Ingredients"Polyglycerol" is a collective term for a family of oligomeric and polymeric polyols formed by the condensation of glycerol (propane-1,2,3-triol) molecules through ether linkages. This condensation or dehydration reaction joins the hydroxyl groups of glycerol molecules together, releasing water and typically producing an ether bond between the glycerol units in a linear configuration. Depending on the number of glycerol units combined — referred to as the degree of polymerization (DP) — the resulting product is called diglycerol (DP 2), triglycerol (DP 3), tetraglycerol (DP 4), and so on, up to decaglycerol (DP 10) and higher. Branched polyglycerols may also form when a beta-hydroxyl group participates in condensation, and conventional synthesis typically produces a mixture of linear, branched, and cyclic polyglycerols.
The CAS registry number most commonly assigned to the generic polyglycerol mixture is 25618-55-7. This substance has been evaluated by EFSA as FCM substance No. 01017. In commerce, polyglycerol is not a single compound but a complex mixture of oligomers with varying chain lengths and branching patterns. Polyglycerol is a clear viscous liquid that is essentially nonvolatile at room temperature.
Polyglycerol does not occur freely in nature at significant levels; rather, glycerol is an attractive renewable building block for the synthesis of polyglycerols, which have numerous applications in the food, feed, textile, cosmetic, and pharmaceutical industries. Glycerol itself is ubiquitous in nature as the backbone of triglyceride fats; thus, polyglycerol is best understood as a semi-synthetic derivative of a natural substrate. Commercially, glycerol used to produce polyglycerol is often recovered as a by-product of biodiesel or soap manufacture. Crude glycerol has been proven to be a promising feedstock for the production of polyglycerol and polyols.
Two main classes of polyglycerol derivatives are authorized as food additives internationally:
In addition to these food-grade derivatives, higher-molecular-weight and hyperbranched polyglycerol architectures are studied extensively for biomedical applications but are not yet authorized therapeutic agents.
Polyglycerol, as a chemically defined substance, has no traditional or ethnobotanical history of use. It is entirely a product of industrial chemistry. The earliest commercial development of polyglycerol fatty acid esters as food emulsifiers dates to the mid-twentieth century. A safety evaluation programme was undertaken in the late 1950s and early 1960s to determine whether the food emulsifier polyglycerol polyricinoleate (PGPR), sold under the Quest International trade name ADMUL WOL, presented any health implications for consumers; this programme included acute toxicity tests, subacute rat and chicken toxicity studies, a rat chronic toxicity/multigeneration reproduction study, rodent metabolism, carcinogenicity testing in rat and mouse, and a human clinical evaluation.
PGPR is a very powerful emulsifier that was primarily developed for the production of water-in-oil emulsions for tin-greasing in the baking trade. However, its main use evolved to be in chocolate, where, in addition to its action as an emulsifier, it also has valuable properties as a viscosity modifier, thus improving the moulding properties of molten chocolate.
The regulatory history of PEFA (E 475) follows a similar trajectory. The latest toxicological evaluation for polyglycerol esters of fatty acids presented by JECFA was published in 1974. 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 the Joint FAO/WHO Expert Committee on Food Additives (JECFA). These substances, therefore, have a documented industrial and regulatory history spanning approximately seven decades, primarily in Western Europe and North America.
Polyglycerols are commonly prepared by mixing glycerol with an alkali metal catalyst, such as sodium or potassium hydroxide, and then heating the mixture to an elevated temperature. This reaction causes the condensation or dehydration of two glycerol molecules' hydroxyl groups. The preferred method for food-grade polyglycerol production is condensation of glycerol in the presence of catalytic amounts of base, preferably NaOH or KOH, at temperatures of 220–260°C and reduced pressure (20–800 mbar) to facilitate removal of reaction water from the mixture.
Alternative synthesis routes include polymerization of glycidol and polymerization of epichlorohydrin. During the re-evaluation of E 475 by the EFSA ANS Panel in 2017, it was noted that epichlorohydrin may be present in E 475 from the possible chemical synthesis of polyglycerols; impurities present in glycerol, used for the manufacturing of polyglycerols, could also be present as carry-over impurities in E 475. For biomedical-grade material, ring-opening polymerization of glycidol under anionic or cationic conditions is frequently employed to produce hyperbranched polyglycerol (HPG) with more controlled architecture.
Cyclic polyglycerols often cause degradation of products into which they are incorporated, detrimentally affecting the colour, taste, performance, or odour of products; therefore, there have been continuing efforts to find a method of preparing linear polyglycerols that produce little, if any, cyclic forms.
Polyglycerols are used, among other things, as textile lubricants, plastic anti-static agents, defoamers, anti-bloom agents for edible coatings, and anti-splattering agents in cooking oil. Polyglycerol fatty acid esters are innocuous, nonionic surfactants used as emulsifiers in food, pharmaceutical, and personal care products; they are biodegradable, making them suitable for lubricating food equipment, agrochemicals, and as antistatic and antifogging agents for food packaging.
Polyglycerol itself is the core structural entity: a polyhydric alcohol with multiple free hydroxyl groups. Polyglycerols are very interesting polyols with a wide range of structures and, accordingly, of applications, particularly in their ester forms for the cosmetics, biomedical, and food sectors; they are water soluble, biocompatible, and highly functional materials.
In the case of PGPR, the constituent fatty acids are critical to biological activity. PGPR consists of polyglycerol as the hydrophilic group and interesterified ricinoleic fatty acids as the hydrophobic group in its structure. After ingestion, 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, while long-chain polyglycerols show lower absorption and are mainly excreted unchanged in faeces.
For PEFA (E 475): Absorption of intact PEFA in the gastrointestinal tract was extremely low. PEFA was rapidly and almost fully hydrolysed to polyglycerols and fatty acids in the gastrointestinal tract. Although the polyglycerol appears to be excreted unchanged, the fatty acids were either rapidly metabolised to carbon dioxide or incorporated in the body.
In advanced biomedical forms (HPG), the key structural features are the hyperbranched architecture and the dense array of surface hydroxyl groups. HPG features excellent physicochemical and biological properties, including anti-biofouling, tunable multi-functionality, favorable biocompatibility, and biodegradability.
The primary functional mechanism of polyglycerol-based food additives is surfactant behavior derived from their amphiphilic molecular structure. Polyglycerol fatty acid esters are highly effective and versatile emulsifiers, capable of stabilizing both oil-in-water (O/W) and water-in-oil (W/O) emulsions depending on their specific chemical composition; their amphiphilic nature — possessing both hydrophilic (water-loving) and hydrophobic (oil-loving) regions — is the key to their functionality. When added to a mixture of oil and water, PGE molecules migrate to the interface between the two phases; the hydrophilic polyglycerol portion orients itself towards the water, while the hydrophobic fatty acid chains extend into the oil; this positioning significantly reduces the interfacial tension between the oil and water, making it easier for them to mix and form an emulsion.
The hydrophilic-lipophilic balance (HLB) of polyglycerol esters can be tuned by altering the degree of polyglycerol polymerization and the chain length and degree of saturation of the esterified fatty acids, giving the formulator considerable control over emulsion type and stability.
PGPR has a uniquely important mechanism in chocolate manufacture that is distinct from its general emulsification function. Polyglycerol polyricinoleate (E 476, PGPR) is unique among food emulsifiers for having a substantial effect on the yield stress of fat-based suspensions. It is used at low levels (below 0.5%) and works by decreasing the friction between the solid particles (e.g., cacao, sugar, milk) in molten chocolate, reducing the yield stress so that it flows more easily, approaching the behaviour of a Newtonian fluid. Polyglycerol polyricinoleate coats solid particles and, with greater molecular weight, extends further into the lipid continuous phase, producing better steric stabilization.
Polyglycerol esters of fatty acids have a dual function of promoting and inhibiting crystal formation; lipophilic polyglycerol esters promote crystal formation, particularly in long-chain saturated fatty acid series, while hydrophilic ones inhibit crystal formation. This property is exploited in margarine, ice cream, and chocolate coatings to control fat crystal polymorphism and texture.
At the biomedical level, the dense hydroxyl surface of hyperbranched polyglycerol mimics the hydrophilic surface of polyethylene glycol (PEG), resisting non-specific protein adsorption (the "stealth" effect). Polyglycerol (PG, also known as polyglycidol), which is highly biocompatible and possesses water-solubility and non-toxicity requirements, has been thoroughly studied as an important polymer candidate in biomedical fields. Hyperbranched polyglycerols (HPGs) with a dendritic configuration have been recognized for their excellent biocompatibility and multifunctionalization; HPGs have been studied for use in the delivery of diagnostic, imaging, and therapeutic molecules in nanobiomedicine, showing superior characteristics to linear polymers and dendrimers such as compact structure, a simple manufacturing process with easy functionalization ability, low viscosity, and high stability; they are now considered promising carriers for drug delivery, diagnostics, imaging, and theranostics applications for cancer treatment.
The use of PGPR in chocolate is the best-studied practical application of any polyglycerol derivative. In the food industry, PGPR is commonly used along with lecithin to diminish the viscosity of chocolate couvertures; it is also employed as an emulsifier in high or low fat content products, such as butter, margarines, and salad dressings. PGPR is not normally used as the sole emulsifier, but in combination with lecithin or ammonium phosphatide; the impact of PGPR on viscosity is quite small, but it has a significant effect on yield value.
A quantitative illustration of this effect is provided by published rheological research: chocolate with 35% cocoa butter content has a similar yield value to that containing 32% cocoa butter and 0.1% PGPR. This finding implies that PGPR addition can reduce the required cocoa butter content of chocolate while maintaining equivalent flow properties — a commercially significant outcome. Studies on optimal lecithin:PGPR blending ratios for different applications have reported values in the range of 2:1 to 3:1 lecithin to PGPR. The effect on yield stress is not observed when PGPR is used as the emulsifying agent at increasing concentrations; rather, a small concentration of PGPR decreases the yield stress.
Evidence characterization: The evidence in this area is primarily from food science laboratory studies, physicochemical and rheological measurements, and technological applications research rather than human clinical trials. The functional efficacy of PGPR as an emulsifier and yield-stress reducer in chocolate is well-established and not scientifically contested.
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. It is authorized for use in baked goods, margarine, non-dairy creamer, and ice cream, among other categories. Polyglycerol esters of fatty acids, up to and including the decaglycerol esters, may be safely used in food when prepared from corn oil, cottonseed oil, lard, palm oil from fruit, peanut oil, safflower oil, sesame oil, soybean oil, tallow, and the fatty acids derived from these substances.
Evidence characterization: As with PGPR in chocolate, the evidence for bakery and other food applications of PEFA is predominantly from food science and technology literature rather than human health intervention trials. No clinical outcome trials examining health benefits of PEFA in baked goods have been identified in the peer-reviewed literature.
The most clinically relevant human study of PGPR was conducted at the Metabolic Unit of Glasgow Royal Infirmary. The potential adverse effects of PGPR were investigated in 19 human volunteers over a period of 2 weeks following 1 week of diet acclimatization; the exposure regimen was 0 g/day for 1 week, 5 g/day for the second week, and 10 g/day for the final week. The human studies showed no adverse effects on tolerance, liver and kidney function, and fat balance at levels up to 10 g/day PGPR.
A separate clinical study with PEFA is summarized in the EFSA 2017 re-evaluation: clinical chemistry and urinalysis from a clinical study with limited information did not reveal any adverse effects in volunteers receiving up to 300 mg/kg bw per day for 3 weeks.
In animal studies, PGPR was found to be 98% digested by rats and utilized as a source of energy superior to starch and nearly equivalent to groundnut oil. There was no interference with normal fat metabolism in rats or in the utilization of fat-soluble vitamins; despite the intimate relationship with fat metabolism, no evidence was found of any adverse effects on such vital processes as growth, reproduction, and maintenance of tissue homeostasis.
Evidence characterization: Human evidence consists of small, short-duration clinical studies (19 volunteers; 3-week period in separate trials) with methodological limitations acknowledged by EFSA. These studies are adequate for establishing an absence of acute and short-term adverse effects at the tested doses but are insufficient to draw conclusions about long-term health outcomes at typical dietary exposure levels. Animal data are more extensive but also have recognized limitations.
An emerging area of scientific inquiry concerns the potential effects of dietary emulsifiers, including PGPR, on the human gut microbiota. Two synthetic emulsifiers in particular, carboxymethylcellulose and polysorbate 80, profoundly impact intestinal microbiota in a manner that promotes gut inflammation and associated disease states; in contrast, the extent to which other food additives with emulsifying properties might impact intestinal microbiota composition and function is not yet well known.
A mouse study published in a peer-reviewed journal examined polysorbate-80 (P80) and PGPR specifically. This study investigated the effects of polysorbate-80 and PGPR on lipid metabolism, bile acid profile, and gut microbiota in normal and high-fat-diet-induced obesity in mice; the results showed that P80 and PGPR had little effect on body weight but significantly increased epididymal-fat weight, total energy intake, and blood lipid levels. However, P80 and PGPR changed the bile acid profile but did not aggravate intestinal inflammation and obesity by altering the composition of the gut microbiota.
A broader in vitro study using a human microbiota maintained ex vivo examined 20 emulsifiers including PGPR. Researchers examined the extent to which a human microbiota, maintained ex vivo in the MiniBioReactor Array model, was impacted by 20 different commonly used dietary emulsifiers; microbiota density, composition, gene expression, and pro-inflammatory potential were measured daily. Several studies have shown that besides P80 and CMC, most common emulsifiers have a negative effect on the gut microbiota, except lecithin and MDGs, and require further investigation.
Evidence characterization: The gut microbiota evidence relating specifically to PGPR is preliminary, mostly from animal models and ex vivo systems, and often conflicting in its conclusions. No adequately powered, controlled human clinical trials have examined the effect of polyglycerol derivatives on the gut microbiome as a primary endpoint. This area requires further investigation and current results cannot be directly extrapolated to human dietary exposure.
A significant and growing body of pre-clinical research investigates hyperbranched polyglycerol (HPG) as a drug delivery scaffold. Hyperbranched polyglycerols and their derivatives are widely regarded as promising biomaterials in a variety of diagnostic and therapeutic applications through solubilization, microencapsulation, or conjugation with diagnostic agents, drugs, genetic materials, proteins, and peptides; HPGs have good chemical stability, inertness under biological conditions, water-solubility with low viscosity and multi-functionalization.
A study published in Pharmaceutics (2023) demonstrated that poly(glycerol) microparticles synthesized via a micro-emulsion method showed biocompatibility: p(Gly) microparticles at concentrations up to 1.0 g/mL were found biocompatible with 85 ± 1% cell viability against L929 fibroblasts; moreover, p(Gly) microparticles were tested for hemocompatibility, and it was found that up to 1.0 mg/mL concentrations the particles were non-hemolytic with 0.4 ± 0.1% hemolysis ratios; blood compatibility index values were found to be 95 ± 2%, indicating that these microparticles are both bio- and hemocompatible.
Research from Yale University examined HPG as an alternative to PEG coatings on drug-delivery nanoparticles. A key attribute for nanoparticles used in medicine is the ability to avoid rapid uptake by phagocytic cells in the liver and other tissues; poly(ethylene glycol) coatings have been the gold standard in this regard for several decades; hyperbranched polyglycerols were examined as an alternate coating on NPs. Researchers synthesized a copolymer of PLA-HPG by a one-step esterification; fluorescent dye or the anti-tumor agent camptothecin (CPT) were encapsulated at high efficiency in the NPs.
Research into dendritic polyglycerol sulfate (dPGS) for neuroinflammation has attracted interest. Hyperbranched or dendritic polyglycerol sulphate have been found to be very efficient for the treatment of neurological disorders arising from inflammation, as therapeutics for the prevention of tissue damage, as substance delivery platforms for transporting drugs to tumour cells, and as imaging agents for the diagnosis of disease.
Evidence characterization: All biomedical drug delivery evidence for polyglycerol and hyperbranched polyglycerol derivatives is at the pre-clinical stage — in vitro cell studies and animal models — with no human clinical trials published as of the time of this writing. While HPG is considered highly promising as a PEG alternative and drug carrier scaffold, its clinical translation status remains investigational.
The gastrointestinal system is the primary site of metabolic interaction with dietary polyglycerol derivatives. Absorption of intact PEFA in the gastrointestinal tract was extremely low; PEFA was rapidly and almost fully hydrolysed to polyglycerols and fatty acids in the gastrointestinal tract. The released polyglycerols are largely excreted unchanged, either via urine (shorter chain forms) or faeces (longer chain forms). Emerging research is investigating whether PGPR and related emulsifiers interact with gut microbiota composition, though this remains unresolved (see Section 6.4).
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. The human study conducted at Glasgow Royal Infirmary specifically confirmed no adverse effects on liver and kidney function at doses up to 10 g/day.
The digestibility of PGPR is 98% and it does not interfere with the normal metabolism of lipids. Animal studies have confirmed that PGPR does not interfere with fat-soluble vitamin absorption or lipid metabolism. A mouse study found elevated epididymal-fat weight and blood lipid changes with PGPR administration, though this was in the context of a high-fat diet, and the effect magnitude and human relevance are uncertain.
At the level of dietary exposure from food, no immunotoxic or pro-inflammatory effects have been demonstrated in humans. Pre-clinical work with modified polyglycerol scaffolds (e.g., dPGS) suggests anti-inflammatory potential in experimental neurological and inflammatory disease models, but this work is entirely pre-clinical.
Hyperbranched polyglycerols are now considered promising carriers for drug delivery, diagnostics, imaging, and theranostics applications for cancer treatment, based on pre-clinical research only. No human trials in oncology have been completed.
Polyglycerol derivatives as food additives are regulated by major authorities globally.
The following doses have been reported in published studies and regulatory assessments. These are reported only as they appear in those sources and do not represent recommendations.
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. The available limited information on the genotoxicity of PEFA did not indicate a genotoxic potential; the available chronic toxicity and carcinogenicity studies with PEFA in mice and rats also had limitations; however, none of these studies gave any indication of a carcinogenic potential of PEFA.
For PGPR specifically: PGPR was not carcinogenic in either 2-year rat or 80-week mouse feeding studies.
EFSA's 2022 follow-up opinions on both E 475 and E 476 identified specific impurity concerns deserving regulatory attention. The Panel concluded that the maximum limits in the EU specifications for the four toxic elements (arsenic, lead, mercury, and cadmium) should be lowered based on actual levels in the commercial food additive E 475; the Panel also concluded that maximum limits for erucic acid, 3-monochloropropanediol, and glycidyl esters should be included in the EU specifications for E 475. The Panel performed a risk assessment of undesirable impurities potentially present in E 476; the Panel concluded that the maximum limits in the EU specifications for the four toxic elements (arsenic, lead, mercury, cadmium) should be lowered based on actual levels in the commercial food additive E 476.
The reproductive toxicity studies showed no adverse effects of PEFA but had major limitations. 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 explicitly acknowledged by EFSA in their 2017 re-evaluations; they influenced the basis for revising the ADI.
In recent reports, dietary emulsifiers have been shown to affect the gut microbiota, contributing to a pro-inflammatory phenotype and metabolic syndrome; it is not yet known whether similar microbiome shifts are observable for a more diverse set of emulsifier types and to what extent these effects vary with the unique features of an individual's microbiome. While the majority of research suggests no negative effect of PGPR on organ health or genotoxicity in humans or animals, one study in mice determined that PGPR could aggravate colon inflammation and increase the percentage of weight from fat; this correlates with newer research suggesting that some emulsifiers may harm the health of the gut microbiota. It bears emphasis that this study is in animals and the dose-relevance to human dietary exposure has not been established.
In 2013, the EFSA Panel on Food Contact Materials, Enzymes, Flavorings, and Processing Aids concluded that polyglycerol is safe to be used as a plasticizer in food contact materials (all food types and at room temperature and below) at a maximum concentration of 6.5% w/w in polymer blends of aliphatic-aromatic polyesters.
Polyglycerol and its fatty acid esters may be derived from both animal and plant sources. Consumers following vegan, halal, or kosher diets should be aware that the source of glycerol and fatty acids used in production varies by manufacturer. PGPR is derived from castor oil fatty acids, which are plant-derived; however, verifying the source of glycerol used in the polyglycerol moiety may be necessary for strict dietary requirements.
Health conditions that Polyglycerol may help support.
Body systems that Polyglycerol may help support.
Go back