 and 8, with optimal activity between pH 4 and 5, and is not degraded by pepsin, thereby remaining fully functional in the stomach.
• Lipases: Hydrolyze dietary fats into fatty acids and glycerol.
• Cellulases and pectinases: Degrade plant cell-wall polysaccharides and fiber.
• Glutaminase: Converts glutamine to glutamic acid, enhancing umami flavor. Glutaminase is used by the food industry to produce glutamic acid-rich food ingredients that are subsequently added to finished foods to improve the savory flavor profile of food.

Secondary Metabolites

Secondary metabolite production by Aspergillus species varies based on fermentation type and conditions. A. oryzae produces various secondary metabolites, including terpenoids, coumarins, and oxylipins.

Prominently characterized secondary metabolites include:

• Kojic acid (5-hydroxy-2-(hydroxymethyl)-4-pyrone): A standout feature of A. oryzae is the production of kojic acid, a versatile secondary metabolite first isolated in 1907 from koji-culture. Kojic acid finds applications as an antibiotic, food preservative, and antioxidant. Its role as a tyrosinase inhibitor has also propelled its use in cosmetics for skin-lightening and in medicine for chloasma treatments.
• Ergothioneine: Ergothioneine is a derivative of amino acid that has strong antioxidative activity. Koji fermented with A. oryzae is reported to contain 59.8 ± 20.4 μg/g ergothioneine.
• Beta-glucan: A cell-wall polysaccharide with recognized immune-modulatory properties.
• ACE-inhibitor peptides: Bioactive peptides released during fermentation that inhibit angiotensin I-converting enzyme. In one study, nine commercial proteases were examined to form ACE-inhibitory peptides from casein, and maximal in vitro ACE inhibitory and potent in vivo anti-hypertensive activities were observed in bioactive peptides released by a protease isolated from Aspergillus oryzae.
• Organic acids: Various strains of A. niger are used in the industrial preparation of citric acid (E330) and gluconic acid (E574); therefore, they have been deemed acceptable for daily intake by the World Health Organization.
• Ferulic acid, glycosylceramides, pyranonigrin A, polyamines, deferriferrichrysin, and 14-dehydroergosterol are among additional bioactive compounds identified in koji preparations, as documented in peer-reviewed reviews of A. oryzae medicinal substances.
• Ergosta-4,6,8(14),22-tetraen-3-one (ETO): A steroid compound produced by A. oryzae that has been studied for anti-inflammatory activity. Research demonstrated that ETO significantly reduced the secretion of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α, and suppressed the activation of the MyD88/NF-κB/MAPK/NLRP3 signaling pathway, indicating its potential as a potent anti-inflammatory agent. ETO is not only abundantly produced by A. oryzae but also exhibits pronounced anti-inflammatory activity, providing a promising foundation for its future development in anti-inflammatory therapeutics. This evidence is currently limited to cell-based (in vitro) models.

Postbiotic Concept

In recent years, fermentation products of A. oryzae have attracted attention in the emerging field of postbiotics. This area aims to provide a comprehensive summary of the potential postbiotic effects of fermentation products from A. oryzae, discussing possible mechanisms of action against the background of the molecular composition determined so far. In particular, cell-wall constituents, enzymes, extracellular polymeric substances, and various metabolites found in A. oryzae fermentation preparations are described in detail. Putative beneficial bioactivities include modulating the microbiota, improving epithelial barrier function, influencing immune responses, metabolic reactions, and signaling through the nervous system.

4. Scientific Evidence by Area of Use

4.1 Digestive Health and Enzyme Supplementation

Mechanistic basis: Thanks to its potent ability to produce amylase and protease, A. oryzae allows decomposition of proteins and different starches into sugars and amino acids. In supplemental enzyme formulations, Aspergillus-derived enzymes are added as exogenous digestive aids intended to compensate for endogenous enzyme insufficiency or to enhance digestion of specific dietary substrates.

Evidence strength: Most evidence for direct digestive benefits in humans derives from mechanistic studies and extrapolation from the well-established industrial enzyme literature. Direct, high-quality clinical trials in human populations specifically using Aspergillus-derived enzyme supplements as an isolated intervention for digestive complaints are limited, and the most robustly studied application involves gluten degradation (see Section 4.2).

4.2 Gluten Degradation (AN-PEP)

The most clinically well-characterized human application of an Aspergillus-derived enzyme is the use of A. niger prolyl endoprotease (AN-PEP) for degradation of dietary gluten. This has been the subject of multiple controlled clinical studies in human volunteers.

Study 1 (Salden et al., 2015, published in Alimentary Pharmacology & Therapeutics): Aspergillus niger prolyl endoprotease (AN-PEP) efficiently degrades gluten molecules into non-immunogenic peptides in vitro. The study aimed to assess the efficacy of AN-PEP on gluten degradation; AN-PEP presents a promising option to degrade inadvertent dietary gluten because it is active at gastric pH and is not degraded by pepsin.

Study 2 (König et al., 2017, Scientific Reports): In this randomized placebo-controlled crossover study, 18 gluten-sensitive subjects consumed a porridge containing 0.5 g gluten together with two tablets either containing a high or low dose of AN-PEP, or placebo. Gastric and duodenal content was sampled over 180 minutes, and areas under the curve of gluten concentrations were calculated. The primary outcome — success rate of high-dose AN-PEP defined as at least 50% gluten degradation compared to placebo in the duodenum — was achieved in 10 of 13 comparisons. In the stomach, gluten levels were significantly reduced in both high- and low-dose AN-PEP groups (p = 0.001); in the duodenum, gluten levels were also significantly reduced with high-dose (p = 0.019) and low-dose (p = 0.015) AN-PEP compared to placebo.

Mechanism of AN-PEP: AN-PEP successfully cleaved immunogenic gluten epitopes into smaller, non-immunogenic peptides of eight amino acids or smaller. AN-PEP is active between pH 2 and 8, with optimal activity between pH 4 and 5. It is not degraded by pepsin, thereby remaining fully functional in the stomach. It specifically degrades gluten epitopes by cleaving behind proline residues.

Limitations: The existing clinical trials are small (n=12–18), conducted in gluten-sensitive but not necessarily celiac disease-diagnosed populations, and focus on surrogate endpoints (gastric/duodenal gluten content) rather than intestinal mucosal healing or long-term clinical outcomes. AN-PEP is not approved as a treatment for celiac disease and is not a substitute for a gluten-free diet.

4.3 Cardiovascular Health: ACE Inhibition and Blood Pressure

Aspergillus oryzae proteases release bioactive peptides from proteins — notably casein, soy, and seafood proteins — that exhibit angiotensin I-converting enzyme (ACE) inhibitory activity. Bioactive peptides from fermented food sources have been identified as natural ACE inhibitors, exerting their effects by binding to ACE and blocking the conversion of angiotensin I to angiotensin II, thereby reducing vasoconstriction and lowering blood pressure.

In animal models, fermented abalone viscera using A. oryzae 001 exhibited increased angiotensin I-converting enzyme (ACE) inhibitory activity and enhanced inhibition of blood pressure elevation in spontaneously hypertensive rats (SHRs). The identified active substance was L-m-tyrosine, which non-competitively inhibited ACE and in a single oral administration significantly reduced blood pressure in SHRs. This study suggested potential use as a functional food.

A human pilot study referenced in the literature (Sano et al., 2005, J Med Food) examined the effect of casein hydrolysate prepared with a protease derived from A. oryzae on subjects with high-normal blood pressure or mild hypertension, but this work requires independent replication. Evidence strength: Mechanistic and in vitro/animal evidence is consistent; direct human RCT evidence for isolated A. oryzae-derived ACE-inhibitory peptides on blood pressure is currently limited and preliminary.

4.4 Anti-inflammatory Activity

A. oryzae fermentation extract (AOFE) suppressed the growth of Mycoplasma pneumoniae and invasion into A549 lung epithelial cells in vitro. AOFE treatment also suppressed Mp-stimulated production of tumor necrosis factor (TNF)-α and interleukin (IL)-6 at mRNA and protein levels in murine MH-S alveolar macrophages. HPLC analysis revealed that the major component of AOFE was kojic acid.

Among the metabolites of A. oryzae, kojic acid and its derivatives have been shown to exhibit a variety of biological functions, including antimicrobial, antioxidant, anti-inflammatory, and wound-healing activities. Evidence strength: These findings are based on cell culture and animal experiments and have not yet been replicated in controlled human trials. They should be considered preliminary and exploratory.

4.5 Antioxidant Properties

Kojic acid finds applications as an antibiotic, food preservative, and antioxidant. Kojic acid has been used as a food additive as an antioxidant, preservative, and flavor enhancer, as well as a skin lightening or bleaching agent in the cosmetics industry. Additionally, kojic acid and many of its derivatives have shown anti-cancer, anti-inflammatory, insecticidal, antifungal, antibacterial, and antiviral properties.

Ergothioneine, found in koji preparations, is independently recognized as a potent antioxidant amino acid derivative. Ergothioneine is a derivative of amino acid that has strong antioxidative activity. Evidence strength: Antioxidant properties of individual constituents are well-characterized in vitro; whether these translate into clinically meaningful antioxidant effects in humans consuming Aspergillus enzyme supplements has not been established in controlled trials.

4.6 Gut Microbiota Modulation

A 2024 narrative review aimed to provide a comprehensive summary of the potential postbiotic effects of fermentation products from A. oryzae by discussing possible mechanisms of action against the background of the molecular composition determined so far. Cell-wall constituents, enzymes, extracellular polymeric substances, and various metabolites found in A. oryzae fermentation preparations were described in detail. Putative beneficial bioactivities include modulating the microbiota, improving epithelial barrier function, influencing immune responses, metabolic reactions, and signaling through the nervous system.

Drawing on existing literature and case studies, A. oryzae is highlighted as a promising source of postbiotics, particularly in the context of animal health and nutrition. Challenges and opportunities in quality control are also addressed, with a focus on the necessity for standardized methods to fully harness the potential of fungal-based postbiotics. This article sheds light on the emerging field of A. oryzae-derived postbiotics and emphasizes the need for further research to fully realize their therapeutic potential.

Evidence strength: Microbiota-modulating properties of A. oryzae preparations are largely derived from animal feeding studies and mechanistic in vitro data. Robust human clinical evidence in this area is not yet available as of the current literature.

4.7 Animal Performance Studies (Context for Supplement Claims)

A substantial body of peer-reviewed evidence for Aspergillus as a dietary supplement derives from veterinary and livestock nutrition contexts. A. awamori supplementation has been shown to improve growth performance and feed efficiency in animals due to the production of vitamins and the secretion of amylase, protease, and lipase, which can increase the digestibility of nutrients in an animal's gut.

A study investigated the effect of different levels and consumption periods of Aspergillus oryzae meal on performance, carcass characteristics, blood variables, and immunity of broiler chickens. Compared with the control, A. oryzae meal used during the entire rearing period increased weight gain, reduced relative weight of abdominal fat, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) serum levels, and increased antibody titers against influenza and Newcastle disease vaccination.

These animal studies provide mechanistic plausibility for enzyme-mediated nutrient digestibility enhancement, but direct extrapolation to human physiology requires caution.

5. Body Systems and Health Areas

Based on the published literature, Aspergillus-derived preparations have been studied in relation to the following body systems and health domains:

• Gastrointestinal system: Enzyme-mediated macronutrient digestion (starch, protein, fat); intestinal morphology; gut microbiota composition; epithelial barrier integrity.
• Cardiovascular system: ACE inhibitor peptide generation; potential blood pressure modulation via the renin-angiotensin system.
• Immune system: Immune modulation via postbiotic cell-wall components (beta-glucan); potential effects on inflammatory cytokine profiles (in vitro and animal data).
• Metabolic health: Indirect effects via improved nutrient absorption; potential hyperlipidemia-related applications under review in emerging research.
• Skin and integument: Kojic acid's tyrosinase-inhibiting and skin-lightening applications are well-documented, primarily in topical cosmetic contexts rather than oral supplementation.
• Cognitive health: Potential applications of ergothioneine and other kojic metabolites are the subject of exploratory review, without established human clinical trial evidence.

The Japanese dynasty and nation have domesticated and utilized koji fermented with non-pathogenic fungus Aspergillus oryzae for more than 1,300 years. A review of the literature introduces potential medical applications of medicinal substances in koji to hyperlipidemia, diabetes, hypertension, cardiovascular and cognitive diseases, chronic inflammation, epidermal permeability barrier disruption, COVID-19, and anti-cancer therapy. The majority of these applications remain at the stage of mechanistic review and exploratory research, and are not supported by definitive, large-scale human clinical trials.

6. Dosage Forms and Reported Dosages

Dosages for Aspergillus-derived preparations vary substantially by application and preparation type. The following dosages appear in the peer-reviewed and regulatory literature cited above:

• AN-PEP (gluten degradation, human clinical trial): In the randomized placebo-controlled crossover study, 18 gluten-sensitive subjects consumed a porridge containing 0.5 g gluten together with two tablets either containing a high or low dose of AN-PEP, or placebo. Exact enzyme activity units for the high and low doses were specified in the original study but doses were presented as tablet units.
• Aspergillus oryzae culture (livestock/ruminant study): 40 g/d of Aspergillus oryzae culture (AOC) increased the dry matter degradation rate of alfalfa hay and corn straw by 18.53% and 18.08%, respectively — this dose is for sheep and is not applicable to human use.
• Aspergillus oryzae meal (poultry study): Two levels — 2 g/kg diet and 4 g/kg diet (as-fed) — of Aspergillus oryzae meal and 4 consumption periods were used in a 2 × 4 factorial arrangement. This is an animal feeding study dose.
• Koji minerals / dried biomass (FDA GRAS submission): Dosage specifications for food-grade koji mineral products have been submitted to the FDA in GRAS notice 829, covering specific product formulations.

No standardized human oral dosage has been established by an authoritative pharmacopeial body (such as USP, EP, or WHO) for Aspergillus-derived enzyme supplement preparations as a drug or nutraceutical ingredient in humans. Commercially available digestive enzyme products contain variable enzyme activity units (measured in DPP-IV units, HUT, SAPU, or similar activity assays) rather than mass-based doses of the organism itself.

7. Safety Considerations and Interactions

Regulatory Status

A. niger fermentation is "generally recognized as safe" (GRAS) by the United States Food and Drug Administration under the Federal Food, Drug, and Cosmetic Act. A. oryzae is generally recognized as safe (GRAS) by the Food and Drug Administration (FDA) and is therefore used for the production of various enzymes, including amylases, proteases, and glutaminases.

Pathogenicity

Invasive growth or systemic infections by A. oryzae in healthy humans have never been reported. In a few cases, however, isolates identified as A. oryzae have been recovered from debilitated patients. A. oryzae has therefore low pathogenic potential but may, like many other harmless microorganisms, grow in human tissue under exceptional circumstances.

Mycotoxin Considerations

A review of the safety of fungal workhorses of industrial biotechnology noted that A. niger can produce the mycotoxins ochratoxin A, fumonisins B2, B4, and B6, and oxalic acid, and A. oryzae can produce the mycotoxins cyclopiazonic acid and β-nitropropionic acid. Importantly, A. oryzae strains are not able to produce aflatoxins due to the presence of disabling mutations in the gene cluster.

A. oryzae does not produce aflatoxins or any other carcinogenic metabolites. The absence of significant levels of mycotoxins in industrial products is regularly checked. Notably, A. oryzae has been wrongly reported as an aflatoxin producer in some literature, due to misclassification of Aspergillus flavus strains.

A risk assessment document notes that A. oryzae can produce a variety of mycotoxins when fermentation is extended beyond the usual time needed for production of these foods, though wild A. flavus isolates readily produce aflatoxins and other mycotoxins while A. oryzae has not been shown to be capable of aflatoxin production.

Allergenicity

Allergic diseases primarily caused by A. oryzae have been reported in few cases, but probably presuppose both a sensitivity to allergenic reactions and a massive exposure to conidia by inhalation. Enzymes such as amylase appear to be associated with allergic responses in certain occupations with high exposure to those materials. The occupational inhalation risk (relevant to bakery and enzyme-manufacturing workers) is distinct from the risk associated with oral consumption of Aspergillus-derived supplements.

Safety of Derived Products (Glutaminase, Citric Acid)

The safety of glutaminase from A. niger (Sumizyme GT) was evaluated in a series of toxicological studies, including a 90-day oral toxicity study in rats, an in vitro bacterial reverse mutation assay, an in vitro mammalian chromosome aberration test, and an in vivo alkaline Comet assay. Sumizyme GT was not mutagenic or genotoxic, and administration by gavage at doses up to 2,570 mg total organic solids (TOS)/kg body weight per day for 90 days was without any systemic toxicity. The no-observed-adverse-effect level (NOAEL) was concluded to be 2,570 mg TOS/kg bw per day, the highest dose tested. The results provide further support of the safety of glutaminase from A. niger when used in food production.

Interactions and Precautions

No specific drug–supplement interactions with Aspergillus-derived enzyme preparations have been formally documented in the peer-reviewed clinical pharmacology literature. The theoretical concern that exogenous proteases could alter the rate of absorption of co-administered peptide-based drugs or oral protein therapeutics has not been systematically studied. Individuals with known mold hypersensitivity or allergy to fungi may experience reactions to products containing live or whole-organism Aspergillus preparations. A. oryzae is not a plant or animal pathogen, and survival in the environment is expected to be limited due to decreased survival characteristics from years of domestication.

Quality Control Considerations

Modern food strains of A. oryzae are non-pathogenic and non-toxigenic, and industry controls focus on verifying the absence of mycotoxins within regulatory limits. It is of paramount importance to accurately describe the mycotoxins that can potentially be produced by a fungal species used as a production organism and to ensure that production strains are not capable of producing mycotoxins during enzyme production.

References

• König et al. / Schreiner et al. (2024). "The postbiotic potential of Aspergillus oryzae – a narrative review." Frontiers in Microbiology. PMC11538067.
• PubMed abstract: "The postbiotic potential of Aspergillus oryzae – a narrative review." PubMed 39507340.
• König J, Holster S, Bruins MJ, Brummer RJ (2017). "Randomized clinical trial: Effective gluten degradation by Aspergillus niger-derived enzyme in a complex meal setting." Scientific Reports. PMC5638938.
• König et al. (2017). "Randomized clinical trial: Effective gluten degradation by Aspergillus niger-derived enzyme in a complex meal setting." Scientific Reports. doi:10.1038/s41598-017-13587-7.
• Salden BN et al. (2015). "Randomised clinical study: Aspergillus niger-derived enzyme digests gluten in the stomach of healthy volunteers." Alimentary Pharmacology & Therapeutics. doi:10.1111/apt.13266.
• Ichishima E (2021). "Medical Application of Substances Derived from Non-Pathogenic Fungi Aspergillus oryzae and A. luchuensis-Containing Koji." Journal of Fungi. PMC8063943.
• Ichishima E (2021). "Medical Application of Substances Derived from Non-Pathogenic Fungi Aspergillus oryzae and A. luchuensis-Containing Koji." J Fungi 7(4):243.
• El-Enshasy HA et al. (2021). "The ancient koji mold (Aspergillus oryzae) as a modern biotechnological tool." Bioresources and Bioprocessing.
• Machida M et al. (2008). "Genomics of Aspergillus oryzae: Learning from the History of Koji Mold and Exploration of Its Future." DNA Research. doi:10.1093/dnares/dsn020.
• ScienceDirect Topics: "Aspergillus oryzae – an overview." Encyclopedia of Food Microbiology (Second Edition), 2014.
• Barbesgaard P, Heldt-Hansen HP, Diderichsen B (1992). "On the safety of Aspergillus oryzae: a review." Applied Microbiology and Biotechnology.
• Schuster E et al. (2002). "On the safety of Aspergillus niger – a review." PubMed 12172605.
• Pahl H et al. (2019). "Safety of the fungal workhorses of industrial biotechnology: update on the mycotoxin and secondary metabolite potential of Aspergillus niger, Aspergillus oryzae, and Trichoderma reesei." PMC6208954.
• Vo TD et al. (2020). "Safety assessment of glutaminase from Aspergillus niger." Food Science & Nutrition. PMC7063383.
• Lin PY et al. (2023). "Aspergillus oryzae Fermentation Extract Alleviates Inflammation in Mycoplasma pneumoniae Pneumonia." PMC9920650.
• Peng X et al. (2023). "Effective production of kojic acid in engineered Aspergillus niger." PMC9969635.
• ScienceDirect Topics: "Kojic Acid – an overview." Handbook of Fermented Food and Beverage Technology.
• U.S. EPA (1997). "Final Risk Assessment of Aspergillus oryzae." Attachment I.
• U.S. EPA (1997). "Final Risk Assessment for Aspergillus niger." Attachment I.
• U.S. FDA GRAS Notice 829: "Dried biomass of Aspergillus oryzae."
• Wikipedia: "Aspergillus niger."
• Wikipedia: "Aspergillus oryzae."
• Zhao X et al. (2020). "The effect of Aspergillus niger as a dietary supplement on blood parameters, intestinal morphology, and gut microflora in Haidong chicks." PMC7704321.
• Zahirian M et al. (2019). "Dietary supplementation of Aspergillus oryzae meal and its effect on performance, carcass characteristics, blood variables, and immunity of broiler chickens." PMC6831530.
• Fujiwara Y et al. (2023). "Abalone Viscera Fermented with Aspergillus oryzae 001 Prevents Pressure Elevation by Inhibiting Angiotensin Converting Enzyme." PMC9967480.
• Alshannaq AF et al. (2018). "Controlling aflatoxin contamination and propagation of Aspergillus flavus by a soy-fermenting Aspergillus oryzae strain." PMC6237848.
• Zhang X et al. (2022). "Supplementation of Aspergillus oryzae Culture Improved the Feed Dry Matter Digestibility and Energy Supply in the Rumen of Hu Sheep." PMC9084320.
• Fermentation Optimization of Ergosta-4,6,8(14),22-Tetraen-3-One From Aspergillus oryzae and Its Anti-Inflammatory Mechanism. PMC12703800.
• Government of Canada (2021). "Final Screening Assessment for Aspergillus oryzae ATCC 11866."
• Frontiers in Marine Science (2023). "Aspergillus niger confers health benefits and modulates the gut microbiota of juvenile Pacific white shrimp."
• Sweis IE, Cressey BC (2018). "Potential role of the common food additive manufactured citric acid in eliciting significant inflammatory reactions." PMC6097542.