IngredientsThe term polyglyceride, as used in the context of food, dietary supplement, and pharmaceutical formulation, refers primarily to a class of compounds known as polyglycerol esters of fatty acids (PGEs, also abbreviated PEFA or PGFEs). These are described chemically as mixed partial esters formed by reacting polymerized glycerol with edible fats, oils, or fatty acids. The most common synonyms include glycerin fatty acid esters and polyglyceryl fatty acid esters. In the European Union, PGEs are regulated under the food additive code E 475, while a closely related compound, polyglycerol polyricinoleate (PGPR), carries the designation E 476.
PGEs are a class of synthetic, nonionic surfactant frequently used in food, pharmaceutical, and cosmetic industries on account of their amphiphilic properties. The hydrophilic part of these amphiphiles consists of oligomeric esters of glycerol, and the hydrophobic part consists of alkyl chains of varying length and degree of unsaturation.
According to Commission Regulation (EU) No 231/2012, PEFA (E 475) is a mixture of reaction products formed by the esterification of polyglycerols with food fats and oils or with fatty acids occurring in foods, fats, and oils. The polyglycerol moiety is predominantly di-, tri-, and tetraglycerol and contains not more than 10% of polyglycerols equal to or higher than heptaglycerol.
The structurally distinct but closely related compound PGPR differs in the nature of its fatty acid component. PGPR is made up of a short chain of glycerol molecules connected by ether bonds, with ricinoleic acid side chains connected by ester bonds; it is a yellowish, viscous liquid, strongly lipophilic, soluble in fats and oils, and insoluble in water and ethanol.
The maximum degree of polymerisation of glycerol in polyglycerol esters of fatty acids which are permitted by law as food additives is 10. This sets the practical upper boundary for the polyglycerol backbone that may be present in regulated preparations. The CAS Registry Number for PEFA (E 475) is 503590-90-7, and for PGPR (E 476) the CAS number is 68936-89-0.
Polyglycerides are not directly isolated from plant or animal tissues in their final ester form; rather, they are manufactured from natural, plant-derived raw materials. PGEs are claimed to be green alternatives to existing emulsifiers used in the chemical industry, as the raw material used for synthesis is obtained from vegetable oils which are renewable, and therefore eco-friendly surfactants for use in a broad number of applications including food, cosmetics, textiles, and personal care.
PGEs are produced by polymerization of glycerol in the presence of an alkaline catalyst followed by esterification with fatty acids. The fatty acids are from corn oil, cottonseed oil, lard, palm oil, peanut oil, sesame oil, sunflower oil, soybean oil, etc. Besides esters, PGEs also contain impurities, such as mono-, di-, and triglycerides, free fatty acids, free glycerol and polyglycerol, and sodium salts of fatty acids may be present.
Under U.S. FDA regulations, polyglycerol esters of fatty acids, up to and including decaglycerol esters, may be safely used in food; they are prepared from corn oil, cottonseed oil, lard, palm oil, peanut oil, safflower oil, sesame oil, soybean oil, and tallow, and the fatty acids derived from these substances (hydrogenated and nonhydrogenated), as well as oleic acid derived from tall oil fatty acids.
The polyglycerol backbone itself is produced by a distinct step: when glycerol is heated with an alkaline catalyst to over 230°C, water is evolved and polymerization occurs to form a whole family of polyglycerols ranging from diglycerol with 3 hydroxyl groups to triacontaglycerol with 32 hydroxyl groups.
For PGPR specifically, the esterification of condensed castor oil fatty acids with polyglycerol gives a powerful water-in-oil emulsifier which is used by the food industry in tin-greasing emulsions and as an emulsifier with lecithin in chocolate couverture and block chocolate.
Glycerol is mainly a natural product obtained from the methanolysis of vegetable oils. In Europe, due to the increasing use of methyl esters as fuel additives, an increase in glycerol production is expected, which could make glycerol a cheaper raw material for chemistry.
The carboxylic acid esters of polyglycerols prepared by direct esterification or by interchange may be solid or liquid; saturated or unsaturated; aliphatic or aromatic; mono-, di-, or polycarboxylic acid esters; mono-, di-, or polyesters of the polyglycerol; single or mixed acid esters; high or low molecular weight; water- or oil-soluble; and with an HLB (hydrophile-lipophile balance) from about 4 to about 13.
PGEs are synthesized by several methods, such as direct esterification of fatty acids and polyglycerols, chemical transesterification of fatty acid methyl esters and polyglycerol, enzymatic transesterification using Lipozyme 435, using glycerol carbonate as raw material, and using microwave irradiation.
Specific named preparations commonly encountered include:
In the labeling of dietary supplements and processed foods, polyglycerides appear under names such as "polyglycerol esters of fatty acids," "polyglyceryl fatty acid esters," "oleic acid polyglyceride," or simply "E 475" or "E 476."
Unlike many herbal or botanical dietary supplement ingredients, polyglycerides are largely an artifact of 20th-century industrial food science rather than a product with ancient traditional use. Their history is therefore primarily one of technological development and regulatory scrutiny, not ethnobotanical tradition.
PGEs have been used as food additives in Europe and America since the 1940s and were approved for food use in the U.S. in the 1960s. Their primary historical role was as emulsifiers and stabilizers to improve the texture, homogeneity, and shelf-life of processed foods. Their use has a historical basis in the food industry, where they have contributed to improved texture, solubility, and shelf-life of various products such as nutritional supplements, baked goods, and infant formulas.
A safety evaluation programme was undertaken in the late 1950s and early 1960s to determine whether the food emulsifier polyglycerol polyricinoleate (PGPR), traded as ADMUL WOL by Quest International, presented any health implications for consumers.
Early formal toxicological evaluations were carried out under the auspices of the Joint FAO/WHO Expert Committee on Food Additives (JECFA). In 1978, the Scientific Committee on Food (SCF) endorsed an acceptable daily intake (ADI) of 25 mg/kg body weight per day previously established by JECFA for polyglycerol esters of fatty acids. For PGPR, JECFA evaluated PGPR in 1969 and in 1974 and established, on the basis of a reproductive toxicity study in rats, an ADI of 0–7.5 mg/kg body weight per day.
In early food applications, polyglycerides were incorporated primarily into baked goods, margarines, and shortenings. In foods, they are used as emulsifying agents in the production of baked goods, chewing gum, and in replacement of fats. Their use in chocolate manufacturing was also longstanding: PGPR is used as an emulsifier in tin-greasing emulsions for the baking trade and for the production of low-fat spreads, and its main application is in the chocolate industry, where, besides its action as an emulsifier, it also has important properties as a viscosity modifier and improves the moulding properties of molten chocolate.
Polyglyceride preparations are not single chemical entities but complex, polydisperse mixtures. Their functional and biological properties derive from the nature of the polyglycerol backbone and the identity of the esterified fatty acids.
Polyglycerol ester, from which these esters are derived, is a polyhydric alcohol produced from glycerol. Polyglycerol can undergo esterification with fatty acids to form a range of esters with varying properties. The polyglycerol backbone is hydrophilic; its chain length (degree of polymerization) and branching pattern determine how strongly water-attracting the final molecule is.
The fatty acid component determines the lipophilic character of the ester. The identity of the fatty acid—saturated versus unsaturated, short-chain versus long-chain—profoundly affects the physicochemical behavior of the final compound. Esterification with fatty acids or transesterification with methyl esters of fatty acids or triglycerides alters the polarity, hydrophilic-lipophilic characteristics, and improves the solubility of polyglycerols in oil. Esterification can take place at any or all of the hydroxyl groups of the polyglycerol chain (usually at least 25%) depending upon the reaction conditions.
PGEs are composed of a fatty acid, which is a lipophilic moiety, and polyglycerol, which is a hydrophilic moiety. This dual-character (amphiphilic) architecture is the structural basis for their emulsifying functionality. The hydrophile-lipophile balance (HLB) value can be engineered across a wide range by varying the polyglycerol chain length and the number and identity of fatty acid esters. PGEs may be water- or oil-soluble, with an HLB from about 4 to about 13.
Due to the complex, non-selective nature of their synthesis, commercially available PGE preparations contain not only the target esters but also unreacted polyglycerols, free fatty acids, mono-, di-, and triglycerides, and sodium salts of fatty acids. Despite widespread application, the composition and properties of these surfactants are still not well characterized. Research has revealed the presence of previously unknown tetra- and penta-antennary constituents in polyglycerol esters, which exhibit very strong sodium affinity.
The primary functional mechanism of polyglycerides is emulsification. The amphiphilic molecular structure allows PGEs to position themselves at the interface between oil and water phases, reducing interfacial tension and stabilizing dispersed droplets. The amphiphilic properties of polyglycerol esters in water exhibit mesomorphic activities, forming liquid crystalline structures.
In food applications such as baked goods, this emulsifying mechanism confers specific technological benefits: compared to alternative emulsifiers such as monoglycerides, the polyglycerol ester has an advantage in providing long-time stability of whipping properties, making it an excellent choice for cake mixes. PGEs can also be used as low-fat shortening and can form emulsion systems with a high amount of water, thus reducing the overall caloric content of a food product. As an α-tending emulsifier, PGEs also have crumb-softening and anti-staling effects and help improve cake volume in baked products, because emulsifiers can reduce the rate of starch retrogradation.
Understanding how polyglycerides are metabolized is central to their safety assessment. Absorption of intact PEFA in the gastrointestinal tract is extremely low. PEFA is rapidly and almost fully hydrolyzed to polyglycerols and fatty acids in the gastrointestinal tract. This hydrolysis is carried out by pancreatic and intestinal lipases, and the process is well documented in both animal and human studies (see Section 7).
For PGPR specifically, PGPR is hydrolysed in the gut resulting in the liberation of free polyglycerols, polyricinoleic acid, and ricinoleic acid. Di- and triglycerol are absorbed and excreted unchanged in the urine; long-chain polyglycerols show lower absorption and are mainly excreted unchanged in faeces.
In pharmaceutical contexts, PGEs act as solubilizers and wettability-enhancing agents for poorly water-soluble drug molecules. The newly developed group of lipid-based polyglycerol ester excipients offers new possibilities in the development of formulations. Approximately 35% of drugs approved today belong to BCS class II (poorly soluble in aqueous environments but with good permeability), and in the development pipeline, 60–70% of all drug candidates have poor solubility. PGEs can improve dissolution and bioavailability of such molecules through micelle formation and self-emulsification.
Selecting a polyglycerol ester of a fatty acid with an appropriate hydrophile-lipophile balance as the matrix can yield a drug with the desired release rate at any pH.
The metabolic fate of polyglycerides is the area with the most extensive investigation, driven primarily by regulatory safety evaluation needs.
Animal studies: Metabolism of tri- (G3) and polyglycerol (G10) and G3 and G10 esters was studied in vivo in the rat and in vitro with pancreatic enzymes, using fatty acid-labeled compounds (oleic acid and eicosanoic acid). Data showed that the ester bonds were hydrolyzed to a large extent prior to absorption, and the free fatty acids were absorbed via the thoracic duct pathway. The free or partially esterified polyglycerols were not as well absorbed as the fatty acids; absorption occurred by a pathway other than the thoracic duct, presumably by the portal venous blood.
In an important early rat study on digestibility: sixteen male and female rats were fed a diet containing 1% groundnut oil and 9% polyglycerol ester, or 10% groundnut oil (as control), for six and twelve weeks. Polyglycerol ester as an energy source was almost equivalent to groundnut oil, as measured by growth rate, and digestibility was calculated as 92%.
A longer-term rat study examining tissue accumulation found: carcass fat contained no polyglycerol and the levels of free fatty acid, unsaponifiable residue, and fatty acid composition of carcass fat were no different from controls. Organ weights, tumor incidence, and tumor distribution were similar in control and test groups, and complete histological examination of major organs showed nothing remarkable.
The toxicological assessment of this group of diverse but related substances is based on an evaluation of satisfactory evidence for one member, assuming that alterations in the fatty acid distribution or polyglycerol content of individual members have no toxicological bearing and only affect the physical and emulsifying properties of each ester. The metabolic studies point to hydrolysis of these polyglycerol esters in the gastrointestinal tract, and the utilization and digestibility studies justify the assumption that the fatty acid moiety is metabolized in the normal manner.
In vitro hydrolysis: Hydrolysis experiments in vitro confirmed that the oleic acid ester bond in G3 and G10 esters was readily cleaved, as is the same bond in triglycerides. The eicosanoate bond was cleaved more slowly than the oleate bond.
Human study: Thirty-seven volunteers, aged 19–24, were fed 2–20 g polyglycerol ester per day for 3 weeks in their diet. No abnormalities were detected in plasma proteins, serum amino acids, thymol turbidity, serum bilirubin, total and free serum cholesterol, serum alkaline phosphatase, and other parameters.
Additionally, from the EFSA clinical review: clinical chemistry and urinalysis from a clinical study did not reveal any adverse effects in volunteers receiving up to 300 mg/kg bw per day for 3 weeks.
Evidence strength: The digestion and metabolic fate data are well-replicated across species and studies, and are considered robust for regulatory purposes. The human data, while limited in number of subjects and duration, are consistent with animal findings.
The technological efficacy of polyglycerides as emulsifiers is well-established and not disputed in the scientific literature. PGEs can be used in whippable emulsions and toppings; they promote fat particle aggregation and water absorption, and help achieve increased viscosity and aeration, and reduced coalescence.
In the chocolate industry, PGPR functions through a physically distinct mechanism. In chocolate, compound chocolate, and similar coatings, PGPR is mainly used with another substance like lecithin to reduce viscosity. It is used at low levels (below 0.5%) and works by decreasing friction between solid particles (e.g., cacao, sugar, milk) in molten chocolate, reducing yield stress so that it flows more easily, approaching the behavior of a Newtonian fluid. An additional property of PGPR in chocolate is its ability to limit fat bloom.
Polyglycerol esters find utility in a wide variety of food products including beverages, desserts, toppings, and baked goods. They are thermally stable and find application in several industrial systems.
This is an active and expanding area of applied research. In the pharmaceutical field, PGFEs can be used for the delivery of drugs and peptides, and can also be used as lipid-based excipients to improve the processing of formulations.
Research on pulmonary (inhaled) formulations has assessed the safety of PGFEs as excipients. In one cell-culture study, cytotoxicity was increased with the increased polarity of PGFA molecules. At concentrations above 1 mg/mL, accumulation in lysosomes, impairment of phagocytosis, secretion of nitric oxide, and increased release of cytokines were noted. The investigated PGFAs at concentrations up to 1 mg/mL can be considered as uncritical and are promising for advanced pulmonary delivery of high powder doses and drug targeting to alveolar macrophages.
For oral controlled-release applications, selecting a polyglycerol ester of a fatty acid with an appropriate hydrophile-lipophile balance as the matrix can yield a drug with the desired release rate at any pH.
Specific pharmaceutical preparations mentioned in the peer-reviewed literature include PGE-based nanoparticles for dermal delivery of tocopherol acetate, and PGE-based nanoemulsions for cosmetic and dermatological applications.
Evidence strength: The pharmaceutical applications of PGEs are at the preclinical and formulation-science stage. The evidence base consists primarily of in vitro studies and formulation development research; there are no published Phase II or Phase III clinical trials assessing PGEs as therapeutic agents in their own right.
In the field of cosmetics, PGFEs are commonly used as emulsifiers, emulsion stabilizers, cleansing agents, and solubilizers. The safety of 274 PGFEs was assessed by the Expert Panel for Cosmetic Ingredient Safety, and PGFEs are considered safe for use in cosmetics in their present uses and concentrations.
High-functioning polyglycerol esters of fatty acids centered on food additives, synthesized by original manufacturing methods, are mild, safe surfactants with a wide range of functions such as emulsion, solubilization, cleaning, and antibacterial properties, used in a variety of cosmetics.
Because polyglycerides are primarily functional food and supplement ingredients (rather than pharmacologically active agents used to treat specific conditions), the body systems they interact with are determined by their route of administration and their metabolic breakdown products.
The gastrointestinal tract is the primary site of interaction with ingested polyglycerides. Absorption of intact PEFA in the gastrointestinal tract is extremely low, and PEFA is rapidly and almost fully hydrolyzed to polyglycerols and fatty acids in the gastrointestinal tract. In the presence of alkali, acids, or by the action of lipases, polyglycerol esters are hydrolyzed.
Analytical studies have produced no evidence of cumulation of the polyglycerol moiety in body tissues. Accordingly, there is no established bioaccumulation of polyglycerol-derived compounds in the gut wall or beyond.
Fatty acid breakdown products from PEFA hydrolysis enter normal lipid metabolism pathways. Carbon dioxide was the major end product of fatty acid catabolism in radiolabeled rat studies, consistent with ordinary beta-oxidation. No alteration in serum cholesterol, liver enzymes, or liver histology was detected in early human volunteer studies at doses of up to 20 g/day for three weeks.
Small polyglycerol units released by hydrolysis are absorbed systemically and cleared renally. Di- and triglycerol are absorbed and excreted unchanged in the urine; long-chain polyglycerols show lower absorption and are mainly excreted unchanged in faeces.
Reproductive toxicity studies showed no adverse effects of PEFA but had major limitations. For PGPR, the single reproductive toxicity study with PGPR was limited and was not an appropriate study for deriving a health-based guidance value. These limitations were acknowledged by regulatory bodies and factored into their safety conclusions.
Research into PGEs as inhaled drug-delivery excipients has identified the lungs as a potential target organ, specifically the alveolar epithelial cells and macrophages. One of the main problems in the development of pulmonary formulations is the low availability of approved excipients; PGFAs are promising molecules for acting as excipients for formulation development and drug delivery to the lung; however, their biocompatibility in the deep lung has not been comprehensively studied.
Polyglycerides hold an unusually consistent global regulatory approval record compared to many dietary supplement ingredients.
United States (FDA): Polyglycerol esters of fatty acids (E 475) are approved worldwide for use in foods; they are recognized as safe (GRAS) by the U.S. FDA and included in the European Union's food additive list. For PGPR, the FDA had no question on Palsgaard's conclusion that PGPR is Generally Recognized as Safe (GRAS) when used as an emulsifier in chocolate-type products based on vegetable fats other than cocoa butter at maximum levels of 0.3%.
European Union (EFSA): PEFA (E 475) was re-evaluated in 2017 by the EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS Panel), which concluded that there was no need for a numerical acceptable daily intake (ADI) and there was no safety concern at the reported uses and use levels. Permitted food categories in the EU include baked goods, fine bakery wares, confectionery, chewing gum, fats, oils, and food supplements.
WHO/FAO (JECFA): At its Seventeenth meeting, JECFA established an ADI of 0–25 mg/kg body weight for polyglycerol esters of fatty acids, based on a long-term study in rats in which there were no effects at 2,500 mg/kg body weight, the highest dose tested.
Typical use levels in food: Typical usage levels for PGEs range from 0.2% to 1.0%, depending on product type and formulation requirements. For PGPR in chocolate, the level is generally below 0.5%.
Dietary exposure estimates (EU children): The highest estimated exposure to PEFA (E 475) used as a food additive was 2.6 and 6.4 mg/kg body weight per day in children at the mean and the 95th percentile, respectively, for the non-brand loyal scenario.
In the food and supplement context, polyglycerides are encountered as minor functional ingredients rather than as primary active nutrients taken at defined therapeutic doses. The following dosage-related data are sourced from regulatory assessments and clinical studies:
The safety of polyglycerols and specific fatty acids has been assessed and no adverse effects were identified in the available studies. No adverse effects of PEFA at any dose have been observed in short-term, subchronic, or chronic toxicity studies.
Acute oral toxicity of PGPR is low, and short-term and subchronic studies indicate PGPR is tolerated at high doses without adverse effects. PGPR (E 476) is not of concern with regard to genotoxicity or carcinogenicity.
Human studies showed no adverse effects on tolerance, liver and kidney function, and fat balance at levels up to 10 g/day PGPR.
No genotoxic potential of PEFA was identified from the limited information available.
Reproductive toxicity studies showed no adverse effects of PEFA but had major limitations. This limitation was recognized by EFSA in its 2017 opinion and cited as a data gap for future research. The overall regulatory conclusion nonetheless remained favorable given the extensive evidence from other study types and low estimated human exposures.
The most recent (2022) EFSA follow-up opinion on PGPR (E 476) highlighted specific manufacturing impurities requiring updated specification limits. The Panel recommended that: the maximum limits for the impurities of toxic elements (lead, mercury, cadmium, and arsenic) in the European Commission specification for PGPR should be revised; a maximum limit for active ricin should be included in the EU specifications for PGPR; and a maximum limit for 3-monochloropropane-1,2-diol (3-MCPD) should be included in the EU specifications for PGPR. These recommendations concern the quality of the manufactured additive, not adverse effects of PGEs per se.
Similarly for PEFA (E 475): the Panel concluded that maximum limits for the four toxic elements (arsenic, lead, mercury, cadmium) should be lowered based on actual levels in commercial food additives, and that maximum limits for glycidyl esters and 3-monochloropropanediol should be included in the EU specifications.
The in vitro pulmonary study referenced above identified a concentration threshold above which PGFAs caused functional impairment of alveolar macrophages. Cytotoxicity was increased with the increased polarity of PGFA molecules; at concentrations above 1 mg/mL, accumulation in lysosomes, impairment of phagocytosis, secretion of nitric oxide, and increased release of cytokines were noted. This finding is relevant only in the context of inhaled pharmaceutical formulations and has no established relevance at typical oral dietary exposure levels.
When the esters are present under the form of unsaturated fatty acids, oxidation can occur. This is a formulation stability issue relevant to product manufacturers and formulators rather than an in vivo toxicological concern.
No specific, source-verified pharmacokinetic drug-drug or nutrient-drug interactions involving dietary polyglycerides at typical food additive exposure levels have been established in the peer-reviewed literature reviewed for this article. The hydrolysis products—glycerol, polyglycerols, and common fatty acids—are all normal components of human metabolism at the exposure levels encountered through food use. Studies indicate that PGEs are hydrolyzed in the gastrointestinal tract into glycerol and fatty acids, both of which are naturally occurring and readily metabolized by the body.
Health conditions that Polyglyceride may help support.
Body systems that Polyglyceride may help support.
Go back