IngredientsEuglena gracilis Klebs is a unicellular, photosynthesizing microalga belonging to the phylum Euglenozoa. It is a eukaryotic, unicellular phytoflagellate in the genus Euglena, characterized by a dynamic and flexible cell structure, and is commercially cultivated as a nutritional food. Vernacular names reflect its unusual taxonomic position: in Japanese it is called ミドリムシ (Midorimushi, literally "green bug"); in Chinese 眼虫 (Yan chong, "eye worm"); in German Augentierchen ("little eye animal"); and in French Euglène. In commerce, the ingredient is typically marketed simply as "Euglena" or as "Euglena gracilis powder."
Euglena gracilis is a unicellular microalga lacking a cell wall, with both autotrophic and heterotrophic growth styles under different cultivation conditions. In recent years, the versatile phototrophic protist Euglena gracilis has emerged as an interesting candidate for application-driven research and commercialisation, as it is an excellent source of dietary protein, pro(vitamins), lipids, and the β-1,3-glucan paramylon, a polysaccharide only found in euglenoids.
E. gracilis is a single-cell microalga which occurs widely in nature and is commonly found in freshwater habitats. Under cultivation, it can grow under autotrophic (light-driven), heterotrophic (dark, carbon-source-fed), or mixotrophic conditions, which significantly alters the proportional yield of its constituent compounds. The Euglena gracilis EOD-1 strain, for example, produces high paramylon yields (70–80%) depending on culture conditions, and paramylon is obtained from cultured E. gracilis EOD-1 with glucose as the carbon source under heterotrophic conditions in the dark.
Three primary supplement forms appear in the literature:
Unlike many plants with centuries of documented traditional use, Euglena gracilis is a modern functional food; its "traditional" use is rooted in Japanese health practices following the development of large-scale cultivation technology in 2005. There is no pre-modern traditional use in any cultural or ethnobotanical system on record. Its adoption as a health food followed rapidly from Japanese commercial biotechnology, and Japan remains the primary market for Euglena-based dietary supplements. Euglena is consumed daily as a dietary supplement to maintain immune health and reduce the risk of infections and is widely used in Japan for this purpose.
Paramylon (Pa) is a water-insoluble linear (unbranched) β-(1,3)-glucan polysaccharide polymer with a molecular mass of about 500 kDa. Paramylon, a β-1,3-glucan, comprises around 20–70% of Euglena on a dry weight basis. Under optimized heterotrophic culture conditions, the paramylon content can reach up to 50–70% of the dried biomass of E. gracilis. Due to its high molecular mass, paramylon has low solubility and poor bioavailability; however, alkalization treatment reduces its molecular mass to 12 kDa, which greatly increases solubility and bioavailability in vitro.
Euglena cells contain many nutrients, such as β-1,3-glucans, tocopherol, carotenoids, essential amino acids, vitamins, and minerals. Ascorbate and other bioproducts like vitamin E remain an important component of commercially available food supplements based on E. gracilis cell mass. In mixotrophic cultures, the α-tocopherol content increases during exponential growth (from 0.04 to 0.18 mg g⁻¹). The anti-inflammatory activity studies also detected β-carotene, neoxanthin, diadinoxanthin, canthaxanthin, and breakdown products such as pheophytins and pheophorbides in fractionated extracts.
The presence of nutritionally crucial chemicals such as fatty acids, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and vitamins in E. gracilis implies that this alga is a valuable therapeutic resource with potential for clinical application. Wax esters are detected in both mixotrophically and heterotrophically grown cells; the majority are esters of C14 and C16 fatty acids and fatty alcohols. Under anaerobic or hypoxic conditions, E. gracilis is known to consume intracellular paramylon to obtain energy without oxygen; this process is accompanied by the production of wax ester, an ester mainly composed of C14:0 saturated fatty acid, myristic acid, and myristyl alcohol.
In addition to being enriched in nutrients such as vitamins, minerals, amino acids, and fatty acids at high concentrations, Euglena has no cell wall and is highly digestible. Initial transcriptomic studies indicated that amino acid synthesis pathways in E. gracilis were similar to those used by plants and bacteria. However, an in-depth proteomic analysis later revealed a unique pathway for arginine biosynthesis in E. gracilis, which is independent from the urea cycle commonly utilised by other eukaryotic organisms.
Based on established production data, the nutritional composition of E. gracilis per gram includes moisture (≥33 mg), protein (≥256 mg), lipid (≥93 mg), ash (≥31 mg), and carbohydrate (≥433 mg); paramylon, an insoluble β-glucan, typically accounts for approximately 70–80% of the carbohydrate content.
β-glucans have potent immunomodulating activity; their action is mediated through receptors present on immune cells, such as Dectin-1 (a C-type lectin receptor), Toll-like receptors, complement receptor 3, scavenger receptor, and lactosylceramide, which elicit specific biological responses. Dectin-1 is indicated as the preferential receptor for linear β-(1,3)-linked glucans. Upon linkage of the glucan effector with Dectin-1, the innate immune response is activated, leading to production of both ROS and inflammatory cytokines through the activation of transcription factors such as NF-κB, enzymes such as phospholipase C, and mitogen-activated protein kinases.
Dectin-1 is the main receptor for β-glucans and is expressed on intestinal immune cells, including dendritic cells (DCs) and macrophages. Upon recognition by Dectin-1, paramylon is internalized by cells, activating the tyrosine kinase SYK and the transcription factor NF-κB, thereby promoting cytokine secretion.
Although the precise mechanism by which paramylon might act as a biological response modifier (BRM) and prebiotic has not yet been fully elucidated, it is proposed that beta-glucans released from digested paramylon in the gut are delivered to the lamina propria through the M cells of Peyer's patches in the small intestine. In vivo Ca²⁺ imaging demonstrated Euglena- and paramylon-mediated Ca²⁺ signaling in intestinal epithelial cells from mice, and that intraperitoneal injection of both Euglena and paramylon stimulated dendritic cells (DCs) in Peyer's patches, indicating that paramylon is an active component of Euglena that affects the immune system.
Sonicated and alkalized paramylon upregulates pro-inflammatory factors (NO, TNF-α, IL-6, and COX-2) in lymphomonocytes; a clear demonstration of this upregulation is the increased transactivation of NF-κB visualized by immunofluorescence microscopy.
Dietary supplementation with paramylon resulted in decreased abdominal fat accumulation and serum LDL cholesterol concentrations via suppression of the digestion and absorption pathway in the ileum and activation of the hepatic PPAR signaling pathway.
Oral administration of this linear β-(1,3)-glucan polymer has been reported to prevent acute hepatic injuries induced by CCl4 administration via antioxidative mechanisms. Paramylon derived from E. gracilis EOD-1 reduces fatigue and fatigue sensation by maintaining immune function and reducing cellular oxidative injury.
Human/Clinical Evidence:
Several randomized controlled trials have investigated the effects of Euglena on immune function in humans.
Evidence Strength: Multiple small-to-moderate RCTs support short-term immune benefits, particularly NK cell activity and cold symptom reduction. Sample sizes are generally small (24–several hundred participants), studies are largely of short duration (4–12 weeks), and some trials were funded by industry partners; nevertheless, the consistent direction of findings provides preliminary but meaningful clinical support. Human evidence specifically on immune modulation is considered emerging, not conclusive.
Human/Clinical Evidence:
A randomized, double-blind, placebo-controlled, parallel-group comparison study was conducted in 66 healthy men and women who ingested a placebo or EOD-1PM daily for 4 weeks (daily life fatigue). The dose per capsule was adjusted so that the test food would contain 175 mg of paramylon derived from E. gracilis EOD-1, whereas the placebo contained dextrin. At the examination days of 0 and 4 weeks, tolerance to fatigue load was evaluated using mental tasks (task-induced fatigue), and fatigue sensation was evaluated using the Visual Analogue Scale, with the work efficiency of the advanced trail making test and serum antioxidant markers also measured. The findings suggested that paramylon derived from E. gracilis EOD-1 reduces fatigue and fatigue sensation by maintaining immune function and reducing cellular oxidative injury.
Evidence Strength: One industry-supported RCT. Results are preliminary; replication in independent trials is needed before firm conclusions can be drawn.
Human/Clinical Evidence:
A randomized, double-blind, placebo-controlled, parallel-group trial studied whether paramylon-rich Euglena gracilis EOD-1 powder supplementation could improve visceral fat obesity; EOD-1 was found to enhance visceral fat area (VFA) loss and increase serum adiponectin concentration.
Animal/Preclinical Evidence: Male C57BL/6J mice were fed a high-fat diet supplemented with either 2.5 or 5% paramylon powder extracted from Euglena gracilis for 74 days. Dietary supplementation with paramylon resulted in decreased food efficiency ratios and abdominal fat accumulation; dose-dependent decreases were observed in postprandial glucose levels, serum LDL-cholesterol, and serum secretary immunoglobulin A (sIgA) concentrations. Animal microarray analysis suggested that paramylon resulted in decreased abdominal fat accumulation and serum LDL cholesterol concentrations via suppression of the digestion and absorption pathway in the ileum and activation of the hepatic PPAR signaling pathway.
Evidence Strength: Animal data are robust and internally consistent. Human clinical evidence is limited to a single published RCT; independent replication in larger populations is needed. Some studies reported that paramylon did not have anti-obesity or anti-inflammatory effects in mice fed a high-fat diet, possibly due to insufficient supplementation of the experimental diets.
Preclinical Evidence: Oral administration of this linear β-(1,3)-glucan polymer has been reported to prevent acute hepatic injuries induced by CCl4 administration via antioxidative mechanisms. Compared with standard paramylon, sonicated and alkalized paramylon (SA-Pa) had lower molecular weights and showed better efficacy in alleviating injury-induced hepatic functions, as well as the transcriptional levels of inflammatory cytokines; SA-Pa treatment also promoted M2 macrophage activation that enhanced anti-inflammatory function in the liver and downregulated STAT3 target genes.
It is suggested that oral administration of Euglena and paramylon inhibited liver fibrosis in a mouse model of non-alcoholic steatohepatitis (NASH). Paramylon intake was proposed to contribute to hepatoprotection through its antioxidant activity.
Evidence Strength: Evidence is entirely preclinical (animal models). No controlled human trials on hepatic outcomes have been published. The findings are considered hypothesis-generating only.
Preclinical Evidence: Sugiyama et al. found that oral consumption of paramylon inhibited the development of atopic dermatitis-like skin lesions in sensitized NC/Nga mice, most likely by reducing serum levels of both IL-4 and IFN-γ as well as the IL-18 and IL-12 contents of the skin lesions. Additionally, live E. gracilis cells and aqueous extract were found to facilitate wound healing by enhancing re-epithelization and reducing fibroplasia without stimulating excessive inflammatory response in a murine burn wound model.
Evidence Strength: Evidence is preclinical only; no human clinical data exist for atopic dermatitis endpoints.
Laboratory/Preclinical Evidence: Both autotrophic and heterotrophic Euglena powders could promote the growth of Lactobacillus, and the antioxidant properties of Lactobacillus were also improved. Metabolomic investigation of 1,398 metabolites of culture medium found that nitrogen metabolism, biosynthesis of amino acids, and biotin metabolism pathways, rather than paramylon alone, were responsible for the improved bacterial growth under Euglena addition.
Evidence Strength: Evidence is in vitro only. No human prebiotic trials are currently available.
Preclinical Evidence: It has been reported that whole Euglena extract and its main components, paramylon, contain biological properties including immunomodulatory, anti-bacterial, anti-viral, and therapeutic properties against various diseases, including cancer. A study on mice showed that paramylon has antitumor effects and reduced preneoplastic aberrant crypt foci in the colon.
Evidence Strength: All anti-cancer evidence is preclinical (cell lines and animal models). While there is increasing interest in the therapeutic potential of E. gracilis and paramylon, the detailed mechanisms of their anti-cancer properties have not previously been clarified. No human clinical data exist.
In Vitro/Preclinical Evidence: In vitro experiments have reported that paramylon activates pro-inflammatory pathways and ROS production in neutrophils, monocytes, macrophages, and lymphocytes. Several different compounds have been reported in extracts from Euglena, depending on protocols and techniques; opposite results can be explained by different biological experimental models and different growing conditions and preparation protocols, leading to variability in concentrations of molecules, degree of purity, or sample contaminations. This duality — paramylon activating immune cells while simultaneously supporting anti-inflammatory outcomes in disease models — reflects the context-dependent nature of β-glucan immunomodulation.
Evidence Strength: In vitro evidence is notable but mixed. In this setting, E. gracilis may sustain or promote human health, but the effects on the intestinal inflammatory milieu are not fully clear. Human anti-inflammatory trials are absent.
The following dosages are reported directly from cited human clinical studies:
In animal studies, paramylon has been administered at concentrations such as 2.5% or 5% of the diet in high-fat diet murine models, for 74 days.
Commercial preparations include encapsulated whole-cell dried powder and purified paramylon capsules. The applicant for EU novel food authorization proposed use in food supplements, foods for total diet replacement for weight control, and food ingredients; the target population is the general population from 12 months of age onwards (for supplements and total diet replacement).
Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of dried whole cell Euglena gracilis as a novel food pursuant to Regulation (EU) 2015/2283. The submitted toxicity studies did not raise safety concerns. No adverse effects were observed in the subchronic toxicity study, up to the highest dose tested, i.e., 3,300 mg NF/kg body weight, which was considered as the No Observed Adverse Effect Level (NOAEL).
The safety of E. gracilis strain EU029 for use as a food ingredient was assessed in a bacterial reverse mutagenesis assay (Ames), rec assay, in vivo micronucleus assay, acute toxicity study in mice, 13-week toxicology study in rats, and a teratology study in mice and rats. EG029 was not genotoxic. The No Observed Adverse Effect Level (NOAEL) in the 13-week study was greater than 1,000 mg/kg/day, the highest dose tested.
Analyses were provided for polycyclic aromatic hydrocarbons (PAHs) and aflatoxins (B1, B2, G1, G2), which were all well below regulatory limits commonly used for other foods such as cereal-based foods. The applicant also investigated the toxin-producing potential of E. gracilis, considering that two other species, Euglena sanguinea and Euglena granulata (but not E. gracilis), from the same genus have been reported to be able to produce toxic secondary metabolites. A certificate of analysis for six samples was provided, all of which were below the limit of detection (<0.1 pg/g) for euglenophycin.
In 2019, E. gracilis was attributed the Qualified Presumption of Safety (QPS)-status with the qualification "for production purposes only," which includes food products based on microbial biomass of the microalga. Euglena and its characteristic beta-glucan, paramylon, have recently undergone safety testing for their use in human food. As noted by one review, compared to other microalgae like spirulina and Chlorella, there is very little published safety data for Euglena as a food ingredient.
In the 8-week NK cell activity RCT, results showed improved immune function with no adverse events or safety concerns reported. The EFSA opinion noted that the evidence base for long-term safety in humans remains limited relative to more established microalgae such as spirulina, and further characterization of consumption risks is warranted given the novelty of this ingredient.
Assessment of the beneficial potential of β-glucan compounds has been often carried on using poorly described, crude preparations, leading to confounding results, misconceptions, and controversies regarding biological effects. Though preparations from plant/algal/fungal sources can achieve a high degree of purity, minute sample contaminations may result in nonspecific immune-modulating effects. This underscores that the immunomodulatory effects of paramylon preparations are sensitive to preparation method and purity, and that results across studies using different preparations may not be directly comparable.
Health conditions that Euglena gracilis may help support.
Body systems that Euglena gracilis may help support.
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