Quillaja

Quillaja (Quillaja saponaria Molina): A Comprehensive Reference

1. Identity

1.1 Botanical and Taxonomic Classification

Quillaja saponaria, the soap bark tree or soapbark, is an evergreen tree in the family Quillajaceae, native to warm temperate central Chile. In Chile it occurs from 32 to 40° South Latitude approximately and at up to 2,000 m (6,500 ft) above sea level. Although Quillaja is native to Chile and Peru, it is now widely cultivated in southern California. The tree is large and evergreen, growing to 18 m by 6 m, with shiny, thick leaves. The generic name is derived from the Chilean word quillean, meaning "to wash," due to the bark's use as a cleansing aid. The bark has an acrid, astringent taste.

The name Quillaja is derived from the indigenous Mapuche name küllay, which means soap, and the Chilean vernacular name for this species, culay. Saponaria means "soap-like." A second species of commercial interest, Quillaja brasiliensis (A. St.-Hill. & Tul.) Mart., is also a well-documented source of related saponins. Quillaja saponaria Molina represents the main source of saponins for industrial applications. Q. saponaria triterpenoids have been studied for more than four decades, and their relevance is due to their biological activities, especially as a vaccine adjuvant and immunostimulant, which have led to important research in the field of vaccine development.

1.2 Common Names and Synonyms

Synonyms for the extract include: Soapbark extract; Quillay bark extract; Panama bark extract; Quillai extract; Murillo bark extract; China bark extract. Common names include China bark, Murillo bark, Panama bark, Quillaja, Soap tree, and Soapbark.

1.3 Regulatory Identity

Quillaja saponaria extract is registered with EC No 273‐620‐4 and CAS No 68990‐67‐0, the same CAS number cited for Quillaia extract Type 1 and Type 2 in the JECFA specifications. In the European Union, Quillaja bark extract has received official authorization under the food additive designation E 999. Quillaja saponins are approved for use as food additives in 187 signatory countries of the Codex Alimentarius, including the European Union, the United Kingdom, the United States, China, and Japan.

1.4 Source Material and Forms of Preparation

The inner bark of Quillaja saponaria can be reduced to powder and employed as a substitute for soap, since it forms a lather with water, owing to the presence of a glycoside saponin, sometimes distinguished as quillaia saponin. The inner bark is separated from the cork and collected for commercial use. According to Commission Regulation (EU) No 231/2012, Quillaia extract (E 999) is obtained by aqueous extraction of Quillaia saponaria Molina, or other Quillaia species, trees of the family Rosaceae. It contains a number of triterpenoid saponins consisting of glycosides of quillaic acid. Sugars — including glucose, galactose, arabinose, xylose and rhamnose — are also present, along with tannin, calcium oxalate and other minor components.

Aqueous extracts of Quillaja saponaria bark are available commercially. These are dark brown, foamy extracts that contain many compounds including tannins, polyphenolics, and saponins. Commercial preparations exist in several grades. Saponins can be obtained industrially as powder or liquid products, and may be in an unpurified, partially, or purified state, mainly used as natural emulsifiers in cosmetics, food, and beverages. In the food industry, two principal extract types are recognized by JECFA: Type 1 (unpurified aqueous extract) and Type 2 (saponin-enriched extract). The European Commission of Cosmetic Ingredients (CosIng) database has listed some Quillaja products as cosmetic ingredients, such as the bark, bark extract, root extract, and wood extract. For vaccine applications, a highly purified fraction designated QS-21 (also called fraction 21 of Quil A) is prepared by semi-preparative reverse-phase high-performance liquid chromatography.

2. Traditional and Historical Use

2.1 Indigenous Use in Chile

Soap bark tree has a long history of medicinal use with the Andean people, who used it as a treatment for various chest problems. The soapbark tree has been utilized by humans for centuries. Indigenous peoples of Chile have traditionally used the bark for its saponin content to create soap and for medicinal purposes. Historically, the indigenous people of South America utilized the bark of the Quillaja saponaria tree for its soap-like properties, using it to clean textiles and as a natural remedy for various ailments. The bark has been used in South America to aid in washing clothes.

2.2 Medicinal Traditions

In traditional medicine, quillaja has been used orally to relieve cough and bronchitis, and topically to relieve scalp itchiness and dandruff. The saponin content of the bark helps to stimulate the production of a more watery mucus in the airways, thus facilitating the removal of phlegm through coughing. Traditionally, quillaja bark was prepared as infusions or powders to address respiratory ailments, including coughs and bronchitis, due to its expectorant properties.

Topically, it has been indicated to treat scalp diseases (dandruff and hair loss) and other dermatological disorders.

2.3 Commercial Emergence in the 18th–19th Centuries

In the eighteenth and nineteenth centuries, the bark was exported for its soap and shampoo properties, while the wood was hard and useful for making stirrups. However, the soapbark tree was not centre stage in terms of its commercial potential. The Chilean soapbark tree, traditionally valued as a source of natural soap, was shown by serendipitous research in France in the 1900s to produce compounds that can boost the immune response to vaccines. One of these compounds, QS-21, was approved for use in human vaccines in 2017 and is now valued at >$100,000/g because of its growing importance as a vaccine adjuvant.

3. Key Constituents and Active Compounds

3.1 Triterpenoid Saponins: Structure and Diversity

Quillaja saponins are triterpenoid saponins comprising a hydrophobic quillaic acid backbone and hydrophilic sugar moieties. Quillaja saponin (QS) is a group of natural surfactants extracted from the Quillaja Saponaria Molina tree; it is a triterpene saponin with a hydrophobic quillaic acid aglycone group and two hydrophilic sugar chains. The molecular weights of the major compounds in the fractions range from approximately 1,200 to approximately 2,300 Da; all fractions test positive for triterpenoids and saccharides.

Three saponins were isolated from a commercial bark extract of Quillaja saponaria Molina and characterized, using mainly NMR spectroscopy, mass spectrometry and chemical methods, as quillaic acid 3-O-[β-D-galactopyranosyl-(1→2)-β-D-glucopyranosiduronic acid], and related compounds with rhamnose and xylose extensions at the 3-position. Among the most studied and commercially significant individual saponin molecules isolated from Quil A are QS-7, QS-17, QS-18, and QS-21, identified by LC-MS and analytical HPLC. Injection of ether solutions of lipids into aqueous solutions of QS-17, QS-18, or QS-21 all resulted in homogeneous ISCOM dispersions, while the combination of lipids and QS-7 produced lamellae and liposomes as the prominent structures.

3.2 QS-21: The Clinically Most Relevant Fraction

QS-21 is defined as a natural product adjuvant derived from the Quillaja saponaria tree that enhances the immune response to coadministered antigens, with two identified isomers, QS-21-Api and QS-21-Xyl, differing by a carbohydrate unit. Studies have shown that its adjuvant property depends on the aldehyde functional group in the aliphatic side chain of the QS molecule, and its conformational change may lead to a decrease in its adjuvant property.

3.3 Other Constituents

The extract contains a number of triterpenoid saponins consisting of glycosides of quillaic acid. Sugars — including glucose, galactose, arabinose, xylose and rhamnose — are also present, along with tannin, calcium oxalate and other minor components. The chemicals of interest for Quillaja saponaria Molina, as listed in EFSA's compendium of botanicals, are triterpenoid saponins (quillaja saponins) and calcium oxalate (11%).

3.4 Amphiphilic Properties and Interfacial Behavior

Commercially available Quillaja saponin products exploit the biological and interfacial activities of Quillaja saponins and their ability to form and stabilize colloidal structures such as emulsions, foams, crystallized lipid particles, heteroaggregates, and micelles. The saponins present in Quillaja extract are amphiphilic molecules, meaning they have both a water-attracting (hydrophilic) and a fat-attracting (lipophilic) portion. This property allows them to accumulate at the interface between water and air or water and oil, forming stable foams and emulsions.

4. Mechanisms of Action

4.1 Immunoadjuvant Mechanisms

Quillaja saponins, alone or incorporated into immunostimulating complexes (ISCOMs), are able to modulate immunity by increasing antigen uptake, stimulating cytotoxic T lymphocyte production (Th1) and cytokines (Th2) in response to different antigens.

QS-21 directly activates human monocyte-derived dendritic cells (moDCs) and promotes a pro-inflammatory transcriptional program. Cholesterol-dependent QS-21 endocytosis followed by lysosomal destabilization and Syk kinase activation are prerequisites for this response. Cathepsin B, a lysosomal cysteine protease, was essential for moDC activation in vitro and contributed to the adjuvant effects of QS-21 in vivo. Collectively, these findings provide new insights into the pathways involved in the direct activation of antigen-presenting cells by a clinically relevant QS-21 formulation.

A unique mechanism of molecular and cellular synergy between a TLR4 ligand, MPL, and the saponin QS-21 — the constituents of the Adjuvant System AS01 — has been described. AS01 is part of the malaria and herpes zoster vaccine candidates that demonstrated efficacy in phase III studies. Hours after injection of AS01-adjuvanted vaccine, resident cells such as NK cells and CD8+ T cells release IFNγ in the lymph node draining the injection site. This effect results from MPL and QS-21 synergy and is controlled by macrophages, IL-12 and IL-18. Depletion strategies showed that this early IFNγ production was essential for the activation of dendritic cells and the development of Th1 immunity by AS01-adjuvanted vaccine.

QS-21 is thought to mediate its adjuvant activity by accumulating CD169+ resident macrophages in the draining lymph node and by activating caspase-1.

4.2 Antimicrobial and Membrane-Disrupting Mechanisms

The main reason for the antimicrobial activities of Quillaja saponins is the affinity of the aglycone with cell membrane cholesterol, leading to changes in the membrane and, consequently, preventing microorganism infection of the cell. Saponins present detergent properties by destroying membrane lipids and, for this reason, they can make the bacterial cell membranes permeable, facilitating the influx of molecules through the bacterial wall, such as antibiotics.

It is believed that saponins offer more than one novel mechanism of antiviral action, including interactions with viral envelopes leading to their destruction, interactions with host-cell membranes leading to a loss of virus binding sites, and coating of cells to prevent virus binding. Additionally, saponins can affect post-entry events such as viral genome replication and protein synthesis. Studies on triterpene-rich extracts have reported reductions in plaque size and progeny production even when added after viral adsorption, suggesting intracellular antiviral activity.

4.3 ISCOMs: Nanoparticulate Delivery Structures

Immune-stimulating complexes (ISCOMs) are stable complexes of cholesterol, phospholipid and Quil A, a triterpene saponin mixture in the size range from 40 to 100 nm. They can be used as antigen carriers in subunit vaccines. The physical properties of ISCOM adjuvants contribute to antigen stability, reduce the haemolytic effects associated with saponins, interact with dendritic cells (DCs) and enhance cross-presentation of the incorporated antigen, generating both antibody and CD4+ and CD8+ T cell responses. ISCOM and ISCOMATRIX™ vaccines are known to induce long-lasting antibody responses, a balanced Th1/Th2 response, and generation of cytotoxic T lymphocytes in mice and humans.

5. Scientific Evidence by Area of Use

5.1 Vaccine Adjuvant Use — Human Clinical Evidence (Strongest Evidence Category)

QS-21, a refined adjuvant based on saponins, is isolated from the bark of the soap-bark tree (Quillaja saponaria). It has garnered significant interest in the creation of next-generation vaccine adjuvants due to its robust ability to elicit Th1-type and Th2-type immunological responses. Despite its successful incorporation into licensed vaccines such as Shingrix® (herpes zoster) and Mosquirix® (malaria), the widespread application of QS-21 remains constrained by several limitations, including limited natural availability, chemical instability, dose-dependent toxicity, and an incompletely elucidated mechanism of action.

5.1.1 Herpes Zoster (Shingrix)

RZV (recombinant zoster vaccine, Shingrix) consists of 50 µg of recombinant VZV glycoprotein E and the AS01B adjuvant system, containing 50 µg of 3-O-desacyl-4'-monophosphoryl lipid A, 50 µg of Quillaja saponaria Molina fraction 21 (QS-21), and liposome. Two large randomized, placebo-controlled phase 3 trials — the Zoster Efficacy Study in Adults 50 Years of Age or Older (ZOE-50) and Zoster Efficacy Study in Adults 70 Years of Age or Older (ZOE-70) — were conducted in 29,300 immunocompetent adults to determine the efficacy of RZV in preventing HZ and PHN.

The overall vaccine efficacy (VE) was 97.2% in the ZOE-50 study in adults ≥50 years old, and an overall VE of 89.8% in the ZOE-70 study involving adults ≥70 years. The adjuvanted recombinant zoster vaccine (RZV, Shingrix, GSK) demonstrated ≥90% efficacy against HZ in all age groups ≥50 years, which was maintained over a 3.2- and 3.7-year follow-up period in the two pivotal phase 3 trials. Follow-up of the ZOE-50 and ZOE-70 studies demonstrated that RZV maintains long-term efficacy against herpes zoster exceeding 82%.

The Herpes Zoster vaccine (HZ/su) (Shingrix™) received a license in 2017 from the FDA and a marketing authorization in the EU in 2018. The FDA first authorized Shingrix® in 2017; it is currently accessible in many nations worldwide and has demonstrated 90% efficacy, even in subjects who are 80 years of age or older. Evidence strength: Very strong — supported by large, multinational, randomized, placebo-controlled phase 3 trials, regulatory approval, and long-term follow-up data.

5.1.2 Malaria Vaccine (Mosquirix / RTS,S)

The RTS,S/AS01 vaccine (Mosquirix™) against malaria was approved by the EMA in 2015 for further implementation in Sub-Saharan countries for routine use. QS-21, a triterpenoid saponin from Quillaja saponaria, is the most extensively studied and has been incorporated into licensed vaccines such as Shingrix, Mosquirix, and Arexvy. Evidence strength: Strong for the adjuvant's contribution to the approved formulation, based on multiple phase 3 studies.

5.1.3 RSV Vaccine (Arexvy)

The FDA approved the Arexvy vaccine in 2023 for the prevention of lower respiratory tract disease caused by respiratory syncytial virus (RSV) in individuals 60 years of age and older. The Novavax vaccine for COVID-19 uses this adjuvant; the zoster vaccine Shingrix also contains QS-21, as well as the RSV vaccine Arexvy. Evidence strength: Strong for Arexvy's regulatory approval; QS-21's specific contribution within AS01E is based on the broader AS01 evidence base.

5.1.4 Cancer and Alzheimer's Disease Therapeutic Vaccines (Exploratory)

Phase I–III clinical trials of QS-21, mostly formulated in adjuvant systems, have been conducted to evaluate efficacy, immunogenicity and safety of adjuvanted prophylactic vaccines against infectious diseases such as malaria, herpes zoster, tuberculosis, AIDS, and therapeutic vaccines against cancer and Alzheimer's disease. However, phase III clinical results in terms of disease-free survival for patients with immunotherapeutic vaccines adjuvanted with QS-21/AS015 against NSCLC and melanoma were disappointing despite promising results of phase II trials. Evidence strength: Insufficient for cancer immunotherapy; phase III trials in these indications have not supported efficacy.

5.1.5 Hepatitis B Vaccines

The Adjuvant Systems containing MPL/QS-21 in combination with HBsAg were shown to induce very strong and persistent humoral and cellular immune responses in healthy adults, with AS01B inducing the strongest and most durable specific cell-mediated immunity after two doses, without serious adverse events. Evidence strength: Moderate-to-strong for immunogenicity; not yet translated to a licensed HBV product in this specific formulation.

5.2 Respiratory and Expectorant Use

The saponin content of the bark helps to stimulate the production of a more watery mucus in the airways, thus facilitating the removal of phlegm through coughing. No reliable clinical trials support use of quillaja for any indication as a standalone oral medicine. In traditional medicine, quillaja has been used topically to relieve scalp itchiness and dandruff and orally to relieve cough and bronchitis, although ingestion of large amounts of quillaja bark is not considered safe. Evidence strength: Traditional use only; no human clinical trial evidence.

5.3 Antimicrobial Activity

The antimicrobial activities of saponins from Quillaja are described in several studies, especially their antibacterial, antifungal, and antiviral activities. The main reason for these activities is the affinity of the aglycone with cell membrane cholesterol, leading to changes in the membrane and, consequently, preventing microorganism infection of the cell.

In an in vitro study, saponins from Q. saponaria demonstrated activity against Trichomonas vaginalis, with maximum cytotoxicity noted at 0.025%. In another in vitro study, quillaja saponin extracts exerted antibacterial effects against Staphylococcus aureus and also demonstrated hemolytic activity. However, results against drug-resistant organisms are complex: a study conducted with clinical strains of multiresistant Escherichia coli isolated from human urine demonstrated that commercial saponin from Q. saponaria barks at 12 µg/mL significantly increased the growth of the six strains tested. Evidence strength: Preclinical (in vitro) only; no human clinical data. Results are mixed.

5.4 Antiviral Activity

Quillaja extracts were found to possess antiviral activity against cells infected with rotavirus and reovirus in an in vitro study. Specifically, these effects were noted at concentrations 1,000-fold lower than concentrations that demonstrate cytotoxicity. Mechanistically, there is strong evidence that the Quillaja extracts are able to "block" rotavirus infection by inhibiting virus–host attachment through disruption of cellular membrane proteins and/or virus receptors. Beyond their well-known surfactant and adjuvant properties, extensive evidence supports that saponins exert broad-spectrum antiviral activities through both direct virucidal effects and host-mediated immune mechanisms. Evidence strength: Preclinical (in vitro and animal) only; no human clinical data.

5.5 Antitumor / Cytotoxic Activity

Saponin fractions of Quillaja saponaria Molina (QS) have cytotoxic activity against cancer cells in vitro, but are too toxic to be useful in the clinic in their free, non-particulate form. The toxic effect was abolished by converting QS fractions into stable nanoparticles through the binding of QS to cholesterol. Two fractions of QS were selected for particle formation: one with an acyl-chain (ASAP) was used to form "killing and growth-inhibiting" (KGI) particles, and the other without the acyl-chain (DSAP) was used to formulate "blocking and balancing effect" (BBE) particles. KGI showed significant growth-inhibiting and cancer cell-killing activities in nine of ten cell lines. Low concentrations of KGI (0.5 and 2 µg/mL) induced irreversible exit from the cell cycle, differentiation measured by cytokine production, and eventually programmed cell death (apoptosis). Evidence strength: In vitro and laboratory only. No human clinical data available.

5.6 Cholesterol Lowering

Quillaja saponins have hypocholesterolaemic, anticarcinogenic, antioxidant and pesticidal properties. Quillaja saponaria (Quillay), an evergreen tree found in Chile, is one of the main sources of saponins. Quillaja saponins have hypocholesterolaemic, anticarcinogenic, antioxidant and pesticidal properties. The proposed mechanism involves formation of insoluble complexes with cholesterol in the gastrointestinal tract, thereby reducing absorption. However, animal and/or in vitro studies have evaluated the antimicrobial, anti-inflammatory, cholesterol-lowering, and cytotoxic effects of various components of quillaja. Evidence strength: Animal and in vitro data only; no human clinical trials have been conducted for this indication.

6. Body Systems and Health Areas

• Immune System: Vaccine adjuvancy — the best-characterized and clinically validated role of Quillaja-derived compounds (specifically QS-21 in AS01B) in licensed human vaccines for herpes zoster, malaria, and RSV.
• Respiratory System: Traditional use as an expectorant and mucolyic agent; the proposed mechanism (stimulating watery airway mucus) is pharmacologically plausible but lacks clinical trial evidence.
• Integumentary System (Skin & Scalp): Traditional topical use for dandruff and scalp conditions; modern cosmetic use exploiting surfactant and foaming properties.
• Cardiovascular System: Preclinical evidence for cholesterol-lowering via intestinal cholesterol-complexation; no human trial data.
• Gastrointestinal System: Use as a food additive foaming and emulsifying agent; EFSA notes the extract is likely to undergo hydrolysis in the GI tract, with the aglycone absorbed only to a limited extent.
• Oncology (Investigational): In vitro cytotoxic and pro-apoptotic effects in cancer cell lines; nanoparticulate formulations under investigation; clinical benefit not established.

7. Dosage Forms and Reported Dosages

7.1 Food Additive (E 999)

Undiluted Quillaja saponaria extracts are used in soft drinks at levels of 100–500 mg/kg (WHO, 2002). According to FEMA, quillaja saponins can be safely used as food additives up to a maximum level of 95 ppm in beverages. The mean intake of Quillaja extracts in the U.S. just from soft drinks (the major food use) is as much as 0.54 mg/kg/day, or 11% of the ADI.

7.2 Vaccine Adjuvant (QS-21 in AS01B)

In the approved Shingrix formulation, each dose contains 50 µg of QS-21 (Quillaja saponaria Molina, fraction 21), co-formulated with 50 µg of MPL and liposomes within the AS01B adjuvant system. The vaccine is administered as two intramuscular doses 2 months apart.

7.3 Oral/Traditional Preparations

There is no clinical evidence supporting specific dosage recommendations for Q. saponaria as a standalone oral supplement. Traditional decoctions and infusions were prepared from the inner bark; however, standardized dosages in this context are not established in the peer-reviewed literature.

8. Safety, Toxicity, and Regulatory Assessments

8.1 GRAS Status and Regulatory Approvals

The Food and Drug Administration (FDA) has classified Quillaja saponaria extract as "Generally Recognized as Safe" (GRAS). Quillaja extract is used in beverages and other foods with no report of any adverse effects. The European Food Safety Authority (EFSA) has evaluated E 999 and concluded that it is safe when used as intended and within the permitted maximum levels.

8.2 Acceptable Daily Intakes

According to the World Health Organization (WHO 2002), the established Average Daily Intake (ADI) of saponins from food additives is about 5 mg/kg body weight per day. Considering that the adverse effects reported were due to the presence of saponins in the extract, and that saponins are present in Quillaia extract Type 1 at around 20%, using an uncertainty factor of 100, the EFSA Panel derived an ADI of 3 mg saponins/kg bw per day for E 999. Food Standards Australia New Zealand (FSANZ) established a group ADI of 0–1 mg quillaia saponins/kg bw to permit the use of both Type 1 (unpurified) and Type 2 (saponin-enriched) extracts. The latest JECFA evaluation established a group ADI of 0–1 mg/kg bw per day for Type 1 and Type 2 extracts, expressed as quillaia saponins.

8.3 Toxicity at High Doses

Quillaja is toxic when ingested orally in large amounts. Severe toxic effects following ingestion of large doses of the bark include liver damage, gastric pain, diarrhea, hemolysis, respiratory failure, convulsions, and coma. The EFSA Panel considered that, from the limited data available, the acute toxicity of Quillaia extract was low. A no-observed-adverse-effect level (NOAEL) of 0.6% Quillaia extract (approximately 400 mg/kg bw per day) was noted from a 13-week study in rats in which relative organ weights were changed at the next higher dose of 1,200 mg/kg bw per day. No histopathological changes were observed at any dose.

8.4 Hemolytic Activity

The widespread application of QS-21 is constrained by several limitations, including dose-dependent toxicity. To mitigate QS-21's hemolytic toxicity and ensure precision delivery, stable liposomal formulations have been developed. The safety of saponins can be problematic; in severe cases, gastrointestinal injury or irritation or lesions may occur, thereby allowing saponins to get into the blood stream. At this point, the lethal dose of intravenous injection can reach 1/1000 of the lethal dose of oral injection. In comparative studies, QH-A was safer than QH-B and QH-C, causing hemolysis only at a concentration ten-times higher. The ISCOM formulation strategy was developed in part to address this problem: in order to reduce the undesirable haemolytic activity that invariably accompanies the adjuvant effect of saponins, different colloidal preparations which can also act as antigen delivery systems have been formulated. One of such preparations, ISCOMs, are 40 nm cage-liked self-assembled structures combining Quil A®, cholesterol, phospholipids and antigen.

8.5 Genotoxicity

The EFSA Panel considered that the data on the chemical composition of the mixture and the genotoxicity data available did not indicate a concern for genotoxicity. Collectively, mutagenicity studies indicate that soapbark extract possesses no genotoxic potential. The U.S. Food and Drug Administration (FDA) has designated Quillaja bark extract as a substance Generally Recognized as Safe (GRAS).

8.6 Reproductive Safety

There have been no reports of adverse reproductive effects resulting from the ingestion of foods containing saponins; this further supports the safety assessment of soapbark extract at food-grade usage levels. Information regarding safety and efficacy in pregnancy and lactation is lacking for medicinal use at doses above food-additive levels.

8.7 Gastrointestinal Absorption and Metabolism

The EFSA Panel considered it likely that intact Quillaia extract saponins are absorbed to a low extent; are hydrolysed in the GI tract; and that the aglycone is absorbed only to a limited extent. Saponins are absorbed only in very small amounts by the human gut. In sensitive individuals, high doses may cause gastrointestinal discomfort such as nausea or bloating.

8.8 Occupational and Allergic Hazards

One case report documented wheezing and dyspnea after exposure to raw bark dust, but only nasal symptoms after exposure to saponin dust. Symptoms improved on weekends and while on vacation. Total immunoglobulin E was markedly elevated at 2,000 units/mL (normal range, 10 to 250 units/mL). The individual developed asthma and anaphylaxis, necessitating epinephrine and intravenous steroids after a bronchial challenge test. Quillaja saponins are in Toxicity Category III for acute oral and acute dermal toxicity, Toxicity Category I for primary eye irritation, and Toxicity Category IV for acute inhalation toxicity and primary dermal irritation.

8.9 Regulatory Compendium Listing

Quillaja saponaria Molina is included in EFSA's Compendium of botanicals reported to contain naturally occurring substances of possible concern for human health when used in food and food supplements. In 2019, the Panel on Food Additives and Flavourings (FAF Panel) of the European Food Safety Authority (EFSA) re-evaluated E 999 and established an Acceptable Daily Intake (ADI) of 3 mg saponins per kg of body weight per day. In 2024, EFSA issued a supplementary opinion regarding this re-evaluation, recommending amendments to the existing EU specifications — specifically, lowering the limits for lead, mercury, and arsenic; introducing maximum limits for cadmium and calcium oxalate; and expressing these limits on a saponin basis.

9. Industrial and Commercial Applications

The extract is used as a food additive and flavoring agent in soft drinks (typically root beer and cream soda). Quillaja contains saponins, which are molecules with a distinctive foaming characteristic. Quillaja is also used as an emulsifier in baked goods, candies, frozen dairy products, gelatins, mayonnaise, puddings, and low-cholesterol dairy products.

These applications make use of the biological and interfacial activities of Quillaja saponins and their ability to form and stabilize colloidal structures such as emulsions, foams, crystallized lipid particles, heteroaggregates, and micelles. The wood is used in cabinetry, and scents derived from the tree are used in perfumes and cosmetics.

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