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Phytase

1. Identity, Chemical Classification, and Natural Sources

Phytase is the common name for a family of phosphohydrolase enzymes that catalyze the stepwise hydrolysis of phytic acid (myo-inositol hexakisphosphate, or InsP6) and its salts (collectively called phytate). Phytases are formally known as myo-inositol hexakisphosphate phosphohydrolase, and are classified under two principal Enzyme Commission (E.C.) numbers: E.C. 3.1.3.8, the 3-phytase of microbial origin, and E.C. 3.1.2.26, the 6-phytase derived from plants.

Phytases belong to the class of phosphohydrolases and initiate the stepwise hydrolysis of phosphates from phytates. Phytates are a derivative of myo-inositol, which is the primary storage form of organic phosphorus in plant cells. Phytic acid stores 60–90% of the inorganic phosphorus in legumes, oil seeds, and cereals, making it inaccessible for metabolic processes in living systems.

Biochemical Classes

Phytases can be categorized into several biochemical types, including histidine acid phosphatases (HAPs), β-purple acid phosphatases (BPPs), purple acid phosphatases (PAPs), and cysteine phytases (CPs). Among these, HAPs are the most extensively studied microbial phytases and have been explored for commercial applications. BPP phytase demonstrates excellent thermal stability, remaining soluble even at 95°C, and plays a significant role in the phytic acid cycle in soil and water environments.

Phylogenetic studies have grouped the microbial HAPs into three clusters: (1) filamentous fungi phytases with 441–539 amino acids and pI (isoelectric point) 4.9–8.5; (2) yeast phytases with 457–479 amino acids and pI 4.4–5.8; and (3) bacterial phytases with 428–523 amino acids and pI 5.5–6.5.

Natural Occurrence

Phytases are produced in nature in a wide range of plant and animal tissues and microorganisms such as bacteria, yeast, and fungi. Phytases are abundantly found in nature; primary sources include plants, microbes (bacteria and fungi), and some animal tissues. Due to their catalytic properties and simplicity of enzyme production, phytases of microbial origin are the most commercially important. Most scientific work has focused on microbial phytases, particularly those obtained from filamentous fungi such as Aspergillus, Myceliophthora, Mucor, Penicillium, Rhizopus, and Trichoderma. Aspergillus ficuum NRRL 3135 has been defined as the most active fungal phytase producer and has most commonly been employed at the commercial level.

Phytases are phosphatases produced by animals, plants, and microorganisms, notably Aspergillus niger, and are employed as an animal feed additive, in the chemical industry, and for ethanol production. Phytases are found in natural sources including not only plants but also microbes; microbial phytase retains its activity when exposed to high temperatures compared with plant phytase.

Commercial Forms and Preparations

Commercial phytase preparations are produced primarily by microbial fermentation. In addition to use as a food processing aid, phytase has been formulated as a human supplemental digestive aid. Phytase in tablet form can be ingested at the time of food consumption to deliver active enzyme to the gastrointestinal tract. Nutritional gains for the consumer are experienced in vivo and the supplement may be taken with foods that cannot be treated with phytase during food processing. 3-Phytases catalyze the hydrolysis of phytic acid (myo-inositol hexakisphosphate) to 1D-myo-inositol 1,2,4,5,6-pentakisphosphate and phosphate. They are intended for use in nine food manufacturing processes, including processing of cereals and grains for the production of baked products, brewed products, starch and gluten fractions, distilled alcohol and non-wine vinegars; processing of plant- and fungal-derived products for the production of coffee extracts, soy sauce, and protein hydrolysates.

The unit of phytase activity used in commerce and research is the FTU (phytase unit), defined as the amount of enzyme that liberates one micromole of inorganic phosphate per minute from sodium phytate at specific standard conditions. Commercial preparations are available in liquid and granular forms for both food processing and dietary supplement use.

2. Traditional and Historical Use

Phytase as an isolated, characterized enzyme is a product of modern biochemistry; however, the enzymatic activity of phytase has been exploited unknowingly by traditional food cultures for millennia. Ancient fermentation techniques—used in cultures around the world for thousands of years—unknowingly promoted phytase activity. For example, soaking, sprouting, and fermenting grains and legumes (as in sourdough, tempeh, or traditional Ethiopian injera) reduces phytic acid content through naturally occurring microbial and plant-derived phytases.

These practices were historically driven by the need to make plant foods more digestible and nutritious without an understanding of the underlying enzymatic mechanisms. Only in the 20th century, with advances in biochemistry and nutrition science, was phytase isolated, characterized, and harnessed for both clinical and agricultural applications.

The activation of the enzyme phytase occurs during soaking, the germination process, the production of sourdough and lactic acid fermentation, as well as during digestion. Even prolonged chewing can break down some of the phytic acid.

Legumes contain endogenous phytase enzyme that is activated by malting to destroy phytate. Across sub-Saharan Africa, South Asia, and East Asia, traditional grain-preparation methods including soaking, malting, and fermentation (e.g., fermented sorghum porridges, fermented soy preparations such as miso and tempeh, and sourdough bread) served to improve mineral bioavailability, effects now understood to operate through endogenous and microbial phytase activity.

Different time–temperature combinations are used during the soaking steps of cereals and pulses. Traditionally, wheat, rice, and pulses are soaked for 6–36, 8–10, and 12–16 hours at 25°C for moisture gain that facilitates further post-harvest processing steps. Soaking solubilizes phytic acid from the cereal and pulse matrix into the soaking solution, reducing the phytic acid-to-mineral ratio. Soaking also activates endogenous phytase enzymes and even the consortium of fermentative microbes that produce phytase, which also plays a crucial role in phytic acid reduction.

3. Key Constituents, Active Compounds, and Mechanisms of Action

The Substrate: Phytic Acid

Phytic acid is abundant in plant-based diets and acts as a micronutrient inhibitor for humans and non-ruminant animals. It forms insoluble plant salt complexes that significantly reduce the bioavailability of bound minerals, inhibiting their absorption in the gastrointestinal tract, and thus leading to potential deficiencies, particularly in populations whose diets are based on foods high in phytic acid. Given its negative charge, phytic acid complexes with divalent cations, starch, and proteins.

Catalytic Mechanism

Phytases catalyze the sequential release of phosphate from phytic acid (IP6), resulting in lower inositol phosphate esters (IP5 to IP1) and free inorganic phosphate. This process releases orthophosphate groups from the inositol ring of phytic acid, producing intermediate myo-inositol phosphates and free inorganic phosphorus.

Phytases dephosphorylate phytic acid (InsP6; myo-inositol-(1,2,3,4,5,6)-hexakis phosphate) and its salts (phytate) contained in feedstuffs of plant origin. InsP6 is degraded stepwise to lesser phosphorylated inositol phosphates and myo-inositol, the core molecule of phytic acid, in the gastrointestinal tract.

Phytase liberates phosphate groups from phytic acid and produces myo-inositol after total dephosphorylation. The degradation products of phytic acids, such as inositol monophosphates or diphosphates, exhibit reduced or negligible ability to chelate minerals and form insoluble complexes.

Downstream Effects: Mineral Liberation

Phytate cannot be digested by the human body and cannot be absorbed in the small intestine due to the lack of endophytases. As a result, minerals chelated in phytic acid are not bioavailable. When exogenous phytase is introduced—either via supplementation or food processing—it degrades phytic acid in the stomach and upper small intestine, releasing chelated minerals and making them available for intestinal absorption.

Myo-inositol, the product of complete phytic acid dephosphorylation, is a highly bioactive substance. In human medical research, positive effects of myo-inositol have been described, including amelioration of insulin sensitivity and lipid metabolism, modulation of endocrine signaling within cells, and influencing immune functions.

The endogenous cereal phytase is mostly a 6-phytase that liberates phosphate from the C6 position of the myo-inositol hexaphosphate ring, yielding 1,2,3,4,5-pentakisphosphate.

4. Scientific Evidence by Area of Use

4.1 Iron Bioavailability

Evidence strength: Moderate to strong (multiple human intervention trials).

Even though iron and zinc are present in significant amounts in the plant-based diets typically consumed in developing countries, their bioavailability is low due to high levels of absorption inhibitors such as phytate.

Phytases are enzymes that break down phytic acid, releasing micronutrients and enhancing their bioavailability, particularly iron and zinc. Deficiencies in iron and zinc are significant public health problems, especially among populations with disease-associated malnutrition or those in developing countries consuming phytic acid-rich diets.

A systematic review published in Food and Nutrition Bulletin (Troesch et al., 2013) examined the human evidence: twelve studies tested the effect of phytase on iron and five tested its effect on zinc bioavailability. Most of these studies used a phytase derived from Aspergillus niger. The reviewers found that phytase from Aspergillus niger significantly increases iron and zinc bioavailability from phytate-rich foods. Phytase clearly has a beneficial effect on iron and zinc absorption from phytate-rich foods. It also has the potential to increase the absorption of magnesium, calcium, and phosphorus in areas such as Southeast Asia where mineral deficiencies are widespread.

A more recent narrative review (Nutrients, 2024) searched PubMed from 1990 to 2024 and identified 42 eligible human intervention trials. Most studies exploring the efficacy of exogenous phytase (9 of 11, 82%) or the efficacy of food dephytinization (11 of 14, 79%) demonstrated augmented iron and zinc bioavailability. Most phytic acid-rich food-feeding studies (13 of 17, 77%) showed compromised iron and zinc bioavailability. Strong evidence supports decreased iron and zinc bioavailability in phytic acid-rich diets and significant improvements with phytase interventions.

Phytate cannot be digested by the human body and cannot be absorbed in the small intestine due to the lack of endophytases, making chelated minerals non-bioavailable. Hallberg et al. removed phytates in bran by endogenous phytase to observe how its removal impacts absorption and reported that iron absorption is significantly increased in the absence of phytate. Troesch et al. reviewed the evidence from human studies investigating the impact of phytase on iron and zinc bioavailability. They concluded that phytase promotes the absorption of iron and zinc from phytate-rich meals and can potentially improve magnesium, calcium, and phosphorus absorption.

A scoping review (Journal of the Canadian Association of Gastroenterology, 2025) confirmed: Most studies exploring the efficacy of exogenous phytase (9 of 11, 82%) or the efficacy of food dephytinization (11 of 14, 79%) presented augmented iron and zinc bioavailability. In agreement with this, most phytic acid-rich food feeding studies (13 of 17, 77%) showed compromised iron and zinc bioavailability. Strong evidence supports decreased iron and zinc bioavailability in phytic acid-rich diets and the improvement potential with phytase interventions. Further studies are needed in larger populations.

4.2 Zinc Bioavailability

Evidence strength: Moderate (multiple human crossover trials, including in children).

One well-designed human crossover trial (published in European Journal of Clinical Nutrition, 2016) tested the effect of phytase on zinc absorption in 35 young healthy Burkinabe children: A stable-isotope zinc absorption study was conducted in young children to investigate the ability of the phytic-acid-degrading enzyme phytase to improve zinc absorption when added to a cereal porridge immediately before consumption. Fractional absorption of zinc (FAZ) was estimated in 35 young healthy Burkinabe children using the double-isotopic tracer ratio method with ⁶⁷Zn as oral tracer and ⁷⁰Zn as intravenous tracer, in a crossover design. The test meal was a millet-based porridge containing 1.4 mg total zinc with a PA:Zn molar ratio of 7.7, with or without the enzyme phytase (20.5 FTU) added immediately before consumption. Mean FAZ increased from 9.5±3.4 to 16.0±5.1% (P<0.0001) when phytase was added to the meal.

A randomized controlled trial in Gambian children (18–23 months old) further confirmed the effect: In a double-blind randomized controlled trial, intraindividual differences in fractional and total absorption of zinc (FAZ and TAZ) from a millet-based porridge containing small-quantity lipid-based nutrient supplements (SQ-LNS) with and without phytase were measured in 30 asymptomatic children 18–23 months of age in the Kiang West district of The Gambia. Mean FAZ increased from 8.6±1.3% to 16.0±1.3% when exogenous phytase was added to the SQ-LNS product (P=0.0002). Mean total absorption of zinc from porridge test meals containing SQ-LNS with phytase was more than double that from test meals containing SQ-LNS without phytase (1.12±0.07 mg and 0.52±0.07 mg, respectively; P<0.0001).

However, using phytase specifically to treat zinc deficiency has not been studied. Existing studies demonstrate improved acute absorption, not correction of clinical deficiency states, and most are of short duration.

4.3 Phosphorus and Calcium Availability

Evidence strength: Preliminary to moderate (human and animal data; mechanistic evidence strong).

Grains and flours treated with phytase have reduced phytin content. The reduced levels of phytin enhance food quality by increasing the nutrient availability of essential minerals such as iron, calcium, and zinc.

Phytic acid chelates calcium, reducing its availability, and this has been studied in the context of bone health. Research also suggests a nuanced relationship: while phytase can potentially free calcium bound to phytate, phytate itself — at physiological concentrations found in food — may exert a protective effect on bone. Data indicate that bone mineral density (BMD) and t-score of lumbar spine increased with increasing phytate consumption, and a phytate consumption higher than 307 mg/day was associated with a normal BMD. These data suggest that phytate may have a protective effect in bone decalcification by adsorbing on the surfaces of hydroxyapatite, and a daily consumption of phytate-rich foods (at least one serving/day of legumes or nuts) may help to prevent or minimize bone-loss disorders, such as osteoporosis.

Phytate has been shown to inhibit calcium salt crystallization and, therefore, to reduce vascular calcifications, calcium renal calculi and soft tissue calcifications. This indicates that the relationship between phytase activity, phytate, and calcium metabolism is complex: complete degradation of all phytate may not always be the optimal nutritional goal.

4.4 Digestive Health and Gut Function

Evidence strength: Mostly preclinical and animal; limited direct human data.

Phytic acid is abundant in plant-based diets and acts as a micronutrient inhibitor for humans and non-ruminant animals. Phytases are enzymes that break down phytic acid, releasing micronutrients and enhancing their bioavailability, particularly iron and zinc. Deficiencies in iron and zinc are common in patients with inflammatory bowel diseases and in those in developing countries consuming phytic acid-rich diets. This observation has prompted interest in phytase supplementation as a strategy in inflammatory bowel disease patients, though direct, well-controlled human trials targeting gut health specifically are lacking.

4.5 Metabolic Effects via Myo-Inositol

Evidence strength: Preliminary; most evidence is indirect or from animal studies.

Phytase liberates phosphate groups from phytic acid and produces myo-inositol after total dephosphorylation. Myo-inositol is a bioactive compound having beneficial modulatory effects on metabolism in humans. In human medical research, positive effects of myo-inositol have been described, including amelioration of insulin sensitivity and of lipid metabolism, modulation of endocrine signaling within cells, and influencing immune functions. However, the cellular mechanisms by which myo-inositol acts on metabolism are not fully clear yet. It is important to note that clinical research on myo-inositol supplementation is distinct from research on phytase supplementation; the release of myo-inositol from dietary phytate by phytase in vivo and its subsequent bioavailability at quantities sufficient to elicit systemic metabolic effects has not been established in human studies.

5. Body Systems and Health Areas Associated with Phytase

• Gastrointestinal system: Phytase acts primarily in the stomach and proximal small intestine, breaking down phytate in food prior to nutrient absorption. It reduces the anti-nutritional effect of phytate on mineral solubility.
• Mineral metabolism and hematopoiesis: Phytases enhance the bioavailability of minerals, particularly iron and zinc. This is directly relevant to prevention and management of iron-deficiency anemia and zinc deficiency, both major global public health problems.
• Skeletal system: Phytase clearly has a beneficial effect on iron and zinc absorption from phytate-rich foods. It also has the potential to increase the absorption of magnesium, calcium, and phosphorus. The relationship of phytase activity with bone health is complex; some evidence suggests that dietary phytate at typical food concentrations is associated with positive bone mineral density, and aggressive phytate degradation may remove this putative benefit.
• Endocrine/metabolic system (indirect): Via the liberation of myo-inositol and facilitation of phosphorus homeostasis, phytase has theoretical metabolic effects, though direct human data are limited.
• Immune function (indirect): Improved zinc status resulting from phytase-mediated bioavailability may support immune function, as zinc is critical for immune cell development and function.

6. Dosage Forms and Dosages Reported in Research

Phytase activity is quantified in phytase units (FTU or PTU), not milligrams of protein. One FTU is defined as the amount of enzyme that liberates 1 µmol of inorganic phosphate per minute from 1 mM sodium phytate at 37°C, typically at pH 5.5.

• Human zinc absorption studies (children): In a millet-based porridge study in young Burkinabe children, the enzyme phytase was added at 20.5 phytase units (FTU) immediately before consumption. Mean fractional absorption of zinc increased from 9.5±3.4 to 16.0±5.1% (P<0.0001) when phytase was added at this dose.
• Gambian children RCT: Children received a millet-based porridge with 20 g SQ-LNS and either exogenous phytase (~500 FTU) or no exogenous phytase in a double-blind randomized controlled trial of 30 asymptomatic 18–23 month old children.
• Food/animal feed applications: An effective amount of phytase in food or feed has been described as from about 10 to 20,000 FTU/kg, with a particularly cited range of about 100 to 2,000 FTU/kg feed or food.
• Preliminary clinical research (zinc citrate + phytase): In patients with deep wrinkles, preliminary clinical research shows that taking 50 mg of zinc citrate and 3,000 units of phytase per day for four days before a botulinum toxin treatment increases the patient-reported duration of the toxin's effects.

There are no official dietary intake recommendations for phytase, and human dosing is based largely on product experience, extrapolation from animal research, and practical considerations rather than long-term clinical trials.

7. Safety Considerations

Regulatory Status

All food enzymes currently on the EU market and intended to remain on that market, as well as all new food enzymes, shall be subjected to a safety evaluation by the European Food Safety Authority (EFSA) and approval via an EU Community list. Only food enzymes included in the European Union (EU) Community list may be placed on the market as such and used in foods.

EFSA has conducted multiple safety evaluations of phytase preparations. A 2024 EFSA opinion evaluated the food enzyme 3-phytase (myo-inositol-hexakisphosphate 3-phosphohydrolase, EC 3.1.3.8) produced with the genetically modified Aspergillus niger strain NPH. The genetic modifications were concluded not to give rise to safety concerns, and the food enzyme was considered free from viable cells of the production organism and its DNA.

For the non-genetically modified Aspergillus niger strain PHY93-08 phytase evaluated by EFSA (2024): genotoxicity tests did not raise safety concerns. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panel considered that the risk of allergic reactions upon dietary exposure cannot be excluded, but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.

Phytase in Foods vs. Supplements

When taken by mouth, phytase is likely safe when eaten in foods. Cereal grains, legumes, and other foods contain phytase. There is not enough reliable information to know if phytase is safe to use as a supplement or medicine, or what the side effects might be.

Potential for Allergic Reactions

The EFSA Panel considered that the risk of allergic reactions upon dietary exposure cannot be excluded, but the likelihood is low. Individuals with documented hypersensitivity to fungi or to fermentation products of Aspergillus species may be at increased risk.

Interaction with Mineral Metabolism Medications

Because phytase improves the bioavailability of multiple minerals (iron, zinc, calcium, magnesium, phosphorus), use in combination with mineral supplements or medications that depend on specific levels of mineral absorption (e.g., iron chelating agents, zinc supplements, or phosphate binders used in renal disease) could theoretically alter the expected pharmacological effects. This area has not been rigorously studied in clinical trials.

Nuance: Phytate Degradation and Protective Phytate Effects

Evidence on the role of phytate in human health is nuanced. Phytate may have a protective effect in bone decalcification by adsorbing on the surfaces of hydroxyapatite, and daily consumption of phytate-rich foods may help to prevent or minimize bone-loss disorders such as osteoporosis. Further studies are needed to gain a better understanding about the mechanism of inhibition of phytate in bone-related diseases. This implies that indiscriminate or high-dose phytase use could potentially remove physiologically beneficial phytate from the diet, though no adverse clinical outcomes from this effect have been documented in human trials.

Pregnancy and Lactation

There is not enough reliable information to know if phytase is safe to use when pregnant or breast-feeding.

8. Evidence Quality Summary

The overall quality of evidence for phytase in human nutrition is moderate to strong for acute mineral bioavailability outcomes (particularly iron and zinc absorption), primarily established by short-term isotope tracer studies in children and adults. Strong evidence supports decreased iron and zinc bioavailability in phytic acid-rich diets and significant improvements with phytase interventions. Evidence for longer-term clinical outcomes (e.g., correction of deficiency, effects on growth, immune function, or chronic disease) is preliminary and insufficient. Most relevant human studies are of short duration, small sample size, or conducted in specific high-risk populations (young children in developing countries). Further studies are needed in larger populations.

References

• Dietary Phytic Acid, Dephytinization, and Phytase Supplementation Alter Trace Element Bioavailability—A Narrative Review of Human Interventions. Nutrients, 2024. PMC11643945.
• Troesch B, et al. Absorption studies show that phytase from Aspergillus niger significantly increases iron and zinc bioavailability from phytate-rich foods. Food and Nutrition Bulletin. 2013;34(2 Suppl):S90-101. PMID 24050000.
• A84 The Use of Phytase to Enhance Dietary Iron and Zinc Absorption – A Scoping Review. Journal of the Canadian Association of Gastroenterology, 2025. PMC11807532.
• Iron Absorption: Factors, Limitations, and Improvement Methods. ACS Omega, 2022. PMC9219084.
• Effect of phytase on zinc absorption from a millet-based porridge fed to young Burkinabe children. European Journal of Clinical Nutrition, 2017. PMID 27759065.
• Effect of exogenous phytase added to SQ-LNS on zinc absorption in young Gambian children: a randomized controlled trial. American Journal of Clinical Nutrition, 2019. NCT02668133.
• Bioprocess for Production, Characteristics, and Biotechnological Applications of Fungal Phytases. Frontiers in Microbiology, 2020. PMC7034034.
• Fungal phytases: from genes to applications. Applied Microbiology and Biotechnology, 2020. PMC7455620.
• Insight into phytase-producing microorganisms for phytate solubilization and soil sustainability. Frontiers in Microbiology, 2023. PMC10128089.
• Fermentation and germination improve nutritional value of cereals and legumes through activation of endogenous enzymes. Food Science & Nutrition, 2018. PMC6261201.
• The Effect of Germination on Antinutritional Components, In Vitro Starch and Protein Digestibility, Content, and Bioaccessibility of Phenolics and Antioxidants of Some Pulses. Food Science & Nutrition, 2025. PMC12061842.
• Enhancing micronutrient absorption through simultaneous fortification and phytic acid degradation. Frontiers in Nutrition, 2023. PMC10290024.
• Understanding the Protective Effect of Phytate in Bone Decalcification Related-Diseases. Antioxidants, 2021. PMC8400850.
• Phytate Intake, Health and Disease: "Let Thy Food Be Thy Medicine and Medicine Be Thy Food". Antioxidants, 2023. PMC9855079.
• EFSA CEP Panel. Safety evaluation of the food enzyme 3-phytase from the genetically modified Aspergillus niger strain NPH. EFSA Journal. 2024;22(1):e8514.
• Safety evaluation of the food enzyme 3-phytase from the non-genetically modified Aspergillus niger strain PHY93-08. EFSA Journal, 2024. PMC11215478.
• Dietary phytase and myo-inositol supplementation are associated with distinct plasma metabolome profile in broiler chickens. Animal, 2020. ScienceDirect.
• Microbial phytase: Their sources, production, and role in the enhancement of nutritional aspects of food and feed additives. Journal of Agriculture and Food Research, 2023. ScienceDirect.