Schizochytrium oil

Schizochytrium Oil

1. Identity: Names, Source, and Preparations

1.1 Taxonomic and Chemical Identity

Thraustochytrids, including Schizochytrium, lack essential features of algae: they are achlorophyllous, lack plastids, do not photosynthesize, and rely exclusively on heterotrophic nutrition. Despite being commonly marketed and regulated as an "algal oil," Schizochytrium is more precisely a unicellular marine protist belonging to the order Thraustochytriales. They were originally thought to be fungi because of their lack of photosynthetic machinery, but subsequent molecular biology work identified them as heterotrophic micro-organisms known as stramenopiles, and they are now regarded as part of a larger phylum referred to as the Labyrinthulomycota, which comprises just two families: the Thraustochytriidae and the Labyrinthulidae.

The taxonomic placement of Schizochytrium is summarised as: Kingdom Chromophyta, Phylum Heterokonta, Order Thraustochytriales, Family Thraustochytriaceae, Genus Schizochytrium. Currently, there are nine genera of the family Thraustochytriidae: Thraustochytrium, Japonochytrium, Schizochytrium, Ulkenia, Aurantiochytrium, Sicyoidochytrium, Parietichytrium, Botryochytrium, and Monorhizochytrium, classified according to their morphological characteristics, ultrastructure, life cycles, and biochemical markers.

Taxonomic revision has substantially altered the nomenclature of commercial strains. The oil is defined as the winterised, deodorised oil derived from cultivated Schizochytrium sp., and due to taxonomical name changes made to the genus, the following taxa are now considered equivalent: Schizochytrium aggregatum, Aurantiochytrium limacinum, Aurantiochytrium mangrovei, Oblongichytrium minutum, and Oblongichytrium octosporum. The key commercially exploited species is Schizochytrium limacinum, which encompasses several strains used in different product categories, including ATCC 20888, ATCC 20889, FCC-3204, WZU477, TKD-1, and CABIO-A-2.

One of the most studied strains, Schizochytrium limacinum SR21, was first isolated from a mangrove zone of Yap Islands, Micronesia. Another commercially used strain, WZU477, was obtained in a marine environment from rotted mangrove forest leaves and was found to belong to the species Schizochytrium limacinum.

In regulatory documents, the extracted oil is referred to by several trade and technical designations. In Europe, Martek Biosciences Corporation (now DSM Nutritional Products) obtained approval to market a DHA-rich oil produced from Schizochytrium that is referred to as DHA-S; another DHA-rich oil that includes eicosapentaenoic acid (EPA) is referred to as DHA-O, where EPA is present at approximately half the amount of DHA. The ingredient may also be described as an oil rich in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), derived from heterotrophically grown marine microalgae, Schizochytrium sp., otherwise known as DHA-O.

1.2 Natural Ecological Source

Thraustochytrids are unicellular heterotrophic marine protists widely distributed in marine and estuarine ecosystems and frequently associated with organic material in decay. Schizochytrium is a genus of marine microalgae found in marine habitats as well as brackish and saline waters. Individual cells of Schizochytrium spp. range in size from 9 to 14 μm.

Fish obtain omega-3 fatty acids from microalgae, which are primary producers in the marine food chain. Schizochytrium thus sits at the base of the oceanic food web and is the primary biological origin of the DHA and EPA that accumulates in fish and seafood.

1.3 Production and Commercial Forms

Schizochytrium and Crypthecodinium are the primary sources for the production of DHA used in aquaculture, nutritional supplements, and infant formulas; they are grown heterotrophically in fermenters using organic carbons such as glucose. It is cultivated in closed systems, enabling continuous year-round production with full control over water quality and environmental parameters. The microalgae responds strongly to changes in the culture medium and environmental conditions, which allows the fatty acid profile — including DHA content — to be actively controlled during fermentation.

Commercial preparations include:

• Refined triglyceride oil (softgel capsules and liquid): The winterised, deodorised oil derived from cultivated Schizochytrium sp. This is the dominant supplement form, encapsulated in soft gelatin or plant-based capsules.
• Oil for infant and follow-on formula: The oil rich in DHA is isolated from the microalgae by mechanical extraction and has been proposed for use in infant formulae (IF) and follow-on formulae (FOF). Another strain-specific product is obtained from microalgae after enzymatic lysis.
• Whole-cell or dried biomass powder: Used in animal nutrition and some human food fortification applications.
• Oleoresin: The oleoresin form offers a vegan alternative to fish oil and is used in food supplements, cosmetics, and animal feed.
• Microencapsulated powder: Used to fortify dry foods and infant formula powders while protecting the highly unsaturated oil from oxidation.

Analysis of the oil has confirmed the absence of the common algal toxins domoic acid and prymnesin. Antioxidants such as ascorbyl palmitate and tocopherols are added to the final product to enhance stability.

2. Traditional and Historical Use

Schizochytrium Oil's direct historical use in traditional medicine is limited — mainly because the cultivation and extraction of microalgae oils is a relatively recent technological advancement. The organism itself was only formally characterised in the mid-twentieth century; the first description of a thraustochytrid was made in 1934, when Thraustochytrium proliferum was isolated from the marine alga Bryopsis plumosa in coastal waters near Woods Hole, Massachusetts.

The concept of obtaining omega-3 fatty acids directly from microalgae for human use was developed as a biotechnological solution rather than emerging from indigenous or traditional medical practice. A major commercial process was developed by OmegaTech Ltd in Boulder, Colorado, USA, based on using a marine organism known as a species of Schizochytrium. The successful development of heterotrophic fermentation methods in the late 1980s and early 1990s enabled the production of sufficient quantities for commercial use. The United States Food and Drug Administration (FDA) first granted GRAS (Generally Recognized As Safe) status for DHA oil from Schizochytrium sp. (as DHASCO-S) as a direct food ingredient in 2004, as documented in DHA Algal Oil derived from Schizochytrium sp. receiving GRAS status and becoming available for food use and for dietary supplements (FDA, 2004).

The underlying rationale — obtaining omega-3 fatty acids to replicate the benefits long associated with fish and marine food consumption — is grounded in decades of epidemiological observation linking traditional fish-eating diets (such as those in Japan, Greenland, and Nordic nations) with favourable cardiovascular outcomes. Schizochytrium oil was thus conceived and developed as a modern, scalable, and sustainable proxy for this traditional dietary pattern, rather than as a product of any specific ethnobotanical or ethnopharmacological tradition.

3. Key Constituents and Active Compounds

3.1 Fatty Acid Composition

The oil's primary and defining constituent is docosahexaenoic acid (DHA, C22:6 n-3). The lipid profile of Schizochytrium sp. oil exhibits exceptional nutritional value, characterised by its remarkably high concentration of docosahexaenoic acid (DHA). This marine protist typically contains 35–50% DHA by total fatty acid content, representing one of the most concentrated natural sources of this essential omega-3 fatty acid.

The fatty acid composition demonstrates a distinctive pattern, with palmitic acid (C16:0) constituting 15–25% of total lipids, while docosapentaenoic acid (DPA, C22:5 n-6) accounts for 3–8%, and oleic acid (C18:1) comprises 5–10% of the fatty acid profile. Different strains produce oils with varying DHA-to-EPA ratios. Standard DHA-S type oil contains predominantly DHA with very little EPA, while the DHA-O type includes both: Algal Oil (DHA-O type) contains approximately 37% DHA and 16% EPA (wt/wt). In ATCC-20889 strain oil, DHA represents 40–43% of fatty acids.

The regulatory minimum standard is stringent: it contains docosahexaenoic acid at not less than 350 mg/g, as established by Australia's Therapeutic Goods Administration (TGA) compositional guideline.

A structurally significant feature of Schizochytrium oil is the form in which DHA is packaged. In Schizochytrium and fish, more than 90% of DHA occurs in triacylglycerols (TAG). This triacylglycerol form contrasts with krill oil, in which DHA is predominantly phospholipid-bound, and has implications for digestion and absorption kinetics.

3.2 Minor Constituents

Beyond its primary lipid components, Schizochytrium oil contains several nutritionally significant minor constituents. The oil naturally contains 0.5–2.0% carotenoid pigments, predominantly astaxanthin and canthaxanthin, which serve as potent antioxidants that enhance oxidative stability. The presence of these pigments is a distinguishing feature compared to refined fish oils, which lose most antioxidant carotenoids during processing.

3.3 Mechanisms of Action

The health effects of Schizochytrium oil are driven by its content of long-chain omega-3 fatty acids, primarily DHA and, secondarily, EPA and DPA. These molecules are incorporated into cell membranes throughout the body, where they influence membrane fluidity, signalling, and the production of bioactive lipid mediators. In the brain and retina, DHA is a structural component of neuronal and photoreceptor membranes.

Schizochytrium-derived omega-3s shift the balance of eicosanoids and related mediators away from pro-inflammatory n-6 arachidonic acid derivatives toward less inflammatory or specialised pro-resolving mediators, contributing to more controlled inflammatory responses rather than complete suppression of the immune system.

At the cellular level, DHA can impact gene expression through nuclear receptors such as PPARs (peroxisome proliferator-activated receptors), influence lipid raft composition in cell membranes, and affect signal transduction pathways connected to insulin sensitivity, neuronal plasticity, and mitochondrial function.

In the cardiovascular system, EPA and DHA modulate triglyceride metabolism, platelet function, and vascular tone. DHA is the predominant fatty acid in the membrane phospholipids of the brain grey matter and is also present in the eye retina.

4. Scientific Evidence by Area of Use

4.1 Cardiovascular Health: Triglycerides and Lipid Profile

This is the most extensively researched area for Schizochytrium-derived DHA in humans, with multiple randomised controlled trials (RCTs) and at least one meta-analysis.

Meta-analysis evidence: A systematic review and meta-analysis published in The Journal of Nutrition (Bernstein et al., 2012) conducted a systematic review of RCTs published between 1996 and 2011, examining the relationship between algal oil DHA supplementation and cardiovascular disease risk factors. The objective was to examine the relation between algal oil supplementation and cardiovascular disease risk factors, using a systematic review of randomised controlled trials and a meta-analysis of the association between algal oil DHA supplementation and changes in triglyceride (TG), LDL-cholesterol, and HDL-cholesterol concentrations. Algae currently being bred in algaculture to create DHA-rich algal oil in the studies analysed included Crypthecodinium cohnii, Schizochytrium species, and Ulkenia species.

An earlier clinical review published in 2009 (Arterburn et al.) synthesised data from 16 published clinical trials: based on data from 16 published clinical trials, the review examined effects of DHA triglyceride (TG) oil derived from algae (algal-DHA) on serum TG levels and related parameters. Study populations included subjects with both normal and elevated TG levels, including those with persistent hypertriglyceridemia treated with concomitant statin therapy. The review found that at doses of 1–2 g/d, algal-DHA significantly lowered plasma TG levels (up to 26%) either administered alone or in combination with statins; the reduction in TG levels was markedly greater in hypertriglyceridemic than in normal subjects.

Algal-DHA modestly increased plasma levels of both high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol. The increased plasma level of LDL-cholesterol was associated with a shift of lipoprotein particle size toward larger, less atherogenic subfractions. In some subjects, blood pressure and heart rate were also significantly reduced.

Key RCT — DHA-O vs fish oil: In a double-blind, parallel trial, 93 healthy adults with hypertriglyceridemia (TAGs 150–499 mg/dL) were randomised to receive either a nutritional oil derived from marine algae (DHA-O; 2.4 g/day DHA and EPA in a 2.7:1 ratio), fish oil (FO; 2.0 g/day DHA and EPA in a 0.7:1 ratio), or a corn oil/soy oil control as 4 × 1 g softgel capsules/day with meals for 14 weeks. Percent changes from baseline for DHA-O, fish oil, and control, respectively, were TAG (−18.9, −22.9, +3.5; p<0.001 DHA-O and fish oil vs. control), LDL-cholesterol (+4.6, +6.8, −0.6; p<0.05 DHA-O and fish oil vs. control), and HDL-cholesterol (+4.3, +6.9, +0.6; p<0.05 fish oil vs. control). This study demonstrated that ingestion of microalgal DHA-O providing 2.4 g/day DHA+EPA lowered TAG levels to a degree that was not different from that of a standard fish oil product. This trial was funded by DSM Nutritional Products and registered at ClinicalTrials.gov (NCT01737099).

Key RCT — overweight adults: One study was designed to examine the effects of DHA on plasma lipid and lipoprotein concentrations and other biomarkers of cardiovascular risk in the absence of weight loss. In this randomised, controlled, double-blind trial, 36 overweight or obese adults were treated with 2 g/d of algal DHA or placebo for 4.5 months; markers of cardiovascular risk were assessed before and after treatment.

Key RCT — cardiovascular risk in healthy men and women: The effect of Schizochytrium oil on cardiovascular risk factors was evaluated using a double-blind randomised placebo-controlled parallel-design trial in 39 men and 40 women. Subjects received 4 g oil/d for 4 weeks; the active treatment provided 1.5 g DHA and 0.6 g DPA. Active treatment increased plasma concentrations of DPA and DHA by 11 and 88 mg/L respectively, and the proportions of DPA and DHA in erythrocyte phospholipids by 78 and 27% respectively. Serum total, LDL, and HDL-cholesterol all increased compared with placebo.

Evidence strength: The evidence for triglyceride lowering is consistent across multiple RCTs and a meta-analysis, and is considered robust for this specific outcome. The LDL-cholesterol elevation seen in several trials is a recognised, though modest, effect of DHA (and fish oil) supplementation and warrants consideration in the context of overall cardiovascular risk. Evidence for hard cardiovascular endpoints (myocardial infarction, stroke, mortality) has not been specifically demonstrated in Schizochytrium oil trials; the available evidence is limited to surrogate biomarkers.

4.2 Bioavailability and Equivalence to Fish-Oil DHA

Clinical trials using DHA-rich oil from Schizochytrium sp. report efficient incorporation of DHA into plasma phospholipids and erythrocyte membranes, comparable to fish-derived TAG sources.

The microalgal oil used in one bioavailability study was derived from Schizochytrium sp. Both microalgal and fish oils were natural triglycerides. Subjects were asked to consume four softgel capsules per day for 14 weeks; each capsule of microalgal oil contained 164 mg EPA and 443 mg DHA (1:3 EPA to DHA ratio, DSM Nutritional Products). A total of 93 healthy adults aged 21 to 82 were enrolled (36 in the placebo arm, 37 in the microalgal oil arm, and 20 in the fish oil arm).

One pilot study investigated DHA levels of healthy participants following a 2-week supplementation period with 600 mg/d of DHA sourced from either fish-oil capsules or algal-oil capsules. According to the analysis, DHA sourced from algal-oil and DHA sourced from fish-oil were not found to be bioequivalent; the omnivorous group administered algal-oil capsules had significantly (p<0.05) higher percentage DHA levels. These mixed findings underscore the need for further studies with standardised methodology.

In comparative lipid profiling research, in Schizochytrium and fish, more than 90% of DHA occurred in triacylglycerols. Krill oils exhibited phospholipid-rich profiles. Nutritional indices highlighted that Schizochytrium-based algal oils even surpassed fish and fish oils in terms of favourable PUFA-to-saturated fatty acid ratios and hypocholesterolemic-to-hypercholesterolemic ratios.

Evidence strength: The bioequivalence data are mixed. The majority of the larger, better-powered studies report that DHA from Schizochytrium oil is incorporated into plasma and erythrocyte membranes at rates comparable to fish oil DHA, but small sample sizes and methodological variability limit definitive conclusions.

4.3 Infant Neurodevelopment and Perinatal Nutrition

EFSA's NDA Panel confirmed an Adequate Intake (AI) for DHA of 100 mg/day for infants and young children between 6 and 24 months, applied also to infants 0–6 months, and concluded that DHA should be added to infant and follow-on formulae due to its structural role in the nervous system and the retina and its involvement in normal brain and visual development.

Adequate DHA supports normal visual development and cognitive function, particularly during late pregnancy, infancy, and early childhood when brain growth is rapid.

Formulae enriched with algal DHA at levels comparable to human milk have been shown to support normal growth and tolerability in term infants. In maternal supplementation, Schizochytrium-derived DHA has been used during pregnancy and lactation to increase maternal and infant DHA status, with reported benefits for gestational length, infant visual acuity, and early cognitive development in some trials. These findings align with the broader literature on DHA in perinatal nutrition.

DHANI Trial: DHANI was a double-blinded, parallel group, randomised, placebo-controlled trial supplementing 957 pregnant women aged 18–35 years from ≤20 weeks gestation through 6 months postpartum with 400 mg/d algal-derived DHA or placebo.

One multicenter, two-arm, randomised, double-blind pilot trial of DHA-rich oil supplementation began either in the last trimester of pregnancy (41 infants) or in the first 5 months after birth (57 infants). Levels of DHA in infant and maternal red blood cell membranes and in breast milk, and inflammatory cytokines were assayed. This pilot trial showed that supplementation of infant diets with DHA-rich oil was safe, with no adverse effects on measured outcomes noted.

EFSA's NDA Panel set an adequate intake (AI) of 250 mg for EPA plus DHA for adults; an AI of 100 mg DHA for infants (>6 months) and young children <24 months; and an increase of 100–200 mg preformed DHA in addition to the AI for adults as an adequate supply of n-3 long chain PUFAs during pregnancy and lactation.

Evidence strength: The safety of Schizochytrium-derived DHA in infant formulae is well established and supported by multiple EFSA safety opinions and clinical studies. Evidence that DHA supplementation in this context improves measurable cognitive or visual outcomes is positive in some trials but remains heterogeneous across the broader literature; the benefits are better established for visual acuity endpoints than for cognitive outcomes.

4.4 Neurological and Cognitive Function

DHA is the predominant fatty acid in the membrane phospholipids of the brain grey matter and is also present in the eye retina. Its deficiency has been related to cognitive decline and neurodegenerative diseases such as Alzheimer's disease.

When DHA algal oil is consumed, the DHA gets incorporated into cell membranes, especially in the brain and eyes. This process helps keep cells flexible and improves the way they communicate with each other. Research shows that DHA plays a critical role in enhancing cognitive performance by supporting cell membrane fluidity.

In animal research, whole cell Schizochytrium sp. is a rich source of omega-3 long-chain polyunsaturated fatty acids including DHA, an important nutrient for brain health. Aged beagle dogs were used to assess efficacy of DHA-rich microalgae based upon DHA weight percentage of total phospholipids and 8-iso-PGF2α concentrations in plasma, and performance on cognitive assessments of visual object discrimination, learning, and memory consolidation after 25 weeks on fortified diet.

Evidence strength: Direct clinical evidence for Schizochytrium oil specifically improving cognitive outcomes in adult humans is limited. Most evidence in this domain comes from studies of DHA broadly (from various sources), and from studies on infants and older adults using composite omega-3 products. Animal model evidence is supportive but cannot be directly extrapolated. This area is currently preliminary in the context of Schizochytrium oil specifically, and stronger mechanistic evidence is still largely derived from in vitro and animal studies.

4.5 Eye Health and Visual Acuity

DHA is the predominant fatty acid in the membrane phospholipids of the brain grey matter and is also present in the eye retina. DHA's role in retinal physiology is well established at the structural level. DHA is an omega-3 fatty acid essential for normal brain function, vision, heart function, and cholesterol maintenance.

Mechanistic research has examined DHA's role in ocular surface and tear film physiology. DHA plays an active role in the organisation of the lacrimal lipid film, reducing the evaporation of the muco-aqueous phase, reducing the surface tension of the inter-phase, and has an antibacterial function. It inhibits apoptosis and controls the secretion of Goblet cells. It normalises the lipid secretion and viscosity of the Meibomian glands.

Evidence strength: The structural importance of DHA for retinal integrity is well established. Clinical evidence for Schizochytrium oil specifically improving vision in adults is indirect; most of the direct trial evidence relates to visual acuity development in infants receiving DHA-supplemented formula. Use for conditions such as dry eye is currently supported by mechanistic studies and early-phase research, but not by large definitive RCTs specific to Schizochytrium oil.

4.6 Inflammation

EPA and DHA obtained from Schizochytrium and Crypthecodinium microalgae possess the ability to reduce plasma triglycerides and decrease systolic blood pressure in animal and human volunteers. These fatty acids also play a role in the prevention of platelet aggregation, reducing the likelihood of thrombosis — a major trigger of cardiovascular incidents.

DHA and EPA synergistically enhance immunity by modulating macrophages, dendritic cells, and lymphocytes, as well as cellular signalling and the immune system.

Evidence strength: Anti-inflammatory mechanisms of DHA (and EPA) at the molecular and cellular level are well characterised. However, translation of these mechanisms into demonstrated clinical anti-inflammatory outcomes specifically from Schizochytrium oil in human RCTs is limited; most of the evidence base consists of in vitro or animal studies, with some supportive human data from non-Schizochytrium omega-3 sources.

5. Body Systems and Health Areas of Association

• Cardiovascular system: Triglyceride lowering, modest HDL increase, LDL particle size shift; platelet function modulation; blood pressure in some studies.
• Central nervous system: Structural component of neuronal membranes; DHA status linked to cognitive development in infants; associated with cognitive maintenance in adults.
• Visual system/eye: Structural component of photoreceptor membranes; supports retinal function; role in tear film physiology.
• Perinatal and infant nutrition: Fetal brain and retinal development; supported by mandatory inclusion in EU infant formulae.
• Immune and inflammatory pathways: Eicosanoid modulation; production of specialised pro-resolving mediators; modulation of macrophage and lymphocyte function.
• Metabolic/hepatic: PPAR-mediated gene expression effects; modulation of hepatic VLDL secretion, which underlies the triglyceride-lowering effect.

6. Dosage Forms and Reported Dosages

Dosages below are drawn directly from clinical studies and regulatory documents as cited; they represent doses used in research, not therapeutic recommendations.

• Adults — cardiovascular/lipid outcomes: At doses of 1–2 g/day, algal-DHA significantly lowered plasma TG levels in multiple published clinical trials. In the DHA-O vs fish oil RCT (14 weeks, 93 subjects), 4 × 1 g softgel capsules/day provided 2.4 g/day DHA+EPA in a 2.7:1 ratio. In an RCT of 36 overweight adults, subjects were treated with 2 g/day of algal DHA for 4.5 months. In a trial of 39 men and 40 women, subjects received 4 g oil/day for 4 weeks, providing 1.5 g DHA and 0.6 g DPA.
• Adults — food supplement (EFSA-evaluated): An applicant proposed to increase the use level of a food supplement from 250 mg DHA/day (currently authorised for the general population) to 3 g DHA/day for adults, excluding pregnant and lactating women. EFSA concluded that supplemental intakes of DHA alone up to about 1 g/day do not raise safety concerns for the general population, and that the NF is safe for use in food supplements at the maximum intake level of 1 g DHA/day for adults (excluding pregnant and lactating women).
• Infant and follow-on formula: The use level defined by the European Commission's Regulation (EU) 2016/127 states the mandatory addition of DHA to infant formulae and follow-on formulae at the level of 20–50 mg/100 kcal.
• Pregnancy and lactation (EFSA reference values): The EFSA NDA Panel set an increase of 100–200 mg preformed DHA in addition to the adult AI of 250 mg EPA+DHA/day as an adequate supply of n-3 long-chain PUFAs during pregnancy and lactation. The DHANI trial used 400 mg/day algal-derived DHA in pregnant women from ≤20 weeks gestation through 6 months postpartum.
• Adults — bioavailability study: Subjects in one bioavailability trial were asked to consume four softgel capsules per day for 14 weeks, with each capsule of microalgal oil containing 164 mg EPA and 443 mg DHA.
• Adults — food supplement dosing in general use: In adults, Schizochytrium oil supplements have been used to increase blood levels of DHA and EPA, often in doses of 200–600 mg DHA per day.

7. Safety, Toxicology, and Interactions

7.1 Regulatory Safety Status

DHA Algal Oil derived from Schizochytrium sp. is generally recognized as safe (GRAS) and available for food use and for dietary supplements (FDA, 2004). An initial GRAS notice (GRN 137) for Schizochytrium sp. oil received GRAS notice status with the US FDA, resulting in a maximum dietary exposure of less than 1.5 g of DHA per day.

In Europe, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a series of opinions on the safety of Schizochytrium sp. oil as a novel food pursuant to Regulation (EU) 2015/2283. Schizochytrium limacinum was attributed the Qualified Presumption of Safety (QPS) status with the qualification "for production purposes only."

The EU's consolidated list of novel foods, detailed in the Annex to Implementing Regulation (EU) 2017/2470, includes "DHA and EPA-rich oil from the microalgae Schizochytrium sp.", as well as oils derived from the microalga itself and specific Schizochytrium sp. strains.

7.2 Genotoxicity

The safety of Algal Oil from Schizochytrium sp. was evaluated by testing for gene mutations, clastogenicity and aneugenicity; the results of all genotoxicity tests were negative. Schizochytrium sp. was considered to be non-mutagenic with respect to gene mutations, clastogenicity, and aneugenicity. These findings are in line with previous reports that algal oils and microalgae do not have genotoxic potential.

7.3 Subchronic (90-day) Toxicology

A 90-day study involved dietary exposure to 0.5, 1.5, and 5 wt.% of Algal Oil and two control diets. There were no treatment-related effects of Algal Oil on clinical observations, body weight, food consumption, behaviour, haematology, clinical chemistry, coagulation, or urinalysis parameters. Increased mean liver weights and alveolar histiocytosis were observed in both the fish oil control and the high-dose Algal Oil-treated animals and were not considered to be adverse. Algal Oil was bioavailable as demonstrated by dose-related increases of DHA and EPA levels in tissues and plasma.

The administration of Algal Oil for 90 days at dietary levels up to 5 wt.% was well tolerated and did not affect health, behaviour, and neurological parameters of Sprague-Dawley rats. Body weights of Algal Oil-treated animals were comparable to controls.

One applicant provided a 90-day repeated dose toxicity study in rats. No adverse effects were observed up to the highest dose tested at 10.2 g/kg body weight per day. Taking into account the toxicity studies performed with DHA oils derived from strains belonging to the genus Schizochytrium, its phylogenetic profile, the production process, the composition of the NF, and the absence of marine biotoxins and viable cells in the NF, EFSA's NDA Panel considered there are no concerns with regard to toxicity, and concluded that the NF is safe under the proposed conditions of use.

7.4 Developmental and Reproductive Toxicology

As part of a comprehensive safety assessment, the developmental toxicity of DHA-rich microalgae from Schizochytrium sp. was assessed in Sprague-Dawley rats (25/group, provided DRM in the diet at 0.6, 6, and 30% on gestation days 6–15) and in New Zealand White rabbits (22/group, dosed at 180, 600, and 1800 mg/kg/day by oral gavage on gestation days 6–19). Fish oil was used as a negative control. Maternal food consumption, body weights, and clinical signs were recorded at regular intervals throughout these studies.

7.5 Marine Biotoxins and Contaminant Safety

Marine biotoxins (including cyanotoxins) in the novel food were below their limits of quantification, as assessed in the EFSA opinion on Schizochytrium sp. strain ATCC-20889. S. limacinum was attributed QPS status with the qualification "for production purposes only," and data provided by the applicant demonstrated the absence of viable cells in the NF. The absence of viable organisms in the final refined oil is required for regulatory approval.

7.6 Clinical Tolerability

Algal-DHA was safe and well tolerated in clinical trials. Unlike fish oil, algal-DHA seldom caused gastrointestinal complaints such as fishy taste and eructation — attributes of importance for patient compliance in high-dose therapy.

A pilot trial showed that supplementation of infant diets with DHA-rich oil was safe; no adverse effects on measured outcomes were noted.

7.7 Bleeding Risk and Drug Interactions

The Institute of Medicine stated that "while there is evidence to suggest that high intakes of n-3 polyunsaturated fatty acids, particularly EPA and DHA, may impair immune response and result in excessively prolonged bleeding times, it is not possible to establish a [tolerable] upper level." This observation applies to high-dose omega-3 supplementation broadly, and is relevant to Schizochytrium oil at doses significantly above the typical 1–2 g/day range.

High doses can increase bleeding risk and may interact with anticoagulant medications or affect lipid control in some people. This is a pharmacodynamic interaction relevant to individuals taking anticoagulant or antiplatelet medications such as warfarin, heparin, or aspirin, where additive antiplatelet effects from DHA and EPA are a recognised concern.

7.8 Upper Safe Level for General Adults

EFSA concluded that supplemental intakes of DHA alone up to about 1 g/day do not raise safety concerns for the general population. The Panel concluded that Schizochytrium limacinum (strain FCC-3204) oil is safe for use in food supplements at the maximum intake level of 1 g DHA/day for adults, excluding pregnant and lactating women. Data were not considered sufficient by EFSA to conclude on safety at the applicant's proposed 3 g DHA/day level in the general population.

7.9 Phytanic Acid Consideration

Regulatory assessments have noted phytanic acid as a minor constituent requiring monitoring in novel algal oils. While phytanic acid is a naturally occurring metabolite in some algal lipids, levels in refined Schizochytrium oils are subject to compositional specification requirements under novel food authorisation. Individuals with Refsum disease, a rare inherited disorder of phytanic acid metabolism, are advised to avoid all marine lipid-rich foods and supplements.

References

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• EFSA NDA Panel (2021). Safety of oil from Schizochytrium limacinum (strain FCC-3204) for use in food supplements as a novel food. PMC / EFSA Journal.
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