IngredientsInulin-propionate ester (IPE) is a semi-synthetic, bioactive dietary ingredient formed by the covalent esterification of inulin — a naturally occurring polysaccharide — with propionic acid, a short-chain fatty acid (SCFA) produced endogenously in the human gut. The compound is constituted by a natural polymer composed mainly of fructose moieties, polysaccharide inulin (65%–95% w/w), esterified with a short-chain fatty acid (SCFA) moiety, propionic acid (5%–35% w/w).
The compound is synthesised by the chemical reaction of inulin with propionic anhydride, under alkaline conditions and controlled temperature. The degree of esterification (DE) — the fraction of inulin's hydroxyl groups substituted by propionate — is a key parameter; experimental variants have ranged from IPE-0 to IPE-61, denoting the approximate weight-percent of propionate in the molecule. Inulin propionate esters containing 0–61 wt% propionate (IPE-0–IPE-61) have been assessed in vitro using batch faecal fermentations.
The compound is constituted by a natural polysaccharide polymer composed mainly of fructose moieties, inulin, esterified with a short-chain fatty acid moiety, propionic acid. Both moieties are naturally present in the food and in the current EU and global food supply for different purposes, such as food additives and food supplements.
Inulin, the carrier backbone, is a naturally occurring fructan polysaccharide found primarily in chicory root (Cichorium intybus), Jerusalem artichoke, dahlia tubers, garlic, leek, and onion. Propionic acid (propanoic acid) is an endogenous SCFA produced in the human large intestine through microbial fermentation of dietary fibre. Propionate is produced naturally when dietary fibre is fermented by microbes in the gut.
SCFAs primarily comprise acetate (40–60%), propionate (20–25%), and butyrate (15–20%). Acetate and propionate are mainly produced by Bacteroidetes, whereas butyrate is primarily generated by Firmicutes — the two dominant bacterial phyla in the adult gut microbiota, which together account for approximately 90% of its composition.
According to Article 3(2) of Regulation (EU) 2015/2283, inulin-propionate ester falls under the category of 'food with a new or intentionally modified molecular structure, where that structure was not used as, or in, a food within the Union before 15 May 1997.' In 2025, the European Food Safety Authority (EFSA) Panel on Nutrition, Novel Foods and Food Allergens (NDA) issued a formal safety opinion on IPE pursuant to this regulation. The target population for the novel food is the general population, and it is intended to be used as an ingredient in cereal bars and fruit smoothie type beverages.
Inulin-propionate ester as a discrete chemical entity has no traditional or historical use in any food system or healing tradition. It does not occur naturally in plants or foods in its esterified form. It is an entirely modern, research-derived ingredient developed in the early 2010s by scientists at Imperial College London and the University of Glasgow.
However, the two component molecules — inulin and propionate — each have extensive independent histories. Inulin has been consumed for millennia as a constituent of dietary plants, and its prebiotic properties have been recognized since the late 20th century. Propionic acid itself occurs at low levels in some fermented foods (such as certain cheeses produced by Propionibacterium freudenreichii) and has been used as a food preservative (E 280 in the EU) since the mid-20th century. In 2014, the EFSA Panel on Food Additives and Nutrient Sources Added to Food (ANS) published an opinion on the re-evaluation of propionic acid (E 280) and its salts. The concept of IPE as a "targeted delivery vehicle" for colonic propionate was developed to circumvent the practical problem that oral propionate supplementation does not efficiently deliver propionate to the colon, and that achieving meaningful increases in colonic propionate through dietary fibre alone requires unrealistically high fibre intakes.
Based on studies investigating the metabolic fate of the novel food, the EFSA Panel considers that IPE is not absorbed intact, but is metabolised mainly in the large intestine to inulin and propionate, which then exhibit the normal metabolic fate of non-digestible dietary fibre and SCFA, respectively.
Once delivered to the proximal colon, the ester bond is hydrolysed by colonic bacteria, releasing free propionate directly at the site of its physiological action. This design is central to IPE's rationale as a delivery system: the amount of inulin-propionate ester used in studies was 10 g, which previous studies show increases propionate production by 2.5 times. To get the same increase from fibre alone, around 60 g per day would be needed — whereas the UK average is 15 g.
In vitro, IPE-27–IPE-54 wt% propionate resulted in a sevenfold increase in propionate production compared with inulin (P < 0.05).
The primary mechanism by which colonic propionate exerts its effects on appetite and metabolism involves activation of G protein-coupled receptors (GPCRs), specifically Free Fatty Acid Receptors 2 and 3 (FFAR2, also known as GPR43, and FFAR3, also known as GPR41).
Putative receptors for SCFAs include the free fatty acid receptors (FFARs) 2 and 3. Both receptors couple to Gi/o, and activation thus leads to raised intracellular calcium and decreased cAMP. FFAR2 also exhibits dual coupling to Gq, an activator of phospholipase C. Localized in the human colon and ileum, FFAR2 and FFAR3 are expressed by enteroendocrine L-cells that secrete PYY.
The ability of propionate, a short-chain fatty acid produced from the fermentation of non-digestible carbohydrates in the colon, to stimulate the release of anorectic gut hormones, such as glucagon-like peptide-1 (GLP-1), is an attractive approach to enhance appetite regulation, weight management, and glycaemic control. Propionate induces GLP-1 release via its G protein-coupled receptor (GPCR), free fatty acid receptor 2 (FFA2), a GPCR that activates Gαi and Gαq/11.
More specifically: propionate-mediated G protein signalling is spatially directed within the cell whereby FFA2 is targeted to very early endosomes. Furthermore, propionate activates a Gαi/p38 signalling pathway, which requires receptor internalization and is essential for propionate-induced GLP-1 release in enteroendocrine cells and colonic crypts.
Propionate stimulated the secretion of both PYY and GLP-1 from wild-type primary murine colonic crypt cultures. This effect was significantly attenuated in cultures from FFA2−/− mice. Intra-colonic infusion of propionate elevated PYY and GLP-1 levels in jugular vein plasma in rats and in portal vein plasma in both rats and mice. However, propionate did not significantly stimulate gut hormone release in FFA2−/− mice.
Acetate, propionate, and butyrate are the predominant SCFAs in the human gut and activate human FFAR2 and FFAR3 with distinct potencies (human FFAR2: Ace = Pro > But; FFAR3: Pro = But > Ace). Among the three SCFAs, propionate has the highest affinity for FFAR2. Of the SCFAs produced in the colon, propionate has the highest affinity for FFAR2, and a lower binding affinity for FFAR3.
Beyond FFAR2/FFAR3 signalling, propionate is known to act as an epigenetic regulator through inhibition of histone deacetylases (HDACs), and to exert metabolic effects in the liver via the portal vein. Propionate is metabolised by hepatocytes and has been shown to increase insulin sensitivity and attenuate the lipogenic pathway, thus lowering liver triglyceride levels. The short-chain fatty acid propionate, produced through fermentation of dietary fibre by the gut microbiota, has been shown to alter hepatic metabolic processes that reduce lipid storage.
Both in vitro and in vivo studies published between 2011 and 2020 confirmed the ability of propionate to inhibit the growth of several cellular pathogens, including Gram-positive and Gram-negative multi-drug resistant bacteria and fungi. In addition, heterogeneous immune-modulatory and, in particular, anti-inflammatory effects of propionate could be assessed, involving a diverse signalling network.
Propionate acts as a signalling molecule through FFAR2/FFAR3 receptors and modulates immunity, energy metabolism, and gut–brain communication.
The most robustly studied property of IPE is its ability to reduce acute food intake through stimulation of anorectic gut hormones. A key early randomised clinical study optimised IPE delivery by comparing variants with different degrees of esterification.
In a randomised, controlled, crossover study, with inulin as control, ad libitum food intake (kcal) was compared after 7 days on IPE-27 or IPE-54 (10 g/day all treatments). IPE-27 led to a reduction in energy intake during the ad libitum test meal compared with both inulin (439.5 vs. 703.9 kcal, P = 0.025) and IPE-54 (439.5 vs. 659.3 kcal, P = 0.025), whereas IPE-54 was not significantly different from the inulin control. IPE-27 significantly reduced food intake, suggesting colonic propionate plays a role in appetite regulation.
In the landmark Chambers et al. (2015) study: Acute ingestion of 10 g inulin-propionate ester significantly increased postprandial plasma PYY and GLP-1 and reduced energy intake.
Evidence on the brain reward system was provided by a crossover study using functional magnetic resonance imaging (fMRI). One study found that increasing colonic propionate by consumption of 10 g of an inulin-propionate ester (thereby delivering 2.36 g propionate to the colon, which is 2.5 times habitual daily propionate production) influenced brain anticipatory reward responses during a functional magnetic resonance imaging (fMRI) food picture evaluation task in non-obese men (Byrne et al., 2016). In parallel, the subjective appeal of high-energy food pictures decreased and energy intake during an ad libitum meal was reduced.
In a randomised crossover design, 20 healthy non-obese men completed a functional magnetic resonance imaging (fMRI) food picture evaluation task after consumption of control inulin or inulin-propionate ester. The blood oxygen level-dependent (BOLD) signal was measured in a priori brain regions involved in reward processing, including the caudate, nucleus accumbens, amygdala, anterior insula, and orbitofrontal cortex (n = 18 had analysable fMRI data). Increasing colonic propionate production reduced BOLD signal during food picture evaluation in the caudate and nucleus accumbens.
Notably, the fMRI study showed that these effects were not exclusively mediated by gut hormones: the administration of inulin-propionate ester was associated with reduced anticipatory reward responses in the human striatum to high-energy foods (Byrne et al., 2016). These results were not linked with changes in plasma PYY or GLP-1, suggesting an effect of propionate on the food reward system independent of GLP-1 and PYY.
Evidence strength: The acute appetite effects are supported by multiple short-term human crossover RCTs in relatively small samples (n = 18–20). Results across studies have shown some inconsistency regarding the specific hormonal mediators (some studies finding GLP-1 increases, others not), as explicitly noted by later researchers. Some conflicting findings have been reported after IPE administration. In contrast to previous findings (Chambers et al., 2015), IPE administration was found to attenuate reward-based eating behaviour (Byrne et al., 2016) and enhance fat oxidation (Malkova et al., 2020) independently of changes in GLP-1 and PYY. On the other hand, another study found that IPE-mediated appetite reduction was associated with increased GLP-1 levels.
The most prominent long-term clinical evidence comes from the Chambers et al. (2015) randomised controlled trial published in the journal Gut:
The long-term effects of inulin-propionate ester on weight gain were subsequently assessed in a randomised, controlled 24-week study involving 60 overweight adults. Over 24 weeks, 10 g/day inulin-propionate ester supplementation significantly reduced weight gain, intra-abdominal adipose tissue distribution, intrahepatocellular lipid content, and prevented the deterioration in insulin sensitivity observed in the inulin-control group.
One out of 25 volunteers given IPE who completed the study gained more than three percent of their body weight, compared with 25 percent given inulin. None of the IPE group gained more than five percent of their body weight, compared with four in the inulin group. After 24 weeks, the IPE group also had less fat in their abdomens and livers compared with the inulin group.
These positive findings in middle-aged overweight adults prompted the iPREVENT multi-centre trial, a larger and longer study involving younger participants. The study, titled iPREVENT, involved 270 participants aged 20 to 40, divided into groups consuming either inulin-propionate ester (IPE) or inulin (control). Neither group gained significant weight over 12 months, and there was a non-significant baseline-adjusted mean difference in weight gain of 1.02 (95% CI: −0.37 to 2.41) kg for IPE versus inulin control. Professor Gary Frost of Imperial College London stated: "Its impact on overall weight management appears limited, warranting further research into age-specific interventions for obesity prevention."
Evidence strength: The positive 24-week RCT in middle-aged overweight adults (Chambers et al., 2015, n = 60) was the most compelling trial to date, but the subsequent iPREVENT trial (n = 270, 12 months, younger adults) did not replicate the primary endpoint. The evidence is therefore mixed and appears to be age- or population-specific. Overall the evidence for long-term weight prevention remains preliminary and requires replication in larger, more diverse samples.
The 24-week Chambers et al. (2015) trial showed IPE prevented deterioration of insulin sensitivity. This was explored mechanistically in a subsequent crossover trial:
Twelve non-diabetic adults with overweight and obesity received 20 g/day of inulin-propionate ester (IPE), designed to selectively deliver propionate to the colon, a high-fermentable fibre control (inulin), and a low-fermentable fibre control (cellulose) in a randomised, double-blind, placebo-controlled, cross-over design. Both IPE and inulin supplementation improved insulin resistance compared with cellulose supplementation, measured by homeostatic model assessment 2 (mean ± SEM: 1.23 ± 0.17 IPE vs. 1.59 ± 0.17 cellulose, p = 0.001; 1.17 ± 0.15 inulin vs. 1.59 ± 0.17 cellulose, p = 0.009), with no differences between IPE and inulin (p = 0.272).
Targeted SCFA supplementation, particularly with propionate or butyrate, improved insulin sensitivity and reduced energy intake. Additionally, propionate is metabolised by hepatocytes and has been shown to increase insulin sensitivity and attenuate the lipogenic pathway, thus lowering liver triglyceride levels.
Evidence strength: The improvement in insulin sensitivity appears credible but is shared with inulin alone, making IPE's specific contribution via propionate difficult to isolate. Studies are small (n = 12–60) and of short duration (42–168 days). Larger and longer trials are needed.
A small randomised trial examined the effects of IPE in adults with non-alcoholic fatty liver disease (NAFLD):
Eighteen adults were randomized to receive 20 g/d of an inulin-propionate ester (IPE), designed to deliver propionate to the colon, or an inulin control for 42 days in a parallel design. The change in intrahepatocellular lipid (IHCL) following the supplementation period was not different between the groups (P = 0.082); however, IHCL significantly increased within the inulin-control group (20.9% ± 2.9% to 26.8% ± 3.9%; P = 0.012; n = 9), which was not observed within the IPE group (22.6% ± 6.9% to 23.5% ± 6.8%; P = 0.635; n = 9).
Evidence strength: This trial is extremely small (n = 9 per arm) and the between-group difference did not reach statistical significance. The result is considered hypothesis-generating only. The mechanistic rationale is supported by evidence that the short-chain fatty acid propionate has been shown to alter hepatic metabolic processes that reduce lipid storage.
The modulation of brain reward circuitry is a unique mechanistic angle for IPE. A small clinical study involving healthy men showed that the administration of inulin-propionate ester, increasing selectively colonic propionate, was associated with reduced anticipatory reward responses in the human striatum to high-energy foods (Byrne et al., 2016). These results were not linked with changes in plasma PYY or GLP-1, suggesting an effect of propionate on the food reward system independent of GLP-1 and PYY.
Evidence strength: This is a single, small (n = 18 analysable), crossover RCT in healthy non-obese men. While novel and mechanistically interesting, this represents very preliminary evidence; replication in broader and more clinically relevant populations is required.
A clinical trial examined the combination of IPE with moderate-intensity exercise training: Malkova and colleagues found that moderate intensity exercise training combined with inulin-propionate ester supplementation increases whole body resting fat oxidation in overweight women (Metabolism, 2020). Moderate intensity exercise training programmes, when combined with daily oral IPE supplementation, may help overweight women to achieve an increase in fat oxidation.
Evidence strength: This is a single trial with a combined intervention design (IPE + exercise), making it difficult to attribute observed changes specifically to IPE. Evidence is preliminary.
Both in vitro and in vivo studies confirmed the ability of propionate to inhibit the growth of several cellular pathogens, including Gram-positive and Gram-negative multi-drug resistant bacteria and fungi. An esterified derivative of propionate, which is more resistant against metabolisation, exhibited similar growth-inhibiting effects.
Considering the mounting clinical evidence supporting the immunomodulatory effects of propionate, there is a pressing need for further well-structured clinical studies, particularly in the context of chronic intestinal inflammations.
Evidence strength: Antimicrobial and immunomodulatory effects of propionate itself are supported by in vitro and some animal data but have not been specifically studied with IPE in human clinical trials. This evidence base remains preclinical.
IPE's fundamental purpose is to act as a site-specific delivery vehicle to the proximal colon. Inulin SCFA esters were developed and tested as site-specific delivery vehicles for SCFA to the proximal colon. The microbiological rationale for targeting propionate is rooted in the three known metabolic pathways through which gut bacteria produce propionate:
Three different biochemical pathways for propionate production are known to be present in the microbiota. Bacteroidetes utilise the succinate pathway via methylmalonyl-CoA, which is also present in several Firmicutes bacteria. Additionally, the acrylate pathway (detecting the lcdA gene, encoding lactoyl-CoA dehydratase) is restricted to only a few human colonic species within the Lachnospiraceae and Negativicutes. The propanediol pathway constitutes the third route. The most abundant propionate producers are Bacteroides spp. (phylum Bacteroidetes), Veillonella (phylum Firmicutes), and Akkermansia muciniphila (phylum Verrucomicrobia).
The cross-over insulin-sensitivity trial also investigated microbiota changes: the study's aim included comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome, and immune responses. Distinct microbiota changes were observed with IPE and inulin, providing evidence that propionate delivery differentially modulates the gut microbial ecosystem compared to fermentable fibre alone.
IPE is prepared as a white to off-white powder intended to be stirred into foods, beverages, or smoothies without significantly affecting taste or texture. It is intended to be used as an ingredient in cereal bars and fruit smoothie type beverages.
The following doses have been explicitly reported in published clinical studies:
Regarding projected population exposure: dietary exposure assessment using the UK NDNS indicates that mean and heavy-level consumption (at the 95th percentile) is not expected to exceed total daily estimates of 10.3 and 21.5 g/day, respectively, in the consumer-only population, based on the maximum intended uses in breads and rolls, breakfast cereals, and fruit juice at 5 g per serving.
Regarding the degree of esterification: in vivo, IPE-27 led to greater ¹³C recovery in breath CO₂ than IPE-54 (64.9 vs. 24.9%, P = 0.001), indicating that IPE-27 releases its propionate load more efficiently in the proximal colon. Most human trials have used IPE-27 (approximately 27 wt% propionate), often described simply as "inulin-propionate ester" in the published literature.
Taking into account physico-chemical properties of the novel food, the production process and metabolic fate of the novel food, which do not raise safety concerns, and given that propionic acid and its salts were previously assessed by EFSA ANS Panel (2014), as well as that a large body of safety data were available on inulin, the Panel considers that no genotoxicity and subchronic toxicological studies are required on the novel food.
Despite the limitations of the provided human studies (primarily designed to investigate efficacy endpoints), the Panel notes that the novel food, at doses up to 20 g/day for durations up to 12 months, appears to be generally well-tolerated. The Panel concludes that inulin-propionate ester is safe for the general population under the proposed conditions of use.
At doses up to 20 g/day for up to 12 months, IPE appears to be generally well-tolerated. The primary adverse effects observed are mild and transient gastrointestinal symptoms, which are common with non-digestible fibres and comparable to those seen with inulin.
Most studies assessed gastrointestinal (GI) tolerance using visual analogue scales (VAS) for symptoms such as nausea, bloating, flatulence, and stomach discomfort, or through general adverse event reporting. The most frequently reported adverse effects related to the consumption of the novel food were gastrointestinal in nature, such as bloating, flatulence, increased bowel movement frequency, nausea, or stomach discomfort.
One key finding from the 24-week RCT was that IPE's tolerability profile compared favourably to inulin alone: the side effect profile was greater in the inulin control group, with a significant increase in bloating and flatulence at week 24 that was not seen in the inulin-propionate ester group.
The gastrointestinal side effects noted following IPE in food products are comparable to those reported following supplementation with inulin, and are common side effects associated with fibre consumption.
Feeding rats with diets containing more than 10% propionate inulin ester resulted in diarrhoea, reductions in food consumption and body weight, as well as an enlargement of the caecum. These effects are known phenomena associated with high intake of fibre and they were not statistically different from those observed following administration of inulin. No toxic effects were reported in rats fed the ingredient at approximately 6,000 mg/kg body weight/day, nor in mice provided 10% inulin-propionate ester in the diet for 21 days (equivalent to approximately 20,000 mg/kg body weight/day).
The ingredient is well tolerated and safe when consumed by human subjects at bolus doses of up to 20 g/day for 6 weeks or at 10 g/day for up to 24 weeks. In the long-term 24-week trial, none of the participants reported any side effects from the intake of propionate esters.
Taking into account physico-chemical properties of the novel food, the production process and metabolic fate of the novel food, which do not raise safety concerns, and given that propionic acid and its salts were previously assessed by EFSA ANS Panel (2014), as well as that a large body of safety data was available on inulin, the Panel considers that no genotoxicity and subchronic toxicological studies are required on the novel food.
SCFAs are generally considered beneficial for intestinal health. However, in inflammatory conditions such as inflammatory bowel disease (IBD), they can have opposing effects. Specifically, propionate may act as a microbial danger signal under inflammatory conditions. Propionate use requires a personalized approach, considering the pathological context, host microbiota composition, and appropriate dosage to avoid adverse effects.
No specific pharmacokinetic drug-drug interactions have been formally identified or studied for IPE. Because IPE is metabolised entirely in the large intestine and the released propionate enters the portal circulation, potential interactions with drugs that are also transported or metabolised hepatically cannot be excluded but have not been documented in published clinical literature. Several studies assessed clinical chemistry parameters including fasting glucose, lipids, liver function tests, HbA1c, and C-reactive protein, with no clinically significant abnormalities reported.
In a crossover RCT, overweight adult subjects were administered an inulin-propionate ester formulation for 24 weeks. The study confirmed that increased propionate levels in the colon effectively prevented weight gain in enrolled subjects. Currently, two clinical trials are underway to evaluate the effect of sodium propionate in subjects with various pathologies.
Risk of bias in existing studies is generally moderate due to small sample sizes and variability in SCFA measurement methods. Overall, fecal SCFAs appear to act as both biomarkers and modulators of metabolic health. Larger, standardised longitudinal studies are required to clarify their causal role and therapeutic potential in obesity, metabolic syndrome, and related conditions.
The divergence between the positive 24-week results in middle-aged adults (Chambers et al., 2015) and the null result of iPREVENT in younger adults highlights important limitations: effects may be age-specific, dose-dependent, and influenced by baseline metabolic state and gut microbiota composition. Unlike butyrate, formulations of propionate used for supplementation have been rarely studied in clinical trials, especially in obesity, diabetes, and cardiovascular disease.
As of 2025, the applicant provided eight publications reporting on human intervention studies using the novel food as the test substance (Byrne et al., 2016, 2019; Chambers et al., 2015; Chambers, Byrne, Morrison, et al., 2019; Chambers, Byrne, Rugyendo, et al., 2019; Malkova et al., 2020; Polyviou et al., 2016; Pugh et al., 2024). The totality of human trial data therefore encompasses eight studies, most originating from the same research group at Imperial College London and the University of Glasgow, which represents an important limitation in terms of independent replication.
Health conditions that Propionate ester may help support.
Body systems that Propionate ester may help support.
Go back